Urinary Iodine and Genetic Predisposition to Hashimoto's Thyroiditis in a Chinese Han Population: A Case-Control Study.

Background: We aimed to examine the association of urinary iodine concentration with Hashimoto's thyroiditis (HT) risk, and particularly, to investigate whether the HT-related genetic variations might modify the effects of urinary iodine on HT in the Chinese Han population. Methods: We conducted a case-control study with 1723 Chinese (731 cases, 992 controls). The associations between urinary iodine concentration and HT risk were analyzed using logistic regression models. The effects of interactions between the genetic risk scores (GRSs) and urinary iodine on HT risk were assessed by including the respective interaction terms in the models. We also applied restricted cubic spline regression to estimate the possible nonlinear relationship. The multinomial logistic regression models were performed to determine the associations of urinary iodine with euthyroid-HT and hypothyroidism-HT. Results: After controlling for potential confounders, the odds of HT increased with increasing quartiles of urinary iodine concentration: adjusted odds ratios (ORs) and 95% confidence intervals [CIs] were 1.45 [1.06-1.99], 1.66 [1.17-2.34], and 2.07 [1.38-3.10] for the quartiles 2, 3, and 4, respectively, compared with the first quartile (p for trend <0.001). Multivariable restricted cubic spline regression analysis further demonstrated that there was a near-linear association between urinary iodine concentration and HT risk (p-overall <0.001; p-nonlinear = 0.074). However, we did not find significant interactions between urinary iodine and GRSs on the risk of HT (all p for interaction >0.05). Interestingly, we found that each increment of urinary iodine was associated with a more than twofold increase in the odds of hypothyroidism-HT (adjusted OR = 2.64 [CI = 1.73-4.05]), but not with euthyroid-HT (p > 0.05). Conclusions: Higher urinary iodine concentration was associated with increased risk of HT, and this association was near linear, indicating that increased urinary iodine has a continuous and graded impact on HT risk. Moreover, the iodine-HT association was not modified by genetic predisposition to HT. Interestingly, urinary iodine concentration was significantly associated with increased risk of hypothyroidism.

Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population.

Subclinical hypothyroidism (SCH) is a common endocrine disorder affecting women of reproductive age. Although SCH and abnormal fatty acid composition are often associated with adverse pregnancy outcomes and metabolic syndrome later in maternal and fetal life, the longitudinal relationship between SCH and serum fatty acids during pregnancy has rarely been studied. Therefore, the aim of this study was to investigate the association between SCH and maternal serum fatty acids throughout gestation. A total of 240 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included in our study. Clinical information and maternal serum samples were collected at three time points during pregnancy: 11-14th, 22-28th, and 32-34th weeks of gestation. Twenty serum fatty acids were quantified using gas chromatography-mass spectrometry (GC-MS) analysis. A majority of the 20 serum fatty acids increased as gestation progressed in women with a normal pregnancy and women experiencing SCH. Levels of arachidic acid, docosahexaenoic acid, and eicosenoic acid were significantly higher in the serum of women with SCH when compared to women with a normal pregnancy, in the second trimester. On the other hand, the levels of eicosadienoic acid and octadecanoic acid were significantly higher in SCH in the third trimester. Our findings demonstrate that serum fatty acid composition during the second and third trimesters was significantly associated with SCH in pregnant Chinese women.

Reduction in Thyroid-Stimulating Hormone Correlated with Improved Inflammation Markers in Chinese Patients with Morbid Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

OBJECTIVE: Bariatric surgery has a significant impact on levels of thyroid hormones and various inflammatory markers in obesity. The relationship between changes in thyroid hormones and inflammatory markers after bariatric surgery is unknown. We aimed to investigate the changes in thyroid hormones and their relations to inflammatory changes after laparoscopic sleeve gastrectomy (LSG) in Chinese patients with morbid obesity. METHODS: Eighty-eight patients with morbid obesity (56.8% female; age 30.9 ± 9.5 years; BMI 39.9 ± 5.7 kg/m2) submitted to LSG were selected. Patients were subdivided into euthyroid group and subclinical hypothyroidism (SH) group. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), inflammatory markers, and related metabolic indexes were analyzed pre- and 12 months post-LSG. RESULTS: SH patients presented significantly higher interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) than euthyroid patients. Twelve-month post-surgery, the SH incidence decreased from 31.8 to 2.3% (P < 0.001). TSH levels were declined significantly in both groups but were more pronounced in SH group (P < 0.001), whereas no change in FT4 in either group. Additionally, we observed marked reduction of IL-6, TNF-α, and CRP in SH group, as well as TNF-α and CRP in euthyroid group. After adjusting for age, baseline BMI, and changes in BMI, decrease in TSH correlated significantly with decreased HOMA-IR and TNF-α in euthyroid group and decreased fasting insulin (FINS), IL-6, TNF-α, and CRP in SH group. CONCLUSION: LSG promotes TSH reduction in patients with morbid obesity that is more pronounced in patients with SH and correlated with improved inflammatory state after surgery.

Patients on levothyroxine replacement in the community: association between hypothyroidism symptoms, co-morbidities and their quality of life.

INTRODUCTION: Patients may be symptomatic, resulting in lower quality of life (QOL), despite L-thyroxine (LT4) therapy for hypothyroidism or having normal thyroid function. We hypothesized that their clinical symptoms of hypothyroidism and co-morbidities were associated with QOL. OBJECTIVE: The study aimed to determine the association between the hypothyroid-related symptoms of Asian patients on LT4 treatment, their co-morbidities and their QOL. METHOD: A questionnaire survey was conducted from November 2015 to July 2016 on consecutive multi-ethnic Asian patients on LT4 treatment for their hypothyroidism in a public primary care clinic in Singapore. Data on their demography, clinical symptoms, morbidity status, QOL scores based on the EQ5D instrument and thyroid function tests were computed and analysed, including logistic regression analysis to identify factors associated with lower QOL. RESULTS: Complete data of 226 Asian patients (79.0% women; 74.2% Chinese, 10.0% Malay, 13.1% Indian and 2.6% other minority groups; median age 57 years; 27.5% had previous thyroid surgery) were analysed. Their QOL was not associated with their socio-demographic profiles, clinical parameters and latest thyroid-stimulating hormone and free thyroxine levels. Patients reporting weight gain, dry or coarse skin, leg swelling, feeling weak and carpal tunnel syndrome had significantly lower QOL; 53.6% of them with any single symptom had lower QOL. More patients had lower QOL if they had two or more symptoms and multiple medical conditions. CONCLUSION: In Asian patients with hypothyroidism, weight gain, feeling tired, feeling weak, having dry or coarse skin, leg swelling and increased number of co-morbidities and symptoms were significantly associated with poorer QOL.

Dietary Selenium Intake and Subclinical Hypothyroidism: A Cross-Sectional Analysis of the ELSA-Brasil Study.

Selenium (Se) participates in several enzymatic reactions necessary for regulating the homeostasis of thyroid hormones. We aimed to analyze the association between dietary Se intake and subclinical hypothyroidism. Baseline data from the Longitudinal Study of Adult Health (Estudo Longitudinal de Saúde do Adulto-ELSA-Brasil) in Brazil were analyzed, with a final sample size of 14,283 employees of both sexes aged 35⁻74 years. Dietary data was collected using a previously validated food frequency questionnaire. Subclinical hypothyroidism was categorized as thyroid-stimulating hormone levels of >4.0 IU/mL and free prohormone thyroxine levels within normal limits, without administering drugs for thyroid disease. A multiple logistic regression model was used to assess the relationship between the presence of subclinical hypothyroidism and tertiles of Se consumption. The prevalence of subclinical hypothyroidism in the study sample was 5.4% (95% confidence interval [CI], 3.8⁻7.0%). Compared with the first tertile of Se intake, the second (odds ratio [OR], 0.79; 95% CI, 0.65⁻0.96%) and third (OR, 0.72; 95% CI, 0.58⁻0.90%) tertiles were inversely associated with subclinical hypothyroidism, however further research is needed to confirm the involvement of Se in subclinical hypothyroidism using more accurate methodologies of dietary assessment and nutritional status to evaluate this relationship.

Evaluation of serum ferritin and thyroid function in the second trimester of pregnancy.

Ferritin is a universal intracellular protein that acts as an iron carrier. Several studies have indicated that iron deficiency affects thyroid function in non-pregnant women. Our objective was to assess the relationship between serum ferritin levels and thyroid function in pregnant women during the second trimester. Pregnant women with sufficient iodine intake and normal antithyroid antibodies during the second trimester were recruited from the obstetric outpatient department of the Fifth People's Hospital of Fudan University. Serum ferritin (SF) levels, thyroid function, anti-thyroid antibodies and vitamin B12 were determined by electrochemiluminescence immunoassay kit. Maternal serum iron (Fe), unsaturated iron binding capacity (UIBC), hemoglobin (Hb), creatinine (Cr), fasting blood glucose (FBG), and alanine aminotransferase (ALT) were also evaluated. Stepwise regressions performed to evaluate the associations between SF and other maternal parameters. In the second trimester, 11.4% pregnant women had a SF concentration less than 12 µg/L, and 7.6% pregnant women were anemic. SF levels were negatively correlated with serum TSH levels (r = -0.219, p < 0.05), and positively correlated with FT4 levels (r = 0.203, p < 0.05). Linear regression analysis showed only SF, age, week of gestation were significant predictors of regression with TSH as the dependent variable (ß: -0.007, -0.059, and 0.118 respectively; all p < 0.05). However consistent relation between the SF levels and FT4 was not observed in stepwise linear regression. Maternal iron status is a determinant of TSH concentrations during pregnancy in pregnant women during the second trimester.

A cross-sectional analysis of the association between age and gender and prescribed minimum benefit chronic disease list conditions among South Africans with concomitant hypertension, diabetes and dyslipidaemia.

BACKGROUND: Prescribed Minimum Benefit Chronic Disease List (PMB CDL) conditions are a regulated list of conditions most common to South Africa. OBJECTIVES: To investigate the prevalence and association between PMB CDL conditions and age and gender among patients with concomitant hypertension, diabetes and dyslipidaemia. METHODS: The study population consisted of patients (n = 17 866) with a prescription containing at least one co-prescribed antilipemics, antihypertensive and antidiabetic (identified using the MIMS Desk Reference). ICD-10 codes on claims for PMB CDL conditions were counted. RESULTS: 39.5% of patients had a PMB CDL condition. Women had higher odds for hypothyroidism (OR 6.30, 95% CI; 5.52, 7.19, p < 0.001) and lower odds for coronary artery disease (CAD) (OR 0.63, 95% CI; 0.55, 0.72, p < 0.001) than men. In combination with hypothyroidism the odds for CAD were reversed and strongly increased; 3.54 (95% CI; 2.38, 5.25, p < 0.001). The odds for females having cardiac failure (CF) was insignificant and low (OR 0.87, 95% CI; 0.75, 1.01, p = 0.063); however combined with hypothyroidism, the odds increased to 5.35 (95% CI; 3.52, 8.13, p < 0.001). CONCLUSION: Hypothyroidism was an important discriminating factor for co-morbidity in women with concomitant hypertension, diabetes and dyslipidaemia, in particular with cardiovascular disease.

Maternal thyroid parameters in pregnant women with different ethnic backgrounds: Do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?

OBJECTIVE: Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a thyroid-stimulating hormone (TSH) upper reference limit (cut-off) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cut-offs (institutional, ethnicity-specific, 2.5 mIU/L [Endocrine Society] and 4.0 mIU/L [American Thyroid Association]). DESIGN: Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women. METHOD: The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-abs), TSH and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with sub-Saharan (SaBg; 28.6%), 754 North African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded. RESULTS: The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; P<.001, respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; P=.006 and .014, respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cut-off, but when 4.0 mIU/L or the institutional cut-off (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1% vs 3.3%, P=.008 and .013, respectively). The use of ethnicity-specific cut-offs did not change the prevalence of SCH as compared to the use of institutional cut-offs. However, when these cut-offs were used, the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; P<.001) relative to the 2.5 mIU/L cut-off. CONCLUSIONS: Pregnant women with a sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cut-offs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cut-off.

Primary hypothyroidism in the community: Lower daily dosages of levothyroxine replacement therapy for Asian patients.

The goal of treatment in patients with primary hypothyroidism is to attain euthyroidism guided by the stipulated thyroid-stimulating hormone (TSH) levels range so as to minimize any potential long-term adverse effects. However, various factors may result in their Levothyroxine (T4) under and over-replacement.Our study aimed to evaluate the mean daily dose of L-T4 replacement for Asian patients with primary hypothyroidism. The secondary aims were to determine the proportion of those who were either over or under-replaced, and the factors associated with their thyroid function status and replacement adherence.Data collected using questionnaire survey from targeted patients managed in a typical public primary care center in Singapore: socio-demographic characteristics, clinical parameters, laboratory investigations, mean daily L-T4-replacement doses, and replacement regimens. The thyroid status of patients was classified based on thyroid function investigations.Complete data of 229 patients were analyzed. A total of 59.8% of patients had TSH within the normal range, 27.5% and 12.7% were under and over-replaced, respectively. About 60% of Asian patients with primary hypothyroidism achieved normal TSH status requiring average of 1.1 µg of daily L-T4/kgBW (kg body weight). Subjects who were over-replaced had a higher daily L-T4 dose/kgBW when compared to the euthyroid and the under replaced groups. Those with L-T4 over-replacement were largely due to excessive dosage. Patients who were younger, from lower socioeconomic strata, and higher BMI were more likely to be over or under-replaced.Majority of Asian patients with hypothyroidism required replacement of 1.1 µg of daily L-T4/kgBW. Their thyroid status was influenced by demographic and dosing factors.

High prevalence of DUOX2 mutations in Japanese patients with permanent congenital hypothyroidism or transient hypothyroidism.

BACKGROUND: Dual oxidase 2 (DUOX2) mutations are a cause of dyshormonogenesis (DH) and have been identified in patients with permanent congenital hypothyroidism (PH) and with transient hypothyroidism (TH). We aimed to elucidate the prevalence and phenotypical variations of DUOX2 mutations. METHODS: Forty-eight Japanese DH patients were enroled and analysed for sequence variants of DUOX2, DUOXA2, and TPO using polymerase chain reaction-amplified direct sequencing. RESULTS: Fourteen sequence variants of DUOX2, including 10 novel variants, were identified in 11 patients. DUOX2 variants were more prevalent (11/48, 22.9%) than TPO (3/48, 6.3%) (p=0.020). The prevalence of DUOX2 variants in TH was slightly, but not significantly, higher than in PH. Furthermore, one patient had digenic heterozygous sequence variants of both DUOX2 and TPO. CONCLUSIONS: Our results suggest that DUOX2 mutations might be the most common cause of both PH and TH, and that phenotypes of these mutations might be milder than those of other causes.

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients.

AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

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.

The attitude toward hypothyroidism during early gestation: time for a change of mind?

BACKGROUND: The approach not to screen thyroid function of all pregnant women is mainly based on conflicting evidence of whether treatment of women with mild hypothyroidism is beneficial. However, there is consensus that all women with overt hypothyroidism (OH) and those with a thyrotropin (TSH) >10 mIU/L should be treated immediately, but data on these conditions are scarce. We assessed the prevalence of OH and a TSH >10 mIU/L during the first trimester of pregnancy. METHODS: Thyroid function was assessed at 10-12 weeks gestation in 4199 Dutch Caucasian healthy pregnant women from three studies conducted in 2002, 2005, and 2013 from the same iodine sufficient area in the southeast of The Netherlands. We defined the first trimester specific cutoffs (2.5th-97.5th percentile) for TSH and free thyroxine (fT4) in thyroid peroxidase antibody (TPO-Ab) negative women in each study to determine the prevalence of women with OH and those with a TSH >10 mIU/L. We extrapolated these figures to the pregnant population of 2012 in The Netherlands, the United Kingdom, and the United States. RESULTS: The prevalence of OH or a TSH >10 mIU/L in these 4199 women was 26 (0.62%) of whom 96% had (highly) elevated TPO-Ab titers. Based on the birth figures of 2012, if all pregnant women from The Netherlands, the United Kingdom or the United States were screened, the conservative annual number of cases would be 1000, 4500, and 25,000 respectively. However, the United Kingdom and parts of the United States have recently been demonstrated to be iodine deficient, which will result in even higher numbers. CONCLUSION: Our findings show that the discussion concerning thyroid screening during pregnancy should be based on data of overt hypothyroidism in healthy pregnant women. Screening of thyroid function is not expensive because all pregnant women have a standardized blood sample test at 8-12 weeks' gestation. Positive patients largely benefit from a cheap, safe, and effective treatment.

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 dysfunction in an adult female population: A population-based study of Latin American Vertebral Osteoporosis Study (LAVOS) - Puerto Rico site.

OBJECTIVE: To determine the prevalence of hypothyroidism in an adult female population in Puerto Rico and to determine the relationship between hypothyroidism, bone mineral density and vertebral and non-vertebral fractures in this population. METHODS: Data from the 400 subjects' database of the Latin American Vertebral Osteoporosis Study (LAVOS), Puerto Rico site was reviewed. Patient's medical history, anthropometric data, current medications, laboratories, and DXA results was extracted. Subjects with thyroid dysfunction were identified based on their previous medical history and levels of TSH. Bone Mineral Density was classified using the World Health Organization criteria. Crude prevalence of thyroid dysfunction were estimated with a confidence of 95% and weighted by the population distribution by age, according to the distribution by age group in the 2000 census. Bone mineral densities and prevalence of vertebral and non-vertebral fractures were compared among the groups. RESULTS: The weighted prevalence of hyperthyroidism in this population was 0.0043% (95% CI: -0.0021%, 0.0107%). The weighted prevalence of hypothyroidism was 24.2% (95% CI: 19.9%, 28.4%). Increased prevalence of hypothyroidism was found in participants 70 years or older. The mean BMD at spine, hip and femoral neck was similar among the groups. No difference in the proportion of participants with vertebral and non-vertebral fractures was found among the groups. CONCLUSION: Our study found a high prevalence of hypothyroidism among adult postmenopausal females in Puerto Rico. No association between hypothyroidism and decreased bone mineral densities, vertebral or non-vertebral fractures was found in this population.

Subclinical hypothyroidism and survival: the effects of heart failure and race.

CONTEXT: Studies examining the association between subclinical hypothyroidism and mortality have yielded conflicting results. Emerging data suggest these associations may depend upon underlying congestive heart failure (CHF) and/or race, but this has not been empirically determined. OBJECTIVE: Our objective was to examine the association between subclinical hypothyroidism and hypothyroidism overall with mortality according to pre-existing CHF and race. DESIGN AND PARTICIPANTS: We examined the associations of subclinical hypothyroidism (TSH higher than assay upper limit of normal; total T4 within reference) and hypothyroidism overall (TSH higher than assay upper limit of normal; total T4 below lower limit of normal or within reference) with all-cause mortality among Third National Health and Nutrition Examination Survey participants stratified by CHF and race using multivariable Cox models. To confirm whether differences between strata were statistically significant, we tested for interaction on the basis of CHF (separately) and race by likelihood ratio testing. RESULTS: There were 14 130 (95.0%) euthyroid controls and 749 (5.0%) participants with hypothyroidism, 691 (4.6%) of whom had subclinical disease. Subclinical hypothyroidism vs euthyroidism was associated with greater mortality in those with CHF but not in those without: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) = 1.44 (1.01-2.06) and 0.97 (0.85-1.11), respectively (P interaction = .03). Similar findings were observed for hypothyroidism overall. Hypothyroidism overall vs euthyroidism was associated with greater mortality in Black participants (HR = 1.44 [95% CI = 1.03-2.03]) but not in non-Blacks (HR = 0.95 [95% CI = 0.83-1.08]) (P interaction = .03). CONCLUSION: Among participants with CHF, subclinical hypothyroidism and hypothyroidism overall are associated with greater death risk. Additional studies are needed to confirm findings and explore possible mechanisms for the differential hypothyroidism-mortality association across race.

Patterns of interferon-alpha-induced thyroid dysfunction vary with ethnicity, sex, smoking status, and pretreatment thyrotropin in an international cohort of patients treated for hepatitis C.

BACKGROUND: Interferon-alpha (IFNα)-induced thyroid dysfunction occurs in up to 20% of patients undergoing therapy for hepatitis C. The diversity of thyroid disease presentations suggests that several different pathological mechanisms are involved, such as autoimmunity and direct toxicity. Elucidating the relationships between risk factors and disease phenotype provides insight into the mechanisms of disease pathophysiology. METHODS: We studied 869 euthyroid patients from the ACHIEVE 2/3 trial, a randomized international clinical trial comparing pegylated-IFNα2a weekly or albumin-IFNα2b every 2 weeks for up to 24 weeks in patients with hepatitis C, genotype 2 or 3, from 136 centers. The study population was 60% male and 55% white. Serum thyrotropin (TSH) and free thyroxine were measured before therapy, monthly during treatment from week 8, and at 4- and 12-week follow-up visits. RESULTS: Overall, 181 (20.8%) participants had at least one abnormal TSH during the study. Low TSH occurred in 71 (8.2%), of whom 30 (3.5%) had a suppressed TSH below 0.1 mU/L. Hypothyroidism occurred in 53 patients (6.1%), with peak TSH above 10 mU/L in 12 patients (1.4%). Fifty-seven patients had a biphasic thyroiditis (6.6%), with extreme values for the nadir and/or peak TSH in all but one. Medical therapy was given to one thyrotoxic patient, four hypothyroid patients, and 26 biphasic thyroiditis patients. Multivariate logistic regression analysis demonstrated that biphasic thyroiditis is associated with being female and higher pretreatment serum TSH, whereas being Asian or a current smoker decreased the risk of thyroiditis. Hypo- and hyperthyroidism are most strongly predicted by the pretreatment TSH. CONCLUSIONS: Biphasic thyroiditis accounted for the majority (58%) of clinically relevant IFNα-induced thyroid dysfunction. We confirmed our recent findings in a related cohort that female sex is a risk factor for thyroiditis but not hypothyroidism. Further, in this large multiethnic study, the risk of thyroiditis is dramatically increased, specifically for white women. Smoking was found to be protective of thyroiditis. These results support closer monitoring of women and those with a serum TSH at the extremes of the normal range during therapy so that prompt intervention can mitigate the consequences of thyroid dysfunction associated with IFNα treatment.

Neurodevelopment in children born to hypothyroid mothers restored to normal thyroxine (T4) concentration by late pregnancy in Japan: no apparent influence of maternal T4 deficiency.

CONTEXT: The importance of maternal T4 for brain development prior to the onset of fetal thyroid function has been suggested in basic studies, and a correlation between mild maternal T4 deficiency in early gestation and disturbance of neurodevelopment in progenies has been shown in large case-control studies. These findings suggest that maternal T4 deficiency in early pregnancy potentially affects neurointellectual development. On the other hand, no apparent adverse effect in children born to mothers with overt hypothyroidism in Japan has been reported where maternal T4 had been restored to normal by late pregnancy. OBJECTIVE: We report five cases in Japan showing no apparent effect of maternal T4 deficiency on neurodevelopment in progenies where low T4 levels had been corrected by late pregnancy. METHODS: Five women with overt hypothyroidism detected at 6-16 wk gestation initiated T4 treatment. Four women restored euthyroidism by the 20th week. One remained in a subclinical hypothyroid state. Developmental scores of their children were evaluated between 25 months and 11 yr of age by either the Tsumori-Inage Infant's Developmental Test or the Wechsler Intelligence Scale for Children-Third Edition and compared to those of corresponding siblings with no exposure to maternal hypothyroidism. RESULTS: The development scores of all the children turned out to be either normal or advanced. CONCLUSIONS: In iodine-sufficient areas, maternal T4 deficiency in early pregnancy does not necessarily affect neurodevelopment. Therefore, other potential factors altering neurodevelopment, such as iodine deficiency, must be investigated.

Autoimmune thyroid disease in patients with vitiligo: prevalence study in India.

OBJECTIVE: To identify the prevalence of autoimmune thyroid disease (AITD) in Asian Indian patients with vitiligo and to compare the clinical profile between thyroid peroxidase (TPO) antibody-positive and TPO antibody-negative groups. METHODS: In this cross-sectional, case-controlled study, 50 patients with vitiligo (29 women and 21 men) were included. Patients with previous disorders, irradiation, or surgical procedures involving the thyroid were excluded from the study. All participants underwent a complete physical examination, and a single fasting blood sample was analyzed for thyroid function (triiodothyronine, thyroxine, thyroid-stimulating hormone, and TPO and thyroglobulin antibodies), inflammatory and immunologic markers (erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor), and serum calcium, phosphorus, and alkaline phosphatase concentrations. All patients underwent thyroid ultrasonography, and the data were analyzed by appropriate statistical methods. RESULTS: The mean age of the study participants was 42.7 ± 17 years, and 14 of 50 patients (28%) had TPO antibody positivity. A goiter was present in 11 of 50 patients, and the thyroid volume by ultrasonography was similar between the 2 groups. Subclinical hypothyroidism was found in 14 of 50 patients (28%) but more frequently in the TPO antibody-positive group (8 of 14 or 57%) than in the TPO antibody-negative group (6 of 36 or 17%). The prevalence of AITD was 20 of 50 patients (40%) when the TPO antibody-positive group and those with subclinical hypothyroidism were considered collectively. None of the patients had overt hypothyroidism or hyperthyroidism. All other clinical, biochemical, and inflammatory variables did not differ significantly between the TPO antibody-positive and antibody-negative groups. CONCLUSION: Our data showed a 40% prevalence of thyroid disease in patients with vitiligo in India. The risk is exacerbated in patients with thyroid autoimmunity; thus, regular screening of patients with vitiligo for AITD is needed.