Is thin fragile skin a symptom of hypercortisolism (Cushing's syndrome) or hypocortisolism?

Thin Fragile Skin is a Symptom of Hypercortisolism (Cushing's Syndrome)

Thin fragile skin is a classic sign of hypercortisolism (Cushing's syndrome) and is not associated with hypocortisolism. 1

Clinical Manifestations of Hypercortisolism Affecting the Skin

Cushing's syndrome, characterized by chronic excessive glucocorticoid exposure, presents with several distinctive cutaneous manifestations:

• Skin atrophy and fragility: Excess cortisol causes thinning of the skin, making it more susceptible to injury and bruising 1, 2
• Excessive bruising: Due to capillary fragility and skin thinning 2
• Purple striae: Distinctive reddish-purple stretch marks, particularly on the abdomen, thighs, and arms 1, 2
• Poor wound healing: Impaired tissue repair due to protein catabolism 2
• Facial plethora: Reddening of the face due to increased perfusion 3
• Hyperpigmentation: Darkening of the skin in certain areas 4, 3

Differentiating Features Between Hypercortisolism and Hypocortisolism

Hypercortisolism (Cushing's Syndrome):

• Thin, fragile skin with easy bruising
• Purple striae
• Central obesity with thin extremities
• Moon facies and buffalo hump (dorsal fat pad)
• Hirsutism and acne
• Hypertension (present in >80% of cases) 1
• Hyperglycemia 1, 5

Hypocortisolism (Adrenal Insufficiency):

• Hyperpigmentation (in primary adrenal insufficiency)
• Hypotension
• Weight loss
• Fatigue and weakness
• Salt craving
• No skin thinning or fragility

Diagnostic Approach for Suspected Cushing's Syndrome

When thin fragile skin is observed along with other suspicious features:

1. Rule out exogenous steroid use - most common cause of Cushing's syndrome 5
2. Initial screening tests:
   • 24-hour urinary free cortisol
   • Late-night salivary cortisol
   • 1mg overnight dexamethasone suppression test 5, 2
3. Determine source of hypercortisolism:
   • Measure plasma ACTH levels to differentiate ACTH-dependent from ACTH-independent causes 5
   • Imaging studies (pituitary MRI, adrenal CT/MRI) 1
   • Bilateral inferior petrosal sinus sampling for suspected pituitary source 5

Clinical Pearls and Pitfalls

• Skin manifestations of Cushing's syndrome may not correlate with biochemical severity of the disease 3
• Thin fragile skin and easy bruising are among the most specific signs of Cushing's syndrome
• Most skin manifestations resolve within 1-2 years after successful treatment, though striae may persist longer 3
• Iatrogenic (exogenous) Cushing's syndrome may have more pronounced hypertrichosis and fungal infections compared to endogenous causes 4
• Hirsutism is more common in endogenous Cushing's syndrome 4

Treatment Considerations

The primary treatment goal is to normalize cortisol levels:

1. Surgery to remove the source of excess cortisol (pituitary adenoma, adrenal tumor, or ectopic source) 5
2. Medical therapy if surgery is contraindicated or unsuccessful:
   • Adrenal steroidogenesis inhibitors (ketoconazole, mitotane) 1
   • Pituitary-directed medications
   • Glucocorticoid receptor antagonists 5
3. Radiation therapy or bilateral adrenalectomy for refractory cases 5

Prompt diagnosis and treatment are essential to reduce morbidity and mortality associated with prolonged hypercortisolism, including cardiovascular complications, osteoporosis, and immunosuppression.