C-17 Hydroxylase Deficiency Treatment & Management

Updated: Dec 16, 2014
  • Author: Gabriel I Uwaifo, MD; Chief Editor: George T Griffing, MD  more...
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Treatment

Medical Care

As with other variants of congenital adrenal hyperplasia (CAH), appropriate glucocorticoid replacement is the cornerstone of therapy. [20, 21]

  • With adequate repletion, natriuresis and normalization of serum renin and potassium occur, and aldosterone levels gradually increase towards normal.
  • Appropriate glucocorticoid replacement normalizes blood pressure. However, hypertension may be sustained if it has not been treated for many years.
  • Hydrocortisone is the ideal glucocorticoid in childhood. The typical hydrocortisone replacement dose is 10-20 mg/m 2/d.
  • Dexamethasone may be used in adults. The dexamethasone doses typically are 0.3-0.5 mg/d.
  • Natriuresis and diuresis may occur, resulting in an acute hypovolemic crisis soon after therapy is begun because of a suppressed renin-angiotensin-aldosterone system. This risk is greater in patients with higher initial blood pressure elevations.
  • The timing of recovery of the renin-angiotensin-aldosterone system following effective glucocorticoid repletion is variable and can take months to years.

Among patients who remain slightly hypertensive even with adequate glucocorticoid replacement, first-line therapy includes the use of a mineralocorticoid antagonist, spironolactone, or eplerenone. Calcium channel blockers are added if hypertension persists.

Moderation of dietary sodium intake is recommended.

Hormone replacement regimens are best begun early in adolescence to achieve their greatest potential. They allow the development of female secondary sexual characteristics and stimulate the normal increase in bone mass that occurs with puberty.

  • Estrogen replacement is initiated at the time of expected puberty; if that time has passed, the replacement therapy is initiated at the time of diagnosis.
  • Patients who are 46,XX require combined estrogen/progestin cyclic or combined therapy to prevent endometrial hyperplasia from unopposed estrogen.
  • Patients who are 46,XY lack müllerian structures and are often treated with estrogen alone if they first come to medical attention during the age of puberty and had hitherto been raised as girls. The decision to instead effect a sex identity change and treat such patients with androgen replacement and extensive genital reconstructive surgery should not be entered into lightly. The treatment should be used only if the patient and parents/guardians decide on this option after being fully educated regarding the implications, ramifications, and possible consequences of such a decision.
  • To stimulate penile development, testosterone replacement may be given to mildly affected 46,XY patients born with ambiguous genitalia. In addition, these patients often require extensive reconstructive surgery of the external genitalia, as well as a gonadectomy. The decision to rear these patients as males is complex.

Unlike in the 11-beta hydroxylase or 21-hydroxylase deficiency variants of CAH, which are associated with virilization, prenatal dexamethasone has no role in this setting. [22]

Goals of treatment

  • Glucocorticoid replacement with avoidance of glucocorticoid excess (iatrogenic Cushing syndrome)
  • Reduction in mineralocorticoid secretion
  • Normalization of blood pressure
  • Adequacy of glucocorticoid repletion
    • This is determined by clinical and biochemical characteristics.
    • Among the clinical indices used most commonly are the child's height and weight velocity and normalization of blood pressure.
  • Normalization of plasma potassium concentrations and restoring plasma renin activity to a measurable range
  • Reduction of serum levels of deoxycorticosterone and corticosterone
    • Normalization of these levels may require overtreatment with glucocorticoids.
    • This should not be a major goal.
  • Replacement of sex steroids
  • Preservation of bone mass and prevention of osteoporosis
    • While adequate hormone replacement may achieve this, calcium and vitamin D supplementation may be needed.
    • Prophylactic or therapeutic bisphosphonate use also may be needed.

DHEA supplementation may be considered, although this has not been approved by the US Food and Drug Administration (FDA). Several reports, including that by Arlt and colleagues, have suggested that DHEA supplementation in females who have adrenal insufficiency significantly improves overall well-being and sexual function. [23, 24]

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Surgical Care

Affected 46,XY patients require gonadectomy to prevent malignant degeneration of their gonads.

  • Because of the significant neoplastic risk of undescended dysplastic testes (whether intra-abdominal or inguinal), they should be surgically removed as soon as the elective procedure can be safely performed and certainly before age 8-10 years (if detected in childhood).
  • If found in adulthood, the testes should be removed as soon as possible, because the neoplastic potential in this setting is considerable.

The reconstruction of ambiguous genitalia may be indicated.

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Consultations

The hypogonadism, infertility, and, in some cases, sexual ambiguity associated with 17-hydroxylase deficiency require a multidisciplinary approach to issues of sexual orientation, sexual identity, body image, and psychosocial support. [25]

  • Consultation with a psychiatrist and/or psychologist often is very useful in helping to resolve some of the conflicts and crises that these patients face. Most patients are diagnosed at an age at which their gender identity has been firmly established; however, patients may have difficulty comprehending the complexity of their condition.
  • If fertility is desired, referral to a fertility specialist is indicated.
    • Patients invariably require donor egg or donor sperm programs to be used with artificial insemination, in-vitro fertilization, or intracytoplasmic sperm transfer.
    • One case has been reported in the literature of a woman with 17-hydroxylase deficiency who responded to the induction of ovarian follicular growth using gonadotrophin-releasing hormone analogs and who subsequently had a successful pregnancy using in-vitro fertilization techniques.
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