Professor, Department of Pediatrics, Director, Adrenal Steroid Disorders Program, Mount Sinai School of Medicine, New York, New York 10029, USA
This presentation is a slightly modified version of a paper that appeared previously as the following chapter: New, M.I. & L. Ghizzoni. 1999. An update on congenital adrenal hyperplasia. In Pediatric Endocrinology, 3rd edit., pp. 305-320 (4th edit., pp. 175-192). F. Lifshitz, Ed. Marcel Dekker. New York.
Address for correspondence: Maria I. New, MD, Professor, Department of Pediatrics, Director, Adrenal Steroid Disorders Program, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1198, New York, NY 10029. Voice: 212-241-7847; fax: (212) 241-5405. maria.new{at}mssm.edu
Congenital adrenal hyperplasia (CAH) is a family of autosomal
recessive disorders caused by mutations that encode for enzymes
involved in one of the various steps of adrenal steroid synthesis.
These defects result in the absence or the decreased synthesis
of cortisol from its cholesterol precursor. The anterior pituitary
secretes excess adrenocorticotrophic hormone (ACTH) via feedback
regulation by cortisol, which results in overstimulation of
the adrenals and causes hyperplasia. Symptoms due to CAH can
vary from mild to severe depending on the degree of ensymatic
defect. In the classical form of CAH, there is a severe enzymatic
defect owing to mutations in the CYP21 gene. Classically affected
female fetuses undergo virilization of the genitalia prenatally
and present with genital ambiguity at birth; however, prenatal
treatment of CAH with dexamethasone to prevent ambiguity has
been successfully utilized for over a decade. In the less severe,
late-onset form of CAH, prenatal virilization does not occur.
The milder enzyme deficiency was termed nonclassical 21-hydroxylase
deficiency (NC21OHD) in 1979 and was later found to be the most
common autosomal recessive disorder in humans. Disease frequency
of NC21OHD varies between ethnic groups with the highest ethnic-specific
disease frequency in Ashkenazi Jews at 1/27. NC21OHD is diagnosed
by serum elevations of 17-OHP that plot on a nomogram between
the range for unaffected individuals and levels observed for
classical CAH and is typically confirmed with molecular genetic
analysis. Similar to classical CAH, nonclassical 21-hydroxylase
deficiency may cause premature development of pubic hair, advanced
bone age, acelerated linear growth velocity and diminished final
height in both males and females. Severe cystic acne has also
been attributed to nonclassical CAH. Women may present with
symptoms of androgen excess, including hirsutism, temporal baldness,
and infertility. Menarche in females may be normal or delayed
and secondary amenorrhea is a frequent occurence. Polycystic
ovary syndrome may also be seen in these patients. In males,
early beard growth, acne, and growth spurt may prompt the diagnosis
of NC21OHD. Although many males appear to be asymptomatic, they
may present with oligozoospermia or diminished fertility. Individuals
presenting to dermatology and infertility clinics with symptoms
of hyperandrogenemia are rarely screened for NC21OHD. However,
with hormonal and molecular genetic screening, previously undiagnosed
patients may be identified and can therefore receive glucocorticoid
treatment, which has been shown to reverse symptoms within 3
months.
