Growth Patterns and Outcomes of Growth Hormone Therapy in Patients with Acrodysostosis

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 2023 Feb 7

PMID 36749450

Authors

D-A Ertl

G Mantovani

G P de Nanclares

F M Elli

A Pereda

A Pagnano

A Sanchis

A M Cueto-Gonzalez

S Berrade

M C Leon

A Rothenbuhler

C Audrain

J Berkenou

N Knight

K Dolman

A Gleiss

J Argente

A Linglart

Affiliations

Soon will be listed here.

Abstract

Introduction: Severe short stature is a feature of acrodysostosis, but data on growth are sparse. Treatment with recombinant human growth hormone (rhGH) is used in some centers to increase final height, but no studies have been published so far. Our objective was to conduct a multicenter, retrospective, cohort study to investigate growth in individuals with both types of acrodysostosis, treated with rhGH or not; we used the new nomenclature to describe acrodysostosis, as this disease belongs to the large group of inactivating PTH/PTHrP signaling disorders (iPPSD); acrodysostosis refers to iPPSD4 (acrodysostosis type 1 due to PRKAR1A mutations) and iPPSD5 (acrodysostosis type 2, due to PDE4D mutations).

Methods: We present auxological data from individuals with genetically characterized iPPSD4, and participants with clinical features of iPPSD5.

Results: We included 20 and 17 individuals with iPPSD4 and iPPSD5, respectively. The rhGH-treated iPPSD4 patients (n = 9) were smaller at birth than those who did not receive rhGH (median - 2.2 SDS vs. - 1.7 SDS); they showed a trend to catch-up growth during rhGH therapy (median 0.5 SDS in the first year). The rhGH-treated patients (n = 5) reached a better final height compared to those who did not receive rhGH (n = 4) (median - 2.8 SDS vs. - 3.9 SDS), suggesting that rhGH is efficient to increase height in those patients. The difference in target height to final height ranged between 1.6 and 3.0 SDS for iPPSD4 not treated with rhGH (n = 4), 2.1-2.8 SDS for rhGH-treated iPPSD4 (n = 5), 0.6-5.5 SDS for iPPSD5 not treated with rhGH (n = 5) and 2.5-3.1 for rhGH-treated iPPSD5 (n = 2).

Conclusion: Final height may be positively influenced by rhGH in patients with acrodysostosis/iPPSD. Our rhGH-treated cohort started therapy relatively late, which might explain, at least in part, the limited effect of rhGH on height.

Citing Articles

A rare case of acrodysostosis type 2 with PDE4D mutation in a young female: a case report.

Hameed M, Maheen M, Sadiq S, Farooq U, Rehman A, Ihtesham A Oxf Med Case Reports. 2025; 2025(1):omae169.

PMID: 39834885 PMC: 11742178. DOI: 10.1093/omcr/omae169.

Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?.

Gardner O, Bai T, Baillie G, Ferretti P Brain Commun. 2024; 6(4):fcae225.

PMID: 38983619 PMC: 11232698. DOI: 10.1093/braincomms/fcae225.

Recombinant growth hormone improves growth and adult height in patients with maternal inactivating GNAS mutations.

Ertl D, Perez de Nanclares G, Juppner H, Hanna P, Pagnano A, Pereda A Eur J Endocrinol. 2023; 189(1):123-131.

PMID: 37440712 PMC: 11077274. DOI: 10.1093/ejendo/lvad085.

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