Studies on the Hypothalamic-Pituitary-Adrenal Function in a State of Malnutrition

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The hypothalamic-pituitary-adrenal axis was investigated in 33 patients with various psychosomatic diseases treated with fasting therapy for 11 days, and a comparative study was made between this group and 13 young women with anorexia nervosa. The results obtained were as follows : 1) The administration of dexamethasone failed to suppress cortisol levels to a normal range in 14 out of 33 patients during fasting 2) The normal circadian rhythm of plasma cortisol was abolished in 9 out of 21 patients during fasting. Plasma cortisol concentrations were significantly elevated at any given time of the day, especially in the dexamethasone nonsuppressive patients. 3) The excretion of urinary 17-OHCS and 17-KS in the 24-hr samples after the oral administration of metopirone was significantly higher in fasting patients as compared with non-fasting patients. The response of plasma ACTH to metopirone showed a non-significant increase. 4) The circadian rhythm of ACTH responsiveness to metopirone administration was normal in patients during fasting. 5) The plasma cortisol response to β1-24 ACTH 0.25 mg im was significantly higher in fasting patients as compared with non-fasting patients. 6) The basal urinary 17-OHCS and 17-KS in the 24-hr sample displayed a biphasic fluctuation with the peaks at 3 and 6 days after the initiation of fasting, 7) The cortisol metabolic clearance rate in fasting patients was prolonged as compared with that in non-fasting patients. 8) After refeeding, pituitary adrenal functions returned to normal in all patients. 9) Anorexia nervosa patients, non-suppressive to dexamethasone, demonstrated elevated plasma cortisol levels, normal responses to metopirone and ACTH, with a decreased excretion of urinary 17-OHCS and 17-KS. It is concluded that high levels of plasma cortisol in both fasting and anorexia nervosa were caused by abnormalities of the negative feedback mechanism and prolongation of cortisol metabolic clearance rate. In addition, it was noted that patients exposed to fasting revealed an adrenocortical hyperfunction.