What hormone disturbances can cause hypokalemia?

Hormone Disturbances Causing Hypokalemia

The primary hormone disturbances causing hypokalemia are primary aldosteronism (most common), Cushing's syndrome, congenital adrenal hyperplasia, and other mineralocorticoid excess syndromes. 1

Primary Aldosteronism (Most Common)

Primary aldosteronism is the most frequent endocrine cause of hypokalemia with hypertension, occurring in 28.1% of all hypertensive patients with hypokalemia and up to 20% of those with resistant hypertension. 2

Key Characteristics:

• Autonomous aldosterone production that is relatively independent of angiotensin II and potassium regulation, leading to sodium retention, potassium excretion, and suppressed plasma renin activity 2
• Approximately 50% due to unilateral aldosterone-producing adenoma and 50% due to bilateral adrenal hyperplasia 2
• The aldosterone-to-renin ratio (ARR) ≥30 is diagnostic when plasma aldosterone is ≥10 ng/dL 3, 2

Clinical Presentation:

• Hypertension (often resistant) with spontaneous or diuretic-induced hypokalemia 1
• Muscle weakness and cardiac arrhythmias from severe hypokalemia 1

Cushing's Syndrome

Hypercortisolism causes hypokalemia through mineralocorticoid effects of excess cortisol. 1

Clinical Features:

• Central obesity, moon facies, dorsal and supraclavicular fat pads, wide (≥1 cm) violaceous striae, hirsutism 1
• Proximal muscle weakness, depression, hyperglycemia, and hypertension 1
• Ectopic ACTH production (from neuroendocrine tumors) is the most frequent cause of Cushing's syndrome presenting with hypokalemia 4

Diagnostic Approach:

• Overnight 1-mg dexamethasone suppression test for screening 1
• 24-hour urinary free cortisol excretion (preferably multiple collections) or midnight salivary cortisol for confirmation 1

Congenital Adrenal Hyperplasia

Two specific enzyme deficiencies cause hypertension with hypokalemia: 1

11-beta-hydroxylase deficiency:

• Elevated deoxycorticosterone (DOC), 11-deoxycortisol, and androgens 1
• Presents with virilization in addition to hypertension and hypokalemia 1

17-alpha-hydroxylase deficiency:

• Decreased androgens and estrogen; elevated deoxycorticosterone and corticosterone 1
• Incomplete masculinization in males and primary amenorrhea in females 1

Diagnostic Pattern:

• Hypertension and hypokalemia with low or normal aldosterone and renin levels distinguish these from primary aldosteronism 1

Other Mineralocorticoid Excess Syndromes

Rare causes include apparent mineralocorticoid excess (AME) due to 11-beta-hydroxysteroid dehydrogenase deficiency, primary glucocorticoid resistance, and exogenous mineralocorticoid exposure (licorice, carbenoxolone). 5

Clinical Pattern:

• Early-onset or resistant hypertension with hypokalemia 1
• Low aldosterone and renin levels differentiate these from primary aldosteronism 1
• Urinary cortisol metabolites and genetic testing for confirmation 1

Secondary Hyperaldosteronism

Renovascular hypertension (renal artery stenosis) causes elevated renin, leading to secondary aldosterone elevation and hypokalemia. 2

Distinguishing Feature:

• Both aldosterone AND renin are elevated (ARR <30), unlike primary aldosteronism where renin is suppressed 3, 2

Hyperthyroidism

Thyroid hormone excess can cause hypokalemia through transcellular potassium shifts. 1, 3

Clinical Features:

• Warm, moist skin; heat intolerance; nervousness; tremulousness; weight loss; diarrhea 1
• Proximal muscle weakness, lid lag, fine tremor 1
• Screen with thyroid-stimulating hormone and free thyroxine 1, 3

Critical Diagnostic Algorithm

When evaluating hypokalemia with hypertension: 2, 6

1. Measure plasma aldosterone and renin to calculate ARR 2
2. If ARR ≥30 with aldosterone ≥10 ng/dL: Primary aldosteronism—refer to endocrinology for confirmatory testing 2
3. If both aldosterone and renin elevated: Consider renovascular hypertension—evaluate with renal artery imaging 3, 2
4. If aldosterone and renin both low: Consider Cushing's syndrome, congenital adrenal hyperplasia, or other mineralocorticoid excess syndromes 1
5. Check thyroid function in all cases, as hyperthyroidism is a common overlooked cause 3