ABNORMAL PANCREATIC ENDOCRINE FUNCTION IN REYE'S SYNDROME SURVIVORS AND THEIR RELATIVES: A PRELIMINARY REPORT

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Abstract

Summary

To explore the possibility that children who develop Reye's syndrome may be metabolically unique, we examined the ability of survivors to respond to endogenous and exogenous metabolic stimuli. Our preliminary results indicate the presence of abnormal insulin and glucagon responses under fasted and stimulated states. Specifically, higher fasting insulin and glucagon values were found in Reye's survivors than their siblings or normal control children. (Insulin levels ± SEM In uU/ml, 21.1 ± 1.86 for Reye's survivors, 15.4 ± 2.31 for siblings and 10.8 ± 1.30 for normal control children. Significance of difference between Reye's survivors and normal control children = p < .001. Glucagon levels ± SEM in pg/ml, 416 ± 46.7 for Reye's survivors and 178 ± 32.4 in siblings, p = < .001. Only one sibling had high fasting insulin“ values (mean 28 uU/ml) and two had fasting glucagon values above 200 pg/ml. Elevated levels of both hormones were not found in any sibling. Higher insulin and glucose responses to oral glucose were seen in 3 of 4 survivors during an OGTT. Higher mean integrated insulin areas above baseline were observed in Reye's survivors and their siblings compared to controls (p < .001. After l-arginine infusion, a clearly discernible double peak in the glucagon response was seen in 2 survivors, 1 sibling and 3 parents examined, a response not observed in the peripheral venous circulation but only reported in portal vein samples. These observations indicate that responses to a variety of pancreatic endocrine stimuli are altered in Reye's survivors and their families.

Speculation

In Reye's syndrome, high levels of circulating glucose substrates and metabolic fuels such as, alanine, lactate, pyruvate, glycerol, non-esterified fatty acids, acetoacetate and β-hydroxybutyrate, are reported (15,37) frequently in the presence of normal plasma glucose concentrations. The regulation of the flux of these substrates is highly influenced by the hormones, insulin and glucagon. Insulin is particularly important in the inhibition of release of such substrates from peripheral stores. Animal and human studies in various hyperinsulinemic states in which hyperglucagonemia is also seen have shown significant reduction in insulin-receptor binding. The possibility is raised that the relative hyperinsulinism expressed by children who have survived Reye's syndrome may have been present before their acute disease and may have contributed to the metabolic manifestations of the acute disorder.

Speculation

Reye's syndrome is a rare pediatric complication of common viral illnesses such as influenza and varicella (4). While epidemics of influenza afflict vast numbers of people throughout the entire age spectrum of man, Reye's syndrome as a sequel to Influenza is limited to less than 1/10th of a percent of children who have influenza (4). This epidemiological feature suggests that age and a susceptibility factor must both be present to selectively produce Reye's syndrome. The latter possibility is further supported by increasing evidence of familial clustering and recurrences of this syndrome (1,10,12,13,17,18,22,27–30,31,34,35).

Speculation

We have searched for a predisposing factor in these children long after they had recovered from their acute Reye's episodes. Because several glucose substrates are elevated in the plasma during the acute disease even in the absence of hypoglycemia in many cases, we chose to examine the ability of survivors to maintain caloric homeostasis under a variety of stimuli.

Speculation

The results of our preliminary studies indicate that these children maintain homeostasis in the presence of increased insulin and glucagon concentrations in the peripheral circulation under fasting conditions and in response to various stimuli. This altered state of metabolic responsiveness was also found in some but not all parents and siblings examined raising the likelihood that genetic factors may be involved in these findings.

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