ESPE Abstracts (2021) 94 P1-146

1Developmental Endocrinology Research Group, University of Glasgow, Royal Hospital for Children, Glasgow, United Kingdom; 2West of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow, United Kingdom; 3Biochemistry Department, Queen Elizabeth University Hospital, Glasgow, United Kingdom; 4Department of Endocrinology, Queen Elizabeth University Hospital, Glasgow, United Kingdom; 5Department of Endocrinology, Gartnavel General Hospital, Glasgow, United Kingdom; 6Department of Endocrinology, Royal Alexandra Hospital, Paisley, United Kingdom; 7Assisted Conception Service, Glasgow Royal Infirmary, Glasgow, United Kingdom; 8Academic Medical Genetics and Pathology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom

Introduction: Hypogonadotropic hypogonadism (HH) is a rare condition, where a definitive diagnosis is often hard to reach.

Objectives: To describe the clinical, biochemical and genetic findings in cases with suspected HH in the West of Scotland who were referred for genetic analysis between 2016 and 2020.

Methods: Information was collected on clinical assessment including family history, biochemical and molecular genetic analysis using a panel of 21 HH genes.

Results: Thirty cases (19 male, 11 female) were included in this study with a median age at genetic testing of 18.3 yrs (range, 1.8,48.3). This cohort included 11 (37%) with Kallmann syndrome (KS) defined as anosmic HH, 14 (47%) with idiopathic HH with normosmia (nHH), 1 (3%) with uncertain sense of smell (uHH), 3 (10%) with multiple pituitary hormone deficiency (MPHD) and 1 (4%) with CHARGE syndrome. A positive family history related to HH was present in 9 (30%). Of the 22 that had neuroimaging, 5 (23%) had hypoplasia or agenesis of the olfactory system. Diagnostic biochemistry was available in 23/30 cases (77%) at the median age of 17.5 years (0.25, 35.4). The median basal and peak stimulated LH were 0.2IU/L (0.1, 4.3) and 1.7IU/L (0.2, 18.9), respectively. The median basal and peak stimulated FSH were 0.7 IU/L (0.2, 6.7) and 2.8IU/L (0.1, 12.1), respectively. The median basal testosterone was 0.5nmol/l (0.4, 10.3) in 12 male participants. In total, 19 gene variants were identified in 14/30 cases (47%); this included 10 variants of uncertain significance in 5 genes in 7 cases (six FGFR1, one CHD7, one FGF8, one PROKR2 and one SPRY4), 4 likely-pathogenic variants in 3 genes in 4 cases (one CHD7, one PROK2, two FGFR1), 5 pathogenic in 4 cases (one each in FGFR1, PROK2, ANOS1, 2 GNRHR). Of these 14 cases, 7 were KS, 5 were nHH and there was one each of uHH and CHARGE syndrome. Of the 16 cases with no gene variants identified, 4 were KS, 9 were nHH and 3 were MPHD. There was no clear relationship between the presence of classic features of HH and the likelihood of detecting a gene variant.

Conclusions: Over 40% of patients with HH who had undergone targeted genetic analysis had a variant identified. A low threshold is required to suspect a diagnosis of HH even if classic features of HH do not exist.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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