ESPE Abstracts (2022) 95 FC9.4


1Service of Pediatric Endocrinology and Diabetology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; 2Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada; 3Service of Endocrinology, Diabetes and Metabolism, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; 4Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland; 5Department of Pediatrics, Hôpitaux Neuchâtelois, Neuchâtel, Switzerland; 6Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland; 7Division of Biostatistics, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland; 8Pediatric Institute of Southern Switzerland, 6500 Bellinzona, Bellinzona, Switzerland; 9Faculty of Biomedical Sciences, University of Southern Switzerland, 6900 Lugano, Lugano, Switzerland

Introduction: Differentiation between constitutional delay of growth and puberty (CDGP) and congenital hypogonadotropic hypogonadism (CHH) during early adolescence is challenging, as patients exhibit a similar clinical picture and there are no definite clinical or biochemical markers that distinguish these 2 pathologies. A delay in diagnosis, especially for CHH, may have short and long-term health consequences. The aims of this study were: 1) To evaluate the utility of clinical and biochemical markers alone or in combination to discriminate between CDGP and CHH; 2) To chart trajectories of patients with delayed puberty (DP) up to final diagnosis; 3) To investigate the added value of machine learning and genetic score for the early diagnosis.

Methods: This prospective observational study included 41 male patients who sought medical attention between 14-16.5 yrs for DP. Patients were followed yearly up to final diagnosis and their clinical trajectories were charted. CDGP was defined by a testicular volume (TV) ≥12 ml, associated with testosterone (T) ≥10 nmol/l, and full virilization by age 18. Complete CHH was defined by a TV < 4 ml, and partial CHH by a TV ≥ 4ml by age 18 both in the setting of T <4mmol/l and low/normal LH and FSH values. Parametric and non-parametric tests, receiver operating characteristic (ROC) analyses, whole exome sequencing and machine learning models were employed to distinguish between CDGP, complete and partial CHH.

Results: Out of 41 DP patients, 27 had CDGP; 6 complete and 8 partial CHH. At presentation, Inhibin B<62 pg/ml, as well as the association of a history of cryptorchidism with either testicular volume <3ml or LH <0.8U/l exhibited a 100% sensitivity and specificity for complete CHH. However, none of the clinical and hormonal markers allowed to differentiate CDGP from partial CHH. Machine learning algorithms improved identification of partial CHH from CDGP with an accuracy of 77%. Further, adding a genetic score increased the prediction by 4%. Longitudinal analyses showed that CDGP differ from partial CHH by age 15.5- 16. Finally, 20% of patients with DP had a final diagnosis of partial CHH. and exhibited 3 distinct clinical trajectories.

Conclusions: Partial CHH is more common than previously thought among DP. Distinction between CDGP and partial CHH is difficult at early adolescence but feasible by age 15.5-16. Machine learning associated with genetic score improves diagnostic accuracy and may be a useful tool in the management of DP patients.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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