Symptoms

It can be asymptomatic, but the following symptoms can be present

• Fatigue

• Headache

• High blood pressure

• Hypokalemia

• Intermittent or temporary paralysis

• Muscle spasms

• Muscle weakness

• Numbness

• Polyuria

• Polydipsia

Cushing's syndrome

(also called hypercortisolism or hyperadrenocorticism) is a rare endocrine disorder caused by high levels of cortisol in the blood. Cortisol is released from the adrenal gland in response to ACTH being released from the pituitary gland. High levels of cortisol can also be induced by the administration of drugs. Cushings disease, or more properly termed secondary hyperadrenocorticism, is very similar to Cushing's syndrome in that all physiologic manifestations of the conditions are the same. Both diseases are characterized by elevated levels of cortisol in the blood, but the cause of elevated cortisol differs between the diseases. Cushing's disease specifically refers to a tumor in the pituitary gland that stimulates excessive release of cortisol from the adrenal gland by releasing large amounts of ACTH. It was discovered by American physician, surgeon and endocrinologist Harvey Cushing (1869-1939) and reported by him in 1932.

Signs and symptoms

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), a round face often referred to as a "moon face", excess sweating, telangiectasia (dilation of capillaries), thinning of the skin (which causes easy bruising) and other mucous membranes, purple or red striae (also caused by thinning of the skin) on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth). A common sign is the growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump). The excess cortisol may also affect other endocrine systems and cause, for example, reduced libido, impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to frank psychosis. Depression and anxiety, including panic attacks, are common.

Other signs include persistent hypertension (due to the aldosterone-like effects) and insulin resistance, leading to hyperglycemia (high blood sugars) which can lead to diabetes mellitus. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation of the skin, due to its ability to stimulate melanocyte receptors.

Diagnosis

When Cushing's is suspected, a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH levels) and 24-hour urinary measurement for cortisol have equal detection rates (Raff & Findling 2003). Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, high cortisol would be indicative of Cushing's syndrome because there is an ectopic source of cortisol or ACTH (eg: adrenal adenoma) that is not inhibited by the dexamethasone. A low cortisol reading would be indicative of Cushing's disease because the dexamethasone inhibited the pituitary adenoma so that its' output of ACTH decreased, resulting in decreased cortisol levels. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late night levels of salivary cortisol are high in Cushingoid patients. Other pituitary hormones may need to be determined, and performing physical examination directed for any visual field defect may be necessary if a pituitary lesion is suspected (which may compress the optic chiasm causing typical bitemporal hemianopia).

When these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of an adrenal or pituitary adenoma. These should be performed when other tests are positive, to decrease likelihood of incidentalomas (incidental discovery of harmless lesions in both organs). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the cortisol levels in various veins in the body by venous catheterisation working towards the pituitary (petrosal sinus sampling) is necessary.