In patients in whom the diagnosis of Cushing’s syndrome has been established clinically and confirmed by a finding of elevated free cortisol in the urine, suppression with large doses of dexamethasone will help to distinguish patients with Cushing’s disease from those with steroid-producing tumors of the adrenal cortex or with the ectopic ACTH syndrome. Dexamethasone is given in a dosage of 0.5 mg orally every 6 hours for 2 days, followed by 2 mg orally every 6 hours for 2 days, and the urine is then assayed for cortisol or its metabolites (Liddle’s test); or dexamethasone is given as a single dose of 8 mg at 11 pm, and the plasma cortisol is measured at 8 am the following day. In patients with Cushing’s disease, the suppressant effect of dexamethasone usually produces a 50% reduction in hormone levels. In patients in whom suppression does not occur, the ACTH level will be low in the presence of a cortisol-producing adrenal tumor and elevated in patients with an ectopic ACTH-producing tumor.
B. Corticosteroids and Stimulation of Lung Maturation in the Fetus
Lung maturation in the fetus is regulated by the fetal secretion of cortisol. Treatment of the mother with large doses of glucocorticoid reduces the incidence of respiratory distress syndrome in infants delivered prematurely. When delivery is anticipated before 34 weeks of gestation, intramuscular betamethasone, 12 mg, followed by an additional dose of 12 mg 18–24 hours later, is commonly used. Betamethasone is chosen because maternal protein binding and placental metabolism of this corticosteroid is less than that of cortisol, allowing increased transfer across the placenta to the fetus. A study of more than 10,000 infants born at 23–25 weeks of gestation indicated that exposure to exogenous corticosteroids before birth reduced the death rate and evidence of neurodevelopmental impairment.
C. Corticosteroids and Nonadrenal Disorders
The synthetic analogs of cortisol are useful in the treatment of a diverse group of diseases unrelated to any known disturbance of adrenal function (Table 39–2). The usefulness of corticosteroids in these disorders is a function of their ability to suppress inflammatory and immune responses and to alter leukocyte function, as previously described (see also Chapter 55). These agents are useful in disorders in which host response is the cause of the major manifestations of the disease. In instances in which the inflammatory or immune response is important in controlling the pathologic process, therapy with corticosteroids may be dangerous but justified to prevent irreparable damage from an inflammatory response—if used in conjunction with specific therapy for the disease process.
Since corticosteroids are not usually curative, the pathologic process may progress while clinical manifestations are suppressed. Therefore, chronic therapy with these drugs should be undertaken with great care and only when the seriousness of the disorder warrants their use and when less hazardous measures have been exhausted.
In general, attempts should be made to bring the disease process under control using mediumto intermediate-acting glucocorticoids such as prednisone and prednisolone (Table 39–1), as well as all ancillary measures possible to keep the dose low. Where possible, alternate-day therapy should be used (see the following text). Therapy should not be decreased or stopped abruptly. When prolonged therapy is anticipated, it is helpful to obtain chest x-rays and a tuberculin test, since glucocorticoid therapy can reactivate dormant tuberculosis. The presence of diabetes, peptic ulcer, osteoporosis, and psychological disturbances should be taken into consideration, and cardiovascular function should be assessed.
TABLE 39–2 Some therapeutic indications for the use of glucocorticoids in nonadrenal disorders.