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Chapter 29: ACTH, Adrenal Steroids, and Pharmacology of the Adrenal Cortex

A 34-year-old man is diagnosed with secondary adrenal insufficiency. He does not require the administration of a mineralocorticoid because

a. the adrenal medulla is intact.

b. the zona glomerulosa is intact.

c. the zona reticularis is intact.

d. the zona fasciculata is intact.

e. 11β-hydroxylase is not inhibited.

Answer is b. The zona glomerulosa is the site of aldosterone synthesis and secretion (see Figure 29-1). In secondary adrenal insufficiency, which usually involves pituitary or hypothalamic dysfunction, mineralocorticoid biosynthesis is preserved.

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Figure 29-1. The adrenal cortex contains 3 anatomically and functionally distinct compartments. The major functional compartments of the adrenal cortex are shown, along with the steroidogenic enzymes that determine the unique profiles of corticosteroid products. Also shown are the predominant physiological regulators of steroid production: angiotensin II (Ang II) and K+ for the zona glomerulosa and ACTH for the zona fasciculata. The physiological regulator(s) of dehydroepiandrosterone (DHEA) production by the zona reticularis are not known, although ACTH acutely increases DHEA biosynthesis.

A 54-year-old man has been diagnosed with hypertension caused by his excessive consumption of licorice. Licorice is a known inhibitor of 11β-hydroxysteroid dehydrogenase that is involved in the inactivation of

a. cortisol.

b. aldosterone.

c. ACTH.

d. dehydroepiandrosterone.

e. progesterone.

Answer is a. 11β-Hydroxysteroid dehydrogenase catalyzes the conversion of cortisol (active) to cortisone (inactive) (see Figure 29-4). Aldosterone is resistant to the enzyme’s actions. The inhibition of the enzyme by licorice results in a state of mineralocorticoid excess resulting in hypertension.

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Figure 29-4. Receptor-independent mechanism by which 11β-hydroxysteroid dehydrogenase confers specificity of corticosteroid action. Type 2 11β-hydroxysteroid dehydrogenase (11β-HSD2) converts cortisol, which binds to both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), to cortisone, which binds to neither MR nor GR, thereby protecting the MR from the high circulating concentrations of cortisol. This inactivation allows specific responses to aldosterone in sites such as the distal nephron. The type 1 isozyme of 11β-HSD (11β-HSD1) catalyzes the reverse reaction, which converts inactive cortisone to active cortisol in such tissues as liver and fat. Only ring C of the corticosteroid is depicted.

A 34-year-old woman with Crohn’s disease has been taking prednisone daily for 1 year. She has been experiencing a thickness in the back of her ...

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