Antidiuretic Hormone (ADH)

1. Overview

Antidiuretic hormone (ADH), also called vasopressin or arginine vasopressin (AVP), is a peptide hormone involved in water homeostasis and vascular tone regulation. It helps the body conserve water by reducing urine output and also causes vasoconstriction at high concentrations. ADH plays a vital role in maintaining plasma osmolality and blood pressure, especially during dehydration or hypovolemia.

2. Location

ADH is synthesized by the magnocellular neurosecretory cells of the hypothalamus, specifically in the supraoptic nucleus and the paraventricular nucleus. Once produced, it is transported down axons through the pituitary stalk and stored in the nerve terminals of the posterior pituitary gland (neurohypophysis), from where it is released into the bloodstream when stimulated.

3. Structure

ADH is a nonapeptide, meaning it consists of 9 amino acids. Its sequence is highly conserved across mammals. The human form is arginine vasopressin (AVP), with the amino acid sequence Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2. The cysteine residues form a disulfide bond, giving ADH a cyclic structure. Being a peptide hormone, it is water-soluble and acts via membrane-bound receptors.

4. Function

The primary functions of ADH include:

• Water reabsorption: Promotes insertion of aquaporin-2 water channels in the collecting ducts of the kidney, increasing water reabsorption and reducing urine volume.

• Vasoconstriction: At higher concentrations, ADH binds to vascular V1 receptors, causing vasoconstriction and raising blood pressure.

• ACTH modulation: ADH can potentiate the release of ACTH from the anterior pituitary when acting with corticotropin-releasing hormone (CRH).

5. Physiological role(s)

ADH is a key regulator in multiple physiological systems:

• Osmoregulation: When plasma osmolality increases (e.g., during dehydration), hypothalamic osmoreceptors stimulate ADH release to conserve water.

• Volume regulation: In hypovolemia or hypotension, baroreceptors in the carotid sinus and aortic arch trigger ADH release, aiding in fluid retention and vasoconstriction.

• Water conservation: Especially during sleep or fasting, ADH minimizes water loss to maintain hydration.

• Stress response: Through effects on ACTH and cortisol, ADH contributes to the endocrine response to physiological stressors.

6. Clinical Significance

Disorders of ADH secretion or response lead to significant water balance abnormalities:

• Diabetes Insipidus (DI):

  • Central DI: Caused by decreased ADH production (e.g., due to trauma, tumors, or surgery). Results in polyuria, polydipsia, and dilute urine.

  • Nephrogenic DI: Kidneys are unresponsive to ADH, often due to genetic defects or drugs like lithium.

  • Treatment involves desmopressin (synthetic ADH) for central DI and thiazide diuretics or dietary measures for nephrogenic DI.

• Syndrome of Inappropriate ADH Secretion (SIADH):

  • Excessive ADH release despite normal or low plasma osmolality. Causes water retention, hyponatremia, and low serum osmolality.

  • Common causes include CNS disorders, lung tumors (e.g., small-cell carcinoma), and certain medications (e.g., SSRIs).

  • Managed with fluid restriction, salt tablets, or vasopressin receptor antagonists (vaptans).

• Head Trauma or Neurosurgery:

  • Can disrupt the hypothalamic-pituitary tract, leading to transient or permanent ADH deficiency and polyuria.

• Congenital ADH Receptor Defects:

  • Rare X-linked mutations in V2 receptor cause congenital nephrogenic DI in males, requiring lifelong hydration management.