| Clinical disorders of cortisol secretion
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| Hyposecretion of cortisol may occur as a result of hypothalamic, pituitary, or adrenal failure
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| The diagnosis of the cause of cortisol hyposecretion relies on the clinical presentation, measurement of cortisol and ACTH, and the extent of the cortisol response to synthetic ACTH (Synacthen).
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| Deficiencies of CRH and ACTH are often accompanied by deficiencies of other hypothalamic or pituitary hormones. Addison's disease is a primary adrenal failure in which secretion of all adrenal hormones is decreased, usually because of autoimmune disease or infection. Biochemically, it is characterized by hyponatremia, an impaired cortisol response to Synacthen, and an elevated plasma ACTH. Cortisol replacement, usually with a mineralocorticoid, is an effective treatment for this life-threatening condition.
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| PRIMARY ADRENAL INSUFFICIENCY - AN ENDOCRINE EMERGENCY |
A 40-year-old woman was admitted as a medical emergency after collapsing at home 2 days after contracting influenza. For 1 year she had been complaining of chronic weakness and fatigue, and lately of abdominal pain, nausea, vomiting, anorexia and confusion. She was dehydrated and hypotensive with pigmentation of the palmar creases and buccal mucosa. Biochemical analysis revealed Na+ 115 mmol/L (135-145 mmol/L); K+ 5.9 mmol/l (3.5-5.0 mmol/L); urea 12 mmol/L (2.5-6.5 mmol/L) and glucose 2.9 mmol/L (4.0-6.0 mmol/L). Baseline serum cortisol was 95 nmol/L rising to 110 nmol/L 30 minutes after administration of synthetic ACTH (Synacthen). |
| Comment. This is an acute presentation of Addison's disease resulting from progressive autoimmune destruction of the adrenal cortex. The nonspecific symptoms of cortisol deficiency became critical after the stress of a minor illness. The hypotension and electrolyte imbalance result from mineralocorticoid deficiency. The pigmentation is due to elevated ACTH and other POMC peptides (notably melanocyte stimulating hormone). The diagnosis is made by the impaired cortisol response to synthetic ACTH (normal increment >200 nmol/L). Treatment is rehydration with intravenous saline, plus a bolus of intravenous hydrocortisone followed by daily maintenance therapy with hydrocortisone and a mineralocorticoid. |
| CUSHING'S SYNDROME - A DIAGNOSTIC DILEMMA |
| A 65-year-old man presented with a history of rapid weight gain, central obesity, a plethoric face (full, moon-shape) and abdominal bruising. He was mildly hypertensive. Urinary cortisol was 1000 nmol/24 h (normal <250 nmol/24 h); serum cortisol was 500 nmol/L at 24.00 h (normal <50 nmol/L) and his 08.00 h cortisol was 550 nmol/L after 1 mg of dexamethasone (a potent synthetic glucocorticoid) (normal <50 nmol/L). Plasma ACTH was 100 ng/L (normal <80 ng/L). |
| Comment. This man has hypercortisolism, known as Cushing's syndrome. The elevated urine cortisol, elevated evening serum cortisol and failure to suppress following dexamethasone administration support the diagnosis. The ACTH result indicates that the cause is either a pituitary tumor or ectopic ACTH secretion from an occult tumor (probably carcinoid). In this case magnetic resonance imaging (MRI) of the pituitary revealed a clear tumor of 0.5 cm diameter; the differential diagnosis is not often this easy. Pituitary surgery is the appropriate treatment in this case. |
| Rarely, cortisol hyposecretion results from a genetic disorder in the steroid biosynthetic pathway: congenital adrenal hyperplasia. The most frequently affected enzyme is the steroid 21-hydroxylase (see Fig. 37.7). Hyponatremia develops in neonates and may be accompanied by ambiguous
genitalia resulting from the metabolism of accumulated 17-hydroxyprogesterone into androgens. A milder form presents in teenage girls where the androgen excess results in hirsutism and menstrual irregularity. A clinical example of this condition is given in Chapter 16 (clinical box on p. 218).
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| Hypersecretion of cortisol results in Cushing's syndrome - easily the most challenging of all endocrine disorders
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| Exogenous glucocorticoids, commonly used to suppress the immune system in a range of gastrointestinal or dermatologic disorders, may cause clinical Cushing's syndrome. However, Cushing's syndrome may also result from a disorder of the hypothalamus, pituitary, or adrenal gland; or it may be the consequence of ectopic ACTH syndrome. The symptoms are often nonspecific and cyclical, but there is general deposition of fat in the face and trunk, wasting of skeletal muscle, and development of glucose intolerance. Once cortisol excess is demonstrated, the diagnosis can be made using ACTH measurements, dexamethasone (a synthetic glucocorticoid) suppressibility tests, and selective venous catheterization of the pituitary or the adrenal glands. Treatment is usually surgical and should be targeted at the primary cause of the condition.
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