2414 Morris Avenue, Suite 110Union, NJ 07083

In New Jersey: 908-364-0272 Toll Free:1-866-CARES37

Fax: 908-686-2019Email: info@caresfoundation.orgWeb: www.caresfoundation.org

Volume 12 • Fall 2009

1

Management of children with CAH is a challenge with regard to growth outcome:

the children are at risk for early pubertal development with decreased pubertal

growth. When regular timing of puberty is achieved by glucocorticoid treatment,

there is the risk of too tight control, which might also result in short stature.

Traditional treatment consists of substitution of cortisol to reduce excessive

androgen production and its consequences. Undertreatment with glucocorticoids

leads to androgen excess with advancement of bone age, and reduced final height.

In overtreatment growth is suppressed by growth inhibiting effects of

glucocorticoids. Further side effects of overtreatment are obesity and osteoporosis.

Alternate approaches in the treatment of CAH have been investigated recently,

Article continued on page 9

Improving health...connecting people...saving lives

© CARES Foundation, Inc. Fall 2009

CARES has engaged the world’s leading clinicians in CAH aswell as individuals and families affected by this condition todevelop guidelines for the establishment of CAH ComprehensiveCare Centers (centers of excellence for CAH) throughout the US.The overarching goal of these centers is to improve care for thoseaffected by CAH throughout their life span. The centers will becomprised of multi-disciplinary teams of healthcare professionals.The teams will include pediatric and adult endocrinologists,urologists, surgeons, gynecologists, fertility experts, psychologists,primary care physicians, geneticists, nurses, nutritionists, and otherspecialists who will care for CAH patients from birth throughadulthood.

Background: As diagnosis and clinical care improves, there is a growingpopulation of adolescent and adult patients with CAH. However,at present there are no centers in the United States recognized asspecializing in the care of teens and adults with this disorder. Theresult is significant disparity in the quality and comprehensivenessof care that patients receive. CAH Comprehensive Care Centerswill ensure a continuum of care throughout the lifecycle of theCAH patient that will lead to better treatment practices andimprove health outcomes. The centers will also serve as aresource for research opportunities which one day may lead to acure. …Together we can make it a reality

An Evidence Based Recommendation forHydrocortisone Dosing during Puberty inClassical Adrenal Hyperplasia (CAH)

Walter Bonfig, MD

University Children´s Hospital, DivisionofPediatric Endocrinology & Diabetology,Ludwig Maximilians University, Lindwurmstr. 4, D-80337 Munich, Germany. e-mail: walter.bonfig@med.uni-muenchen.de

Imagine the possibilities…Have you ever had trouble locatingan endocrinologist well versed inCAH? Have you needed care fromother specialties, but the physiciansdo not communicate with eachother? We are working withexperts in the CAH healthcarearena to change that.

For more information on this initiative, click on: http://www.caresfoundation.org/productcart/pc/comprehensive_care_cah.html

CAH Comprehensive Care Centers

2 © CARES Foundation, Inc. Fall 2009

A Message from the Executive DirectorIN THIS ISSUE

CAH Comprehensive 1Care Centers

CAH Article 1,9-10An Evidence BasedRecommendation forHydrocortisone Dosing during Puberty in Classical Adrenal Hyperplasia (CAH)

Message from the Executive Director 2

Welcome Aboard 3Dr. Heather Applebaum

Kind Words 3

Founders, Board, Staff 3

No Sweat Run For A Cure 4

Family Fundraisers 4,5

CAH Studies 6,7

Personal Story 8

Advocacy 11,12

Dear Friends:

This is a very exciting, as well as,challenging time for our organization.Exciting because, we are workingon projects that will have asignificant impact on the lives ofthose living with CAH—namelyprepar ing to es tabl i sh CAHComprehensive Care Centers and

advocating for EMS protocols during an adrenal crisis.Our greatest challenge is doing this while funding, bothpublic and private, continues to decrease. Both of theseprojects will have a tremendous impact on CAHpatients, but we need your help to move forward. Yoursupport is critical to the success of our new endeavors,as well as to our ability to continue existing programssuch as research, physician referral, one on one support,and education.

Our last newsletter included two pages of fun and easyways that individuals can raise funds for CARES. If youmissed it, it’s on our website. Try using social networkssuch as Facebook and Twitter to raise awareness andfunds. The holidays provide a perfect opportunity toraise funds for CARES. Teachers get plenty of mugs,candy, ornaments and other knick knacks. Why notshow your appreciation with a CARES cookbook orwith a donation in honor of your child’s teacher thisyear? You will help raise funds and spirits. If everyCARES family raises $500, it will total one milliondollars. Imagine what we can do with that… Together,we can do it.

CARES Charity CookbookThe CARES Foundation Charity Cookbook is here! It’sfilled with many wonderful recipes sent in by CARESfamilies and friends. 100% of the profits raised by thisbook will fund CAH support, education, advocacy andresearch. Consider purchasing extra copies for friends,family and special occasions, such as: birthday,anniversary, wedding shower, hostess, Mother’s orFather’s Day, teachers, thank you, house-warming, or justbecause. The book can be purchased through ourwebsite (www.caresfoundation.org) for the low costof $20. Get yours today!

No-Sweat Run for a CureIt’s not too late to make a donation for the No-SweatRun for a Cure! You can still contribute through theCARES website. Proceeds from this year’s campaign aresignificantly lower than previous years and will impactthe services and programs that we can provide goingforward. Please help us get closer to our goal by makingyour donation today at www.caresfoundation.org!

CAH Comprehensive Care Centers (Centers of Excellence)If you are an adult who has experienced a lack ofquality care, you understand the significance ofhaving a place where you can access care that willencompass all your needs, provided by a leading CAHexpert. If you are the parent of a child with CAH,remember that as your child grows, his or her needswill also grow and when they reach adulthood, theywill require continued specialized care.

CARES is working with a group of top, internationalexperts in the care of CAH to create guidelines toestablish CAH Comprehensive Care Centers. InSeptember, these professionals gathered together at ameeting in Bethesda, MD to write these guidelines.We look forward to publishing and presenting theguidelines and to begin the process of opening thefirst Comprehensive Care Center.

We are very excited about a future that includes thebest and most comprehensive care for those affectedby CAH and hope that you will support us as wework hard to make this a reality.

CARES Education SeriesIt is with much regret that we announce thecancelation of the CARES Education Series (formerlythe CARES Family Conference). Canceling the Serieswas a difficult decision, but the lack of funding andthe high cost of financing it made it impossible forus to continue with our plans. We are looking at cost-effective ways to provide patient education and willnotify you of our efforts in the future.

Personal StoriesMany of our newsletters have included inspirationalpersonal stories about living with CAH. We wouldlove to be able to include a personal CAH story ineach and every newsletter, so I’m inviting you to tellyours. We are especially interested in stories aboutyour experience during an adrenal crisis. These willhelp CARES demonstrate the need for EMS protocolsfor adrenal insufficiency. If you’d like to share yourexperience with the rest of our membership, pleasesend your story, with a picture or two, to SuzanneLevy at suzanne@caresfoundation.org. We lookforward to reading your story!

Thank you for supporting our efforts as we meet theneeds of the CAH community.

Warm regards,

Dina© 2009 CARES Foundation,Inc. All rights reserved.Republication or redistributionof CARES newsletter content,including by framing or similarmeans, is prohibited withoutprior written consent ofCARES Foundation, Inc.

3

Welcome Aboard!

© CARES Foundation, Inc. Fall 2009

FOUNDERSKelly and Adam Leight

Staff & ConsultantsDina M. Matos, Executive DirectorDina@caresfoundation.org

Meryl I. Stone,Chief Operating OfficerMeryl@caresfoundation.org

Suzanne Levy, Program DirectorSuzanne@caresfoundation.org

Mazal Wolfskehl, BookkeeperMazal@caresfoundation.org

Odaly Roche, Administrative AssistantOdaly@caresfoundation.org

Camela Cruz, InternCamela@caresfoundation.org

Gretchen Alger Lin, Public AffairsGretchen@caresfoundation.org

BOARD OF TRUSTEESGregory Kraff, PresidentVictoria Shenderovich, Vice PresidentVivian Altman Quintanilla, TreasurerStephanie R. Fracassa, SecretaryDeborah Brown, R.N.Louise Fleming, R.N.Monica L. HeinzeTonya Judson, R.N.Kelly Rosso Leight, Esq., President EmeritusAlan MacyStephen MaebiusJodi MandellCatherine PetersonKarthik RadhakrishnanDiane Snyder, M.D.Daniel TaylorJessica Hall UpchurchMichael P. Wajnrajch, M.D.

SCIENTIFIC & MEDICALADVISORY BOARDHenry Anhalt, D.O.Heather Applebaum, M.D.Richard J. Auchus, M.D., Ph.D.Ricardo Azziz, M.D.Susan W. Baker, Ph.D.Sheri A. Berenbaum, Ph.D.Felix A. Conte, M.D.Alejandro Diaz, M.D.Walter Futterweit, M.D.Mitchell E. Geffner, M.D.Gary D. Hammer, M.D., Ph.D.Karen J. Loechner, M.D., Ph.D.Claude Migeon, M.D.Walter L. Miller, M.D.Maria I. New, M.D.Sharon E. Oberfield, M.D.Dix P. Poppas, M.D.Richard C. Rink, M.D.Scott A. Rivkees, M.D.Richard Ross, M.D.David E. Sandberg, Ph.DEllen Seely, M.D.Phyllis W. Speiser, M.D.Bradford L. Therrell, Ph.D.Maria Vogiatzi, M.D.Garry Warne, M.D.Selma Feldman Witchel, M.D.

This newsletter is published 4 times a year.

Please join us in welcoming Dr. Heather Applebaum to the CARESFoundation Scientific & Medical Advisory Board.

An obstetrician and gynecologist, Dr. HeatherApplebaum has a special interest in congenitalanomalies of the reproductive tract, pediatric pelvicreconstructive surgery, pediatric and adolescentgynecologic surgery, minimally invasive/laparoscopicsurgery, ovarian cysts, endometriosis, and polycysticovarian syndrome. A graduate of Emory UniversitySchool of Medicine in Atlanta, Georgia, she completedher post-doctorate training at the Mt. Sinai School ofMedicine in New York.

Dr. Applebaum currently holds academic appointments at the Albert Einstein Collegeof Medicine and Long Island Jewish Center/Schneider Children’s Hospital and seespatients at the Ann and Jules Gottlieb Women’s Comprehensive Health Center and LongIsland Jewish Medical Center/Schneider Children’s Hospital in New York.

KIND WORDSOn a happy note, Abby, our CAHdaughter, has been asked by People toPeople to travel to Australia for 20days next summer as a StudentAmbassador. I truly believe thatwithout the information receivedfrom CARES, Dr. Migeon, Dr. Merkeand Carol Van Ryzin and the supportfrom Kelly that I received after shewas diagnosed, that Abby would notbe able to take advantage of thisopportunity.

I want to tell you that I truly appreciate all that you have done for our family.When Abby was first diagnosed we were told that she would be lucky to reach5'2"—thanks to the medical care that we were able to contact through CARES,she is now just over 5"6", which I think is a dramatic example of how goodher care has been. Thank you.

Krista Breeding

Abby Breeding

4

FAMILY FUNDRAISERS

© CARES Foundation, Inc. Fall 2009

Family Fundraisers are a significant source of support for CARES.Many families have found creative ways to raise money. We are highlighting twoexamples of how families turned asking for donations into fun-filled events. Our profoundappreciation goes to all of the wonderful families who help us fulfill our mission.

YOUR NAME AND PHOTO HEREWe will happily publicizeyour fundraising event andits success in our upcomingnewslet ter. (With yourpermission of course.) Justemail info and photo to:suzanne@caresfoundation.org

Creative fundraisers are thekey to surviving in thischallenging economy. Pleasekeep us posted on yourresults!

The Harpers’ Family Fundraiser

CARES,We couldn’t be more pleased to tell you that ourFirst Annual Cook Out For A Cause raised$1800! We decided to do something differentthis year with our annual donation to yourfoundation. Instead of simply mailing you acheck, we used that money and put it towardsmaking an elaborate, mostly homegrown andmade dinner for our friends. Using vegetablesand fruit from our garden, plus fresh caughtHalibut, Salmon and Elk, we made appetizers,dinner and dessert for our 50+ guests. Drinks andentertainment were provided as well including arubber duck race down the creek. People paid $1per duck; winner took half and CARES receivedhalf. In lieu of making contributions to the meal,we asked people to make donations to you. Our$250 was turned into $1800 in one night–greatreturn! We hope this contribution helps yourorganization, individuals with CAH and theirfamilies.Thanks for all you do for us,Dawn, Mark, Luke & Wyatt Harper

2009a virtual event for a real cause

ResultsThanks to the wonderful work of our community, more than $45,000 has been raised to date through the 2009 No-Sweat Run for a Cure!Congratulations to all of our teams!

HIGHEST FUNDRAISERSKimura/Ohana Team raised $6,790Team Racin' Jason raised $3,265

GREATEST NUMBER OF DONORSElizabeth Shaker & Nick Araujo—36 donors raised $4,145 New team!Ray & Emily Harmer—27 donors raised $2,207

Two CARES Foundation board members deserve special recognition forleading outstanding teams and making tremendous contributions:Rhonda & Gregory Kraff raised $4,772 Jessica & Matthew Upchurch—raised $4,452

Thank you for taking time out of your busy lives to make a difference!

FUNDRAISING

© CARES Foundation, Inc. Falll 2009 5

Kraff FamilyChili Cook-Off Friends, family and neighbors gatheredon September 26th for the 1st AnnualKraff Family Chili Cook-Off in supportof the Cares’2009 No-Sweat Run for aCure. Gregory, Rhonda & Ally Kraffhosted sixty-five guests with promisesof savoring some yummy south-westeats. Fourteen Chilis were submitted tothe gaggle of eager tasters, with nameslike “Cha Cha Chili,” “Mini-Mall Chili” &“CARESili Chili for Cares”.

Bragging rights were at stake for the 14chili chefs in the categories of People’sChoice, Most Original and Most Likelyto Make You Sweat! One would thinkwith a name like “Pit Viper”, this chiliwould pack a punch comparable to aviper’s bite. Luckily for Chef JosephTaffurelli, his Pit Viper Chili had just theright amount of spice to win over thevoters and snag the People’s Choiceaward.

Da’ Best Chili (Seafood Version) wasawarded Most Original, an honor forthe 13 year old cook, Timothy Feyrer.

Da’ Best Chili was filled with the flavorsof the sea, including delicious scallopswhich won over the hostess of thenight, Rhonda Kraff.

“CARESili Chili for Cares,” a white chilimade from a very secret recipe, wasvoted Most Likely to Make You Sweat,which was a fitting win for the hot-headed Kevin Kraff! The sweetest chiliof all was submitted by Ally Kraff & hercousin Maggie Feyrer. This delectableChocolate Chili was the perfect desertto cap off a spicy competition.

In addition to having a family-fun-filledfiesta, the Kraff Family Chili Cook-Offraised over $2000.00 for CARESFoundation! Now that is a healthyportion we can all appreciate!

People’s Choice Winner—Joseph Tafurelli(pictured with his winning apron and Allyson); theyalso received CARES Cookbooks.

IN THE SPIRITOF THE HOLIDAY SEASON…

A delicious holiday giftthat is sure to delightfamily, friends, andcolleagues is CulinaryCreations…from OurFamily to Yours, a oneof-a-kind CARES Foundation Charity Cookbookfilled with favorite recipes from CARES families and friends aroundthe world. 100% of the proceeds from each book will go to supportCARES and its efforts to serve those touched by CAH. Price: $20.00

To order online: www.caresfoundation.org Click on CARES Shop

A contribution to CARES—in honor of family, friends, associates andthose to whom you’d like to show your appreciation—is a wonderfulgift that will resonate throughout the year! We will be delighted tosend a personal card to the folks you wish to honor, telling them ofyour gift. For Tribute Donation info, please visit:

https://www.caresfoundation.org/productcart/pc/tribute.asp

Bon appétit !

6

CAH STUDIES

© CARES Foundation, Inc. Fall 2009

CAH and OsteoporosisScreening Study UNCChapel Hill, North Carolina

WHO: Children with CAH who are 8-12years old (bone age 14 years) and arestill growing. Siblings (6-14 years old,bone age 14 years old) of those childrenwith CAH who otherwise meet thesame eligibility criteria except that theydo not have CAH and are not onglucocorticoids.

WHY: Although cortisol replacement isessential to treat children with CAH,there is the potential risk of over-treatment with glucocorticoids that canresult in abnormal weight gain,decreased linear growth and, morerecently reported in adults, the risk ofosteoporosis. We are now testing if thereexists a risk for osteoporosis in childrenwith CAH and if this risk is related to thedosing of glucocorticoid used, as wouldbe expected with any medical conditionin which steroids are required for long-term treatment. We are also examining ifthe subtype of CAH contributes to therisk for osteoporosis.

WHERE: Children will be enrolled inthe study at the General ClinicalResearch Center at the University ofNorth Carolina, Chapel Hill.

WHAT: Your child would have: 1. Bone Age X-ray

2. DXA scans (to screen for osteoporosisand for subtle spine fractures)

3. Special X-ray of his/her arm to look at the effects of glucocorticoid dosing (Cortef, for example) on bone structure itself

4. Blood and urine tests to determine the degree of his/her “control” of CAH

5. Blood test for genotyping for all children in the study. In this way, “control” siblings can find out if theyare “unaffected” or “carriers”

WHEN: This would all occur in a one-time visit (3 hours) for your child withCAH and/or sibling.

HOW MUCH:: The clinical visit,including laboratory testing, radiologicevaluation and physical exam will bepaid for by this protocol. Overnightaccommodations can be arranged, arental car to/from the airport andparking at UNC will be covered. Travelassistance is possible (please inquire fordetails). There is a $50 compensationprovided for incidental costs for eachchild enrolled.

For more information, please contact:Karen J. Loechner, M.D./Ph.D. Director, UNC Pediatric OsteoporosisClinic,Assistant Professor, Pediatric Endocrine Unit 919.216.5946 • 919.966.2423 (fax) karen_loechner@med.unc.edu (email)

NCAH Study at Children'sHospital of Los AngelesThe Division of Endocrinology atChildren's Hospital Los Angeles iscurrently recruiting subjects for aresearch study aimed at determiningthe stress-fighting ability in subjectswith Non-classical Congenital AdrenalHyperplasia (NCAH) and comparingthese responses to those in subjectswith Classical Congenital AdrenalHyperplasia (CAH) and those incarriers of either disorder. If you haveNCAH, CAH or are a family member(parent or sibling) of someone witheither disease, and are interested inparticipating in this study, pleasecontact:Bhavna Bali, MD at 323.361.8705 bbali@chla.usc.eduorMitchell Geffner, MD at 323.361.7032mgeffner@chla.usc.edu

Identifying the UnmetNeeds of Individuals withCAHWHO: Women (18 & older) with CAH.

WHY: Due to the sensitive nature ofthe issues associated with CAH, it islikely that individuals with CAH willhave needs that are not met in themanagement and treatment of thedisorder. If so, genetic counselors maybe in a position to fulfill some of theneeds of these individuals. The purposeof this study is to identify the unmetneeds of women with CAH, and toinvestigate how genetic counselors mayexpand their role in the management ofthis disorder to better meet women’sneeds. The results of this study couldalso have implications for the role ofother health care providers in themanagement of this disorder.

WHERE: Participants will be enrolledthrough e-mail or telephone contact. Toset up an interview or request moreinformation, please contact me or myfaculty sponsor. Contact information isprovided below.

WHAT: The study will consist of onetelephone interview.

WHEN: The interview will lastapproximately 30-45 minutes.

HOW MUCH: There will be no costsinvolved with participation. There willbe no compensation for participating inthis study. If interested, please contact:Kristin Zelley, principal investigatorkzelley@arcadia.eduKathleen Valverde, faculty sponsorvalverdk@arcadia.edu 215-572-4058)

Please pass this information on to anywomen you know with CAH who’d beinterested in participating in this study.Thank you.

7© CARES Foundation, Inc. Fall 2009

See the chart below to find out if your

Newborn Screening card is available

STATE NBS CARD STORAGE TIME

Alabama 3 monthsAlaska 3 yearsArkansas 2 yearsArizona 3 monthsCalifornia IndefinitelyColorado 3 monthsConnecticut 6 monthsDelaware 4 monthsDistrict of Columbia 2 years min.Florida IndefinitelyGeorgia 6 wks-10 yrsHawaii 1 yearIdaho Not GivenIllinois 2–4 monthsIowa 1 monthIndiana 23 yearsKansas 1 monthKentucky 6 monthsLouisiana 2–4 weeksMaine 5 yearsMaryland 6 monthsMassachusetts 1991-presentMichigan 21.5 yearsMinnesota 7 yearsMissouri 6 monthsMississippi 2 year minimumMontana 2-6 monthsNebraska 3 monthsNevada 1 yearNew Hampshire IndefinitelyNew Jersey 23 yearsNew Mexico 3 monthsNew York 27 yearsNorth Carolina IndefinitelyNorth Dakota 10 yearsOhio 21 yearsOklahoma 1 monthOregon 1 yearPennsylvania 3 monthsRhode Island 23 yearsSouth Carolina Parent’s choiceSouth Dakota 2 monthsTennessee 3 monthsTexas 6 monthsUtah 3 monthsVermont IndefinitelyVirgin Islands 1 yearVirginia 6 monthsWashington 21 yearsWest Virginia 3 monthsWisconsin 1 yearWyoming Not Given

Blood Spot Sample StudyWhile significant advancements to improve newborn screening for CAHhave been made in recent years, there remains considerable room forimprovement. Currently, CAH has been fully implemented into newbornscreening programs across all 50 states. Newborn screening has been mosteffective in detecting the cases of CAH caused by 21-hydroxylase deficiency,but current methods have not proven as reliable in detecting less commonforms, including 11-ß-hydroxylase deficiency.

Based on previous work, Dr. Dietrich Matern and colleagues in theBiochemical Genetics Laboratory at Mayo Clinic are working to furtherimprove current screening strategies by determining the analyte ranges thatcorrespond to CAH caused by other enzyme deficiencies, in addition to 21-hydroxylase. In order to accomplish this, the Biochemical GeneticsLaboratory aims to collect and analyze leftover newborn screening samplesof patients diagnosed with any form of CAH. The results from this study areexpected to enhance newborn screening for CAH two-fold: a) by allowingfor the identification of individuals with less common forms of CAH; and b)by reducing the number of false positive results through steroid profileanalysis. Early detection and diagnosis allows for treatment of affectedinfants prior to the onset of symptoms.

Call for Samples—Participate in Ongoing Research at Mayo ClinicMembers of CARES Foundation may be able to help in this effort by allowingMayo Clinic to analyze any leftover newborn screening samples that maystill be available in the newborn screening lab of the state where a CAHpatient (less than 8 years old) was born (see chart to determine if your bloodspot sample may still be available or call the respective screening laboratoryto determine if a sample may still be available). Analysis of such precioussamples would allow Mayo Clinic’s Biochemical Genetics Laboratory toaccelerate the completion of this study and achieve more quickly theultimate goal of improving newborn screening for CAH.

http://genes-r-us.uthscsa.edu/resources/consumer/statemap.htm

If you would like to participate and a newborn screening sample may stillbe available, please contact a biochemical genetic counselor by e-mail atbiochemicalgenetics@mayo.edu or phone at 507-266-8158 for assistance inrequesting this sample from the respective newborn screening laboratory.If you have any questions or concerns, Dr. Matern or a member of hisresearch team would be happy to discuss the study with you in more detail.Please call with any inquiries or to assist with initiating participation in thestudy. Thank you in advance for considering this request. We greatlyappreciate your time and cooperation.

Elyse Grycki, M.S.Genetic Counselor+6Biochemical Genetics LaboratoryPhone: (507) 266-8158Fax: (507) 266-2888E-mail: grycki.elyse@mayo.edu

Dietrich Matern, M.D., FACMGAssociate Professor of Laboratory MedicineBiochemical Genetics LaboratoryPhone: (507) 778-1581Fax: (507) 266-2888E-mail: matern@mayo.edu

© CARES Foundation, Inc. Fall 20098

As the parent of a child with SWCAH, you know the daywill come when you have to give your child his firstinjection. What you don’t know is where you will be, willyou be able to calm down to do it and will you have some-one there to help you. Here is how it happened for me.

I was a trainer at a workshop in Denver whenmy son, Clay, became ill with the stomach flu.And as we know, the stomach flu for a childwith SWCAH can be serious—this time itwas, as we ended up in the ER in an adrenalcrisis. I got the call that he had thrown-up soI immediately left the workshop and headedto the hotel room. We followed the oral stressdose protocol but he continued to vomit—and that is when it hit and it took all oftwenty minutes but it felt like a second. He was limp, eyesrolling into the back of his head, pale and cold—and I wasscared to death!

I called 911 as my fear was coming alive in front of me, myson was in dire need and I had to act fast. The paramedicsand hotel staff arrived in minutes—so quickly in fact, I hadjust pulled his injection and solu-cortef from the medicalbag I carry with us. Oh help me, give me the strength toslow this down because I knew I had to give him a shot—and this was the first time.

Adrenal Crisis and EMS:One Family’s StoryJessica Hall-Upchurch

At that point they put an oxygen mask on my angel, hewas only three years old at the time, and started askinglots of questions. Of course, they told me they could notgive him his injection. Imagine, here we were with trainedpersonnel surrounding us and they couldn’t “legally” give

my son a shot that would save his life.Reason being “the attending doctor at thehospital to which we were beingtransported didn’t prescribe it.” It was upto me!

Literally, I had to tell them to “stop” as theywere trying to load he and I onto thegurney and I still hadn’t given him his shot.I got them to stop, and with a kindparamedic next to me, he coached me

through it. The injection was completed and within 10minutes, my little angel was blinking his big brown eyes,color was back in his skin and I was in tears of relief andgratitude. If it wasn’t for CARES, I wouldn’t have been asprepared and informed when it came to saving my ownchild’s life. And that is what I did that day, I saved his life.

Thank you CARES for providing me with the knowledgeand skills to save my son. I am forever grateful for theguidance and support you provide our family!

PERSONAL STORY

© CARES Foundation, Inc. Fall 2009

Hydrocortisone Dosing during Pubertycontinued from page 1

9

including the use of antiandrogens and aromatase inhibitors.Adequacy of treatment is best evaluated by monitoring growthrate and skeletal maturation. In addition, urinary and serumanalysis of steroid hormones and determination of 17-hydroxy-progesterone in saliva are used for evaluation of therapy.

Reports on long-term follow-up and final height outcome inpatients with CAH are heterogeneous. Previously we foundthat total pubertal growth is significantly reduced in patientswith CAH, who have received traditional steroid treatmentwith hydrocortisone or prednisone (Bonfig et al, J ClinEndocrinol Metab 2007;92(5):1635-9). In the present study wetried to determine an evidence based hydro- cortisone doserecommendation during puberty by evaluating data from 92patients with CAH—all followed inour clinic—who have reached finalheight and who have been treatedwith hydro-cortisone exclusivelysince diagnosis of CAH until finalheight.

Patients and MethodsThe effects of glucocorticoidtreatment for classical CAH wereretrospectively analyzed in 92 patients(57 females, 35 males) with 21-hydroxylase deficiency. Growthpattern, final height and mean dailyhydrocortisone dose were recorded.All patients were exclusively treatedwith hydrocortisone. The patientswere born between 1969 and 1987. The diagnosis of CAH wasbased on both clinical symptoms and signs, and on hormonalanalysis and genotyping later on. At the time of diagnosisnewborn-screening for CAH was not yet available. 54 patientshad salt-wasting CAH (32 females, 22 males), and 38 patientshad the simple virilizing form (25 females, 13 males). Patientswith nonclassical forms of CAH were not included in thisstudy. All patients were continuously cared for in our clinic,with follow-up appointments every three months during thefirst two years of life, and every six months in childhood andadolescence. All 92 patients had received hydrocortisone(three times daily) for glucocorticoid substituition and patientswith salt-wasting CAH received fludrocortisone in addition.None of the patients had received GnRH analog treatment todelay onset of puberty. Since patients were followed at a singlecenter, we present data on a homogeneously treated group ofpatients with CAH.

A logistic regression model and a receiver operating curveanalysis (ROC-analysis) were assessed to estimate ahydrocortisone dose recommendation during puberty. ROCanalysis and logistic regression were performed with thestatistical computing package “R”, version 2.7.1, R,Development Core Team (2008), R: A language andenvironment for statistical computing, R Foundation forStatistical Computing, Vienna, Austria. (ISBN 3-900051-07-0,URL http://www.R-project.org). The ROC-curve wassmoothed using the LOWESS (“locally weighted leastsquares”) method.

ResultsPatients with salt-wasting CAH (n=54, 32f, 22m) were

diagnosed early at a mean age of 0.2 years[range 0-2.7 yr, median 0 yr], whereaspatients with the simple virilizing form(n=38, 25f, 13m) were diagnosed at a meanage of 2.2 years [range 0-6 yr, median 2 yr].None of the patients had suffered fromadrenal crisis once salt-wasting CAH wasdiagnosed.

Pubertal growth was significantly reducedin all patients: salt-wasting females 13.8±7.4cm, simple virilizing females 13.1±6.2 cmvs. reference population 20.3±6.8 cm,p<0.05, and salt-wasting males 17.7±6.7cm, simple virilizing males 16.2±5.7 cm vs.reference population 28.2±8.2 cm, p<0.05.Decreased pubertal growth resulted in final

height (FH) at the lower limit of genetic potential(corrected FH in salt-wasting females -0.6±0.9 heightstandard deviation score, simple virilizing females -0.3±0.9height standard deviation score, salt-wasting males -0.8±0.8height standard deviation score and simple virilizing males-1.0±1.0 height standard deviation score). Overall correctedFH in our patients with 21-hydroxylase deficiency waswithin one standard deviation of target height.

During puberty mean daily hydrocortisone dose was17.2±3.4 mg/m² body surface area in females (salt-wastingfemales 17.0±3.3, simple virilizing females 17.4 ±3.5) and17.9±2.5 mg/m² body surface area in males (salt-wastingmales 17.4±2.0, simple virilising males 18.7±3.1). In alogistic regression model a significant correlation betweenthe mean daily hydrocortisone dose and FH was found(p<0.01, Figure 1) and in a Receiver Operating Curve (ROC)analysis the positive predictive value for short stature rosefrom <30% to >60%, when a hydrocortisone dose >17mg/m² body surface area was administered (Figure 2).

continued on page 10

In conclusion, maintenance of normal

growth velocity is a very important variable in the assessment of control

of CAH, especially during the first six months of life

and during puberty, when growth velocity

is fastest.

influence of sex hormones on growth is suppressed, resulting ina less profound growth spurt. The pubertal growth was notpoor due to prepubertal undertreatment with an advancedbone age at the onset of puberty (except for males with simplevirilizing CAH), since bone age was within one year ofchronological age in more than two thirds of the patients at thattime. Acceleration of bone age in males with simple virilizingCAH used to be caused by delayed diagnosis, but is no longer aproblem since newborn screening is available by now.

In conclusion, maintenance of normal growth velocity is a veryimportant variable in the assessment of control of CAH,especially during the first six months of life and during puberty,when growth velocity is fastest.

In summary, final height in CAH patients receiving traditionaltherapy is within the lower range of genetic potential. Totalpubertal growth is significantly decreased in this cohort.Accuracy of treatment should not be monitored only bybiochemical assessment, but also by careful follow-up of growthvelocity especially during puberty. Thus glucocorticoid dosesshould be adjusted (below 17 mg hydrocortisone per m² bodysurface area) in this rapid phase of growth.

Figure 1. Logistic regression model. Each circle represents onepatient and patients with normal stature are plotted at 0.0, patientswith short stature are plotted at 1.0. The line represents the fittedlogistic model and represents the predicted fraction of short patientsat the mean daily hydrocortisone dose during puberty.

Figure 2: ROC Analysis. The positive predictive value for short staturerises from below 30% to 40-60%, when the mean daily hydrocortisonedose exceeds 17 mg/m² body surface area. The grey line is a LOWESSsmoother curve.

© CARES Foundation, Inc. Fall 200910

Hydrocortisone Dosing during Pubertycontinued from page 9

Body mass index (BMI) was found to be above average inCAH patients irrespective of the sex. At onset of pubertymales had a mean BMI standard deviation score of 1.2±0.9,which decreased to 0.9±0.9 when FH was reached. Maleswith simple virilizing CAH had significantly higher BMIstandard deviation score than males with salt-wasting CAH(p<0.05). In females there was no change of mean BMIstandard deviation score with 0.6±1.2 at start of pubertyand 0.6±1.3 at FH. There was no significant differencebetween females with simple virilizing or salt-wasting CAH.

DiscussionWe conclude from our results that an optimalhydrocortisone dose during puberty should not exceed 17mg/m² body surface area. To our knowledge this is the firststudy to prove the correlation between pubertalglucocorticoid dose and FH and also to suggest a cut-off forthe maximum hydrocortisone dose during puberty inpatients with CAH. Of course this is just a generalrecommendation and individual patients may have differentsensitivity to glucocorticoids, which has to be considered.In previous studies the growth suppressant effects ofglucocorticoid overtreatment during the first two years oflife have been demonstrated (Manoli et al, 2002 ClinEndocrinol;57:669-676, Stikkelbroeck et al, 2003 J ClinEndocrinol Metab;88:3525-3530, Kirkland et al, 1978 J ClinEndocrinol Metab;47:1320-1324). In contrast in aretrospective study with 54 patients no associationbetween glucocorticoid dose and adult height was found(Muirhead et al, 2002 J Pediatr;141:247-252).

According to the consensus statement on 21-hydroxylasedeficiency from the Lawson Wilkins Pediatric EndocrineSociety and The European Society for PediatricEndocrinology typical hydrocortisone doses during infancyrange between 10-15 mg/m² body surface area, but higherdoses up to 25 mg/m² body surface area may be necessaryinitially. No specific hydrocortisone dose recommendationsare mentioned for the pubertal age (Joint LWPES/ESPE CAHWorking Group 2002 J Clin Endocrinol Metab;87(9): 4048-4053). Especially in boys during puberty the androgensecretion from the adrenals is relatively low compared tothat of the testes and therefore it is less critical to suppressadrenal androgens in boys than in girls during puberty.

With regard to growth potential puberty is an extremelycritical period in the treatment of CAH. Total pubertalgrowth was significantly decreased in both forms ofclassical CAH, irrespective of the sex. An explanation forthe decreased pubertal growth spurt could be a too tightcontrol of the disease at the onset of puberty, so that the

11© CARES Foundation, Inc. Fall 2009

EMSC: A Piece of the

EMR PuzzleIn both of our last two newsletters, we have

written about Emergency Medical Services forChildren (EMSC) and its pivotal role in CARES

Foundation’s campaign for immediate,appropriate emergency medical treatment of

adrenal insufficiency. In the Spring ’09 newsletterwe wrote of CARES and our EMS initiative beingintroduced to the EMSC community across the nationthrough a story in FAN Mail. Then in our Summer ’09issue, we reported that two CARES family members hadthe unique opportunity to represent CARES and theadrenal insufficient community at the EMSC nationalconference this past June in Washington DC.

What is EMSC?As noted on the EMSC website (www.childrensnational.org/emsc), EMSC is a federally fundedprogram “designed to ensure that all children andadolescents, no matter where they live, attendschool, or travel, receive appropriate care in ahealth emergency.” The Program is administeredby the U.S. Department of Health and HumanServices, Health Resources and ServicesAdministration (HRSA), Maternal and Child HealthBureau (MCHB). The Program provides grantfunding to EMSC programs in all 50 states, theDistrict of Columbia, and five U.S. territories.

In 1991, the EMSC Program established the EMSC NationalResource Center (NRC) which is housed within theChildren’s National Medical Center in Washington, DC.Among the many responsibilities of the NRC is overseeingthe EMSC Family Advisory Network (FAN).

Created by the NRC in 1999, FAN is committed toensuring the inclusion of family voices in every stateEMSC Program. EMSC State Family Representatives serve

on EMSC advisory committees, assist with special

community outreach programs and work ondeveloping and implementing EMSC policy objectivesand educational opportunities within their state. TheNRC also distributes FAN Mail, a semi-annual newsletterdistributed to the EMSC community.

What is the importance of EMSCand FAN to CARES’ EMS initiative?EMSC is vital to introducing CARES’ campaign foremergency medical treatment of adrenal insufficiencyto EMS leaders across the nation. It was through theNRC’s introduction that CARES was featured in theWinter ’09 issue of FAN Mail and CARES familyrepresentatives were invited to the EMSC nationalconference. EMSC’s involvement in our campaign nowcontinues at the state level where EMSC programmanagers and family representatives are playing pivotalroles in having our request placed before state EMSmedical advisory boards. A complete list of state EMSCprogram managers and family representatives can be

found at:http://www.childrensnational.org/files/PDF/EMSC/GrantPrograms/State_Grantee_List.pdf

Emergency Medical Response for CAH—UpdateThe New York State Emergency Medical AdvisoryCommittee (SEMAC) met on September 2, 2009. Thecommittee considered a motion brought forward bythe State Emergency Medical Services Council(SEMSCO) to add Solu-Cortef® to the state formularybased on the strong recommendation of the EmergencyMedical Services for Children (EMSC) AdvisoryCommittee. Despite unanimous agreement bycommittee members present to add Solu-Cortef® to theformulary, no formal vote could be taken due to lack ofa quorum. These recommendations will go before thecommittee again in December 2009. If therecommendations are adopted at this time, they willthen go out to the various regions of New York in theform of an advisory. Each region will then have to formallyadopt the new protocols. To make EMR for CAH andother adrenal insufficiencies a reality in New York, our

continued on page 12

Advocacy

Disclaimer: Any communication from CARES Foundation, Inc. is intended for informational and educational purposes only and in no way should be taken to be theprovision or practice of medical, nursing or professional healthcare advice or services. The information should not be considered complete or exhaustive and shouldnot be used in place of the visit, call, consultation or advice of your physician or other healthcare provider. You should not use the information in this or any CARESFoundation, Inc. communication to diagnose or treat CAH or any other disorder without first consulting with your physician or healthcare provider. The articlespresented in this newsletter are for informational purposes only and do not necessarily reflect the views of CARES Foundation, Inc.

2009 CARES Foundation, Inc. All rights reserved. Republication or redistribution of CARES newsletter content, including by framing or similar means, is prohibitedwithout prior written consent of CARES Foundation.

© CARES Foundation, Inc. Fall 200912

Please rememberthat CARES Foundation has “Gone Green”and that our newsletters are now onlyavailable electronically. Please make surewe have your most current e-mail addressand contact information to ensure thatyou receive newsletters and otherimportant information from CARES.

Send your updated information toOdaly Roche at

Odaly@caresfoundation.org.

EMR continued from page 11

efforts will switch from a state-wide to region-by-region campaign at that time. If you live in New Yorkand would be interested in representing your region inthis campaign, please contact CARES Support GroupLeader Deborah Brown at ny3.support@caresfoundation.org.

In Maryland, Support Group Leader Debbie Ham metwith the State Protocol Development Committee inAugust. A medical director was assigned as a sponsorto our request for the addition of Solu-Cortef® to theformulary and associated protocols for emergencytreatment of adrenal insufficiency. CARES Foundationis working on the protocol request submissionapplication with the assigned medical director.

Families and healthcare professional memberscontinue work on EMS campaigns in the states ofArkansas, Colorado, Massachusetts, Michigan,Nebraska, Nevada, North Carolina, Tennessee andVirginia. To learn more about CARES EMS Campaign

visit: http://www.caresfoundation.org/productcart/pc/ems_cah.html

If you are interested in adding your voice to that ofCARES Foundation and our family and healthcareprofessional members in any of these arenas or wishto learn more about organizing an initiative in yourown state, please contact Gretchen Alger Lin atgretchen@caresfoundation.org.

2009 CARES FoundationEducation SeriesCARES is feeling the effects of the pooreconomy as both private donations andcorporate grants have decreased significantly. As aresult, we were forced to cancel the 2009Education Series (formerly CAH FamilyConference) which was to take place onNovember 1, 2009. In lieu of the EducationSeries, we plan to offer some regional events inthe coming year and will notify you of those inyour area.

Despite our financial challenges, we continueto work hard to improve the lives of thoseliving with CAH. Currently, we are engaged intwo critical initiatives—the establishment ofcomprehensive care centers for CAH (multi-disciplinary clinics) and EMS protocols foradrenal insufficiency.

Please note that our phone and fax numbers have changed.

Our new phone number is(908) 364-0272

and our new fax number is (908) 686-2019

Our toll-free number is still 1-866-227-3737

CANCELLATION

NOTICE

Advocacy