ESPE Abstracts

Introduction: Diagnosing growth hormone deficiency (GHD) in children is complex. Spontaneous growth hormone (GH) pulses during late night may influence the pituitary GH response to provocation tests. We evaluated refractoriness during arginine-insulin-tolerance test (AITT) when having a GH-peak during a short spontaneous nocturnal profile in children with short stature.

Methods: Altogether 257 children 0-18 years were examined with spontaneous nocturnal profile, with blood samples for GH levels every 30 minutes between 04.00 – 08.00, and subsequent AITT. They were classified in subgroups depending on their GH response at the spontaneous nocturnal profile and AITT, and medical records were reviewed retrospectively. Refractory children were defined as having a GH-peak ≥7 µg/l during spontaneous nocturnal profile, but no GH-peak ≥7 µg/l during AITT. Prevalence of refractoriness for cut off level GH ≥5 µg/l and GH ≥10 µg/l was also evaluated.

Results: In total, 44/257 children were refractory, corresponding to 17.1% of all individuals and 21.9% of children with at least one GH-peak ≥7 µg/L. The proportion of males (P=0.033) and the body mass index (BMI) standard deviation score (SDS) (P=0.037) was higher in the refractory group compared to all children with a GH-peak ≥7 µg/L. The proportion of children with an adequate hypoglycaemia <2.2 mmol/l did not differ significantly between refractory and non-refractory children. The period between last spontaneous nocturnal profile peak ≥ 7 µg/l and GHmax AITT, was 210 (30 – 390) minutes in median. The maximum GH-peak at AITT occurred 30 minutes earlier for children who did not have a peak ≥7 µg /l during the spontaneous nocturnal profile (P=0.004). Using the cut off GH ≥ 5 µg/l, 35/257 (13.6%) of the study population were refractory, and for the cut off GH ≥ 10 µg/l 34/257 (13.2%) were refractory. Of all children, median age was 8.0 years, 138 (53.7%) were male and 212 (82.5 %) were prepubertal. The median height of the prepubertal children was -2.9 SDS. Only 7 (2.7%) were primed with sex steroids. Comorbidity that might affect the GH secretion and/or growth was found in 31.1% (n = 80).

Conclusions: A considerable number of children were refractory when examined with both spontaneous nocturnal profile and AITT, and among them few clinical characteristics were found. The possibility of refractoriness needs to be taken into consideration when evaluating children for possible GHD to avoid over diagnosing.