Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dsfunction in apparently healthy subjects.

In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (chi2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves' disease at booking, 1 developed Graves' disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (chi2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, chi2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction. In conclusion: 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies.     

Longitudinal study of thyroid function in children with mild hyperthyrotropinemia at neonatal screening for congenital hypothyroidism

OBJECTIVE: Long-term outcome of thyroid function in children with very short-lasting neonatal hyperthyrotropinemia ("false positive" at neonatal screening) was studied in an observational, prospective study. Thyroid function and morphology were evaluated in 44 "false positive" children up to advanced childhood (8.0 +/- 0.7 yr of age). In these children a high prevalence (50%) of subclinical hypothyroidism in early childhood (2.8 +/- 0.5 yr) had already been described. RESULTS: At an average of 5.3 yr, subclinical hypothyroidism persisted in 19 of 44 (43.2%) children and, more specifically, in two of three of those who had increased TSH in early childhood. Euthyroidism was present in all cases that were euthyroid in early childhood, although they had TSH and free T(3) values significantly higher than control children with a normal TSH at birth (TSH = 2.6 +/- 0.7 vs. 1.5 +/- 0.6 mU/liter, P < 0.001; free T(3) = 4.9 +/- 0.8 vs. 3.9 +/- 0.9 pmol/liter, P < 0.01). Thyroid morphology alterations were frequent in the group of children with subclinical hypothyroidism. At an average of 8.0 yr, subclinical hypothyroidism persisted in 14 of 44 (31.8%) children. In all other children, TSH and thyroid hormones were confirmed within the normal range. CONCLUSIONS: This prospective longitudinal study confirms that newborns "false positive" at neonatal screening have a high risk to develop persistent subclinical hypothyroidism. The prevalence of hypothyroidism decreases with increasing age, but it is still high (>30%) in late childhood. Even those "false positive" children that maintain euthyroidism in late childhood have an average TSH value that, although within the normal range, is higher than in normal controls, a possible marker of minor congenital thyroid function abnormalities.     

开展亚临床甲状腺功能减退症的临床研究

亚临床甲状腺功能减退症 (甲减 )是一种常见的内分泌专业亚临床疾病 ,主要诊断依据是血清TSH水平增高 ,而血清FT4正常。亚临床甲减的主要不良后果是发展为临床甲减和促进缺血性心脏病的发生。影响亚临床甲减发展为临床甲减的主要因素有两个 :血清TSH水平和甲状腺自身抗体 ,两个因素有叠加作用。甲状腺激素替代治疗对于阻止亚临床甲减发展为临床甲减的效果尚不确切 ;亚临床甲减与高胆固醇血症、高血压、吸烟和糖尿病一样 ,构成动脉粥样硬化和心肌梗塞的独立危险因素 ,其对此两病的危险度分别为 1.9和 3 .1。甲状腺素纠正亚临床甲减对降低血清胆固醇有一定效果 ;妊娠妇女的亚临床甲减对后代的智力影响已经引起高度关注。我国一组根据对流行病学调查的结果 ,提出了血清TSH、甲状腺自身抗体 (TPOAb、TgAb)的正常值范围 ,以及与疾病相关的甲状腺自身抗体的切割点值 ,可供参考。     

The spectrum of thyroid disorders in systemic lupus erythematosus

To study the spectrum of thyroid disorders in systemic lupus erythematosus (SLE). Hundred SLE patients as per American Rheumatology Association(ARA) classification criteria underwent clinical examination, including assessment of disease activity (SLEDAI) and laboratory evaluation for serum triiodothyronine (T3),free thyroxine (FT4), thyroid stimulating hormone (TSH), antithyroperoxidase (TPO) antibody and antithyroglobulin (TG) antibody. Hundred age- and sex-matched apparently healthy individuals served as control. Thirty-six (36%) lupus patients had thyroid dysfunction when compared to 8 (8%) of controls and all of them were women. Primary hypothyroidism was the commonest dysfunction in 14 (14%), while subclinical hypothyroidism and subclinical hyperthyroidism was seen in 12 (12%) and 2 (2%), respectively. Eight (8%) had isolated low T3 consistent with sick euthyroid syndrome. Eighteen (50%) of thyroid dysfunction were autoimmune in nature (autoantibody positive) and rest 18 (50%) were non-autoimmune. Euthyroid state with the elevation of antibodies alone was seen in 12 (12%) of the lupus patients. In contrast, only 5 (5%) of controls had primary hypothyroidism and 3 (3%) had subclinical hypothyroidism, while none had hyperthyroidism. SLEDAI score and disease duration were compared between lupus patients with thyroid dysfunction to those with normal thyroid function. A statistically significant association was found between SLEDAI and thyroid dysfunction of sick euthyroid type.SLE disease duration had no statistically significant association with thyroid dysfunction. Prevalence of thyroid autoantibodies in lupus patients was 30% when compared to 10% of controls. Ninety-six (96%) of the SLE patients were ANA positive, while 4 (4%) of them were ANA negative but were anti-Sm antibody positive. There were no suggestions of any other autoimmune endocrine diseases like diabetes or Addison’s disease (clinically and on baseline investigations) in our lupus cohort and hence no further work up was done for these diseases. Thyroid disorders are frequent in SLE and are multifactorial with a definite higher prevalence of hypothyroidism as well as thyroid autoantibodies.     

Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia

Newborns with high TSH at birth and with normal free T(4) and normal or slightly elevated TSH at the confirmatory examination are considered false positive for congenital hypothyroidism. We evaluated thyroid function, thyroid antibodies, thyroid volume and morphology, thyroperoxidase and TSH receptor genes, and auxological data in 56 false positive children at 16-44 months of age. In these children thyroid function at confirmatory examination was fully normal in 33 (TSH, 0.8-4.9 mU/liter; group I) and nearly normal (borderline elevated TSH, 5.0-11.7 mU/liter) in the other 23 (group II). Compared with 65 control children with normal TSH at birth, false positive children had significantly higher basal serum TSH (mean +/- SD, 4.38 +/- 2.2 vs. 1.4 +/- 0.8 mU/liter; P < 0.01). Subclinical hypothyroidism, indicated by increased basal TSH and/or increased TSH response to TRH, was present in 36% children in group I and 70% in group II. Free T(4) was within the normal range in all children. Compared with the control group, false positive children had significantly higher free T(3) values (4.9 +/- 0.8 vs. 3.7 +/- 1.0 pmol/liter; P < 0.01) and a higher prevalence of antithyroid antibodies (25% vs. 1.5%; P < 0.001). Frequent thyroid morphology abnormalities and frequent thyroperoxidase and TSH receptor gene sequence variations were also observed. In conclusion, newborns classified false positive at congenital hypothyroidism screening have a very high risk of subclinical hypothyroidism in infancy and early childhood.     

Thyroid autoantibodies and thyroid function in subjects exposed to Chernobyl fallout during childhood: evidence for a transient radiation-induced elevation of serum thyroid antibodies without an increase in thyroid autoimmune disease

CONTEXT: An increase in the prevalence of thyroid autoantibodies (ATAs) was reported 6-8 yr after the Chernobyl accident in radiation-exposed children and adolescents. OBJECTIVE: Our objective was to reassess the effects of childhood radiation exposure on ATAs and thyroid function 13-15 yr after the accident. DESIGN AND SETTING: We measured the antithyroglobulin (TgAbs) and antithyroperoxidase (TPOAbs) antibodies and TSH in 1433 sera collected between 1999 and 2001 from 13- to 17-yr-old adolescents born between January 1982 and October 1986 in paired contaminated and noncontaminated villages of Belarus, Ukraine, and Russia. A total of 1441 sera was collected from age- and sex-matched controls living in Denmark and Sardinia (Italy). Free T(4) and free T(3) were measured when TSH was abnormal. RESULTS: TPOAb prevalence was higher in contaminated than in noncontaminated Belarusian children (6.4 vs. 2.4%; P = 0.02) but lower than previously reported (11%) in a different contaminated Belarus village. No difference in TPOAb prevalence was found in Ukrainian and Russian villages. TgAbs showed no difference between contaminated and noncontaminated Belarus and Ukraine, whereas in Russia they showed a relative increase in the exposed subjects with respect to the unexposed, who showed an unexpectedly lower prevalence of TgAbs. Besides radiation exposure, female gender was the only variable significantly correlated with ATAs in all groups. ATA prevalence in nonexposed villages of Belarus, Ukraine, and Russian Federation did not differ from that found in Sardinia and Denmark. With few exceptions, thyroid function was normal in all study groups. CONCLUSIONS: TPOAb prevalence in adolescents exposed to radioactive fallout was still increased in Belarus 13-15 yr after the Chernobyl accident. This increase was less evident than previously reported and was not accompanied by thyroid dysfunction. Our data suggest that radioactive fallout elicited a transient autoimmune reaction, without triggering full-blown thyroid autoimmune disease. Longer observation periods are needed to exclude later effects.     

93例亚临床甲状腺功能减退症的随访研究

目的 研究不同碘摄入量地区亚临床甲状腺功能减退症(甲减)的流行病学特点和影响转归的因素。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)，在入户调查的基础上行采样调查。测定血清TSH、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)、尿碘浓度及进行甲状腺B超检查，TSH异常者测定FT3、FT4，筛选出118例亚临床甲减患者。盘山和彰武社区于2年后、黄骅社区于1年后进行随访，再次进行以上检查。结果 盘山、彰武和黄骅社区亚临床甲减的患病率分别为0．73％、2．90％和5．96％。亚临床甲减的病因33．1％是自身免疫性甲状腺疾病。在随访到的93例亚临床甲减患者中有4例女性进展为临床甲减。结论 随着碘摄入量的增加亚临床甲减的患病率增加，但无明显性别差异。随访研究证实女性、甲状腺自身抗体阳性是亚临床甲减患者进展至临床甲减的危险因素，碘摄入量与亚临床甲减的转归无关。     

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。     

Evaluation of thyroid functions with respect to iodine status and TRH test in chronic autoimmune thyroiditis

Objective: Chronic autoimmune thyroiditis (CAT) is the most common form of thyroiditis in childhood and a frequent cause of acquired hypothyroidism. The objective of this study was to evaluate the thyroid status of childrenand adolescents with CAT with respect to iodine status and diagnostic values of thyrotropin-releasing hormone (TRH) test. Methods: Seventy-one children (mean age: 11.6 years) were studied in a retrospective analysis. Free thyroxine (T4), thyrotropin (TSH), TSH response to TRH test, thyroid autoantibodies, thyroid sonography, and urinary iodine excretion (UIE) were evaluated. Results: At diagnosis, 8.5% of patients had overt hypothyroidisim and 36.6% subclinical hypothyroidism; 5.6% had overt hyperthyroidisim and 8.5% had subclinical hyperthyroidism. Of them, 40.8% were euthyroid. Median UIE was 51 mg/L in overt hypothyroidism and 84 mg/L in subclinical hypothyroidism. The values were 316 mg/L and 221 mg/L in overt and subclinical hyperthyroidism, respectively. Basal TSH showed a strong correlation with peak TSH level on TRH test. Thirty-four percent of patients with normal basal TSH level showed an exaggerated TSH response. Conclusion: Iodine deficiency was seen more in cases with hypothyroidism, while excess of iodine was observed to be more frequent in hyperthyroid patients. Iodine status was a strong predictorof the thyroid status in CAT. TRH test may be helpful in further delineating patients with subclinical hypothyroidism. Conflict of interest:None declared.     

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus.

OBJECTIVE: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and morphological abnormalities by ultrasonography in young diabetics. SUBJECTS AND METHODS: Among young IDDM patients less than 18 years old and living in the county of Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children matched for sex and age. Routine thyroid function parameters (thyroxine (T4), tri-iodothyronine (T3), T3 resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography. RESULTS: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of subclinical hypothyroidism were found. There were no significant differences in thyroid function variables or thyroid volume between diabetics and controls. Thyroid volume correlated significantly with age and weight in both groups. Among diabetics, 17 had thyroid autoantibodies (13 with TPOab, 14 with Tgab and 10 with both) compared with 2 children in the control group (P<0.001). Forty-four with IDDM as opposed to 11 of the controls (P<0.001) had morphological abnormalities at ultrasonography. Most of them had various degrees of hypoechogenicity thought to be a marker of thyroid autoimmunity. Among the 17 diabetics with autoantibodies, 10 had morphological abnormalities at ultrasonography. CONCLUSIONS: A high proportion of young IDDM patients without any clinical signs of thyroid disease have markers of thyroid autoimmunity. Many have thyroid autoantibodies, but even more have abnormalities by thyroid ultrasonography.     

Comparison of some different methods for analysis of thyroid autoantibodies: importance of thyroglobulin autoantibodies.

Blood samples from 141 children and adolescents were used to evaluate differences between commercial kits and radioimmunoassay (RIA) methods for detecting thyroid autoantibodies. Thyroglobulin autoantibodies (Tg-Ab) were analyzed with a hemagglutination kit and a RIA; thyroid peroxidase autoantibodies (TPO-Ab) were measured with a gelagglutination assay and a RIA. The results of the antibody tests were compared with thyroid function tests (triiodothyronine [T3], thyroxine [T4], thyrotropin [TSH]) and with the results of ultrasound of the thyroid in antibody-positive patients. The correlation of antibody levels between the two methods was higher for TPO-Ab than for Tg-Ab. Moderate to high levels of TPO-Ab correlated to elevated TSH levels. Autoimmune thyroiditis (AIT) was found in 6 of the 141 children. The RIA-based thyroglobulin assay was the only test that identified autoantibodies in all 6 cases. In contrast, the hemagglutination kit thyroglobulin assay failed to identify 4 of the 6 AIT cases.     

Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism

PURPOSE: To determine the incidence and predictability and to elucidate the pathogenesis of amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism (AIH). PATIENTS AND METHODS: A prospective study was performed in 58 consecutive euthyroid patients living in an area with moderately sufficient iodine intake, who had never been treated for thyroid disease and who started amiodarone therapy for the first time. MAIN OUTCOME MEASURES: Development of thyrotoxicosis or hypothyroidism. RESULTS: The follow-up period was 6 to 54 months (mean, 21 months). The incidence of AIT was 12.1%. A steady occurrence of new cases was observed. The development of AIT was unpredictable and of unexplained sudden onset. The incidence of AIH was 6.9%. All AIH cases occurred early in the course of amiodarone therapy. The development of AIH was related to pre-existent thyroid disease: the relative risk for women with microsomal and/or thyroglobulin autoantibodies prior to treatment was 13.5 (95% confidence interval 3.2 to 57.4). The development of AIT or AIH was not related to the extent of iodine overload or to the occurrence of de novo thyroid autoantibodies. When a decreased thyrotropin (TSH) response to thyrotropin-releasing hormone occurred (in the absence of AIT), continuation of amiodarone medication was associated with a normalization of the TSH response in eight of 11 cases (73%); in contrast, an increased TSH response (in the absence of AIH) returned to normal in one of four cases (25%). CONCLUSION: In euthyroid subjects living in an area with a moderately sufficient intake of iodine, there is a higher incidence of AIT than of AIH. AIH is an early event, occurring especially in women with thyroid autoantibodies prior to treatment. Cases of AIT continue to occur during amiodarone therapy; its development is unpredictable and of unexplained sudden onset. The value of regular thyroid function testing is therefore limited during amiodarone administration.     

Thyroid peroxidase antibodies, levels of thyroid stimulating hormone and development of hypothyroidism in euthyroid subjects

ObjectiveThyroid peroxidase antibodies (TPOAbs) have been found to be related to the levels of thyroid stimulating hormone (TSH) and to predict future development of thyroid failure in selected populations. We investigated these relations in a euthyroid general population.DesignCross-sectional investigation of the relationship of TPOAbs and levels of TSH in euthyroid subjects. Prospective investigation of the association of TPOAbs and TSH with development of hypothyroidism. Incident hypothyroidism was defined as initiation of l-thyroxine in the absence of thyreostatic medication.SubjectsThe study was performed in a random sample of 2703 participants of the PREVEND study. A total of 309 subjects were excluded from analyses, mainly because of TSH outside the reference range (0.35–4.94 mIU/l; n = 115).ResultsMean (SD) baseline age was 47.7 (12.5) years, with 50.8% females. Prevalence of positive TPOAbs (≥ 12 kU/l) was 8.4%. TSH concentrations were increased in subjects with TPOAbs (P < 0.001). During a median follow-up of 9.1 years, 15 (0.6%) subjects developed hypothyroidism (3.5% in TPOAbs positive vs. 0.4% in TPOAbs negative subjects; P < 0.001). Female sex (P = 0.02), and TSH (P < 0.001) were also significantly associated with incident hypothyroidism. In multivariate analysis, TSH and TPOAbs remained independent predictors (both P < 0.001).ConclusionsWe confirmed the positive relationship of the presence of TPOAbs with levels of TSH and showed that TPOAbs and TSH predict future development of hypothyroidism. These results are consistent with the presence of TPOAbs necessitating a compensatory increase in levels of TSH for maintenance of euthyroidism, even in the euthyroid range.     

Thyroid status two decades after salt iodization: country-wide data in school children from India

Objective Country‐wide evaluation of thyroid disorders in school children following two decades of universal salt iodization (USI) has not been carried out till date. This study was planned with aim to assess thyroid status of school children two decades after the launch of USI programme. Design Population survey. Patients We collected data from 25 schools in 19 cities across five different geographical zones of India. Those children who were evaluated for anthropometry, and goitre status by palpation formed ‘total population’. Children who consented to give blood samples were defined as ‘study population’. Measurements Serum free T3, free T4, TSH, anti‐TPO antibody and thyroid ultrasound. Results A total of 38 961 children aged 5–15 years formed total population. Goitre rate was 15·5% while thyroid hypoechogenicity was found in 4404 (11·3%) children. In the study population (13 790 children), 2258 (16·4%) had goitre, 505 (3·7%) had positive anti‐TPO antibody titres, 1001 (7·3%) had hypothyroidism (TSH > 5·2 μIU/ml) and 41 (0·3%) had thyrotoxicosis (TSH < 0·1 μIU/ml). Among goitrous children, 203 (9·0%) had anti‐TPO positivity, 365 (16·1%) had hypoechogenicity of thyroid and either of these were present in 488 (21·6%) children. Conclusions Endemic goitre in school children persisted nationwide, despite more than two decades of USI programme. Thyroid autoimmunity only partially explains the increase in goitre prevalence.     

Increased mean serum thyrotropin in apparently euthyroid hypercholesterolemic patients: does it mean occult hypothyroidism?

Serum thyroid hormones and antithyroid autoantibodies (AAB) were assayed in 87 randomly selected hypercholesterolemic persons compared to 80 controls with normal serum total cholesterol (TC). Of the 87 hypercholesterolemic persons 22 (25%) had positive AAB compared to 5 (6%) controls. Furthermore, 8 of the hypercholesterolemic patients had a serum TSH level above 5 mU/l, i.e. the had subclinical hypothyroidism, not diagnosed before, whereas thyroid function was normal in all normocholesterolemic persons. The new and unexpected finding was that the hypercholesterolemic persons had on average a significantly higher serum TSH than the controls, and this was true even when persons with positive AAB were excluded. There was a significant correlation between TC and serum TSH. It is concluded that hypothyroidism may not be an all-or-none phenomenon, and that many hypercholesterolemic persons with thyroid tests within the conventional normal range may have a slight impairment of their thyroid function.     

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.     

Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes

OBJECTIVE: In a follow-up study, we determined the prevalence, incidence, and natural course of positive antithyroperoxidase antibodies (TPOAbs) and antithyroglobulin antibodies (TgAbs) in the general population and examined the influences of iodine intake. DESIGN: The study was conducted in Panshan, Zhangwu, and Huanghua, regions with mildly deficient, more than adequate, and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 3018 participated in the 5-yr follow-up study. Serum TSH, TPOAb, and TgAb levels were measured. RESULTS: Among subjects in Panshan, Zhangwu, and Huanghua, the prevalence of positive TPOAbs was 11.23, 11.83 and 12.02%, respectively, whereas 11.23, 11.17, and 11.26% of subjects were TgAb positive, respectively. In the older population (> or =45 yr), TgAb-positive individuals were more frequent in Huanghua than Panshan and Zhangwu (P < 0.05). The 5-yr cumulative incidence of positive TPOAb was 2.08, 3.84, and 2.84% in Panshan, Zhangwu, and Huanghua, respectively, whereas 2.91, 3.64, and 5.07% of subjects were TgAb positive, respectively (P < 0.05), corresponding to the increase in iodine intake. Subjects who were TPOAb and/or TgAb positive at baseline developed thyroid dysfunctions more frequently than those without antibodies (14.44 vs. 3.31%, P < 0.01); their incidence of elevated TSH levels was 1.32, 8.46, and 15.38% in Panshan, Zhangwu, and Huanghua, respectively (P < 0.05). CONCLUSIONS: Subjects who were TPOAb and TgAb positive at baseline developed thyroid dysfunctions more frequently than seronegative subjects. High iodine intake was a risk factor for developing hypothyroidism in antibody-positive subjects. A constant exposure to excessive iodine intake increased the incidence of positive TgAb.     

Prevalence of thyroid dysfunction in Thai HIV-infected patients

Increasing prevalence of thyroid function abnormality has been reported in HIV-infected patients. We aim to evaluate the prevalence and assess risk factors of thyroid dysfunction in Thai HIV-infected patients. A cross-sectional study was conducted. Serum thyroid hormone concentrations (FT4, FT3, and TSH) and thyroid autoantibodies (TgAb and TPOAb) were measured by electrochemiluminescence immunoassay. A total of 200 HIV-infected outpatients were included. Ninety-seven patients (48.5%) were men (mean age of 36.3 +/- 8.3 years). Duration of HIV infection was 49.6 +/- 35.1 months and 53% had previous opportunistic infections (OI). Mean CD4 cell count was 340.6 +/- 173.1 cells/mm(3). Of these, 167 patients (83.5%) received antiretroviral therapy (ARV). Abnormal thyroid function test was detected in 32 patients (16%). Twenty-seven patients (13.5%) had decreased thyroid function (primary hypothyroidism 3, subclinical hypothyroidism 12, and low FT4 with low or normal TSH 12) whereas 5 patients had increased thyroid function (overt hyperthyroidism 1, subclinical hyperthyroidism 1, and isolated high FT3 3). None had clinical features of thyroid hormone dysfunction. Thirteen patients (6.5%) had thyroid antibody positive. Patients who received ARV had higher mean FT3 levels than those who were na?ve to ARV (p = 0.017). History of previous OI was found to be an independently significant risk factor for decreased thyroid function with the odds ratio of 3.28 (95% CI =1.183-9.099; p = 0.022). Hypothyroidism was common among Thai HIV-infected patients, especially in those who had history of previous OI. It is therefore suggested that screening and/or monitoring of thyroid hormone in HIV-infected patients should be considered.     

Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism

We report a 22-yr-old male patient with idiopathic hypothalamic hypogonadism who showed secondary resistance to gonadotropin (Gn) therapy over 3 yr after successful treatment with hCG combined with human menopausal Gn. The patient simultaneously developed subclinical hypothyroidism. Endocrine examination revealed low levels of testosterone (0.3 ng/ml), free T4 (0.91 ng/dl), and increased levels of TSH (31.1 microU/ml) in the serum. Serum autoantibodies to thyroid gland were all negative. Interestingly, thyroid function was improved after discontinuation of Gn therapy. In vitro assays by immunoprecipitation using 125I-hCG or 125I-TSH elucidated the presence of anti-hCG antibody in the serum 13 months after commencement of Gn therapy but anti-TSH antibody was not detected in the serum. Furthermore, the anti-hCG antibody specifically bound to hCG but not to other glycoproteins including TSH and FSH based on a competitive displacement assay. Bioassays using porcine thyroid cells revealed that the serum gamma-globulin fraction enables the suppression of cyclic AMP (cAMP) synthesis stimulated by TSH. Our findings suggest that anti-hCG and/or anti-idiotypic hCG antibodies induced by hCG therapy impaired TSH-dependent cAMP production through interfering with binding of TSH to its receptor, and this resulted in subclinical hypothyroidism in this patient.     

L-thyroxine Stabilizes Autoimmune Inflammatory Process in Euthyroid Nongoitrous Children with Hashimoto’s Thyroiditis and Type 1 Diabetes Mellitus

Objective: To investigate if L-thyroxine (T4) treatment may influence the clinical course of autoimmune thyroiditis (AIT) or prevent progression to subclinical or overt hypothyroidism in euthyroid nongoitrous pediatric patients with type 1 diabetes mellitus (T1DM) and AIT.Methods: The study was performed in four Polish pediatric diabetes centers. Of 330 children with T1DM and AIT followed between 2008 and 2012, 101 received L-T4 and 160 underwent clinical observation for 24 months. Thyroid stimulating hormone (TSH), free T4 (fT4), anti thyroid peroxidase antibody (anti-TPO), anti thyroglobulin antibody (anti-TG), glycosylated hemoglobin (HbA1c) levels, and lipid profile were assessed in all patients. Ultrasonographic evaluation was also performed in all children at each examination.Results: Patients treated with thyroid hormones had higher TSH levels (3.99; interquantile 3.5 to 4.52 vs. 2.09 mIU/L; interquantile 1.55 to 3.06; p<0.0001). A fall in TSH level (0.87 mIU/L 95% CI 0.43-1.30; p<0.0001) was documented after the first year of treatment. FT4 level did not differ between the groups at baseline (p=0.7434), but rose in the treatment group and fell in the control group [mean difference 0.78 95% CI-0.22-1.53 pmol/L (p=0.02) after 12 months and 0.98 95% CI 0.04-1.76 (p=0.005) after 24 months]. Higher levels of anti-TPO were initially found in the treated patients (p<0.0001) and significantly decreased over the 24-month period (p<0.0001). Children in the treatment group had higher anti-TG levels (p<0.0001), which showed a borderline decrease (p=0.08) in time. In the control group, anti-TG levels rose marginally (p=0.06) during the study.Conclusions: The data demonstrate that treatment with L-T4 in euthyroid pediatric patients with T1DM and AIT stabilizes autoimmune inflammation in the thyroid gland and is to be recommended as soon as the diagnosis is established.Conflict of interest:None declared.