Cushing's Disease (Answer: e)
The most likely diagnosis is Cushing's disease, given the constellation of central obesity resistant to diet and exercise, facial swelling and flushing (moon facies and plethora), and preferential weight gain around the waist despite lifestyle interventions.
Clinical Reasoning
The key diagnostic features in this patient point specifically toward hypercortisolism:
- Central obesity with waist predominance that fails to respond to appropriate diet and exercise interventions 1
- Facial changes including swelling (moon facies) and flushing (facial plethora) 2, 3
- Weight gain despite active weight loss efforts - a hallmark feature distinguishing pathologic causes from simple obesity 1
Why Cushing's Disease Over Other Options
Physical examination findings are critical here. Guidelines specifically recommend that when evaluating patients with obesity and weight gain, clinicians should inspect for thin, atrophic skin associated with Cushing's disease 1. The combination of central obesity, moon facies, and facial plethora creates a high pretest probability for Cushing syndrome 3.
Ruling Out Alternative Diagnoses:
Hypothyroidism (a): Would typically present with diffuse weight gain, not preferential central distribution, and would show fatigue, cold intolerance, and bradycardia rather than facial flushing 1
Acromegaly (b): Causes enlargement of hands, feet, and facial features (prognathism, frontal bossing), not the moon facies and central obesity pattern described 2
Diabetes mellitus (c): Does not cause the characteristic facial changes or explain resistance to weight loss efforts; it's more commonly a consequence rather than cause of this presentation 1
Hyperthyroidism (d): Typically causes weight loss, not gain, along with tachycardia, heat intolerance, and tremor 1
Diagnostic Approach
The next step should be biochemical confirmation with a low-dose dexamethasone suppression test, which has 95% sensitivity and 80% specificity for diagnosing Cushing syndrome 3. The standard protocol involves administering 0.5 mg dexamethasone every 6 hours for 48 hours, with failure to suppress cortisol to <50 nmol/L (<1.8 μg/dL) confirming the diagnosis 3.
Alternative first-line tests include 24-hour urinary free cortisol or late-night salivary cortisol, though the dexamethasone suppression test is preferred for rapid and reliable confirmation 3.
Clinical Pitfalls to Avoid
Do not attribute treatment-resistant weight gain solely to poor compliance or psychosocial stressors (such as the recent divorce in this case). While the patient initially attributed her weight gain to divorce-related stress, the physical examination findings and failure to respond to appropriate lifestyle interventions should trigger evaluation for secondary causes of obesity 1.
The AGA guidelines emphasize that when history and physical examination raise suspicion for identifiable causes of obesity, patients should undergo appropriate screening rather than assuming lifestyle factors alone are responsible 1.
Buffalo hump (dorsocervical fat pad) is another key finding to assess, as it commonly associates with Cushing syndrome alongside central obesity, moon facies, and facial plethora 2.