Adrenocorticotropic hormone (ACTH) is a tropic hormone produced by the anterior pituitary. The hypothalamic-pituitary axis controls it. ACTH regulates cortisol and androgen production. Diseases associated with ACTH include Addison disease, Cushing syndrome and Cushing disease.
Pro-opiomelanocortin (POMC) gives rise to ACTH and melanocyte-stimulating hormone (MSH). This association is clinically important for Addison disease.
ACTH receptors are in the adrenal cortex, in particular, the zona fasciculata and zona reticularis. The receptors are G protein-coupled receptors thus stimulating adenylyl cyclase. This leads to an increase in intracellular cAMP and activation of protein kinase A.
Memory tool for secretory products of Adrenal Cortex
CRH is released from the hypothalamus. CRH stimulates the anterior pituitary to release ACTH. ACTH acts on the adrenal cortex to release cortisol and androgens. The increase in cortisol provides a negative feedback system to then decrease the amount of CRH released from the hypothalamus.
ACTH works on G protein-coupled receptors on extracellular membranes on zona fasciculata and zona reticularis of the adrenal cortex. cAMP is the secondary messenger system. Activation of the g-couple receptor activates adenylyl cyclase, thus increase cAMP production.
ACTH plays a role in glucose metabolism and immune function.
The circadian rhythm influences cortisol secretion. The highest levels of cortisol are seen in the early morning, and the lowest levels are in the evening. This concept is important for diagnostic testing.
Pathophysiology associated with ACTH can stem from 3 different mechanisms. Issues can be with the pituitary, adrenals, or ectopic secretion.
The pituitary can be hypofunctioning or hyperfunctioning leading to either a decrease or increase, respectively, in ACTH. Pituitary insufficiency is usually the result of an adenoma that destroys the gland. It can also be caused by pituitary apoplexy, a sudden hemorrhage into a pituitary tumor causing sudden loss of ACTH. Sheehan syndrome is a less common cause of pituitary insufficiency. It is a pituitary infarct since after massive blood loss during childbirth.
The adrenal can also be hypofunctioning or hyperfunctioning. Diseases associated with the adrenals include Addison and Cushing.
Ectopic secretion refers the production of a hormone outside of its normal physiology mechanism. Benign or malignant tumor secrete hormone. Normal feedback loop mechanisms do not control the production of the hormone. Cushing syndrome is associated with ectopic ACTH production.
Addison disease involves the autoimmune destruction of all 3 layers of the adrenal cortex, which leads to decrease productions of mineralocorticoids, glucocorticoids, and steroids. Other causes of destruction include congenital enzyme deficiencies, tuberculosis, AIDS, and metastasis.
Hypercortisolism has many different etiologies, all with similar patient presentations. Cortisol is a necessary hormone that influences glucose metabolism and immune function. Etiology include exogenous glucocorticoid use, increased adrenal production of cortisol, increased pituitary production of ACTH, or ectopic production of ACTH.
Infantile Spasms (IS): West Syndrome
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