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Assessment of thyroid parameters in Alcoholic liver disease
Abstract
Normal level of thyroid hormone is important for normal hepatic function as it maintains the metabolism of bilirubin by playing a role in the enzymatic activity of glucuronyl transferase and by regulating the level of ligandin. The liver in turn glucuronidates and sulphates the thyroid hormone, excretes into bile and regulates their systemic endocrine effects. Therefore, hepatic dysfunction is commonly observed in patients with thyroid disease. Mean levels of Gamma-glutamyl transferase are increased in alcoholic cirrhosis with alcohol abuse of < 10 years duration. In this study thyroid function tests and liver function tests were performed on the 200 subjects, of which 100 subj ects were patients with Alcoholic Liver Disease, 100 were healthy controls and it was found that the serum tri-iodothyronine and free tri-iodothyronine levels were decreased and levels of Thyroid stimulating hormone were increased in patients with Alcoholic Liver Disease as compared to controls.
... This is in correlation with the studies by Punekar et al [20] , and Mobin A et al [24] where 71% and 76.3% of the patients showed reduced FT3 levels respectively. This finding also goes in consistency with D Costa L et al [25], Saleem WM et al [26] , Kayacetin E et al [27] , El Sawy AA et al [28] . Among the study population, 27 patients (27%) had reduced FT4, 69 patients had normal FT4(69%) and 4 had increased FT4 (4%). ...
Introduction: liver diseases are associated with endocrine disturbances and secondary dysfunction of endocrine organwhich apparent hormonal imbalance. This study aims to find out the correlation between the levels of FT3, FT4, TSH andseverity of liver disease in Chronic Liver Disease patients.Materials and Method: A total of 100 subjects with Chronic Liver disease satisfying inclusion and exclusion criteriavisiting medicine OPD and admitted in IPD of Muzaffarnagar Medical College during the period of 18 months was takenfor study which was a Cross Sectional Observational Study.Thyroid function tests which includes FreeT3, FreeT4, TSHwas done for all patients and tests such as Anti-TPO antibodies, USG neck, Doppler thyroid, FNAC thyroid was donewherever indicated The liver function tests including total and direct bilirubin, total protein and albumin, AST and ALT,APTT, PT, INR was done for all patients and USG abdomen and Oesophago-gastro-duodenoscopy was done whereverindicated.Results: The mean duration of liver disease in our study population was 5.92 ± 4.61 years (range 1-26 years). The meanFT3 levelwas 2.3059 ± 0.8883 p Mol/L. The mean FT4 level was1.1689 ± 1.0806 ng/dL . The mean TSH level was 3.3198 ±1.0173 m IU/mL The mean total bilirubin was 8.445 ± 4.3438 mg/dL .Conclusion: Thyroid dysfunction forms important part of spectrum of Chronic liver disease. Patients with liver diseaseshould be evaluated for thyroid dysfunction periodically.
... erefore, the changes of FT3 and FT4 were selected to observe the changes in thyroid hormone in patients with liver cirrhosis in meta-analysis. It was reported in the literature that the levels of FT3 and FT4 were low in patients with liver cirrhosis [29][30][31]. en, the study report showed that TSH levels were higher with liver cirrhosis [32,33]. Our results were consistent with these studies, and the results were reliable. ...
Background:
The aims of this study were to expound the effect of thyroid hormone on the occurrence of liver cirrhosis and the severity classification of liver cirrhosis with meta-analysis.
Methods:
A comprehensive search of PubMed, EMbase, The Cochrane Library, Web of Science, Google Scholar, CNKI, and WanFang Data databases and reference lists of retrieved articles was performed since the inception of each database until September 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias by RevMan 5.3 software. In continuous variable analysis, the standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated through a random-effect model.
Results:
Eighteen case-control studies involving 3336 subjects were included for review. The results of the meta-analysis showed free triiodothyronine (FT3) and free thyroxine (FT4) levels in the liver cirrhosis group were lower than the control group (SMD = -1.29, 95% CI [-1.85, -0.74], P < 0.001), (SMD = -0.61, 95% CI [-0.96, -0.26], P < 0.001), thyroid-stimulating hormone (TSH) levels in liver cirrhosis group were higher than the control group (SMD = 0.34, 95%CI [0.06, 0.63], P < 0.001) and that FT3 levels in Child-Pugh A VS B and Child-Pugh B VS C group were higher than the control group (SMD = 1.08, 95%CI [0.80, 1.37], P = 0.008), (SMD = 0.68, 95%CI [0.38, 0.98], P < 0.001).
Conclusions:
Cirrhosis has decreased FT3 and FT4 levels and increased TSH levels. FT3 levels correlate negatively with the Child-Pugh score, and it is a measure of the severity of liver cirrhosis dysfunction. FT3 serum levels of thyroid hormones are a prognostic marker in liver cirrhosis.
... 18 Some studies show that Free T3 (FT3) and Free T4 (FT4) levels are significantly lower and TSH levels are significantly higher in liver cirrhosis patients. [19][20][21][22][23][24] An association between thyroid disorder and PH has been reported, 25 but few studies have evaluated the association between thyroid function and PoPH. In the current study, patients with PoPH had higher TSH levels than those without, while Free T3 and Free T4 were in the normal range. ...
Purpose
Metabolic parameters are important for the development of portopulmonary hypertension (PoPH) during nonalcoholic steatohepatitis (NASH)-associated cirrhosis. This study evaluated patients with NASH-associated cirrhosis to determine metabolic risk factors for portopulmonary hypertension.
Patients and Methods
Data on 171 patients (120 men and 51 women) with NASH-associated cirrhosis who were seen in Florence Nightingale Hospital’s gastroenterology Clinic from 2009 to 2018 was obtained from the Hospital database. A pulmonary artery systolic pressure >35 mmHg was defined as PH (pulmonary hypertension) according to standard transthoracic echocardiography. Portal hypertension was diagnosed from clinical symptoms and dilated portal veins shown by abdominal ultrasound or computed tomography (CT). Pulmonary patients with portal hypertension were diagnosed with portopulmonary hypertension (PoPH).
Results
A total of 171 patients with NASH-associated cirrhosis were included in this study. Of these, 43 patients had PoPH. These patients had increased TSH (p=0.004), bilirubin (p=0.023) and triglyceride (p=0.048) levels, higher MELD scores (p=0.018) and decreased hemoglobin (p=0.05). MELD score and hemoglobin, total bilirubin, TSH, and triglyceride levels were all included in a multivariate logistic regression model and TSH levels were independently associated with increased risk of PoPH.
Conclusion
Increased TSH is an independent risk factor for PoPH.
... In several studies, low FT3 levels were the most consistent finding. In Deepika et al., D'costa and Dhume, Saleem and Wadea, El-Sawy and Tawfi, the levels of FT3 were significantly low in patients with liver cirrhosis [18][19][20][21]. ...
Background
Thyroid hormones modulate hepatic function through regulation of basal metabolic rate in addition; the liver metabolizes the thyroid hormones and regulates their endocrine effects.
Objectives
To assess thyroid functions in children with acute and chronic liver diseases.
Methods
85 studied children were divided into 4 groups; group 1 (20 children) with acute hepatitis (AH), group 2 (20 children) chronic liver disease1 (CLD1; relatively preserved liver functions including Child-Pugh stage A), group 3 (20 children) chronic liver disease2 (CLD2; includes Child-Pugh stage B or C), group 4 (25 children) controls. All groups were subjected to detailed history, physical examination, Complete blood count, liver, renal function tests, viral markers, and thyroid functions (FT3, FT4, TSH).
Results
Free T3 levels were lower in children with AH, CLD1 and CLD2. There was significant increase in TSH serum levels in CLD2.In acute hepatitis a negative correlation between serum free T4 and AST (r = -0.991), positive correlation between serum TSH and AST, VLDL, and cholesterol levels (r= 0.503, 0.533 and 0.498). A positive correlation between free T3 levels and prothrombin concentration (r= 0.991). Negative correlations between free T3 levels and PT, serum bilirubin and LDL serum levels in children with CLD2 (r= -0.992) (r= -0.902) and (r= -0.946)
Conclusion
Acute and chronic liver diseases affect thyroid function in children and is correlated with the disease severity.
... In several studies, low FT3 levels were the most consistent finding. In Deepika et al., [13] D'costa and Dhume, [14] Saleem and Wadea, [15] Kayacetin et al., [5] El-Sawy and Tawfi, [16] etc., the levels of FT3 were significantly low in liver cirrhosis patients. FT3 levels were significantly low also in all cirrhotic nonsurvivors compared to all cirrhotic survivors (P = 0.005). ...
Introduction
Liver plays an important role in the metabolism of thyroid hormones, as it is the most important organ in the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) by Type 1 deiodinase.
Materials and Methods
This case–control study included 100 decompensated liver cirrhosis patients (71 males and 29 females) and 100 apparently healthy controls (71 male and 29 female). Serum FT3, FT4, and thyroid-stimulating hormone (TSH) levels were measured using electrochemiluminescence immunoassay and analyses between cases versus healthy controls (Group 1) and further analyses in subgroups, cirrhosis with hepatic encephalopathy (HE) cases (n = 38) versus cirrhosis without HE cases (Subgroup 1), cirrhosis survivors (n = 84) versus cirrhosis nonsurvivors (Subgroup 2), HE survivors (n = 23) versus HE nonsurvivors (Subgroup 3). Results were also analyzed for severity of liver disease according to Child–Turcotte–Pugh (CTP) (Class A, B, and C), model for end-stage liver disease (MELD) score, and HE grades.
Results
Most common etiology was alcohol (46%) and presentation was gross ascites (74%). Cirrhosis patients had statistically significant lower level of FT3 (P < 0.0001) and FT4 (P < 0.0001) but had higher level of TSH (P < 0.0001) compared with the controls. Cirrhosis with HE (n = 38) had significantly lower lever of FT3 (P < 0.0001) compared with cirrhosis without HE (n = 62), whereas there was no statistically significant difference in FT4 (P < 0.09) and TSH (P < 0.60) levels. FT3 level significantly low in HE Grade 4 patients compared with HE Grade 1 patients (P = 0.0001). In all cirrhotic patients, FT3 and FT4 were negatively correlated, but TSH level was positively correlated with total leukocyte counts, serum total bilirubin, aspartate transaminase, alanine transaminase, globulin, prothrombin time (PT), blood urea, serum creatinine, CTP, and MELD score. Overall, the most common abnormality seen was low T3 (low FT3) syndrome 41% (41 out of 100) in cases, 50% (19 out of 38) in cirrhosis with HE, and 32% (5 out of 16) in Non-survivors cases.
Conclusion
The mean FT3 and FT4 levels were significantly decrease and mean TSH levels were significantly increase in liver cirrhosis patients compared to healthy controls. Level of FT3, FT4, and TSH also correlate with the severity of liver disease, level of FT3 can be used as prognostic marker for liver cirrhosis patients.
Thyroid hormones exert their effect on all tissue and modulate the rate of metabolic activity. Alterations in thyroid function can affect the various organ system of body and perturb measures like AST, ALT, GGT, ALP, CPK and LDH. Both hypothyroidism and hyperthyroidism have potentially fatal systemic manifestations. The main aim of study was to determine the relationship between thyroid alteration and serum enzymes level. The study included 110 subjects visiting Endocrinology Unit of Department of Biochemistry, MTH, Pokhara, with the request of TFT. Thyroid profile and serum enzymes were analyzed using standard kits. Each thirty hyperthyroid and hypothyroid cases show slight elevation of AST, ALT and GGT. However, the values were higher in hyperthyroid subjects. ALP, CPK and LDH were markedly elevated both in hyperthyroidism and hypothyroidism as compared to controls. In conclusion, conducted study demonstrated that there is a positive association between increased serum AST, ALT, GGT, CPK, ALP and LDH in hyperthyroidism and hypothyroidism.
These recommendations provide a data-supported approach. They are based on the following: (i) a formal review and analysis of the recently published world literature on the topic (Medline search); (ii) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines (1); (iii) guideline policies, including the American Association for the Study of Liver Diseases (AASLD) Policy on the development and use of practice guidelines and the AGA Policy Statement on Guidelines (2); and (iv) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to the standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the quality of evidence supporting the recommendations, the Practice Guideline Committee of the AASLD requires a Class (reflecting the benefit vs. risk) and Level (assessing the strength or certainty) of Evidence to be assigned and reported with each recommendation (Table 1, adapted from the American College of Cardiology and the American Heart Association Practice Guidelines) (3,4).
Thyroid hormones (THs) play critical roles in the differentiation, growth, metabolism, and physiological function of virtually all tissues. TH binds to receptors that are ligand-regulatable transcription factors belonging to the nuclear hormone receptor superfamily. Tremendous progress has been made recently in our understanding of the molecular mechanisms that underlie TH action. In this review, we present the major advances in our knowledge of the molecular mechanisms of TH action and their implications for TH action in specific tissues, resistance to thyroid hormone syndrome, and genetically engineered mouse models.
Thyroxine and tri-iodothyronine are essential for normal organ growth, development and function. These hormones regulate the basal metabolic rate of all cells, including hepatocytes, and thereby modulate hepatic function; the liver in turn metabolizes the thyroid hormones and regulates their systemic endocrine effects. Thyroid dysfunction may perturb liver function, liver disease modulates thyroid hormone metabolism, and a variety of systemic diseases affect both organs. We highlight the intricate relations between the thyroid gland and the liver in health and disease.
When an alcoholic becomes abstinent, his serum 7-glutamyltranspeptidase decreases to normal in a few weeks according to an exponential law with a constant of 4.1 to 14.5 · 10−2 days −1. It is thus valueless to establish 7-glutamyltranspeptidase reference values in a population in which all alcohol-drinking subjects have not been excluded.RésuméDès l'arrêt de l'intoxication, la 7GT des éthyliques diminue et revient à la normale en quelques semaines en suivant une loi exponentielle. La constante de décroissance varie de 4.1 à 14.5 · 10−2 jours −1. Ce phénomène rend illusoire toute tentative de détermination des valeurs de référence de la 7GT dans une population dont tous les sujets qui ont l'habitude de boire, n'auraient pas été exclus.
γ-Glutamyltransferase (GGT, EC 2.3.2.2) is an enzyme involved in glutathione metabolism and drug and xenobiotic detoxification. Using human hepatoma Hep G2 GGT cDNA as probe, we isolated a cDNA from a human pancreatic cDNA library. Analysis of the nucleotide sequences revealed a 2244-bp insert that includes an open reading frame of 1710 bp, encoding a protein identical to the Hep G2 and human placenta GGTs. Similarly, the 5' untranslated region, though shorter, is highly homologous to that of Hep G2 cDNA. These data suggest strongly that the same gene encodes human GGT in the placenta, Hep G2 and the pancreas. We further studied the distribution of the corresponding mRNA, called type I mRNA, in different human tissues. Using a highly sensitive method associating reverse transcription with specific amplification by polymerase chain reaction, cDNA was synthesized from total RNA isolated from the tissues and GGT specific fragments were amplified. We observed the presence of a specific cDNA fragment corresponding to the type I mRNA in the human tissues and cells tested, providing the evidence for a ubiquitous expression of this GGT mRNA in human tissues.
There are clinical and laboratory associations between thyroid and liver disease. Patients with chronic liver disease may have thyroiditis, hyperthyroidism, or hypothyroidism. Occasionally, alcoholics with active cirrhosis will show eye signs or laboratory evidence of hyperthyroidism, and yet be euthyroid on further testing. Patients with subacute thyroiditis or hyperthyroidism may have abnormalities in liver function tests which return to normal as the thyroid condition improves. In similar fashion, patients with acute or chronic liver disease may have changes in thyroid function tests which improves as the liver inflammation resolves. These interrelationships must be remembered if errors in patient care are to be avoided.
Thyrotoxicosis is defined as increased synthesis and secretion of thyroid hormones; when associated with defused goitre it is known as grave's disease. Hepatic changes in thyrotoxiosis are fatty changes, cirrhosis and centrilobular necrosis, resulting in elevated serum levels of liver specific enzymes ALT, AST and ALK. Objective of the study was to determine a correlation between plasma levels of 3 liver enzymes, and thyroid hormones in thyrotoxic cases, and matched controls in Hazara Division.
This study was conducted at Ayub Teaching Hospital Abbottabad from 1st July 2004 to 30th June 2007. The controls were selected from staff and students of Ayub Medial College Abbottabad. Fifty cases of thyrotoxicosis and 50 controls were included in this study by convenience sampling. Their thyroid profile for T3, T4, TSH and liver enzymes profile for ALT, AST, ALK were determined and analysed for a correlation.
Mean T3 of cases was 5.23 +/- 1.95 and of controls 1.95 +/- 0.35. Mean T4 of case was 248.88 +/- 62.75, and of controls was 113.40 +/- 19.01. Mean TSH of cases was 0.07 +/- 0.25 and that of controls was 2.24 +/- 0.80. Mean ALT of cases was 38.78 +/- 4.96 while that of controls was 23.98 +/- 5.27. Mean AST of cases was 39.76 +/- 5.05 and of controls was 26.52 +/- 4.49. Mean ALK of cases was 299.68 +/- 22.32 and of controls was 155.10 +/- 37.07.
Although liver enzymes levels were slightly elevated in many thyrotoxic cases, no significant correlation emerged between any of the thyroid hormones and any of the liver enzymes, either in cases or controls.
Thyroid function and creatine kinase activity was measured in 50 patients of thyroid disorders. Thedecreased serum levels of triiodothyronine (T3), thyroxine (T4) and increased level of Thyroid stimulatinghormone (TSH) in hypothyroid patients is well established but whether there is any correlation of creatinekinase (CK) with hypothyroidism is not well established. Therefore, a study of serum CK and thyroidprofile was carried out. In hypothyroid patients with decrease in serum T3, there is a significant increasein CK and findings were reversed in hyperthyroid patients. Serum creatine kinase levels thus, show aninverse relation with serum T3 and T4 levels.
Gamma-Glutamyl-3-carboxy-4-nitroanilide has been tested as donor substrate in the assay of gamma-glutamyltransferase activity in serum, glycylglycine being used as acceptor substrate. This donor substrate is highly solube even in neutral solutions, in contrast to the commonly used gamma-glutamyl-4-nitroanilide. The enzyme which apparently acts accordingly to a ping-pong bi bi kinetic mechanism, shows an absolute KM value for gamma-glutamyl-3-carboxy-4-nitroanilide of about 0.64 mmol/l, and for glycylglycine of about 13.4 mmol/l. The former KM value is significantly lower than that previously found for gamma-glutamyl-4-nitroanilide. The carboxyl derivative exhibits a marked competitive inhibitory effect on the gamma-glutamyltransferase. This effect is more pronounced than that of gamma-glutamyl-4-nitroanilide. The carboxyl derivative has somewhat higher absorbance in the range of wave length (400-420 nm) used to monitor the formation of the product. It is concluded that as donor substrate in the assay of gamma-glutamyltransferase activity of serum, the new derivative is not substantially superior to the gamma-glutamyl-4-nitroanilide conventionally used.
To evaluate the potential contribution of thyroidal secretion to the relative excess of triiodothyronine (T3) production in hyperthyroidism and to investigate the effects of treatment, iodine (127I), T3 and thyroxine (T4) were measured in digests of thyroid tissue obtained at surgery from 13 patients with Graves' disease. In 11 normal human thyroid glands, 127I content was 630 +/- 60 (all values mean +/- SE in mug/ wet weight) T4, 254 +/- 39 and T3 21 +/-3. The T4I was 26 +/- 3% of the total iodine and the molar ratio T4/T3 was 11 +/- 1. The 13 patients with Graves' disease were divided into three groups. Eleven were clinically euthyroid (Groups I and II) and had received either iodide or iodide plus a thiourea derivative before surgery. Two subjects (Group III) received only propranolol. In Group I (n = 8), mean thyroidal 127I content was 320 +/- 50, T4 was 115 +/- 9 and T3 22 +/- 4. The molar ratio T4/T3 was 5.9 +/- 1 and T4I was 26 +/- 2% of the total. Group II patients (3) had the lowest preoperative serum T4 (less than 2.5 mug/dl) and T3 (less than ng/dl) concentrations with TSH elevated in only one (7 muU/ml). Thyroidal 127I was 100 +/- 26, T49 +/- and T3 1.3 +/- 0.3. The % T4I was 5 +/-2. The two chemically hyperthyroid subjects had a mean tissue 127I of 450; T4, 295 and T3, 56, the T4/T3 ratio was 4.5 and % T4I was 42. There was no correlation between tissue 127I and T4/T3 within either the normal or Graves' disease group. Since adequate clinical and chemical control of hyperthyroidism with antithyroid drugs and iodine was attained in the 8 Group I subjects without a decrease in the % T4I or T3I below that of normal thyroids, it suggests that inhibition of iodotyrosine coupling is not required for this effect. The % T4I was below normal only in patients with marked suppression of serum T4 and T3 concentraions. The lack of correlation between tissue 127I and T4/T3 ratio in the treated patients suggests that the lower T4/T3 ratio in Graves' thyroids is independent of intrathyroidal iodine concentrations. This hypothesis is strengthened by the similarly low T4/T3 ratio in untreated subjects with near normal tissue 127I content. Assuming that the thyroid hormones are secreted in the ratios present in these digests, one can estimate that direct secretion by the thyroid could contribute most, of not all, of the excess T3 production in Graves' disease.
The relationship between alcoholic liver disease and circulating thyroid hormones was investigated in 124 hospitalized patients treated with placebo or propylthiouracil (PTU) for a maximum of 46 days in a double-blind study. Serum triiodothyronine (T3) levels on admission were significantly (P less than 10(-6) and inversely correlated with the severity of alcoholic liver disease. After hospitalization, changes in T3-levels in patients with low admission T3 significantly correlated (P less than 0.001) with the degree of spontaneous improvement of liver function (placebo group). Treatment with 300 mg of PTU daily (Orrego et al. Gastroenterology 76:105--115, 1979) markedly increased the rate of improvement in severely ill patients with low T3 on admission. In this group, serum T3-levels were also increased after PTU, but this increase did not correlate with the change in the patient's condition. It is suggested that the known inhibitory effect of PTU on peripheral deiodination of T4 to T3 is marked by a more marked improvement in liver function in this group. PTU treatment in this group reduced the free T4-index and increased TSH levels markedly (16%; P less than 0.02) toward levels found in hypothyroidism. PTU did not improve the condition of mildly ill patients with normal admission T3-levels, nor did it alter free T4-index or serum TSH levels in these patients. Serum T3-levels provide a sensitive indicator of the severity of alcoholic liver disease and of its response to conventional treatment. Serum T3-levels also distinguish between a group of patients, in whom low-dose PTU administration results in a beneficial effect, and another group, in whom no therapeutic effect of PTU is observed.
Liver dysfunction in hyperthyroid patients has not been well characterized. We analyzed the clinical records of 43 patients with hyperthyroidism to define the spectrum of clinical and liver test abnormalities. The patients were divided into three categories: (a) 18 patients with uncomplicated hyperthyroidism (HT) (b) 19 with hyperthyroidism and congestive heart failure (HT/CHF), and (c) 6 with hyperthyroidism and concomitant unrelated liver disease (HT/ULD). Hepatomegaly and/or spenomegaly were noted in 15 of 19 (79%) patients with HT/CHF as compared to 6 of 18 (33%) patients with HT and 3 of 6 (50%) patients with HT/ULD. Four patients with HT/CHF had ascites. Serum aminotransferase levels greater than 250 IU/L were noted in only 1 of 37 (3%) patients without unrelated liver disease. Patients with HT/ULD or HT/CHF had markedly low prothrombin time. Serum bilirubin levels as high as 323 microM were noted in patients with HT. No characteristic liver histology due to hyperthyroidism was noted. Severe liver test abnormalities, including deep jaundice and prolonged prothrombin time, can occur in patients with hyperthyroidism alone or with HT/CHF. This makes the diagnosis of concomitant, unrelated liver disease difficult until the hyperthyroidism has been controlled.
Introduction THE pituitary glycoprotein hormone TSH is synthesized and secreted by the thyrotropes in the anterior pituitary. TSH acts on the thyroid gland to increase the production of the thyroid hormones T3 and T4, which then act on organs throughout the body to modulate growth and various metabolic processes. High levels of the thyroid hormones in turn feed back at the level of the pituitary to suppress synthesis and secretion of TSH, and the thyroid hormone concentration is the most important physiological regulator of TSH levels (1–5). Additional regulation can occur via hypothalamic hormones such as TRH and dopamine, which stimulate and suppress TSH levels, respectively (1, 2) (Fig. 1). Thyroid and hypothalamic hormones interact to modulate both circulating levels of TSH and the transcription of the genes encoding the hormone. TSH is one of three pituitary glycoprotein hormones that consists of two dissimilar noncovalent subunits, α and β. The α-subunit is common to all three, including TSH and the...
The thyroid hormones T4, T3, rT3 and TSH were assayed in 134 adult patients evaluated and accepted as potential liver transplant candidates at the Universty of Pittsburgh from March, 1981 to December, 1983. The subsequent course of these patients was evaluated with respect to the levels of these hormones obtained at the time of acceptance for transplantation. T4 levels were increased significantly while their T3 levels were reduced (both p < 0.01) in those who survived and were discharged home as compared to either those who died waiting to be transplanted or died following the procedure. As a result, the ratio of T3/T4 was reduced markedly (p < 0.01) in those who were transplanted and survived as compared to those not transplanted or dying following transplantation. Importantly, the rT3 levels clearly separated (p < 0.01) those who would die prior to transplantation from those who would survive to be transplanted. Finally, the ratio rT3/T3 even more clearly separates those who will die prior to transplantation (p < 0.01) from the other two groups.
These data suggest that thyroid hormone levels, particularly rT3 levels, might be useful in setting priorities for which patients referred for a transplantation evaluation should be accepted into the program and in determining who among accepted patients should be operated upon in preference to others also accepted and waiting to be transplanted.
The clone C2 derived from a rat hepatoma cell line was used to investigate the mechanism of the induction of gamma-glutamyltransferase by ethanol. gamma-glutamyltransferase activity was detected in the C2 cell (1.4 mU per mg protein), and its kinetic properties were similar to normal rat liver gamma-glutamyltransferase. Ethanol provoked a dose- and time-dependent increase in gamma-glutamyltransferase activity, the maximum (2- to 3-fold) occurring 48 hr after the addition of ethanol (180 mM). In contrast, the activity of five other enzymes tested were not markedly modified by ethanol. Propanol was more potent than ethanol in inducing gamma-glutamyltransferase (5-fold stimulation), whereas methanol had no effect. The release of the enzyme in the medium was increased by ethanol and propanol. Several observations argue in favor of an increase in the biosynthesis of gamma-glutamyltransferase after ethanol addition: (i) ethanol increased the maximal velocity of the enzyme and did not modify the affinity for its substrates. It did not alter gamma-glutamyltransferase subcellular distribution; (ii) ethanol had no immediate effect when added directly to the assay mixture; (iii) the lag period and the time course of the increase in gamma-glutamyltransferase activity were those expected for an induction process; (iv) the increase in gamma-glutamyltransferase activity was prevented by cycloheximide and actinomycin D suggesting that ethanol acted at the transcriptional level. The effect of ethanol was not mimicked by acetaldehyde. In conclusion, we have demonstrated that ethanol increases the biosynthesis of gamma-glutamyltransferase in a rat hepatoma cell line which provides a new in vitro system.
The pattern of gammaglutamyl transpeptidase levels was studied in the sera of 25 subjects with hyperthyroidism and 11 subjects with hypothyroidism, before and after treatment, and in 14 age- and sex-matched control subjects. Gammaglutamyl transpeptidase levels were significantly increased in hyperthyroidism (65 +/- 59 U/l) (p less than 0.01) and significantly decreased under treatment (40 +/- 27 U/l) (p less than 0.001). Before treatment, gammaglutamyl transpeptidase levels correlated with alkaline phosphatase levels and 5'-nucleotidase levels, the correlation persisting after treatment with 5'-nucleotidase. Alkaline phosphatase levels significantly increased under treatment (p less than 0.01). The percentages of gammaglutamyl transpeptidase variation correlated with thyroxine (r = 0.44, p less than 0.03), triiodothyronine (r = 0.47, p less than 0.02) and latent fixation capacity (r = 0.44, p less than 0.03) variations. Subjects with hypothyroidism had significantly decreased gammaglutamyl transpeptidase levels before treatment (18 +/- 9 U/l, p less than 0.01). Alkaline phosphatase levels were significantly decreased before treatment, and significantly increased after treatment. For all subjects with hyperthyroidism of hypothyroidism, the percentages of gammaglutamyl transpeptidase variations correlated with thyroxine (r = 0.48, p less than 0.003) and triiodothyronine (r = 0.39, p less than 0.016) variations. These results suggest that variations in gammaglutamyl transpeptidase levels in hyperthyroidism and hypothyroidism are, at least in part, in relation with variations in thyroid hormone levels.
We measured serum total and free thyroxine (T4) and triiodothyronine (T3) concentrations, free T4 and T3 indexes, thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) concentrations in 98 patients hospitalized for acute medical illnesses. The free thyroxine index (FT4I) or TSH level was abnormal in 16 percent, but only 3 percent had thyroid disease. Serum fre T4 measurements by equilibrium dialysis were abnormal in 25 percent, but no additional patients who initially had abnormal concentrations of serum free T4 were subsequently proved to have thyroid disease. Patients with supranormal serum free T4 concentrations (21 percent) ahd higher serum T4, lower serum T3, and higher serum reverse T3 (rT3) concentrations than other patients, but the measured changes in serum T4, TBG and TBPA levels could only partly account for the magnitude of the free T4 elevation. In these acutely ill patients, an accurate diagnosis of thyroid disease could be achieved by determination of FT4I and TSH level and a history of medication usage. We conclude that other tests are rarely necessary for this purpose in a patient population such as this.
To reexamine the prevalence and sequential changes of liver and bone biochemical abnormalities in patients with hyperthyroidism.
A consecutive series of 95 patients with hyperthyroidism and 66 controls with euthyroid goiter seen during same period were studied. The patients were treated with propylthiouracil (PTU) 300 mg/day for 2 months, followed by 100-150 mg/day for 3 months and a subsequent maintenance dose of 100 mg/day. Serum aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin, ALP isoenzymes, and hepatitis markers were studied before therapy and at 2 and 5 months after PTU therapy was begun.
Seventy-two [75.8%, confidence interval (CI) 67.2-84.4%] of the 95 patients had at least one biochemical abnormality. AST, ALT, ALP, GGT, and bilirubin were elevated in 27.4%, 36.8%, 64.2%, 16.8%, and 5.3%, respectively. Of the 34 patients with ALT elevation, 62% showed gradual normalization of ALT, whereas 38% (CI 21.9-54.5%) showed transient, asymptomatic, but significant (p < 0.025) further elevation of ALT during PTU therapy. Overt hepatitis developed in one patient. None of these changes was due to hepatitis A, B, C, or delta virus infection or autoimmune hepatitis. Changes of serum GGT parallel those of ALT. In contrast, serum ALP (primarily bone isoenzyme) rose significantly (p < 0.01) as T4 and T3 levels declined at 2 months after therapy.
The results suggest that hyperthyroidism is often associated with abnormal biochemical tests, particularly ALP elevation, and thus may pose diagnostic confusion. The increase of bone isoenzyme accounts for the elevations in total ALP level before and during therapy. Serum ALT and GGT abnormalities usually subside during PTU therapy, but transient asymptomatic PTU hepatotoxicity occurs in one-third of the patients. Discontinuation of PTU is not required unless overt hepatitis develops.
The type I iodothyronine deiodinase (ID-I) in liver and kidney converts the prohormone thyroxine (T4) by outer ring deiodination (ORD) to bioactive 3,3',5-triiodothyronine (T3) or by inner ring deiodination (IRD) to inactive 3,3',5-triiodothronine (rT3), while it also catalyzes the IRD of T3 and the ORD of rT3, with the latter as the preferred substrate. Sulfation of the phenolic hydroxyl group blocks the ORD of T4, while it strongly stimulates the IRD of both T4 and T3, indicating that sulfation is an important step in the irreversible inactivation of thyroid hormone. This review summarizes recent studies concerning this interaction between sulfation and deiodination of iodothyronines, the characterization of iodothyronine sulfotransferase activities, the measurement of iodothyronine sulfates in humans and animals, and the possible physiological importance of iodothyronine sulfation.
Selenocysteine has been identified in the active center of types 1 and 3 iodothyronine deiodinases, two important enzymes regulating the formation and degradation of the active thyroid hormone, 3,5,3'-triiodothyronine (T3). Selenium is thus required for such complex processes as normal growth, brain development, and metamorphosis, all of which are thyroid hormone dependent. Structural and functional analyses of the type 1 deiodinase mRNA allowed identification of the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the 3' untranslated region of the mRNA. SECIS elements with conserved sequence and structural features are also present in the 3' untranslated regions of the mRNAs encoding selenoprotein P and the glutathione peroxidase family of selenoproteins. These elements are necessary and sufficient for directing selenocysteine incorporation into the deiodinases and the other mammalian selenoproteins.
T4 is the main product secreted by the thyroid follicular cells and is regarded as a precursor of the bioactive hormone T3, most of which is produced by outer ring deiodination of T4 in peripheral tissues. Both T4 and T3 are inactivated by inner ring deiodination. Three deiodinases have been identified with outer and/or inner ring deiodinase activities, which play an important role in the tissue-specific regulation of thyroid hormone bioactivity. All three enzymes have recently been shown to contain selenocysteine residues. The second important pathway of thyroid hormone metabolism involves the conjugation of the phenolic hydroxyl group with sulfate or glucuronic acid. The glucuronides are excreted in bile, acting as intermediates in the enterohepatic cycle and fecal excretion of thyroid hormone. Sulfation accelerates the deiodination of different iodothyronines by the type I deiodinase and, thus, initiates the irreversible degradation of the hormone. If type I deiodinases activity is low, e.g. in the fetus, T3 sulfate may function as a reservoir from which active T3 is recovered by tissue sulfatase activity.
Abnormal thyroid hormone concentrations are common in patients with serious nonthyroidal illnesses. Early evidence suggests that thyroid hormone levels may predict the prognosis for some patients. Abnormal thyroid function is usually reversible, but thyroid function tests should be repeated when the nonthyroidal illness is resolved. Whether active intervention using thyroid hormone supplements is beneficial or not remains controversial and requires future large-scale investigation.
Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.
Although overt thyroid dysfunction is associated with some liver abnormalities, there is a dearth of information on liver function tests across thyroid function tests. We assessed the relationship between serum liver enzyme activity and thyroid function tests in a cohort of adult individuals.
We performed a retrospective analysis on the database of the Clinical Chemistry Laboratory at the Verona University Hospital to retrieve results of serum liver enzyme activities [alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT)] and thyroid function tests (TSH and free T4), which have been performed on the whole cohort of outpatient adults consecutively referred by general practitioners for routine blood testing during the last 3 years.
Cumulative results for serum GGT, ALT and TSH concentrations were retrieved for 10 292 (68.3% females) outpatient adults with a wide range of age and thyroid function tests. Subjects were categorized according to serum TSH concentrations as follows: < 0.1, 0.1-0.35, 0.36-4.5, 4.6-10 and >10 mU/l. Serum GGT and ALT concentrations increased steadily across the increasing TSH categories (P < 0.0001 for trends), ranging from mean values of 36 to 62 U/l for GGT and from 29 to 41 U/l for ALT, respectively. Similarly, there was a negative, graded, relationship between serum GGT and ALT concentrations and free T4 categories. The results did not change after adjusting for gender, age, lipids and fasting glucose concentrations.
Our findings suggest that hypothyroidism and thyroid function tests, even within the reference range, are associated with slightly increased serum GGT and ALT activity concentrations.
Influence of thyroid hormones on biochemical parameters of liver function: a casecontrol study in North Indian population
- A Yadav
- S Arora
- V Saini
- M K Arora
- R Singh
- J Bhattacharjee
Yadav A., Arora S., Saini V., Arora MK., Singh R.,
Bhattacharjee J. Influence of thyroid hormones on
biochemical parameters of liver function: a casecontrol study in North Indian population. Internet
Journal of Medical Update. 2013;8(1):4-8
Alcoholic Liver Disease MedLinePlus: Trusted Health Information for You. Bethesda, MD: US National Library of Medicine & National Institutes of Health
- George F Longstreth
- David Zieve
Longstreth, George F.; Zieve, David. Alcoholic
Liver Disease. MedLinePlus: Trusted Health
Information for You. Bethesda, MD: US National
Library of Medicine & National Institutes of Health.
2009 October.
Transport of Thyroid Hormone and Cell Uptake In The Thyroid and Its Diseases
- Lj Degroot
- Pr Larsen
- S Refetoff
- Jb Stanbury
DeGroot LJ, Larsen PR, Refetoff S, Stanbury JB.
Transport of Thyroid Hormone and Cell Uptake In
The Thyroid and Its Diseases. 1984;62-66.
Alcoholic liver disease:AASLD Practice Guidelines
- O ' Shea
- Rs Dasarathy
- S Mccullough
O'Shea RS, Dasarathy S, McCullough AJ.
Alcoholic
liver
disease:AASLD
Practice
Guidelines. Hepatology. 2010 January; 51 (1):
307–28.
Alcoholic Liver Disease. MedLinePlus: Trusted Health Information for You
- George F Longstreth
- David Zieve
Longstreth, George F.; Zieve, David. Alcoholic
Liver Disease. MedLinePlus: Trusted Health
Information for You. Bethesda, MD: US National
Library of Medicine & National Institutes of Health.
2009 October.
Gammaglutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues
- C Courtay
- T Oster
- F Michelet
- A Visvikis
- M Diederich
- M Wellman
- G Siest
Courtay C, Oster T, Michelet F, Visvikis A,
Diederich M, Wellman M, Siest G. Gammaglutamyltransferase: nucleotide sequence of the
human pancreatic cDNA. Evidence for a
ubiquitous
gamma-glutamyltransferase
polypeptide in human tissues. Biochemical
Pharmacology.1992 Jun;
43 (12): 2527-2533.
Transport of Thyroid Hormone and Cell Uptake In The Thyroid and Its Diseases
- L J Degroot
- P R Larsen
- S Refetoff
- J B Stanbury
DeGroot LJ, Larsen PR, Refetoff S, Stanbury JB.
Transport of Thyroid Hormone and Cell Uptake In
The Thyroid and Its Diseases. 1984;62-66.
The liver in endocrine disorders. The Liver in Systemic Disease
- S Fagiuoli
- D H Van Thiel
Fagiuoli S, Van Thiel DH. The liver in endocrine
disorders. The Liver in Systemic Disease. 1993;
285-287.