Cushing’s Syndrome

Definition

Cushing’s syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. It can be due to endogenous factors such as adrenal tumours or exogenous factors such as long-term use of corticosteroid medications.

Aetiology

Cushing’s syndrome can be caused by a variety of factors:

Exogenous: Prolonged use of corticosteroid medications is the most common cause.
Endogenous:
- ACTH-dependent causes, such as pituitary adenomas (Cushing's disease) or ectopic ACTH production by tumours.
- ACTH-independent causes, such as adrenal adenomas or carcinomas.

Pathophysiology

Cortisol is a glucocorticoid hormone produced by the adrenal glands. It helps regulate metabolism, immune response, and stress. In Cushing’s syndrome, excess cortisol can lead to:

Increased gluconeogenesis and insulin resistance, causing hyperglycaemia and diabetes.
Protein catabolism, leading to muscle weakness and thinning of the skin.
Redistribution of body fat, resulting in central obesity, moon face, and buffalo hump.
Suppression of the immune system, increasing susceptibility to infections.
Hypertension due to increased mineralocorticoid activity.

Risk Factors

Long-term use of corticosteroid medications
Adrenal or pituitary tumours
Ectopic ACTH-producing tumours
Family history of endocrine disorders

Signs and Symptoms

Common signs and symptoms of Cushing’s syndrome include:

Weight gain, particularly around the abdomen and face
Rounded face (moon face)
Fatty hump between the shoulders (buffalo hump)
Thinning of the skin, easy bruising
Muscle weakness
Purple or pink stretch marks (striae) on the skin
High blood pressure
Osteoporosis
Hirsutism (excess hair growth) in women
Irregular or absent menstrual periods
Mood changes, such as depression, anxiety, and irritability

Investigations

Clinical history and physical examination
24-hour urinary free cortisol test: Measures cortisol levels in urine over 24 hours
Low-dose dexamethasone suppression test: Assesses cortisol suppression response
Midnight serum or salivary cortisol levels: Evaluates cortisol levels at night
Imaging studies: CT or MRI of the adrenal glands and pituitary gland to identify tumours or abnormalities
Blood tests: To measure ACTH levels and differentiate between ACTH-dependent and ACTH-independent causes

Management

Primary Care Management

Referral to endocrinologist: For confirmation of diagnosis and specialised management
Monitoring: Regular follow-up to assess symptoms, cortisol levels, and response to treatment
Education: Informing patients about the condition, its symptoms, and the importance of medication adherence

Specialist Management

Surgical removal of tumours: Adrenalectomy for adrenal tumours or transsphenoidal surgery for pituitary adenomas
Radiation therapy: For pituitary tumours that cannot be completely removed by surgery
Medications: To control cortisol production (e.g., ketoconazole, metyrapone, mitotane, or mifepristone)
Management of complications: Treatment for diabetes, hypertension, osteoporosis, and infections
Hormone replacement therapy: For patients who undergo adrenalectomy or pituitary surgery

Example Management for Cushing’s Syndrome

A patient diagnosed with Cushing’s syndrome due to a pituitary adenoma (Cushing's disease) should be referred to an endocrinologist for specialised management. Surgical removal of the tumour (transsphenoidal surgery) is often the first-line treatment. If surgery is not feasible or the tumour cannot be completely removed, radiation therapy or medications to control cortisol production may be used. The patient should be monitored regularly to assess symptoms, cortisol levels, and the response to treatment. Management of complications such as hypertension, diabetes, and osteoporosis is also crucial.

References

NICE. (2024). Cushing’s Syndrome: Diagnosis and Management. Retrieved from NICE
NHS. (2023). Cushing’s Syndrome. Retrieved from NHS
Endocrine Society. (2022). Clinical Practice Guidelines for Cushing’s Syndrome. Retrieved from Endocrine Society
European Society of Endocrinology (ESE). (2021). Management of Cushing’s Syndrome. Retrieved from ESE