Modified Clonidine Testing for Growth Hormone Stimulation Reveals α(2)-Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency

INTRODUCTION: The association between short stature and increased risk of ischemic heart disease has been subject to studies for decades. The recent discussion of cardiovascular risk during growth hormone therapy has given new importance to this question. We have hypothesized that the autonomic system is a crucial element relating to this subject. METHODS: Heart rate variability calculated from 24-hour electrocardiogram data is providing insight into the regulatory state of the autonomous nervous system and is an approved surrogate parameter for estimating cardiovascular risk. We have calculated heart rate variability during clonidine testing for growth hormone stimulation of 56 children. As clonidine is a well-known effector of the autonomous system, stimulating vagal tone and decreasing sympathetic activity, we compared the autonomous reactions of children with constitutional growth delay (CGD), growth hormone deficiency (GHD) and former small for gestational age (SGA). RESULTS: During clonidine testing children with CGD showed the expected α(2)-adrenoreceptor mediated autonomous response of vagal stimulation for several hours. This vagal reaction was significantly reduced in the SGA group and nearly non- existent in the GHD group. DISCUSSION: Children with GHD show a reduced autonomous response to clonidine indicating α(2)-adrenoreceptor sub sensitivity. This can be found prior to the start of growth hormone treatment. Since reduction of HRV is an approved surrogate parameter, increased cardiovascular risk has to be assumed for patients with GHD. In the SGA group a similar but less severe reduction of the autonomous response to clonidine was found. These findings may enrich the interpretation of the data on growth hormone therapy, which are being collected by the SAGhE study group.