NEUROENDOCRINE EFFECTS OF TOXIC AND LOW BLOOD LEAD LEVELS IN CHILDREN

From 3 million to 4 million children in America have lead poisoning. This environmental toxin affects 1 in every 6 children younger than 6 years of age in the United States. The marked effects of lead toxicity on the central nervous system are well known, ie, lowering IQ and impairing memory, reaction time, and the ability to concentrate. Children are at greatest risk for the central nervous system effects of lead because the central nervous system is at its peak in development during the first few years of life. The negative correlation of stature and blood lead level (bPb) found in the National Health and Nutrition Examination Survey directed the authors to evaluate the possible neuroendocrine effects of this toxin in children. Twelve children were studied during toxic (greater-than-or-equal-to 40-mu-g/dL) and low bPb (<40-mu-g/dL). Classic provocative stimuli, L-dopa (15 mg/kg by mouth) and insulin (0.1 U/kg given intravenously), were used to determine human growth hormone (hGH) responses during toxic bPb and after chelation therapy in six of the subjects. An additional four subjects were studied during low bPb. In two patients LGH levels were determined every 20 minutes for 24 hours during toxic bPb. Thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone were also determined. All children studied showed growth retardation during toxic bPb. Mean peak hGH responses to provocative stimuli were lower during toxic bPb, but the responses were all within normal limits. The mean 24-hour hGH values were low in the two patients (0.8 +/- 0.2 [SE] ng/mL and 2.0 +/- 0.8 ng/mL) studied compared with normal control patients (6.4 +/- 0.3 ng/mL). Insulin-like growth factor I values showed an inverse correlation with toxic blood bPb, up to 40-mu-g/dL. Basal thyroid-stimulating hormone, prolactin, thyroxine, and triiodothyronine concentrations were not affected by bPb. In addition, thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone were not affected by toxic or low bPb. Cortisol responses to insulin-induced hypoglycemia were normal (P less-than-or-equal-to .05). These observations, taken together, confirm the inadequacy of acute hGH responses to secretagogue as a reliable indicator of hGH secretion and indicate that lead-induced short stature may be due to diminished hGH secretion, which in turn results in reduced insulin-like growth factor I secretion, or that Pb may also directly inhibit insulin-like growth factor I formation.