ESPE2021 ePoster Category 1 Growth B (10 abstracts)
Sex differences in growth response to GH treatment: more prepubertal and less pubertal gain in girls diagnosed with IGHD, ISS, SGA. Analysis of data from GH-SAFETY-database, including all children treated with rhGH- 1986-2009 in Sweden, in National-GH-Registry and rhGH-clinical-trials.
Elena Lundberg 1 , Berit Kriström 1 , Aldina Pivodic 2 & Kerstin Albertsson-Wikland 3
1Institute of Clinical Science/Pediatrics, Umeå University, Umea, Sweden; 2Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; 3Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Background: Due to fewer girls than boys being GH-treated, after 50yrs the knowledge about sex-differences in both GH-response and GH-responsiveness before and during puberty remains limited.
Aim: To describe factors explaining growth response to GH-treatment, separately in girls and boys from GHstart to adult height (AH).
Methods: Children diagnosed with IGHD/ISS/SGA from GH-SAFETY-database1. Complete data was required: gestational age (GA) ≥32weeks; birth-size>-4SDS2; from birth-to-AH longitudinal heights/weights, pubertal stage(B2/testis ≥4ml); mid-parental-height(MPH); GHmaxAITT/12-24h-GHprofile; rhGHstart≥3yrs; available rhGH-dose(µg/kg/day). Growth-response outcomes were: change vs population3 (∆heightSDS), vs parents (DiffH-MPHSDS) for prepubertal 1styr, 2yr< prepubertal (GHstart-to-last-prepubertal visit using prepubertal reference), pubertal (last-prepubertal visit-to-AH using 18yrs reference), and total (GHstart-to-AH) GH-treatment periods. Fisher’s non-parametric permutation-test and linear regression was applied.
Results: Girls, compared to boys of similar GA/birth-size, grew less during infancy, resulting in more pre-treatment deficit to both parents and population. Girls responded, on higher GH-doses, with more prepubertal 1yr-growth and more prepubertal growth. During puberty, on similar GH-doses, mean ∆heightSDS was reduced for girls while maintained in boys until AH. Thus, the total gain, on similar GH-doses, became similar for girls vs boys.
| Birth/infancy | Boys=420 Mean(SD) | Girls=184 Mean(SD) | p-value |
| BirthLengthSDS | -1.60(1.14) | -1.70(1.15) | 0.31 |
| BirthWeightSDS | -1.06(1.09) | -0.98(1.18) | 0.42 |
| Infancy∆HeightSDS0-2yrs | -0.51(1.11) | -0.82(1.09) | 0.0019 |
| DiffH-MPHSDS2yrs | -1.12(1.03) | -1.38(1.02) | 0.0042 |
| Pre-treatment | -0.03(0.23) | 0.02(0.23) | 0.015 |
| ∆HeightSDSPre-treatment | |||
| GHmaxAITT/GHprofile | 16.1(19.1) | 15.7(14.4) | 0.81 |
| at GHstart Age(yr) | 8.65(2.12) | 7.86(2.17) | <.0001 |
| HeightSDSGHstart | -2.72(0.52) | -2.97(0.58) | <.0001 |
| Outcome | |||
| ∆HeightSDS1yr | 0.71(0.26) | 0.80(0.29) | 0.0011 |
| ∆HeightSDSPrepubertal | 1.48(0.65) | 1.63(1.12) | 0.012 |
| GHdose(µg/kg/day)Prepubertal | 35.8(8.0) | 39.0(11.6) | 0.0002 |
| ∆HeightSDSPubertal | -0.005(0.69) | -0.36(0.68) | <.0001 |
| GHdose(µg/kg/day)Pubertal | 30.1(10.0) | 30.3(9.8) | 0.80 |
| ∆HeightSDSGHstart-AH | 1.47(0.80) | 1.27(0.80) | 0.0037 |
| GHdose(µg/kg/day)GHstart-AH | 32.5(7.9) | 33.9(8.8) | 0.051 |
| At AH Height(cm) | 172.2(6.0) | 157.2(5.4) | <.0001 |
| HeightSDS | -1.25(0.92) | -1.70(0.89) | <.0001 |
| DiffH-MPHSDS | -0.26(0.93) | -0.57(0.83) | 0.0002 |
Conclusion: This group of girls responded more than the boys did before puberty, being more GH-responsive4 as they were younger and shorter vs parents and population at GHstart; in addition, they received higher GH-doses. In girls, 20% of the prepubertal gain was lost during puberty whereas maintained in boys on similar GH-doses.
References: 1Albertsson-Wikland.JCEM.2016;101(5): 2149-59.
2Niklasson&Albertsson-Wikland.BMC.2008;8: 8.
3Albertsson-Wikland.ActaPead.2002;91(7): 739-54.
4Kriström.BMC.2009;12(9)1: 1.
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