The hypothalamic-pituitary (HP) axis is the master neuroendocrine regulatory system connecting the nervous system to the endocrine system through hierarchical hormone cascades with negative feedback loops. The hypothalamus produces releasing and inhibiting hormones that travel via the hypothalamic-hypophyseal portal system to the anterior pituitary, which produces tropic hormones that stimulate peripheral endocrine glands. The HP-Thyroid (HPT) axis: hypothalamic TRH → anterior pituitary TSH → thyroid T3/T4 → negative feedback on TRH and TSH. Primary thyroid failure (Hashimoto) shows high TSH, low T4. Secondary (pituitary) shows low TSH, low T4. The HP-Adrenal (HPA) axis: hypothalamic CRH → anterior pituitary ACTH → adrenal cortisol → negative feedback on CRH and ACTH. Cortisol follows a diurnal pattern (peak early morning). Chronic exogenous glucocorticoids suppress the HPA axis — abrupt withdrawal causes adrenal crisis. The HP-Gonadal (HPG) axis: hypothalamic GnRH (pulsatile) → anterior pituitary FSH/LH → gonads (testosterone/estrogen/progesterone) → negative feedback. Continuous GnRH (vs pulsatile) paradoxically suppresses FSH/LH — basis for GnRH agonist therapy (leuprolide for prostate cancer, endometriosis). Growth hormone axis: hypothalamic GHRH (+) and somatostatin (−) → anterior pituitary GH → liver...