Laboratory Workup for Moon Face and Weight Gain
Order an overnight 1-mg dexamethasone suppression test, 24-hour urinary free cortisol (2-3 collections), and late-night salivary cortisol (2-3 samples) to screen for Cushing's syndrome, as moon facies with weight gain is a highly specific clinical presentation for hypercortisolism. 1
Clinical Context
Moon face combined with weight gain—particularly when centrally distributed—represents one of the most specific physical findings for Cushing's syndrome and warrants immediate biochemical screening. 1 The combination of abnormal fat distribution affecting the face, neck, and trunk with metabolic derangements is highly specific for cortisol excess and distinguishes true Cushing's syndrome from simple obesity. 2, 3
Essential Pre-Test Step
Before ordering any biochemical tests, obtain a comprehensive medication history to exclude all sources of exogenous glucocorticoids—including oral tablets, inhaled steroids (fluticasone), topical creams, intra-articular/epidural injections, and over-the-counter supplements. 4, 5 Failure to exclude iatrogenic Cushing's syndrome leads to unnecessary testing without clinical benefit. 1, 4
First-Line Screening Tests (Order All Three)
1. Overnight 1-mg Dexamethasone Suppression Test
- Protocol: Give 1 mg dexamethasone orally between 11 PM-midnight; measure serum cortisol at 8 AM the next morning. 1, 5
- Interpretation: Cortisol ≥1.8 μg/dL (≥50 nmol/L) indicates abnormal suppression; cortisol >5 μg/dL (138 nmol/L) indicates overt Cushing's syndrome. 4, 5
- Enhanced accuracy: Consider measuring dexamethasone levels concomitantly with cortisol to confirm adequate drug absorption and exclude false-positive results from rapid metabolism. 1, 4, 5
- Advantages: Does not depend on fixed bedtime collection, making it suitable for patients with irregular sleep schedules. 5
- Pitfalls: Oral contraceptives/estrogen therapy can cause false-positive results by elevating cortisol-binding globulin; CYP3A4 inducers (phenytoin, rifampin, carbamazepine) accelerate dexamethasone metabolism causing false-positives. 4, 5
2. 24-Hour Urinary Free Cortisol (UFC)
- Protocol: Collect 2-3 separate 24-hour urine samples on different days. 1, 4, 5
- Interpretation: Values >100 μg/24 hours (1.6 μmol/24 hours) on multiple collections are diagnostic in symptomatic patients. 4, 5
- Critical requirement: Measure urine volume and total creatinine excretion to verify collection completeness—incomplete collections are the most common cause of false results. 4
- Rationale for multiple collections: UFC can vary by up to 50% between collections due to biological variability. 4, 5
- Pitfalls: Renal impairment or polyuria invalidates results; copper contamination of collection containers causes spurious results. 4
3. Late-Night Salivary Cortisol (LNSC)
- Protocol: Collect saliva samples at the patient's usual bedtime (11 PM-midnight) on 2-3 consecutive nights. 4, 5
- Interpretation: Values >3.6 nmol/L (>0.1 μg/dL) indicate loss of normal circadian rhythm. 4, 5
- Diagnostic performance: Sensitivity 92-100%, specificity 93-100%—the highest specificity among all first-line screening tests. 5
- Advantages: Easiest for patient compliance; multiple short-duration collections are simpler than 24-hour urine. 1, 5
- Absolute contraindication: Do NOT perform in night-shift workers or anyone with disrupted sleep-wake cycles, as the test relies on normal nocturnal cortisol nadir. 5
- Pitfalls: Topical hydrocortisone preparations contaminate samples; blood contamination from dental work or oral trauma within 1-2 hours falsely elevates results. 4
Interpretation Algorithm
If ≥2 Screening Tests Are Abnormal
If Only 1 Test Is Abnormal
- Repeat 1-2 screening tests to confirm hypercortisolism before proceeding to ACTH measurement. 5
- Consider cyclic Cushing's syndrome if results remain inconsistent—this condition produces weeks to months of normal cortisol interspersed with excess. 4, 5
If All Tests Are Normal
- Cushing's syndrome is unlikely if clinical suspicion is low to moderate. 5
- If clinical suspicion remains high despite normal tests, refer to endocrinology for extended monitoring with multiple sequential LNSC measurements over 3-6 months. 4, 5
Additional Considerations
Pseudo-Cushing's States (False-Positive Screening)
The following conditions can mimic Cushing's syndrome biochemically and must be considered when interpreting abnormal results: 4, 5
- Severe obesity
- Major depression or anxiety disorders
- Chronic alcoholism
- Uncontrolled diabetes
- Polycystic ovary syndrome
- Pregnancy
Management: Treat the underlying condition and repeat biochemical testing after 3-6 months. 5
Paraneoplastic Cushing's Syndrome
In patients with known or suspected lung cancer (especially small cell lung cancer or bronchial carcinoid), moon facies with weight gain should raise suspicion for ectopic ACTH production. 1 Additional features include: 1
- Skin hyperpigmentation (more prominent with ectopic ACTH)
- Hypokalemia with metabolic alkalosis
- Rapid onset of symptoms
- Weight loss (occurs in ~10% of SCLC-associated cases)
Thyroid Function Testing
Although less likely given the specific presentation, consider adding TSH and free T4 to exclude hypothyroidism, which can also present with weight gain and facial puffiness (though not true moon facies). 1 This is particularly relevant if the patient has additional features such as cold intolerance, constipation, or delayed ankle reflexes. 1
Critical Pitfalls to Avoid
- Never proceed to ACTH measurement or imaging without first confirming hypercortisolism with abnormal screening tests. 5
- Never use bilateral inferior petrosal sinus sampling to diagnose hypercortisolism—it is reserved solely for localizing ACTH source after biochemical confirmation. 5
- Always verify that exogenous glucocorticoids have been excluded before interpreting any cortisol test. 4, 5
- Do not rely on a single abnormal screening test—repeat testing is essential to minimize false-positive diagnoses. 5