Pathophysiology
Clinical meaning
Thyroid-stimulating hormone (TSH) is a glycoprotein produced by the anterior pituitary gland and is the single most sensitive and specific test for evaluating thyroid function. The hypothalamic-pituitary-thyroid (HPT) axis operates through a negative feedback loop: the hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to release TSH, which then acts on the thyroid gland to produce thyroxine (T4) and triiodothyronine (T3). T4 is the predominant circulating hormone (>80% of thyroid output) and is converted to the active form T3 by deiodinase enzymes in peripheral tissues. Free T4 and T3 exert negative feedback on both the hypothalamus and pituitary, suppressing TRH and TSH secretion. The TSH-free T4 relationship follows a log-linear pattern: small changes in free T4 produce exponential changes in TSH. This means TSH is abnormal long before free T4 falls outside the normal range, making TSH the earliest and most sensitive marker of thyroid dysfunction. Normal TSH reference range is typically 0.4-4.0 mIU/L, though upper limits vary by laboratory, age (increases with age), and pregnancy (lower in first trimester due to hCG cross-stimulation of TSH receptor). Interpretation...