Hypothyroidism (HT) is a common endocrine disorder that adversely affects different body functions. Saraca asoca (SA) is traditionally used as a remedy for gynaecological disorders. Although thyroid hormones are essential for reproductive function, no data are available so far on the impact of SA on thyroid function. Therefore, the current study attempted to evaluate the effects of SA in regulating HT through in vivo and in silico approaches. HT was induced in rats by administering 0.05% 6-propyl-thiouracil (PTU) in their drinking water for 4 weeks and the effects of standardized dose of SA extract (100 mg/kg), derived after a preliminary study, were examined in HT-induced rats for 14 days. LC-MS/MS analysis identified the two triterpenoids in SA. Molecular docking was used to predict the interaction between betulinic acid (BA) and lupeol (LPL) with the thyroid hormone receptors TSHR and TRβ. Oral administration of SA effectively ameliorated PTU-induced HT as revealed by decreased TSH, increased thyroid hormones,5'D1 activity, antioxidants and decreased inflammatory marker, TNF-α with improved liver histology. LC-MS analysis identified the notable presence of (BA) and (LPL) in the test extract. Molecular docking study predicted strong binding energies between BA and LPL and thyroid receptors, TRβ and TSHR, supporting the role of BA and LPL in the management of hypothyroidism. Our study proposed for the first time that BA and LPL may act as potential thyroid agonists, playing a crucial role in the thyroid stimulatory nature of SA. However, further mechanistic study is needed to solidify our findings.

A common concern during thyroid hormone replacement therapy is over-substitution leading to increased risk of primarily osteoporotic fracture, and adverse cardiac outcomes in particular. The addition of synthetic triiodothyronine (T3) to treatment regimens for hypothyroidism has been singled out as being associated with a higher risk of such adverse effects. While thyroid-stimulating hormone (TSH) has been a universally accepted, useful parameter for monitoring treatment responses in thyroid diseases, it is not perfect. This is highlighted by the fact, that 5-10% of patients with hypothyroidism continue to exhibit hypothyroid symptoms, despite normal circulating TSH levels.

Lymphocytic hypophysitis (LYH), attributed to autoimmune mechanisms, typically causes multiple anterior pituitary hormone deficiencies, with corticotroph dysfunction occurring earliest; predominant thyrotroph dysfunction is uncommon. A 65-year-old woman presented with headache, fever, and diplopia. Laboratory tests revealed marked systemic inflammation and cerebrospinal fluid (CSF) pleocytosis. Pituitary magnetic resonance imaging (MRI) demonstrated diffuse enlargement and homogeneous contrast enhancement of the pituitary gland and stalk. Endocrinological evaluation showed paradoxically decreased thyroid-stimulating hormone (TSH) despite low thyroid hormone levels, contrasting with elevated adrenocorticotropic hormone (ACTH) levels. Endocrinological stimulation tests revealed a markedly blunted TSH response, with preserved gonadotropin and growth hormone responses, indicating predominant thyrotroph dysfunction despite preserved corticotroph function. Glucocorticoid therapy resulted in prompt improvement of clinical, laboratory, and MRI findings, with complete recovery of anterior pituitary functions. A presumptive diagnosis of LYH with reversible predominant thyrotroph dysfunction and meningitis secondary to direct extension of pituitary inflammation was established. This case demonstrates that LYH can present with atypical anterior pituitary hormone dysfunction, may be complicated by aseptic meningitis, and requires prompt glucocorticoid therapy for favorable outcomes.

Background: Thyroid function tests are frequently requested, but manufacturer reference intervals often lack age- or sex-based stratification. This study established indirect reference intervals for thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) in a large adult population. We evaluated unsupervised algorithms and conventional partitioning to identify subgroups, compared multiple limit estimation methods, and assessed the diagnostic performance of the derived intervals against an independent, clinically defined external validation cohort. Methods: Data from 37,255 adults (age ≥ 18) collected between 2022 and 2024 were analyzed; a reference population of 5870 individuals was established following standardized exclusion criteria. Age-based subgroups were identified through hierarchical clustering with the Elbow method, and variable importance was assessed using Random Forest analysis. Reference intervals were calculated using non-parametric, Bhattacharya, refineR, and reflimR algorithms, applied to three population frameworks: (1) the total population without stratification, (2) subgroups derived from hierarchical clustering and (3) subgroups defined by the conventional Harris-Boyd partitioning method. Diagnostic performance was subsequently evaluated in an independent external cohort (National Health and Nutrition Examination Survey [NHANES]; N = 2297) for all estimated reference intervals. Three classification scenarios were assessed: TSH-only, fT4-only, and combined TSH + fT4, with sensitivity, specificity, Youden index, and decision curve analysis performed for each. Results: Random Forest analysis identified age as the dominant variable influencing TSH, fT4 and fT3 distributions (mean decrease in accuracy: TSH 41.62, fT4 44.18, fT3 43.7), while sex showed the lowest impact. Clustering yielded six age-based subgroups for analytes. Harris-Boyd partitioning yielded six age-based subgroups for TSH, two sex-based subgroups for fT4, and six combined age-and-sex subgroups for fT3. TSH limits were broadly concordant across all three approaches (six-subgroup partitioning: 0.36-0.68 to 4.75-5.67 mIU/L). For fT4, conventional (sex-based) and clustering (age-based) partitioning produced similar ranges (11.33-20.08 pmol/L), except reflimR's notably lower limit (10.90 pmol/L). For fT3, conventional (age + sex) and clustering (age-only) partitioning showed comparable ranges (3.36-7.03 pmol/L), with clustering revealing a clearer age-related decline in the oldest group. Diagnostic performance varied markedly by analyte. TSH-only classification achieved positive discrimination across all 13 methods (Youden index: 0.173-0.239). In contrast, fT4-only and combined TSH + fT4 classifications performed at or below chance for most methods, with 75% of the cohort falling outside fT4 reference intervals, indicating an inter-platform harmonization issue rather than a partitioning failure. Decision curve analysis confirmed TSH-only classification's superiority, exceeding universal testing from pt ≈ 0.20 onward across all methods. Conclusions: Age-stratified reference intervals combined with limit estimation showed potential diagnostic advantages over manufacturer and non-stratified intervals; however, an independent external validation using a clinically defined outcome indicated that this advantage was not consistently reproduced and was dependent on the clinical decision threshold considered. These results suggest that age stratification and algorithm choice merit further clinically adjudicated validation before broad clinical adoption, and that unsupervised clustering offers a practical, objective alternative to manual subgrouping for laboratories pursuing this approach.

Euthyroid autoimmune thyroiditis (Hashimoto's disease) has been shown to negatively affect female sexual health; however, this adverse impact appears to be mitigated by vitamin D therapy. Emerging research suggests that vitamin E may reduce susceptibility to autoimmune thyroiditis and that supplementation could contribute to improved sexual health outcomes. The present study aimed to investigate whether vitamin E status influences the effects of exogenous vitamin D on female sexual function and depressive symptoms in individuals with this condition. This pilot study included three cohorts of young women with Hashimoto's disease, matched for age, thyroid antibody titers, and 25-hydroxyvitamin D levels, all exhibiting normal TSH and free thyroid hormone concentrations. The cohorts differed in vitamin E intake: below the recommended daily allowance (group 1), adequate intake (group 2), and high intake (exceeding 400 IU daily; group 3). All participants received vitamin D at a daily dose of 100 µg for six months. Serum hormone levels, thyroid antibody titers, and calculated indices of thyroid homeostasis were evaluated at enrollment and at the conclusion of the study. Female sexual function and depressive symptoms were also evaluated at both time points using validated instruments: the Female Sexual Function Index (FSFI) and the Beck Depression Inventory-II (BDI-II). At enrollment, group 2 scored higher than the other cohorts in the sexual desire and arousal domains. Vitamin D supplementation increased serum 25-hydroxyvitamin D in all groups. The decrease in antibody titers was most pronounced in group 2, and only in this group did vitamin D enhance thyroid secretory capacity and increase testosterone levels. In group 2, treatment led to improvements across all FSFI domains and the total score. In group 1, positive effects were limited to the lubrication and lack of pain/discomfort domains, whereas group 3 showed no changes in sexual function. Improvements in female sexual function correlated with vitamin E intake, reductions in antibody titers, and increases in testosterone levels. Significant improvements in depressive symptoms, as measured by the BDI-II, were observed exclusively in group 2. Adequate vitamin E intake is essential to achieve the full effects of vitamin D on female sexual function and mood in young euthyroid patients with Hashimoto's disease.

Although toxicological studies suggest that synthetic phenolic antioxidants and their transformation products (SPAs/TPs) may disrupt thyroid function, epidemiological evidence and exposure safety thresholds remain limited. This study included 810 adults from Jiangsu Province, China, and measured serum concentrations of 12 SPAs, 3 TPs, and 7 thyroid function indicators (TFIs). Multiple linear regression (MLR) and restricted cubic spline (RCS) analyses were used to evaluate associations between individual SPAs/TPs and TFIs, whereas quantile g-computation (qgcomp) and Bayesian kernel machine regression (BKMR) were applied to assess the joint effects of mixed exposure. In addition, the Benchmark Dose Software (BMDS) was used to estimate the benchmark dose (BMD) and its lower confidence limit (BMDL) for serum SPAs/TPs, and to derive the corresponding reference doses (RfDs). The results showed widespread exposure to multiple SPAs/TPs among the study participants. Both individual and mixed exposure to SPAs/TPs were significantly associated with increased levels of free thyroxine (FT4) and total triiodothyronine (T3), as well as decreased levels of thyroid-stimulating hormone (TSH) and the T4/T3 ratio. Among the detected compounds, BHT-COOH (3,5-di-tert-butyl-4-hydroxybenzoic acid) and AO245 (triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate) were the primary contributors to elevated FT4 and T3 levels. Under a benchmark response (BMR) of 5%, the estimated RfDs were 0.018 mg/kg/day for BHT-COOH and 0.181 mg/kg/day for AO245, and potential health risks may exist (HQc > 1). This study is the first to evaluate the effects of exposure to SPAs/TPs on thyroid homeostasis, providing a scientific basis for the formulation and improvement of targeted regulatory policies.

The adrenergic system is known for its ability to influence various physiological and metabolic processes; however, its involvement in thyroid function in non-mammalian vertebrates remains poorly explored. Adult male lizards were treated with β-adrenergic agonists (isoproterenol, terbutaline, and L-isopropylamino-3-(2-thiazoloxy)-2-propanol) and the α-adrenergic antagonist (phentolamine). The effects of β-adrenergic agonists and the α-adrenergic antagonist administered as single and repeated injections were evaluated on plasma TSH, thyroid hormones, hepatic 5'-T4 ORD (type II monodeiodinase) activity, hepatic thyroid hormone contents, blood glucose levels, and thyroid gland histology. β-adrenergic stimulation produced a dose-dependent decrease in plasma TSH, accompanied by significant increases in circulating T3 and T4 levels. These changes were associated with enhanced hepatic monodeiodinase activity, increased hepatic T3 content, reduced hepatic T4 levels, and histological features indicative of thyroid activation. Repeated administrations amplified these effects. In contrast, phentolamine treatment increased plasma TSH levels but reduced circulating and hepatic T3, increased hepatic T4, and tended to decrease deiodinase activity, indicating impaired peripheral thyroid hormone activation. Histological analysis showed reduced follicular synthetic activity, although colloid resorption vacuoles were still present. IPT treatment produced no significant effects. All treatments induced hyperglycaemia, with stronger responses after repeated administrations, suggesting coordinated regulation of thyroid function and energy metabolism by adrenergic pathways. The results demonstrate that β-adrenergic signaling promotes thyroid activation and peripheral hormone conversion, whereas α-adrenergic blockade disrupts thyroid hormone homeostasis. These findings highlight a key role of adrenergic mechanisms in the neuroendocrine and metabolic regulation of reptiles, supporting their importance in physiological adaptation to environmental variability.