Pathophysiology
Clinical meaning
The hypothalamic-pituitary-thyroid (HPT) axis regulates thyroid hormone production through negative feedback. TRH from the hypothalamus stimulates TSH release from the anterior pituitary, which stimulates the thyroid gland to produce T4 (thyroxine, 80-90%) and T3 (triiodothyronine, 10-20%). T4 is the prohormone converted to active T3 by deiodinase enzymes (type 1 and 2) in peripheral tissues. T3 binds nuclear receptors regulating metabolism, thermogenesis, cardiac function, and neurodevelopment. Hypothyroidism (elevated TSH, low fT4) most commonly results from Hashimoto thyroiditis (autoimmune, anti-TPO positive) or iatrogenic causes (thyroidectomy, radioactive iodine, medications). Hyperthyroidism (suppressed TSH, elevated fT4/fT3) is most commonly caused by Graves disease (TSH receptor stimulating antibodies), toxic multinodular goitre, or toxic adenoma. Subclinical disease (abnormal TSH with normal fT4) requires careful NP decision-making regarding treatment thresholds.