Patients with Non Classic 21-OH Deficiency typically show 60-min stimulated 17-OHP values between 1,500 and 10,000 ng/dl. This chart
shows how the 17-OHP values cluster at three areas for normal (below
1,500), Non-Classical CAH (1500-10,000) and, and Classical CAH (above
10,000).(6) A useful chart showing the CAH testing algorithm is available.(7)
Genetic Testing for 21-OH Deficiency
Genetic testing is now available and very useful. This Quest Lab test shows whether or not there is a mutation in the CYP21A2 gene coding for the 21-Hydroxylase Enzyme.(8) The CAHDtex test by Esoterix is also useful in showing the exact mutation in the CYP21A2 gene.(9) Once the exact mutation in the CYP21A2 gene is known, refer to this chart to determine the severity of the enzyme defect.(10) Genetic testing of other family members is usually recommended once a sibling is found with the mutation. Dr. Maria New has her own in-house lab in New York which does genetic testing for CAH.(11)
Clinical Presentation in Children
In children, the signs of non-classical CAH include premature onset of puberty, cystic acne, accelerated growth, and advanced bone age. Premature development of pubic hair may occur as early as 6 months of age (due to elevated testosterone). The severe cystic acne may be unresponsive to oral antibiotics and retinoic acid (Accutane). Although the child may be taller than the other kids in early childhood, this early growth spurt finishes early (because of epiphyseal fusion), and final height ends up shorter than usual. Thus, these kids are tall children but short adults. Another feature may be male pattern baldness in a female involving the top of the head and sparing the sides.
Teenagers and Young Adults - Major Cause of Infertility
Teenage girls may present with features of elevated testosterone such as facial hair (hirsutism), acne and menstrual irregularities or anovulation. Young adult females may present with the chief complaint of infertility. It has been generally recognized that infertility of undetermined cause in women may be reversed with glucocorticoid (cortef or prednisone) therapy, which most likely treats an occult Non-Classical CAH Syndrome. William Mc Jefferies MD successfully treated thousands of such cases describerd in his 1976 medical classic, The Safe Uses of Cortisol.(12) Dr. McJefferies speculated correctly that an abnormality in adrenal steroid synthesis was present in many young girls with infertility, and only years later was the exact molecular and genetic basis elucidated. In retrospect, non-classical CAH should be called McJefferies syndrome to give this great clinician credit for his early work.
Treatment of Non Classical CAH with Cortisol Restores Fertility
Oral tablets containing low dose cortisol successfully treat Non-Classical CAH and reverse the symptoms restoring fertility. The cortisol suppresses ACTH and reduces the testosterone production by the adrenal.
Dr. Maria I New is the present day national expert on non-classical CAH, and she has followed a large group of 400 patients with Non-Classical CAH. Dr. New treats them with 0.25 mg. dexamethasone at the hour of sleep, and notes that it takes about 3 months for reversal of acne and infertility. Hirsutism takes longer to respond, about 30 months. (3)(13)
Left Image Courtesy of Maria I New MD.(13)
The cost for a dexamethasone tablet is $0.50, and the 3-month treatment cost is estimated to be $45. Compare this $45 dollars to the infertility treatment cost of $30,000 for one cycle of in vitro fertilization. Dr. Maria New says that many patients presenting with infertility actually have NonClassical CAH, and fertility could be restored easily with treatment with oral cortisol tablets such as Dexamethasone, Prednisone or even the Cortef recommended by McJefferies.(3) Before spending a fortune on in-vitro fertilization for infertility, it would be prudent to rule out Non-Classical CAH with a simple genetic test.
Safety of Low Dose Cortisol
Low dose Cortef, Prednisone or Dexamethasone treatment is safe without the adverse side effects associated with high dose treatment. However, there is a chance of mild adrenal suppression which could require additional or extra doses of medication under periods of higher stress or illness such as the flu or when undergoing a surgical operation. Therefore McJefferies routinely gave instructions to increase the cortisol dosage when a flu illness is noted coming on or under similar stresses. He also advised his patients to wear a warning bracelet containing the information that the patient has non classical CAH, with cortisol dosage and timing.(12)
Jeffrey Dach MD
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TABLE 7. National health care burden for treatment of hyperandrogenic signs associated with NC21OHD. EXTENSIVE CLINICAL EXPERIENCE Nonclassical 21-Hydroxylase Deficiency Maria I. New The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4205-4214
(2) http://jeffreydach.com/2008/02/13/understanding-pcos-the-hidden-epidemic-by-jeffrey-dach-md.aspx Understanding PCOS, the Hidden Epidemic by Jeffrey Dach, M.D.
EXTENSIVE CLINICAL EXPERIENCE. Nonclassical 21-Hydroxylase Deficiency by Maria I. New MD.The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4205-4214.
Consensus Statement on Treatment of 21-Hydroxylase Deficiency. JCEM 87(9):4048-4053, 2002.
Adrenal Steroid Pathways chart Quest Labs
FIG. 5. Nomogram relating baseline to ACTH-stimulated serum concentrations of 17-OHP. From Maria New article.
Congenital Adrenal Hyperplasia Test Guide Quest Labs
Quest Lab Test Code 14755X - a genetic test for the common mutations for CAH 21 hydroxylase deficiency
DNA TESTING FOR 21-HYDROXYLASE DEFICIENCY. Esoterix introduces a new DNA test to identify deficiency in the 21-hydroxylase gene, the most common cause of congenital adrenal hyperplasia (CAH). CAHDetx evaluates the CYP21 gene, detecting mutations and gene deletion/conversions that account for approximately 90% to 95% of all CAH cases.
TABLE 1. Common gene mutations of the 21-hydroxylase gene CYP21A2 from MAria New
Safe Use of Cortisol is a Unique Medical Classic, December 7, 2007 By Jeffrey Dach MD
Dr. Maria I. New is one of the world's leading pediatric endocrinologists and children's advocates. Professor of Pediatrics, Director, Adrenal Steroid Disorders Program, Mount Sinai School of Medicine1 Gustave L. Levy Place, Box 1198, New York, NY 10029-6574
PCOS ICD-9 256.4 Amenorrhea ICD-9 626.0 CAH 255.2
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