Background: Final height in patients with congenital adrenal hyperplasia (CAH) is generally assumed to be lower than the population norm. Besides CAH subtype and age at diagnosis, timing of pubertal development is considered to have a significant impact on final height. In most CAH patients, puberty starts within normal ranges, although at a somewhat earlier mean age compared to reference populations. CAH-complicating gonadotropin-dependent precocious puberty has been reported in few cases, especially in conditions of late CAH diagnosis and treatment initiation, and often requires additional treatment with GnRH-analogues.
Patients and Methods: We retrospectively assessed frequency, clinical parameters and height outcome of GnRH-analogue treated CAH-patients from the German CAH registry (DGKED-QS), comprising longitudinal data of a total of >1500 CAH-patients.
Results: Sixty-four CAH patients (28 female) received GnRH-analogue treatment. The majority of them (n=53, 82.8%) were born before nationwide introduction of 17-OHP newborn screening in Germany in 2000, and mean age at CAH-diagnosis among these patients decreased significantly over time (<1990: 5.31 years, 19901999: 4.38 years, >2000: 1.05 years). Compared to the frequency distribution in the total DGKED-QS/CAH-cohort with >66% salt wasting CAH, only 42.1% of the patients treated with GnRH-analogues were classified to have salt-wasting CAH. Mean age at first database entry of GnRH-analogue treatment was 8.81 years in girls and 9.24 years in boys. In addition, a significant proportion of treated children had no documented clinical signs of gonadarche (e.g. testicular volume <4 ml in about one quarter of boys) at the time of treatment initiation, indicating that the rationale for GnRH-analogue treatment was primarily based on auxological reasons in these individuals. Mean height-SDS at the beginning of GnRH-analogue treatment was +1.18 in girls and +0.62 in boys, while bone age was significantly accelerated in both genders (girls: +3.29 years, boys: +3.35 years). At the last documented visit before transition, height-SDS had decreased to −1.13 (−0.15, target height-corrected) in girls and −2.15 (−1.43, TH-corrected) in boys.
Conclusion: GnRH-analogue treatment in CAH patients is rare, especially in the newborn screening era. A significant decrease of GnRH-analogue use over the last three decades is paralleled by decreasing mean age at CAH diagnosis, supporting the concept that chronic hyperandrogenemia (or its cessation) can trigger central precocious puberty. The auxological data of our retrospective cohort analysis seems to indicate that GnRH-analogue treatment may have a beneficial effect on final height in this subgroup of CAH patients.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology