Neuroendocrine aspects of attention deficit hyperactivity disorder

This article provides an initial description of a limited number of boys with attention deficit hyperactivity disorder (ADHD) who underwent two GH challenge tests. The study demonstrates that it is likely that more than one monamine substrate is involved in the regulation of symptoms of ADHD. Both prepubertal and postpubertal groups demonstrate the interaction of at least two monamine systems, rather than a simple neurochemical explanation. Normal children can be partially differentiated from ADHD individuals when the peak GH response to L-dopa and clonidine are considered together. These differences are found only when the pubertal stage, by Tanner staging, is controlled. Prepubertal children have a low peak GH response to L-dopa, and the ratio of the peak to baseline response to clonidine is low. Postpubertal children are discriminated from normal children on the basis of a relatively lower peak GH response to L-dopa, and either a lower GH response to clonidine or the failure of GH level in response to clonidine to return to low levels at 180 minutes after the stimulation test. The clinical observation that ADHD children often improve in their motoric symptoms with puberty may be a reflection of this change in the noradrenergic system. The low response to L-dopa remains fairly constant, possibly reflecting the continuance of attentional problems. The multiple neurochemical effects of sympathomimetics that produce well-established clinical improvement in ADHD children and adolescents are supported by the finding that there is dysregulation in both systems. The recent finding of the efficacy of monamine oxidase inhibitors as well as the mild efficacy of tricyclics such as desipramine, which block the re-uptake of norepinephrine, are also consistent with these multiple substrate findings. This study implies that it may some day be possible to establish biochemical markers for children with ADHD. Previous studies by Garfinkel and colleagues and Shaywitz and coworkers demonstrate that children can be differentiated on the basis of GH response to amphetamine or methylphenidate. This more selective sampling of the neurotransmitter systems provides a mechanism for identifying peak GH response, which may lead to predictions of which children should receive a specific medication. Medication response could be monitored to document whether or not these neuroendocrine changes are predictive of behavioral response. Use of these more precise GH measurements may also determine neuroendocrinologic subgroups of prepubertal and postpubertal children with ADHD. With further refinement, these neuroendocrine challenge tests may become a useful adjunct to aid in clinical diagnosis, treatment outcome, and pharmacologic management of children with ADHD.