Adrenal Steroid Hormone Synthesis & Congenital Adrenal Hyperplasias High-Yield Review for Step 1 Tim Boswell Created: 3/11/15

17-hydroxypregnenolone dehydroepiandrosterone cholesterol cholesterol desmolase 17α-hydroxylase pregnenolone 17-hydroxypregnenolone dehydroepiandrosterone 3β-hydroxysteroid dehydrogenase 3β-hydroxysteroid dehydrogenase 3β-hydroxysteroid dehydrogenase 17α-hydroxylase progesterone 17-hydroxyprogesterone androstenedione 21β-hydroxylase 21β-hydroxylase 11-deoxycorticosterone deoxycortisol testosterone 11β-hydroxylase 11β-hydroxylase corticosterone cortisol aldosterone synthase aldosterone

Recap: Key points Memory aid: GFR + “The deeper you go, the sweeter it gets” Glomerulosa Aldosterone Salt Fasciculata Cortisol Sugar Reticularis Testosterone Sex What are the primary actions of aldosterone? retain Na+ -> elevated BP excrete K+ excrete H+ Which intermediate has mineralocorticoid activity? 11-deoxycorticosterone (11-DOC) ACTH -> increased activity of cholesterol desmolase AT-II -> increased activity of aldosterone synthase

Congenital Adrenal Hyperplasias Caused by deficiencies of certain enzymes in the adrenal steroid synthesis pathway Low cortisol levels fail to perform feedback inhibition on the anterior pituitary -> excessive ACTH ACTH activates the rate-limiting and integral first step of the entire steroid synthesis pathway, ramping up the adrenal steroid synthesis pathway Intermediates are shunted into the intact branches of the pathway, excess steroid products accumulate This ACTH stimulation induces hyperplasia of the adrenal cortex which causes the adrenal gland to be enlarged (detectable on imaging) Presentations are logical with signs/symptoms following from deficiency and/or excess of steroid hormones. Main features are: Abnormalities in sexual differentiation (virilization, precocious puberty, etc.) Abnormalities in blood pressure and potassium level Age of presentation (usually present early in life) and specific presenting features depend on severity of deficiency and gender

17α-hydroxylase deficiency

21β-hydroxylase deficiency

11β-hydroxylase deficiency

Congenital Adrenal Hyperplasias Enzyme Deficiency Hormone Levels Vitals/Labs/Clinical Presentation 17α-hydroxylase Aldosterone Cortisol Testosterone 21β-hydroxylase 11β-hydroxylase

Recap: Important points Hypertension + hypokalemia = possible hyperaldosteronism normal potassium range = 3.5 - 5.0 21β-hydroxylase deficiency is the most common cause of CAH Sexual differentiation: external genitalia are female by default (without influence of significant androgens) Recommendation: memorize framework

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