12th April 2024

Cushing’s syndrome

Cushing syndrome is an umbrella term for the body being exposed to excessive cortisol. The causes of Cushing Syndrome can be divided into three groups: ACTH-dependent, ACTH-independent and exogenous sources. ACTH-dependent sources can be central causes, such as ACTH-secreting pituitary tumours (Cushing’s disease) or peripheral from non-pituitary tumours. ACTH-independent would be from sources that are overproducing cortisol without the influence of ACTH, such as adrenal hyperplasia or tumours. The most common cause of Cushing’s syndrome would be from exogenous sources such as steroidal use.

A typical presentation of Cushing’s syndrome would involve excessive central fat deposition leading to buffalo hump (behind the neck), moon facies and purple abdominal striae. Peripheral limbs would be less affected, leading to thin limbs with proximal muscle weakness. Common complications include depression, bruising, osteopenia/osteoporosis, recurrent infection, infertility, reduced libido, and hirsutism in women. Though Cushing syndrome in adulthood has no impact on growth, high cortisol levels are known to suppress the secretion of growth hormone and could affect growth if present in childhood.

Investigations

When Cushing syndrome is suspected, two different tests are used to confirm the diagnosis. The initial investigations involve a 24-hour urine-free cortisol test measuring total cortisol. The other test is the 48-hour low-dose dexamethasone suppression test, where those with Cushing syndrome would have a high cortisol result.

The high-dose dexamethasone suppression test allows localisation of the abnormality. After this dose is administered, a low cortisol would indicate Cushing disease. A result showing high cortisol and low ACTH localises to the adrenal glands as it is non-ACTH dependent. A high cortisol with a high ACTH indicates ectopic ACTH. Dexamethasone suppression tests can be affected by illness/stress, obesity, alcohol, exogenous steroids, increased oestrogen and malnutrition.

Management

Treatment is dependent on the cause of Cushing Syndrome and may involve removal of the source of stimulation (adrenal/ectopic tumours), radiotherapy if surgery is unsuccessful or not possible and medications such as somatostatin analogues (pasireotide), dopamine agonists (cabergoline), cortisol antagonists (mifepristone).