Cushing’s syndrome is a disorder of the adrenal gland where there are too much of adrenal hormones produced. Also called “hypercortisolism”, this is effectively a result of glucocorticoid activity (steroid hormones can be classified as either glucocorticoid or mineralocorticoid). This can be caused by an over-secretion of endogenous cortisol from the adrenal cortex, or a large exogenous supply of glucocorticoid drugs. The symptoms of Cushing’s syndrome are described below, under a separate heading. These symptoms most commonly occur from large exogenous doses of glucocorticoid medications; however, there is a number of endogenous causes of over-secretion of cortisol, including:
– Pituitary tumors, causing increased release of adrenocorticotrophic hormone (ACTH), which stimulates the adrenal cortex to secrete excessive amounts of cortisol. This is the most common non-iatrogenic (iatrogenic = a condition caused by an inadvertent action from a physician/doctor) form of Cushing’s syndrome, and is also known as Cushing’s disease. This condition is usually benign, and is more common in women than men. This is not a problem with the adrenal gland itself; rather it is the over-stimulation of the adrenal glands, resulting in the excess secretion of cortisol from both glands.
– Ectopic ACTH or corticotrophin-releasing hormone (CRH) secretion occurs when there are tumor cells elsewhere in the body that secrete ACTH or CRH. This condition is more common in men than in women. The ectopic source is often due to tumors in the lung, but it may also be in the pancreas or thyroid. As with a pituitary tumor, this is not a problem with the adrenal gland itself; rather it is the over-stimulation of the adrenal glands, resulting in the excess secretion of cortisol from both glands.
– Adrenal tumors are rare, and result in excessive secretion of several adrenal hormones, depending on what types of cells are cancerous. If it is a tumor of the adrenal cortex, then there is an increased secretion of any type of cortico-hormones. Thus, this tumor could result in Cushing’s syndrome from an excess secretion of cortisol. Alternatively, other androgenic or mineralocorticoid hormones could be secreted, resulting in effects associated with those hormones. The tumor usually only occurs in one adrenal gland.
While there is some variation in the symptoms of Cushing’s syndrome depending on the level of exposure to glucocorticoids, it generally presents in a typical way. The common effects or symptoms include hypertension, thinning of skin, osteoporosis, poor glucose tolerance and increased susceptibility to infection. Alterations in weight distribution cause obvious changes in appearance, notably increased abdominal fat, collection of fat on the dorsocervical region (buffalo hump) and rounding of the cheeks (moon face).
Treatment of Cushing’s syndrome involves the removal of the glucocorticoid source. If there is an exogenous source, this must be removed slowly to avoid a Hypothalamus-Pituitary-Adrenal (HPA) crisis, otherwise known as acute adrenal insufficiency. An endogenous cause of hypercortisolism is confirmed by a “Dexamethasone Suppression Test”, where levels of cortisol in the blood are assayed following a 1mg dose of dexamethasone. This exogenous dose would normally result in suppression of cortisol production via negative feedback of dexamethasone on CRH and ACTH secretion. In Cushing’s disease, cortisol will still be secreted regardless of this exogenous stimulation of the negative feedback loop.
Treatment of an endogenous cause requires the identification and removal of the reason for the excessive cortisol secretion. This diagnosis is complex, and is achieved by assessing urinary and/or blood levels of ACTH, cortisol and other hormones in the body, as well as the use of MRI and CT scans to locate the tumor. Once identified, the tumor is usually surgically removed, in which case temporary glucocorticoid replacement may be required until normal adrenal function returns.
There is only limited evidence for pharmacological treatment of primary Cushing’s disease. Some drugs have been identified as potentially useful. These include metyrapone, aminoglutethimide, ketoconazole and mitotane.
CONCLUSION AND PRACTICE POINTS
Chronic therapeutic use of corticosteroids requires finding a dose which controls the condition, while minimizing the Cushing-like side effects. Patients and carers of people taking corticosteroids should be educated to identify the signs and symptoms of glucocorticoid oversupply, reporting these to their doctor who can oversee any necessary dose modification. If there is an iatrogenic cause of Cushing’s syndrome, reduction of therapy should be done gradually so as to avoid the onset of acute adrenal insufficiency.