Plasma ACTH in diagnosis and control of adrenal disorders

Abstract

Unstimulated plasma ACTH concentrations remain at or below the detection limit of conventional immunoassays. Grossly elevated ACTH concentrations are diganostic in suspected adrenal insufficiency, remain elevated well above 200 ng/l during substitution therapy and obviate the need of further tests. For the diagnosis of secondary adrenal failure, plasma ACTH, cortisol and 11-desoxycortisol response to a single midnight dose of metyrapone (1.2 g/m2 = 30 mg/kg) discriminates between a normal (morning ACTH above 100 ng/l), diminished (morning ACTH detectable, but below 100 ng/l), and an absent (ACTH below 20 -40 ng/l) ACTH reserve. In congenital adrenal hyperplasia, plasma ACTH concentrations mirror, together with 17-alpha-hydroxyprogesterone, the extent of ACTH suppression. Elevated ACTH concentrations were suppressed by prednisolone (25 %), dexamethasone (2 % of the hydrocortisone dose) or by addition of cyproterone acetate (100 mg/m2/day). Using selective venous catheterisation in clinically and biochemically proven Cushing's syndromes, a pituitary adenoma could be identified and localized in 6 of 8 patients by measuring ACTH concentrations in the left and right petrosal sinus before and after stimulation with corticotrophin releasing hormone.

Molecular Identification of the Human Melanocortin-2 Receptor Responsible for Ligand Binding and Signaling

“…Mutations of the hMC2R have been identified in a potentially fatal disease called familial glucocorticoid deficiency (FGD) in which affected individuals are deficient in cortisol and likely to succumb to hypoglycemia or overwhelming infection in infancy or childhood if they are not treated (8,10,16,35,39,40,44,49,50,52,(58)(59)(60). Over expression of this receptor is also found in adrenal adenomas or hyperplasia associated with glucocorticoid overproduction (Cushing syndrome) (1,22,37,38).Extensive studies had been performed to determine the molecular basis of ACTH in receptor function in the last two decades but the results are not consistent. In early years, ACTH1-14, ACTH11-19 and ACTH11-24 were reported to increase corticosterone levels in the isolated adrenal cell system and ACTH11-24 plays an important role in adipocyte function (14,24,42,45).…”

“…Mutations of the hMC2R have been identified in a potentially fatal disease, called familial glucocorticoid deficiency (FGD), in which affected individuals are deficient in cortisol and prone to succumb to hypoglycemia or overwhelming infection in infancy or childhood if not treated (8,10,16,35,39,40,44,49,50,52,(58)(59)(60). Overexpression of this receptor is also found in adrenal adenomas or hyperplasia associated with glucocorticoid overproduction (Cushing's syndrome) (1,22,37,38).…”