Adrenocorticotropic hormone deficiency

Proopiomelanocortin (POMC) is the precursor peptide of hormones and neuropeptides expressed in the pituitary and the hypothalamus (adrenocorticotropic hormone (ACTH), lipotropin, a-melanocyte-stimulating hormone (aMSH), yMSH, 3-endorphin, and others). The main clinical consequences of POMC deficiency are adrenal insufficiency (due to absence of ACTH), red hair pigmentation (due to absence of MSH) and severe early-onset obesity (due to the lack of aMSH). 

Adrenocorticotropic Hormone Receptor Mutations and Isolated Glucorticoid Deficiency... 

A deficiency in adrenal hormones can be caused by problems with the pituitary gland or problems with the adrenal gland. Healthcare providers determine the cause by administering corticotropin (Acthar), which is the adrenocorticotropic hormone. If after 60 minutes there are increased levels of glucocorticoids, there is a pituitary gland insufficiency. If no increase occurs, there is an adrenal gland insufficiency. 

Figure 51-15 Formation of steroids in patients with adrenogenital syndrome caused by 21 -hydroxylase deficiency. Bold lettering indicates steroids that are found elevated in the circulation. ACTH, Adrenocorticotropic hormone SpSDH 3p-hydroxysteroid dehydrogenase.

Deficiency of 21-hydroxylase inhibits the synthesis of glucocorticoids (e.g., cortisol) and mineralocorticoids (e.g., aldosterone), leading to overproduction of testosterone in the adrenal glands and underproduction of cortisol. The latter effectively increases adrenocorticotropic hormone (ACTH), which stimulates the adrenals to grow and synthesize steroids, exacerbating the testosterone overproduction. This leads to masculinization of females. 

Cortisone Reductase DeGciency. In hirsutism and virilization in females, cortisone reductase deficiency has been described. Patients with this disorder convert all their cortisol into cortisone. This gives rise to an apparent cortisol deficiency. Adrenocorticotropic hormone increases and stimulates the adrenal steroid synthesis. The urinary steroid profile is characterized by a very high excretion of THE, cortolones, and adrenal androgens, and low excretion of THF and 5a-THF [33]. 

---