Peripheral plasma corticotropin-releasing hormone (CRH) in an aged patient with fasting hypoglycemia associated with an insufficient secretion of insulin: an implication of plasma CRH in glucose metabolism

Abstract

We present a 66-year-old man with morning fasting hypoglycemia from an unknown cause associated with markedly suppressed levels of insulin. In this patient we examined the diurnal changes of plasma corticotropin-releasing hormone (CRH). ACTH, cortisol, glucose, insulin and body temperature, and the correlations among them. We also discussed an implication of plasma CRH in glucose metabolism by taking these findings together with results from previous studies on plasma CRH in diabetic or hypoglycemic animals and human beings. In this case, the stress induced by severe spontaneous hypoglycemia in the morning fasting state increased CRH in plasma compared to the euglycemia state and simultaneously activated the hypothalamic-pituitary-adrenal system as well as the sympathetic nervous system remarkably. The daily intravenous infusion of glucose brought the fasting hypoglycemia to normal and hypothermia to normothermia in the morning, and improved no or blunt responsiveness of insulin to glucose. On the 50th day of therapy, the i.v. infusion of glucose quickly produced moderate hyperglycemia and an increase in plasma insulin, and inhibited secretions of CRH, ACTH and cortisol. The source of plasma CRH remains obscure. However, the positive correlations of plasma CRH with both plasma ACTH and cortisol and several lines of evidence indicate that CRH in peripheral plasma is derived from both the hypothalamus and extrahypothalamic peripheral tissue and that during stressed conditions, in particular, the CRH increase in plasma is derived mainly from the paraventricular nucleus of the hypothalamus. The role of CRH not only in the systemic circulation but also in the endocrine pancreases for glucose metabolism remains to be clarified.