Diagnostic Considerations

Impaired hepatic drug metabolism may be a problem in patients with P450 oxidoreductase (POR) deficiency,^[13]but further study is necessary before specific recommendations can be made. Because patients with P450 oxidoreductase (POR) deficiency can present with multiple clinical manifestations and have defects in various steroidogenic enzymes, they may be mistakenly diagnosed.^[31]Differentiating 17-hydroxylase deficiency syndrome from POR deficiency is important because patients with POR deficiency have the additional potential for adrenal insufficiency.^{[13, 14]}POR deficiency should be suspected in patients with adrenal insufficiency and genital anomalies who have associated skeletal malformations.

The 46,XX karyotypes resemble Turner syndrome with Müllerian structures and absent secondary sexual characteristics; however, patients with 17-Hydroxylase (17-OH) deficiency syndrome lack the other Turner stigmata (lymphedema, wide carrying angle, cardiac defects) and are typically normal height or tall.^[32]

The 46,XY karyotype somewhat resemble complete androgen insensitivity syndrome due to the blind vaginal pouch without Müllerian structures or body hair, but 17OH deficiency will respond to androgens if administered.^[32]

Differential Diagnoses

Workup

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Media Gallery

17-Hydroxylase Deficiency Syndrome. Normal adrenal steroid biosynthesis results in three products: mineralocorticoids (aldosterone), glucocorticoids (cortisol), and androgens (androstenedione). Cortisol production is regulated by feedback with adrenocorticotropic hormone (ACTH). ACTH stimulates the enzyme P-450scc (20,22 desmolase), with subsequently increased production of all adrenal steroids.
17-Hydroxylase Deficiency Syndrome. Representation of typical congenital adrenal hyperplasia (CAH). This example shows a deficiency in both the mineralocorticoid and glucocorticoid pathways. Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. Increased ACTH secretion causes overproduction of adrenal steroids preceding the missing enzyme as well as those not requiring the missing enzyme. The example depicts a deficiency of 21-hydroxylase, resulting in deficient mineralocorticoid and glucocorticoid production and excessive androgen production.
17-Hydroxylase Deficiency Syndrome. C-17α-hydroxylase is necessary to convert pregnenolone to 17-hydroxypregnenolone (17-OH Preg) and progesterone to 17-hydroxyprogesterone (17-OH Prog). Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production. Low levels of cortisol result in increased adrenocorticotropic hormone (ACTH) stimulation of steroids prior to the 17-hydroxylase step, resulting in increased accumulation and secretion of 17-deoxysteroids by the zona fasciculata, including pregnenolone, progesterone, deoxycorticosterone (DOC), and corticosterone.
17-Hydroxylase Deficiency Syndrome. Graphic illustration of deficiency. Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production.