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. 2022 Jul 18:51:101556.
doi: 10.1016/j.eclinm.2022.101556. eCollection 2022 Sep.

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

Johanna Hietamäki  1 , Juho Kärkinen  1 , Anna-Pauliina Iivonen  2 , Kirsi Vaaralahti  2 , Annika Tarkkanen  1   2 , Henrikki Almusa  3 , Hanna Huopio  4 , Matti Hero  1 , Päivi J Miettinen  1 , Taneli Raivio  1   2
Affiliations

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

Johanna Hietamäki et al. EClinicalMedicine. .

Abstract

Background: Childhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease VSports手机版. 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 V体育安卓版. .

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)) V体育ios版. .

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 VSports最新版本. .

Funding: Päivikki and Sakari Sohlberg Foundation, Biomedicum Helsinki Foundation, and Emil Aaltonen Foundation research grants V体育平台登录. .

Keywords: CPHD; Growth sreening; Hypopituitarism; Hypopituitarism etiology; Hypopituitarism genetic; Incidence VSports注册入口. .

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Conflict of interest statement

The authors have nothing to disclose.

Figures

Figure 1
Figure 1
Flowchart on the formation of the patient cohort. Through a comprehensive search for panhypopituitarism and related ICD-9/10 diagnosis codes, we identified n=124 pediatric CPHD patients diagnosed or treated in the Helsinki University Hospital Children and Adolescents between 1985 and 2018. Patients with at least two pituitary hormone deficiencies were included in the study (Supplementary Table 2). Cases with partial laboratory testing were evaluated by experienced clinicians (PJM, MH, TR) based on patient records and growth charts. ICD, International Classification of Diseases; CPHD, combined pituitary hormone deficiency; GH, growth hormone; GHD, growth hormone deficiency
Figure 2
Figure 2
The etiology of CPHD varies according to the age at presentation and diagnosis. Scattered min-max boxplots depicting the age at presentation (panel a) and age at diagnosis (panel b) for patients with acquired and congenital CPHD. For patients with congenital CPHD, the data is additionally shown as divided into main diagnostic subgroups. For one patient with congenital CPHD and an established genetic diagnosis, the phenotype was consistent with SOD. The patient is depicted as a triangle in the ‘Congenital with genetic diagnosis +ve’ group. Panel a: Patients with congenital CPHD presented at a younger age compared to acquired CPHD, p<0·0001, effect size r=-0·573. Data were available in 71/76 and 40/48 patients with acquired and congenital CPHD, respectively. Panel b: Patients with congenital CPHD received the diagnosis at a younger age compared to acquired CPHD p<0·0001, effect size r=-0·451. Data were available in 73/76 and 47/48 patients with acquired and congenital CPHD, respectively. +ve, positive; -ve, negative; SOD, septo-optic dysplasia; CPHD, combined pituitary hormone deficiency.
Figure 3
Figure 3
Neonatal features suggesting hypopituitarism in patients with congenital CPHD. Neonatal features were present in 26/35 patients; 23 patients had neonatal hypoglycaemiaa, 17 patients had neonatal jaundiceb, and eight male patients presented with a neonatal genitalc phenotype. The quantitative Venn diagram indicates the approximate proportional quantities and overlap of the respective features. a any note of neonatal hypoglycaemia and intravenous glucose treatment in the patient charts; 16/23 patients with hypoglycaemia had defined hypoglycaemia (a hypoglycaemic seizure or apnea, or treatment with intravenous glucose for >3 days, or at >3 days of age). b patients who had received phototherapy, or had the remark “prolonged jaundice” in the patient charts; 9/17 of the patients with jaundice had defined jaundice (phototherapy at >7 days of age, or remark “prolonged jaundice”) c micropenis and/or bilateral cryptorchidism. CPHD, combined pituitary hormone deficiency.
Figure 4
Figure 4
Individual growth curves of patients with congenital CPHD including GHD prior to treatment with GH Rx, or until 6 years of age, if no previous GH supplementation. Panel a: Patients with growth deflection at the age of ≤6 months (Group I, n=8; four patients with the start of GH Rx treatment prior to the age of 0·25 years not depicted); Panel b: Patients with growth deflection at the age of 6 months to 4 years (Group II, n=11). One patient with the first growth deflection at the age of 12 years not shown. HSDS, Height SDS.
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