Cushing’s Syndrome

Definition/diagnostic criteria

Cushing’s syndrome is defined by the presence of elevated cortisol levels for an extended period, leading to specific clinical manifestations. Diagnostic criteria involve both clinical assessment and biochemical tests to confirm hypercortisolism and its causative factors.

Epidemiology

Cushing’s syndrome is uncommon, with new cases estimated at 1.2-2.4 per million annually in the UK. The condition is more frequent in females, with the highest incidence observed between 20 and 50 years of age.

Diagnosis

Clinical features

Typical presentations include central obesity, moon face, buffalo hump, purple striae, muscle weakness, and easy bruising. Additional signs may include hypertension, diabetes, and psychological issues.

Investigations and causes

Initial diagnosis relies on biochemical tests to demonstrate elevated cortisol levels, including late-night salivary cortisol, 24-hour urinary free cortisol, and low-dose dexamethasone suppression tests, where results significantly exceeding normal ranges suggest Cushing’s syndrome.

Determining the underlying cause is crucial, as Cushing’s syndrome can stem from various sources:

• ACTH-dependent causes include Cushing’s disease (pituitary adenoma) or ectopic ACTH secretion by tumours.
• ACTH-independent causes: adrenal adenomas or carcinomas directly producing excess cortisol; also iatrogenic Cushing’s syndrome (the commonest cause), which is drug-induced, primarily due to exogenous glucocorticoids for chronic conditions.

Further diagnostic procedures might involve high-dose dexamethasone suppression tests, corticotropin-releasing hormone (CRH) stimulation tests, and imaging (pituitary MRI or adrenal CT scans) to pinpoint the exact cause.

Treatment

Surgical removal of the tumour is generally the preferred initial treatment, targeting the direct source of excess cortisol production. For inoperable cases or adrenal carcinoma, medications such as mitotane, ketoconazole, and metyrapone are options. In certain ACTH-dependent scenarios where surgery is unsuccessful or not viable, pituitary radiotherapy may be considered.

Comorbidity management, including for hypertension, diabetes, and osteoporosis, is also crucial.

In iatrogenic causes, reduction or cessation of the causative agent is idea but may not be possible.

Prognosis

The outlook varies by cause and treatment efficacy, with high remission rates following successful surgical intervention but potential for recurrence. Lifelong follow-up is often necessary for monitoring and management of long-term effects or comorbidities.