ACTH resistance




ACTH resistance is a rare inherited genetic disorder characterized by adrenal insufficiency due to the adrenal gland's inability to respond to ACTH (adrenocorticotropic hormone) and hence produce the hormone called cortisol.


  • Low cortisol level
  • High ACTH level
  • Recurring hypoglycemia
  • Increased pigmentation
  • Infant feeding problems
  • Low urine level of 17-OCHS
  • Chronic asthenia
  • Frequent infections
  • Increased allergy risk


Adrenal hypofunction occurs when more than 90% of both adrenal glands are destroyed, an occurrence that typically results from an autoimmune process in which circulating antibodies react specifically against the adrenal tissue. Other causes include tuberculosis (once the chief cause; now responsible for less than 10% of adult cases), bilateral adrenalectomy, hemorrhage into the adrenal gland, neoplasms, and infections (acquired immunodeficiency syndrome, histoplasmosis, and cytomegalovirus). Rarely, a familial tendency to autoimmune disease predisposes the patient to adrenal hypofunction and other endocrinopathies. Secondary adrenal hypofunction that results in glucocorticoid deficiency can stem from hypopituitarism (causing decreased corticotropin secretion), abrupt withdrawal of long-term corticosteroid therapy (long-term exogenous corticosteroid stimulation suppresses pituitary corticotropin secretion and results in adrenal gland atrophy), or removal of a nonendocrine, corticotropin-secreting tumor. Adrenal crisis follows when trauma, surgery, or other physiologic stress exhausts the body’s stores of glucocorticoids in a person with adrenal hypofunction. Adrenal hypofunction affects 1 in 16,000 neonates congenitally. In adults, it affects 8 in 100,000 people, and males and females are affected equally. There is no racial predilection.


For all patients with primary or secondary adrenal hypofunction, corticosteroid replacement, usually with cortisone or hydrocortisone (both of which also have a mineralocorticoid effect), is the primary treatment and must continue throughout life. Adrenal hypofunction may also necessitate treatment with I.V. desoxycorticosterone, a pure mineralocorticoid, or oral fludrocortisone, a synthetic mineralocorticoid; both prevent dangerous dehydration and hypotension. Adrenal crisis requires prompt I.V. bolus administration of hydrocortisone. Later, doses are given I.M. or are diluted with dextrose in saline solution and given I.V. until the patient’s condition stabilizes. With proper treatment, adrenal crisis usually subsides quickly; the patient’s blood pressure should stabilize, and water and sodium levels should return to normal. After the crisis, maintenance doses of hydrocortisone preserve physiologic stability.


  • NIH