Endogenous Cushing syndrome (CS) in children is rare, and most referrals are triggered by rapid weight gain plus height deceleration. But not every child with CS is obese. This review compares pediatric CS with vs. without obesity, showing that obesity shapes some presenting features, yet non-obese children can still have substantial hypercortisolemia and typical CS complications.
Key Points
- Weight gain is common, not universal: Prior series report weight gain in up to ~98% of children, but obesity occurs in only a subset.
- Non-obese CS exists: These patients may lack obvious adiposity yet still have growth failure, hypertension, hyperglycemia, muscle weakness, and skin changes.
- Obesity modifies the picture: In cohorts, obesity correlated with specific demographic patterns and appeared to amplify metabolic features (e.g., higher BMI, insulin resistance), whereas some CS features (e.g., hypertension, hyperglycemia) can also be present without obesity.
- Contrast with older adults: Elderly CS patients often show lower BMI despite high cardiometabolic burden—highlighting that BMI alone is a poor screen across ages.
How to Spot CS When BMI Is “Normal”
Look beyond weight. Red flags include:
- Height deceleration (falling percentiles vs. mid-parental target)
- New or worsening hypertension (age/sex/height-adjusted)
- Hyperglycemia (fasting glucose, HbA1c) or insulin resistance (elevated HOMA-IR)
- Catabolic signs: proximal myopathy, easy bruising, violaceous striae, skin fragility
- Pubertal changes: menstrual irregularity/oligomenorrhea, androgenic signs
- Neurocognitive/behavioral changes and sleep disturbance
Diagnostic Notes (Pediatrics)
- Use pediatric-adapted criteria: abnormal 24-h urinary free cortisol (UFC) (often expressed as fold-ULN), late-night serum/salivary cortisol, and low-dose dexamethasone non-suppression (weight-adjusted).
- ACTH-dependence workup: plasma ACTH, CRH/DDAVP tests, pituitary MRI, and inferior petrosal sinus sampling when needed.
- ACTH-independent clues: adrenal CT and evaluation for adrenal lesions.
- Screen comorbidities: BP category, fasting lipids (dyslipidemia), ALT for MASLD, glucose/HbA1c.
Why It Matters
- Delays in diagnosis are common when BMI is normal.
- Early recognition prevents irreversible growth impairment, bone fragility, cardiometabolic disease, and neurocognitive effects.
- Management and outcomes depend on timely etiology-specific treatment (pituitary, adrenal, or ectopic sources) and systematic follow-up.
Takeaway
Normal BMI does not exclude pediatric Cushing syndrome. In any child with growth slowdown plus new cardiometabolic or catabolic signs, pursue targeted CS testing—even if the child isn’t obese.