The CRH-ACTH-cortisol axis regulates cortisol levels. Cortisol has negative feedback effects on CRH-producing neurons and pituitary corticotropes in the hypothalamus. In individuals with a disorder affecting the production of mineralocorticoids (aldosterone, DOC, and corticosterone), they may have difficulty retaining salt and maintaining extracellular volume, resulting in hypotension. If there is a blockage at the next step, 11β-hydroxylase (CYP11B1), DOC levels may accumulate, leading to salt and water retention and hypertension due to the significant mineralocorticoid activity of DOC. Stressors such as proinflammatory cytokines, hypoglycemia, neurogenic stress, and hemorrhage, as well as diurnal input, also regulate cortisol. Adrenal androgens, including DHEA, DHEAS, and androstenedione, serve as precursors for androgens and contribute to about 50% of circulating androgens in women. Their role in men is unclear. Adrenal androgens in women stimulate pubic and axillary hair growth and libido, but excessive levels can cause virilization and ovarian dysfunction. Aldosterone, the most potent mineralocorticoid in humans, is produced in the zona glomerulosa of the adrenal cortex. It promotes the reabsorption of sodium and water while promoting the secretion of potassium and hydrogen ions in the distal tubule and collecting duct. Aldosterone also aids in sodium and water absorption in the colon and salivary glands, and it has proinflammatory and profibrotic effects on the cardiovascular system, leading to left ventricular hypertrophy and remodeling. Angiotensin II stimulates the growth and vascularity of the zona glomerulosa, increases StAR and CYP11B2 enzyme activity, and enhances aldosterone synthesis in the adrenal cortex. The main stimuli for aldosterone production are an increase in angiotensin II and serum potassium levels, while atrial natriuretic peptide (ANP) acts as an inhibitory signal. Addison's disease refers to adrenocortical insufficiency and is characterized by symptoms such as hypotension, hyperpigmentation, muscle weakness, anorexia, hypoglycemia, and hyperkalemic acidosis. Cushing's syndrome occurs due to excessive cortisol levels. If the disorder originates from increased pituitary adrenocorticotropin secretion, it is known as Cushing's disease. Common symptoms of Cushing's syndrome include fat distribution towards the center of the body, muscle wasting, proximal muscle weakness, thinning of the skin with abdominal striae, capillary fragility, insulin resistance, and polycythemia. Congenital adrenal hyperplasia results from a congenital enzyme deficiency that impairs cortisol production, leading to elevated cortisol precursors.
Cortisol is regulated by the CRH-ACTH-cortisol axis. Cortisol negatively feeds back at the hypothalamus on both CRH-producing neurons and pituitary corticotropes. CRH is regulated by several fetuswillbemasculinized.Becausetheyareunabletoproducethemineralocorticoids,aldosterone,DOC,andcorticosterone,patientswiththisdisorderhavedifficultyretainingsaltandmaintainingextracellularvolume.Consequentlytheyarelikelytobehypotensive.Iftheblockageisatthenextstep,11β-hydroxylase (CYP11B1),DOC willbeformedandlevelsofDOCwillaccumulate(see
Figs.43.8 43.9C ).BecauseDOChassignificantmineralocorticoid activity anditslevelsbecomehigh,theseindividualstendtoretainsaltandwaterandbecomehypertensive.
forms of stress, including proinflammatory cytokines, hypoglycemia, neurogenic stress, and hemorrhage, and by diurnal input.
8.
The adrenal androgens DHEA, DHEAS, and androstenedione are androgen precursors. They can be converted to active androgens peripherally and provide about 50% of circulating androgens in women. In men the role of adrenal androgens if any remains obscure. In women, adrenal androgens promote pubic and axillary hair growth and libido. Excessive adrenal androgens in women can lead to various degrees of virilization and ovarian dysfunction.
9.
The zona glomerulosa of the adrenal cortex is the site of aldosterone production. Aldosterone is the strongest naturally occurring mineralocorticoid in humans. It promotes Na+ and water reabsorption by the distal tubule and collecting duct while promoting renal K+ and H+ secretion. Aldosterone promotes Na+ and water absorption in the colon and salivary glands. It also has a proinflammatory, profibrotic effect on the cardiovascular system and causes left ventricular hypertrophy and remodeling.
10.
Major actions of angiotensin II on the adrenal cortex are increased growth and vascularity of the zona glomerulosa, increased StAR and CYP11B2 enzyme activity, and increased aldosterone synthesis.
11.
Major stimuli for aldosterone production are a rise in angiotensin II and a rise in serum [K+]. The major inhibitory signal is ANP.
12.
Addison’s disease is adrenocortical insufficiency. Common symptoms include hypotension, hyperpigmentation, muscle weakness, anorexia, hypoglycemia, and hyperkalemic acidosis.
13.
Cushing’s syndrome results from hypercortisolemia. If the basis of the disorder is increased pituitary adrenocorticotropin secretion, the disorder is called Cushing’s disease. Common symptoms of Cushing’s syndrome include centripetal fat distribution, muscle wasting, proximal muscle weakness, thin skin with abdominal striae, capillary fragility, insulin resistance, and polycythemia.
14. Congenital adrenal hyperplasia is caused by a congenital enzyme deficiency that blocks production of cortisol. The enzyme blockage results in elevated
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