Primary hyperaldosteronism differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

Primary hyperaldosteronism must be differentiated from other diseases that cause hypertension and hypokalemia, such as renal artery stenosis, cushing's syndrome, congenital adrenal hyperplasia, Liddle's syndrome, diuretic use, licorice ingestion, and renin-secreting tumors.

Differentiating Primary Hyperaldosteronism from other Diseases

Primary hyperaldosteronism (PA) should be differentiated from other diseases causing hypertension and hypokalemia for example:

• Renal artery stenosis
• Cushing's syndrome
• Congenital adrenal hyperplasia (CAH)
  • 17 alpha hydroxylase deficiency
  • 11 beta hydroxylase deficiency
• Liddle's syndrome
• Diuretic use
• Licorice ingestion
• Renin-secreting tumors

Hypertension and Hypokalemia

Plasma renin activity

Normal or High (Plasma Renin/Aldosterone ratio <10)

Suppressed (Plasma Renin/Aldosterone ratio > 20)

• Renin-secreting tumors • Diuretic use • Renovascular hypertension • Coarctation of aorta • Malignant hypertension

Urinary aldosterone

Elevated

Normal

Low

Conn's syndrome (Primary aldosteronism)

Profound K depletion

• 17 alpha hydroxylase deficiency • 11 beta hydroxylase deficiency • Liddle's syndrome • Licorice ingestion • Deoxycortisone producing tumor

Add Mineralocrticoid antagonist for 8 weeks

BP response

No BP response

• Deoxycorticosterone excess (Tumor, 17 alpha hydroxylase, and 11 beta hydroxylase deficiency) • Licorice ingestion • Glucocorticoid resistance

Liddle's syndrome

Differential Diagnoses	Clinical features									History Findings	Laboratory Findings
	Headache and hypertension	Nausea and vomiting	Palpitations	Shortness of breath	Diminished pulses	Fatigue	Constipation	Pruritis	Ambiguous genitalia
Renin-Secreting tumors	✔	✔	✔	✔	-	-	-	-	-	Drug-resistant hypertension Chronic headaches	Normal renal function tests Normal liver function tests Metabolic alkalosis (pH > 7.45) Hypokalemia Plasma renin-aldosterone ratio <10
Coarctation of aorta	✔	✔	✔	✔	✔	✔	-	-	-	Young patients (neonates) may have history of: Failure to thrive Poor feeding Lethargy Turner's syndrome Familial predisposition Ventricular septal defects Adults may have a history of: Claudication Epistaxis	Bicuspid aortic valves Notching of ribs Metabolic alkalosis (pH > 7.45) Hyperkalemia Plasma renin-aldosterone ratio <10
11-beta hydroxylase deficiency	✔ (Hypertensive crisis due to increased 11-deoxycorticosterone-11-DOC)	✔	✔	-	-	✔	-	-	✔	Females: Clitoral enlargement Labioscrotal fusion Males: Penile enlargement (If not diagnosed at birth, may present as premature adrenarche, developing body odor with axillary and pubic hair development)	Hypokalemia Increased 11-DOC levels Increased androgens Low urinary aldosterone level
17-alpha hydroxylase deficiency	✔	✔	✔	-	-	-	-	-	✔	Phenotypically females at birth Lack of pubertal development in females Incompletely developed external genitalia in males	Increased serum mineralocorticoids Decreased androgen levels Hypokalemia Low urinary aldosterone level
Uremia		✔	✔	✔	-	✔	✔	✔	-	Patients have chronic kidney disease and maybe on dialysis Features of uremic neuropathy: Autonomic features with postural hypotension, Impaired sweating Diarrhea Impotence Paraesthesia Delayed deep tendon reflexes Muscle wasting Encephalopathy	Increased blood urea nitrogen (BUN) and creatinine (Cr) Hyperkalemia Decreased serum vitamin 1,25 dihydroxy vitamin D3 level
Liddle's syndrome	✔	✔	✔	-	-	-	✔	-	-	Family history of Liddle's syndrome (autosomal dominant inheritance) Nephropathy Arrythmias SCNN1B or SCNN1G gene mutation	Hyporeninemic hypoaldosteronism Hypertension Hypokalemia Enhanced erythrocyte sodium influx  Low urinary aldosterone