GH excess; GPR101; X-LAG; acromegaly; gigantism; neurofibromatosis type 1; optic pathway glioma; overgrowth; pituitary tumor; Medicine (all); General Medicine
Abstract :
[en] Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of 10 children and adults with NF1 referred to a tertiary care clinical research center. Six children (median age = 4 years, range of 3−5 years), one 14-year-old adolescent, and three adults (median age = 42 years, range of 29−52 years) were diagnosed with NF1 and GH excess. GH excess was confirmed by the failure to suppress GH (<1 ng/mL) on oral glucose tolerance test (OGTT, n = 9) and frequent overnight sampling of GH levels (n = 6). Genetic testing was ascertained through targeted or whole-exome sequencing (n = 9). Five patients (all children) had an OPG without any pituitary abnormality, three patients (one adolescent and two adults) had a pituitary lesion (two tumors, one suggestive hyperplasia) without an OPG, and two patients (one child and one adult) had a pituitary lesion (a pituitary tumor and suggestive hyperplasia, respectively) with a concomitant OPG. The serial overnight sampling of GH levels in six patients revealed abnormal overnight GH profiling. Two adult patients had a voluminous pituitary gland on pituitary imaging. One pituitary tumor from an adolescent patient who harbored a germline heterozygous p.Gln514Pro NF1 variant stained positive for GH and prolactin. One child who harbored a heterozygous truncating variant in exon 46 of NF1 had an OPG that, when compared to normal optic nerves, stained strongly for GPR101, an orphan G protein-coupled receptor causing GH excess in X-linked acrogigantism. We describe a series of patients with GH excess and NF1. Our findings show the variability in patterns of serial overnight GH secretion, somatotroph tumor or hyperplasia in some cases of NF1 and GH excess. Further studies are required to ascertain the link between NF1, GH excess and GPR101, which may aid in the characterization of the molecular underpinning of GH excess in NF1.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Hannah-Shmouni, Fady ; Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA
Trivellin, Giampaolo ; Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA ; Laboratory of Cellular and Molecular Endocrinology, Humanitas Research Hospital-IRCCS, 20089 Rozzano, Italy
Beckers, Pablo ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique ; Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA
Karaviti, Lefkothea P; Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA
Lodish, Maya; Department of Pediatrics, University of California, San Francisco, CA 94143, USA
Tatsi, Christina ; Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA
Adesina, Adekunle M; Immunology and Pediatrics-Hematology/Oncology, Neuropathology and Molecular Neuropathology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA
Adamidou, Fotini; Department of Endocrinology, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
Mintziori, Gesthimani; Department of Endocrinology, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
Josefson, Jami L; Division of Endocrinology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Quezado, Martha; Laboratory of Pathology, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA
Stratakis, Constantine A; Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD 20892, USA ; Human Genetics & Precision Medicine, Institute of Molecular Biology and Biotechnology (IMBB), Foundation for Research & Technology Hellas, 70013 Heraklion, Greece ; Experimental-Research Center ELPEN, 19009 Athens, Greece
Language :
English
Title :
Neurofibromatosis Type 1 Has a Wide Spectrum of Growth Hormone Excess.
NIH - National Institutes of Health [US-MD] [US-MD]
Funding text :
Funding: This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (project number Z1A HD008920).Conflicts of Interest: C.A.S. holds patents on the PRKAR1A, PDE11A and GPR101 genes and/or their function and his laboratory has received research funding from Pfizer Inc. Trivellin holds a patent on the GPR101 gene and its function (US Patent No. 10,350,273, Treatment of Hormonal Disorders of Growth). The authors declare that they have no conflicts of interest that may interfere with the contents of this article.
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