Redistribution of body composition in patients with Graves' disease after iodine-131 treatment.

OBJECTIVE: The objective of this study was to investigate body composition redistribution at 3 months after radioactive iodine therapy (RAI). METHODS: Eighty patients with Graves' disease (GD) for RAI and 18 volunteers were recruited. All patients underwent thyroid status test and dual-energy x-ray absorptiometry at baseline and 3 months after RAI. According to the second thyroid status test, patients were divided into the following groups: A, with aggravated hyperthyroidism; B-1, with improved hyperthyroidism; B-2, with euthyroidism; and B-3, with hypothyroidism. RESULTS: Total lean mass (LM) but fat mass (FM) and bone mineral content (BMC) of whole GD patients after RAI recovered to be not different with controls. Compared with baseline, in group A, FM in the left leg increased, and LM in left arm, right arm, trunk and total LM decreased (P<0.05). In B-2, FM in the head increased, and LM in the head, right arm, trunk and total LM increased (P<0.05). In B-3, FM in the right leg and total body fat percentage decreased, but FM in the head, android-to-gynoid fat ratio and body mass index increased (P<0.05); LM of all sites, weight and total mass increased (P<0.05); BMC in lumbar spine and left leg, and total BMC decreased (P<0.05). Body composition of unmentioned sites was retained after RAI in each group (P>0.05). CONCLUSIONS: Replenishment of LM gets priority rather than FM and BMC during the first 3 months after RAI, and the increase in LM starts from the upper body; head is the regional site in which FM recovery occurs first.

Subclinical thyroid dysfunction and cardiac function amongst minority ethnic groups in the UK: a cross sectional study.

BACKGROUND: Subclinical thyroid disease is associated with abnormal cardiovascular haemodynamics and increased risk of heart failure. The burden of raised/low thyroid stimulating hormone (TSH) levels amongst South Asian (SA) and African-Caribbean (AC) minority groups in the UK is not well defined. Given that these groups are particularly susceptible to CVD, we hypothesised that STD would reflect abnormal cardiac function and heightened cardiovascular risk in these ethnic groups. METHODS: We examined SA (n=1111, 56% male, mean age 57.6 yrs) and AC (n=763, 44% male, mean age 59.2 yrs) participants from a large heart failure screening study. Euthyroidism is defined as TSH (0.4 - 4.9 mlU/l), subclinical hypothyroidism is defined as a raised TSH with normal serum free thyroxine (FT4) concentrations (9-19 pmol/l). Subclinical hyperthyroidism is defined as a low TSH with both FT4 and free triiodothyronine (FT3) concentrations within range (2.6-5.7 pmol/l). RESULTS: Across ethnic groups, prevalence of subclinical hypothyroidism was 2.9% (95% CI 2.1-3.7), and of hyperthyroidism was 2.0% (1.4-2.7). Hyperthyroidism was more common amongst SA compared to AC (2.8% vs. 0.9%, P=0.017), while rates of subclinical hypothyroidism were similar. On multivariate analysis of variations in subclinical thyroid function, ethnicity was not independently significant. CONCLUSION: The prevalence of subclinical thyroid disorders amongst SA and AC minority groups in Britain reflects levels reported in other populations. The clinical cardiovascular significance of subclinical thyroid disease is unclear, and it does not appear to be ethnically specific.

Thyroid hyperactivity with high thyroglobulin in serum despite sufficient iodine intake in chronic cold adaptation in an Arctic Inuit hunter population.

OBJECTIVE: Adult man hosts brown adipose tissue with the capacity to consume energy and dissipate heat. This is essential for non-shivering thermogenesis and its activation depends on sympathetic activity and thyroid hormones. This led us to evaluate the impact of chronic cold exposure on thyroid activity and thyroid hormones in serum in Arctic residents. DESIGN: Comparative, population-based study (n = 535) performed in Greenland. METHODS: Hunters were compared with other men, and Inuit in remote settlements in East Greenland with no modern housing facilities were compared with the residents of the capital city in West Greenland and residents of a major town in East Greenland in a cross-sectional study. We used interview-based questionnaires, measured TSH, free thyroxine, free triiodothyronine (fT(3)), thyroglobulin (TG) antibody and TG (a measure of thyroid activity) in serum, and iodine and creatinine in spot urine samples. RESULTS: Serum TG was the highest among hunters (P = 0.009) and settlement dwellers (P = 0.001), who were most markedly exposed to cold, even though they had the highest urinary iodine excretion (hunters, P < 0.001; settlement dwellers, P < 0.001). Hunters and settlement dwellers also had the lowest fT(3) (hunters, P < 0.001; settlement dwellers, P < 0.001) after adjusting for gender, age, smoking habits, alcohol intake and iodine excretion in multivariate linear regression models. TSH was not influenced by measures of cold exposure (hunter, P = 0.36; residence, P = 0.91). CONCLUSIONS: Cold exposure influenced thyroid hormones and TG in serum in Arctic populations consistent with consumption of thyroid hormone and higher thyroid hormone turnover. Findings emphasise that changes in thyroid activity are essential in cold adaptation in Arctic residents.

Development of thyroid dysfunction and autoantibodies in Graves' multiplex families: an eight-year follow-up study in Chinese Han pedigrees.

BACKGROUND: This 8-year follow-up study is aimed at determining the relapse and development of Graves' disease (GD) and the potential risk factors that could be associated with the development of thyroid dysfunction and autoantibodies in Chinese pedigrees. METHODS: Fifty-four Chinese Han GD pedigrees (322 members) were recruited in 2000. Forty-five pedigrees (263 members) were followed up. Their clinical and laboratory characteristics and fasting urinary iodine were measured with the same method at the two time points. RESULTS: We found that the mean age for onset of GD in offspring was much younger than that of their parents (p=0.013). At baseline, the prevalence of hyperthyroidism, hypothyroidism, and subclinical hypothyroidism in first-degree relatives were 5.5%, 1.6%, and 1.1%, respectively. Individuals with thyroid dysfunction were positive for thyroid autoantibodies. The prevalence of positive thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), or TSH receptor antibody (TRAb) in the first-degree relatives with euthyroidism in these pedigrees was 18.6%, 17.4%, or 56.9%, respectively. At follow-up, individuals with positive TPOAb were at risk of developing thyroid dysfunction, whereas patients with positive TRAb had increased risk for relapse even after drug treatment. The percentage of nonsmokers with positive TPOAb and TgAb was significantly higher than that of smokers (p<0.05), but the levels of serum TRAb were significantly higher in smokers at follow-up than baseline (p<0.01). CONCLUSIONS: Genetic factors are crucial for the development of autoimmune thyroid disease (AITD), thyroid dysfunction, and the outcomes of Graves' patients following treatment with medicines. Although smoking was negatively associated with the presence of thyroid antibodies (TPOAb/TgAb), smoking may induce or aggravate GD.

Expanding clinical spectrum of non-autoimmune hyperthyroidism due to an activating germline mutation, p.M453T, in the thyrotropin receptor gene.

OBJECTIVE: To describe clinical and genetic features of a Thai family with non-autoimmune hyperthyroidism (NAH) caused by an activating germline mutation in the thyrotropin receptor (TSHR) gene. PATIENTS: Three affected individuals from the same family (a father and his two children) were studied. Clinical and imaging findings were reviewed and compared. GENETIC ANALYSIS: Genomic DNA was extracted from peripheral blood leukocytes and mutation analysis of the entire coding sequence of the TSHR gene was performed in both children and their parents by direct DNA sequencing. RESULTS: A heterozygous germline T to C transition in exon 10 of the TSHR gene (c.1358T-->C) resulting in the substitution of methionine (ATG) by threonine (ACG) at codon 453 (p.M453T) was identified in the father and his two children. They presented with different clinical severity and variable age of onset. In addition to hyperthyroidism, ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers were consistently found in all affected individuals. CONCLUSIONS: Ventriculomegaly and bilateral shortening of the fifth metacarpal bones and the middle phalanges of the fifth fingers might be characteristic features of NAH because of an activating TSHR germline mutation. In addition, the shortening of the middle phalanges of the fifth fingers has never been previously described, expanding the phenotypic spectrum of the disease.

Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002).

OBJECTIVE: Describe thyrotropin (TSH) and thyroxine (T4) levels in the U.S. population and their association with selected participant characteristics. DESIGN: Secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES) collected from 4392 participants, reflecting 222 million individuals, during 1999-2002. RESULTS: Hypothyroidism prevalence (TSH > 4.5 mIU/L) in the general population was 3.7%, and hyperthyroidism prevalence (TSH < 0.1 mIU/L) was 0.5%. Among women of reproductive age (12-49 years), hypothyroidism prevalence was 3.1%. Individuals aged 80 years and older had five times greater odds for hypothyroidism compared to 12- to 49-year-olds (adjusted odds ratio [OR] = 5.0, p = 0.0002). ORs were adjusted for sex, race, annual income, pregnancy status, and usage of thyroid-related medications (levothyroxine/thyroid, estrogen, androgen, lithium, and amiodarone). Compared to non-Hispanic whites, non-Hispanic blacks had a lower risk for hypothyroidism (OR = 0.46, p = 0.04) and a higher risk for hyperthyroidism (OR = 3.18, p = 0.0005), while Mexican Americans had the same risk as non-Hispanic whites for hypothyroidism, but a higher risk for hyperthyroidism (OR = 1.98, p = 0.04). Among those taking levothyroxine or desiccated thyroid, the adjusted risk for either hypothyroidism (OR = 4.0, p = 0.0001) or hyperthyroidism (OR = 11.4, p = 4 x 10(-9)) was elevated. CONCLUSIONS: Associations with known factors such as age, race, and sex were confirmed using this data set. Understanding the prevalence of abnormal thyroid tests among reproductive-aged women informs decisions about screening in this population. The finding that individuals on thyroid hormone replacement medication often remain hypothyroid or become hyperthyroid underscores the importance of monitoring.

Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period.

OBJECTIVE: To evaluate thyroid function and the prevalence of thyroid peroxidase (TPO) antibody and autoimmunity in African-American and white women during pregnancy and the postpartum period. METHODS: Five hundred eighty-nine women were evaluated prospectively. Serum thyroid-stimulating hormone (TSH), free thyroxine (T4), and TPO, Ro, and La antibodies were obtained during pregnancy, at delivery, and postpartum. Levels of hCG were determined during pregnancy. Urinary iodine levels were evaluated in the third trimester in another group of women. All TPO antibody-positive patients were to be followed up at 3 and 6 months postpartum. RESULTS: African-American women had lower TSH values than white women at all times. Thyroid-stimulating hormone increased, and free T4 decreased from the first to third trimester of pregnancy for both groups. African Americans had higher hCG levels than whites in the first trimester but not in the third trimester. There was no difference in urine iodine excretion between African-American and white women. Finally, there was no difference in TPO antibody seropositivity between African-American and white women. Overall, 5 patients (0.8%) were diagnosed with subclinical hypothyroidism during pregnancy. CONCLUSION: Fluctuations in TSH and free T4 during pregnancy parallel reported obstetric values. African Americans demonstrated consistently lower TSH levels than whites. These differences were unexplained by racial differences in either TPO antibody seropositivity, iodine status, or chorionic gonadotropin levels.

High thyroid volume in children with excess dietary iodine intakes.

BACKGROUND: There are few data on the adverse effects of chronic exposure to high iodine intakes, particularly in children. OBJECTIVE: The objective of the study was to ascertain whether high dietary intakes of iodine in children result in high thyroid volume (Tvol), a high risk of goiter, or both. DESIGN: In an international sample of 6-12-y-old children (n = 3319) from 5 continents with iodine intakes ranging from adequate to excessive, Tvol was measured by ultrasound, and the urinary iodine (UI) concentration was measured. Regressions were done on Tvol and goiter including age, body surface area, sex, and UI concentration as covariates. RESULTS: The median UI concentration ranged from 115 microg/L in central Switzerland to 728 microg/L in coastal Hokkaido, Japan. In the entire sample, 31% of children had UI concentrations >300 microg/L, and 11% had UI concentrations >500 microg/L; in coastal Hokkaido, 59% had UI concentrations >500 microg/L, and 39% had UI concentrations >1000 microg/L. In coastal Hokkaido, the mean age- and body surface area-adjusted Tvol was approximately 2-fold the mean Tvol from the other sites combined (P < 0.0001), and there was a positive correlation between log(UI concentration) and log(Tvol) (r = 0.24, P < 0.0001). In the combined sample, after adjustment for age, sex, and body surface area, log(Tvol) began to rise at a log(UI concentration) >2.7, which, when transformed back to the linear scale, corresponded to a UI concentration of approximately 500 microg/L. CONCLUSIONS: Chronic iodine intakes approximately twice those recommended-indicated by UI concentrations in the range of 300-500 microg/L-do not increase Tvol in children. However, UI concentrations >/=500 microg/L are associated with increasing Tvol, which reflects the adverse effects of chronic iodine excess.

Transient hyperthyroidism of hyperemesis gravidarum.

OBJECTIVE: To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum. DESIGN: Prospective observational study. SETTING: Hospital inpatient gynaecological ward. POPULATION: Women admitted with hyperemesis gravidarum and found to have hyperthyroidism. METHODS: Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation. MAIN OUTCOME MEASURES: Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes). RESULTS: Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile. CONCLUSIONS: In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.