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Antidiuretic Hormone (ADH): Physiology, Regulation & Disorders

Antidiuretic Hormone (ADH), also called arginine vasopressin (AVP), is a nonapeptide hormone synthesized in the hypothalamus (supraoptic & paraventricular nuclei) and released from the posterior pituitary.

Primary Function

Water conservation – ADH binds V₂ receptors on renal collecting duct principal cells → inserts aquaporin-2 water channels → increases water reabsorption → concentrated urine, reduced volume.

Regulation

  • Osmoreceptors (hypothalamus): Plasma osmolality ↑ (threshold ~280–290 mOsm/kg) → ADH ↑. Primary driver.
  • Baroreceptors (carotid sinus, aortic arch, atria): Effective arterial volume ↓ (hypovolemia, hypotension) → ADH ↑ (non-osmotic).
  • Other stimuli: Nausea, pain, stress, opioids, nicotine → ADH ↑. Alcohol → ADH ↓.

Disorders

ConditionMechanismKey Labs
SIADHEctopic/autonomous ADH secretion (lung CA, CNS disease, drugs)Hyponatremia, low serum osmolality, high urine osmolality, euvolemia
Central Diabetes InsipidusADH deficiency (pituitary surgery, trauma, infiltrative)Hypernatremia, high serum osmolality, low urine osmolality, polyuria
Nephrogenic DIRenal resistance to ADH (Li, hyperCa, genetic AVPR2)Similar labs; no response to desmopressin
Cerebral Salt WastingRenal Na⁺ loss + ADH ↑ (neurosurgery, TBI)Hyponatremia, hypovolemia, high urine Na⁺

Clinical Measurement

  • Plasma ADH (copeptin surrogate) – specialized, not routine.
  • Water deprivation test + desmopressin challenge – differentiates DI types.

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