Cortisol is a steroid hormone, produced by the adrenal gland. It is released in response to stress and low blood-glucose concentration. It functions to increase blood sugar, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. It also decreases bone formation. Cortisol levels normally fluctuate throughout the day and night in a circadian rhythm that peaks at about 8 AM and reaches it lowest around 4 AM. Secretion of the hormone is controlled by the hypothalamus, the pituitary gland and the adrenal gland. Hypothalamus secretes CRH (corticotropin-releasing hormone) that stimulates the pituitary gland to secrete ACTH (adrenocorticotrophic hormone), which in turn stimulates adrenal gland to secrete cortisol. Release of CRH is controlled by the level of cortisol in blood.
Prolonged exposure of the body to cortisol results in a condition known as Cushing’s syndrome. The most common cause is the taking excessive cortisol-like medication such as prednisone. Certain tumour produce or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing’s disease. It is the second most common cause of Cushing’s syndrome after medication. In pituitary Cushing’s, a benign pituitary adenoma secretes ACTH. It is responsible for 70% of endogenous Cushing’s syndrome.
Tumours of the Adrenal gland, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia also produce excess cortisol. Tumours outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. It is called ectopic or paraneoplastic Cushing’s disease and is seen in diseases such as small cell lung cancer. Rare cases of CRH-secreting tumours have been reported, which stimulates pituitary ACTH production.
Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, fatty deposits, especially in the midsection, the face (causing a round, moon-shaped face)(Fig.3.1) and between the shoulders and the upper back (causing a buffalo hump), weak muscles, weak bones, acne, and purple stretch marks on breasts, arms, abdomen (Fig.3.2), and thighs. Skin becomes thin and gets bruised easily. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headache, and a chronic feeling of tiredness.
Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done to determine if the pituitary is involved.
Treatment of Cushing syndrome is directed by the primary cause of the syndrome. In general, therapy should reduce the cortisol secretion to normal to reduce the risk of comorbidities associated with hypercortisolism. The treatment of choice for endogenous Cushing syndrome is surgical resection of the tumour. The primary therapy for Cushing disease is transsphenoidal surgery. The goal of surgery is to remove the adenoma, preserving as much pituitary function as possible. Pituitary irradiation is employed when transsphenoidal surgery is not successful or not possible. The primary therapy for adrenal tumours is adrenalectomy.
When surgery is not successful or cannot be undertaken, as in ectopic adrenocorticotropic hormone (ACTH) or metastatic adrenal carcinoma, control of hypercortisolism may be attempted with medication. However, medication failures are common, and adrenalectomy may be indicated in ACTH-mediated Cushing syndrome.
