For diagnostic purposes, measurement of the excretion of cortisol over 24 h in the urine is the most expeditious test and superior to serum sampling because of fluctuations in the serum levels of ACTH. If a 24-h urine collection is not feasible, it is advisable to obtain two or three daily urine determinations, as the values may vary considerably. The normal value for urinary excretion of cortisol is approximately 12 to 40 mg in 24 h, but some assays that measure additional metabolites of the hormone may allow normal values up to 100 mg. This should be followed by lowor high-dose dexamethasone suppression testing. A test using high doses of dexamethasone (2 mg every 6 h orally for 2 d, or a single dose of 8 mg at midnight) is the most dependable screening method for separating Cushing disease from ectopic secretion of ACTH. In the latter condition, the urinary excretion of cortisol is not suppressed by the administration of dexamethasone; in contrast, 60 to 70 percent of patients with Cushing disease show a 90 percent reduction in urinary cortisol excretion.
Treatment is governed by the cause of the syndrome. A pituitary adenoma, if not extending out of the sella and encroaching on the optic chiasm (microadenoma), is ideally treated by transsphenoidal pituitary microsurgery, as discussed in Chap. 31. The alternative is focused proton beam or gamma radiation, but the long latency of response to these forms of treatment, 6 months or more, makes them less desirable. If such indirect methods of treatment are used, hypercortisolism may be suppressed in the interim by adrenal enzyme inhibitors such as ketoconazole, metapyrone, or aminoglutethimide. The rate of cure for pituitary microadenoma by transsphenoidal surgery approaches 80 percent, although operative complications—CSF leakage, transient diabetes insipidus, visual abnormalities, meningitis—occur in as many as 10 percent of patients. In approximately 20 percent of patients, removal of the tumor is incomplete and symptoms persist or recur. In such circumstances reoperation is often undertaken, with total excision of the gland and a consequent requirement for extensive hormone replacement in many cases. As an alternative, radiotherapy may be used after failed surgery. If there is an urgent need to suppress the effects of hypercortisolism, bilateral adrenalectomy is effective but has obvious limitations.
Depending on the functional status of the pituitary after any mode of successful treatment, replacement therapy may be needed for a variable period or for the patient’s lifetime.
The classic form of adrenal insufficiency, described by Addison in the nineteenth century, is a result of primary disease of the adrenals. It is characterized by pigmentation of the skin and mucous membranes, nausea, vomiting, and weight loss, as well as muscle weakness, languor, and a tendency to faint. Since Addison’s time, hypotension, hyperkalemia, hyponatremia, and low serum cortisol concentrations have come to be recognized as important laboratory features.