Prepubertal growth & treatment (Rx) management of children with Congenital Adrenal Hyperplasia (CAH) caused by 21-Hydroxylase gene defects: new insights from the Lyon retrospective observational reference centre series assessment

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 29-49-Congenital Adrenal Hyperplasia & Ectopic Cushing's
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-30
Juan Pablo Llano*1, Michel David2, Yves Morel3, Patricia Bretones4, Veronique Tardy2, Calire-Lise Gay4, Ingrid Plotton5, Pierre Mouriquand2, Daniela Gorduza6, Marc P Nicolino7 and Pierre Chatelain8
1ICDH, Bogota, Colombia, 2Universite Claude Bernard Lyon 1 - Lyon France, 3Hôpital Mère-Enfant INSERM 329 - Lyon France, 4Hopital Mere-Enfant - Lyon France, 5Universite Claude Bernard Lyon1 - Lyon France, 6Hopital Mere-Enfant de Lyon, 7Universite Claude Bernard Lyon 1 - Lyon France, France, 8Univ Claude Bernard Lyon 1 - Lyon France, Saint Genis Laval, France
Birth screening & early Rx have reduced death rate in CAH. Altered bone maturation (BA) height & weight gain, difficulty in Hydrocortisone (HC) Rx balance are often encountered leading to short adult height & obesity.

Aims:To describe growth, BA and identify biological markers levels to adjust treatment from a series of prepubertal CAH children followed in Lyon.

 

Methods: Children were screened-diagnosed at birth (5 prenatally) & started with a standardized Rx protocol at a mean 8 days postnatally: HC split in 3 , Fludrocortisone (FC) and NaCl in 2 oral daily sub-doses. Auxology, BA, before Rx fasting 08:00 a.m. plasma 17-Hydroxyprogesterone (17-OHP nmol/l) Testosterone (T nmol/l) & Renin (R ng/L), plus 12:00 and 04:00-07:00 p.m. 17-OHP (“17-OHP cycle”) were assessed every six month (mo). HC dose was adjusted at weekly dedicated staff based on body surface (> 10 & < 15 mg/m²/d), growth (delta height SDS < or = 0), BA progression (< or = 1y/y), T (<1) & 17-OHP cycle values (<50). FC was adapted on R.  Analysis aimed at a/analysing growth b/determining for fasting T and each 17-OHP cycle sampling time the trigger level of “proper control” c / identifying if one cycle sampling time is more informative to ease future follow up.

 

Results:69 CAH children (33 boys; 36 girls) were followed from 0 to 8 year (1975-2010). No death occurred. Genotype (n): SW (50) & SV (19).

Growth data identified 4 phases & HC likely overdosing during the first 36 mo. At 6, 36 , 60 & 96 mo Mean Ht SDS [corrected for MPHt] (n), were -0.25 ± 1.3 (376), -0.54 ± 1.2, -0.23 ± 1.1 & + 0.26 ± 1.1  (277) respectively and mean BA/CA were 0.85 ±0.4,   0.89±0.3,  1.06±0.3 & 1.16±0.2  respectively. At a mean daily HC dose equal to 14 mg/m² above 60 mo excessive both height gain & bone aging (HC underdosing ?) are observed.

Positive correlation was found between T and 8 am or noon  or 4-7 pm 17-OHP (r²=0.35, 0.27 & 0.16 ) and between 8 am, noon and 4-7 pm 17-OHP ( r²=0.47, 0.36 & 0.38).

Means auxological and hormonal level based on their distribution (all data from 6 to 96 mo) below vs above the 75th percentile of their distribution were respectively: Mean HTSDS -0.39 ± 1.1 vs +0.14 ± 1.1 **,  BA/CA  1.03 ± 0.2  vs  1.12 ±0.2**, T 0.13 ± 0.1 vs 0.76± 0.4**, 17 OHP [08 am= 18 ± 86 vs  155 ±21**, noon =6 ± 38 vs 39 ±101** & 4-7 pm=  3 ± 39 vs 29 ±10**] (*p<0.005 **p<0.001).
17-OHP levels distribution on samples drawn at a/ 8 am or b/ noon  or c/ 4-7 pm  (all data from 6 to 96 mo) was subdivided either below  or above the 75th percentile . Mean 8am fasting T observed in these 17-OHP subgroups were respectively : a/ 0.14± 0.1 vs 0.78± 0.4**,  b/ 0.14± 0.3 vs 0.53± 0.5**   c/ 0.15± 0.2  vs 0.56± 0.5**  (**p<0.0001)…  pointing that T > 0.53 nmol/L (although normal prepubertal <1) seems too high.  

Conclusion: In children with CAH morning 17-OHP correlated with that of noon or evening but best correlated with morning fasting T. These data help identifying improved algorithm & new T and 17-OHP cut off value for HC Rx adjustment.

Nothing to Disclose: JPL, MD, YM, PB, VT, CLG, IP, PM, DG, MPN, PC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm