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.
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What this article covers
- Overview
Rare enzymatic block in adrenal and gonadal steroidogenesis: 17-alpha-hydroxylase deficiency is caused by loss-of-function mutations in CYP17A1, the enzyme that adds a 17-hydroxyl group to…
- Epidemiology
One of the rarest forms of CAH: 21-hydroxylase deficiency is by far the most common form; 17-alpha-hydroxylase deficiency accounts for only a small minority of CAH cases.
- Risk factors
Biallelic pathogenic CYP17A1 variants: the disease requires two loss-of-function alleles; heterozygous carriers are unaffected.
- Pathophysiology
CYP17A1 has two enzymatic activities, both lost: 17-alpha-hydroxylase activity converts pregnenolone to 17-hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; 17,20-lyase activity then…
- Clinical features
Hypertension with hypokalemia in a patient with sexual infantilism or ambiguous genitalia is the defining combination, distinct from every other common cause of ambiguous genitalia or delayed…
- Differential diagnosis
21-hydroxylase deficiency: the most common CAH; distinguished by hypotension or normal blood pressure and virilization from androgen excess, unlike the hypertension and sex-steroid deficiency here.
- Diagnosis
The diagnosis is established by an ACTH stimulation test showing elevated corticosterone and deoxycorticosterone with an absent or blunted DHEA response, in a patient with hypertension, hypokalemia…
- Management
Start glucocorticoid replacement as the first action: hydrocortisone 15-25 mg/day PO divided into 2-3 doses, largest on waking (children: 8-10 mg/m²/day PO divided three times daily), continued…
- Complications
Sustained hypertension leading to left ventricular hypertrophy and cardiovascular disease if diagnosis or treatment is delayed.
- Prognosis
Normal life expectancy with adequate glucocorticoid replacement and blood pressure control.
- Prevention
Newborn screening programs targeting classic CAH (21-hydroxylase deficiency via 17-hydroxyprogesterone) do not reliably detect 17-alpha-hydroxylase deficiency, because 17-hydroxyprogesterone is low…
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Related articles
- 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.
- 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.
- Primary adrenal insufficiency
Primary adrenal insufficiency (Addison disease) is destruction or dysfunction of the adrenal cortex, most often autoimmune, causing combined cortisol and aldosterone deficiency with hyperpigmentation, hyponatremia, and hyperkalemia. Lifelong glucocorticoid replacement with hydrocortisone plus mineralocorticoid replacement with fludrocortisone is required, with sick-day dose increases to prevent adrenal crisis.