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Assessment of hypothyroidism among adult patients suffering from beta thalassemia major
... Blood transfusion therapy plays an important role in thalassemia patients to treat anemia, but iron deposition as a side effect of transfusion can trigger problems in the body's endocrine and metabolic processes (Ibrahim et al., 2023). The Patho mechanism of endocrine gland damage is triggered by iron deposition directly in the endocrine gland itself as primary hypothyroidism or through the hypothalamic-pituitary axis resulting in central hypothyroidism (Haghpanah et al., 2021). ...
Aims: This study aims to analyze thyroid function in beta-thalassemia major patients receiving transfusions at Ulin Regional General Hospital, Banjarmasin, based on the duration of deferiprone therapy and the patients' age. Study Design: This is analytical observational research with a cross-sectional design. Place and Duration of Study: Pediatric patients diagnosed with beta-thalassemia major who received oral deferiprone iron chelation for at least one year at the Department of Child Health, Ulin Banjarmasin General Hospital, during the period from January 2022 to July 2024. Methodology: The study samples were collected using total population sampling, with a total of 37 participants. Bivariate analysis was performed using the Fisher's Exact test with a 95% confidence level. Results: The mean age of the total 37 samples was 11.12 ± 4.61 years, with a predominance of male patients at 64%. The average levels of ferritin and hemoglobin were 4990.07 ± 2856.37 ng/mL and 8.42 ± 1.35 g/dL, respectively. A total of 36 samples were in a euthyroid state and 1 sample was in a hypothyroid state. Bivariate analysis using Fisher's Exact test showed no significant association between age, the duration of deferiprone therapy, and thyroid function in beta-thalassemia major patients at Ulin Regional General Hospital, with p-values of 1.00 and 0.378, respectively. Conclusion: Most beta-thalassemia major patients at Ulin Regional General Hospital receiving deferiprone iron chelation therapy exhibited normal thyroid function, with only 1 patient found to be hypothyroid. There is no significant relationship between age or the duration of deferiprone therapy and thyroid function in beta-thalassemia major patients at Ulin Regional General Hospital.
Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care and follow-up, ideally in specialized centers and by multidisciplinary teams of experts. Despite the significant progress in TDT diagnosis and treatment over the past decades that has dramatically improved patients' prognosis, its management remains challenging. On one hand, diagnostic and therapeutic advances are not equally applied to all patients across the world, particularly in several high-prevalence eastern regions. On the other, healthcare systems in low-prevalence western countries that have recently received large numbers of migrant thalassemia patients, were not ready to address patients' special needs. Thalassaemia International Federation (TIF), a global patient-driven umbrella federation with 232 member-associations in 62 countries, strives for equal access to quality care for all patients suffering from thalassemia or other hemoglobinopathies in every part of the world by promoting education, research, awareness, and advocacy. One of TIF's main actions is the development and dissemination of clinical practice guidelines for the management of these patients. In 2021, the fourth edition of TIF's guidelines for the management of TDT was published. The full text provides detailed information on the management of TDT patients and the clinical presentation, pathophysiology, diagnostic approach, and treatment of disease complications or other clinical entities that may occur in these patients, while also covering relevant psychosocial and organizational issues. The present document is a summary of the 2021 TIF guidelines for TDT that focuses mainly on clinical practice issues and recommendations.
Disease-related complications and management are different among patients with thalassemia. This study was aimed to review the prevalence, clinical risk factors for the complications and the management in patients with thalassemia in Thailand. A multicenter cross-sectional study was conducted in patients with thalassemia aged ≥ 18 years old. Thalassemia-related complications and management were reviewed. The clinical parameters significantly associated with the complications were analyzed by logistic regression methods. The prevalence of thalassemia-related complications was 100% in patients with transfusion-dependent thalassemia (TDT) and 58.8% in patients with non-transfusion-dependent thalassemia (NTDT). Advanced age was statistically associated with extramedullary hematopoiesis in both TDT and NTDT patients. Splenectomy was a significant risk factor for pulmonary hypertension in both groups of patients. Severe iron overload started earlier in patients with TDT than NTDT and was associated with diabetes mellitus (adjusted odds ratio (AOR) = 6.2, p-value = 0.02). Disease-related complications are more prevalent in patients with TDT than patients with NTDT. Splenectomy and advanced age were important risk factors for developing major complications in both groups. Early screening and management for specific disease-related complications should be considered in patients with thalassemia according to their clinical risk factors.
Background
Hypothyroidism (HT) and hypoparathyroidism (HPT) are common endocrine complications in thalassemia major (TM) patients.
Objectives
In the present study, we assessed the frequency of HT and HPT in a population of TM patients in Southeast of Iran.
Methods
This cross sectional study was performed on 194 TM patients in Zabol, Sistan and Baluchestan Province, Iran, during February - July 2016. The demographic, clinical, and laboratory data were collected via interviews and history - taking. For hormone measurements, specific ELISA kits were used. Statistical analysis was performed in SPSS version 16.
Results
A total of 103 (53.1%) and 91 (46.9%) females and males were recruited in this study, respectively. The mean age of the patients was 15 ± 7.5 years. HT and HPT showed overall frequencies of 8.2% (18/194) and 18% (35/194), respectively. Subclinical and overt HT were observed in 13 (6.7%) and 5 (2.6%) patients, respectively. There was no significant association between HT and age, while patients with HPT were significantly older than those without HPT (20.1 ± 5.8 vs. 13.9 ± 6.2 years; P < 0.001). HPT was significantly associated with the mean received blood per transfusion (P = 0.009), total transfused blood per year (P = 0.01), splenomegaly (P < 0.001), splenectomy (P < 0.001), hepatomegaly (P = 0.01), and chelation regimen (P < 0.001). The ferritin level was correlated with neither HT nor HPT. Also, no significant difference was observed between patients with or without HT or HPT regarding the cooccurrence of either diabetes or hepatitis C virus (HCV) infection. In the multivariate analysis, splenectomy remained an independent risk factor for HPT after correction for potential covariates (OR, 6.5; 95% CI, 1 - 39.2; P = 0.04).
Conclusions
In patients with TM, HT was a complication with a relatively low frequency, while HPT was more common. Based on the findings, HPT was more frequent in older patients receiving regular blood transfusions, thereby necessitating close monitoring of these patients.
Introduction: It is well known that the older generation of adult TM patients has a higher incidence of morbidities and co-morbidities. At present, little information is available on adult TM patients with multiple endocrine complications (MEC). The main objectives of this longitudinal retrospective survey were: 1) to establish the incidence and progression of MEC (3 or more) in TM patients; 2) to compare the clinical, laboratory and imaging data to a sex and age-matched group of TM patients without MEC; 3) to assess the influence of iron overload represented by serum ferritin (peak and mean annual value at the last endocrine observation). Patients and methods: The study was started in January 1974 and was completed by the same physician at the end of December 2015. The registry database of the regularly followed TM patients from diagnosis included 145 adults (> 18 years). All TM patients were of Italian ethnic origin. Eleven out of 145 patients (7.5 %) developed MEC. Twenty-four other patients (12 females and 12 males) had a normal endocrine function (16.5 %) and served as controls. Results: In our survey, four important, relevant aspects emerged in the MEC group. These included the late age at the start of chelation therapy with desferrioxamine mesylate (DFO); the higher serum ferritin peak (8521.8 ± 5958.9 vs 3575.2 ± 1801.4 ng/ml); the upper proportion of splenectomized (81.8 % vs. 28.5%) patients and poor compliance registered mainly during the peripubertal and pubertal age (72.7 % vs.16.6 %) in TM patients developing MEC versus those without endocrine complications. Furthermore, a negative correlation was observed in all TM patients between LIC and final height (r:-0.424; p = 0.031). Conclusions: Our study supports the view that simultaneous involvement of more than one endocrine gland is not uncommon (7.5 %). It mainly occurred in TM patients who started chelation therapy with DFO late in life and who had irregular/poor compliance to treatment. Therefore, prevention of the endocrine complications through adopting early and regular chelation therapy appears mandatory for improving the quality of life and psychological outcome of these patients. When diagnosing and managing patients with MEC, it is of paramount importance that the multidisciplinary team have excellent knowledge relating to these complications. In ideal circumstances an endocrinologist with experience of TM will form part of the regular multidisciplinary team caring for such patients. Citation: De Sanctis V., Elsedfy H., Soliman A.T., Elhakim I.Z., Kattamis C., Soliman N.A., Elalaily R. Clinical and biochemical data of adult thalassemia major patients (TM) with multiple endocrine complications (MED) versus TM patients with normal endocrine functions: a
Aim: Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40–50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and
appearance of severe complications from the heart and endocrine glands that require special health care from well‑informed specialists.
Objectives: The aims of our study were to: (1) Imprint the clinical profile of long‑lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients’ health needs. Design: A retrospective cross‑sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic. Participants: Forty‑three long‑lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8–59.5 years; 23 females) were studied. Patients and Methods: An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained. Results: The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second
decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml). Conclusions: These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow‑up. Physicians’ strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide‑established long‑term treatment protocols for hypogonadism and osteoporosis are needed.
Objective:
Endocrine complications characterised patients with β thalassaemia (βT). In particular, thyroid dysfunction occurs frequently in βT major, but its long-term natural history is poorly understood.
Design:
A total of 72 βT patients were followed for 8 years. The incidence of thyreopathies, defined as the primary study endpoint, was assessed. The aim of this study was to analyse the prognostic role of ferritin for thyreopathies in patients with major and intermedia βT. The power of different iron chelators to treat iron overload and to prevent or reverse thyreopathies was also assessed.
Methods:
Patients were treated with chelators with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying thyroid dysfunction in thalassaemic patients. Kaplan-Meier curves were generated to assess incidence of thyreopathy. Adjusted risk estimates for thyreopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis.
Results:
PATIENTS WITH THYROID DYSFUNCTION WERE CHARACTERISED BY HIGHER FERRITIN WHEN COMPARED WITH PATIENTS WITHOUT THYREOPATHIES (1500 (8722336) VS 513 (370698) G/L; P0.0001). PATIENTS WITH FERRITIN VALUES ABOVE 1800G/L EXPERIENCED A SIGNIFICANTLY FASTER EVOLUTION TO ENDPOINT (LOG-RANK ((2)): 7.7; P=0.005). Ferritin predicted high risk of thyroid dysfunction independently of confounding factors (hazard ratio: 1.20; P<0.0001). The intensification of chelation therapy led to an amelioration of thyroid function.
Conclusions:
Ferritin represents a prognostic marker for βT patients and a predictive factor for progression to thyroid dysfunction. Intensive chelation therapy allows the prevention and reversibility of thyroid complications.
Despite improved hematologic care, multiendocrine dysfunction is a common complication of homozygous transfusion-dependent beta-thalassemia. In this study our goal was to estimate the prevalence of thyroid dysfunction in a large homogenous group of thalassemic patients. Two hundred patients with beta-thalassemia major (100 males and 100 females; mean age, 23.2 +/- 6.7 years; age range 11-43 years), regularly transfused and desferioxamine chelated, were randomly selected from a pool of approximately 800 patients with beta-thalassemia followed in our department. Thyroid function and iron-load status were evaluated by measurements of free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH), and serum ferritin levels. Of the subgroup of patients who proved to have normal thyroid hormone values, 26 (12 males, 14 females; mean age, 23.6 +/- 6.8 years; age range, 15-36 years) were randomly selected and underwent a standard TRH stimulation test. Thyroid dysfunction was defined as follows: overt hypothyroidism: low FT4 and/or FT3, increased TSH levels; subclinical hypothyroidism: normal FT4, FT3, increased TSH levels; exaggerated TSH response: normal FT4, FT3, normal basal TSH, deltaTSH > or = 21 microIU/mL (TSH levels measured prior and 30 minutes after intravenous TRH administration). Normal thyroid hormone values were found in 167 (83.5%) of the 200 patients studied. Eight (4%) of the remaining patients had overt hypothyroidisim, and 25 (12.5%) had subclinical hypothyroidism. Exaggerated TSH response to TRH was revealed in 7 of the 26 patients with normal hormone values tested (26.9%). Antithyroglobulin and anti-thyroid peroxidase (TPO) antibody titers were negative in 191 patients (95.5%). Mean ferritin levels in hypothyroid and euthyroid patients were 2707.66 +/- 1990.5 mg/L and 2902.9 +/- 1997.3 mg/L, respectively, (p = 0.61), indicating no correlation between ferritin levels and thyroid functional status. Mean ferritin levels in the patients who responded normally to TRH stimulation and in those who overresponded, were 2,586 +/- 1791 mg/L and 3,228 +/- 2473 mg/L, respectively (p = 0.46; NS). Thyroid failure is a rather rare endocrine complication in patients with beta-thalassemic from Greece. In our series, no case of central hypothyroidism was observed. No correlation was found between thyroid functional status and ferritin plasma levels. Approximately 1 of 5 beta-thalassemic patients with normal thyroid hormone values showed an exaggerated TSH response to TRH test. It is to be investigated how many of these patients will establish overt or subclinical hypothyroidism in the future.
Patients with multi-transfused thalassaemia major may develop severe endocrine complications due to iron overload. The anterior pituitary is particularly sensitive to iron overload which disrupts hormonal secretion resulting in hypogonadism, short stature , acquired hypothyroidism and hypoparathyroidism. Glucose intolerance and diabetes mellitus are also common in thalassaemic patients. The severity of the clinical manifestation and laboratory findings in thalassaemia largely depends on the genotype; thus homozygotes or compound heterozygotes for the mutations beta0 or beta+ depend for life on frequent transfusions. A multicenter study in Cyprus including 435 patients showed hypogonadotrophic hypogonadism in 32.5%, short stature in 35%, acquired hypothyroidism in 5.9%, hypoparathyroidism in 1.2% and diabetes mellitus in 9.4%. A slowing down of growth velocity and a reduced or absent pubertal growth spurt is observed in early adolescence leading to short adult height. Delayed or absent puberty and hypogonadism may result in fertility problems which affect enormously the life of thalassemics. Glucose intolerance in adolescence and diabetes mellitus later in life are also frequent complications mainly due to iron overload, chronic liver disease and genetic predisposition. Primary hypothyroidism and hypoparathyroidsm usually appear in the second decade of life; are related to iron overload and may be reversible at an early stage by intensive chelation. Osteopenia and osteoporosis due to a complicated pathogenesis represent prominent causes of morbidity in young adults of both genders with thalassaemia. Early recognition and prevention of the endocrine complications, by early and regular chelation therapy, is mandatory for the improvement of the quality of life and psychological outcome of these patients.
Purpose
Transfusion-dependent beta-thalassemia (TDT) patients suffer from various endocrinopathies. The main contributing factor associated with these complications is iron overload, secondary to frequent blood transfusions. To improve patients’ quality of life, we evaluated the prevalence of endocrine disorders while considering the associated factors for further assessment.
Methods
Seven hundred thirteen transfusion-dependent thalassemia patients with age range 10–62 years were enrolled in this study. Serum calcium, phosphorous, fast blood sugar, ferritin, 25-OH vitamin D, free thyroxin, thyroid-stimulating hormone and parathyroid hormone were assessed. Bone mineral density was measured by dual-energy X-ray absorptiometry.
Results
In total, 86.8% of the TDT patients suffered from at least one endocrinopathy. The prevalence of endocrinopathies in descending order of frequency was low bone mass (72.6%), hypogonadism (44.5%), diabetes mellitus (15.9%), hypoparathyroidism (13.2%), and hypothyroidism (10.7%). Age, body mass index and splenectomy were significantly associated with most of the endocrine disorders.
Conclusion
Endocrine complications are frequently observed in TDT patients. Splenectomy is a major risk factor and should be generally avoided unless it is highly indicated. Periodic surveillance of endocrine function and proper management of iron overload are advised.
Background: Thalassemia is a common genetic disorder which is associated with a lot of complications. Frequent blood transfusions result in increased iron deposition in various tissues leading to dysfunction of many organs of our body. Endocrine disorders constitute a major part of such complications increasing the morbidity of thalassemia manifold in the affected patients.Methods: This is a prospective study carried out in 64 thalassemia major patients attending thalassemia day care centre at SMGS Hospital Jammu from December 2014 to November 2015. Patients were examined and investigated for presence of one or more endocrine disorders including diabetes mellitus, hypothyroidism and delayed puberty.Results: Endocrine disorders were detected in a total of 22 patients. Diabetes mellitus was detected in 4.7% (n=3) patients, hypothyroidism in 4.7% (n=3) patients and delayed puberty was found in 26.6% (n=17) patients. Mean serum ferritin level was found to be 2885.5 ng/ml and there was no significant difference in patients affected with endocrine disorder and those without any endocrine disorder.Conclusions: Endocrine complications occur commonly in patients of thalassemia major. Increasing life span of thalassemia patients has increased the number of patients living with these disorders. A lot of morbidity occurs due to the presence of one or more of these disorders. Hence timely detection of these disorders by screening in all patients of thalassemia should be done to initiate treatment at the earliest so as to limit the morbidity caused by these disorders.
Remarkable advances in blood transfusion and iron-chelation therapy have improved and prolonged the survival of patients with thalassemic syndromes. Because of this increase in mean survival, new therapeutic strategies have been designed in order to limit the most important complications involving heart, liver and endocrine tissues. Endocrine disorders are rarely reported as cause of death in thalassemics but they can worsen the quality of life of these patients. Most authors have reported high incidence of endocrine abnormalities in thalassemics and the iron overload is frequently indicated as the most important pathogenetic factor [1]. De Sanctis et al. [2], in a multicenter study, reported that endocrine abnormalities involve more than 50% of thalassemic patients. Particularly the incidence of thyroid disorders has shown a large variability, according to the findings reported in the various studies [3–5]. The aim of this study was to evaluate the thyroid function in 58 thalassemic patients in order to evaluate possible correlations with age, serum ferritin values, and liver impairment.
Long-term survival of patients with thalassemia major has been improved by regular transfusion and chelation therapy [1]. However, multiple endocrine disturbances, including thyroid dysfunction, attributed to the chronic transfusional iron overload and causing morbidity and mortality in thalassemic patients are still a major problem [2, 3]. The purpose of the present study was to determine the incidence of pituitary-thyroid dysfunction and its relationship to various clinical and laboratory measurements in thalassemic patients.
: The incidence of endocrine dysfunction in relation to the detailed genotype of β-thalassaemia is investigated in this study. In addition, the association of genotype to specific clinical features of β-thalassaemia is examined, together with the relationship between serum ferritin levels and endocrine complications. Ninety-seven patients were included, all with transfusion dependent β-thalassaemia. Patients were divided into 2 categories; group 1 consisted of patients with a β0/β0 genotype with or without a concomitant α-globin gene deletion as well as patients with β0/β+ or β+/β+ genotype and normal α-globin chain synthesis. Group 2 included patients with β+/β+ or β+/β0 genotype and one α-globin chain deletion and those with a moderate amount of β-globin chain synthesis (β++) and normal α-globin chain synthesis. The results showed that group 1 patients were more likely to have severe clinical disease (p = 0.005). Sixty-four patients (66%) had at least 1 endocrine disorder and 39 (40%) had multiple endocrinopathies; the most common abnormality was hypogonadotrophic hypogonadism (HH). There was a significant association between patients with group 1 genotypes and the presence of HH and impaired glucose tolerance or diabetes. A positive correlation was demonstrated between serum ferritin concentrations and the presence of thyroid or parathyroid dysfunction.
Abstract The importance of spleen iron and splenectomy has been investigated in 28 male and 19 female β-thalassemia major (β-ΤΜ), adult patients. In one study an increase from about five (615g;19.5 × 11.0 × 6.0 cm) to twenty (2030g; 25.0 × 17.5 × 12.0 cm) times higher than the normal size and weight of spleen has been observed in twenty patients following splenectomy. In a second study the mean size for the liver (19.4cm, range 13.5-26.0 cm) and spleen (15.6 cm, range 7.0-21.0 cm) measured by magnetic resonance imaging (MRI) and by ultrasound imaging for spleen (15.1 cm, range 9.0-21.0 cm) of sixteen patients indicated that on average the spleen is about 80% of the size of the liver. In the third study, comparison of the iron load using MRI T2* and iron grading of stained biopsies indicated that substantial but variable amounts of excess iron are stored in the spleen (0-40%) in addition to that in the liver. Following splenectomy, total body iron storage capacity is reduced, whereas serum ferritin (P= 0.0085) and iron concentration in other organs appears to increase despite the reduction in the rate of transfusions (P=0.0001). Spleen iron seems to be cleared faster than liver iron using effective chelation protocols. Spleen iron is a major constituent of the total body iron load in β-ΤΜ patients and should be regularly monitored and targeted for chelation. Normalization of the body iron stores at an early age could maintain the spleen in near normal capacity and secondary effects such as cardiac and other complications could be avoided.
273 patients with thalassaemia major followed from diagnosis in the Ferrara Centre were divided into 3 cohorts (C) according to the year of birth (C1=1954-1964, 85 patients; C2=1965-1974, 129 patients; C3=1975-2001, 59 patients) in order to study the trends of endocrine complications. Menarche occurred in 52 out of 112 patients (46%), without significant differences among the 3 groups, at the mean age of 13.9+/-1.4 years. Sixty-five percent of these patients had secondary amenorrhoea at the mean age of 18.8+/-3.7 years. In males complete pubertal development occurred in 48% of patients (C1:31%, C2: 44%, C3: 63%, p<0.05) followed by secondary hypogonadism in 24% of patients above 21 years of age. Primary (80%) and central 20%) hypothyroidism were diagnosed in 31% of patients (C1: 55%, C2: 31.5%, C3: 13.4%, p<0.05), diabetes mellitus (DM) in 17% of patients (C1: 28.6%, C2: 17.2%, C3: 3.4%, p<0.05), and hypoparathyroidism in 10.6% of cases (C1: 18.7%, C2: 10.1%, C3: 3.4%, p<0.05). No difference was found in patient mean age of diagnosis of hypothyroidism, DM or hypoparathyroidism (20.4+/-8.2 years, 19+/-5 yrs and 18.5+/-5.8 yrs respectively) but in all three groups age at diagnosis significantly increased over time (hypothyroidism and DM: p<0.001; hypoparathyroidism: p<0.01). Over time the prevalence of hypothyroidism, diabetes mellitus and hypoparathyroidism increased to 24.4%, 14.7%, and 6.7%, respectively, at the time of the study. Incidences peaked in the early 1980's, and declined in the following years (primary hypothyroidism from 6.5% in 1981 to 0.9% in 2007, p<0.01; DM from 3.9% in 1986 to 0.8% in 2007, p<0.05; hypoparathyroidism 2.4% in 1984 to 0% in 2007, p<0.01) and correlated with the decrease in annual mean serum ferritin levels in all patients (p<0.001). The main risk factors associated with endocrine complications were high serum ferritin levels, poor compliance with desferioxamine (DFO) therapy, early onset of transfusion therapy (only for hypogonadism) and splenectomy (only for hypothyroidism). Serum ferritin levels of approximately 2000 ng/ml were found to correlate with hypogonadism, and 3000 ng/ml for hypothyroidism, hypoparathyroidism and DM. The incidences of hypothyroidism, DM and hypoparathyroidism were not significantly different in 18 patients on long term treatment with deferiprone (DPO) compared with 64 patients continuously treated with DFO, from 1995 to 2007. In conclusion, our longitudinal study shows that in the last 30 years in the Ferrara Centre the incidences of hypothyroidism, diabetes mellitus, and hypoparathyroidism declined, and pubertal development in males with thalassemia major improved in patients, on DFO treatment, born after 1976. The efficacy of alternative chelation regimes with deferiprone or deferasirox to monotherapy with desferioxamine remains to be established.
Sixty transfusion-dependent thalassemic patients were studied by simultaneous measurement of circulating thyroid hormones, basal thyroid-stimulating hormone (TSH) and TSH response to thyrotropin-releasing hormone with the aim of evaluating the frequency of hypothyroidism in such patients, and the relationship between hypothyroidism and compliance with treatment and iron overload. Thyroid failure was present in 31 of the 60 patients. A correlation was found between impairment of thyroid functions, duration of chronic hypoxia and the activities of various transaminases. The results of this study emphasize the importance of early evaluation of thyroid function in thalassemic patients and suggest that anemia and hypoxia may potentiate the toxicity of iron deposition in endocrine glands.
Amiodarone may induce hyper- or hypothyroidism. Patients with beta-Thalassemia Major (beta-Thal) have an increased prevalence of primary hypothyroidism and often require amiodarone for hemosyderotic cardiomyopathy. Aim of this study was to retrospectively evaluate thyroid function in beta-Thal adult patients on long-term amiodarone. The study group consisted of twenty-two (21 males, 1 female; age: 23-36 yr) beta-Thal patients submitted to long-term (3-48 months) amiodarone therapy from January 1991 to July 1996. Controls included 73 beta-Thal patients (23 males and 50 females aged 25-35 yr) not treated with amiodarone. In all cases serum free thyroid hormones, thyrotropin and thyroid autoantibodies were evaluated. A higher prevalence of overt hypothyroidism (5/22 [22.7%]) as compared to controls (3/73 [4.1%], p=0.02) was found in beta-Thal patients < or = 3 months after starting amiodarone, while the prevalence of subclinical hypothyroidism was similar in amiodarone-treated (18.2%) and untreated (15%) beta-Thal patients. Overt hypothyroidism resolved spontaneously after amiodarone withdrawal in 1 case, while the remaining patients were maintained euthyroid on amiodarone by L-thyroxine administration. After 21-47 months of amiodarone therapy, 3 patients (13.6%) developed thyrotoxicosis (2 overt and 1 subclinical), which remitted shortly after amiodarone withdrawal. No case of hyperthyroidism was observed in beta-Thal controls (p=0.012 vs amiodarone-treated patients). In conclusion, amiodarone administration is often associated in adult beta-Thal patients to a rapid progression of the pre-existing subclinical hypothyroidism, but transient thyrotoxicosis may also be observed after a longer period of therapy. These findings should be carefully considered in the management of these patients.
Short stature is common in thalassaemia major. Hypothyroidism resulting from haemosiderosis has been implicated, but this complication has not been investigated in Sri Lanka.
To estimate the thyroid hormone level of patients with thalassaemia major and correlate height with age, iron status and thyroid hormone level.
University Unit, Lady Ridgeway Hospital, Colombo.
A cross-sectional comparative study.
33 patients with thalassemia major (19 males) aged 2 years 6 months to 23 years were studied. 21 healthy age and sex matched subjects from the same neighbourhood as the patients served as controls. Anthropometric measurements, skeletal maturity, serum ferritin and thyroid hormone levels were estimated.
The height centiles and height standard deviation scores (SDS) were significantly lower in the patient group. Skeletal maturation was delayed by more than 1 year in 69% of patients. Undernutrition was not seen. The height SDS showed significant reduction with age (r = -0.5, 95% confidence limit -0.72 to -0.18) and with elevated serum ferritin levels (r = -0.8, 95% confidence limit = -0.9 to 0.62). Serum ferritin levels were elevated in the entire patient group with 70% being heavily iron overloaded (serum ferritin > 7000 ng/ml). The thyroxine (T4) levels were within the normal range in all 33 patients. The TSH levels were normal in 32 patients. The patient too had a normal T4 level. The control group had TSH levels comparable with the patients.
Hypothyroidism was not present in our iron overloaded thalassaemic patients. The thyroid hormone levels were similar in patients with mild and heavy iron overload. We conclude that routine surveillance for hypothyroidism is unnecessary in thalassaemia major. Other causes for delayed skeletal maturation and short stature need investigation.
As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with apparently identical genotypes can have many different clinical conditions even in simple monogenic disorders. Beta thalassemia occurs when there is a deficiency in the synthesis of beta globin chains. The clinical manifestations of beta thalassemia are extremely diverse, spanning a broad spectrum from severe anemia and transfusion-dependency to the asymptomatic state of thalassemia trait. The remarkable phenotypic diversity of the beta thalassemias is prototypical of how a wide spectrum of disease severity can be generated in single gene disorders. The most reliable and predictive factor of disease phenotype is the nature of the mutation at the beta globin locus itself. However, relating phenotype to genotype is complicated by the complex interaction of the environment and other genetic factors at the secondary and tertiary levels, some implicated from family studies, and others, as yet unidentified. This article reviews the clinical and hematologic diversity encountered in beta thalassemia with an overview of the modifier genes that moderate their disease expression.
Longitudinal study on thyroid function in patients with thalassaemia major
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Thyroid disorders in thalassemia: an update, current trends in endocrinology
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Vincenzo De, S., Ashraf, S., Saveria, C., et al., 2012. Thyroid disorders in thalassemia: an update, current trends in endocrinology. Curr. Trends Endocrinol. 6, 17e27.