24 NonClassical CAH
Irregular Menstrual Cycles, Acne, and Hirsutism
by Jeffrey Dach MD
Our nation spends millions of dollars on laser hair removal treatments, and acne skin treatments.(1) Infertile women spend small fortunes on sophisticated in-vitro fertilization techniques. These symptoms can be found in a common genetic disorder called Non-Classic CAH which occurs 3% of certain ethnic groups, and the diagnosis may be missed by the medical system. Curative treatment is an inexpensive tablet costing pennies a day, called Dexamethasone, given at bedtime which restores fertility and cycle regularity, and eliminates the hirsutism (facial hair) and acne.
An
estimated ten percent of Poly Cystic Ovary Syndrome (PCOS) patients
may have underlying Non-Classical CAH causing symptoms of irregular
menstrual periods, acne, hirsutism (unwanted facial hair) and
infertility. Click here for an earlier report on Understanding PCOS, the Hidden Epidemic.(2) Left Image: Hirsutism, unwanted hair grrowth under chin caused by CAH. Courrtesy of Wikipedia.
What is NonClassical CAH?
Also called: NonClassical Congenital Adrenal Hyperplasia, Non-Classical 21 Hydroxylase Deficiency (NC21OHD)
This chart shows incidence of CAH among various ethnic groups.
Non-Classical CAH is in the central rectangle. Courtesy of Maria New MD(3)
Non-Classical CAH or 21-Hydroxylase Deficiency is the most common genetic disease known, occurring in 1% of New Yorkers, and up to 3% in ethnic groups such as of Ashkenazi Jews, Hispanics, Italians, and Yugoslavs (3).
Adrenal Gland Enzyme Deficiency, and Reduced Ability to Make CortisolThe underlying genetic disorder causes an enzyme deficiency in the adrenal gland which reduces the ability of the adrenal to make cortisol. Instead of making cortisol, the adrenal steroid pathways are shunted towards testosterone causing elevated testosterone and the typical symptoms of hair growth (hirsutism), and acne and there may also be menstrual irregularities, anovulation, and infertility.(3)(4)
Left Image: The Adrenal Gkands Courtesy of Wikipedia
What is the 21 Hydroxylase Enzyme?
This is a key enzyme in the adrenal gland involved in the conversion of cholesterol into cortisol. In the Classical form of CAH, the 21 hydroxylase enzyme (21-OH) is severely deficient with resulting low cortisol levels, and high testosterone levels. In the Non-Classical form however, the 21 hydroxylase (21-OH) enzyme is still working fairy well with only a slight reduction in activity, and cortisol levels are usually normal, while testosterone levels may be elevated to a variable degree. The Adrenal Steroid synthesis pathways and the adrenal enzymes involved can be understood on a chart on the Quest web site.(5)
How to Make the Diagnosis of Non-Classical CAH? Use Cortrosyn Stimulation.
The most definitive diagnosis is done with a Cortrosyn Stimulation test (0.25 mg) which measures 17-hydroxyprogesterone (17-OHP) at 0 and 60 minutes after SQ injection of the Cortrosyn (ACTH). This test in simple terms is described here:
First a preliminary (baseline ) blood test is done for various hormones including 17-OHP, this is followed by a subcutaneous injection of 0.25 mg of a drug called Cortrosyn which is a form of ACTH which stimulates the adrenal glands to make more hormones. An hour (60 minutes) after the Cortrosyn injection, a post stimulation blood sample is drawn for lab testing for 17-OHP and other hormones.
.
Classification of CAH depends on 17-OH-Progesterone (17-OHP) values on stimulated test. Normal is lowest circle, non-classical CAH is middle circle, and classical full blown CAH is the upper circle. Courtesy of Maria New MD review article.(3)
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
4700 Sheridan Suite T
Hollywood, Fl 33021
954 983 1443
www.jeffreydach.com
www.drdach.com
www.naturalmedicine101.com
www.truemedmd.com
REFERENCES
(1) http://jcem.endojournals.org/cgi/content/full/91/11/4205/T7
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.
(3) http://jcem.endojournals.org/cgi/content/full/91/11/4205
EXTENSIVE CLINICAL EXPERIENCE. Nonclassical 21-Hydroxylase Deficiency by Maria I. New MD.The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4205-4214.
(4) http://www.mcg.edu/pediatrics/pedsendo/21.pdf
Consensus Statement on Treatment of 21-Hydroxylase Deficiency. JCEM 87(9):4048-4053, 2002.
(5) http://www.questdiagnostics.com/hcp/intguide/EndoMetab/Gen_Misc/TG_CAH/TG_CAH_Fig1.pdf
Adrenal Steroid Pathways chart Quest Labs
(6) http://jcem.endojournals.org/cgi/content/full/91/11/4205/F5
FIG. 5. Nomogram relating baseline to ACTH-stimulated serum concentrations of 17-OHP. From Maria New article.
(7) http://www.questdiagnostics.com/hcp/intguide/jsp/showintguidepage.jsp?fn=EndoMetab/Gen_Misc/TG_CAH/TG_CAH.htm
Congenital Adrenal Hyperplasia Test Guide Quest Labs
(8) http://www.questdiagnostics.com/hcp/intguide/EndoMetab/EndoManual_AtoZ_PDFs/CAH_Common.pdf
Quest Lab Test Code 14755X - a genetic test for the common mutations for CAH 21 hydroxylase deficiency
(9) http://www.esoterix.com/files/ss_cah.pdf
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.
(10) http://jcem.endojournals.org/cgi/content-nw/full/91/11/4205/T1
TABLE 1. Common gene mutations of the 21-hydroxylase gene CYP21A2 from MAria New
(11) http://www.marianew.com/Laboratory.html
CONGENITAL ADRENAL HYPERPLASIA DNA TESTING FOR 21-HYDROXYLASE DEFICIENCY FACT SHEET. MAria New MD Laboratory
(12) http://www.amazon.com/review/R2IPB7XGMO20NE/ref=cm_cr_rdp_perm
Safe Use of Cortisol is a Unique Medical Classic, December 7, 2007 By Jeffrey Dach MD
(13) http://www.marianew.com/index.html
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
Disclaimer www.drdach.com http://www.drdach.com/wst_page20.html
Link to original article here:
http://jeffreydach.com/2008/02/27/a-commonly-missed-cause-of-infertility-nonclassical-cah-by-jeffrey-dach-md.aspx
Disclaimer:
The reader is advised to discuss the comments on these pages with
his/her personal physicians and to only act upon the advice of his/her
personal physician Also note that concerning an answer which appears as
an electronically posted question, I am NOT creating a physician --
patient relationship. Although identities will remain confidential as
much as possible, as I can not control the media, I can not take
responsibility for any breaches of confidentiality that may occur.
Finally, the material produced by myself may be reproduced for personal
use, provided that appropriate credit and a link is given.
Copyright (C) 2008,2009,2010 All Rights Reserved Jeffrey Dach MD
(C) Copyright 2021, Jeffrey Dach MD, All Rights Reserved.
This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.
http://www.drdach.com http://www.TrueMedMD.com http://www.jeffreydach.com http://www.bioidenticalhormones101.com
FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.
