ESPE Abstracts (2016) 86 P-P1-630

GH-Pattern with High Trophs are Often Found after Daily sc rhGH-Injection in Children

Elena Lundberga, Bjorn Anderssona, Berit Kristroma, Sten Rosbergb & Kerstin Albertsson-Wiklandb

aInstitute of Clinical Science/Pediatrics, Umea University, Umea SE-90185, Sweden; bDepartmen of Physiology/Endocrinology, Institute of Neurosciences and Physiology, Salhgrenska Academy, University of Gothenburg, Gothenburg SE-40530, Sweden

Background: Endogenous GH pattern is characterized by high peaks (growth signal) and low trophs (metabolic signal). Exogenous GH is given by subcutaneous injection (scGH-injection) daily at bedtime.

Objective and hypotheses: To study the factors influencing intra-/interindividual variation of pharmacokinetics and pattern of scGH-injection in GH treated children.

Method: One hundred and twenty eight subjects followed yearly ≤ 8 years for GH-curves after deep sc 12 mm needles, GH33/GH67μg/kg. EXPerimental setting (59 GH-curves in 15 MPHD patients) and CLINical setting (429 GH-curves in 117 IGHD/ISS patients). Tmax (h) at maximal GH-concentration Cmax (mU/l), area under the curve (AUC) mU/l and GHpeak width were estimated.

Results: Interindividual variability, median (coefficient of variance, %), was for Cmax 71(44), AUC 534(42); intra-individual variability was for Cmax 71(38), AUC 534(36). A positive GH-concentration dependency 16 vs 4 IU/ml, P=0.025 and a GHinj time dependency, evening vs morning (P=0.0014) was found. There was a dose-dependency with Cmax 63(51) vs 103(46), P<0.001, and AUC 464(45) vs 865(37), P<0.001, GH33 vs GH67 respectively. Forty-three percent of both Cmax and AUC-variation could be explained by the GH-dose and indirect measurements of the injection depth ie GHpeakwidth, BMISDS. Fifteen percent of the EXP-GHcurves and 60% of the CLIN-GHcurves had not returned to zero-level before the next injection.

Conclusion: The GH pattern of the scGHinj was characterized by a peak around 3 h, higher after a deep evening injection with high GH dose and high GH concentration (signal for growth) with great intra-/interindividual variability that in many of the GH-curves had not returned to undetectable level before the next injection which implies a non-physiological signal for metabolism.

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