Assessment of thyroid function in two hundred patients with beta-thalassemia major.

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.     

Hashimoto's thyroiditis: countrywide screening of goitrous healthy young girls in postiodization phase in India

Countrywide salt iodization, to prevent nutritional iodine deficiency, has been achieved in India recently. The current study was planned to evaluate the prevalence of goiter and thyroid autoimmunity and assess thyroid functional status in a cohort of 6283 healthy schoolgirls from different parts of the country in the postiodization phase. Goitrous girls (n = 1810; 28% of subjects) were investigated for serum T4 and TSH, antithyroid microsomal antibody (TMA) and antithyroglobulin antibody (TGA), urinary iodine excretion, and cytomorphology by fine-needle aspiration cytology (FNAC). FNAC carried out successfully in 764 goitrous girls revealed juvenile autoimmune thyroiditis (JAT) in 58 (7.5%), which included Hashimoto's thyroiditis in 43 (5.6%) and focal lymphocytic thyroiditis in 15 (1.9%). TMA and TGA estimated in 722 goitrous girls detected significantly positive titers of TMA (> or =1:1600) and TGA (> or =1:160) in 52 (7.2%) and 4 (0.55%) girls, respectively. Only 29 (67.4%) girls with Hashimoto's thyroiditis were TMA positive. In patients with FNAC-proven JAT, overt clinical and biochemical hypothyroidism was seen in three (6.5%) and subclinical hypothyroidism in seven (15%). Subclinical hyperthyroidism was detected in 5.1% cases of JAT, and none had overt hyperthyroidism. No definite correlation was seen between urinary iodine excretion and thyroid autoimmunity.     

碘致甲状腺功能减退症的流行病学对比研究

目的：研究不同碘摄入量人群的临床甲减和亚临床甲减患病率,方法：选择盘山,彰武和黄骅3个农村社区（分别为低碘,适碘和高碘地区（）,在入户问卷调查的基础上行采样调查,共问卷调查16287人,采样3761人,所有采样对象接受体格检查,,测定血清TSH,甲状腺过氧化的酶抗体（TPOAb),甲状腺球蛋白抗体（TGAb)和甲状腺球蛋白（TG）,测定尿碘浓度及进行甲状腺B超检查,TSH异常者测定FT4,FT3和TSH受体抗体（TRAb)。结果：盘山,彰武和黄骅社区成人尿碘水平分别为103．1ug/L,374.8ug/L和614.6ug/L,盘山,彰武和黄骅社区临床甲减患病率分别为0．27％,0．95％和2．05％, 临临床甲减的患病率分别为0．91％,2．90％,和5．96％,引起临床甲减的主要原因是自身免疫性甲状腺炎,亚临床甲减中三分之一患者甲状腺自身抗体阳性,结论：横断面的流行病学对比研究证实碘摄入量增加有可能导致甲状腺功能减退症患病率增加。     

轻度碘缺乏城市食盐加碘后甲状腺疾病流行病学调查研究

 目的 评价轻度碘缺乏城市贵阳食盐加碘25年后的碘营养状态及各种甲状腺疾病的患病情况。
方法 采用分层整群抽样方法,抽取贵阳市云岩区宅吉社区20岁及以上居民1509人,测定其血清促甲状腺素（TSH）、游离T₃、游离T₄、甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TgAb）水平、尿碘水平及甲状腺B超检查;同时抽取8~10岁学龄儿童80名,测定其尿碘水平。
结果 8~10岁儿童尿碘中位数为228.7 μg/L。成人临床甲状腺功能减退症（甲减）、亚临床甲减、临床甲状腺功能亢进症（甲亢）及亚临床甲亢的患病率分别为1.79%、14.12%、1.52%及1.06%,亚临床甲减的患病率显著高于临床甲减（P < 0.05）;TPOAb及TgAb的阳性率分别为14.38%及 13.59%,自身免疫性甲状腺炎的患病率为4.44%。甲状腺肿大患病率为1.06%,其中,弥漫性甲状腺肿（0.86%）较结节性甲状腺肿（0.20%）多见（P < 0.05）。
结论 食盐加碘25年后,贵阳市处于碘超足量状态,成人临床甲减、亚临床甲减、甲状腺自身抗体阳性及自身免疫性甲状腺炎的患病率均较高。     

The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area.

OBJECTIVE: The aim of the present study was to analyze the current status of morphologic and functional thyroid abnormalities in a previously iodine-deficient area. METHODS: The population based Study of Health in Pomerania (SHIP) comprised 4310 participants, aged 20-79 years. Thyroid function (thyrotropin [TSH] free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. Data from 3941 participants with no known thyroid disorders were analyzed. RESULTS: The median iodine urine excretion was 12.4 microg/dL. The rate of decreased serum TSH levels (<0.3 mIU/L) was 11.3%; 2.2% of participants had suppressed serum TSH levels (<0.1 mIU/L). The prevalence of subclinical hyperthyroidism was 1.8%, the prevalence of overt hyperthyroidism 0.4%. Elevated TSH levels were found in 1.2% of individuals. Subclinical hypothyroidism was observed in 0.5%, overt hypothyroidism in 0.7% of the sample. Elevated TPOAb were detected in 7% of subjects, 4.1% of participants had TPOAb greater than 200 IU/mL. The prevalence of goiter was 35.9%. An inhomogeneous echo pattern was detected in 35.2% and nodules in 20.2% of participants. Diffuse autoimmune thyroiditis was diagnosed in 47 subjects (1.2%). CONCLUSION: There are a number of thyroid disorders in this previously iodine-deficient region. Further studies are required to investigate the change of thyroid disorders during iodine supplementation programs.     

河北某水源性高碘地区成人甲状腺疾病的流行病学调查

目的：调查水源性高碘地区－河北省黄骅市歧口村、高头村≥14岁人群甲状腺疾病的流行状况,方法：入户问卷调查4230人的基础上,采样调查1074人,所有采样调查对象均详细填与甲状腺疾病调查表,接受体检查和B超检查,测定血清促甲状腺激素（TSH）、甲状腺自身抗体（TAA）和甲状腺球蛋白（TG）,留取空腹尿样测量尿碘、TSH异常者测定甲状腺激素和TSH受体抗体（TRAb）。结果：采样人群的尿碘中位数为614．61μg/L。临床甲状腺功能亢进症（甲亢）和亚临床甲亢的患病率分别为1．21％和1．12％;临床甲亢中92．3％为Graves病所致,亚临床甲亢中75％TRAb阳性;回顾性分析普遍食盐碘化前后临床甲亢平均年发病率差异无显著性,临床甲状腺功能减低症（甲减）和亚临床甲减的患病率分别为1．96％和6．05％,患者TAA阳性率分别为85．71％和29．23％。采样人群甲状腺过氧化物酶抗体（TPOAb）和甲状腺球蛋白抗体（TGAb）阳性率分别为11．6％和9．3％。弥漫性甲状腺肿,结节性甲状腺肿、单发结节和多发结节的患病率分别为3．26％、2．61％、1．77％和6．4％。甲状腺癌病率为91．58／10万,结论：在尿磺中位数为614．61μg/L的碘营养状态下,甲状腺功能减退症和甲状腺癌患病率显著增高,提示这一碘摄入量并不安全。     

Transitory subclinical and permanent hypothyroidism in the course of subacute thyroiditis (de Quervain)

Sixty-two patients affected with subacute thyroiditis (SAT) were followed for a mean period of 14 months (range 1-40), by monitoring thyroid hormone levels in basal condition, pituitary TSH reserve, antithyroglobulin (TgAb) and antimicrosomal antibodies ( MsAb ), in order to study the natural course of the disease and to characterize its intermediate phase. In the first phase the mean serum iodothyronine levels were within normal limits, nevertheless elevated T3 and T4 levels were detected in 34 (54%) and 20 (32%) patients, respectively. The next phase was characterized by normal serum iodothyronine levels; TRH stimulation test, however, showed a significant increase of pituitary TSH reserve in 35 (56%) patients. All parameters reverted gradually towards normal in all but 3 patients, who showed overt permanent hypothyroidism. TgAb and MsAb were positive in the early stage in 15 (24%) and 40 (64%) patients, respectively, disappearing at the end of the follow-up period in all but one patient; this particular patient belonged to the group of 3 patients affected with permanent hypothyroidism. Our data indicate that the onset of SAT is characterized by transient hyperthyroidism and that transient subclinical hypothyroidism characterizes the next phase. TRH stimulation test is required for the diagnosis of the latter and for the identification of the few who develop permanent hypothyroidism.     

The prevalence of thyroid dysfunction in a population with borderline iodine deficiency

OBJECTIVE: We lack information on the influence of borderline iodine deficiency on the occurrence of thyroid dysfunction. Iodine deficiency has been reported to facilitate the development of toxic nodular goitre, whereas a high iodine intake may increase the prevalence of autoimmune hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of a random sample of the general population in our region with borderline iodine deficiency 2656 (65%) of 4073 men and women aged 41 to 71 years participated. Records were made of previous thyroidal illness. Blood samples were drawn for thyroid parameters and TPO Ab values. Iodine and creatinine was assessed in casual urine samples. RESULTS: Previous or present hyperthyroidism was reported by 1.4% of the participants whereas 0.6% had unknown biochemical hyperthyroidism. All cases of undiagnosed hyperthyroidism were among women. Previously diagnosed and treated hypothyroidism was reported by 1.0% and undiagnosed hypothyroidism was found in 0.4%. Subclinical hyperthyroidism was found in 1.3% and subclinical hypothyroidism in 0.7%. TPO Ab titres >200 kU/l were found in 16.9% of the women and 6.6% of the men, and 83% of participants with TSH >5 mU/l had TPO Ab titres >200 kU/l. Participants with TPO Ab titres between 100 and 200 kU/l had no increased frequency of thyroid dysfunction. The median iodine excretion rate was estimated as 103 microg/day. Serum TSH values were higher in women than in men and showed higher dispersion in women as well as in old age. Serum free T3 was found to be higher in women than in men and increased with age. Serum free T4 showed no sex difference but values increased with increasing age. CONCLUSION: In our region with borderline iodine deficiency more than 5% of the general population has clinical or subclinical thyroid dysfunction. We found a relatively high prevalence of hyperthyroidism, especially previously undiagnosed disease, but a low prevalence of hypothyroidism as would be expected in an area of iodine deficiency. Hypothyroidism was related to TPO Ab titres of >200 kU/l. Thyroid hormone levels varied with age and sex.     

Socio demographic wise risk assessment of thyroid function abnormalities in far western region of Nepal: A hospital based descriptive study

Objective

To know the status of thyroid disorder in population of far western region of Nepal.

Methods

A total of 808 cases (133 men and 675 non pregnant women) were included and study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalgunj Teaching Hospital between 1st January, 2011 and 28th February, 2012. The variables collected were age, sex, and thyroid function profile including free T3, free T4 and TSH.

Results

The percentage of thyroid disorders was 33.66% in far western region of Nepal. The people were highly affected by overt hyperthyroidism (14.9%) followed by subclinical hyperthyroidism (9.9%). The subclinical hypothyroidism was 7.9% while 1% overt hypothyroidism only in a far western region of Nepal. Females were highly affected by overt hyperthyroidism (17.8%), followed by subclinical hyperthyroidism (11.9%). A total of 5.9% females were affected by subclinical hypothyroidism while only 1.2% by overt hypothyroidism. Males were affected only by subclinical hypothyroidism (18.0%) in this present study. High number of total thyroid dysfunction was observed in 21 to 40 years of age groups, followed by 41 to 60 years of age groups. Less than 40 years people were having 1.03, 0.99, 2.51 and 1.15 times risk of developing overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism and subclinical hyperthyroidism respectively compared to greater than 40. Female were having 0.29 times risk of developing subclinical hyperthyroidism compared to male. But overt hyperthyroidism, subclinical hyperthyroidism and overt hypothyroidism female were having more risk of developing compared to male.

Conclusions

The thyroid disorder, especially overt hyperthyroidism (14.9%) and subclinical hyperthyroidism (9.9%) was high. Further studies are required to characterize the reasons for this high prevalence.     

Thyroid function and amiodarone. Consequences on dysthyroidism testing

Amiodarone induces a decrease in serum T3 whereas T4 and rT3 increase. An increase of the thyroid iodine content (TIC) is observed in all patients at the exception of those who develop hypothyroidism under treatment. Actually, no method are available to predict an induced thyroid toxicosis (ITT) and there is no reason to perform systematically thyroid function tests except if past of the patient or clinical or morphological thyroid examinations suggest thyroid abnormality. In case of suspicion of ITT it is necessary to perform T4, T3 determinations and a TRH test. TIC measurement can be useful in order to eliminate a subacute or silent thyroiditis. Hypothyroidism is generally observed in patients with autoimmune thyroiditis. Antithyroid antibodies and TSH determinations after some months of treatment can detect subclinical hypothyroidism which is due to a high susceptibility to iodide.     

Statut iodé et fonction thyroïdienne chez 330 femmes de la région niçoise évaluées en deuxième partie de grossesse

Background

Iodine deficiency (ID) is still common in Western Europe and its prevention remains a challenge, particularly during pregnancy.

Methods

We studied 330 pregnant women in the third trimester of pregnancy for ioduria (UIE) and thyroid tests (TSH, fT4). We collected information on personal history of thyroid disease and treatment with thyroid hormones or iodinated pregnancy tablets.

Results and discussion

Median UIE was 64 μg/l, reflecting inadequate iodine intake in our population. According to the UIE threshold used for diagnosis (100 to 150 μg/l), ID was present in 74.3% to 85.8% of women; 5.4% had excessive iodine intake, including one taking iodine fortified tablets. Only 8.8% had adequate intake, suggesting that current strategies to eradicate ID are inefficient in our country. Among the 22 women taking iodine supplements, only three had adequate UIE and four had UIE below the detection level, which could suggest either poor compliance or insufficient supplementation. Median fT4 was 12.3 pmol/l (8-20.1) and TSH 1.93 mUI/l (0.24-6.57). We used different thresholds proposed in the literature to diagnose: hypothyroxinemia: 41.2% were less than 12 pmol/l, 10% less than 10.3 pmol/l and 1.8% less than 9 pmol/l (lower limit of our reference range); subclinical hypothyroidism: 26.3% had TSH greater than 2.5 or 3.9% greater than 4 mUI/L, 1.2 to 13% had combined low fT4 (<9 pmol/l or <12 pmol/) and higher TSH (>2.5 mUI/l). There was no correlation between UIE and thyroid tests, nor maternal predicting factors for ID.

Conclusion

ID is common in our population. The wide range of hypothyroxinemia and subclinical hypothyroidism prevalence should also trigger reflection of diagnostic thresholds and therapeutic intervention.     

Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin,thyroid reserve,and thyroid antibodies

Subclinical hypothyroidism is a frequent syndrome affecting about 10 million people in the United States. The management of such patients is open to debate. In a long-term prospective study we analyzed the spontaneous course and the value of predictive factors in the development of overt thyroid failure. We studied 82 female patients with subclinical hypothyroidism prospectively over a mean observation period of 9.2 yr. TSH, thyroid hormones, thyroid reserve after TRH administration, thyroid antibodies, and clinical parameters were assessed at yearly intervals. The cumulative incidence of overt hypothyroidism was calculated using life-table analysis and Kaplan-Meier curves. According to the initial serum TSH concentrations (TSH, 4-6/>6-12/>12 mU/liter), Kaplan-Meier estimates of the incidence of overt hypothyroidism were 0%, 42.8%, and 76.9%, respectively, after 10 yr (P < 0.0001). When only patients with TSH levels greater than 6 mU/liter were analyzed, the cumulative incidence was 55.3%. The incidence of overt hypothyroidism increased in patients with impaired thyroid reserve (52.6% vs. 38.1%; P = 0.05) and positive microsomal antibodies (58.5% vs. 23.2%; P = 0.03). This prospective long-term study demonstrates that only a part of the cohort of patients with subclinical hypothyroidism develops overt hypothyroidism over time and that a major group remains in the subclinical state after 10 yr. The measurement of TSH, microsomal (thyroperoxidase) antibodies, and thyroid reserve allows initial risk stratification for the development of overt thyroid failure (risk ratio ranging from 1.0-15.6). Our study helps to recognize the spontaneous course of subclinical hypothyroidism and in the identification of patients most likely to progress to overt hypothyroidism.     

A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure

OBJECTIVE: Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism. DESIGN: A population study including 4649 randomly selected subjects. MEASUREMENTS: Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. RESULTS: Thyroid volume was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (> 3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0.001) was due to confounding by sex and age (multivariate model, P = 0.23). CONCLUSION: We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.     

Thyroid function and histology in forty-five patients with hyperthyroid Graves' disease in clinical remission more than ten years after thionamide drug treatment

Thyroid function was determined in 45 patients with hyperthyroidism due to Graves' disease who had been diagnosed and treated with thionamide drugs between 1965 and 1971 and had remained clinically euthyroid for greater than 10 yr after discontinuation of therapy. Physical examination revealed that only 2 patients had signs of mild hyperthyroidism; all others were euthyroid. Measurements of serum concentrations of thyroid hormones and TSH revealed elevated free T4 index values and serum T3 in 3 (6.7%), T3 toxicosis in 4 (8.9%), and subclinical hypothyroidism in 2 patients (4.4%). The remaining 36 patients were biochemically euthyroid. TRH tests were performed in these 36 patients, and hyporesponsiveness was found in 3 and hyperresponsiveness in 5 patients. T3 suppression tests were performed in 15 of the 36 patients; 10 were suppressible and 5 were nonsuppressible. All suppressible patients responded to TRH. Large needle biopsies performed in 8 biochemically euthyroid patients and 1 patient with subclinical hypothyroidism revealed chronic lymphocytic thyroiditis in 7 and normal biopsies in 2 patients. Diffuse epithelial hyperplasia was not found in any of the specimens. Antithyroid antibody titers were significantly higher than in 1972 at the time of discontinuation of therapy using the same methods. These results suggest that Graves' disease may evolve into chronic thyroiditis in some patients who are in permanent remission, and some patients in apparent permanent remission have hyperthyroidism and concomitant chronic thyroiditis.     

Should we treat mild subclinical/mild hyperthyroidism? No

The management of a patient with subclinical hyperthyroidism or mild thyroid over-activity is controversial. Subclinical hyperthyroidism is defined as a serum thyrotrophin (TSH) below the reference range but a normal thyroxine (T₄) and triiodothyronine (T₃) level in a patient who is either asymptomatic or has only non-specific symptoms. Epidemiological studies report an overall prevalence of approximately 3%, with men and women over 65 years and those in iodine deficient regions having the highest prevalence. Approximately 50% of subjects are taking levothyroxine. The aetiology for those with endogenous subclinical hyperthyroidism is Graves' disease, toxic nodular goitre or rarely a solitary toxic adenoma or thyroiditis. Non-thyroidal illness is an important cause of false positive low serum TSH test results. Subjects with low but detectable serum TSH values (0.1-0.4 mU/L) usually recover spontaneously when re-tested. It has been estimated that in those with an undetectable serum TSH (< 0.1 mU/L) conversion to overt hyperthyroidism occurs at a rate up to 5% per year. Advocates of intervening for subclinical hyperthyroidism argue that early treatment might reduce mortality, prevent the later development of atrial fibrillation, osteoporotic fractures, and overt hyperthyroidism but data supporting improvement in outcomes are sparse. No appropriately powered prospective, randomised, controlled, double-blinded trial of intervention for subclinical hyperthyroidism exists. For the vast majority of patients adopting a “wait and see” policy rather than intervention may avoid unnecessary treatment or the potential for harm. Any potential benefits of therapy in subclinical hyperthyroidism must be weighed against the significant morbidity associated with the treatment of hyperthyroidism.     

Long-term follow-up of thyroid function in patients who received bone marrow transplantation during childhood and adolescence

An increasing number of long-term surviving bone marrow transplant (BMT) recipients have recovered from their primary disease but are at risk of developing failure of endocrine organs. We investigated 147 patients who underwent allogeneic BMT. Thyroid function was evaluated by serial measurement of basal TSH and free T4 levels as well as by TRH provocative test. Thyroid ultrasound examination was performed for evaluation of thyroid tumor after BMT. Five patients were found to have overt thyroid dysfunction (hypothyroidism in four patients and hyperthyroidism in one patient). Twenty-three patients in the under 9-yr-old group at BMT and 16 patients in the over 10-yr-old group at BMT had subclinical compensated hypothyroidism. Younger age at BMT was the strongest factor for developing thyroid dysfunction, compared with older age (P < 0.001). Only in patients with subclinical compensated hypothyroidism did median basal and peak TSH increase to the upper half of the normal range by 8 yr after BMT and then returned slightly to the middle of the normal range spontaneously. These results suggest that thyroid dysfunction in long-term BMT survivors depends on age at BMT, with a greater risk among younger patients, indicating the need for life-long surveillance.     

Epidemiology and prevention of clinical and subclinical hypothyroidism.

Iodine deficiency is the most common cause of hypothyroidism worldwide. In persons living in iodine-replete areas, causes are congenital, spontaneous because of chronic autoimmune disease (atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis [Hashimoto's thyroiditis]), or iatrogenic because of goitrogens, drugs, or destructive treatment for thyrotoxicosis. Screening for congenital hypothyroidism exists and its use prevents mental retardation. The prevalence of spontaneous hypothyroidism is between 1% and 2% and is more common in older women and 10 times more common in women than in men. A significant proportion of subjects have asymptomatic chronic autoimmune thyroiditis and 8% of women (10% of women over 55 years of age) and 3% of men have subclinical hypothyroidism. Approximately one third of patients with newly diagnosed overt hypothyroidism have received destructive therapy for hyperthyroidism and indefinite surveillance is required. There is not much that can be done to prevent the occurrence of spontaneous autoimmune hypothyroidism, but if identified early, something can be done to prevent progression to overt disease. Controversy exists as to whether healthy adults would benefit from screening for autoimmune thyroid disease because a significant proportion of subjects tested will have evidence of mild thyroid failure. Case finding in women at menopause or visiting a primary care physician with nonspecific symptoms appears justified.     

The immunofluorometric TSH assay as first-line test for suspected thyroid dysfunction

In this study of 103 patients with suspected thyroid dysfunction, the diagnostic value of a single basal immunofluorometric (IFMA) TSH measurement was evaluated and compared with the classical TRH test with RIA-TSH measurements, plasma TT4 concentrations and FT4I. A single basal TSH determination accurately predicted the TRH-stimulated TSH response, making the TRH test redundant in most patients. Because undetectable basal TSH did not always exclude a small rise in TSH, the TRH test could still be indicated in patients receiving thyroxine suppression therapy for thyroid cancer. Basal TSH differentiated accurately between euthyroidism and thyroid dysfunction, especially at the decision values of 0.20 and 4.0 mU/l, as proposed in this study. For diagnosis of clinical and subclinical hypo- and hyperthyroidism, additional measurement of TT4 and/or FT4I is necessary. A 2-yr follow-up of patients with subclinical thyroid dysfunction did not show progression to clinical disease. In some of the patients with subclinical hypothyroidism, substitution therapy with thyroxine had been started after initial testing. Indications for treatment of subclinical thyroid dysfunction are discussed.     

Incidence of thyroid dysfunction during interferon alfa-2b and ribavirin therapy in men with chronic hepatitis C: a prospective cohort study

BACKGROUND: Thyroid dysfunction is a known complication of interferon monotherapy in women with hepatitis C virus (HCV) infection. The aims of this study were to determine the incidence and long-term outcome of thyroid dysfunction in HCV-infected men receiving interferon and ribavirin combination therapy. METHODS: We prospectively studied 225 HCV-infected men with baseline levels of thyrotropin (TSH) within the reference range who were treated with subcutaneous interferon alfa-2b (3 million units 3 times per week) and oral ribavirin (1000-1200 mg/d) for 24 to 48 weeks. Patients underwent screening of TSH levels every 12 weeks during HCV therapy and at weeks 12 and 24 after completion of treatment. Patients with abnormal TSH levels underwent a comprehensive thyroid evaluation. RESULTS: Among the 225 patients, overt thyroid disease developed in 6.7% (95% confidence interval, 3.8%-10.8%), and subclinical thyroid disease was diagnosed in 4.0% (95% confidence interval, 1.8%-7.4%). In the 12 patients with overt hypothyroidism, antithyroglobulin antibodies were present in 11 and antithyroid peroxidase antibodies were present in 10, whereas thyroid-stimulating immunoglobulins were present in 2 of the 3 individuals with overt hyperthyroidism. Most of the patients with thyroid dysfunction completed HCV therapy, and thyroid disease resolved in 10 of the 12 patients with overt hypothyroidism, 2 of the 3 with overt hyperthyroidism, and all 9 with subclinical thyroid disease. CONCLUSIONS: Men with HCV infection treated with interferon and ribavirin should undergo routine screening for thyroid disease. Treatment of HCV can be safely continued in these patients because thyroid disease responds well to treatment and is reversible in most individuals.     

Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. 99mTc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and discharge of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I [5.4 +/- 0.8% (+/- SE) at 60 min] was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by 99mTc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients. 2) The organification defect induced by iodine excess is greater in iodide-induced hypothyroidism than in eu- or hyperthyroidism. These findings may be explained by the increased TSH secretion in hypothyroidism and/or by decreased thyroidal concentration of an unknown specific iodinated compound (whose concentration and action vary with the total organic iodine content of the thyroid) that mediates the inhibition of iodide transport.