From the Guidelines
17-hydroxylase deficiency and 21-hydroxylase deficiency are distinct congenital adrenal enzyme deficiencies with different clinical presentations and biochemical profiles, as noted in the 2018 guidelines 1. The key differences between these two conditions lie in their effects on hormone production and the resulting clinical manifestations.
- 17-hydroxylase deficiency leads to decreased production of cortisol and sex hormones (estrogens and androgens), causing hypertension, hypokalemia, and issues with sexual development, such as primary amenorrhea in females and undervirilization in genetic males, due to the accumulation of mineralocorticoids like deoxycorticosterone.
- In contrast, 21-hydroxylase deficiency, the most common form of congenital adrenal hyperplasia, results in cortisol and aldosterone deficiency while increasing androgen production, typically presenting as salt-wasting crisis, hypotension, and hyperkalemia in severe cases, along with virilization of female genitalia and precocious puberty in males due to excess androgens. The treatment approaches also differ:
- For 17-hydroxylase deficiency, treatment includes glucocorticoid replacement (e.g., hydrocortisone 15-20 mg/day in divided doses) to suppress ACTH and mineralocorticoid excess, plus sex hormone replacement.
- For 21-hydroxylase deficiency, treatment involves lifelong glucocorticoid replacement, mineralocorticoid replacement (fludrocortisone 0.05-0.2 mg daily), and salt supplementation in salt-wasting cases. These conditions are fundamentally different in their hormonal imbalances: 17-hydroxylase deficiency is characterized by low androgens with high mineralocorticoids, whereas 21-hydroxylase deficiency is marked by high androgens with low mineralocorticoids, as outlined in the guidelines 1.
From the Research
Overview of 17-Hydroxylase and 21-Hydroxylase Deficiencies
- 17-Hydroxylase deficiency and 21-hydroxylase deficiency are two distinct forms of congenital adrenal hyperplasia (CAH) that affect the production of sex steroids and cortisol 2, 3.
- Both deficiencies are caused by mutations in specific genes: CYP17A1 for 17-hydroxylase deficiency and CYP21A2 for 21-hydroxylase deficiency 2, 4.
Clinical Presentation
- 17-Hydroxylase deficiency is characterized by low blood levels of estrogens, androgens, and cortisol, leading to hypertension, primary amenorrhea, and delayed puberty in females, and female external genitalia, a blind vagina, and intra-abdominal testes in males 2.
- 21-Hydroxylase deficiency, on the other hand, presents with an impairment of both aldosterone and cortisol biosynthesis, leading to virilization of female fetuses, salt wasting, and simple virilizing forms 3, 4.
Diagnosis and Treatment
- Diagnosis of 17-hydroxylase deficiency involves measuring plasma levels of 17-hydroxyprogesterone, androstenedione, and testosterone, while 21-hydroxylase deficiency is diagnosed by measuring plasma levels of 17-hydroxyprogesterone and urinary steroid profiles 2, 5.
- Treatment for 17-hydroxylase deficiency involves glucocorticoid and sex steroid replacement, while treatment for 21-hydroxylase deficiency requires hydrocortisone and 9α-fludrocortisone replacement therapies 2, 5.
Key Differences
- The primary difference between 17-hydroxylase and 21-hydroxylase deficiencies lies in the specific enzyme affected and the resulting clinical presentation 2, 3.
- 17-Hydroxylase deficiency is associated with low levels of sex steroids and cortisol, while 21-hydroxylase deficiency is characterized by an accumulation of 17-hydroxyprogesterone and androstenedione 2, 3.
- The treatment approaches also differ, with 17-hydroxylase deficiency requiring sex steroid replacement and 21-hydroxylase deficiency requiring mineralocorticoid replacement 2, 4.