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

Abstract

Background Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating 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. Objectives Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls. Methods We included 190 patients; 26 received rhGH. Height, weight, body mass index (BMI) at various time-points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models. Results Adult height was available for 11/26 of rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 SDS after one year (CI +0.5 to +0.8, p<0.001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, p<0.001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared to untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, p<0.001). BMI SDS did not vary significantly upon rhGH therapy. Conclusion rhGH treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.