_{What is ACTH?}

Adrenocorticotropic Hormone (ACTH, also known as Corticotropin) is the principal hormone required for the synthesis and secretion of adrenal glucocorticoids. ACTH is primarily synthesized by the anterior pitutiary gland and is composed of 39 amino acids. It is indeed part of a much larger amino acid precusor know as pro-opiomelanocortin POMC (a 241 aminoacid sequence).

POMC is typically broken down in a tissue-specific manner to produce smaller peptide hormones. Firstly, Proprotein convertase 1, also known as prohormone convertase,  cleaves POMC into  β-lipoprotein (β-LPH) and pro-ACTH.

The first 24 of 39 amino acids present in ACTH are common to all species and is responsible for most of the biological activity of this peptide hormone. Indeed a synthetic version of ACTH 1–24 (Synacthen/Cortrosyn) is ubiquitously utilized in the field of endocrinology for dynamic testing of the the hypothalamic–pituitary–adrenal (HPA) axis.

Melanocyte-stimulating hormones (a, β, and γ) are additional byproducts of the cleavage of POMC. As the name implies, MSH plays an important in the hyperpigmentation seen in patients with either Addison’s disease or Nelson’s syndrome. It is however worth noting that elevated levels of ACTH binding to the melanocortin-1 receptor (MCR-1) plays a significant role in the dark hue noted amongst lighter skinned individuals with this condition.

_{Clinical application}

Cortrosyn stimulation test

Rationale 

A dynamic test for the evaluation of suspected adrenal insufficiency. The test cannot distinguish between primary and secondary AI

Limitations of this test

• Estrogen in OCPs may increase corticosteroid-binding globulin and thus increase total serum cortisol.
• Low albumin can lead to a spuriously low serum cortisol
• It does not distinguish between primary and secondary AI (normal stimulation test if adrenocortical atrophy has not set in yet)

Procedure

1. Draw a baseline serum cortisol (at any time, need not be in the early morning)
2. Inject 250mcg of Cosyntropin(Cortrosyn), IM or IV
3. Draw serum cortisol (total) at 30 and 60 minutes

Interpretation

Peak serum cortisol >18mcg/dL or an increment of >7mcg/dL over the baseline cortisol level rules out adrenal insufficiency.***

*** Update : Newer cortisol assays, a level of >14mcg/dl effectively rules out AI