High prevalence of subclinical thyroid dysfunction and the relationship between thyrotropin levels and cardiovascular risk factors in residents of the coastal area of China

OBJECTIVES:

To investigate the prevalence of subclinical thyroid dysfunction and the relationship between thyrotropin levels and cardiovascular risk factors in residents of the coastal area of China.

METHODS:

Atotalof4256individuals(mean[±SD]age50.51±14.24years; 2079 males, 2177 females,) were enrolled in the present study. Sex, blood pressure, body mass index, waist-to-hip ratio, serum levels of fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid and smoking status were measured. The relationship between thyrotropin levels and cardiovascular risk factors was analyzed.

RESULTS:

The overall prevalence of thyroid dysfunction was 11.07%. The prevalence of subclinical hypothyroidism (6.32%) was higher than that of hyperthyroidism (1.53%). The prevalence of thyroid dysfunction among female subjects was higher than that among male subjects (16.54% versus 5.34%, respectively; P<0.001). Significant differences were detected with respect to body mass index (P=0.026), waist-to-hip ratio (P<0.001), fasting glucose levels (P=0.001), total cholesterol levels (P=0.013), triglyceride levels (P=0.003) and smoking status according to different thyrotropin levels.

CONCLUSION:

The prevalence of thyroid dysfunction was high in residents of China’s coastal area. Significant differences were detected with regard to body mass index, waist-to-hip ratio, fasting glucose levels, total cholesterol levels, triglyceride levels and smoking status according to different thyrotropin levels.     

COPD and Thyroid Dysfunctions

Background

Chronic obstructive pulmonary (COPD) is one of the major causes of morbidity and mortality in the world. COPD is characterized by chronic inflammation in the pulmonary compartment and in the systemic circulation. This disorder is associated with clinically significant alterations in biochemistry and organ function; thyroid dysfunctions are common in chronic diseases, such as COPD. Several characteristics of COPD patients could increase their likelihood of developing hypothyroidism or hyperthyroidism. The purpose of our study was to assess the impact of thyroid dysfunction in patients with COPD.

Methods

We evaluated the pulmonary function tests, arterial blood gases, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and thyroid functions in patients with COPD, recruited between admissions in Respiratory Diseases Unit, Policlinico Umberto I, Rome, Italy, from June 2012 to May 2013. We selected patients with subclinical hypothyroidism (ScH), overt hypothyroidism, and hyperthyroidism, and a control group without thyroid disturbance.

Results

Our results indicate that patients with overt hypothyroidism have lower levels of pO₂, MIP, and MEP compared with subjects with ScH, hyperthyroidism, and the control group. We also found a substantial tendency towards pCO₂ levels increase in patients with hypothyroidism (p = 0.06).

Conclusions

Patients with thyroid dysfunctions have a greater impairment of MIP and MEP and a negative correlation was observed between hypoxemia and TSH. Further studies are needed to investigate whether the treatment of thyroid disfunction could have a beneficial effect on COPD patients’ lung function and prognosis.     

Thyroid Dysfunction in Chinese Patients with Chronic Hepatitis C Treated with Interferon Alpha: Incidence,Long-Term Outcome and Predictive Factors

Background

Thyroid dysfunction (TD) represents an extra-hepatic manifestation of chronic hepatitis C (CHC) and it may also be a side effect of interferon-alpha (IFN-α) based treatment. However, previous studies have shown a wide variation in the incidence of TD in patients with CHC. Furthermore, the long-term outcomes and the predictive factors of TD in patients who receive IFN-α based treatment have still not been fully studied.

Objectives

The purpose of this study was to describe the incidence and long-term outcomes of TD in Chinese patients with CHC receiving IFN-αbased treatment. We also aimed to identify the predictive factors of TD associated with this type of therapy.

Patients and Methods

A retrospective case-series study of 592 consecutive CHC patients with normal baseline thyroid functions, who received IFN-αbased therapy, was performed. Thyroid function was assessed at baseline and every three months during treatment, as well as in the follow-up after cessation of therapy. The incidence and long-term outcomes of TD were observed. The prevalence of pretreatment thyroid peroxidase antibodies (TPOAb) were assayed in a sex- and age-matched nested case-control study. Multivariable stepwise regression analysis was used to explore the independent effects of the baseline factors, on the incidence of TD.

Results

At the end of the IFN-αbased therapy, 68 patients (11.5%) in the study had developed TD, 58 patients (85.3%) presented with subclinical TD, and only 10 patients (14.7%) developed overt thyroiditis. The thyroid function of 46 patients (67.8%) spontaneously returned to normal in the six months of follow-up and only three patients (4.4%) had persistent overt TD symptoms after the 24 month follow-up period. Multivariate stepwise analysis suggested that gender and pretreatment TPOAb were the independent factors related to the incidence of TD. Both female patients (OR, 4.31; 95%CI, 2.06–7.31; P = 1.26×10-4) and participants with a positive pretreatment TPOAb (OR = 3.9, 95%CI, 1.72–8.54, P = 0.008) had an increased risk for the development of TD.

Conclusions

The incidence of TD in Chinese patients with CHC during IFN-αbased therapy was 11.5%, the majority of which was subclinical, while only a very small group had long-term overt TD requiring ongoing medical therapy. Female gender and pretreatment TPOAb positivity are risk factors for the development of TD during IFN-αbased therapy.     

Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in Koreans

Objective  Dyslipidaemia is a well-known manifestation of thyroid dysfunction. Recently, small low-density lipoprotein (LDL) particle size has been linked with development of cardiovascular disease. To better understand the effects of thyroid dysfunction on the development of cardiovascular disease, we examined LDL particle size and lipid profiles in subjects with different thyroid function.
Methods  Included were 46 patients with overt hypothyroidism, 57 patients with subclinical hypothyroidism, 46 patients with overt hyperthyroidism, 51 patients with subclinical hyperthyroidism, and 110 age- and sex-matched healthy control subjects. We measured LDL particle size and lipid profiles in these subjects.
Results  No significant differences were found in LDL particle size between the groups with different thyroid function. Serum total cholesterol and LDL-cholesterol levels were significantly higher in the cases of hypothyroidism than in the cases of hyperthyroidism and the healthy control subjects. Serum triglyceride levels were higher in subjects with overt hypothyroidism than in those with overt hyperthyroidism or healthy control subjects.
Conclusions  LDL particle size, the emerging risk factor for atherosclerosis, did not appear to be significantly affected by the degree of thyroid dysfunction. Increased risk of atherosclerosis in hypothyroidism does not appear to be associated with LDL particle size, the non-traditional cardiovascular risk factor.     

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.     

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.     

Vasoactive intestinal polypeptide concentrations in heart atria of hypothyroid rats

OBJECTIVES:

To determine putative effects of various protocols of propylthiouracil (PTU)-induced hypothyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels in the atria of developing and adult female rats.

ANIMALS AND METHODS:

Perinatal hypothyroidism was induced by treating pregnant rats with 0.05% PTU in drinking water from late gestation till the age of 60 days (P-PTU). Adult rats were given PTU for 10, 30 or 70 days (PTU-10, PTU-30 and PTU-70, respectively). Corresponding age-matched controls were left intact (P-Cont, Cont-10, Cont-30 and Cont-70, respectively). Resting heart rate, serum total thyroxine concentration, body weight and atrial weight were determined in all animals. VIP-LI levels in tissue extracts were measured by radioimmunoassay.

RESULTS:

The values of heart rate, serum total thyroxine, body weight and atrial weight showed that 10-day treatment did not suppress thyroid gland function completely. However, the remaining experimental protocols were sufficient to reach stable hypothyroid conditions. Thyroid hormone deficiency led to a significant increase in VIP-LI levels in both atria of PTU-30 and PTU-70 rats (P<0.01 versus corresponding controls). Interestingly, in P-PTU atria, VIP-LI reached significantly higher values than in rats treated with PTU for the same time during adulthood (PTU-70).

CONCLUSIONS:

These results provide new evidence that hypothyroidism interferes with VIP-ergic innervation in rat heart atria. The impact of thyroid hormone deficiency on VIP-LI levels differed in P-PTU and PTU-70 rats suggesting that thyroid hormone may play an important part in the development of VIP-ergic innervation in rat heart atria.     

Associations of Triiodothyronine Levels with Carotid Atherosclerosis and Arterial Stiffness in Hemodialysis Patients

Summary

Background and objectives

End-stage renal disease is linked to alterations in thyroid hormone levels and/or metabolism, resulting in a high prevalence of subclinical hypothyroidism and low triiodothyronine (T3) levels. These alterations are involved in endothelial damage, cardiac abnormalities, and inflammation, but the exact mechanisms are unclear. In this study, we investigated the relationship between serum free-T3 (fT3) and carotid artery atherosclerosis, arterial stiffness, and vascular calcification in prevalent patients on conventional hemodialysis.

Design, setting, participants, & measurements

137 patients were included. Thyroid-hormone levels were determined by chemiluminescent immunoassay, carotid artery–intima media thickness (CA-IMT) by Doppler ultrasonography, carotid-femoral pulse wave velocity (c-f PWV), and augmentation index by Sphygmocor device, and coronary artery calcification (CAC) scores by multi-slice computerized tomography.

Results

Mean fT3 level was 3.70 ± 1.23 pmol/L. Across decreasing fT3 tertiles, c-f PWV and CA-IMT values were incrementally higher, whereas CACs were not different. In adjusted ordinal logistic regression analysis, fT3 level (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97), age, and interdialytic weight gain were significantly associated with CA-IMT. fT3 level was associated with c-f PWV in nondiabetics but not in diabetics. In nondiabetics (n = 113), c-f PWV was positively associated with age and systolic BP but negatively with fT3 levels (odds ratio = 0.57, 95% confidence interval 0.39 to 0.83).

Conclusions

fT3 levels are inversely associated with carotid atherosclerosis but not with CAC in hemodialysis patients. Also, fT3 levels are inversely associated with surrogates of arterial stiffness in nondiabetics.     

Evaluation of right ventricular function in patients with thyroid dysfunction

BACKGROUND: Thyroid gland dysfunction affects the structure and function of the heart. Tissue Doppler echocardiography is a new technique, and it has been used frequently in the evaluation of ventricular function. In the present study, right ventricular function was assessed in patients with overt or subclinical hypothyroidism and hyperthyroidism and in healthy subjects using the tissue Doppler method, and results were compared. PATIENTS AND METHODS: 20 healthy subjects and 63 patients diagnosed with overt and subclinical hypothyroidism and hyperthyroidism were included in the study. Annular and myocardial systolic peak velocities, early and late diastolic peak velocities, precontraction, total contraction and relaxation times of the right ventricle were recorded by tissue Doppler echocardiography. The results of the patients were compared to those of the controls. RESULTS: Myocardial systolic velocity was significantly higher in patients with hyperthyroidism. Annular and myocardial late diastolic velocities were found to be significantly lower in patients with overt hypothyroidism. Annular precontraction time was increased in patients with overt and subclinical hypothyroidism. Myocardial precontraction time was decreased in patients with hyperthyroidism, and increased in patients with overt hypothyroidism patients. Annular relaxation time was increased in patients with overt hypothyroidism. CONCLUSIONS: Right ventricular function is affected in patients with thyroid diseases. The tissue Doppler technique is a suitable tool to detect impairments in right ventricular function. There is a significant correlation between serum thyroid hormone levels and right ventricular velocities and time intervals.     

Prevalence of thyroid disease in patients with obstructive sleep apnea

Objectives

Studies have suggested that ethnicity and environment may influence thyroid disease. We aim in this study to determine the prevalence of thyroid disease among Saudi (Arab) patients with laboratory-diagnosed obstructive sleep apnea (OSA) and the characteristics and predictors of thyroid disease associated with OSA.

Methods

Serum thyroid-stimulating hormone (TSH) and free-thyroxine (FT4) levels were measured in all patients referred to the sleep disorders center for an overnight sleep study. The levels were measured within 4 weeks of the sleep study. Type I attended polysomnography (PSG) was performed for all patients.

Results

During the study period, 271 patients with OSA and a mean age of 48.7 ± 14.1 yr, a body mass index (BMI) of 37.7 ± 9.6 kg/m² and an AHI of 55.2 ± 37/hr as well as 76 non-OSA patients with a mean age of 40.8 ± 14.9 yr, a BMI of 33.7 ± 8.9 kg/m² and an AHI of 3.8 ± 3.1/hr underwent thyroid function tests. In the OSA patients, the prevalence of newly diagnosed clinical hypothyroidism was 0.4%, and the prevalence of newly diagnosed subclinical hypothyroidism was 11.1%. In the non-OSA patients, the prevalence of newly diagnosed clinical hypothyroidism was 1.4%, and the prevalence of newly diagnosed subclinical hypothyroidism was 4%. There were no cases of clinical or subclinical hyperthyroidism in the studied group. Female gender was the only predictor of clinical hypothyroidism.

Conclusion

In the OSA patients, the prevalence of newly diagnosed clinical hypothyroidism was low; however, subclinical hypothyroidism was common among patients with OSA.     

Prognostic impact of subclinical thyroid dysfunction in heart failure

Background

Therapeutic and prognostic implications of subclinical thyroid dysfunction in patients with heart failure (HF) are unclear. We compared the prognostic impact of euthyroidism, subclinical thyroid dysfunction, and euthyroid sick syndrome (ESS) in systolic HF.

Methods

We included 1032 patients hospitalized for systolic HF (left ventricular ejection fraction [LVEF] ≤ 40%) who participated in a randomized trial assessing the effects of a HF disease management program. Patients with incomplete thyroid function tests or thyrotropic medication were excluded. In the remaining 758 subjects, the risk of all-cause death was estimated based on TSH only, or full thyroid function profile. Changes of thyroid function after six months were assessed in 451 subjects.

Results

Subclinical thyroid dysfunction was present in 103 patients at baseline (14%). No differences were found between groups regarding NYHA class (P = 0.29), and LVEF (P = 0.60). After a median follow-up of three years patients with ESS (n = 13) had a 3-fold age-adjusted increased risk of death compared to euthyroid patients (P = 0.001). However, neither subclinical hyperthyroidism (HR 1.18, 95%CI:0.82–1.70) nor hypothyroidism (HR 1.07, 95%CI:0.58–1.98) were associated with increased age-adjusted mortality risk. Subclinical thyroid dysfunction had normalized spontaneously at follow-up in 77% of patients. However, persistent subclinical thyroid dysfunction was also not associated with worse outcome.

Conclusions

In this large well-characterized HF cohort, subclinical thyroid dysfunction did not predict an increased mortality risk. Thus, in patients with moderate to severe HF, further diagnostic and therapeutic procedures for subclinical thyroid dysfunction appear dispensable. ESS was an infrequent but important indicator of a poor prognosis in HF.

Clinical trial registration

URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.     

No association between HIV disease and its treatment and thyroid function

OBJECTIVES: The aims of the study were (i) to investigate the prevalence of overt and subclinical thyroid disease in HIV-positive patients in a London teaching hospital; (ii) to determine risk factors associated with the development of thyroid dysfunction, including highly active antiretroviral therapy (HAART) and individual antivirals, and (iii) to determine the occurrence of thyroid dysfunction longitudinally over 3 years. METHODS: The study consisted of retrospective analyses of thyroid function tests (TFT) in HIV-positive patients. The period prevalence of and factors associated with clinical and subclinical thyroid dysfunction were investigated. Patients with normal TFT but previous thyroid disease were identified from pharmacy records and included in the overt category. RESULTS: A total of 1565 patients (73% of the clinic population) had at least one TFT taken since 2001. Overall, 3584 samples were analysed. Of the patients included in the study, 1233 (79%) were male, 1043 (66%) were white and 365 (23%) were black African, and in 969 (62%) the main risk for HIV was homosexual sex. Median age at baseline was 37 years. Nine hundred patients (58%) were on HAART at the start of the study. Thirty-nine (2.5%) were found to have overt hypothyroidism, and eight (<1%) had overt hyperthyroidism. Sixty-one (4%) had subclinical hypothyroidism, five (<1%) had subclinical hyperthyroidism and 263 (17%) had a nonthyroidal illness. A normal TFT was obtained for 1118 patients (75.5%). Multivariate analysis suggested that no independent variables were significantly associated with overt hypothyroidism, including HAART and stavudine use specifically. Repeated measurements over 3 years were available for 825 patients and only eight new cases (1%) of overt thyroid disease occurred. CONCLUSIONS: The prevalence of overt thyroid disease was low in this cohort, suggesting that screening is not warranted.     

Long term thyroid function after subtotal thyroidectomy for Graves' disease

Between 1973 and 1980, 93 patients with Graves' disease underwent subtotal thyroidectomy by the same surgeon (the size of thyroid remnant was 4 g per side). No case of operative mortality, no case of thyroid storm nor of surgical complications occurred. Three months after surgery 40% of patients were euthyroid, 25% had overt hypothyroidism, 35% had subclinical hypothyroidism. In the following yr important variations of thyroid function were observed. The number of patients with subclinical hypothyroidism decreased slowly (22% and 9% at 3 and 6 yr, respectively), and some became euthyroid, some hypothyroid, others relapsed. Seven patients had recurrent hyperthyroidism. In particular at 3 yr 45% of patients were euthyroid, 28% had overt hypothyroidism, 22% had subclinical hypothyroidism, 4% had recurrence; at 6 yr 56% were euthyroid, 32% had overt hypothyroidism, 9% had subclinical hypothyroidism, 3% had recurrence. Four out of the 8 patients operated under 20-yr-old became hypothyroid in comparison with only 2 out of the 15 patients over 50-yr-old. Relapses were present only in patients operated at less than 40-yr and only in females. No correlation was found between thyroid lymphocytic infiltration and thyroid function after surgery, nor between the presence of antithyroid antibodies and hypothyroidism. All cases who relapsed had high TMA titers both before and after operation. This study confirms the need for accurate follow-up after subtotal thyroidectomy for Graves' disease.     

Etiologic discussion and clinical relevance of thyroid ultrasonography in subclinical hypothyroidism. A retrospective study in 1845 patients

Background

Acquired subclinical hypothyroidism in adulthood is mainly due to autoimmune thyroiditis. In the absence of a goiter or a palpable firm thyroid, measurement of thyroid antibodies can improve the diagnosis. Whether thyroid antibodies are detected or not, what might be the clinical relevance of ultrasonography in this setting?

Methods

We studied 1845 cases of subclinical hypothyroidism in adults recruited for symptoms indicative of hypothyroidism or thyroid pathology. All patients were screened for thyroid antibodies and underwent an ultrasonographic thyroid examination.

Localisation

Multicentric retrospective study.

Results

Chronic autoimmune thyroiditis was confirmed in 70% of patients. Thyroid antibodies were undetectable in 30% of patients. In all patients, thyroid ultrasound facilitated measurement of the thyroid volume and detection of non-palpable nodules and therefore allowed biopsy. In patients negative for thyroid antibodies, ultrasonography suggested autoimmune thyroiditis in 31% of cases. Ultrasonography did not contribute to diagnosis in a large number of patients without nodules and in case of normal echostructure. The strategy of thyroid hormone replacement therapy was not influenced by ultrasonographic data. Thyroid biopsies detected smears suspected to be cancerous in 10 patients (4%). Cancer was confirmed in nine patients after surgery. Ultrasonography displayed suspicious aspects in six patients.

Conclusion

In subclinical hypothyroidism, thyroid ultrasonography is not required for the diagnosis of autoimmune thyroiditis but is useful for patients with abnormal thyroid palpation and allows detection of non-palpable thyroid nodules. For patients that were negative for thyroid antibodies, thyroid ultrasonography can improve diagnosis for some patients, allowing detection of autoimmune thyroiditis.     

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 Abnormalities and Cognitive Impairment in Elderly People: Results of the Invecchiare in Chianti Study

OBJECTIVES: To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition.
DESIGN: Cross-sectional.
SETTING: Community-based.
PARTICIPANTS: One thousand one hundred seventy-one men and women aged 23 to 102.
MEASUREMENTS: Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs ≥65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders.
RESULTS: Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P <.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P <.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61±6.88 vs 24.72±4.52, P <.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P =.003).
CONCLUSION: Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.     

Yield and cost of performing screening tests for constipation in children

BACKGROUND:

Chronic constipation is one of the most common reasons for pediatric outpatient visits. Clinical guidelines recommend that the work-up for chronic refractory constipation include thyroid function tests, celiac serology, and measurement of calcium and lead levels. Data to justify routine screening of constipated children using these laboratory tests are lacking.

OBJECTIVES:

To study the prevalence of celiac disease, hypothyroidism, hypercalcemia and lead poisoning in children with chronic constipation; and to estimate the health care costs of applying the guideline recommendations.

METHOD:

Charts of constipated children from 2007 to 2011 were reviewed for the present retrospective cohort study. Results and costs of thyroid function tests, celiac panel, total immunoglobulin (Ig) A, and determination of lead and calcium levels were analyzed.

RESULTS:

A total of 7472 children (mean age 7.9 years; 3908 female) were evaluated: 1731 patients were screened for celiac antibodies; 55 had elevated tissue transglutaminase IgA levels and 29 had biopsy-positive celiac disease. Only three celiac patients had constipation as the sole presenting symptom; 1703 patients were screened for total IgA levels; 55 had IgA deficiency and two had biopsy-positive celiac disease; 2332 had free T4 and/or thyroid-stimulating hormone levels; and 14 had hypothyroidism. Only two patients had constipation as the sole presenting symptom; 4651 patients had calcium levels measured, 10 of whom had high levels but normal repeat values. Three patients had normal lead levels. The mean cost per patient was USD$1,014. Total screening cost for all patients was USD$4.7 million.

CONCLUSION:

Constipation alone did not increase the likelihood of celiac disease or hypothyroidism above the population prevalence. No benefit of screening for hypercalcemia was found. High health care costs were associated with the use of screening tests for organic constipation.     

轻度碘缺乏城市食盐加碘后甲状腺疾病流行病学调查研究

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

A clinical and therapeutic approach to thyrotoxicosis with thyroid-stimulating hormone suppression only

Subclinical hyperthyroidism is defined as normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations and persistently suppressed thyroid stimulating hormone (TSH) concentrations. The most common cause of subclinical hyperthyroidism is the use of suppressive doses of L-thyroxine for treatment of hypothyroidism or, less commonly, diffuse nontoxic goiter or thyroid carcinoma (exogenous subclinical hyperthyroidism). Endogenous subclinical hyperthyroidism may be caused by a variety of thyroid disorders that result in overproduction and release of thyroid hormones from the gland with normal/high 24-hour thyroid radioiodine uptake or by inflammation in the thyroid resulting in release of excess thyroid hormones and low 24-hour thyroid radioiodine uptake. Several groups have investigated whether persistent endogenous or exogenous subclinical hyperthyroidism, like overt hyperthyroidism, causes symptoms, adverse effects on the cardiovascular and the skeletal systems, and increased mortality, whether endogenous subclinical hyperthyroidism evolves to overt thyrotoxicosis, and whether or not it should be treated. The present report reviews the most important and recent studies of subclinical hyperthyroidism and attempts to draw conclusions based upon the literature and the authors' experience.     

Screening of HHEX Mutations in Chinese Children with Thyroid Dysgenesis

Objective:

Congenital hypothyroidism (CH) is a frequent neonatal endocrine disease with an incidence of about 1:2500 worldwide. Although thyroid dysgenesis (TD) is the most frequent cause of CH cases, its pathogenesis remains unclear. The aim of this study was to screen the hematopoietically-expressedhomeobox gene (HHEX) mutations in Chinese children with TD.

Methods:

Genomic deoxyribonucleic acid was extracted from peripheral blood leukocytes in 234 TD patients from Shandong Province. Mutations in all exons and nearby introns of HHEX were analyzed by direct sequencing after polymerase chain reaction amplification.

Results:

Sequencing analysis of HHEX indicated that no causative mutations were present in the coding regionof the TD patients. However, a genetic variant (IVS2+ 127 G/T, 10.26%) was observed in the intron 2 in HHEX.

Conclusion:

Our results indicate that the frequency of HHEX mutation is very low and may not be the main causative factor in Chinese TD patients. However, these results need to be replicated using larger datasets collected from different populations.