Thyroid function derangement and childhood obesity: an Italian experience

Background

In recent years, there has been an increasing attention to thyroid function in paediatric obese patients. In the present study we aimed 1) to determine the prevalence of abnormally elevated thyroid-stimulating hormone (TSH) levels in Italian obese children and adolescents 2) to investigate whether hyperthyrotropinemia in obese children cardiovascular and metabolic risk factors 3) to verify if TSH elevation is reversible after weight loss.

Methods

We examined 938 obese children and adolescents (450 females). Anthropometric, metabolic and hormonal variables were determined at baseline and, in a subgroup of children with hyperthyrotropinemia, after a six month weight loss program.

Results

Hyperthyrotropinemia (TSH ≥4.2 μUI/ml) was diagnosed in 120 patients (12,8%). Body mass index (BMI) z-score (p = 0.02) and free T3 (fT3) levels (p = 0.03) were higher in patients with elevated TSH compared to the group with normal TSH. There were not significant differences in other metabolic parameters between the two groups. A positive correlation between baseline TSH and BMI z-score (p = 0.0045) and between Ft3 and BMI z-score (p = 0.0034) was observed, while there was no correlation between TSH and lipids. Twenty-three patients among those with hyperthyrotropinemia who participated to weight reduction intervention (64 patients), presented substantial weight loss and concomitantly a significant decrease in TSH and in fT3.

Conclusions

These results suggest that: (1) a moderate elevation of TSH concentrations, is frequently found in obese children; (2) in obese children increase of TSH is not associated to metabolic risk factors, (3) hyperthyrotropinemia is reversible after weight loss and these data suggest that it should not be treated.     

The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma

Background

Thyroid physiology is closely related to oxidative changes. The aim of this controlled study was to evaluate the levels of nutritional anti-oxidants such as vitamin C, zinc (Zn) and selenium (Se), and to investigate any association of them with parameters of thyroid function and pathology including benign and malignant thyroid diseases.

Methods

This controlled evaluation of Se included a total of 1401 subjects (1186 adults and 215 children) distributed as follows: control group (n = 687), benign thyroid disease (85 children and 465 adults); malignant thyroid disease (2 children and 79 adults). Clinical evaluation of patients with benign thyroid disease included sonography, scintigraphy, as well as the determination of fT3, fT4, TSH, thyroid antibodies levels, Se, Zn, and vitamin C. Besides the routine oncological parameters (TG, TSH, fT4, ultrasound) Se was also determined in the cases of malignant disease. The local control groups for the evaluation of Se levels were taken from a general practice (WOMED) as well as from healthy active athletes. Blood samples were collected between 8:00 and 10:30 a.m. All patients lived in Innsbruck. Statistical analysis was done using SPSS 14.0. The H_o stated that there should be no differences in the levels of antioxidants between controls and thyroid disease patients.

Results

Among the thyroid disease patients neither vitamin C, nor Zn nor Se correlated with any of the following parameters: age, sex, BMI, body weight, thyroid scintigraphy, ultrasound pattern, thyroid function, or thyroid antibodies. The proportion of patients with benign thyroid diseases having analyte concentrations below external reference cut off levels were 8.7% of cases for vitamin C; 7.8% for Zn, and 20.3% for Se. Low Se levels in the control group were found in 12%. Se levels were significantly decreased in cases of sub-acute and silent thyroiditis (66.4 ± 23.1 μg/l and 59.3 ± 20.1 μg/l, respectively) as well as in follicular and papillary thyroid carcinoma. The mean Se level in the control group was 90.5 ± 20.8 μg/l.

Conclusion

The H₀ can be accepted for vitamin C and zinc levels whereas it has to be rejected for Se. Patients with benign or malignant thyroid diseases can present low Se levels as compared to controls. Low levels of vitamin C were found in all subgroups of patients.     

Is there a link between blastomere contact surfaces of day 3 embryos and live birth rate?

Background

Limitations in our current knowledge of normative physiologic changes in thyroid function during the periconception window narrow our ability to establish an optimal approach to screening and diagnosis of thyroid disease in pregnant women. The objective of this study was to characterize changes in thyroid function during the transition from the pre-pregnant to pregnant state in normal fertile women.

Methods

Women (N = 60) ages 30-42 years without a history of thyroid disease, who were planning pregnancy, were observed prospectively before and during early pregnancy. Thyroid function (thyroid stimulating hormone, TSH and free thyroxine, FT4) was measured before conception and between 6 and 9 weeks gestation. Pre-pregnancy samples were analyzed for thyroid antibodies. Bivariate analyses and longitudinal curves (general estimating equation models) were used to analyze changes in thyroid function during the periconception window by antibody status.

Results

Pre-pregnancy TSH values were significantly higher than early pregnancy TSH (p < 0.001), but FT4 values did not differ (p = 0.53). TSH declined as gestational age increased (P < 0.01). Thyroid antibody positive women had a higher pre-pregnancy TSH compared to antibody negative women (p < 0.01). Periconceptional change in thyroid function was more variable among women with antibodies (p < 0.001). 50% of women with elevated pre-pregnancy TSH values (TSH > 3.0 mIU/L) had normal TSH values (TSH < 2.5 mIU/L) in pregnancy.

Conclusions

TSH values decline during the transition from pre-pregnancy to early pregnancy. The change in TSH appears to be less predictable in women with thyroid antibodies. Periconceptional changes in thyroid function should be considered in formulating prenatal thyroid screening guidelines.     

Wasting syndrome with deep bradycardia as presenting manifestation of long-standing severe male hypogonadotropic hypogonadism: a case series

Background

Non-thyroidal illness (NTI) refers to changes in thyroid hormone levels in critically ill patients in the absence of primary hypothalamic-pituitary-thyroid dysfunction, and these abnormalities usually resolve after clinical recovery. However, NTI can be accompanied by primary thyroid dysfunction. We report herein a case of a woman with NTI accompanied by primary hyperthyroidism.

Case presentation

A 52-year-old female was admitted to the intensive care unit with heart failure and atrial fibrillation. She had a longstanding thyroid nodule, and a thyroid function test revealed low levels of triiodothyronine and free thyroxine as well as undetectable thyroid stimulating hormone (TSH). She was diagnosed with NTI, and her TSH level began to recover but not completely at discharge. The thyroid function test was repeated after 42 months to reveal primary hyperthyroidism, and a thyroid scan confirmed a toxic nodule.

Conclusion

This case suggests that although NTI was diagnosed, primary hyperthyroidism should be considered as another possible diagnosis if TSH is undetectable. Thyroid function tests should be repeated after clinical recovery from acute illness.     

Using Hashimoto thyroiditis as gold standard to determine the upper limit value of thyroid stimulating hormone in a Chinese cohort

Background

Subclinical hypothyroidism, commonly caused by Hashimoto thyroiditis (HT), is a risk factor for cardiovascular diseases. This disorder is defined as merely having elevated serum thyroid stimulating hormone (TSH) levels. However, the upper limit of reference range for TSH is debated recently. This study was to determine the cutoff value for the upper normal limit of TSH in a cohort using the prevalence of Hashimoto thyroiditis as “gold” calibration standard.

Methods

The research population was medical staff of 2856 individuals who took part in health examination annually. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, thyroid peroxidase antibody (TPAb), thyroglobulin antibody (TGAb) and other biochemistry parameters were tested. Meanwhile, thyroid ultrasound examination was performed. The diagnosis of HT was based on presence of thyroid antibodies (TPAb and TGAb) and abnormalities of thyroid ultrasound examination. We used two different methods to estimate the cutoff point of TSH based on the prevalence of HT.

Results

Joinpoint regression showed the prevalence of HT increased significantly at the ninth decile of TSH value corresponding to 2.9 mU/L. ROC curve showed a TSH cutoff value of 2.6 mU/L with the maximized sensitivity and specificity in identifying HT. Using the newly defined cutoff value of TSH can detect patients with hyperlipidemia more efficiently, which may indicate our approach to define the upper limit of TSH can make more sense from the clinical point of view.

Conclusions

A significant increase in the prevalence of HT occurred among individuals with a TSH of 2.6–2.9 mU/L made it possible to determine the cutoff value of normal upper limit of TSH.

     

The homeostatic set point of the hypothalamus-pituitary-thyroid axis – maximum curvature theory for personalized euthyroid targets

Background

Despite rendering serum free thyroxine (FT4) and thyrotropin (TSH) within the normal population ranges broadly defined as euthyroidism, many patients being treated for hyperthyroidism and hypothyroidism persistently experience subnormal well-being discordant from their pre-disease healthy euthyroid state. This suggests that intra-individual physiological optimal ranges are narrower than laboratory-quoted normal ranges and implies the existence of a homeostatic set point encoded in the hypothalamic-pituitary-thyroid (HPT) axis that is unique to every individual.

Methods

We have previously shown that the dose–response characteristic of the hypothalamic-pituitary (HP) unit to circulating thyroid hormone levels follows a negative exponential curve. This led to the discovery that the normal reference intervals of TSH and FT4 fall within the ‘knee’ region of this curve where the maximum curvature of the exponential HP characteristic occurs. Based on this observation, we develop the theoretical framework localizing the position of euthyroid homeostasis over the point of maximum curvature of the HP characteristic.

Results

The euthyroid set points of patients with primary hypothyroidism and hyperthyroidism can be readily derived from their calculated HP curve parameters using the parsimonious mathematical model above. It can be shown that every individual has a euthyroid set point that is unique and often different from other individuals.

Conclusions

In this treatise, we provide evidence supporting a set point-based approach in tailoring euthyroid targets. Rendering FT4 and TSH within the laboratory normal ranges can be clinically suboptimal if these hormone levels are distant from the individualized euthyroid homeostatic set point. This mathematical technique permits the euthyroid set point to be realistically computed using an algorithm readily implementable for computer-aided calculations to facilitate precise targeted dosing of patients in this modern era of personalized medicine.

     

Anti-inflammatory effect of rosiglitazone is not reflected in expression of NFκB-related genes in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus

Background

The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).

Methods

Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc^99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.

Results

Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.

Conclusion

Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.

Trial registration

ClinicalTrials.gov, NCT00571090     

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36 weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60 months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.     

Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients

Context

Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.

Objective

To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback.

Design

Retrospective study.

Setting

Academic hospital.

Patients

1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.

Measurements

TSH, FT4 and FT3 concentrations by immunoassays.

Results

FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.

Conclusions

Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.     

Soluble RAGE but not endogenous secretory RAGE is associated with albuminuria in patients with type 2 diabetes

Aims

Type 2 diabetes is characterised by increased plasma concentrations of pro-inflammatory cytokines [such as tumour necrosis factor – alpha; TNF-α] and soluble forms of adhesion molecules involved in leukocyte – endothelial interactions. These molecules are synthesised as transmembrane proteins and the plasma soluble forms are generated by ectodomain cleavage from the cell surface by members of the ADAM [a disintegrin and metalloproteinase] proteinase family. We hypothesised that plasma low density lipoprotein [LDL] from subjects with Type 2 diabetes would influence in vitro monocytic ADAM and matrix metalloproteinase [MMP] gene expression differently compared to control LDL.

Methods

We examined relative mRNA expression by real time PCR in a monocytic cell line [THP-1] cultured for 4, 8 and 24 hrs with human plasma LDL derived from subjects with [n = 5] or without [n = 4] Type 2 diabetes. Gene expression for MMP-1 and 9, and ADAM – 8, 15, 17 and 28 was studied.

Results

Type 2 diabetes LDL significantly increased gene expression of MMP – 1 [p < 0.01] MMP – 9 [p < 0.001], and ADAM 17 [p < 0.05], – 28 [p < 0.01] and – 15 [p < 0.01] compared to control LDL. Type 2 diabetes LDL had disparate effects on inhibitors of MMP.

Conclusion

These data suggest that Type 2 diabetes LDL could lead to increased adhesion molecule and TNF alpha cell surface shedding, and vascular plaque instability, by promoting increased expression of ADAM and MMP genes.     

Reference intervals for the echocardiographic measurements of the right heart in children and adolescents: a systematic review

Background

Transthoracic echocardiography is the primary imaging modality for the diagnosis of right ventricular (RV) involvement in congenital and acquired heart diseases. There is increasing recognition of the contribution of RV dysfunction in heart diseases affecting children and adolescents, but there is insufficient information on reference intervals for the echocardiographic measurements of the right heart in children and adolescents that represent all the continental populations of the world.

Objective

The aim of this systematic review was to collate, from published studies, normative data for echocardiographic evaluation of the right heart in children and adolescents, and to identify gaps in knowledge in this field especially with respect to sub-Saharan Africans.

Methods

We performed a systematic literature search to identify studies of reference intervals for right heart measurements as determined by transthoracic echocardiography in healthy children and adolescents of school-going age. Articles were retrieved from electronic databases with a combination of search terms from the earliest date available until May 2013.

Results

Reference data were available for a broad range of variables. Fifty one studies out of 3096 publications were included. The sample sizes of the reference populations ranged from 13 to 2036 with ages varying from 5 to 21 years. We identified areas lacking sufficient reference data. These included reference data for determining right atrial size, tricuspid valve area, RV dimensions and areas, the RV % fractional area change, pulmonary artery pressure gradients and the right-sided haemodynamics, including the inferior vena cava dimensions and collapsibility. There were no data for sub-Saharan African children and adolescents.

Conclusion

Reliable reference data are lacking for important echocardiographic measurements of the RV in children and adolescents, especially for sub-Saharan Africans.     

Trimester-specific thyroid hormone reference ranges in Sudanese women

Background

Trimester-specific reference ranges for T3, T4, and TSH need to be established in different communities. Neither Sudan nor other African countries have established trimester-specific reference ranges for TSH, free T3 (FT3), and free T4 (FT4) in healthy pregnant women. This study aimed to establish trimester-specific reference ranges for TSH, FT3, and FT4 in healthy pregnant Sudanese women.

Results

We performed a longitudinal study, which included 63 women with singleton pregnancies who were followed since early pregnancy until the third trimester. The study was performed in Saad Abu-Alela Hospital, Khartoum, Sudan, during January to October 2014. An equal number of age- and parity-matched non-pregnant women were enrolled as a control group. Basic clinical and obstetrics data were gathered using questionnaires. TSH, FT3, and FT4 levels were measured. Median (5th–95th centile) values of TSH, FT3, and FT4 were 1.164 IU/ml (0.079–2.177 IU/ml), 4.639 nmol/l (3.843–6.562 nmol/l), and 16.86 pmol/l (13.02–31.48 pmol/l) in the first trimester. Median values of TSH, FT3, and FT4 were 1.364 IU/ml (0.540–2.521 IU/ml), 4.347 nmol/l (3.425–5.447 nmol/l), and 13.51 pmol/l (11.04–31.07 pmol/l) in the second trimester. These values were 1.445 IU/ml (0.588–2.460 IU/ml), 4.132 nmol/l (3.176–5.164 nmol/l), and 12.87 pmol/l (9.807–23.78 pmol/l) in the third trimester, respectively. TSH levels increased throughout the trimesters. FT3 and FT4 levels were significantly higher in the first trimester compared with the second and third trimesters. TSH, FT3, and FT4 levels were significantly lower in pregnant women compared with non-pregnant women (P?<?0.001).

Conclusions

The present study is the first to establish trimester-specific reference ranges of TSH, FT3, and FT4 in Sudanese women with normal pregnancies. Our results suggest that pregnancy is likely to suppress TSH, T3, and T4 levels in healthy women.

     

Thyroid function and metabolic syndrome in the population-based LifeLines cohort study

Background

The metabolic syndrome (MetS) is a combination of unfavourable health factors which includes abdominal obesity, dyslipidaemia, elevated blood pressure and impaired fasting glucose. Earlier studies have reported a relationship between thyroid function and some MetS components or suggested that serum free thyroxine (FT4) or free triiodothyronine (FT3) levels within the normal range were independently associated with insulin resistance. We assessed how thyroid function relates to MetS prevalence in a large population-based study.

Methods

Data of 26,719 people of western European descent, aged 18–80 years from the Dutch LifeLines Cohort study, all with normal thyroid stimulating hormone (TSH), FT4 and FT3 levels (electrochemiluminescent immunoassay, Roche Modular E170 Analyzer), were available. MetS was defined with the revised National Cholesterol Education Programs Adults Treatment Panel III (NCEP ATP III) criteria. We calculated prevalence of all MetS components according to TSH, FT4 and FT3 quartiles.

Results

At similar TSH levels and age (mean 45 yrs), men had significantly higher levels of FT4, FT3, blood pressure (BP), heart rate, total and LDL-cholesterol, triglycerides (TG), and creatinine, but lower HDL-cholesterol compared to women (all p < 0.001). In total, 11.8% of women and 20.7% of men had MetS. In men, lower FT4 levels were associated with higher prevalence of MetS and all MetS components. In women, lower FT4 quartile was only associated with a higher prevalence of elevated TG, waist circumference, and MetS. However, when corrected for confounding factors like age, BMI, current smoking and alcohol consumption, a significant relationship was found between FT3 and three MetS components in men, and all five components in women. Moreover, the highest quartiles of FT3 and the FT3FT4 ratio predicted a 49% and 67% higher prevalence of MetS in men, and a 62 and 80% higher prevalence in women.

Conclusions

When corrected for possible confounding factors, higher plasma levels of FT3 are associated with several components of the MetS. Only in men, lower FT4 is related to MetS. In the highest FT3 and FT3FT4 quartiles, there is a 50–80% increased risk of having MetS compared to the lowest quartile. Further studies are needed to assess the possible causality of this relationship.

     

Association of <Emphasis Type="Italic">TSHR</Emphasis> Gene Copy Number Variation with TSH Abnormalities

Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and promotes thyroid growth and function, with increased TSH levels typically associated with hypothyroidism. By consulting the literature, we found that the TSHR, PAX8, and PDE4B genes are associated with thyroid function. Recently, copy number variations (CNVs) have been used as genetic markers to investigate inter-individual variation. Therefore, we investigated the relationship between the TSHR, PAX8, and PDE4B gene CNVs and TSH abnormalities, by calculating variations in gene copy number. Four hundred and eighty-one participants, 232 healthy controls and 249 patients with TSH abnormalities, were selected from three distinct areas in China with different iodine statuses. RT-PCR was used to detect CNVs. Urinary iodine concentrations (UIC) were measured by As³⁺–Ce⁴⁺ catalytic spectrophotometry. There was an association between a CNV at the TSHR gene and TSH abnormalities (p?=?0.002). The distribution of PAX8 and PDE4B gene CNVs between patients with TSH abnormalities and healthy controls was not significantly different. UIC >?200 μg/l (OR?=?1.49, 95% CI?=?1.01–2.22) and the TSHR gene (OR?=?6.01, 95% CI?=?1.96–18.41) were found to be risk factors for TSH abnormalities. PAX8 and PDE4B gene CNVs were not significantly associated with TSH abnormalities. There was no significant interaction between UIC and any of the examined CNVs. In conclusion, the TSHR gene CNV was associated with the development of TSH abnormalities. No significant associations were revealed between urinary iodine levels and candidate gene CNVs.     

Thyroid Hormones and Electrocardiographic Parameters: Findings from the Third National Health and Nutrition Examination Survey

Introduction

Altered thyroid status exerts a major effect on the heart. Individuals with hypo- or hyperthyroidism showed various changes in electrocardiograms. However, little is known about how variations in thyroid hormone levels within the normal range affect electrical activities of the heart in the general population.

Methods and Results

We conducted a cross-sectional analysis of 5,990 men and women from the Third National Health and Nutrition Examination Survey. Serum total T4 was measured by immunoassay and TSH was measured by chemiluminescent assay. We categorized T4 and TSH into 7 groups with cut-offs at the 5^th, 20^th, 40^th, 60^th, 80^th, and 95^th percentiles of the weighted population distribution. Electrocardiographic parameters were measured from the standard 12-lead electrocardiogram. We found a positive linear association between serum total T4 level and heart rate in men, and a U-shape association between T4 and PR interval in men and women. TSH level was positively associated with QRS interval in men, while a U-shape association between TSH and QRS was observed in women. No clear graded association between thyroid hormones and corrected QT or JT was found, except that men in the highest category of T4 levels appeared to have longer corrected QT and JT, and men in the lowest category of T4 appeared to have shorter corrected QT and JT.

Conclusions

Variation in thyroid hormone levels in the general population, even within the normal range, was associated with various ECG changes.     

Prevalence of inherited ichthyosis in France: a study using capture-recapture method

Background

Inherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France.

Methods

Capture – recapture method was used for this study. According to statistical requirements, 3 different lists (reference/competence centres, French association of patients with ichthyosis and internet network) were used to record such patients. The study was conducted in 5 areas during a closed period.

Results

The prevalence was estimated at 13.3 per million people (/M) (CI95%, [10.9 – 17.6]). With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 – 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 – 5.9]) and 1.9/M (CI 95% [1.6 – 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 – 1.5]). Prevalence of syndromic forms (all clinical forms together) was estimated at 1.9/M (CI 95% [1.6 – 2.6]).

Conclusions

Our results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies.     

A multinodular goiter as the initial presentation of a renal cell carcinoma harbouring a novel VHL mutation

Background

The major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease.

Case presentation

A 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipple's disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipple's disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipple's disease.

Conclusion

This is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipple's disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.     

Circulating Thyroxine,Thyroid-Stimulating Hormone,and Hypothyroid Status and the Risk of Prostate Cancer

Background

Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Methods

Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2∶1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status.

Results

Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1–4: OR = 0.70, 95% CI: 0.51–0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28–0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9).

Conclusions

In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.     

A Modest Protective Effect of Thyrotropin against Bone Loss Is Associated with Plasma Triiodothyronine Levels

Background

The independent skeletal effect of thyrotropin (thyroid stimulating hormone, TSH) has been suggested in animal studies. However, clinical data on the association between bone loss and variations in TSH levels is inconsistent. This study aimed to investigate the relationship between TSH levels and bone mineral density (BMD).

Methods

We conducted a cross-sectional study with 37,431 subjects (33,052 cases with euthyroidism and 4,379 cases with subclinical thyroid dysfunction) aged over 35 years. We performed thyroid function tests and measured BMD at the lumbar spine, femur neck, and total hip.

Results

Levels of TSH and T3 were positively correlated in women (r = 0.076, P = 0.001) and uncorrelated in men. In both men and women, TSH levels correlated positively and T3 levels correlated negatively with BMD at all skeletal sites in age and body mass index adjusted analyses. BMD increased steadily with TSH levels from the subclinical hyperthyroid to subclinical hypothyroid range in subjects with T3 levels in the highest tertile (119.5–200.0 ng/dL), but was no longer significant in subjects with lower plasma T3 levels.

Conclusions

The variations in TSH levels within the euthyroid and subclinical range were positively correlated with BMD in healthy men and women. The negative effect of T3 on BMD appears to be compensated for by increased TSH in subjects with plasma T3 levels in the upper normal range.