Can Primary Cushing's Disease Present Without Buffalo Hump, Excessive Hair Growth, and Striae?
Yes, primary Cushing's disease can absolutely present without buffalo hump, hirsutism, or striae—the absence of these classic physical findings does not exclude the diagnosis. 1
Clinical Reality of Variable Presentation
The clinical features of Cushing's syndrome are highly variable, and no single pattern is seen in all patients 2. While the classic triad you mention represents common findings, they are not universally present:
- Buffalo hump (dorsocervical fat pad) is a specific finding when present, but its absence does not rule out disease 1
- Hirsutism occurred in only 9.5% of patients in a major clinical trial of 137 Cushing's disease patients 3
- Wide purple striae are characteristic when present (>1 cm width), but the American Heart Association notes their absence does not exclude Cushing's disease 1
Most Specific Diagnostic Features to Seek
The most discriminating physical findings for Cushing's syndrome include 2:
- Abnormal fat distribution in supraclavicular and temporal fossae (more specific than buffalo hump alone)
- Proximal muscle weakness or wasting, particularly in lower limbs 1, 2
- Facial plethora (reddish-purple facial appearance) 1
- Central obesity with moon facies 1
These features have higher specificity than the triad you mentioned and should be actively sought during examination.
Documented Case of Minimal Phenotype
A compelling case report demonstrates this principle: a 20-year-old woman with confirmed pituitary-dependent Cushing's disease presented with normal fat distribution (BMI 20.9), absence of hirsutism, no myopathy or bruising, and normal blood pressure (115/70-122/82 mmHg) 4. She was investigated only because of secondary amenorrhea and a mildly elevated random cortisol. This case involved a partial defect in cortisol metabolism that protected her from the classic phenotype, but it proves that biochemically confirmed Cushing's disease can exist without the typical cushingoid appearance 4.
Pediatric Considerations
In children, the Endocrine Society recommends screening for Cushing's syndrome when obesity is combined with either decreased height velocity or declining height standard deviation score—without requiring striae to be present 1. This guideline explicitly acknowledges that classic features may be absent.
Diagnostic Approach When Classic Features Are Absent
When clinical suspicion exists despite absent classic features, proceed with biochemical screening 5, 1:
Initial screening with 2-3 tests 5:
- 24-hour urinary free cortisol (UFC)
- Late-night salivary cortisol
- 1 mg overnight dexamethasone suppression test (morning cortisol should suppress to <1.8 μg/dL or <50 nmol/L) 5
Look for associated metabolic features 6:
Consider screening triggers beyond classic cushingoid appearance 7:
Common Pitfall to Avoid
The most dangerous error is dismissing Cushing's disease based solely on the absence of buffalo hump, striae, or hirsutism 1, 2. The prevalence of Cushing's syndrome is low (<0.1% of the general population), but when metabolic abnormalities or unexplained symptoms are present, biochemical testing should proceed regardless of whether classic physical findings are present 7.
Clinical Trial Data Supporting Variable Presentation
In the pivotal ISTURISA trial of 137 Cushing's disease patients 3:
- Only 9.5% developed hirsutism during the study
- The mean age was 41 years with 77% female
- 96% had received previous treatments, indicating these were established cases
- Yet the physical examination findings varied considerably among confirmed cases
This real-world data confirms that the full cushingoid phenotype is not universal, even in biochemically proven disease.