Objectives The study aimed to explore the relationship of thyroid function and resistance indices with subsequent risk of gestational diabetes (GDM). Design This was a longitudinal study embedded in the Huizhou Birth Cohort. Methods A total of 2,927 women of singleton pregnancy were recruited from January to October of 2019. Thyroid central resistance indices were evaluated by Thyroid Feedback Quartile-Based index (TFQI), Thyrotrophy T4 Resistance Index (TT4RI), and TSH Index (TSHI) based on plasma-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels during the first half of pregnancy. Thyroid peripheral sensitivity was assessed by free triiodothyronine (FT3) to FT4 ratio (FT3/FT4), a proxy of deiodinase activity. GDM was diagnosed between 24 and 28 weeks of gestation by a standardized 75 g oral glucose tolerance test. Multivariable linear and logistic regression was applied to examine the associations of thyroid markers with GDM risk. Results FT3 and FT3/FT4 were positively associated with both fasting and post-load glucose levels, while TSH, TSHI, TT4RI, and TFQI were negatively associated with 1 and 2 h post-load glucose levels. Compared with the lowest quartile, GDM risk in the highest quartile increased by 44% [odds ratio (OR) = 1.44; 95%CI, 1.08–1.92; ptrend = 0.027] for FT3 and 81% (OR = 1.81; 95%CI, 1.33–2.46; ptrend < 0.001) for FT3/FT4, while it lowered by 37% (OR = 0.63; 95%CI, 0.47–0.86; ptrend = 0.002] for TSHI, 28% for TT4RI (OR = 0.72; 95%CI, 0.54–0.97; ptrend = 0.06), and 37% for TFQI (OR = 0.63; 95%CI, 0.46–0.85; ptrend < 0.001). Conclusions This longitudinal study indicated that higher FT3 and FT3/FT4 and lower central thyroid resistance indices were associated with increased risk of GDM.

https://www.frontiersin.org/articles/10.3389/fendo.2022.806256/pdf

Increased Central and Peripheral Thyroid Resistance Indices During the First Half of Gestation Were Associated With Lowered Risk of Gestational Diabetes—Analyses Based on Huizhou Birth Cohort in South China

Context Thyroid hormones influence glucose homeostasis through central and peripheral regulation. To date, the association between thyroid hormone sensitivity and elevated blood glucose (EBG) in patients with coronary heart disease (CHD) remains unknown. The purpose of this study was to investigate the association between thyroid hormone sensitivity and risk of EBG in patients with CHD, and to further explore their association in different sexes and ages. Methods This large multicenter retrospective study included 30,244 patients with CHD (aged 30–80 years) between 1 January 2014 and 30 September 2020. Parameters representing central and peripheral sensitivity to thyroid hormones were calculated. Central sensitivity to thyroid hormones was assessed by calculating the Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), and Thyrotropin Thyroxine Resistance Index (TT4RI), and Parametric Thyroid Feedback Quantile-based Index (PTFQI); peripheral sensitivity to thyroid hormones was evaluated using the ratio of free triiodothyronine (FT3) /free thyroxine (FT4). Taking normal glucose tolerance (NGT) as a reference, logistic regression was used to analyse the relationship between central and peripheral thyroid hormone sensitivity and EBG in patients with CHD. Results Among the 30,244 participants, 15,493 (51.23%) had EBG. The risk of EBG was negatively correlated with TSHI (OR: 0.91; 95%CI: 0.91 to 0.92; P < 0.001), TT4RI (OR: 0.99; 95% CI: 0.99 to 0.99; P<0.001), TFQI (OR: 0.82; 95%CI: 0.80 to 0.84; P <0.001) and PTFQI (OR: 0.76; 95%CI: 0.74 to 0.78; P<0.001). Compared to males and patients aged 60 and below, the OR value for EBG was lower in females and in patients aged over 60 years old. Conversely, EBG risk was positively associated with FT3/FT4 (OR: 1.08; 95% CI: 1.07 to 1.09; P <0.001) and in the sex-categorized subgroups, males had higher OR values than females. Conclusions This study showed that thyroid hormone sensitivity is significantly associated with EBG in patients with CHD. This association is higher in females than in males, and the association in those aged over 60 years old is higher than that in patients aged 60 years and below.

/pdf/impaired-sensitivity-to-thyroid-hormones-is-associated-with-183myip4.pdf

Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Blood Glucose in Coronary Heart Disease

Correlation between thyroid function, sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease in euthyroid subjects with newly diagnosed type 2 diabetes

Central and peripheral sensitivity to thyroid hormones and glucose metabolism in prepubertal children with obesity: pilot multicenter evaluation

Genetic variants in the apolipoprotein E (APOE) gene are associated with lipid metabolism and lipid-related traits in the non-Hispanic population. There have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Hispanic population; therefore, our aim for this study is to examine the APOE gene’s associations with cholesterol level and its related phenotypes. The APOE gene consists of three different alleles, e2, e3, and e4, with e4 being associated with dementia and cardiovascular diseases. A total of 1,382 subjects were collected from the Texas Alzheimer’s Research and Care Consortium (TARCC, N = 1320) and the Initial Study of Longevity and Dementia from the Rio Grande Valley (ISLD-RGV, N = 62). Questionnaires on demographics, medical history, and blood/saliva samples were collected and APOE genotypes were performed. We observed allele frequencies of the APOE e3 (96.7%), e4 (22.6%) and e2 (6.8%) alleles, respectively. Multivariable logistic regression revealed a significant association between the APOE e4 allele and hypercholesteremia (p = 1.8 × 10−4) in our studied Hispanic population. We prove for the first time, that the APOE e4 allele increases the risk for hypercholesterol in Hispanics. Further research is needed to confirm and supports our current findings.

APOE Gene Associated with Cholesterol-Related Traits in the Hispanic Population

Context Thyroid hormone influences glucose homeostasis through central and peripheral regulations. To date, the link between sensitivity to thyroid hormones and prediabetes remains unknown. We aimed to investigate the association between thyroid hormones sensitivity and risk of prediabetes in both general and euthyroid populations. Methods Participants with serum free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) measurements from the health checkup programs of the First Hospital of China Medical University were collected. We measured the parameters representing central and peripheral sensitivities to thyroid hormones (central sensitivity, assessed by calculating Thyroid Feedback Quantile-based Index (TFQI), TSH Index (TSHI), and Thyrotroph Thyroxine Resistance Index (TT4RI); peripheral sensitivity, evaluated by FT3/FT4 ratio). Associations between thyroid hormones sensitivities and risk of prediabetes were assessed with logistic regression. Results A total of 4378 participants (mean age ± SD, 49 ± 11 years) were included, with 1457 (33%) subjects had prediabetes. The risk of prediabetes was negatively associated with levels of TSHI (odds ratio [OR] 0.91; 95% confidence interval [CI], 0.85-0.97), TT4RI (OR 0.91; 95% CI, 0.84-0.99) and Parametric TFQI (PTFQI) (OR 0.89; 95% CI, 0.83-0.95) among all subjects. The association remained significant in euthyroid subjects and euthyroid subjects with negative thyroid autoimmunity. Higher FT3/FT4 ratio was associated with a mild increased risk of prediabetes (95% CI 1.09; 1.02-1.16). Compared with subjects in the lowest quartile of PTFQI, those in the highest quartile had lower risk of prediabetes (0.70; 95% CI, 0.58-0.84). Conclusions Decreased central sensitivity to thyroid hormones is associated with lower risk of prediabetes. This demonstrates the complex interaction between thyroid system and glucose metabolism. Future studies are warranted to confirm our findings and underlying mechanisms.

/pdf/sensitivity-to-thyroid-hormones-and-risk-of-prediabetes-a-4k50jmk6jp.pdf

Sensitivity to Thyroid Hormones and Risk of Prediabetes: A Cross-Sectional Study.

Background: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) is a rare cause of hyperthyroidism. To date there have been only thirteen cases reporting the coexistence of TSHoma with Graves' disease (GD). The diagnosis and management for such hyperthyroidism due to both etiologies remain challenging. Case Report: A 55-year-old Chinese female presented with signs and symptoms of thyrotoxicosis. Thyroid function tests showed elevated thyroid hormones and mildly suppressed TSH values. Her anti-thyrotropin receptor antibody (TRAb) was positive. Octreotide suppression test successfully decreased her TSH. Magnetic resonance imaging showed a pituitary macroadenoma. She underwent endoscopic trans-sphenoidal resection and surgical pathology confirmed a TSH producing pituitary adenoma. Methimazole was prescribed after surgery and her clinical course was monitored. Conclusions: Here we report a case of a 55-year-old female with TSHoma and Graves' disease whose TSH level was mildly suppressed. This case emphasizes the importance of thoroughly evaluating the thyroid function test during the diagnosis of hyperthyroidism. It also highlights the challenges in the diagnosis and treatment of this rare condition.

/pdf/concurrent-graves-disease-and-tsh-secreting-pituitary-5ec5mjyn0v.pdf

Concurrent Graves' Disease and TSH Secreting Pituitary Adenoma Presenting Suppressed Thyrotropin Levels: A Case Report and Review of the Literature.

Serum lipids have been shown to regulate inflammatory and immune processes, but little is known about their association with thyroid autoimmunity. This study aimed to investigate the association of serum lipids with thyroid autoantibody positivity in the general population with normal thyroid-stimulating hormone (TSH) levels. Data regarding the 7688 subjects’ baseline characteristics were retrospectively collected. All subjects were categorized into four groups according to thyroid autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) positivity and serum lipid levels were compared. Binary logistic regression models were used to evaluate the risk of TgAb or TPOAb positivity with increasing serum lipid levels. In 6456 included subjects, after adjusting for confounders, the risk of TgAb positivity was positively associated with increasing low-density lipoprotein cholesterol (LDL-C) levels (OR 1.14, 95% CI 1.03–1.27, P = 0.011) and negatively correlated with the increasing high-density lipoprotein cholesterol (HDL-C) levels (OR 0.77, 95% CI 0.61–0.98, P = 0.035). In female subjects, the association between increasing LDL-C (OR 1.16, 95% CI 1.04–1.28, P = 0.007) or HDL-C levels (OR 0.77, 95% CI 0.61–0.99, P = 0.037) and TgAb positivity become more pronounced. We have shown the associations of HDL-C and LDL-C with TgAb positivity in the general population with normal TSH levels in a gender-dependent manner. This study highlights that serum lipids may be new predictors of thyroid autoimmunity even when TSH is within the reference range.

/pdf/serum-lipids-are-novel-predictors-for-thyroid-autoimmunity-14fkw1pkro.pdf

Jinrong Fu

Papers

Sensitivity to Thyroid Hormones and Risk of Prediabetes: A Cross-Sectional Study.

Concurrent Graves' Disease and TSH Secreting Pituitary Adenoma Presenting Suppressed Thyrotropin Levels: A Case Report and Review of the Literature.

Serum lipids are novel predictors for thyroid autoimmunity in the general population with normal TSH levels from a cross-sectional study