Alterations in the glucocorticoid molecule influence its affinity for glucocorticoid and mineralocorticoid receptors as well as its protein-binding affinity, side chain stability, rate of elimination, and metabolic products. Halogenation at the 9 position, unsaturation of the Δ1–2 bond of the A ring, and methylation at the 2 or 16 position prolong the half-life by more than 50%. The Δ1 compounds are excreted in the free form. In some cases, the agent given is a prodrug; for example, prednisone is rapidly converted to the active product prednisolone in the body.
The actions of the synthetic steroids are similar to those of cortisol (see above). They bind to the specific intracellular receptor proteins and produce the same effects but have different ratios of glucocorticoid to mineralocorticoid potency (Table 39–1).
A. Diagnosis and Treatment of Disturbed Adrenal Function 1. Adrenocortical insufficiency a. Chronic (Addison’s disease)—Chronic adrenocortical insufficiency is characterized by weakness, fatigue, weight loss, hypo-tension, hyperpigmentation, and inability to maintain the blood glucose level during fasting. In such individuals, minor noxious,
TABLE 39–1 Some commonly used natural and synthetic corticosteroids for general use. See Table 61–2 for dermatologic corticosteroids.
1Potency relative to hydrocortisone. 2Outside United States. 3Triamcinolone acetonide: Up to 100.
traumatic, or infectious stimuli may produce acute adrenal insufficiency with circulatory shock and even death.
In primary adrenal insufficiency, about 20–30 mg of hydrocortisone must be given daily, with increased amounts during periods of stress. Although hydrocortisone has some mineralocorticoid activity, this must be supplemented by an appropriate amount of a salt-retaining hormone such as fludrocortisone. Synthetic glucocorticoids that are long-acting and devoid of salt-retaining activity should not be administered to these patients.
b. Acute—When acute adrenocortical insufficiency is suspected, treatment must be instituted immediately. Therapy consists of large amounts of parenteral hydrocortisone in addition to correction of fluid and electrolyte abnormalities and treatment of precipitating factors.
Hydrocortisone sodium succinate or phosphate in doses of 100 mg intravenously is given every 8 hours until the patient is stable. The dose is then gradually reduced, achieving maintenance dosage within 5 days.
The administration of salt-retaining hormone is resumed when the total hydrocortisone dosage has been reduced to 50 mg/d.
2. Adrenocortical hypoand hyperfunction a. Congenital adrenal hyperplasia—This group of disorders is characterized by specific defects in the synthesis of cortisol. In pregnancies at high risk for congenital adrenal hyperplasia, fetuses can be protected from genital abnormalities by administration of dexamethasone to the mother.