Clinical Features of Pituitary Cushing Syndrome (Cushing Disease)
Pituitary Cushing syndrome presents with distinctive clinical features that differ significantly between children and adults, with growth failure being the most sensitive discriminator in prepubertal children, while classic cushingoid features like wide purple striae, proximal muscle weakness, and abnormal fat distribution are most specific across all ages. 1, 2
Key Clinical Features by Age Group
Children and Adolescents (Prepubertal)
- Growth failure with weight gain is the hallmark presentation—inexplicable weight gain combined with either decreased height standard deviation score or decreased height velocity 1, 2
- Male predominance (71% prepubertal, 63% overall in children vs. 79% female in adults) 1
- Boys tend to have more aggressive disease with elevated BMI, shorter height, and higher plasma ACTH levels than girls 1
- Microadenomas (≤2 mm) account for 98% of cases in children, compared to only 2-5% macroadenomas 1
- Mean age at presentation is 12.3 ± 3.5 years (range 5.7–17.8 years) 1
Critical caveat: Growth failure sensitively discriminates simple obesity from Cushing syndrome in prepubertal children but becomes unreliable in post-pubertal adolescents, who should be assessed using adult criteria 2, 3
Adults and Post-Pubertal Adolescents
The most specific clinical features include:
- Wide purple striae (particularly >1 cm width) on abdomen, thighs, or arms 4, 5, 6
- Abnormal fat distribution: supraclavicular fat pads, temporal fossa fullness, dorsocervical fat pad ("buffalo hump"), truncal obesity with thin extremities 5, 6, 7
- Proximal muscle weakness (difficulty rising from chair, climbing stairs) 5, 6, 7
- Facial plethora (facial redness) 5, 8, 9
- Easy bruising without significant trauma 5
Common but Less Specific Features
These occur frequently but are not diagnostic alone:
- Hypertension 5, 8, 9
- Hyperglycemia/diabetes mellitus 5, 8, 9
- Generalized obesity 5, 9
- Mood disorders and neurocognitive changes (depression, anxiety, irritability) 5, 8
- Menstrual irregularities/reproductive dysfunction 8, 7
- Hirsutism and acne 8
- Osteoporosis and increased fracture risk 8
- Immunosuppression with increased infection risk 5, 8
Important pitfall: No single clinical feature has 100% sensitivity—the absence of purple striae does not exclude Cushing syndrome, and biochemical testing remains essential for diagnosis 4
Diagnostic Approach When Clinical Features Are Present
Screening Tests (Require at least 2-3 abnormal results)
- Late-night salivary cortisol (LNSC): First-line test with sensitivity 95%, specificity 100% 4, 2, 3
- 24-hour urinary free cortisol (UFC): Diagnostic cut-off >193 nmol/24h (>70 μg/m²), sensitivity 89%, specificity 100% 2, 3
- Dexamethasone suppression testing: Overnight 1-mg test or low-dose dexamethasone suppression test 2, 3
- Midnight serum cortisol: Cut-off ≥50 nmol/L (≥1.8 μg/dL), sensitivity 100%, specificity 60% 2, 3
Critical step: Eliminate exogenous glucocorticoid use before any biochemical testing 1, 2
Determining Pituitary vs. Other Causes
- Morning plasma ACTH level: >1.1 pmol/L (>5 ng/L) indicates ACTH-dependent disease 2, 3, 5
- Pituitary MRI: Detects adenomas with sensitivity 63%, specificity 92% 2, 3
- Bilateral inferior petrosal sinus sampling (IPSS): Gold standard to differentiate pituitary from ectopic ACTH sources 2, 5
- CRH stimulation test: Sensitivity 74-100% for pituitary source 2, 3
Common Diagnostic Pitfalls to Avoid
- Never rely on a single test—at least two abnormal results are required for diagnosis 2
- Beware of pseudo-Cushing states: Severe obesity, uncontrolled diabetes, depression, and alcoholism can cause false positives 2
- Consider cyclic Cushing syndrome: Document active phase with confirmatory tests before dynamic testing 2
- Repeat equivocal tests rather than dismissing the diagnosis 2
- In children: Screen only when weight gain is inexplicable AND combined with growth deceleration—not for obesity alone 1, 2, 3