What are the endocrine causes and treatments of facial puffiness?

Endocrine Causes of Facial Puffiness

The two primary endocrine causes of facial puffiness are hypothyroidism (presenting with periorbital puffiness) and Cushing's syndrome (presenting with "moon face"), with hypothyroidism being far more common at <1% prevalence versus <0.1% for Cushing's syndrome. 1

Primary Endocrine Causes

Hypothyroidism

• Periorbital puffiness is the characteristic facial manifestation, accompanied by coarse skin, cold skin, and delayed ankle reflexes 1
• Additional clinical features include dry skin, cold intolerance, constipation, hoarseness, weight gain, and goiter 1
• The underlying mechanism involves myxedema—edematous skin changes from glycosaminoglycan deposition in long-standing hypothyroidism 2
• Screen with thyroid-stimulating hormone (TSH) and free thyroxine (T4) 1
• Treatment is thyroid hormone replacement (levothyroxine), which resolves the facial puffiness as thyroid function normalizes 3

Cushing's Syndrome

• "Moon face" (rounded facial appearance) is the hallmark facial feature, occurring with central obesity and dorsal/supraclavicular fat pads 1
• Facial puffiness was present in 76% of patients with ectopic Cushing syndrome in one series 4
• Associated features include rapid weight gain with central distribution, wide (≥1 cm) violaceous striae, proximal muscle weakness, depression, hyperglycemia, and hirsutism 1
• Screen with overnight 1-mg dexamethasone suppression test 1
• Confirm with 24-hour urinary free cortisol excretion (preferably multiple collections) or midnight salivary cortisol 1
• Treatment depends on etiology: surgical resection of ACTH-secreting or cortisol-secreting tumors, medical therapy with ketoconazole or metyrapone for hypercortisolism control, or bilateral adrenalectomy in refractory cases 4

Important Diagnostic Considerations

Pseudo-Cushing's Syndrome

• Conditions like polycystic ovary syndrome, obesity, and chronic alcoholism can mimic Cushing's syndrome with similar facial features 5
• Use late night salivary cortisol measurements, 24-hour urinary free cortisol, and dexamethasone suppression test for initial evaluation 5
• Advanced testing (Dex-CRH test, serial late night salivary cortisol, desmopressin stimulation test) helps differentiate from true Cushing's disease 5
• Repeat testing after 3-6 months of treating the underlying condition to assess improvement 5
• Single cortisol measurements are unreliable; multiple tests over time provide more accurate assessment 5

Hyperthyroidism (Graves' Disease)

• Severe eyelid puffiness can occur as part of Graves' ophthalmopathy, which is highly disease-specific 2
• Peripheral edema may develop with or without heart failure 2
• Other features include warm/moist skin, heat intolerance, nervousness, tremulousness, insomnia, weight loss, lid lag, and fine tremor 1
• Screen with TSH and free T4; confirm with radioactive iodine uptake and scan 1

Rare Endocrine Causes

Acromegaly

• Coarsening and enlargement of facial structures from glycosaminoglycan deposition and soft tissue thickening 3
• Acral features, large hands/feet, frontal bossing, enlarging shoe/glove/hat size 1
• Screen with serum growth hormone ≥1 ng/mL during oral glucose load; confirm with elevated age- and sex-matched IGF-1 level and pituitary MRI 1

Common Pitfalls to Avoid

• Do not rely on single cortisol measurements—they are unreliable and require serial testing 5
• Do not use bilateral inferior petrosal sinus sampling (IPSS) to diagnose hypercortisolism—it is only for localizing the source after biochemical confirmation 5
• Central obesity is uncommon in ectopic Cushing syndrome (only 14% in one series), so its absence does not exclude the diagnosis 4
• Hyperpigmentation and proximal myopathy are more common in ectopic ACTH syndrome than classic Cushingoid features 4
• Early control of hypercortisolemia is critical to prevent life-threatening infections and metabolic complications 4

Management of Associated Complications

• For hypertension in Cushing's syndrome or pseudo-Cushing's: use spironolactone or eplerenone 5
• For hyperglycemia: appropriate glucose-lowering therapy 5
• For hypokalemia: potassium supplementation 5
• Continue monitoring cortisol levels until normalization and manage metabolic complications until resolution 5