ESPE Abstracts

Background: Early identification of idiopathic hypogonadotropic hypogonadism (HHI) and constitutional pubertal delay is quite challenging for pediatricians. In males, serum inhibin B levels are detectable throughout life, with marked changes during puberty. We present the case of a young male with GHD in rhGH treatment without progression in Tanner pubertal stages during follow-up.

Case report: A fourteen-year-old male patient presented to our institution for "slow growth in height”, not fitting in target height. Physical examination demonstrated moderate short stature with a height of 153.1cm (< 3rd percentile, -2.5 standard deviation (SD)), tanner stage Ph2-G1-Ah-/- (testicular volume 3ml). We excluded the most frequent causes of short stature: thyroid hormones were normal and celiac disease was excluded. A diagnosis of complete GHD was confirmed. The growth hormone stimulation test showed low GH peak levels (0.2μg/L) and low-dose rhGH treatment was administered. After one year of rhGH treatment, his height reached 159.7cm (3rd percentile). The annual growth rate was approximately 8cm per year (97^th percentile). During follow-up we observeved no pubertal activation at examinations and no hormonal changes in the blood test. In the suspicion of hypogonadism we searched LH/FSH (0.1/1.2 UI/ml), Testosterone (13.7ng/dl), INI-B (83.80 pg/ml) and AMH (38 ng/ml) measurements. The literature does not agree on the INI-B cutoff to be used for HHI. Activation of the GnRH-FSH/LH-testosterone axis was not observed. GnRH-testing for FSH/LH was made with activation of the axis after pharmacological stimulation. The transdermal testosterone gel was started without progression in Tanner pubertal stages after three months (testicular volume 3ml). The genetic testing for hypogonadism was made. A missense variant c:2642>G,pGlu881Gly, in maternal heterozygous state of the WDR11 gene, and an intronic variant c.745+9G>T, in maternal heterozygous state of the FGFRI gene were found. At the current state of scientific knowledge, both of these variants had uncertain significance, so it was not possible to attribute Matteo's pubertal delay to a genetic condition. However, nine months later the patient showed signs of pubertal development (tanner stage Ph2-G2-Ah+/-, testicular volume 5ml), so testosterone therapy was stopped and only GH therapy was continued.

Discussion/Conclusion: In conclusion, an early differential diagnosis in children with HHI and constitutional delay of puberty is supported by a good understanding of the clinical features and hormonal tests. INI-B may become a first-line test in the coming years in the differential diagnosis of HHI. Expert research is necessary.