{"id":4422394,"date":"2025-01-11T16:18:18","date_gmt":"2025-01-11T22:18:18","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/congenital-adrenal-hyperplasia-cah\/"},"modified":"2025-01-12T18:04:49","modified_gmt":"2025-01-13T00:04:49","slug":"congenital-adrenal-hyperplasia-cah","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/congenital-adrenal-hyperplasia-cah\/","title":{"rendered":"Congenital Adrenal Hyperplasia (CAH)"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">CLASSIC CONGENITAL ADRENAL HYPERPLASIA (CAH)<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">General Overview<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Definition<\/strong>: CAH comprises a group of autosomal recessive disorders characterized by enzyme deficiencies in the cortisol synthetic pathway.<\/li>\n\n\n\n<li><strong>Pathophysiology<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Decreased Cortisol<\/strong> \u2192 Lack of negative feedback \u2192 \u2191ACTH \u2192 <a href=\"https:\/\/myendoconsult.com\/learn\/non-classical-adrenal-hyperplasia\/\" data-wpil-monitor-id=\"166\">Adrenal hyperplasia<\/a> &amp; accumulation of precursor steroids.<\/li>\n\n\n\n<li>Depending on the specific enzyme block, there may be <strong>loss or excess<\/strong> of mineralocorticoids or androgens.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Classic vs. Nonclassic<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Classic<\/strong>: Severe enzyme deficiencies, typically presenting in infancy.<\/li>\n\n\n\n<li><strong>Nonclassic (late-onset)<\/strong>: Milder enzyme defects, presenting later in childhood or adulthood.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3000\" height=\"2100\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis.png\" alt=\"\" class=\"wp-image-4422811\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis.png 3000w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-300x210.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-768x538.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-1536x1075.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-2048x1434.png 2048w\" sizes=\"auto, (max-width: 3000px) 100vw, 3000px\" \/><figcaption class=\"wp-element-caption\">Adrenal Steroidogenesis<\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">CONGENITAL LIPOID HYPERPLASIA<\/h2>\n\n\n\n<p>(<strong>StAR or P450scc Mutation<\/strong>)<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Enzyme\/Protein Defect<\/strong>\n<ul class=\"wp-block-list\">\n<li>Mutations in <strong>Steroidogenic Acute Regulatory Protein (StAR)<\/strong> or <strong>P450 side-chain cleavage enzyme (P450scc)<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormone Deficiency<\/strong>\n<ul class=\"wp-block-list\">\n<li>Deficiency in <strong>all adrenal<\/strong> and <strong>gonadal<\/strong> steroid hormones (glucocorticoids, mineralocorticoids, sex steroids).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Pathology<\/strong>\n<ul class=\"wp-block-list\">\n<li>Marked accumulation of <strong>cholesterol esters<\/strong> in the <a href=\"https:\/\/myendoconsult.com\/learn\/the-formation-and-structure-of-the-adrenal-cortex\/\" data-wpil-monitor-id=\"168\">adrenal cortex<\/a> (due to ACTH drive with no steroid synthesis).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Severe <a href=\"https:\/\/myendoconsult.com\/learn\/primary-adrenal-insufficiency-sick-day-rules\/\" data-wpil-monitor-id=\"169\">adrenal insufficiency<\/a><\/strong> in neonates (hypotension, hyponatremia, hyperkalemia, vomiting).<\/li>\n\n\n\n<li>In 46,XY infants: No testicular androgens \u2192 <strong>female <a href=\"https:\/\/myendoconsult.com\/learn\/male-external-genitalia-exam\/\" data-wpil-monitor-id=\"170\">external genitalia<\/a><\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory Findings<\/strong>\n<ul class=\"wp-block-list\">\n<li>Low serum cortisol &amp; <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/aldosteronism\/\"  data-wpil-monitor-id=\"333\">aldosterone<\/a>, high ACTH, high plasma renin activity.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Outcome and Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Lethal if untreated<\/strong>.<\/li>\n\n\n\n<li><strong>Glucocorticoid + mineralocorticoid<\/strong> replacement therapy is essential.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">3\u03b2-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY<\/h2>\n\n\n\n<p>(<strong>3\u03b2-HSD2 Mutation<\/strong>)<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Function<\/strong>\n<ul class=\"wp-block-list\">\n<li>3\u03b2-HSD converts <strong>pregnenolone \u2192 progesterone<\/strong>, also DHEA \u2192 androstenedione.<\/li>\n\n\n\n<li>Type 2 isoenzyme (3\u03b2-HSD2) is present in adrenal cortex and gonads.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormone Deficiency<\/strong>\n<ul class=\"wp-block-list\">\n<li>Cortisol, aldosterone, gonadal steroid production severely reduced.<\/li>\n\n\n\n<li>\u2191\u0394\u2075-steroids (pregnenolone, 17-hydroxypregnenolone, DHEA, DHEA-S).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Severe deficiency<\/strong>: Neonatal salt-wasting <a href=\"https:\/\/myendoconsult.com\/learn\/adrenal-crisis-in-addisons-disease\/\" data-wpil-monitor-id=\"171\">adrenal crisis<\/a> (cortisol &amp; aldosterone deficiency).<\/li>\n\n\n\n<li><strong>Mild virilization in 46,XX<\/strong> infants (excess DHEA).<\/li>\n\n\n\n<li><strong>46,XY<\/strong> phenotype can vary from normal male to ambiguous or female genitalia.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory Findings<\/strong>\n<ul class=\"wp-block-list\">\n<li>Low cortisol, low aldosterone, <strong>\u2191DHEA, DHEA-S<\/strong>, but <strong>androstenedione not elevated<\/strong> (needs 3\u03b2-HSD).<\/li>\n\n\n\n<li>\u2191Renin activity (salt-wasting).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Glucocorticoid &amp; mineralocorticoid<\/strong> replacement + sex steroid replacement at puberty if needed.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">17\u03b1-HYDROXYLASE DEFICIENCY<\/h2>\n\n\n\n<p>(<strong>CYP17A1 Mutation<\/strong>)<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Enzyme\/Pathway<\/strong>\n<ul class=\"wp-block-list\">\n<li>17\u03b1-hydroxylase (P450c17) required for 17-hydroxylation \u2192 glucocorticoids &amp; sex steroids.<\/li>\n\n\n\n<li>Also has 17,20-lyase activity \u2192 androgens.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormonal Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>\u2191Mineralocorticoid precursors (11-deoxycorticosterone, corticosterone) \u2192 <strong>hypertension, hypokalemia<\/strong>.<\/li>\n\n\n\n<li>\u2193Androgens &amp; estrogens \u2192 lack of pubertal sexual development.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li>Often found at <strong>puberty<\/strong> due to sexual infantilism.<\/li>\n\n\n\n<li><strong>46,XX<\/strong>: <a href=\"https:\/\/myendoconsult.com\/learn\/evaluation-of-primary-amenorrhea\/\" data-wpil-monitor-id=\"167\">Primary amenorrhea<\/a>, no secondary sexual characteristics, HTN, hypokalemia.<\/li>\n\n\n\n<li><strong>46,XY<\/strong>: Phenotypic female (externally), but no internal female structures, intraabdominal testes, no puberty, HTN, hypokalemia.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory Findings<\/strong>\n<ul class=\"wp-block-list\">\n<li>Hypokalemia, low plasma renin, low aldosterone (corticosterone suffices for MR effect).<\/li>\n\n\n\n<li>High DOC, high corticosterone, low 17-hydroxyprogesterone, low cortisol, low sex steroids.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Glucocorticoid<\/strong> replacement to suppress ACTH.<\/li>\n\n\n\n<li><a href=\"https:\/\/myendoconsult.com\/learn\/topics\/disorders-of-sex-development\/\"  data-wpil-monitor-id=\"334\">Sex steroid replacement for pubertal development<\/a>.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">21-HYDROXYLASE DEFICIENCY<\/h2>\n\n\n\n<p>(<strong>CYP21A2 Mutation<\/strong>)<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Incidence<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>&gt;90%<\/strong> of <a href=\"https:\/\/myendoconsult.com\/learn\/courses\/cah\/\" data-wpil-monitor-id=\"172\">CAH<\/a> cases, autosomal recessive.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormone Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>Defect in conversion:\n<ul class=\"wp-block-list\">\n<li><strong>Progesterone \u2192 11-deoxycorticosterone<\/strong> (mineralocorticoid branch).<\/li>\n\n\n\n<li><strong>17-hydroxyprogesterone \u2192 11-deoxycortisol<\/strong> (glucocorticoid branch).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Excess<\/strong>: 17-hydroxyprogesterone, progesterone, adrenal androgens.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Classic Salt-Wasting<\/strong>: Severe deficiency \u2192 life-threatening neonatal salt-losing crisis, ambiguous genitalia in 46,XX.<\/li>\n\n\n\n<li><strong>Classic Simple Virilizing<\/strong>: Some mineralocorticoid function preserved; virilization but no salt-wasting.<\/li>\n\n\n\n<li>Nonclassic (late-onset): Milder, partial enzyme defect.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory Findings<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>\u219117-hydroxyprogesterone<\/strong> (often &gt; 6x normal).<\/li>\n\n\n\n<li>Low cortisol, low aldosterone in salt-wasters, \u2191ACTH, \u2191renin.<\/li>\n\n\n\n<li>\u2191Androstenedione, \u2191testosterone, decreased 11-deoxycortisol.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Diagnosis<\/strong>\n<ul class=\"wp-block-list\">\n<li>Newborn screening (17-hydroxyprogesterone test).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Glucocorticoid &amp; mineralocorticoid<\/strong> replacement.<\/li>\n\n\n\n<li><strong>Surgical correction<\/strong> of ambiguous genitalia if needed.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">11\u03b2-HYDROXYLASE DEFICIENCY<\/h2>\n\n\n\n<p>(<strong>CYP11B1 Mutation<\/strong>)<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Enzyme\/Pathway<\/strong>\n<ul class=\"wp-block-list\">\n<li>Converts 11-deoxycortisol \u2192 cortisol in fasciculata, and 11-deoxycorticosterone (DOC) \u2192 corticosterone in glomerulosa.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormonal Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>\u219111-deoxycortisol, \u2191DOC, \u2191adrenal androgens.<\/li>\n\n\n\n<li>DOC has mineralocorticoid activity \u2192 <strong>hypertension, hypokalemia<\/strong>, suppressed renin, low aldosterone.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical Presentation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Severe deficiency<\/strong>: Neonatal virilization (46,XX ambiguous genitalia), salt retention (HTN).<\/li>\n\n\n\n<li>Partial deficiency: Hypertension, possible <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/precocious-puberty\/\"  data-wpil-monitor-id=\"335\">precocious puberty<\/a>, or young adult onset of HTN, hirsutism, oligomenorrhea.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Laboratory Findings<\/strong>\n<ul class=\"wp-block-list\">\n<li>\u219111-deoxycortisol, \u2191DOC, \u2191DHEA, DHEA-S, androstenedione, testosterone.<\/li>\n\n\n\n<li>Hypokalemia, low renin, low aldosterone, high ACTH.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Treatment<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Glucocorticoid<\/strong> replacement \u00b1 mineralocorticoid considerations (though often suppressed renin\u2013aldosterone axis already).<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">APPARENT MINERALOCORTICOID EXCESS<\/h2>\n\n\n\n<p>(<strong>11\u03b2-HSD2 Deficiency<\/strong>)<\/p>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Enzyme<\/strong>\n<ul class=\"wp-block-list\">\n<li>11\u03b2-hydroxysteroid dehydrogenase type 2 normally inactivates <a href=\"https:\/\/myendoconsult.com\/learn\/cortisol-cortisone-shunt\/\"  data-wpil-monitor-id=\"336\">cortisol \u2192 cortisone<\/a> in kidney.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Pathophysiology<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Decreased 11\u03b2-HSD2<\/strong> \u2192 cortisol not inactivated \u2192 binds mineralocorticoid receptor \u2192 HTN, hypokalemia, metabolic alkalosis, low renin, low aldosterone, normal cortisol levels.<\/li>\n\n\n\n<li>May be hereditary or from <strong>licorice (glycyrrhizic acid)<\/strong> ingestion.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Diagnosis<\/strong>\n<ul class=\"wp-block-list\">\n<li>Abnormal 24-hour urinary ratio of <strong>cortisol : cortisone<\/strong> (&gt;10:1).<\/li>\n\n\n\n<li>Also seen in <strong>ectopic ACTH<\/strong> with massive cortisol production overwhelming 11\u03b2-HSD2.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Clinical<\/strong>\n<ul class=\"wp-block-list\">\n<li>Severe HTN, hypokalemia, suppressed RAAS.<\/li>\n\n\n\n<li>Treated with <strong>mineralocorticoid receptor antagonists<\/strong> (e.g., spironolactone) or correct the underlying cause.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">MAJOR BLOCKS IN ABNORMAL STEROIDOGENESIS (SUMMARY)<\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Congenital Lipoid Hyperplasia<\/strong> (StAR or P450scc)<\/li>\n\n\n\n<li><strong>3\u03b2-HSD Deficiency<\/strong><\/li>\n\n\n\n<li><strong>17\u03b1-Hydroxylase Deficiency<\/strong> (CYP17A1)<\/li>\n\n\n\n<li><strong>21-Hydroxylase Deficiency<\/strong> (CYP21A2)<\/li>\n\n\n\n<li><strong>11\u03b2-Hydroxylase Deficiency<\/strong> (CYP11B1)<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Additional Points<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Aldosterone Synthase (P450c11AS)<\/strong> in <a href=\"https:\/\/myendoconsult.com\/learn\/the-zona-glomerulosa-of-the-adrenal-gland\/\" data-wpil-monitor-id=\"173\">zona glomerulosa<\/a> converts corticosterone \u2192 aldosterone (via 18-hydroxylation).<\/li>\n\n\n\n<li><strong>Zona Glomerulosa<\/strong> lacks 17\u03b1-hydroxylase, cannot synthesize cortisol.<\/li>\n\n\n\n<li><strong>Zona Reticularis<\/strong>: high cytochrome b5 \u2192 strong 17,20-lyase activity \u2192 DHEA production.<\/li>\n\n\n\n<li><strong>Interconversion<\/strong>: 11\u03b2-HSD1 (liver) \u2192 cortisone \u2192 cortisol; 11\u03b2-HSD2 (kidney) \u2192 cortisol \u2192 cortisone.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>CLASSIC CONGENITAL ADRENAL HYPERPLASIA (CAH) General Overview CONGENITAL LIPOID HYPERPLASIA (StAR or P450scc Mutation) 3\u03b2-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY (3\u03b2-HSD2 Mutation) 17\u03b1-HYDROXYLASE DEFICIENCY (CYP17A1 Mutation) 21-HYDROXYLASE DEFICIENCY (CYP21A2 Mutation) 11\u03b2-HYDROXYLASE DEFICIENCY (CYP11B1 Mutation) APPARENT MINERALOCORTICOID EXCESS (11\u03b2-HSD2 Deficiency) MAJOR BLOCKS IN ABNORMAL STEROIDOGENESIS (SUMMARY) Additional Points<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[684],"class_list":["post-4422394","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-adrenal-gland","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422394","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":6,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422394\/revisions"}],"predecessor-version":[{"id":4422816,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422394\/revisions\/4422816"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422394"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422394"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}