Recombinant growth hormone improves growth and adult height in patients with maternal inactivating GNAS mutations.
iPPSD
pediatric
pseudohypoparathyroidism
recombinant human growth hormone
short stature
Journal
European journal of endocrinology
ISSN: 1479-683X
Titre abrégé: Eur J Endocrinol
Pays: England
ID NLM: 9423848
Informations de publication
Date de publication:
20 Jul 2023
20 Jul 2023
Historique:
received:
29
03
2023
revised:
15
05
2023
accepted:
01
06
2023
medline:
26
7
2023
pubmed:
13
7
2023
entrez:
13
7
2023
Statut:
ppublish
Résumé
Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder type 2 of maternal inheritance (iPPSD2). Patients present with resistance to PTH and other hormones, subcutaneous ossifications, brachydactyly, short stature, and early-onset obesity. They can be born small for gestational age (SGA) and may present with growth hormone (GH) deficiency. The use of recombinant human GH (rhGH) therapy has been sporadically reported, yet we lack data on the long-term efficacy and safety of rhGH, as well as on adult height. Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls. We included 190 patients, of whom 26 received rhGH. Height, weight, body mass index at various time points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models. Adult height was available for 11/26 rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 standard deviation scores (SDS) after 1 year (CI +0.5 to +0.8, P < .001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, P < .001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared with untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, P < .001). Body mass index SDS did not vary significantly upon rhGH therapy. Recombinant human growth hormone treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.
Sections du résumé
BACKGROUND
BACKGROUND
Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder type 2 of maternal inheritance (iPPSD2). Patients present with resistance to PTH and other hormones, subcutaneous ossifications, brachydactyly, short stature, and early-onset obesity. They can be born small for gestational age (SGA) and may present with growth hormone (GH) deficiency. The use of recombinant human GH (rhGH) therapy has been sporadically reported, yet we lack data on the long-term efficacy and safety of rhGH, as well as on adult height.
OBJECTIVE
OBJECTIVE
Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls.
METHODS
METHODS
We included 190 patients, of whom 26 received rhGH. Height, weight, body mass index at various time points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models.
RESULTS
RESULTS
Adult height was available for 11/26 rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 standard deviation scores (SDS) after 1 year (CI +0.5 to +0.8, P < .001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, P < .001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared with untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, P < .001). Body mass index SDS did not vary significantly upon rhGH therapy.
CONCLUSION
CONCLUSIONS
Recombinant human growth hormone treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.
Identifiants
pubmed: 37440712
pii: 7223915
doi: 10.1093/ejendo/lvad085
doi:
Substances chimiques
Growth Hormone
9002-72-6
Human Growth Hormone
12629-01-5
Recombinant Proteins
0
GNAS protein, human
EC 3.6.1.-
Chromogranins
0
GTP-Binding Protein alpha Subunits, Gs
EC 3.6.5.1
Types de publication
Observational Study
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
123-131Subventions
Organisme : European Reference networks Endo-ERN
ID : DSA 20200518 iPPSD
Organisme : Ministry of Economy and Competitiveness
Organisme : European Regional Development Fund
ID : PI20/00950
Organisme : European Society for Paediatric Endocrinology
ID : IO-COHO-03
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.