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Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review
Abstract
Thyroid disorders commonly impact on the gastrointestinal system and may even present with gastrointestinal symptoms in isolation; for example, metastatic medullary thyroid carcinoma typically presents with diarrhoea. Delays in identifying and treating the underlying thyroid dysfunction may lead to unnecessary investigations and treatment, with ongoing morbidity, and can potentially be life-threatening. Similarly, gastrointestinal diseases can impact on thyroid function tests, and an awareness of the concept and management of non-thyroidal illness is necessary to avoid giving unnecessary thyroid therapies that could potentially exacerbate the underlying gastrointestinal disease. Dual thyroid and gastrointestinal pathologies are also common, with presentations occurring concurrently or sequentially, the latter after a variable time lag that can even extend over decades. Such an association aetiologically relates to the autoimmune background of many thyroid disorders (e.g. Graves' disease and Hashimoto's thyroiditis) and gastrointestinal disorders (e.g. coeliac disease and inflammatory bowel disease); such autoimmune conditions can sometimes occur in the context of autoimmune polyglandular syndrome. Emphasis should also be given to the gastrointestinal side effects of some of the medications used for thyroid disease (e.g. anti-thyroid drugs causing hepatotoxicity) and vice versa (e.g. interferon therapy causing autoimmune thyroid dysfunction). In this review, we discuss disorders of the thyroid-gut axis and identify the evidence base behind the management of such disorders.
Copyright © 2015. Published by Elsevier B.V.
... The most common clinical signs of hypothyroidism are related to decreased metabolic rate and dermatological changes, while less frequent but well-documented clinical manifestations include neurological, cardiovascular, and reproductive abnormalities [1]. In both human and veterinary medicine, hypothyroidism is a well-known cause of alteration of multiple gastrointestinal processes [1][2][3]. Patients can suffer mainly from constipation [3] as a result of abnormal peristalsis [4] due to alterations of hormonal receptors and neuromuscular disorders using mucopolysaccharides infiltration. However, chronic diarrhea has also been reported as a consequence of increased bacterial growth due to intestinal hypomotility [5][6][7]. ...
... In both human and veterinary medicine, hypothyroidism is a well-known cause of alteration of multiple gastrointestinal processes [1][2][3]. Patients can suffer mainly from constipation [3] as a result of abnormal peristalsis [4] due to alterations of hormonal receptors and neuromuscular disorders using mucopolysaccharides infiltration. However, chronic diarrhea has also been reported as a consequence of increased bacterial growth due to intestinal hypomotility [5][6][7]. ...
... In human medicine, subclinical hypothyroidism may be associated with an increased risk of developing liver disease [3,9], especially Non-Alcoholic Fatty Liver Disease and fibrosis [10]. The increased risk of liver disease in hypothyroid patients has been associated with different mechanisms, such as dyslipidemia and higher body mass index, lack of intrahepatic lipolysis induced by thyroid hormones, decreased triglyceride clearance and increased hepatic accumulation of triglycerides, and lipogenesis induced by hypothyroidism-related insulin resistance [11]. ...
Few observations about gastrointestinal (GI) signs in hypothyroid dogs (hypo-T dogs) are available. We aimed to evaluate the prevalence and characteristics of concurrent GI signs in hypo-T dogs, describe clinicopathological, hepato-intestinal ultrasound findings in hypo-T dogs, investigate changes in GI signs after thyroid replacement therapy (THRT). Medical records of suspected hypo-T dogs from two hospitals were retrospectively reviewed. The inclusion criteria were: (1) having symptoms and clinicopathological abnormalities related to hypothyroidism (i.e., mild anemia, hyperlipemia); (2) not being affected by systemic acute disease; (3) not having received any treatment affecting thyroid axis. Hypothyroidism had to be confirmed using low fT4 or TT4 with high TSH and/or inadequate TSH-stimulation test response; otherwise, dogs were assigned to a euthyroid group. Clinical history, GI signs, hematobiochemical parameters, and abdominal ultrasound findings were recorded. Hypo-T dogs were assigned to the GI group (at least 2 GI signs) and not-GI group (1 or no GI signs). Follow-up information 3–5 weeks after THRT was recorded. In total, 110 medical records were screened: 31 dogs were hypo-T, and 79 were euthyroid. Hypo-T dogs showed a higher prevalence of GI signs (44%), especially constipation and diarrhea (p = 0.03 and p = 0.001), than euthyroid dogs (24%) (p = 0.04). Among hypo-T dogs, no difference in hematological parameters between GI and non-GI groups was found. Hypo-T dogs had a higher prevalence of gallbladder alterations than euthyroid dogs (20/25; 80% and 32/61; 52% p = 0.04). The hypo-T GI group showed a significant improvement in the GI signs after THRT (p < 0.0001). Specific investigation for concurrent GI diseases in hypo-T dogs was lacking; however, improvement in GI signs following THRT supports this association between GI signs and hypothyroidism.
... What is stressful to one individual may not prove so to another. In this regard, physical and psychological stressors can activate the hypothalamic-pituitary-thyroid axis (Kyriacou et al., 2015). Fluctuations in thyroid hormones are linked to psychiatric disease (Baumgartner, 2000;Kyriacou et al., 2015), sexual behavior (Dellovade et al., 1996) and even evolution (Crockford, 2003). ...
... In this regard, physical and psychological stressors can activate the hypothalamic-pituitary-thyroid axis (Kyriacou et al., 2015). Fluctuations in thyroid hormones are linked to psychiatric disease (Baumgartner, 2000;Kyriacou et al., 2015), sexual behavior (Dellovade et al., 1996) and even evolution (Crockford, 2003). There are no conclusive results on whether stress reduces or increases thyroid hormones. ...
... Moreover, it is worth briefly mentioning the utility of thyroid sonography in the diagnostic work-up of medication-induced thyrotoxicosis. With amiodarone (24), interferon (25) and the newer immunecomplex inhibitors (24)(25)(26), the distinction is usually between a destructive thyroiditis and hyperthyroidism. Thyroiditis is, more often than not, associated with reduced vascularity and echogenicity on USS and little or no diffuse thyroid enlargement. ...
... Moreover, it is worth briefly mentioning the utility of thyroid sonography in the diagnostic work-up of medication-induced thyrotoxicosis. With amiodarone (24), interferon (25) and the newer immunecomplex inhibitors (24)(25)(26), the distinction is usually between a destructive thyroiditis and hyperthyroidism. Thyroiditis is, more often than not, associated with reduced vascularity and echogenicity on USS and little or no diffuse thyroid enlargement. ...
In this mini-review, we examine the utilization of thyroid sonography as a ‘point-of-care’ tool for assessing and managing patients with (suspected) hyperthyroidism who present to the endocrine outpatients. Thyroid USS may aid the distinction between hyperthyroidism and destructive thyroiditis. Presence of intense vascularity (‘thyroid inferno’) on power Doppler has a very high positive predictive in identifying hyperthyroidism. It may also allow the sub-classification of hyperthyroidism into autoimmune and nodular hyperthyroidism. The presence of thyroid nodules is important to acknowledge at an early stage as this may affect management. Not only toxic nodules are managed with definitive treatment, but the presence of nodules is important to be clarified in Graves’ disease because of the evidence of an increased risk of malignancy and, possibly, more aggressive behaviour if malignant disease is confirmed. Current guidelines on hyperthyroidism do not clearly state thyroid sonography as a first line investigation although recent authoritative reviews point in that direction. Given the aforementioned benefits of thyroid sonography, alongside the reduced costs and widespread availability of high-resolution (including portable) ultrasound devices, there is an argument for thyroid sonography to be applied as a first line investigation for all patients with hyperthyroidism. More precisely, formally trained endocrinologists could perform thyroid sonography as an extension of their clinical examination when patients first present with hyperthyroidism in the endocrine clinic.
... Bis zu ein Viertel der PatientInnen kann unter einer milden bis moderaten Diarrhö leiden, es kann eine erhöhte Defäkationsfrequenz [9] oder sogar eine Steatorrhö vorliegen [9]. In etwa ein Fünftel der prämenopausalen Frauen mit Hyperthyreose weist eine Oligomenorrhö auf, eine Amenorrhö ist bei Hyperthyreose aber selten [10]. ...
... Bis zu ein Viertel der PatientInnen kann unter einer milden bis moderaten Diarrhö leiden, es kann eine erhöhte Defäkationsfrequenz [9] oder sogar eine Steatorrhö vorliegen [9]. In etwa ein Fünftel der prämenopausalen Frauen mit Hyperthyreose weist eine Oligomenorrhö auf, eine Amenorrhö ist bei Hyperthyreose aber selten [10]. ...
Zusammenfassung
Die häufigsten Ursachen für die Entstehung einer Hyperthyreose sind die Immunthyreopathie Basedow sowie die Schilddrüsenautonomie. Für die Diagnosestellung sind die Bestimmung der TSH-Rezeptor-Antikörper (TRAK) nebst Thyroidea-stimulierendem Hormon (TSH), freiem Thyroxin (fT4) und freiem Trijodthyronin (fT3) wichtig. Die Bestimmung der T3/T4-Ratio kann in der Abgrenzeng einer Immunthyreopathie Basedow zu einer destruktiven Thyreoiditis hilfreich sein. Bei der Immunthyreopathie Basedow sind das typische sonographische Bild einer hypoechogenen Schilddrüse mit erhöhter Vaskularisation und zunehmend auch die quantitative Bestimmung der Durchblutung in Form der „peak systolic velocity“ (PSV) weitere diagnostische Hilfsmittel. Die Szintigraphie hat bei der Diagnosestellung der Schilddrüsenautonomie nach wie vor ihren Stellenwert.
Therapeutisch steht bei der Immunthyreopathie Basedow die medikamentöse, thyreostatische Therapie vorrangig mit Thiamazol in Form des Titrationsschemas im Vordergrund, die für 12–18 Monate durchgeführt wird. Liegen die TRAK dann im Normbereich, kann ein Absetzversuch unternommen werden. Wenn nicht, oder wenn es zum Auftreten eines Rezidivs kommt, sollte eine definitive Therapie mittels Radiojodtherapie oder Thyreoidektomie erwogen werden. Zur symptomatischen Behandlung können Betablocker wie Propranolol eingesetzt werden. Es gibt Hinweise, dass die lange praktizierte Jodrestriktion im Management der Immunthyreopathie Basedow vermieden werden sollte. Zum Einsatz von Selen liegen positive, aber noch großteils inkonsistente Daten vor, sodass eine Therapieempfehlung derzeit nicht ausgesprochen werden kann. In der Therapie der Schilddrüsenautonomie stehen Radiojodtherapie und die Operation im Vordergrund. Die Diagnose einer thyreotoxischen Krise ist eine klinische und wird anhand des Burch-Wartofsky-Scores gestellt – das Management erfordert meist intensivmedizinische Betreuung.
... L'ipertiroidismo è causa infrequente [1]. Un aumento di motilità intestinale con incremento di evacuazioni/die e, talvolta, riduzione di consistenza fecale compare nel 10-50% dei casi [1][2][3][4]. ...
... Costituiscono però una causa "organica" e, pertanto, devono essere considerate quando le cause più probabili sono state escluse [1]. Con vari meccanismi, non sempre legati Gastrinoma 30-70% Malassorbimento [12] Sindrome da carcinoide 60-80% Ipersecrezione intestinale [1,8,11,12] alla diarrea, tendono tutte a causare calo ponderale, la cui presenza può suggerire una sottostante patologia organica [1][2][3][4][5][6][7][8][9][10][11]. Tra le patologie classiche, sono epidemiologicamente rilevanti solo ipertiroidismo, individuabile con il dosaggio del TSH incluso nell'approccio iniziale della BSG, e diabete mellito, in cui la diarrea, legata alla neuropatia autonomica, tende a comparire tardivamente in casi già inquadrati. ...
... 30 kg/m 2 [2]. Definitions for Asians are somewhat lower (23)(24)(25)(26)(27).5 kg/m 2 ) [3]. Recent estimates ...
... However, observational studies and randomized controlled trials were included where appropriate. This style of narrative review has been previously published [25]. ...
... Medullary carcinoma of thyroid (MCT) is a rare tumor, arising from C-cells or parafolicular cells of thyroid gland, accounting for 3-10% of the thyroid carcinomas in UnitedStates.52,53 Although these tumors most commonly occur sporadically, hereditary forms, part of Flushing associated with gastrointestinal system Page 16 Copyright © 2017 Marshfield Clinic Health System multiple endocrine neoplasia (MEN) syndromes types 2A and 2B syndrome arise due to a germline mutation in the RET proto-oncogene.53 ...
... Cutaneous flushing is found in 10% of patients in association with other symptoms such as diarrhea, hoarseness and dysphagia.53,54 Diarrhea occurs in two-thirds of patients with metastatic disease, due to the hypersecretory state and/or increased bowel motility induced by neuropeptides.52 ...
Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. The paper is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract. Part 1 covered is neuroendocrine tumors, (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid) polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils. Part 2 covered is dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.
... SCiEnTiFiC REPORTS | (2018) 8:4552 | DOI: 10.1038/s41598-018-19564-y relationships between thyroid disorders and gastrointestinal disorders 9 , but the responsible molecular mechanisms remains unclear. ...
... It has revealed that these rats of CS model suffered from thyroid dysfunction with decreased serum level of T3, T4, fT3 (free triiodothyronine) and fT4 (free thyroxine), comparing with the normal control (NC) group. Moreover, further investigations indicated that neurological disorder and immunosuppression were also induced in hypothalamus and colon respectively, implying that thyroid disorder might have effect on gut and brain 7,9,16 . In order to test whether the gastrointestinal disorders had effect on HPT axis or not, we also duplicated a TNBS-induced ulcerative-colitis (UC) rat model, according to previous studies 17,18 . ...
Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. So far, the molecular mechanisms of response to stressors still remain elusive. In the current study, after 10 days of repeated chronic stress (hot-dry environment and electric foot-shock), a murine model of combined-stress (CS) was created in the SPF Wistar rats. Meanwhile, we established an ulcerative-colitis (UC) rat model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol enema according to previous studies. The blood, hypothalamus, and colon tissues of these rats from CS, normal control (NC), UC and sham (SH) groups, were collected for further investigations. Comparing to the NC group, the serum levels of T3, T4, fT3 and fT4 were obviously decreased in the CS group after chronic stress, indicating that thyroid dysfunction was induced by long-term combined stress. Moreover, the application of RNA-seq and subsequent analyses revealed that neurological disorder and immunosuppression were also caused in the hypothalamus and colon tissues, respectively. Comparing with SH group, besides the induced colon inflammation, thyroid dysfuntion and neurological disorder were also produced in the UC group, suggesting that hypothalamic-pituitary-thyroid (HPT) axis and gastrointestinal system might not function in isolation, but rather, have intricate crosstalks.
... Thyroid disorders commonly impact on the gastrointestinal tract and gut disorders can affect the thyroid functions [3]. CD is associated with a number of autoimmune conditions, including autoimmune thyroiditis disease (ATD), be HT or Grave's disease (GD). ...
... CD is associated with a number of autoimmune conditions, including autoimmune thyroiditis disease (ATD), be HT or Grave's disease (GD). In fact, multiple epidemiological, clinical, serological, pathological, pathophysiological, genetic and immunological aspects are shared between CD and HT [3][4][5][6][7][8][9][10]. Increased prevalence of CD associated antibodies is well described in ATD. ...
Prevalence of autoimmune thyroiditis is increased in patients with celiac disease and vice versa. Both diseases are frequent autoimmune diseases sharing multiple aspects lodging at the two ends of the gut-thyroid axis where the cross-talks' pathways are still unrivalled. Many authors recommend screening patients with thyroid autoimmunity for celiac disease associated antibodies. However, routine screening of celiac patients for anti-thyroid antibodies is less clear. Despite the fact that the latter screening fulfills most of the criteria for screening a disease, the timing and cost-effectiveness remains undetermined. For now, in face of celiac disease, the increased prevalence of autoimmune thyroid diseases needs to be taken in account and the accurate diagnosis should not be delayed.
... Approximately 94% of thyroid hormones are secreted by the thyroid gland as thyroxine or tetraiodothyronine (T4) and 6% as triiodothyronine (T3) (Fig. 1). T4 is catalytically converted to the more metabolically active T3 in peripheral tissues by deiodinases and a portion of peripherally-produced T3 returns to the circulation and it is because of this peripheral conversion that the plasma T4 to T3 ratio is approximately 4:1 [2,3]. Both T4 and T3 are mostly bound to carrier proteins in the serum, chiefly thyroxine-binding globulin (TBG). ...
... Nevertheless, MMI is the agent most widely used outside of pregnancy and its administration is more convenient (once daily vs. split dosing). During the second and third trimester, MMI is recommended in preference to PTU [8,9,70], in view of rare reports of severe hepatotoxicity with the latter (about 1 in 10,000) [2]. However, in daily practice switching of ATD can be somewhat 'messy' as it may lead to variations in TFTs in the short-term. ...
... Approximately 94% of thyroid hormones are secreted by the thyroid gland as thyroxine or tetraiodothyronine (T4) and 6% as triiodothyronine (T3) (figure 1). T4 is catalytically converted to the more metabolically active T3 in peripheral tissues by deiodinases and a portion of peripherally-produced T3 returns to the circulation and it is because of this peripheral conversion that the plasma T4 to T3 ratio is approximately 4:1 [2,3]. Both T4 and T3 are mostly bound to carrier proteins in the serum, chiefly thyroxine-binding globulin (TBG). ...
... Nevertheless, MMI is the agent most widely used outside of pregnancy and its administration is more convenient (once daily vs. split dosing). During the second and third trimester, MMI is recommended in preference to PTU [8,9,70], in view of rare reports of severe hepatotoxicity with the latter (about 1 in 10000) [2]. However, in daily practice switching of ATD can be somewhat 'messy' as it may lead to variations in TFTs in the short-term. ...
Thyroid dysfunction is the commonest endocrine disorder in pregnancy apart from diabetes. Thyroid hormones are essential for fetal brain development in the embryonic phase. Maternal thyroid dysfunction during pregnancy may have significant adverse maternal and fetal outcomes such as preterm delivery, preeclampsia, miscarriage and low birth weight. In this review we discuss the effect of thyroid disease on pregnancy and the current evidence on the management of different thyroid conditions in pregnancy and postpartum to improve fetal and neonatal outcomes, with special reference to existing guidelines on the topic which we dissect, critique and compare with each other.
Overt hypothyroidism and hyperthyroidism should be treated appropriately in pregnancy, aiming to maintain euthyroidism. Subclinical hypothyroidism is often pragmatically treated with levothyroxine, although it has not been definitively proven whether this alters maternal or fetal outcomes. Subclinical hyperthyroidism does not usually require treatment and the possibility of non-thyroidal illness or gestational thyrotoxicosis should be considered.
Autoimmune thyroid diseases tend to improve during pregnancy but commonly flare-up or emerge in the post-partum period. Accordingly, thyroid auto-antibodies tend to decrease with pregnancy progression.
Postpartum thyroiditis should be managed based on the clinical symptoms rather than abnormal biochemical results.
... In their study, 37% and 35% of the primary hypothyroid patients had elevated AST and ALT levels, respectively. 14 Thyroid abnormalities in hepatic diseases are the subject of numerous studies, [15][16][17] whereas hepatic dysfunctions in thyroid disorders have been studied selectively, especially when serum aminotransferase levels are concerned. ...
Introduction: Due to the complicated interactions between the thyroid gland and liver, thyroid hormone dysfunction may affect the liver function tests, and could be of clinical importance. We aimed to compare the hepatic function parameters between hypothyroid and euthyroid patients visiting tertiary care center of western Nepal. Materials and Methods: This hospital-based cross-sectional study was conducted among 113 hypothyroid and 111 euthyroid patients. After consent, thyroid function and liver function parameters were analyzed using automated analyzers. Mann-Whitney U test, Spearman’s correlation, and multiple linear regression analysis were performed for analysis. A p-value of <0.05 was considered statistically significant. Results: Among hypothyroid group, the majority were subclinical hypothyroid (n=74, 65.49%) and the rest (n = 39, 34.51%) were overt hypothyroid. The serum bilirubin and liver enzymes levels were significantly higher in hypothyroid compared to euthyroid. The serum albumin levels were significantly lower in the hypothyroid group. Serum liver enzymes and bilirubin levels were correlated negatively and positively with the thyroid hormones (fT3, fT4) and TSH levels, respectively. Conclusion: Patients with hypothyroidism and euthyroid patients had significantly different liver function test results. Although serum albumin was lower in the hypothyroid group, serum bilirubin and liver enzymes were higher.
... Overall, our data and those previously published emphasize the finding that lactose intolerance prevalence is not negligible in patients with HT, and its presence possible should be taken into account. In this regard, even though we observed a high prevalence of gastrointestinal symptoms in patients with HT, a finding consistent both with the prevalence of functional bowel disorders in the female general population and with the expected gastrointestinal complaints in patients with thyroid disease, we observed that a more detailed assessment of gastrointestinal symptoms showed that change in bowel habits was significantly more represented among patients with lactose intolerance, and this finding may guide selectively test patients who report this symptom, rather than screening for lactose intolerance all HT patients [31,32]. ...
Purpose:
to determine lactose intolerance (LI) prevalence in women with Hashimoto's thyroiditis (HT) and assess the impact of LI on LT4 replacement dose.
Methods:
consecutive patients with HT underwent Lactose Breath Test and clinical/laboratory data collection. Unrelated gastrointestinal disorders were carefully ruled out. Lactose-free diet and shift to lactose-free LT4 were proposed to patients with LI.
Results:
we enrolled 58 females (age range, 23-72 years) with diagnosis of HT. In total, 15 patients were euthyroid without treatment, and 43 (74%) euthyroid under LT4 (30 of them with a LT4 formulation containing lactose). Gastrointestinal symptoms were present in 84.5% of patients, with a greater prevalence in change in bowel habits in lactose-intolerant patients (p < 0.0001). The cumulative LT4 dose required did not differ in patients with or without LI. No significant difference in both TSH values and LT4 dose were observed in patients shifted to lactose-free LT4 and diet at 3 and 6 months compared to baseline.
Conclusion:
the prevalence of LI in patients with HT was 58.6%, not different from global prevalence of LI. In the absence of other gastrointestinal disorders, LI seems not to be a major cause of LT4 malabsorption and does not affect the LT4 required dose in HT patients.
... Other potential causes of GI symptoms relate to the coexistence of autoimmune diseases such as celiac disease (CD) and thyroid disease. Autoimmune thyroid disorders are commonly associated with type 1 diabetes and may affect swallowing and intestinal motility (3), and intestinal dysmotility may contribute to delayed gastric emptying (4). CD is also more prevalent in patients with type 1 diabetes, at rates 5 to 7 times the general population, and is increasingly recognized as a potential cause of GI distress in both pediatric and adult patients with diabetes (5)(6)(7). ...
Purpose
To assess reported rates of Gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with Type 1 Diabetes.
Methods
The Gastrointestinal Symptom Scale (GISS) was used to assess GI symptom type and severity in 2,370 patients with Type 1 Diabetes aged 8-45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical and other diabetes-related factors were evaluated.
Results
Overall, 1368 adults (57.7%) aged 19-45 years and 1002 (42.3%) pediatric patients aged 8-18 years were studied. At least one GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P<0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher Hemoglobin A1c (HbA1c) levels [68 ± 14mmol/mol] (8.35 ± 1.37%) than those without symptoms [66 ± 15mmol/mol] (8.22 ± 1.40%) (P=0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95%CI: 1.26 to 2.60; P<0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (OR=1.1; 95%CI: 0.86-1.42; P=0.45).
Main Conclusions
These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of Type 1 diabetes, HbA1c and microvascular complications, but not with autoimmune co-morbidities including CD.
... The role of decreased thyroid hormones in her digestive problems is not known but it may have been a factor [35] [21]. Thyroid destruction has been observed to produce reduced RBC synthesis with preserved lifetimes in dogs that is not correctable with vitamin B-12 although parenteral iron may be helpful in cases [8]. ...
This is one in a series of works released as notes/draft form as it achieves the intended purpose of documenting a result while not being exactly publication quality. This demonstrates some successes and problems tracking dog diets and health outcomes similar to the prior ones mostly on heartworm and vitamin K. This paper finally gets to an older dog and hopefully some issues common in old age. Even though the main text is short, a few redundancies were left in intentionally where the same point or definition may be independently relevant in multiple locations. For information only, not to be used for any particular purpose. See all disclaimers. Caveat Emptor This work describes the history of an older chihuahua, Spicey, over the course of several years at the end of her life as procedures and software were developed for generating useful data from diet history and observable outcomes. It illustrates a cessation of a recurring problem with bloody diarhea by adding well formulated nutrient mixes to her diet. The nutrients included amino acids, metals, and B-vitamins combined in such a way as to be mutually compatible in any given mixture and easily absorbed. A partial solution to a hypothyroid condition was implemented with a processed thyroid product as the veterinarian and dog owner were reluctant to pursue thyroid replacement hormone. Dessicated thyroid, containing natural amounts of thyroxine, may have been beneficial but was difficult to locate. While most of her overt symptoms improved, she deteriorated rapidly under unfortunate circumstances. It remains unclear if the thyroid insufficiency, some other disease progression, or specific unhealthy substances contributed to her deterioration. This history illustrates some real-world problems inherent in real-world data as well as some possible success of a diet with broader implications for general purpose use among older dogs. Contents
... 11 At certain times, the thyroid disease 12,13 leads to more secretion of the thyroid gland in the neckline, showing the symptoms that are directly associated with the enlargement in the size of the organ (such as uneasiness in front of the neck and trouble in swallowing). [14][15][16] As a result, there occurs a critical requirement to analyze the thyroids, immediately as feasible. The disorders caused due to thyroid 17 could be treated by medicines or at certain conditions, surgery can also be adopted for overcoming the disease. ...
Thyroid is a widespread disease, affecting most victims. The diagnosis of thyroid remains a complex process, as its detection in patients is highly intricate. Hence, the doctors are needed to be aware of the risk factors and symptoms of the disease. This paper aims to propose a novel thyroid diagnosis scheme, involving three major phases: (a) feature extraction, (b) optimal feature selection, and (c) classification. Initially, the thyroid image and the related data serve as input for diagnosing the disease. In the first phase, the features like, gray level co‐occurrence matrix (GLCM), gray level run length matrix (GLRM), local binary pattern (LBP), local vector pattern (LVP), and local tetra patterns (LTrP) are extracted from the input image. Additionally, the features from data are extracted using Principal Component Analysis (PCA) for resolving the issue of “curse of dimensionality.” The optimal features are then selected using a hybrid optimization approach. The optimally selected features of the image and the data are then subjected to the classification process via convolutional neural network (CNN) and neural network (NN), respectively. Both the classified outputs undergo “AND” binary operation to yield the final classified output. To yield effective classification, the NN model is trained by tuning its weights using the proposed algorithm. Further, this paper introduces a new hybrid algorithm, termed firefly updated lion optimization (SLnO) algorithm (FU‐SLnO), for attaining optimal outcomes. Finally, the efficiency of the proposed work is compared over few other conventional approaches and its superiority is proven.
... The mechanism of thyroid hormones affecting rumen physiology is unknown, but in the human body, thyroid disorders are associated with gastrointestinal dysfunction (92). It is proposed that thyroid hormones affect gut motility either directly or via a central stimulatory effect on the chemoreceptor trigger zone. ...
Methane is formed from the microbial degradation of feeds in the digestive tract in ruminants. Methane emissions from ruminants not only result in a loss of feed energy but also contribute to global warming. Previous studies showed that brassica forages, such as forage rape, lead to less methane emitted per unit of dry matter intake than grass-based forages. Differences in rumen pH are proposed to partly explain these low emissions. Rumen microbial community differences are also observed, but the causes of these are unknown, although altered digesta flow has been proposed. This paper proposes a new mechanism underlying the lower methane emissions from sheep fed brassica forages. It is reported that feeding brassica forages to sheep can increase the concentration of free triiodothyronine (FT3) in serum, while the intramuscular injection of FT3 into sheep can reduce the mean retention time of digesta in the rumen. The short retention time of digesta is associated with low methane production. Glucosinolates (GSLs) are chemical components widely present in plants of the genus Brassica. After ruminants consume brassica forages, GSLs are broken down in the rumen. We hypothesize that GSLs or their breakdown products are absorbed into the blood and then may stimulate the secretion of thyroid hormone FT3 in ruminants, and the altered thyroid hormone concentration may change rumen physiology. As a consequence, the mean retention time of digesta in the rumen would be altered, resulting in a decrease in methane emissions. This hypothesis on mitigation mechanism is based on the manipulation of animal physiological parameters, which, if proven, will then support the expansion of this research area.
... Gastrointestinal symptoms and complications are also common with dysphagia, atrophic gastritis, nausea with/without vomiting, frequent bowel movements and, rarely, steatorrhoea and lactose intolerance. 40 With advancing age, weight loss and reduced appetite become commoner, whilst usual symptoms such as heat intolerance and irritability are less common 41 ; hence, a high index of suspicion for hyperthyroidism is required when unintentional weight loss occurs in older persons. ...
Kyriacou A, Kyriacou A, Makris KC, Syed AA, Perros P. Weight gain following treatment of hyperthyroidism—A forgotten tale. Clin Obes. 2019;e12328.
Hyperthyroidism causes weight loss in the majority, but its effect is variable and 10% of patients gain weight. Its treatment usually leads to weight gain and some studies have reported an excess weight regain. However, there is considerable inter‐individual variability and a differential effect on body weight by different treatments, with some studies reporting more weight increase with radioiodine, and perhaps surgery, compared with anti‐thyroid drugs. The excess weight regain may relate to treatment‐induced hypothyroidism. Furthermore, the transition from hyperthyroidism to euthyroidism may unmask, or exacerbate, the predisposition that some patients have towards obesity. Other risk factors commonly implicated for such weight increase include the severity of thyrotoxicosis at presentation and underlying Graves' disease. Conflicting data exist whether lean body mass or fat mass or both are increased post‐therapy and whether such increments occur concurrently or in a sequential manner; this merits clarification. In any case, clinicians need to counsel their patients regarding this issue at presentation. Limited data on the effect of dietary interventions on weight changes with treatment of hyperthyroidism are encouraging in that they cause significantly lesser weight gain compared to standard care. More research is indicated on the impact of the treatment of hyperthyroidism on various anthropometric indices and the predisposing factors for any excessive weight gain. Regarding the impact of dietary management or other weight loss interventions, there is a need for well‐designed and, ideally, controlled intervention studies.
... Hashimoto's thyroiditis (HT) is one of the most common autoimmune endocrine diseases. Celiac disease is associated with a number of autoimmune conditions, including HT. Changes in microbiota and short-chain fatty acuds (SCFAs) are clearly related to the pathogenisis of CD, but their role in thyroid immunity induction or protection remains to be investigated [79][80][81][82][83][84][85][86][87]. ...
... In advanced stages of the disease, secretion of calcitonin and other active peptides by tumoral cells can cause systemic symptoms such as diarrhea or facial flushing. 2 The only potential curative treatment for MTC is surgical and consists of total thyroidectomy with cervical lymph node dissection of the central compartment and, in some cases, modified radical neck dissection. 3 ...
A case is presented of a 57-year-old man consulting for chronic diarrhea. Based on subsequent findings (thyroid nodule and
metastases), the possibility of metastatic medullary thyroid carcinoma (MTC) was raised. Thyroidectomy allowed diagnosing a
multicentric left lobe MTC. MTC is a rare cause of diarrhea, but should be considered, especially in the presence of signs or symptoms
of alarm or nonresponse to empirical therapy.
... How GI parasites interact with T3 is still unclear. The infection of GI parasites leads to emaciation and dyspepsia, which is similar to the clinical symptoms of thyroid disorders [15]. The analysis of associative patterns between GI parasite infection and fecal T3 levels can facilitate the health management of captive endangered species, and help us to explore the adaptive strategies of hosts responding to GI parasite infections. ...
The objective of this study was to evaluate the effects of sex, breeding center and age on fecal triiodothyronine levels in captive forest musk deer Moschus berezovskii, and to explore the age-intensity model of gastrointestinal parasites. Furthermore, the association between fecal triiodothyronine levels and parasite egg shedding was also analyzed. We collected musk deer fecal samples from two breeding centers located in Shaanxi and Sichuan province, China. Enzyme-linked immunosorbent assays were utilized to estimate the fecal triiodothyronine concentrations and profiles, and fecal parasite eggs or oocysts were counted using the McMaster technique. Female deer from both breeding centers consistently showed higher triiodothyronine concentrations than those observed in males, which indicates that a distinct physiology pattern occurs by sex. The triiodothyronine concentration in Sichuan breeding center was significantly higher than that in Shaanxi center for both sexes, suggesting that differences in environment, diet and management practices are likely to affect the metabolism. In addition, a negative relationship between triiodothyronine concentrations and age was found (r = - 0.75, p < 0.001), and parasite egg shedding was also negatively associated with age (r = - 0.51, p < 0.001), by which we can infer that older animals evolves a more developed immune system. Finally, a positive association between parasite egg shedding and triiodothyronine levels was found, which could be explained by the additional energy metabolism resulting from parasitic infection. Results from this study might suggest metabolic and immunological adaptations in forest musk deer. These baseline data could be used to unveil metabolic status and establish parasite control strategies, which has great potential in captive population management as well as their general health evaluations.
... Iodine malabsorption and reduced enterohepatic T3 reuptake are risk factors for hypothyroidism, and most thyroid diseases present with GI symptoms. 39 We did not adjust for malabsorption because this is inadequately recorded in the registers and the direction of causality would be unclear. Lastly, some drugs may influence thyroid function, for example, lithium and amiodarone. ...
Background
Long-term iodine exposure may influence the frequency of thyroid disease treatments through fluctuations in thyroid diseases. Yet, the long-term fluctuations in thyroid disease treatments upon iodine fortification (IF) are not fully known. We aimed to examine the development in thyroid disease treatments in Denmark before and following the implementation of IF in 2000.
Methods
Nationwide data on antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment were obtained from Danish registries. Negative binominal regression was applied to analyze annual changes in treatment rates adjusted for region of residence, sex, and age.
Results
Incidence of antithyroid medication transiently increased but fell and reached steady state from 2010 at an incidence rate ratio (RR) of 0.72 (95% confidence interval [CI] 0.67–0.77) compared to year 2000. Thyroid hormone therapy increased and reached steady state in 2010 at an incidence RR of 1.75 (95% CI 1.62–1.89) compared to year 2000. Thyroid surgery was constant except for higher rates in 2014–2015, and radioiodine treatment fluctuated with no apparent pattern.
Conclusion
Ten years after IF, a steady state was observed for incident antithyroid medication below the level at IF, and thyroid hormone therapy above the level at IF. Only small changes were observed in thyroid surgery and radioiodine treatment. In the same period, changes in diagnostic and treatment practices and lifestyle factors are likely to have occurred and should be considered when evaluating the effects of IF on treatment of thyroid diseases.
... The liver is a major organ responsible for metabolizing the thyroid hormones, as well as for producing thyroid binding proteins, such as thyroid binding globulin, transthyretin, and albumin. 19 Conversely, thyroid hormones play a significant role in the activity of glucoronyltransferase involved in bilir- ubin metabolism. 20 Therefore, it is necessary to evaluate the thyroid function in patients with liver disease and inversely liv- er function in patients with thyroid disease. ...
Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.
... A number of studies have reported that the thyrotoxic condition decreases serum creatinine levels [21,22] and improves lipid profiles, including total cholesterol [23,24]. Thyrotoxicosis increases liver enzyme levels owing to relative hypoxia in the hepatic perivenular regions [25,26]. Although reports have conflicted, relatively low platelet counts in thyrotoxic patients have also been reported [27,28]. ...
Background
Symptoms and signs of thyrotoxicosis are nonspecific and assessing its clinical status is difficult with conventional physical examinations and history taking. Increased heart rate (HR) is one of the easiest signs to quantify this, and current wearable devices can monitor HR.
Objective
We assessed the association between thyroid function and resting HR measured by a wearable activity tracker (WD-rHR) and evaluated the clinical feasibility of using this method in patients with thyrotoxicosis.
Methods
Thirty patients with thyrotoxicosis and 10 controls were included in the study. Participants were instructed to use the wearable activity tracker during the study period so that activity and HR data could be collected. The primary study outcomes were verification of changes in WD-rHR during thyrotoxicosis treatment and associations between WD-rHR and thyroid function. Linear and logistic model generalized estimating equation analyses were performed and the results were compared to conventionally obtained resting HR during clinic visits (on-site resting HR) and the Hyperthyroidism Symptom Scale.
ResultsWD-rHR was higher in thyrotoxic patients than in the control groups and decreased in association with improvement of thyrotoxicosis. A one standard deviation–increase of WD-rHR of about 11 beats per minute (bpm) was associated with the increase of serum free T4 levels (beta=.492, 95% CI 0.367-0.616, P
... 3,45,46 • Severely malabsorptive procedures can impair bio- availability of THs, which can presumably impair L-t4 absorption. 3 ...
... Increased interest on the thyroid-intestinal epithelium is supplied by the finding of 40% of patients with HT with lymphocytic colitis, higher intraepithelial lymphocyte counts, dilated tight junctions, and shorter and thicker microvilli. The gastrointestinal dysfunctions in thyroid disorders were most recently reviewed (11). ...
Autoimmune thyroiditis has an increased prevalence in patients with celiac disease and vice versa. The objective of the current review is to highlight the epidemiological, clinical, serological, pathological, pathophysiological, hormonal, genetic and immunological factors shared between the two entities. They might represent the two ends of the gut-thyroid axis where the cross-talks' pathways are still unrivalled. New observations are reviewed, highlighting some gut- thyroid interrelated pathways that potentially might lead to new therapeutic strategies.
... Most notably, MAHMI Web-based interface enables the comparison of user-submitted amino acidic sequences against database contents and thus, it can be ideally used to identify peptides that may be used to manipulate altered immune responses. MAHMI has a clear application in the framework of IBD, but also in other immune-associated diseases where the gut microbiota plays a part, including Irritable Bowel Syndrome (20,21), Celiac Disease (22,23) and Type-1 Diabetes (24,25). ...
The Mechanism of Action of the Human Microbiome (MAHMI) database is a unique resource that provides comprehensive information about the sequence of potential immunomodulatory and antiproliferative peptides encrypted in the proteins produced by the human gut microbiota. Currently, MAHMI database contains over 300 hundred million peptide entries, with detailed information about peptide sequence, sources and potential bioactivity. The reference peptide data section is curated manually by domain experts. The in silico peptide data section is populated automatically through the systematic processing of publicly available exoproteomes of the human microbiome. Bioactivity prediction is based on the global alignment of the automatically processed peptides with experimentally validated immunomodulatory and antiproliferative peptides, in the reference section. MAHMI provides researchers with a comparative tool for inspecting the potential immunomodulatory or antiproliferative bioactivity of new amino acidic sequences and identifying promising peptides to be further investigated. Moreover, researchers are welcome to submit new experimental evidence on peptide bioactivity, namely, empiric and structural data, as a proactive, expert means to keep the database updated and improve the implemented bioactivity prediction method. Bioactive peptides identified by MAHMI have a huge biotechnological potential, including the manipulation of aberrant immune responses and the design of new functional ingredients/foods based on the genetic sequences of the human microbiome. Hopefully, the resources provided by MAHMI will be useful to those researching gastrointestinal disorders of autoimmune and inflammatory nature, such as Inflammatory Bowel Diseases. MAHMI database is routinely updated and is available free of charge.
Database URL:http://mahmi.org/
... These symptoms usually improve with treatment of the thyroid dysfunction. A bidirectional relationship also occurs between the thyroid and the liver that is important for health, and is disrupted with disease [32]. This includes conditions such as non-alcoholic fatty liver disease (NAFLD), which has also been shown to improve with normalization of thyroid function [33]. ...
There is nothing like seeing the patient. The approach to a patient with liver disease concerns a history, and a physical examination, from which an assessment and plan are generated. The clinician identifies risk factors for liver disease, including the use of illegal substances, prescription medications and herbal remedies, and high alcohol intake. The presence of comorbidities may identify risk factors for liver disease, including fatty liver and iron overload. Low blood pressure is common in patients with advanced liver disease because of the profound vasodilation that characterizes portal hypertension. A decrease in oxygen saturation is an indication to exclude hepatopulmonary syndrome in patients with suspected portal hypertension. Inspection allows for the identification of cutaneous stigmata of chronic liver disease. Obesity and acanthosis nigricans suggest insulin resistance. The abdomen is the territory of the hepatogastroenterologist. Abdominal distension suggests ascites. Palpation from the right lower quadrant to the ribcage allows for the identification of massive hepatomegaly, and hepatic auscultation may identify a vascular liver mass. Splenomegaly must be sought. Ascites with abdominal tenderness suggests peritonitis. A neurological examination identifies asterixis, a sign of hepatic encephalopathy; however, a decreased attention span during the interview also may suggest encephalopathy. A liver disease work up to exclude viral hepatitis, autoimmune and metabolic disease, and imaging studies provides support for the differential diagnosis generated from a detailed history and physical examination.
The diagnosis of thyroid via appropriate interpretation of thyroid data is the vital classification issue. Only little contributions are made so far in the automatic diagnosis of thyroid disease. In order to solve Thyroid disorder this paper intends to propose a new thyroid diagnosis model, utilising two-phases includes Feature Extraction and Classification. In the first phase, two sorts of features are extracted that include image features like neighbourhood-based and gradient features, and Principal Component Analysis (PCA) is used to extract the data features as well. Subsequently, two sorts of classification processes are performed. Specifically, Convolutional Neural Network (CNN) is used for image classification by extracting deep features. Neural Network (NN) is used for classifying the disease by obtaining both the image and data features as the input. Finally, both the classified results (CNN and NN) are combined to increase the accuracy rate of diagnosis. Further, as the main aim of this work is to increase the accuracy rate, this paper aims to trigger the optimisation concept. The convolutional layer of CNN is optimally selected, and while classifying under NN the given features should be the optimal one. Hence, the required features are optimally selected. For these optimisations, a new modified algorithm is proposed in this work namely Worst Fitness-based Cuckoo Search (WF-CS) which is the modified form of Cuckoo Search Algorithm (CS). Finally, the performance of proposed WF-CS is compared over other conventional methods like Conventional CS, Genetic Algorithm (GA), FireFly (FF), Artificial Bee Colony (ABC), and Particle Swarm Optimisation (PSO) and proves the superiority of proposed work in detecting the presence of thyroid.
Thyroid hormone is essential for brain development and brain function in the adult. During development, thyroid hormone acts in a spatial and temporal-specific manner to regulate the expression of genes essential for normal neural cell differentiation, migration, and myelination. In the adult brain, thyroid hormone is important for maintaining normal brain function. Thyroid hormone excess, hyperthyroidism, and thyroid hormone deficiency, hypothyroidism, are associated with disordered brain function, including depression, memory loss, impaired cognitive function, irritability, and anxiety. Adequate thyroid hormone levels are required for normal brain function. Thyroid hormone acts through a cascade of signaling components: activation and inactivation by deiodinase enzymes, thyroid hormone membrane transporters, and nuclear thyroid hormone receptors. Additionally, the hypothalamic-pituitary-thyroid axis, with negative feedback of thyroid hormone on thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) secretion, regulates serum thyroid hormone levels in a narrow range. Animal and human studies have shown both systemic and local reduction in thyroid hormone availability in neurologic disease and after brain trauma. Treatment with thyroid hormone and selective thyroid hormone analogs has resulted in a reduction in injury and improved recovery. This article will describe the thyroid hormone signal transduction pathway in the brain and the role of thyroid hormone in the aging brain, neurologic diseases, and the protective role when administered after traumatic brain injury. © 2021 American Physiological Society. Compr Physiol 11:1-21, 2021.
Objective: To explore the characteristics of oral and intestinal microbiota of pregnant women with hypothyroidism during pregnancy, and to find the correlations between the changes of flora and pregnancy outcome of pregnant women with hypothyroidism during pregnancy.Methods: In this study, oral and intestinal microbial composition was surveyed using 16S rRNA sequencing approach in 61 pregnant women (30 with hypothyroidism and 31 normal controls). Sequentially, we validated the differential microbial features using Quantitative Real-Time PCR (QPCR) approach of 10 randomly selected pregnant women (5 with hypothyroidism and 5 normal controls). Furthermore, general clinical data and serological indices were added to the analysis to examine the links between oral and intestinal microbiota and pregnancy outcomes.Results: The 16S rRNA results showed that the relative abundances of Gammaproteobacteria of pregnant women in the hypothyroidism group were higher than those in the control group, while the levels of Firmicutes in the control group were higher than those in the hypothyroidism group. The serum CRP level, the weight gain during pregnancy and the incidence of fetal distress in the hypothyroidism group were higher than control group. The QPCR results also showed the same changes of the intestinal in the two groups.Conclusion: There were significant differences in the oral and intestinal microbiota between pregnant women with hypothyroidism and normal pregnant women. The changes of microbiota is one of the factors influencing the occurrence and development of hypothyroidism during pregnancy.
Overt primary hypothyroidism is characterized by a state of decreased circulating thyroid hormones associated with low FT4/TT4 (free and total thyroxine) and elevated thyroid-stimulating hormone (TSH) (thyrotropin). In this chapter, we discuss the epidemiology, pathophysiology, and etiology of overt hypothyroidism. The clinical spectrum is presented according to the manifestations of hypothyroxinemia at each body system. The basis for laboratory diagnosis is discussed, as well as some pitfalls on the interpretation of TSH assays. Finally, we discuss peculiarities of the diagnosis of overt hypothyroidism in special situations, such as pregnancy, depression, and in the elderly. Treatment of overt hypothyroidism is discussed in a separate chapter.
Die Leber hat eine wesentliche Rolle bei der Regulierung des Stoffwechsels und ist zudem Zielorgan unterschiedlicher Stoffwechselstörungen. Die Wechselwirkungen und Rückkopplungsmechanismen zwischen der Leber und endokrinen Organen spiegeln sich dadurch wider, dass eine Fehlfunktion des einen Organsystems häufig relevante Auswirkungen auf das andere hat. Die Hypo- und Hyperthyreose sind häufig mit Veränderung der Leberfunktion assoziiert. Schilddrüsenerkrankungen müssen daher in der Abklärung unklar erhöhter Transaminasen ausgeschlossen werden. Lebererkrankungen können zudem den Stoffwechsel der Schilddrüsenhormone verändern. Ethanol wirkt ebenso nicht nur toxisch auf die Leber, sondern führt auch zu einem veränderten Metabolismus von Schilddrüsenhormonen. Ethanol kann zudem den Kortisolstoffwechsel beeinflussen und zum klinischen Bild eines Pseudo-Cushing-Syndroms führen. Kontrovers wird die Wechselwirkung von Leber und Nebennierenrindeninsuffizienz diskutiert, insbesondere als sog. hepatoadrenales Syndrom. Zunehmende Bedeutung haben Knochenerkrankungen bei Leberschäden, insbesondere die Osteoporose. Sexualhormone haben einen relevanten Einfluss auf die Leberfunktion und können toxische Leberschäden verursachen bzw. zu Adenomen und anderen Lebertumoren führen. Chronische Lebererkrankungen führen zu einem veränderten Sexualhormonstoffwechsel. Dies kann z. B. eine Feminisierung bei Männern und Unfruchtbarkeit und Amenorrhoe bei Frauen induzieren. In der klinischen Praxis sollte man daher die zahlreichen komplexen Wechselwirkungen zwischen der Leber und dem endokrinen System berücksichtigen. Hierfür müssen die entsprechenden Manifestationsformen erkannt werden, um Komplikationen frühzeitig zu therapieren und eine weitere Verschlechterung der Organsystems zu verhindern.
Polyglanduläre Autoimmunsyndrome umfassen verschiedene assoziierte Autoimmunerkrankungen, die klinisch variabel und zeitlich versetzt auftreten können. Rheumatische und/oder gastroenterologische Beschwerden bei Patienten mit Autoimmunendokrinopathien können auf eine zusätzliche rheumatische und/oder gastroenterologisch-hepatologische Autoimmunerkrankung hindeuten. Klinisch relevant sind insbesondere die Erkrankungen Autoimmungastritis, Zöliakie, Autoimmunhepatitis, rheumatoide Arthritis, Sjögren-Syndrom und systemischer Lupus erythematodes. Zusätzlich müssen jedoch unspezifische gastrointestinale und rheumatische Begleitsymptome der bestehenden Autoimmunendokrinopathie erwogen werden. Außerdem sind Erkrankungen des polyglandulären Autoimmunsyndroms, beispielsweise ein Diabetes mellitus Typ 1, gehäuft mit bestimmten gastroenterologischen Erkrankungen wie der bakteriellen Überwucherung assoziiert. Die optimale Versorgung von Patienten mit autoimmunen Systemerkrankungen erfordert eine komplexe differenzialdiagnostische Abklärung und unterstreicht die Bedeutung einer interdisziplinären Zusammenarbeit.
Background:
Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD) but estimates have varied substantially. We aim to examine the prevalence of CD in patients with ATD.
Methods:
Data source: Systematic review of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included "celiac disease" combined with "hypothyroidism" or "hyperthyroidism" or "thyroid disease".
Data synthesis:
Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups.
Results:
A pooled analysis, based on 6,024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% (95% CI=1.3-1.9%). Heterogeneity was large (I2 = 70.7%). The prevalence was higher in children with ATD (6.2%; 95%CI=4.0-8.4%), than in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6%; 95%CI=0.7-4.4%) than in hypothyroidism (1.4%; 95%CI=1.0-1.9%) Conclusions: About 1 in 62 patients with ATD have biopsy-verified CD. We argue that patients with ATD should be screened for CD given this increased prevalence.
To the Editor: Talley and Ford (Nov. 5 issue)(1) omit chronic abdominal-wall pain, a common disorder that is often attributed to abdominal cutaneous-nerve entrapment,(2) as a possible cause of epigastric pain. Chronic abdominal-wall pain is often localized to the upper abdomen - for example, in 33.9%(3) and 71.4%(4) of patients in two series. Before diagnosis, patients typically have fruitless and costly health care visits, diagnostic tests, and drug therapy.(3),(4) Characteristic features of the pain(2) and physical-examination findings described nearly 90 years ago(2)-(5) underlie the diagnosis, which can be confirmed by the response to a local anesthetic injection.(2), . . .
To the Editor: Talley and Ford (Nov. 5 issue)(1) omit chronic abdominal-wall pain, a common disorder that is often attributed to abdominal cutaneous-nerve entrapment,(2) as a possible cause of epigastric pain. Chronic abdominal-wall pain is often localized to the upper abdomen - for example, in 33.9%(3) and 71.4%(4) of patients in two series. Before diagnosis, patients typically have fruitless and costly health care visits, diagnostic tests, and drug therapy.(3),(4) Characteristic features of the pain(2) and physical-examination findings described nearly 90 years ago(2)-(5) underlie the diagnosis, which can be confirmed by the response to a local anesthetic injection.(2), . . .
Background:
The approach not to screen thyroid function of all pregnant women is mainly based on conflicting evidence of whether treatment of women with mild hypothyroidism is beneficial. However, there is consensus that all women with overt hypothyroidism (OH) and those with a thyrotropin (TSH) >10 mIU/L should be treated immediately, but data on these conditions are scarce. We assessed the prevalence of OH and a TSH >10 mIU/L during the first trimester of pregnancy.
Methods:
Thyroid function was assessed at 10-12 weeks gestation in 4199 Dutch Caucasian healthy pregnant women from three studies conducted in 2002, 2005, and 2013 from the same iodine sufficient area in the southeast of The Netherlands. We defined the first trimester specific cutoffs (2.5th-97.5th percentile) for TSH and free thyroxine (fT4) in thyroid peroxidase antibody (TPO-Ab) negative women in each study to determine the prevalence of women with OH and those with a TSH >10 mIU/L. We extrapolated these figures to the pregnant population of 2012 in The Netherlands, the United Kingdom, and the United States.
Results:
The prevalence of OH or a TSH >10 mIU/L in these 4199 women was 26 (0.62%) of whom 96% had (highly) elevated TPO-Ab titers. Based on the birth figures of 2012, if all pregnant women from The Netherlands, the United Kingdom or the United States were screened, the conservative annual number of cases would be 1000, 4500, and 25,000 respectively. However, the United Kingdom and parts of the United States have recently been demonstrated to be iodine deficient, which will result in even higher numbers.
Conclusion:
Our findings show that the discussion concerning thyroid screening during pregnancy should be based on data of overt hypothyroidism in healthy pregnant women. Screening of thyroid function is not expensive because all pregnant women have a standardized blood sample test at 8-12 weeks' gestation. Positive patients largely benefit from a cheap, safe, and effective treatment.
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC). These 21 recommendations focus on MTC patients with distant metastases and a detailed follow-up protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6-12 months, or at longer intervals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients.
Background:
Thyroid hormones are important determinants of energy expenditure, and in rodents, adipose tissue affects thyroid hormone homeostasis via leptin signaling. The relationship between thyroid hormones and nutritional status in humans has been assessed primarily in drastic dietary or bariatric surgery interventions, while limited information is available on serial assessment of this axis during moderate, prolonged dietary restriction.
Methods:
To evaluate the effects of moderate dietary restriction on thyroid hormone homeostasis, 47 subjects with a body mass index (BMI) of 25-45 kg/m(2) were enrolled in a longitudinal intervention study; 30 nonoverweight volunteers were also enrolled as controls. Overweight and obese subjects underwent a 12-month individualized dietary intervention aimed at achieving a 5-10% weight loss.
Results:
The intervention resulted in a 6.3±0.9 kg (6.5±1.0%) weight loss. At baseline, thyrotropin (TSH) and T3 concentrations correlated significantly with fat mass (R=0.257, p=0.024 and R=0.318, p=0.005, respectively). After weight loss, T3 decreased significantly (from 112.7±3.1 to 101.8±2.6 ng/dL, p<0.001) in the absence of significant changes in TSH or free T4 (fT4). The decrease in serum T3 correlated with the decrease in weight (R=0.294, p<0.001). The T3:fT4 ratio decreased significantly (p=0.02) in individuals who lost >5% body weight.
Conclusions:
T3 concentration closely correlates with individual nutritional status, and moderate weight loss results in a decrease in T3 with minimal changes in other thyroid hormone homeostasis parameters. The data suggest that a decrease in peripheral conversion of the prohormone T4 into its hormonally active metabolite T3 is at least in part responsible for the observed changes in thyroid hormone homeostasis.
Obesity and weight loss influence thyroid hormone physiology. The effects of weight loss by calorie restriction versus Roux-en-Y gastric bypass (RYGB) in obese subjects have not been studied in parallel. We hypothesized that differences in transient systemic inflammation and the catabolic state between the intervention types could lead to differential effects on thyroid hormone physiology.
We included 12 lean, 27 obese normal glucose tolerant (NGT) females and 27 obese females with type 2 diabetes mellitus (T2DM). Weight loss was achieved by restrictive treatment (Gastric Banding (GB) or high-protein-low-calorie (VLCD)) or by Roux-en-Y-Gastric Bypass (RYGB). Fasting serum leptin, thyroid stimulating hormone (TSH), triiodothyronine (T3), reverse T3 (rT3) and free levothyroxine (fT4) concentrations were measured at baseline, and 3 weeks and 3 months after start of the interventions.
Obesity was associated with higher TSH, T3 and rT3 and normal fT4 in all subjects as compared to controls. After 3 weeks, calorie restriction and RYGB induced a decline in TSH and a rise in rT3 and fT4. The increase in rT3 correlated with serum Il-8 levels. After three months, fT4 and rT3 returned to baseline levels, whereas TSH and T3 were persistently decreased as compared with baseline. No differences in the effects on thyroid hormone parameters between the interventions or between NGT and T2DM were observed at any time-point.
In summary, weight loss directly influences thyroid hormone regulation, independently of the weight loss strategy that is used. The effects may be explained by a combination of decreased leptin and changes in peripheral thyroid hormone metabolism.
Background: The rate of thyroid disorders is reported to be increased in patients with Ulcerative Colitis (UC) and Crohn's disease (CD) than the normal population. The purpose of this study is to evaluate the prevalance of Thyroid disorders in a group of patients with inflammatory bowel diseases (IBD). Material and Methods: 146 IBD patients (113 UC and 33 CD patients) and 66 healthy control subjects were enrolled into the study. Serum free T4 (FT4), free T3 (FT3), TSH and anti TPO levels of the patients were analyzed retrospectively and and compared with a control group. These cases were also investigated with thyroid ultrasound and nuclear (scintigraphy) imaging. Results: The mean age of IBD patients (76 women) was 42.9 ± 12.4 years. Among the control group 42 were female and their mean age was 40.9 ± 12.1 years. Thyroid gland disease was found in 14 (9.5%, 8 female, 6 male) of 146 IBD patients. The frequency of thyroid disorders has been found to be higher than the control group in patients with control group (14/146 vs. 1/66, p = 0.042). No statistically significant difference has been observed at the thyroid disorder rates between the UC and CD patients (11/113 vs. 3/33, p = 0.912). Hashimoto thyroiditis has been found at 4 (2.7%) of the IBD patients. Conclusion: In accordance with several works published in literature, we have found a higher rate of thyroid disease apperance at IBD patients.
Thyroid disorders are prevalent and their manifestations are determined by the dietary iodine availability.
Data from screening large population samples from USA and Europe.
The most common cause of thyroid disorders worldwide is iodine deficiency, leading to goitre formation and hypothyroidism. In iodine-replete areas, most persons with thyroid disorders have autoimmune disease.
Definition of thyroid disorders, selection criteria used, influence of age and sex, environmental factors and the different techniques used for assessment of thyroid function.
Increasing incidence of well-differentiated thyroid cancer. Environmental iodine influences the epidemiology of non-malignant thyroid disease.
Iodine supplementation of populations with mild-to-moderate iodine deficiency. An evidence-based strategy for the risk stratification, treatment and follow-up of benign nodular thyroid disease. Is there any benefit in screening adults for thyroid dysfunction?
Roux-en-Y gastric bypass (RYGB) modifies the anatomical structure of the upper intestine tract, reduces gastric acid secretion, and may impair LT4 absorption. The aim of this study was to evaluate the LT4 absorption in morbidly obese patients before and after RYGB.
Thirty morbidly obese patients were divided in two groups: The NS group included 15 patients before RYGB surgery (BMI = 43.1 ± 4 kg/m(2)), and the S group included 15 patients after surgery (BMI = 37.3 ± 4 kg/m(2)). Two baseline samples were collected, and 600 μg of oral LT4 tablets were administered. Blood samples were collected at 30, 60, 120, 180, 240, 300, and 1440 min. Serum-free T4 (FT4), total T4 (TT4), and TSH were measured at each time point. The increase in TT4, FT4, and TSH (ΔTT4, ΔFT4, and ΔTSH) was calculated, subtracting from the baseline mean value.
The pharmacokinetics parameters regarding LT4 absorption, maximum ΔTT4, and area under the curve(AUC) of both ΔTT4 and ΔFT4 were significantly higher in the S group compared with the NS group (p < 0.05). It was observed, however, that there was a significant delay in the absorption of LT4 in the S group. Basal serum TSH and leptin levels were higher in the NS group (p = 0.016 and 0.026, respectively), whereas basal serum TT4, FT4, ΔTSH, and the AUC of ΔTSH were similar between groups.
In this study, we have demonstrated that Roux-en-Y bypass surgery does not diminish LT4 absorption. A small but significant delayed absorption of LT4, however, was observed in patients after surgery.
Gastrointestinal motility and serum thyroid hormone levels are closely related. Our aim was to analyze whether there is a disorder in esophagogastric motor functions as a result of hypothyroidism.
The study group included 30 females (mean age +/- SE 45.17 +/- 2.07 years) with primary hypothyroidism and 10 healthy females (mean age +/- SE 39.40 +/- 3.95 years). All cases underwent esophagogastric endoscopy and scintigraphy. For esophageal scintigraphy, dynamic imaging of esophagus motility protocol, and for gastric emptying scintigraphy, anterior static gastric images were acquired.
The mean esophageal transit time (52.56 +/- 4.07 sec for patients; 24.30 +/- 5.88 sec for controls; P = .02) and gastric emptying time (49.06 +/- 4.29 min for the hypothyroid group; 30.4 +/- 4.74 min for the control group; P = .01) were markedly increased in cases of hypothyroidism.
Hypothyroidism prominently reduces esophageal and gastric motor activity and can cause gastrointestinal dysfunction.
The mechanisms behind the changes in serum triiodothyronine (T(3)), thyroxine (T(4)) and TSH that occur in the non-thyroidal illness syndrome (NTIS) are becoming clearer. Induction of a central hypothyroidism occurs due to a diminution in hypothalamic thyrotropin-releasing hormone. This can be signalled by a decrease in leptin caused by malnutrition and possibly a localised increase in hypothalamic T(3) catalyzed by altered expression of hypothalamic iodothyronine deiodinases D2 and D3. Data from D1 and D2 knockout mice suggest that these enzymes may have little contribution to the low serum T(3) found in acute illness. The decline in serum T(3) and T(4) in models of acute illness precedes the fall in hepatic D1, suggesting that much of the initial fall in these hormones may be attributable to an acute phase response giving rise to a reduction in the thyroid hormone binding capacity of plasma. When measured by reliable methods, changes in serum free T(4) and free T(3) are modest in comparison to the fall seen in total thyroid hormone. Thyroid hormone transporter expression is up-regulated in many models of the NTIS, thus if diminished tissue uptake of hormone occurs in vivo, it is likely to be the result of impaired transporter function caused by diminished intracellular ATP or plasma inhibitors of transporter action. In man, chronic illness leads to an upregulation of thyroid hormone receptor (THR) expression at least in liver and renal failure. In contrast, human and animal models of sepsis and trauma indicate that expression of THRs and their coactivators are decreased in acute illness.
Thyroid hormones define basal metabolism throughout the body, particularly in the intestine and viscera. Gastrointestinal manifestations of dysthyroidism are numerous and involve all portions of the tract. Thyroid hormone action on motility has been widely studied, but more complex pathophysiologic mechanisms have been indicated by some studies although these are not fully understood. Both thyroid hormone excess and deficiency can have similar digestive manifestations, such as diarrhea, although the mechanism is different in each situation. The liver is the most affected organ in both hypo- and hyperthyroidism. Specific digestive diseases may be associated with autoimmune thyroid processes, such as Hashimoto's thyroiditis and Grave's disease. Among them, celiac sprue and primary biliary cirrhosis are the most frequent although a clear common mechanism has never been proven. Overall, thyroid-related digestive manifestations were described decades ago but studies are still needed in order to confirm old concepts or elucidate undiscovered mechanisms. All practitioners must be aware of digestive symptoms due to dysthyroidism in order to avoid misdiagnosis of rare but potentially lethal situations.
Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When data that will withstand objective scrutiny are not available, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of choices in any health-care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. Expert opinion is solicited from the outset for the document. The quality of evidence upon which a specific recommendation is based is as follows: Grade A: Homogeneous evidence from multiple well-designed randomized (therapeutic) or cohort (descriptive) controlled trials, each involving a number of participants to be of sufficient statistical power. Grade B: Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case-control analytic studies, or well-designed meta-analysis. Grade C: Evidence based on clinical experience, descriptive studies, or reports of expert committees. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.
To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent...
Patients in the intensive care unit (ICU) typically present with decreased concentrations of plasma tri-iodothyronine, low thyroxine, and normal range or slightly decreased concentration of thyroid-stimulating hormone. This ensemble of changes is collectively known as non-thyroidal illness syndrome (NTIS). The extent of NTIS is associated with prognosis, but no proof exists for causality of this association. Initially, NTIS is a consequence of the acute phase response to systemic illness and macronutrient restriction, which might be beneficial. Pathogenesis of NTIS in long-term critical illness is more complex and includes suppression of hypothalamic thyrotropin-releasing hormone, accounting for persistently reduced secretion of thyroid-stimulating hormone despite low plasma thyroid hormone. In some cases distinguishing between NTIS and severe hypothyroidism, which is a rare primary cause for admission to the ICU, can be difficult. Infusion of hypothalamic-releasing factors can reactivate the thyroid axis in patients with NTIS, inducing an anabolic response. Whether this approach has a clinical benefit in terms of outcome is unknown. In this Series paper, we discuss diagnostic aspects, pathogenesis, and implications of NTIS as well as its distinction from severe, primary thyroid disorders in patients in the ICU.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Objective
To examine the seroprevalence, correlates, and characteristics of undetected coeliac disease in a large adult population sample in Cambridge, UK.
Methods
The Cambridge General Practice Health Study invited individuals from 12 general practices, aged 45–76 years, to attend for a health survey that included a bone density measurement, between 1990 and 1995. A total of 7550 participants’ serum samples were tested for antiendomysial antibody (EMA). Seroprevalence of undetected coeliac disease was based on EMA positivity. Differences between EMA positive and negative participants of various physiological correlates and reported characteristics were estimated by multivariate logistic and linear regression and adjusted for age, sex, social class, and smoking behaviour.
Results
The seroprevalence of undetected coeliac disease in this general population sample aged 45–76 was 1.2% (95% confidence interval (CI) 0.9–1.4). EMA positive participants (n=87) were on average slightly lighter by 2.2 kg (p=0.08), were more likely to have reported their general health as being “good or excellent” (odds ratio (OR) 1.76 (95% CI 0.90–3.46)), and were less likely to report being a current smoker (OR for current versus never 0.36 (95% CI 0.14–0.90)) than EMA negative participants. EMA positivity was associated with an 8% reduction in mean serum cholesterol (0.5 mmol/l; p<0.01) and reductions in mean haemoglobin (0.3 g/dl; p<0.01), total protein (1.0 g/l; p<0.05), and corrected serum calcium (0.02 mmol/l; p<0.05). There was an increased risk of osteoporosis in EMA positive participants (OR 3.1 (95% CI 1.3–7.2)) and of mild anaemia (OR 4.6 (95% CI 2.5–8.2)) compared with EMA negative participants.
Conclusions
Undetected coeliac disease is likely to affect approximately 1% of the population of England aged 45–76 years, a value similar to several other countries. Those affected report “better health” but they do have an increased risk of osteoporosis and mild anaemia. In contrast, they have a favourable cardiovascular risk profile that may afford protection from ischaemic heart disease and stroke.
Background
Weight loss in morbidly obese patients is associated with changes in thyroid function. Studies have demonstrated equivalent changes following bariatric surgery. Changes in thyroid function were reported following laparoscopic Roux-en-Y gastric bypass (LRYGB), biliopancreatic diversion (BPD), and laparoscopic adjustable gastric banding (LAGB). No data exists on changes in thyroid function following laparoscopic sleeve gastrectomy (LSG). The aim of the current study is to evaluate changes in thyroid function following LSG in patients with normal thyroid function.
Methods
Data were retrieved from a prospectively collected database of patients who underwent LSG for morbid obesity. Euthyroid patients were evaluated for changes in TSH and free thyroxine (FT4), 6–12 months after surgery. Correlation between changes in thyroid hormone levels, excess weight loss (EWL), and baseline TSH were evaluated.
Results
Thirty-eight patients were included in the study. Mean BMI decreased from 42.4 to 32.5 kg/m2 (P
Background:
Critically ill patients typically present with low or low-normal plasma thyroxine, low plasma triiodothyronine (T3), increased plasma reverse T3 (rT3) concentrations, in the absence of a rise in thyrotropin (TSH). This constellation is referred to as nonthyroidal illness syndrome (NTI). Although it is long known that the severity of NTI is associated with risk of poor outcomes of critical illness, the causality in this association has not been well investigated.
Summary:
In this narrative review, the different faces of NTI during critical illness are highlighted. Acute alterations are dominated by changes in thyroid hormone binding, peripheral thyroid hormone uptake, and alterations in the expression and activity of the type-1 and type-3 deiodinases. It was recently shown that at least part of these acute changes are brought about by concomitant macronutrient restriction, and this part appears adaptive and beneficial. However, the face of the NTI in the prolonged phase of critical illness is different, when patients are fully fed but continue to depend on intensive medical care. In that prolonged phase of illness, hypothalamic thyrotropin releasing hormone (TRH) expression is suppressed and explains reduced TSH secretion and whereby reduced thyroidal hormone release. During prolonged critical illness, and in the presence of adequate nutrition, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type-2 deiodinase activity, and increased sensitivity at the receptor level. Infusing hypothalamic releasing factors in these prolonged critically ill patients can reactivate the thyroid axis and induce an anabolic response.
Conclusions:
It is clear that the name "NTI" during critical illness refers to a syndrome with different faces. Tolerating the early "fasting response" to critical illness and its concomitant changes in thyroid hormone parameters appears to be wise and beneficial. This thus applies to the NTI present in the majority of the patients treated in intensive care units. However, the NTI that occurs in prolonged critically ill patients appears different with regard to both its causes and consequences. Future studies should specifically target this selected population of prolonged critically ill patients, and, after excluding iatrogic drug interferences, investigate the effect on outcome of treatment with hypothalamic releasing factors in adequately powered randomized controlled trials.
The healthy thyroid is vital for the liver metabolism. The liver also plays an important role in the metabolism of thyroid hormones. Thyroid and liver diseases can apparently have an adverse effects on each other organs. The main concept behind this present review is to analyze the coordination existed among thyroid and liver and the pathophysiology surrounding these two vital organs in human metabolism.
Context:
TSH receptor antibodies (TRAb) cause Graves' disease (GD) hyperthyroidism. Widely available TRAb measurement methods have been significantly improved recently. However, the role of TRAb measurement in the differential diagnosis of hyperthyroidism, the prediction of remission of GD hyperthyroidism, the prediction of fetal/neonatal thyrotoxicosis, and the clinical assessment of Graves' ophthalmopathy (GO) are controversial.
Evidence acquisition:
We reviewed and analyzed the literature reporting primary data on the clinical use of TRAb. We focused our analyses on clinical studies analyzing third-generation TRAb assays.
Evidence synthesis:
The performance of TRAb in the differential diagnosis of overt hyperthyroidism is excellent, with sensitivity and specificity in the upper 90%. TRAb can accurately predict short-term relapses of hyperthyroidism after a course of antithyroid drugs but are less effective in predicting long-term relapses or remissions. Pregnancies in women with GD with negative TRAb are highly unlikely to result in fetal hyperthyroidism, whereas high titers of TRAb in pregnancy require careful fetal monitoring. GD patients with GO frequently have high TRAb levels. However, there are insufficient data to use the test to predict the clinical course of GO and response to treatment.
Conclusions:
Third-generation TRAb assays are suitable in the differential diagnosis of hyperthyroidism. In GD, TRAb should be tested before deciding whether methimazole can be stopped. TRAb should be used in pregnant women with GD to assess the risk of fetal thyrotoxicosis. The use of TRAb in GO requires further studies.
Background:
The absorption of levothyroxine (LT4) is affected by many factors. Bariatric surgery is recommended in severely obese patients. The aim of this study was to determine the consequences of bariatric surgery on LT4 pharmacokinetic parameters, and to identify the regions of the gastrointestinal tract where LT4 is absorbed in patients with severe obesity before and after surgery.
Methods:
We studied 32 severely obese nonhypothyroid patients who underwent sleeve gastrectomy (SG; n=10), Roux-en-Y gastric bypass (RYGBP; n=7), or biliopancreatic diversion with long limbs (BPD-LL; n=15). Before surgery, from 8:00 a.m., blood samples were collected before and every 30 minutes after the oral administration of a solution of 600 μg of LT4. The same procedure was repeated 35 days after surgery. We estimated the pharmacokinetic parameters of LT4 before and after surgery, including the area under the curve (AUC), the peak thyroxine concentration (Cmax), and the time to peak thyroxine concentration (Tmax).
Results:
Following surgery, in the SG group, the mean AUC was higher than it was before surgery (18.97±6.01 vs. 25.048±6.47 [μg/dL]·h; p<0.01), whereas the values of Cmax and Tmax were similar to those before surgery. In the RYGBP group, mean AUC, Cmax, and Tmax were similar before and after surgery. In the BPD-LL group, mean AUC and Cmax were higher after surgery than before (14.18±5.64 vs. 25.51±9.1 [μg/dL]·h, p<0.001; 5.62±1.34 vs. 8.16±2.57 μg/dL, p<0.001, respectively), whereas Tmax was similar.
Conclusions:
The pharmacokinetic parameters of LT4 absorption are improved following SG and BPD-LL types of bariatric procedures. We conclude that the stomach, the duodenum, and the upper part of the jejunum are not sites for LT4 absorption, because in the above-mentioned bariatric procedures these are bypassed or removed.
A retrospective analysis of patients with medullary carcinoma of the thyroid was undertaken to determine the frequency and characteristics of diarrhea associated with this tumor. Of 111 patients, 36 had diarrhea as a clinical symptom either before diagnosis of the primary neoplasm or during the course of the metastatic malignant disease. The diarrhea was usually modest in frequency and loose or watery; two patients had mild steatorrhea. An additional two patients had significantly elevated urinary secretion of 5-hydroxyindoleacetic acid. Medullary carcinoma can produce a variety of circulating substances, some of which may have a significant effect on gastrointestinal motility.
BACKGROUND
The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial.METHODS
The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system.RESULTSFifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort.CONCLUSIONS
Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value. Cancer 2000;88:1139–48. © 2000 American Cancer Society.
Consider hypothyroidism as a cause of non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is increasingly recognised as a cause of chronic liver disease (affecting in some series 30-40% of the population1) and the commonest cause of abnormal liver function tests. The disease spans a spectrum of histopathological abnormalities, ranging from simple hepatic steatosis and steatosis with necroinflammation to steatosis with necroinflammation accompanied by varying degrees of fibrosis (which may progress to cirrhosis and its complications, including liver failure and hepatocellular carcinoma).2
Non-alcoholic fatty liver disease is characterised by a bright liver echo pattern on abdominal ultrasonography, and although it is often accompanied by raised liver enzymes, in many cases liver biochemistry is normal.3 Most patients are asymptomatic, with liver disease identified incidentally from abnormalities discovered in routine biochemistry tests or imaging performed for other reasons.
Although obesity is the commonest and primary metabolic cause, non-alcoholic fatty liver disease may arise secondary to several other endocrine disorders, including thyroid dysfunction, growth hormone deficiency, adrenal insufficiency, and polycystic ovary syndrome.4 It is important to consider and screen for underlying conditions in the diagnostic approach to non-alcoholic fatty liver disease.
We report the case of a young man diagnosed with non-alcoholic fatty liver disease in whom an underlying cause was discovered.
A 33 year old, previously healthy man presented to his general practitioner with a hot swollen ankle of recent onset. He had no other joint involvement and no systemic symptoms apart from general lethargy, which he attributed to his shift work. He did not drink alcohol and was not taking any prescribed medication or over the counter drugs. He had a history of untreated obstructive sleep apnoea. His general practitioner diagnosed gout and recommended treatment with non-steroidal anti-inflammatory drugs but arranged to check renal function and liver …
Obesity is positively associated with serum thyrotropin (TSH) concentrations at the high end of the normal range. The relationship between weight loss and thyroid function is less clear and studies to date have yielded inconsistent results. Our aim was to describe changes in thyroid function in obese people in relation to durable and significant weight loss after Roux-en-Y gastric bypass (RYGB) surgery. We recorded percentage of excess weight loss (% EWL), serum TSH and free thyroxine (fT4) before and median 4.5, 15 and 24 months after RYGB in 55 euthyroid patients with morbid obesity ranging in age from 18 to 64 years in a retrospective cohort analysis in a university hospital in Greater Manchester. Mean ± standard error preoperative weight was 135.13 ± 4.23 kg and BMI 48.08 ± 1.58 kg m−2. Patients attained nadir %EWL of 68% by median 15 months after RYGB. TSH was 2.00 ± 0.14 mU L−1 at baseline and 2.02 ± 0.22 mU L−1 at 24 months after RYGB (non-significant). Baseline fT4 was 13.46 ± 0.28 pmol L−1, and increased significantly to 15.14 ± 0.55 pmol L−1 at 24 months (P < 0.004). In conclusion, we report that weight loss after RYGB was accompanied by significant increase in serum fT4 but no change in TSH concentrations. Further study to elucidate the effect of significant weight loss on the thyroid axis is required.
A 49-year-old man was referred to our endocrine clinic because of rising thyroid-stimulating hormone (TSH) levels despite increasing doses of levothyroxine. The patient had a history of Graves disease, which had been successfully treated with radioiodine ablation 15 years earlier. Over the past several years, his serum TSH levels had risen to 31.5 (normal 0.4–4.5) mU/L, and the dose of levothyroxine he was prescribed had been increased to 225 μg per day, or 2.7 (usual recommended dose 1.6) μg/kg daily. The patient’s weight was 82 kg, and he did not report any change to his weight. The patient reported feeling well, and his physical exam was unremarkable. His level of free thyroxine was 15.8 (normal 10–25) pmol/L. The patient reported taking his antihypertensive medication (diltiazem) regularly as prescribed, and he was not taking any over-the-counter medications or herbal supplements.
To confirm our patient’s adherence to the drugs he had been prescribed, and to exclude impaired bioavailability of the medication, we performed a medically supervised test for the absorption of levothyroxine. The results of the test showed that only 30% of the medication administered was absorbed. We proceeded to rule out levothyroxine maldigestion related to gastric hypochlorhydria.
Laboratory investigations included a biochemistry panel and tests for serum levels of parathyroid hormone, 25-hydroxyvitamin D, ferritin, vitamin B12 and gastrin, all of which showed normal results. A serological test to determine the presence of Helicobacter pylori was negative, and the patient’s parietal cell antibody titers were normal. Given these results, it was unlikely that the patient’s treatment-refractory hypothyroidism was related to hypochlorhydria.
In our investigation of intestinal malabsorption, the screening serum test for gluten enteropathy was abnormal; the level of immunoglobulin A antibodies against transglutaminase was 75.4 (negative 16.0) units/mL. A subsequent endoscopic biopsy of the patient’s bowel was consistent with a diagnosis of celiac disease. The patient was directed to follow a low-gluten diet. The patient’s histological abnormalities resolved, and his serum level of TSH normalized with his usual dose of thyroxine (225 μg daily).
Because of the patient’s previous Graves disease, we decided to investigate for an autoimmune polyglandular syndrome. Subsequent tests showed elevated antiadrenal and 21-hydroxylase antibodies, suggesting autoimmune adrenalitis. A short intravenous adrenocorticotropic hormone (ACTH) stimulation test was consistent with diminished adrenal cortisol reserve.
Thyroid autoimmunity (TA) is often associated with coeliac disease (CD).
To evaluate, in children and adolescents with CD on a gluten-free diet (GFD): (1) the prevalence of TA; (2) the impact of TA on growth and the need for L-thyroxine (L-T4) treatment, during a longitudinal survey.
Between January and December 2005, 545 patients with CD, prospectively followed up until December 2007, and 622 controls were screened for TA. Antithyroperoxidase and antithyroglobulin antibodies were assayed and, if positive, serum free tri-iodothyronine, free thyroxine and thyroid-stimulating hormone (TSH) assays and thyroid ultrasound were performed. L-T4 was started if TSH was >5.5 mU/ml at two successive measurements.
There was no significant difference in TA prevalence between patients with CD on a GFD (10%) and controls (8.2%). Duration of GFD differed significantly in coeliac patients with TA in comparison with those without TA (7.9±0.9 and 10.2±0.3 years, p<0.001), but no significant difference was found for weight and height gain (1.8±1.0 vs 3.7±1.5 and 2.1±1.2 kg/year vs 4.0±1.1 cm/year, respectively). At the end of the follow-up an increase of 7% in the prevalence of patients with CD with TA requiring L-T4 was found.
TA seems no more common in paediatric and adolescent patients with CD on a GFD than in controls; its clinical evolution does not seem to impact on growth. Therefore, a long-term regular screening programme for thyroid disease may not be necessary for all patients with CD on a GFD, but only for those who are suspected of having thyroid diseases.
The central role of thyrotropin receptor antibodies (TRAbs) in the pathogenesis of Graves' disease has been recognised for several decades. However, the practical application of testing for TRAbs in clinical decision making remains the subject of controversy. The diagnosis of Graves' disease can be made in most cases simply based on a patient's clinical presentation. The TRAb test is therefore of most value in ambiguous clinical scenarios such as in the differential diagnosis of unilateral exophthalmos, euthyroid Graves' ophthalmopathy, subclinical hyperthyroidism, thyrotoxicosis associated with hyperemesis gravidarum, amiodarone-induced thyrotoxicosis and painless thyroiditis. It may also have a role in predicting the risk of a recurrence of Graves' disease following a course of antithyroid drug treatment. One further clinical utility of the TRAb test is in pregnancy where antibody titre measured during the third trimester is used to predict the risk of neonatal thyroid dysfunction. The TRAb titre not only aids in clinching a difficult diagnosis but can also help guide treatment in some patients. Although the TRAb assay has become more affordable in recent years, cost remains an important factor when considering its use routinely. Nonetheless, this is an underutilised blood test that could augment standard endocrine investigations in the differential diagnosis of hyperthyroidism.
Thyroid function and body mass are related, but the causal relationship remains unclear. Our objective was to investigate the longitudinal relationship between thyroid stimulating hormone (TSH) and body mass measures [body weight, body mass index (BMI), waist circumference (WC) and waist-hip-ratio (WHR)].
We used data from two waves of a population-based study: HUNT 2 (1995-1997) and 3 (2006-2008). Average follow-up time was 10·5 years. Multivariable general linear and logistic regression models were used to assess the relation between TSH and the body mass measures.
In total 9954 women and 5066 men without self-reported thyroid disease and TSH within the reference range (0·5-3·5 mU/l) at baseline and <10 mU/l at follow-up.
For each mU/l increase in TSH among women, weight increased 0·9 kg (95% CI 0·8, 1·1), BMI 0·3 kg/m(2) (95% CI 0·3, 0·4) and WC 0·6 cm (95% CI 0·3, 0·8). In men, the corresponding figures were 0·8 kg (95% CI 0·5, 1·0), 0·2 kg/m(2) (95% CI 0·2, 0·3) and 0·5 cm (95% CI 0·2, 0·8). In line with this, a weight gain of more than 5 kg was associated with a TSH increase of 0·08 mU/l (95% CI 0·06, 0·11) in women and 0·15 mU/l (95% CI 0·12, 0·18) in men. Women who lost more than 5 kg decreased their TSH by 0·12 mU/l (95% CI 0·09, 0·16) and men by 0·03 mU/l (95% CI -0.02, 0·09).
Weight gain is accompanied by increasing TSH, and weight loss in women is related to decreasing TSH.
Thyroid disease is common, and its effects on the gastrointestinal system are protean, affecting most hollow organs. Hashimoto disease, the most common cause of hypothyroidism, may be associated with an esophageal motility disorder presenting as dysphagia or heartburn. Dyspepsia, nausea, or vomiting may be due to delayed gastric emptying. Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth and improve with antibiotics. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudoobstruction. Ascites in myxedema is characterized by a high protein concentration. Graves' disease accounts for 60% to 80% of thyrotoxicosis. Hyperthyroidism is accompanied by normal gastric emptying with low acid production, partly due to an autoimmune gastritis with hypergastrinemia. Transit time from mouth to cecum is accelerated, resulting in diarrhea. Steatorrhea is due to hyperphagia and stimulation of the adrenergic system. Diarrhea in medullary carcinoma of the thyroid (MCT) may be due to elevated calcitonin, prostaglandins, or 5-hydroxyindoleacetic acid. Ileal or colonic function may be abnormal. The esophagus may be compressed by benign processes, but more often by malignancies. MRI and CT scans are the best diagnostic modalities. The gastrointestinal manifestations of thyroid disease are generally due to reduced motility in hypothyroidism, increased motility in hyperthyroidism, autoimmune gastritis, or esophageal compression by a thyroid process. Symptoms usually resolve with treatment of the thyroid disease.
Bilio-pancreatic diversion (BPD) induces permanent weight loss in previously severe obese patients through a malabsorptive mechanism. The aim of the study was to evaluate the modifications of circulating thyroid hormones after BPD, a surgical procedure which interferes with the entero-hepatic circulation of biliary metabolites.
Forty-five patients were studied before and 2 years after BPD. Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid antibodies, iodine urinary excretion, lipid profile, insulin and glucose plasma levels were assessed. The insulin-resistance HOMA IR index was calculated, and colour Doppler ultrasonography of the neck was performed.
The subjects (23%) had subclinical hypothyroidism prior to BPD (TSH levels above the normal range with normal fT3 and fT4 levels). After 2 years 40.42% of the population showed subclinical hypothyroidism, while 6.3% became frankly hypothyroid, all of them with no evidence of auto-immune thyroiditis. Most of the patients, who became sub-clinically hypothyroid only following BPD, had already thyroid alterations at the sonogram (multi-nodular euthyroid goiter and thyroidal cysts) prior to surgery.
BPD increases the prevalence of subclinical or even frank hypothyroidism, without causing a defect in thyroid function itself, through several integrated mechanisms. (1) It induces iodine malabsorption, which is partially compensated by iodine excretion contraction. (2) The entero-hepatic open circulation determines fT3 loss, which induces subclinical or frank hypothyroidism in patients with pre-existing thyroid alterations, interfering also with the weight loss progress. Iodine supplementation should be recommended in those patients reporting thyroid alterations at the sonogram prior to BPD, LT4 therapy should be strictly monitored in patients suffering of subclinical hypopthiroidism and T3 therapy should eventually be considered for patients diagnosed with frank hypothyroidism prior to BPD.
Studies on thyroid function in obesity yielded inconsistent results; high thyroid-stimulating hormone (TSH) levels were generally shown; high free triiodothyronine (fT)-3 or fT4 levels were described in some, but not in other studies. After weight loss, TSH and thyroid hormones have been described to either increase or decrease. Our aim was to describe TSH, fT3, and fT4 in obese subjects with normal thyroid function before and after durable and significant weight loss, obtained through laparoscopic gastric banding (LAGB), in comparison with nonobese subjects. TSH, fT3, fT4, and fT3/fT4 ratio (an index of D1 and D2 deiodinase activity), were evaluated in 99 healthy controls and in 258 obese subjects, at baseline and 6 months, 1 year, and 2 years after LAGB, together with indexes of glucose (glucose, insulin, homeostasis model assessment of insulin resistance index) and lipid (triglycerides, total and high-density lipoprotein-cholesterol) metabolism, and anthropometric measures (BMI and waist circumference). Under basal conditions, TSH, fT3, and fT4 were all in the normal range, but higher in obese than in nonobese subjects, and fT3/fT4 ratio was normal; with weight loss, fT3 and fT3/fT4 ratio decreased in obese subjects, while fT4 increased and TSH remained steady; all values were again within the normal range. Albumin and cholesterol levels remained steady, while triglycerides, insulin, and homeostasis model assessment of insulin resistance decreased, and high-density lipoprotein-cholesterol increased. These changes, however, do not modify TSH, letting us to hypothesize that the changes are due to a decrease of D1 and D2 deiodinase activities.
To provide a clinical update on Graves' hyperthyroidism and pregnancy with a focus on treatment with antithyroid drugs.
We searched the English-language literature for studies published between 1929 and 2009 related to management of hyperthyroidism in pregnancy. In this review, we discuss differential diagnosis of hyperthyroidism, management, importance of early diagnosis, and importance of achieving proper control to avoid maternal and fetal complications.
Diagnosing hyperthyroidism during pregnancy can be challenging because many of the signs and symptoms are similar to normal physiologic changes that occur in pregnancy. Patients with Graves disease require prompt treatment with antithyroid drugs and should undergo frequent monitoring for signs of fetal and maternal hyperthyroidism and hypothyroidism. Rates of maternal and perinatal complications are directly related to control of hyperthyroidism in the mother. Thyroid receptor antibodies should be assessed in all women with hyperthyroidism to help predict and reduce the risk of fetal or neonatal hyperthyroidism or hypothyroidism. The maternal thyroxine level should be kept in the upper third of the reference range or just above normal, using the lowest possible antithyroid drug dosage. Hyperthyroidism may recur in the postpartum period as Graves disease or postpartum thyroiditis; thus, it is prudent to evaluate thyroid function 6 weeks after delivery. Preconception counseling, a multidisciplinary approach to care, and patient education regarding potential maternal and fetal complications that can occur with different types of treatment are important.
Preconception counseling and a multifaceted approach to care by the endocrinologist and the obstetric team are imperative for a successful pregnancy in women with Graves hyperthyroidism.
Demand for bariatric surgery has risen exponentially and bariatric patients often have multiple indications for post-operative pharmacotherapy. The purpose of this study was to systematically review the published literature examining the effect of bariatric surgery on drug absorption. Studies were sought through searches of MEDLINE, EMBASE, the Cochrane Controlled Trials Registry and hand searches of reference lists. Two reviewers independently assessed studies for inclusion. Twenty-six studies (15 case reports/case series evaluating 12 different agents and 11 non-randomized controlled studies examining 15 different agents) were found. Evidence for diminished drug absorption was found in 15/22 studies involving jejunoileal bypass, 1/3 studies of gastric bypass/gastroplasty and 0/1 studies examining biliopancreatic diversion. The effect of bariatric surgery on drug absorption appears drug-specific. Drugs that are intrinsically poorly absorbed, highly lipophilic and/or undergo enterohepatic recirculation exhibited the greatest potential for malabsorption. The most consistent evidence for diminished absorption was found for cyclosporine, thyroxine, phenytoin and rifampin. Reduced drug absorption may occur post-bariatric surgery and this effect appears drug-specific. Individual dose-adjustment and therapeutic monitoring may be required. Rigorously conducted controlled studies are needed to evaluate the effect of modern bariatric procedures on drug absorption.
Thyroid hormones play an essential role in lipid mobilization, lipid degradation, and fatty acid oxidation. Hypothyroidism has been associated with nonalcoholic steatohepatitis; however, the association between thyroid diseases and hepatocellular carcinoma (HCC) in men and women has not been well established. We investigated the association between hypothyroidism and HCC risk in men and women in a case-control study, which included 420 eligible patients with HCC and 1104 healthy controls. We used multivariate unconditional logistic regression models to control for the confounding effects of established HCC risk factors. A long-term history of hypothyroidism (>10 years) was associated with a statistically significant high risk of HCC in women; after adjusting for demographic factors, diabetes, hepatitis, alcohol consumption, cigarette smoking, and family history of cancer, the odds ratio (OR) was 2.9 (95% confidence interval [CI], 1.3-6.3). Restricted analyses among hepatitis virus-negative subjects, nondrinkers, nondiabetics, nonsmokers, and nonobese individuals indicated a significant association between hypothyroidism and HCC, with an approximate two-fold to three-fold increased risk of HCC development. We observed risk modification among women with diabetes mellitus (OR = 9.4; 95% CI = 2.7-32.7) and chronic hepatitis virus infection (OR = 31.2; 95% CI = 6.3-153.2). A history of hyperthyroidism was not significantly related to HCC (OR = 1.7; CI = 0.6-5.1). We noted significant elevated risk association between hypothyroidism and HCC in women that was independent of established HCC risk factors. Experimental investigations are necessary for thorough assessment of the relationship between thyroid disorders and HCC.
Primary biliary cirrhosis (PBC) is frequently associated with autoimmune diseases, including thyroid disease, although it is uncertain that this association is higher than in other liver diseases.
We compared the prevalence and incidence of thyroid dysfunction (TD) in a series of patients with PBC (n=67) with patients with primary sclerosing cholangitis (PSC) (n=79) and non-alcoholic fatty liver disease (NAFLD) (n=97) seen in a tertiary referral centre who had previously participated in clinical trials.
At initial evaluation, prevalence of TD in PBC was 13% compared with 11% in PSC (P=0.71) and 25% in NAFLD (P=0.08). Incidence of TD was 2.9 patients per 100 person-years in PBC compared with 2.1 patients per 100 person-years in PSC (P=0.57) and 1.8 patients per 100 person-years in non-alcoholic liver disease (P=0.45). Older age, female gender, biochemical abnormalities and concurrent autoimmune disorders were not predictive of the development of TD.
TD was unexpectedly as common in patients with PBC as in patients with PSC and NAFLD, yet significantly more common than expected in the general population. Further investigation of thyroid disease in PSC and NAFLD is warranted.
High levels of substance P-like immunoreactivity were demonstrated by radioimmunoassay in the plasma and tumour of a patient with a medullary carcinoma of the thyroid.
In this paper, we have examined the relationship between the changes in the resting metabolic rate (RMR) and the changes in hepatic metabolism induced by hypothyroidism and 24 h fasting. The results show that hypothyroidism induces a significant decrease in RMR, while 24 h fasting reduces RMR in euthyroid but not in hypothyroid rats. We have also measured oxygen consumption in isolated hepatocytes from euthyroid and hypothyroid rats, fed or fasted for 24 h. The results show that hypothyroidism is characterized by reduced hepatic oxygen consumption. On the other hand, 24 h fasting induces an increase in oxygen consumption in both euthyroid and hypothyroid rat liver cells, although the respiratory rates of hypothyroid rats were lower than those of euthyroid rats. The above findings, as a whole, show that hypothyroidism and 24 h fasting have similar effects on RMR but opposite effects on hepatic metabolism. In addition, a normal thyroid state does not appear to be necessary for the observed changes in hepatic metabolism due to 24 h fasting.
