Adult Height of Patients with <b><i>SHOX</i></b> Haploinsufficiency with or without GH Therapy: A Real-World Single-Center Study

Abstract

Introduction: Isolated SHOX haploinsufficiency is a common monogenic cause of short stature. Few studies compare untreated and rhGH-treated patients up to adult height(AH). Our study highlights a growth pattern from childhood to AH in patients with SHOX haploinsufficiency and analyzes the real-world effectiveness of rhGH alone or plus GnRHa or aromatase inhibitors (AI). Methods: Forty-seven patients (18 untreated and 29 rhGH-treated) with SHOX haploinsufficiency were included in a longitudinal retrospective study. Adult height was attained in 13 untreated and 18 rhGH-treated [rhGH alone (n=8) or plus GnRHa or AI (n=10)] patients. Results: The untreated group decreased height SDS from baseline to AH [-0.8 (-1.1; -0.4)], with an increase in the prevalence of short stature from 31% to 77%. Conversely, the rhGH-treated group had an improvement in height SDS from baseline to AH [0.6 (0.2;0.6); p&lt;0.001)], with a reduction in the prevalence of short stature (from 61% to 28%). AH in the rhGH-treated patients was 1 SD (6.3 cm) taller than in untreated ones. Regarding the use of GnRHa or AI, the subgroups (rhGH alone or plus GnRHa/AI) attained similar AH, despite the higher prevalence of pubertal patients and worse AH prediction at the start of rhGH treatment in patients who used combined therapy. Conclusion: The use of rhGH treatment improves AH in patients with SHOX haploinsufficiency, preventing the loss of height potential during puberty. In peripubertal patients, the addition of GnRHa/AI to rhGH allows AH attainment similar to the AH of patients who start rhGH alone in the prepubertal age.

The Half-Empty Glass of GH Treatment in Dyschondrosteosis

“…Pooling the very consistent data from these four different studies, one can see that on average 4.8 years of treatment started at the age of 10.5 years at a dose of 44.4 μg/kg day allows to reach an adult height of −2.4 DS, that is to say, a gain of 0.9 DS (3.15 cm approximately). The article by Dantas et al [1] provides an interesting explanation for this mitigated result, which the authors do not discuss sufficiently in our opinion. Indeed, over the years of treatment, the annual growth rate, which reached 8.5 cm on average in the first year, progressively decreased to 5.3 cm in the fourth year.…”

“…This is clearly the case with the treatment of short stature caused by dyschondrosteosis with growth hormone alone. The recent article by Dantas et al [1] in 29 patients adds to the small studies by Blum et al [2, 3] and to the larger study of Bennabad et al [4] in the GeNeSIS cohort to give a very coherent view of the results of this treatment. Pooling the very consistent data from these four different studies, one can see that on average 4.8 years of treatment started at the age of 10.5 years at a dose of 44.4 μg/kg day allows to reach an adult height of −2.4 DS, that is to say, a gain of 0.9 DS (3.15 cm approximately).…”

The Changing Face of Paediatric Human Growth Hormone Therapy

“…The approved dose was significantly higher than for GH deficiency, being in the region of 50 µg/kg/day [1]. Other non-GH deficient disorders followed, such as short stature related to birth size small for gestational age (SGA) [21,22], idiopathic short stature (ISS) [23]-which was approved in the USA but not in Europe-Prader-Willi syndrome, SHOX deficiency [24] and Noonan syndrome [25] (Figure 2). Growth failure in chronic renal insufficiency had previously been approved for in 1963.…”