Asymptomatic, normotensive subjects with primary glucocorticoid resistance do not require any treatment. On the contrary, patients with symptomatic generalized glucocorticoid resistance are treated with high, individualized doses of oral dexamethasone (0.5-1.0 mg two or three times daily), a synthetic, potent glucocorticoid with minimal intrinsic mineralocorticoid activity. The goal is to suppress ACTH and, therefore, endogenous cortisol, DOC, corticosterone, and adrenal androgen secretion, correcting the mineralocorticoid and androgen excess states of these patients (20).  Adequate suppression of the HPA axis is of particular importance in cases of severe impairment of GR function, given that longstanding corticotroph hyperstimulation in association with decreased glucocorticoid negative feedback may lead to the development of an ACTH-secreting adenoma (48)

Hypertensive patients should receive the smallest dose that lowers the serum concentration of mineralocorticoids and corrects electrolyte abnormalities. Hirsute patients should be treated with doses able to reduce the androgen excess.

Although, dexamethasone doses used to treat patients with glucocorticoid resistance are clearly pharmacologic for normal people, these patients do not manifest any side effects and/or Cushingoid features. Long-term dexamethasone dosage should be carefully individualized and titrated to normalize the biochemical picture and to control the clinical manifestations of the disease.

Untreated patients have no risk of adrenal insufficiency and do not need extra doses of dexamethasone in particularly stressful situations, such as surgery and illness. On the contrary, patients undergoing chronic treatment should receive the appropriate glucocorticoid coverage.