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.

Introduction Hypothyroidism affects skeletal metabolism. Thyroid hormones regulate bone remodeling, and their deficiency may alter bone turnover markers (BTMs), increasing the risk of osteoporosis. Levothyroxine therapy restores euthyroid status, but its impact on bone metabolism requires further evaluation. Aim This study aims to evaluate the effect of levothyroxine therapy in hypothyroidism on thyroid function and bone turnover markers (C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (P1NP)). Methods This cross‑sectional comparative study included 150 participants who were further categorized into three groups: Group I (treated hypothyroidism, n=50), Group II (newly diagnosed untreated hypothyroidism, n=50), and Group III (healthy controls, n=50). Baseline clinical data, thyroid function tests (thyroid-stimulating hormone (TSH), total thyroxine (T4), and total triiodothyronine (T3)), and bone turnover markers (serum CTX and P1NP) were measured. For statistical evaluation, chi‑square and one‑way analysis of variance (ANOVA) tests were used, with p<0.05 considered significant. Results Group II showed significantly elevated TSH (12.8±4.6 mIU/mL) with reduced T4 and T3 compared to Groups I and III (p<0.001). Serum CTX was highest in Group II (0.48±0.12 ng/mL) versus Group I (0.32±0.08 ng/mL) and Group III (0.28±0.07 ng/mL) (p<0.01). Similarly, P1NP was elevated in Group II (62±15 ng/mL) compared to Group I (45±12 ng/mL) and Group III (40±10 ng/mL) (p<0.01). Conclusion Untreated hypothyroidism is found to be linked to more bone resorption and compensatory bone formation, while long‑term levothyroxine therapy normalizes thyroid function and stabilizes bone turnover markers. Early treatment and monitoring of BTMs may help prevent skeletal complications in hypothyroid patients.

Severe hypothyroidism left untreated can lead to the progression of a distinct hypothyroid myopathy. This unique thyroid myopathy is characterized by weakness of the proximal limb muscles with an increase in muscle mass, muscle stiffness, and cramps. There is no consistent concept or guidelines for diagnostic work-up with the typical findings of this specific myopathy. While muscle biopsy can provide additional clinical information, the majority of cases can be diagnosed clinically by the hallmark signs of muscular weakness and pseudohypertrophy of muscles in combination with elevated creatine kinase (CK) and thyroid-stimulating hormone (TSH) levels. We present a patient who developed the hallmark findings of this rare hypothyroid myopathy, in which physical exam and laboratory data provided the diagnosis. Magnetic resonance imaging or muscle biopsy could have been performed to confirm the presence of muscular pseudohypertrophy, but the cost of testing would not have altered the treatment course. Therefore, the diagnosis can be cost-effectively made without invasive diagnostic and radiologic measures.