Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency : A single center experience from over 30 years

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Hietamäki , J , Kärkinen , J , Iivonen , A P , Vaaralahti , K , Tarkkanen , A , Almusa , H , Huopio , H , Hero , M , Miettinen , P J & Raivio , T 2022 , ' Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency : A single center experience from over 30 years ' , EClinicalMedicine , vol. 51 , 101556 . https://doi.org/10.1016/j.eclinm.2022.101556

Title: Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency : A single center experience from over 30 years
Author: Hietamäki, Johanna; Kärkinen, Juho; Iivonen, Anna Pauliina; Vaaralahti, Kirsi; Tarkkanen, Annika; Almusa, Henrikki; Huopio, Hanna; Hero, Matti; Miettinen, Päivi J.; Raivio, Taneli
Contributor organization: HUS Children and Adolescents
Raivio Group
Helsinki University Hospital Area
Children's Hospital
STEMM - Stem Cells and Metabolism Research Program
Medicum
Department of Physiology
University of Helsinki
Institute for Molecular Medicine Finland
Clinicum
Timo Pyry Juhani Otonkoski / Principal Investigator
Centre of Excellence in Stem Cell Metabolism
Date: 2022-09
Language: eng
Number of pages: 21
Belongs to series: EClinicalMedicine
ISSN: 2589-5370
DOI: https://doi.org/10.1016/j.eclinm.2022.101556
URI: http://hdl.handle.net/10138/346677
Abstract: Background: Childhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease. We aimed to describe the clinical spectrum and genetic etiologies of CPHD in a single tertiary center and estimate the population-level incidence of congenital CPHD. Methods: The retrospective clinical cohort comprised 124 CPHD patients (48 with congenital CPHD) treated at the Helsinki University Hospital (HUH) Children's Hospital between 1985 and 2018. Clinical data were collected from the patient charts. Whole exome sequencing was performed in 21 patients with congenital CPHD of unknown etiology. Findings: The majority (61%;76/124) of the patients had acquired CPHD, most frequently due to craniopharyngiomas and gliomas. The estimated incidence of congenital CPHD was 1/16 000 (95%CI, 1/11 000-1/24 000). The clinical presentation of congenital CPHD in infancy included prolonged/severe neonatal hypoglycaemia, prolonged jaundice, and/or micropenis/bilateral cryptorchidism in 23 (66%) patients; despite these clinical cues, only 76% of them were referred to endocrine investigations during the first year of life. The median delay between the first violation of the growth screening rules and the initiation of GH Rx treatment among all congenital CPHD patients was 2·2 years, interquartile range 1·2–3·7 years. Seven patients harbored pathogenic variants in PROP1, SOX3, TBC1D32, OTX2, and SOX2, and one patient carried a likely pathogenic variant in SHH (c.676G>A, p.(Ala226Thr)). Interpretation: Our study suggests that congenital CPHD can occur in 1/16 000 children, and that patients frequently exhibit neonatal cues of hypopituitarism and early height growth deflection. These results need to be corroborated in future studies and might inform clinical practice. Funding: Päivikki and Sakari Sohlberg Foundation, Biomedicum Helsinki Foundation, and Emil Aaltonen Foundation research grants.
Description: Publisher Copyright: © 2022 The Authors
Subject: CPHD
Growth sreening
Hypopituitarism
Hypopituitarism etiology
Hypopituitarism genetic
Incidence
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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