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Background: The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T 4 ) versus those receiving no therapy. Objectives: (a) To evaluate thyroid tests under L-T 4 and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Design: Group A children were treated for 24 months and TSH and FT 4 levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. Results: The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. Conclusions: (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH.

Introduction Thyroid disease (TD), particularly hypothyroidism, is an important etiology of hyperprolactinemia (HPRL). We conducted a systematic review of the clinical characteristics, management, and outcomes of adults (> 18 years) with this clinical association. Materials and methods We searched PUBMED, SCOPUS, and EMBASE to find eligible articles published in English from any date till 15th December 2022. Results The final systematic review included 804 patients from 47 articles, of which the majority (85.9%) were females. Menstrual irregularity was the most prominent symptom of HPRL (74.3%). Subclinical hypothyroidism (57.1%) was the most reported TD. Individual patient data were available for 62 patients from 35 studies. The median age was 32 (25–42) years, TSH was 110.25 (50-345.4) mU/L, and PRL level was 60 (37.6–91) ng/ml. On treating TD, 38 (70.4%) patients had complete resolution and 10 (18.5%) had an improvement in HPRL. Of 38 patients with pituitary imaging, 26 (68.4%) showed pituitary enlargement, and 13 (34.2%) showed a suprasellar extension. 13 (76.5%) patients had complete resolution and 3 (17.6%) had an improvement in pituitary enlargement on TD treatment. A positive correlation was observed between higher serum TSH levels and higher serum prolactin levels. Patients with pituitary enlargement on imaging had a higher TSH level compared to those without any pituitary enlargement (Median of 263 (61–602) vs. 50 (24.3–128) mU/L; p -value = 0.01). Conclusion Thyroid hormone replacement can lead to resolution of HPRL and pituitary enlargement in the majority of patients with HPRL due to overt or subclinical hypothyroidism without the need for dopamine agonist treatment.

INTRODUCTION: The pathology mechanism of subclinical hypothyroidism and subclinical hypothyroidism complicated with type 2 diabetes remained uncertain. We aimed to find potential related long non-coding RNAs (lncRNAs) and mRNAs in the above diseases. MATERIAL AND METHODS: Transcriptome sequencing was performed in three patients with subclinical hypothyroidism (S), three patients with subclinical hypothyroidism complicated with type 2 diabetes (SD), and three healthy controls (N). Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were screened in S vs. N, SD vs. N, and SD vs. S group, and the nearby and co-expressed DEmRNAs of DElncRNAs were screened in S vs. N and SD vs. N. Moreover, functional analysis of DEmRNAs was then performed by Metascape. RESULTS: In total, 465, 1058, and 943 DEmRNAs were obtained in S vs. N, SD vs. N, SD vs. S, respectively, and 191 overlapping genes were obtained in S vs. N and SD vs. N group. Among which, LAIR2, PNMA6A, and SFRP2 were deduced to be involved in subclinical hypothyroidism, and GPR162, APOL4, and ANK1 were deduced to be associated with subclinical hypothyroidism complicated with type 2 diabetes. A total of 50, 100, and 88 DElncRNAs were obtained in S vs. N, SD vs. N and SD vs. S, respectively. Combining with the interaction network of DElncRNA-DEmRNA, PAX8-AS1, co-expressed with KIR3DL1, was identified to function in subclinical hypothyroidism, and JHDM1D-AS1, co-expressed with ANK1, was deduced to play a role in subclinical hypothyroidism complicated with type 2 diabetes. CONCLUSIONS: Dysfunctional lncRNAs and mRNAs may be involved in the development of subclinical hypothyroidism and subclinical hypothyroidism complicated with type 2 diabetes.

Subclinical hypothyroidism (SCH) was reported to be associated with accelerating endothelial dysfunction, which is recognized as one of the upstream mechanisms that leads to glomerular injury (lower glomerular filtration rate (GFR)). SCH was also reported to be associated with hyperglycemia, which is associated with higher hemoglobin A1c (HbA1c) levels and induces endothelial dysfunction. Therefore, SCH status could influence the association between HbA1c and reduced eGFR. To clarify those associations, we conducted a prospective study of 1580 Japanese individuals who participated in an annual health check-up in 2014 with 2.8 years of follow-up. All participants had free triiodothyronine (T3) and free thyroxine (T4) levels in the normal range. Among study participants, 88 were diagnosed as having SCH. Even though no significant correlation was observed between HbA1c and annual change in estimated GFR among participants without SCH (multi-adjusted standardized parameter estimate (β) = 0.03, p = 0.250), a significant inverse association was observed among participants with SCH (β = −0.26, p = 0.014). When those analyses were performed among participants who were not taking glucose lowering medication, the observed associations were essentially the same: β = 0.03, p = 0.266 for participants without SCH and β = −0.32, p = 0.006 for participants with SCH, respectively. Therefore, SCH status could influence the association between HbA1c and renal function.

Background Subclinical hypothyroidism (SH) is associated with adverse obstetric outcomes and neurodevelopment disorders. Both iodine deficiency and excess are associated with SH; however, few data regarding iodine nutrition status of pregnant women with SH are available. This study aimed to clarify whether iodine deficiency or excess is associated with SH, especially, when test results for anti-thyroid autoantibodies are negative. Methods A total of 115 women with SH and 104 women with euthyroidism (EH) in early pregnancy in Tianjin, China were investigated, and their serum thyroid-stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroid peroxidase antibody (TPOAb), anti-thyroid globulin antibody (TGAb), urinary iodine (UIC), and urinary creatinine (UCr) concentrations were measured. Thyroid ultrasonography was performed to determine thyroid echogenicity and volume. The UIC, UIC/UCr ratio, prevalence of TPOAb and TGAb positivity, and thyroid gland volume were compared between the EH and SH groups. UIC and ultrasonographic features were analysed in subjects in the SH group who were negative for TPOAb and TGAb. Results Median UIC of SH (154.0 μg/L) and EH (150.1 μg/L) met the World Health Organization criterion for iodine sufficiency in pregnant women. Neither UIC nor the UIC/UCr ratio differed significantly between groups. The prevalence of TPOAb and TGAb positivity in the SH group was significantly higher than that in the EH group ( P  < 0.01). The percentage of subjects with UIC ≥ 250 μg/L in the SH group was significantly higher than that in the EH group ( p  = 0.004). The percentage of subjects negative for autoantibodies and UIC ≥ 250 μg/L in the SH group tended to be higher than that in subjects in the EH group negative for autoantibodies, but the difference was not statistically significant ( p  = 0.025, adjusted test level α = 0.0167). Eight of 18 subjects in the SH group with negative results for TPOAb and TGAb were diagnosed with Hashimoto thyroiditis by means of thyroid ultrasonography. Conclusions Women in early pregnancy with SH in Tianjin were iodine sufficient, but still at risk of iodine deficiency as pregnancy progressed. UIC ≥ 250 μg/L was associated with increased risk of SH. Serological negative autoimmune thyroiditis and UIC ≥ 250 μg/L may play a role in pathogenesis of SH cases with negative results for autoantibodies.

Mild thyroid stimulating hormone （TSH） elevations are highly prevalent whereas large proportion of individuals with TSH elevations is without chronic autoimmune thyroid diseases.TSH secretion exhibits a daily circadian rhythm,and we previously reported that individuals with sleep disorders have significantly higher TSH levels than controls.

Abstract Context With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. Objective To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. Design Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). Setting Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. Participants The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. Main Outcome Measures Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. Results In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. Conclusion Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. Trial registration ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.

ABSTRACT Purpose: To determine the prevalence and association of atherogenic lipid profile in postmenopausal women with subclinical hypothyroidism. Materials (Subjects) and Methods: This as a prospective clinical study included 140 postmenopausal women. In all subjects, basic sociodemographic and anthropometric data, hormonal status of the thyroid gland, and lipid profile were determined. The subjects were followed for a period of 30 months. Results: The subclinical hypothyroidism in postmenopausal women was significantly associated with higher levels of serum cholesterol, triglycerides, LDL-C, and lower HDL-C (p=0.009, p=0.01, p=0.023, p=0.001, respectively). Furthermore, the analysis of repeated measures showed that subclinical hypothyroidism, irrespective of age and duration of postmenopause, was associated with higher levels of serum cholesterol (adjusted beta: 0.43, CI: 0.12, 0.74, p=0.007), triglycerides (adjusted beta: 0.52, CI: 0.21, 0.84, p=0.001) and LDL-C (adjusted beta: 0.35, CI: 0.03, 0.67, p=0.03), and lower levels of serum HDL-C (adjusted beta: -0.48, CI: -0.81, 0.15, p=0.004) Conclusion: Subclinical hypothyroidism is associated with atherogenic lipid profile in postmenopausal women.

Objective: Thyroid disease is a common endocrine disease with important effects on the cardiovascular system. As an adaptive response to myocardial ischemia, coronary collateral circulation (CCC) plays an important role in obstructive coronary artery disease (CAD). The association between serum thyroid hormone levels and development of CCC was investigated in the present study. Methods: In total, 430 consecutive patients who underwent coronary angiography procedure and had documented total occlusion in at least 1 major coronary artery were investigated retrospectively. Degree of CCC was classified according to Cohen-Rentrop method. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were assessed by the chemiluminescence immunoassay technique. Results: In spite of diabetes mellitus (p=0.019), smoking (p<0.001), and TSH (p<0.001), FT3 (p<0.001), FT4 (p=0.015), and subclinical hypothyroidism (SCH) (p<0.001) ratios were significantly different between groups. In regression analysis, SCH (p=0.024), DM (p=0.021), smoking (p<0.001), and heart failure (p=0.029) were independent predictors of poor CCC development in multivariate model 1. When regression analyses were performed based on multivariate model 2, TSH (p<0.001), FT3 (p<0.001), heart failure (p=0.022), smoking (p<0.001), and hyperlipidemia (HPL) (p=0.046) were independent predictors of poor CCC development. Conclusion: In addition to traditional risk factors, SCH, higher serum TSH, and lower FT3 levels were associated with development of poor CCC in patients with obstructive CAD.

Abstract Context Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. Objective We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. Methods Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis. Results Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. Conclusions Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.