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Moon Face: Pathophysiology, Differential Diagnosis, and Link to Cushing's Syndrome

Moon face (moon facies) describes a rounded, plethoric facial appearance resulting from centrifugal fat redistribution and fluid retention. It is a classic clinical sign of hypercortisolism (Cushing's syndrome).

Pathophysiology in Cushing's Syndrome

  • Excess cortisol → enhanced lipoprotein lipase activity in visceral/cervicofacial adipose → preferential fat deposition.
  • Cortisol's mineralocorticoid activity (at high concentrations) → sodium/water retention → facial edema.
  • Protein catabolism → proximal muscle wasting (thin extremities) contrasts with central adiposity.

Etiologies of Cushing's Syndrome

Differential Diagnosis of Moon Facies

  • Long-term systemic corticosteroid use (most common cause overall)
  • Hypothyroidism (myxedematous facies—non-pitting, coarse features)
  • Nephrotic syndrome (periorbital edema, generalized anasarca)
  • Superior vena cava syndrome (facial plethora, distended neck veins)
  • Acromegaly (coarsening, prognathism—not true moon face)
  • Obesity (centripetal fat distribution without other stigmata)

Diagnostic Workup

  1. 24-hour urinary free cortisol (UFC) × 2
  2. Late-night salivary cortisol × 2
  3. 1 mg overnight dexamethasone suppression test
  4. If abnormal: plasma ACTH → pituitary MRI vs. chest/abdomen imaging for ectopic

Moon face is a visible clue to systemic cortisol excess—prompt endocrine evaluation is warranted.

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CategoryExamples
ACTH-dependent (80%)Pituitary adenoma (Cushing's disease, 70%), ectopic ACTH (small cell lung cancer, bronchial carcinoid, thymic NET)
ACTH-independent (20%)Adrenal adenoma, adrenal carcinoma, bilateral macronodular hyperplasia, PPNAD
Iatrogenic (exogenous)Glucocorticoid therapy (prednisone, dexamethasone, inhaled, topical high-potency)