What endocrine disorders can cause orthostatic hypotension?

Endocrine Disorders Causing Orthostatic Hypotension

The primary endocrine disorders causing orthostatic hypotension are diabetic autonomic neuropathy, adrenal insufficiency (both primary and secondary), isolated hypoaldosteronism, and rarely pheochromocytoma. 1, 2

Major Endocrine Causes

Diabetic Autonomic Neuropathy

• Diabetic cardiovascular autonomic neuropathy (CAN) is the most common endocrine cause of orthostatic hypotension, representing an advanced stage of autonomic dysfunction 3
• Orthostatic hypotension in diabetes suggests advanced CAN that should be confirmed by cardiovascular autonomic reflex tests (CARTs) after excluding other causes 3
• Diabetic patients can present with either a "hyperadrenergic" pattern (early autonomic neuropathy with preserved but inappropriate sympathetic responses) or "hypoadrenergic" pattern (advanced neuropathy with blunted catecholamine responses) 4
• Screening for orthostatic symptoms is advisable in any diabetic patient, with yearly orthostatic hypotension testing recommended regardless of symptoms, particularly in patients over age 50 3, 1

Adrenal Insufficiency

• Primary adrenal failure (Addison's disease) causes hypotension through combined glucocorticoid and mineralocorticoid deficiency with hyperreninism 2
• Congenital 21-hydroxylase deficiency with salt loss represents a specific form of primary adrenal insufficiency causing orthostatic hypotension 2
• Secondary adrenal insufficiency from hypopituitarism causes hypotension with hyporeninism due to isolated glucocorticoid deficiency 2
• Acute adrenal crisis should be considered in any acute hypotensive event 2

Hypoaldosteronism

• Primary isolated hypoaldosteronism is rare in adults but can occur with selective injury to the zona glomerulosa or in intensive care settings 2
• Secondary isolated hypoaldosteronism (hyporeninemic hypoaldosteronism) is more common, associated with diabetes mellitus with dysautonomia, chronic kidney disease, advanced age, and certain medications 2
• These conditions typically present with hyponatremia and particularly hyperkalemia alongside hypotension 2
• Pseudohypoaldosteronism (congenital or acquired aldosterone resistance) can also cause orthostatic hypotension 2

Pheochromocytoma

• Pheochromocytoma rarely presents with orthostatic hypotension rather than hypertension, but this paradoxical presentation does occur 2, 5
• Orthostatic hypotension is particularly seen during surgical removal when patients have not been adequately prepared with calcium channel blockers 2
• Screening for pheochromocytoma should be considered in cases of new-onset recurrent syncopal episodes due to orthostatic hypotension 5

Other Neuroendocrine Causes

• Carcinoid syndrome can cause hypotension during carcinoid crisis, typically presenting with flushing and hypotension that responds to subcutaneous somatostatin analogs 2

Diagnostic Approach

Initial Assessment

• Measure blood pressure after 5 minutes supine, then at 1 and 3 minutes of standing to diagnose orthostatic hypotension (≥20 mmHg systolic or ≥10 mmHg diastolic drop) 6
• Assess medication history for culprit drugs (diuretics, psychotropics, alpha-blockers) that may cause or exacerbate orthostatic hypotension 3, 1
• Evaluate volume status and look for signs of dehydration or blood loss 1

Endocrine-Specific Testing

• For suspected adrenal insufficiency: morning cortisol, ACTH, aldosterone, and plasma renin activity to differentiate primary from secondary causes 2
• For diabetic patients: perform CARTs including heart rate variability testing, Valsalva maneuver, and deep breathing tests to confirm CAN 3
• For hypoaldosteronism: check serum potassium (typically elevated), sodium (often low), plasma renin, and aldosterone levels 2
• For pheochromocytoma: 24-hour urinary or plasma fractionated metanephrines in cases of unexplained orthostatic hypotension with episodic symptoms 5

Clinical Pitfalls

• Diabetic patients with orthostatic hypotension often have impaired renin-angiotensin responses despite preserved renal function, contributing to their orthostatic intolerance 4
• Both hyperadrenergic and hypoadrenergic presentations in diabetic orthostatic hypotension represent a spectrum of autonomic dysfunction, not separate entities—the hyperadrenergic pattern indicates early-stage neuropathy 4
• Supine hypertension commonly coexists with orthostatic hypotension in autonomic failure, complicating treatment goals 3, 1, 7
• Treatment should focus on minimizing symptoms and improving functional capacity rather than normalizing blood pressure, while carefully balancing standing blood pressure improvement against worsening supine hypertension 3, 1