ACTH Resistance

Definition

Definition of ACTH Resistance
ACTH has an important tropic effect on adrenal development via the melanocortin-2 receptor (MC2R, ACTH receptor) and subsequent downstream signalling pathways. Abnormalities in these signalling processes result in adrenal hypoplasia due to ACTH resistance.

The adrenocorticotropin (ACTH) hormone, a 39-amino acid peptide, is synthesized by the corticotroph cells of anterior pituitary from a large precursor molecule, the pro-opio-melano-cortin (POMC). ACTH is highly conserved in mammals since only amino acids 31 and 33 vary between higher mammals and primates. ACTH is the principal regulator of cortisol production by the adrenal cortex. The biological activity of the ACTH molecule depends on the first 24 amino-terminal amino acids while fragments of less than 20 amino acids are ineffective. The residue 25-39 is important for stability increasing the half-life of the molecule.

Symptoms

Symptoms of ACTH Resistance
The list of signs and symptoms mentioned in various sources for ACTH resistance includes the 9 symptoms listed below:

1. Low cortisol level
2. High ACTH level
3. Recurring hypoglycemia
4. Increased pigmentation
5. Infant feeding problems
6. Low urine level of 17-OCHS
7. Chronic asthenia
8. Frequent infections
9. Increased allergy risk

Causes

Causes of ACTH Resistance
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 affectConsult with your doctor.ed equally. There’s no racial predilection.

Diagnosis

Diagnosis of ACTH Resistance
The phrase-”signs of ACTH resistance-” should, strictly speaking, refer only to those signs and symptoms of ACTH resistance that are not readily apparent to the patient. The word ”symptoms of ACTH resistance” is the more general meaning; see symptoms of ACTH resistance.The signs and symptom information on this page attempts to provide a list of some possible signs and symptoms of ACTH resistance. This medical information about signs and symptoms for ACTH resistance has been gathered from various sources, may not be fully accurate, and may not be the full list of ACTH resistance signs or ACTH resistance symptoms. Furthermore, signs and symptoms of ACTH resistance may vary on an individual basis for each patient. Only your doctor can provide adequate diagnosis of any signs or symptoms and whether they are indeed ACTH resistance symptoms.

Prognosis

Prognosis of ACTH Resistance
Consult with your doctor.

Treatment

Treatment of ACTH Resistance
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.

Prevention

Prevention of ACTH Resistance
Consult with your doctor.