A patient with primary adrenal insufficiency (Addison's disease) is noted to have hyperpigmentation, hyponatremia, and hyperkalemia. The mechanism of hyponatremia in Addison's disease involves primarily:

• A Cortisol deficiency causing SIADH-like non-osmotic ADH release that is not suppressible
• B ACTH excess increasing renal prostaglandins that block ENaC channels
• C Cortisol deficiency alone causing cellular shift of Na+ into cells
• D Aldosterone deficiency reducing Na+ reabsorption in the collecting duct, causing urinary Na+ wasting and volume depletion that stimulates non-osmotic ADH release, diluting serum Na+ ✓

Explanation

In Addison's disease (primary adrenal insufficiency), both aldosterone and cortisol are deficient. Aldosterone deficiency is the primary driver of hyponatremia and hyperkalemia: without aldosterone, ENaC channels in collecting duct principal cells are not upregulated, so Na+ is not reabsorbed and K+ is not excreted (ROMK channels not stimulated). Urinary Na+ wasting leads to hypovolemia, which is a powerful non-osmotic stimulus for ADH release, causing additional water retention and further dilutional hyponatremia. Cortisol deficiency also impairs free water excretion by independent mechanisms (cortisol normally facilitates suppression of ADH), contributing to hyponatremia. The combined defects of Na+ wasting + ADH stimulation produce the characteristic hyponatremia. Hyperpigmentation is due to excess ACTH (and MSH from POMC processing) stimulating melanocytes.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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