Cushing's syndrome refers to increased levels of glucocorticoids and can be due to a number of causes. Cushing's disease arises from a benign ACTH-secreting tumour of the pituitary. Iatrogenic Cushing's syndrome arises from administration of glucocorticoids. Functional adenomas of the adrenal gland that produce gluocorticoids are very rare. In the paraneoplastic sense, Cushing's syndrome arises from ectopic production of ACTH or ACTH-like peptides from non-pituitary and non-adrenal tumours.
In malignancy, ACTH is produced without oversight from the hypothalamus. This leads to excessive production and release of glucocorticoids (cortisone) from the adrenal glands. This exerts a multitude of effects of the brain, skin, soft tissues, vascular system and immune system and leads to the classical symptoms and signs below. The duration of the disease is important for the development of symptoms and signs as it is often a gradual process over months.
Patients almost always develop central adiposity of the trunk, neck and face. Skin manifestations are very common, particularly thinning and bruising. Proximal myopathy develops due to wasting and mineral is lost from the bones. Diabetes may develop. Psychological manifestations are also common but of varying severity. Patients become immunosuppressed.
Small cell carcinoma of the lung is responsible for over 50% of paraneoplastic Cushing's syndrome; about 1% of patients with small cell lung cancer develop Cushing's syndrome. Other neuroendocrine tumours and other malignancies may also cause the syndrome with much lower frequency.
Treatment of the underlying malignancy should result in reduction of cortisol levels. In patients with metastatic disease, inhibition of adrenal function (eg. ketoconazole) may reduce circulating levels of cortisol. In some cases, adrenalectomy (medical or surgical) is considered.