Which endocrine disorder causes orthostatic hypotension?

Endocrine Pathology Causing Orthostatic Hypotension

Adrenal insufficiency is the primary endocrine disorder that causes orthostatic hypotension, with diabetic autonomic neuropathy being the most common endocrine cause in clinical practice. 1, 2

Primary Endocrine Causes

Adrenal Insufficiency (Most Critical)

• Insufficient cortisol production during stress leads to progressive loss of vasomotor tone and impaired alpha-adrenergic receptor responses to noradrenaline, resulting in orthostatic hypotension that progresses to supine hypotension and potentially fatal shock if uncorrected. 1
• Adrenal insufficiency can be primary (adrenal gland failure with hyperreninism) or secondary (central/pituitary origin with hyporeninism). 3
• Orthostatic hypotension is an early warning sign of impending adrenal crisis—monitoring should include both sitting and supine blood pressure measurements to detect orthostatic changes before volume-resistant hypotension develops. 1
• Congenital 21-hydroxylase deficiency with salt loss represents a specific form of primary adrenal insufficiency causing orthostatic hypotension. 3

Hypoaldosteronism

• Isolated hypoaldosteronism causes orthostatic hypotension and characteristically presents with hyponatremia and hyperkalemia. 3
• Primary hypoaldosteronism (with hyperreninism) is rare in adults but can occur with selective injury to the zona glomerulosa. 3
• Secondary hypoaldosteronism (with hyporeninism) occurs with diabetes mellitus complicated by dysautonomia, chronic kidney disease, advanced age, and certain medications. 3
• Pseudohypoaldosteronism represents congenital or acquired resistance to aldosterone, causing similar orthostatic symptoms. 3

Diabetic Autonomic Neuropathy

• Diabetic cardiovascular autonomic neuropathy (CAN) is the most common endocrine cause of orthostatic hypotension in clinical practice, representing an advanced stage of autonomic dysfunction. 2
• Yearly orthostatic hypotension testing is recommended in diabetic patients regardless of symptoms, particularly after age 50. 2
• Diagnosis should be confirmed by cardiovascular autonomic reflex tests (CARTs) including heart rate variability, Valsalva maneuver, and deep breathing tests after excluding other causes. 2
• Diabetic dysautonomia causes secondary hypoaldosteronism with hyporeninism, contributing to the orthostatic hypotension. 3

Less Common Endocrine Causes

Pheochromocytoma

• Paradoxically, pheochromocytoma can cause hypotension, particularly during surgical removal when patients have not been adequately prepared with calcium channel blockers. 3

Neuroendocrine Tumors

• Carcinoid syndrome can present with flushing and hypotension (carcinoid crisis), which responds to subcutaneous somatostatin analogs. 3

Key Diagnostic Considerations

• The fundamental pathophysiology in endocrine-related orthostatic hypotension is failure of peripheral vascular resistance to increase appropriately upon standing, not primary cardiac pump failure. 4, 2
• In neurogenic orthostatic hypotension (including diabetic autonomic neuropathy and adrenal insufficiency), the heart rate response is blunted (typically <10 beats per minute increase), whereas non-neurogenic causes show preserved or enhanced heart rate response. 1, 4
• Supine hypertension commonly coexists with orthostatic hypotension in autonomic failure, complicating treatment goals. 2

Clinical Pitfalls to Avoid

• Do not attribute orthostatic hypotension solely to medications or volume depletion without screening for underlying endocrine pathology, particularly adrenal insufficiency and diabetic autonomic neuropathy. 2, 3
• Persistent pyrexia in the perioperative period may indicate adrenal insufficiency rather than infection—steroid supplementation should not be withdrawn while the patient is febrile. 1
• In patients with known adrenal insufficiency, monitor for early signs of crisis (malaise, somnolence, cognitive dysfunction, orthostatic hypotension) before volume-resistant hypotension develops, as the latter may be a late or agonal event. 1
• Treatment goals should focus on minimizing symptoms and improving functional capacity rather than normalizing blood pressure, carefully balancing standing blood pressure improvement against worsening supine hypertension. 2