Hypoaldosteronism differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2] Akshun Kalia M.B.B.S.[3]

Overview

Hypoaldosteronism must be differentiated from other diseases that cause hypotension and muscle weakness such as Addison's disease, salt-depletion nephritis, myopathies, celiac disease, Peutz-Jeghers syndrome, anorexia nervosa, syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, and bronchogenic carcinoma. In addition, measurement of plasma renin activity (PRA), serum aldosterone, and serum cortisol is used to differentiate among various subtypes of hypoaldosteronism.

Differentiating Hypoaldosteronism from other Diseases

• Various subtypes of hypoaldosteronism can be differentiated on the basis of plasma renin activity (PRA), serum aldosterone, and serum cortisol. These tests are performed after maintaining an upright position for three hours. Under normal conditions, maintaining an upright position for long duration activates the neuro-hormonal regulation by the kidneys which leads to increased renin and aldosterone release.
• The following table distinguishes among various subtypes of hypoaldosteronism:

Disorder	Plasma Renin Activity	Plasma Aldosterone	Plasma Cortisol
Hyporeninemic hypoaldosteronism	Low	Low	Normal
Hypereninemic hypoaldosteronism	Increased	Low	Normal/↓
Primary adrenal insufficiency	High	Low	Low
Pseudohypoaldosteronism type I	High	High	Normal
Pseudohypoaldosteronism type II	Normal/↓	Normal/↓	Normal

• Hypoaldosteronism must be differentiated from other diseases that cause hypotension and muscle weakness such as Addison's disease, myopathies, celiac disease, Peutz-Jeghers syndrome, anorexia nervosa, syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.

Disease	Differentiating symptoms							Differentiating laboratory findings			Gold standard test
	Hypotension	Abdominal pain	Anorexia/ weight loss	Muscle weakness	Hypoglycemia	Skin pigmentation	Other symptoms	Hyponatremia	Cortisol levels	Other labs
Hypoaldosteronism	+	-	+/-	+	-	+/-	Muscle tenderness	+/-	Normal	---
Addison's disease	+	+	+	+	+	+	N/A	+	Low	---	ACTH stimulation test
Salt-depletion nephritis	+	Flank pain	-	-	-	-	Fever Dysuria Pyuria Oliguria	+	Elevated	<15:1 BUN:CR	---
Myopathies (polymyositis, hereditary myopathies)	-	-	-	+	-	Heliotrope rash and Gottron's sign	Muscle tenderness	-	Normal	N/A	Muscle biopsy
Anorexia nervosa	+	-	+	+	+	-	Distorted body image Oligomenorrhea	-	Elevated	N/A	Psychiatric condition
Celiac disease	-	+	+	-	-	Dermatitis herpetiformis	Greasy stools Increased fecal fat	-	Normal	N/A	Abnormal small bowel biopsy
Syndrome of inappropriate anti-diuretic hormone (SIADH)	-	-	-	-	-	-	N/A	+	Normal	Decreased osmolality Euvolemia Sodium in urine typically >20 mEq/L	Water deprivation test
Neurofibromatosis	-	-	+	+	-	Axillary- and inguinal-area freckling	Occasional development of peripheral sarcomas May have overgrowth of subcutaneous tissues	-	-	N/A	Biopsy of skin tissue
Peutz-Jeghers syndrome	N/A	+	N/A	N/A	N/A	+	Melanotic hyperpigmentation of the skin and mucous membranes	-	Normal	N/A	Colonic imaging showing the small intestinal polyps
Porphyria cutanea tarda	-	+	-	-	-	Blisters on sun-exposed sites	Associated liver disease (usually hepatitis C) Hypertrichosis	-	Normal or elevated	High level of porphyrins in the urine
Bronchogenic carcinoma	-	-	+	+/-	-	+	Cough Dyspnea Hemoptysis	-	Elevated	Increased ACTH and Hypokalemia	Cytological or histological evidence of lung cancer in sputum, pleural fluid, or tissue