Medical Care
Classic 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency: Patients with classic salt-losing 3-beta–hydroxysteroid dehydrogenase require replacement of glucocorticoids, mineralocorticoids, and sex steroids.
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Exogenous orally administered hydrocortisone (or other glucocorticoid) is used to suppress adrenocorticotropic hormone (ACTH) secretion and decreases plasma concentrations of pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA). Dose requirements are variable. Some patients require larger-than-normal glucocorticoid doses and may still not achieve adequate androgen suppression. [11]
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Hydrocortisone tablets are the preferred glucocorticoid choice for treatment. Tablets may be crushed in liquid immediately prior to dosing for infants and small children. Premixed, oral suspensions of hydrocortisone should be avoided, as should long-acting glucocorticoid preparations in pediatric patients. [20]
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Mineralocorticoid replacement is achieved with the oral administration of fludrocortisone acetate (9-alpha-fluorohydrocortisone, Florinef). Patients with non–salt-losing variants do not require mineralocorticoid replacement.
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At puberty, patients with complete 3-beta–hydroxysteroid dehydrogenase deficiency require sex steroid replacement, including testosterone in males and cyclic estrogen-progesterone therapy in females. Such therapy promotes development of secondary sexual characteristics in both males and females, and cyclic menstrual bleeding in 46,XX females.
Late-onset (nonclassic) 3-beta–hydroxysteroid dehydrogenase deficiency: The need for replacement therapy varies, depending on the severity of the defect. Hydrocortisone (or other glucocorticoid) replacement suppresses excess androgens in children with premature pubarche and may correct menstrual irregularities and decrease hirsutism and acne in pubertal and postpubertal females.
Although the literature and experience regarding treatment of pediatric patients is extensive, little has been published regarding treatment of adults with congenital adrenal hormone deficiencies. [21, 22] Treatment in adults is aimed at preventing adrenal insufficiency and suppressing excess androgens, while avoiding the extremes of overtreatment and undertreatment. [20]
A survey in the United Kingdom demonstrated that the most widely used glucocorticoid in adult patients was hydrocortisone, followed by dexamethasone and prednisolone. [23] Sixty percent of physicians surveyed used larger doses of glucocorticoids at night (reverse circadian pattern) to achieve adrenocorticotropic hormone (ACTH) suppression, and only 16% of treating physicians used body weight or surface area to determine dosage.
Complications
Benign testicular adrenal rest tumors are found in adult men in association with poorly controlled congenital adrenal hyperplasia (CAH). Such men may have gonadal dysfunction and infertility, perhaps due to obstruction of seminiferous tubules. [24]
High-resolution ultrasonography has recently been used to estimate the prevalence of testicular adrenal rest tumors in male children with CAH, with a reported incidence ranging from 21-24%. [25, 24]
Although the testes are by far the most common location for such rest tumors, ectopic adrenal rest tumors may be present elsewhere. [26]
Long-Term Monitoring
Follow up with infants and young children about every 3-4 months for evaluation of height and weight, blood pressure, and laboratory monitoring (ie, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone [DHEA], plasma renin levels). Individualize adjustment of hydrocortisone and fludrocortisone acetate dosages based on the results of the physical examination and laboratory studies.
A left-hand radiograph may be obtained yearly for evaluation of skeletal maturation.
Sex hormone replacement may be required at the time of expected puberty in patients with complete 3-beta–hydroxysteroid dehydrogenase (3BHSD) deficiency. Because commercial estrogen preparations in the United States contain high doses of estradiol that induce rapid epiphyseal maturation, replacement therapy is often delayed until the bone age is 12 years or more to preserve linear growth. Ideally, testosterone or estrogen should begin at very low doses and gradually increase as the child ages and matures.
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Normal adrenal steroid biosynthesis results in 3 products: mineralocorticoid (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 subsequent increased production of all adrenal steroids.
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Representation of typical congenital adrenal hyperplasia (CAH). In this example, both the mineralocorticoid and glucocorticoid pathways are deficient. Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. Increased ACTH secretion results in overproduction of adrenal steroids preceding the missing enzyme as well as those not requiring the missing enzyme. In this example, a deficiency of 21-hydroxylase results in deficient mineralocorticoid and glucocorticoid production and excessive androgen production.
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3-beta-hydroxysteroid dehydrogenase (3BHSD) is required for the synthesis of all three groups of adrenal steroids: mineralocorticoids, glucocorticoids, and sex steroids. 3BHSD catalyzes the conversion of pregnenolone to progesterone (mineralocorticoid pathway), 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone (glucocorticoid pathway), and dehydroepiandrosterone to androstenedione (sex steroid pathway). Complete absence of this enzyme thus impairs all steroid production. 17OH Preg = 17-alpha-hydroxypregnenolone; DHEA = Dehydroepiandrosterone; 17OH Prog = 17-alpha-hydroxyprogesterone; Andros = Androstenedione; DOC = Deoxycorticosterone; Cmp S = Compound S.
