17-Hydroxylase Deficiency Syndrome Clinical Presentation

Updated: Mar 16, 2021
  • Author: J Paul Frindik, MD, FACE; Chief Editor: Stephen Kemp, MD, PhD  more...
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In general, patients with 17-hydroxylase (17-OH) deficiency have no history of adrenal insufficiency nor adrenal crisis, presumably due to elevated levels of corticosterone. Patients may have a history of hypertension; alternatively, hypertension may be the presenting complaint. Both the age of onset and degree of severity of hypertension seem to vary between patients. [3]

46,XX karyotype with P450c17 deficiency

Virilization and development of ambiguous genitalia do not occur in 46,XX patients with 17-hydroxylase deficiency.

Unless hypertension is discovered, females may have no historical complaints or findings until puberty.

The ovaries are unable to secrete either androgens or estrogens necessary for sexual maturation, and the adrenal glands cannot secrete androgens necessary for pubic and axillary hair growth. Consequently, adolescent or older females present with complaints of delayed puberty, [3] primary amenorrhea, [30] and lack of secondary sexual characteristics.

46,XY karyotype with P450c17 deficiency

Under-masculinization always occurs in 46,XY individuals with complete P450c17 deficiency. [3] The genitals of such patients vary from phenotypic female to ambiguous male genitalia. Males with phenotypic female genitalia may go undetected until puberty, at which time they present with complaints similar to those of 46,XX patients.

The diagnosis may be suspected in an apparent female infant or young child with a history of an abdominal hernia, inguinal mass, or otherwise unexplained hypertension.


Physical Examination

Mildly to severely elevated blood pressure may be the primary finding in patients with 17-hydroxlase deficiency syndrome.

46,XX karyotype with P450c17 deficiency

Affected 46,XX individuals have phenotypic female normal external and internal female differentiation.

Adolescent and older women may exhibit sexual infantilism and little or no pubic or axillary hair.

The first described female patient presented with hypertension, hypokalemia, no breast development, primary amenorrhea, and lack of pubic and axillary hair.

Internally, patients have a small prepubertal uterus and may have multicystic ovaries, presumably from gonadotropic stimulation.

46,XY karyotype with P450c17 deficiency

Genitals of affected 46,XY individuals vary from phenotypic female to ambiguous male genitalia.

Gynecomastia has been reported in a male patient with ambiguous genitalia.

The patient may present as an otherwise phenotypic normal female; however secondary sexual characteristics are missing. Closer physical examination reveals the vagina to be a blind pouch, and the patient lacks internal genitalia.

Testes may be undescended or located in the inguinal canal.

Histology of the testes reveals atopic tubules, Sertoli cells, and Leydig cell hyperplasia.

Although rarely diagnosed in younger children, an abdominal hernia or inguinal mass in a phenotypic female infant or child, especially if combined with hypertension, suggests a diagnosis of 17-hydroxylase deficiency.

P450 oxidoreductase deficiency

Patients with P450 oxidoreductase (POR) deficiency have varying degrees of adrenal insufficiency and genital anomalies. Skeletal malformations, including craniosynostosis, radio-ulnar synostosis, midface hypoplasia, and bowed femurs (Antley-Bixler syndrome), may be caused by fibroblast growth factor 2 receptor mutations, but have also been reported in patients with POR deficiency. Genital anomalies are found in both male and female patients with POR deficiency. Affected males may be ambiguous as would be expected from the low levels of sex steroids. However, affected females with POR can actually present with severe virilization. Virilization in such affected 46 XX females may be due to an alternative androgen pathway involving dihydrotestosterone synthesis, but the exact mechanism remains incompletely explained. [13, 14, 15]