Congenital adrenal hyperplasia
Congenital adrenal hyperplasia is a family of autosomal recessive enzyme defects in adrenal steroidogenesis that impair cortisol synthesis, drive ACTH-mediated adrenal hyperplasia, and shunt steroid precursors toward androgen or mineralocorticoid excess depending on which enzyme is deficient. First-line treatment is lifelong glucocorticoid replacement, with mineralocorticoid replacement added when salt wasting is present.
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What this article covers
- Overview
Definition: Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders in which a defective enzyme in the adrenal steroidogenesis pathway impairs cortisol synthesis, leading to…
- Epidemiology
Classic 21-hydroxylase deficiency: The most common cause of CAH and the most common cause of ambiguous genitalia in a genetically female newborn.
- Risk factors
Autosomal recessive inheritance: Two carrier parents, each with one abnormal allele for the same enzyme, are required for a child to be affected; a family history of CAH or of unexplained neonatal…
- Pathophysiology
Blocked step in steroidogenesis: Cortisol synthesis in the adrenal cortex proceeds through a sequence of enzymatic steps from cholesterol; a defective enzyme at any step blunts cortisol output and…
- Clinical features
Diagnostic anchor: Establishing which CAH subtype is present requires the pattern of mineralocorticoid activity, blood pressure, and sex hormone excess or deficiency, together with the specific elevated precursor for that enzyme block.
- Differential diagnosis
Polycystic ovary syndrome: Shares hirsutism, acne, and menstrual irregularity with nonclassic CAH but does not have an elevated 17-hydroxyprogesterone, distinguishing the two biochemically.
- Diagnosis
Clinching diagnostic basis: CAH is confirmed by demonstrating sharply elevated levels of the steroid precursor immediately proximal to the deficient enzyme, together with low cortisol, in a patient…
- Management
First, treat any adrenal crisis or salt-wasting emergency immediately: Give isotonic fluid resuscitation for dehydration and hypotension, correct hypoglycemia, and give stress-dose hydrocortisone 100…
- Complications
Adrenal crisis: Untreated or under-treated salt-wasting CAH can progress to life-threatening hypotension, hyperkalemia, and hypoglycemia, especially during intercurrent illness if stress dosing is not adjusted upward.
- Prognosis
Good with adherent lifelong therapy: With consistent glucocorticoid and, when needed, mineralocorticoid replacement, most patients with classic CAH achieve normal growth, pubertal development, and…
- Prevention
Universal newborn screening: Screening every newborn for elevated 17-hydroxyprogesterone allows classic 21-hydroxylase deficiency to be identified and treatment started before a salt-wasting crisis…
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Related articles
- 21-hydroxylase deficiency
21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an autosomal recessive block in cortisol and aldosterone synthesis that shunts precursors into androgen production, causing salt wasting, hypotension, and virilization in the classic form. First-line treatment is lifelong glucocorticoid replacement, with fludrocortisone and sodium chloride added when salt wasting is present.
- 11-beta-hydroxylase deficiency
11-beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, an autosomal recessive block in cortisol synthesis that shunts precursors into deoxycorticosterone and androgens, causing hypertension, hypokalemia, and virilization rather than the salt wasting of 21-hydroxylase deficiency. First-line treatment is lifelong glucocorticoid replacement to suppress ACTH and precursor overproduction.
- 17-alpha-hydroxylase deficiency
17-alpha-hydroxylase deficiency is a rare autosomal recessive form of congenital adrenal hyperplasia in which CYP17A1 loss blocks cortisol and sex-steroid synthesis while shunting precursors into mineralocorticoid excess, producing hypertension, hypokalemia, and sexual infantilism. First-line treatment is daily glucocorticoid replacement (hydrocortisone) to suppress ACTH-driven deoxycorticosterone and corticosterone overproduction, combined with sex-hormone replacement to induce puberty.
- Adrenal crisis
Adrenal crisis is life-threatening acute glucocorticoid deficiency, most often precipitated by infection or another physiologic stress in a patient with known or unrecognized adrenal insufficiency, presenting with dehydration, hypotension, or shock out of proportion to the concurrent illness. Treatment is immediate intravenous hydrocortisone 100 mg followed by 50 mg every 6 hours plus isotonic saline with dextrose, without waiting for confirmatory labs.
- Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder of chronic anovulation and is the most common cause of hirsutism and anovulatory infertility in women. First-line treatment is weight loss for patients with an elevated BMI, combined oral contraceptives for menstrual dysfunction and hirsutism when fertility is not desired, and clomiphene citrate or letrozole for ovulation induction when fertility is desired.
- Cushing syndrome
Cushing syndrome is the clinical state of chronic glucocorticoid excess from any cause, most often exogenous glucocorticoid use, diagnosed by demonstrating loss of normal cortisol suppression or diurnal rhythm with at least two of three screening tests. Treatment targets the underlying source: withdrawal or tapering of exogenous steroid, transsphenoidal surgery for a pituitary cause, or adrenalectomy for an adrenal or ectopic tumor, with steroidogenesis inhibitors reserved for persistent or unresectable disease.