Addison's disease differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Differentiating Addison's disease from other Diseases

Addison's disease should be differentiated from the following diseases:

• Acanthosis nigricans
• Anorexia nervosa
• Chronic fatigue syndrome
• Depression
• Disorders of oral pigmentation
• Hyperthyroidism
• Laugier-Hunziker Syndrome
• Lentigo
• Malignant melanoma
• Melasma
• Occult malignancy
• Oral manifestations of systemic diseases
• Peutz-Jeghers syndrome
• Type 1 diabetes mellitus
• Vitiligo

Addison's disease (primary adrenal insufficiency) must be first differentiated from secondary and tertiary adrenal insufficiency as all the three of them present with similar symptoms due to cortisol and mineralocorticoid hormone deficiencies.

Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as 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.

	Symptoms							Laboratory findings			Gold standard test
	Hypotension	Abdominal pain	Anorexia/ weight loss	Muscle weakness	Hypoglycemia	Skin pigmentation	Other symptoms	Hyponatremia	Cortisol levels	Other labs
Myopathies (polymyositis, hereditary myopathies)	-	-	-	+	-	Heliotrope Gottron's sign	Muscle tenderness	-	Normal	-	Muscle biopsy
Celiac disease	-	+	+	-	-	Dermatitis Herpetiformis	Greasy stools Increased fecal fat	-	Normal	-	Abnormal small bowel biopsy
Syndrome of inappropriate anti-diuretic hormone (SIADH)	-	_	-	-	-	-	-	+	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	-	-	-	Biopsy of skin tissue
Peutz-Jeghers syndrome		+				+	Melanotic hyperpigmentation of the skin and mucous membranes,	-	Normal		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
Salt-depletion nephritis	+	Flank pain	-	-	-	-	Fever Dysuria Pyuria Oliguria	+	Elevated	<15:1 BUN:CR
Bronchogenic carcinoma	-	-	+	-	-	+	Cough Dyspnea Hemoptysis	-	Elevated	Increased ACTH Hypokalemia	Cytological or histological evidence of lung cancer in sputum, pleural fluid, or tissue
Anorexia nervosa	+	-	+	+	-	-	Distorted body image Oligomenorrhea	-	Elevated	-	Psychiatric condition