From the Guidelines
Cushing syndrome should be diagnosed using a stepwise approach, starting with screening tests such as 24-hour urinary free cortisol measurement, late-night salivary cortisol testing, and the overnight dexamethasone suppression test (1 mg), as recommended by the most recent guidelines 1.
Symptoms of Cushing Syndrome
The symptoms of Cushing syndrome include weight gain with central obesity, "buffalo hump" (fat accumulation at the base of the neck), moon face, purple striae on the abdomen, proximal muscle weakness, easy bruising, poor wound healing, and thinning of the skin. Patients often experience hypertension, glucose intolerance or diabetes, menstrual irregularities in women, decreased libido, depression, and mood changes.
Diagnosis of Cushing Syndrome
Diagnosis involves a stepwise approach beginning with screening tests to confirm hypercortisolism, followed by tests to determine the cause.
- Initial screening typically includes:
- 24-hour urinary free cortisol measurement
- Late-night salivary cortisol testing
- The overnight dexamethasone suppression test (1 mg)
- If these tests suggest Cushing syndrome, the next step is to determine whether the excess cortisol is ACTH-dependent or ACTH-independent using plasma ACTH levels.
- For ACTH-dependent cases, a high-dose dexamethasone suppression test and CRH stimulation test help differentiate between pituitary (Cushing disease) and ectopic ACTH sources.
- Imaging studies such as pituitary MRI, chest and abdominal CT scans are used to locate tumors.
- Inferior petrosal sinus sampling may be necessary to confirm a pituitary source when imaging is inconclusive, as recommended by recent guidelines 1.
Importance of Early Diagnosis
Early diagnosis is crucial as untreated Cushing syndrome leads to significant morbidity and increased mortality from cardiovascular disease, infections, and other complications, highlighting the need for prompt and accurate diagnosis and treatment 1.
From the Research
Symptoms of Cushing Syndrome
- Cushing syndrome is a constellation of signs and symptoms caused by excessive exposure to exogenous or endogenous glucocorticoid hormones 2
- The clinical presentation is variable and includes hypertension, diabetes, obesity, osteoporosis, facial rounding, dorsocervical fat pad, thin skin, purple striae, hirsutism, and mood disorders 3
- Some patients have an atypical clinical presentation with only isolated symptoms, making diagnosis challenging 4
Diagnosis of Cushing Syndrome
- The recommended diagnostic tests are 24-h urinary free cortisol, 1-mg overnight dexamethasone suppression test, and late-night salivary cortisol 4, 5, 6, 2, 3
- These tests have high sensitivity and specificity for the diagnosis of Cushing's syndrome, but each has its own distinctive features and potential pitfalls 5, 3
- Measuring cortisol with antibody-based immunoassays can generate false-positive results due to cross-reactivity between cortisol, cortisone, and other metabolites 3
- Structurally-based assays, such as liquid chromatography with tandem mass spectrometry, only measure cortisol and have recently become available for use in routine clinical practice 3
Diagnostic Approach
- Once the diagnosis of Cushing's syndrome is established, the next step is the measurement of plasma ACTH 4
- Dynamic tests and appropriate imaging procedures are the most useful noninvasive investigations for the differential diagnosis 4
- Bilateral inferior petrosal sinus sampling is considered the gold standard for establishing the origin of ACTH secretion, and is recommended in patients with ACTH-dependent Cushing's syndrome whose clinical, biochemical, or radiological studies are discordant or equivocal 4