ESPE Abstracts (2022) 95 RFC9.2

1Istanbul University, Istanbul Faculty of Medicine, Department of Paediatrics, Paediatric Endocrinology Unit, Istanbul, Turkey; 2Istanbul University, Istanbul Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey; 3Istanbul University, Institute of Health Sciences, Istanbul, Turkey

Background: Deficiency of one or more pituitary hormones, often with growth hormone (GH) deficiency, is defined as multiple pituitary hormone deficiencies (MPHD) or congenital hypopituitarism (CH). CH cases are mostly sporadic and have a prevalence of 1/3000-4000 live births. There are many known and yet unknown molecular pathways explaining the complex structure and functions of the pituitary gland. Many different gross and small sequence variants in the genes encoding the transcription factors that play a role in the embryological development of the pituitary gland are found in association with CH.

Aim: To investigate the molecular etiology of MPHD in our cohort and to determine the genotype-phenotype correlation.

Patients and Methods: In our cohort, 102 patients (38 girls, 64 boys) with the clinical diagnosis of MPHD were investigated. Clinical and laboratory findings were retrospectively collected from medical files, and inheritance patterns were determined from pedigrees. A targeted next-generation sequencing (NGS) panel for MPHD (including 25 genes) was performed. Multiplex ligation-dependent probe amplification (MLPA P-216; GHRHR, LHX3, POU1F1, PROP1, LHX4, GH1, HESX1) was used to determine gene/exon deletions in patients with normal panel results.

Results: The median age at admission to endocrinology was seven years (range: 0.01-17), and the median age of the patients during the molecular studies was 19 years (2-35). The median duration of follow-up was 11 years (1-25). The rate of consanguineous marriage was 35.6%. Dysmorphic features were seen in 25% of patients. Pituitary anomaly in magnetic resonance imaging was detected in 60%. There were two hormone deficiencies in 40.8% of the patients, three in 26.5%, four in 26.5%, and five in 6.1%. Frequency of pituitary hormone deficiencies were as follows; GH 90.4%, thyroid-stimulating hormone (TSH) 77.9%, gonadotropins 42.3%, adrenocorticotropic hormone (ACTH) 37.5%, prolactin 28.8%, anti-diuretic hormone (ADH) 2.0 %. We identified 21 (20.5%) pathogenic/likely pathogenic gross and small variants in genes associated with MPHD: PROP1; n=4, WDR11; n=3, IGSF1; n=2, GH1; n=2, HESX1; n=2, LHX3; n=2, POU1F1; n=2, PROKR2; n=2, GHSR and HHIP (n=1 each).

Conclusion: Advances in molecular genetic technologies allow investigators to determine the etiology of MPHD. Implementing genetic diagnosis in clinical practice and genotype-phenotype correlation may enable a personalized medicine approach.

Keywords: Multiple pituitary hormone deficiencies, Next-generation sequencing, Congenital hypopituitarism

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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