MPP II 3.3 - ADRENAL GLAND (PART 1) (LOWERY)

Adrenal Cortex Hormones

• Glucocorticoids affect glucose and protein metabolism; an example is cortisol.
• Mineralocorticoids affect sodium and potassium excretion; an example is aldosterone.
• Androgens are steriods associated with masculine characteristics; examples are dehydroepiandrosterone (DHEA) and testosterone.

Adrenal Gland Structure

• The adrenal gland has two components with different embryonic origins and functions.
• The cortex makes up 90% of the weight and has a mesodermal origin.
• The medulla makes up 10% of the weight and has a neural crest origin.

Summary of Adrenal Gland Products

• The medulla produces epinephrine, which is a catecholamine regulated by stress (autonomic nervous system).
• The cortex has three zones: the zona glomerulosa, zona fasciculata, and zona reticularis.
• The zona glomerulosa produces aldosterone, a mineralocorticoid regulated by angiotensin II.
• The zona fasciculata produces cortisol, a glucocorticoid regulated by ACTH.
• The zona reticularis produces DHEA, an adrenal androgen regulated by ACTH.

Regulation of Adrenal Cortex by Hypothalamus/Pituitary

• Glucocorticoid and adrenal androgen release are under physiological control by the hypothalamic-pituitary-adrenal axis.
• ACTH is a cleavage product of proopiomelanocortin (POMC).
• ACTH is synthesized and released by corticotrophs under the control of CRH.
• ACTH's half-life in circulation is only 10 minutes.
• ACTH release is stimulated by emotional stress, fear, anxiety, apprehension, and injury.
• ACTH is also released in a diurnal rhythm.

Adrenal Cortex Function

• Steroid hormones are produced by the conversion of cholesterol into stepwise products.
• The initial steps are the same for each class of steroid hormones.
• Synthesis is determined by the availability of substrates and appropriate enzymes.

Cortisol

• The effects of cortisol are broadly catabolic.
• Cortisol stimulates proteolysis and gluconeogenesis.
• Cortisol inhibits muscle protein synthesis.
• Cortisol increases fatty acid mobilization.
• Cortisol causes immunosuppression.
• The hallmark of glucocorticoid function is to increase blood glucose concentration.
• Cortisol circulates with a normal range of 5-25 ug/dL in a morning blood draw.
• The majority of cortisol is reversibly bound to carrier proteins.
• The most important carrier protein is CBP (cortisol-binding protein), synthesized by the liver.
• CBP is saturable above 20 ug/dL, allowing an increase in free fraction of cortisol.
• Cortisol also binds to albumin.
• The half-life of cortisol is about 90 minutes.
• Cortisol elevations inhibit the synthesis and secretion of CRH and ACTH, creating negative feedback.
• Cortisol is metabolized by the liver into less active 17-hydroxycorticosteroid metabolites (e.g., cortisone).
• Cortisol can be measured in urine to assess adrenal status.

Clinical Summary 1 of Cortisol production

• Diseases of excess and deficient production or responsiveness to cortisol are found in humans.
• Excess cortisol is associated with hyperglycemia, hypertension, and central obesity.
• Excess cortisol can result in Cushing disease, which requires ACTH
• Cushing syndrome may be ACTH-dependent (ectopic tumor) or ACTH-independent (adrenal tumor or iatrogenic source).
• Treatment options for hypercortisolism include surgery and medications.
• Metyrapone or osilodrostat can block glucocorticoid synthesis.
• Mifepristone is a glucocorticoid receptor inhibitor.

Clinical Summary 2 of Cortisol

• Cortisol deficiencies are less common and are linked to hypoglycemia, hypotension, and bronzing of skin.
• Cortisol deficiencies can be caused due to adrenal dysfunction (Addison's Disease), or lack of ACTH stimulation (secondary deficiency).
• The most common cause in the USA is withdrawal following exogenous corticosteroid use.
• Treatment options for hypocortisolism include administration of exogenous glucocorticoid (e.g., hydrocortisone).