thyroid-stimulating hormone

TSH is composed of alpha and beta subunits; the alpha subunit is shared with LH, FSH, and hCG, while the beta subunit confers specificity. TSH secretion is stimulated by hypothalamic thyrotropin-releasing hormone (TRH) and inhibited by somatostatin, dopamine, and negative feedback from free T3/T4 acting on both the pituitary and hypothalamus. TSH binds to the TSH receptor (Gs-coupled) on thyroid follicular cells, activating adenylate cyclase and increasing cAMP, which stimulates iodide uptake, thyroglobulin synthesis, and release of T3/T4. Clinically, TSH is the first-line screening test for thyroid dysfunction: elevated TSH with low free T4 indicates primary hypothyroidism, while low TSH with elevated free T4 indicates primary hyperthyroidism (e.g., Graves' disease). Secondary (central) hypothyroidism shows low or inappropriately normal TSH with low T4, suggesting pituitary or hypothalamic pathology. In Graves' disease, TSH receptor autoantibodies (TSI) mimic TSH action, causing continuous stimulation and hyperthyroidism despite low TSH. TSH-secreting pituitary adenomas are a rare cause of hyperthyroidism with inappropriately normal/elevated TSH. TSH is also used to monitor thyroid hormone replacement therapy and to distinguish subclinical from overt thyroid disease. Diurnal variation exists, with peak levels at night. Understanding the hypothalamic-pituitary-thyroid axis is essential for interpreting these tests correctly in board exams.