Clinical meaning
The diagnostic approach to hypothyroidism follows a systematic algorithm starting with TSH measurement — the most sensitive screening test for thyroid dysfunction. TSH is elevated in primary hypothyroidism because the pituitary increases TSH output to stimulate the failing thyroid gland (negative feedback). Elevated TSH with low FT4 = overt primary hypothyroidism. Elevated TSH with normal FT4 = subclinical hypothyroidism. Low/normal TSH with low FT4 = secondary (central) hypothyroidism (pituitary/hypothalamic failure — the pituitary cannot appropriately increase TSH). Subclinical hypothyroidism management is nuanced: treat if TSH >10 mIU/L (high risk of progression to overt); for TSH 5-10, consider treatment if symptomatic, positive anti-TPO antibodies (predicts progression), pregnant or planning pregnancy, hypercholesterolemia, or goiter. Monitoring during treatment: recheck TSH 6-8 weeks after starting or changing levothyroxine dose (T4 half-life is 7 days; 4-5 half-lives needed for steady state). Goal TSH varies: 0.5-2.5 for most adults, <2.5 in first trimester pregnancy, 4-6 in elderly >70 (higher TSH may be physiological with aging). Causes to differentiate: Hashimoto (anti-TPO+, most common), post-RAI/surgery, medications (amiodarone — type 1 hypothyroidism from iodine excess in susceptible gland; lithium — blocks T4/T3 release and may trigger autoimmunity), iodine deficiency, subacute thyroiditis (hypothyroid phase follows thyrotoxic phase), postpartum thyroiditis, and central hypothyroidism (check other pituitary axes).