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Alterations of the Adrenocorticotropin-Cortisol Axis in Normal Weight Bulimic Women: Evidence for a Central Mechanism^*

J. F. MORTOLA, D. D. RASMUSSEN and S. S. C. YEN

Department of Reproductive Medicine, School of Medicine (T-002), and the General Clinical Research Center, University of California-San Diego La Jolla, California 92093

Address all correspondence and requests for reprints to: Dr. S. S. C. Yen, Department of Reproductive Medicine, University of California-San Diego, La Jolla, California 92093.

We studied pituitary-adrenal function in eight women with normal weight bulimia and seven normal women by measuring plasma ACTH and serum cortisol levels at 20-min intervals for 24 h and the responses to human CRH (hCRH) and to a noon meal. The bulimic women had increased 24-h transverse mean plasma ACTH [1.09 ± 0.06 (±SE) vs. 0.75 ± 0.14 pmol/L; P < 0.05] and serum cortisol (235 ± 21 vs. 152 ± 9 nmol/L; P < 0.005) concentrations. While the 24-h ACTH and cortisol pulse frequencies were unaltered, the bulimic women had higher (P < 0.05) mean peak ACTH (1.46 ±0.09 vs.1.03 ± 0.15 pmol/L) and cortisol values (331 ± 33 vs. 239 ± 17 nmol/L). Despite having higher mean and peak plasma ACTH and serum cortisol values, the bulimic women had a blunted response of both ACTH (P < 0.001) and cortisol (P < 0.005) to hCRH, which included a lower mean maximal plasma ACTH response, decreased (P < 0.05) integrated area under the ACTH response curve (161 ± 12 vs. 231 ± 23 pmol/min·L), a lower (P < 0.05) maximum cortisol response (284 ± 35 vs. 413 ± 19 nmol/L), and decreased (P < 0.05) area under the cortisol curve (11.1 ± 1.9 vs. 15.9 ± 1.3 x 10³ nmol/min·L). The circadian variations of both ACTH and cortisol were maintained in the bulimic women; the nadir and acrophase times were similar to those of the normal women. However, the rise in serum cortisol that occurred within 1 h after the lunch meal in the normal women (104 ± 35 nmol) did not occur in the bulimic women (P < 0.05).

These data demonstrate that marked changes in hypothalamic-pituitary-adrenal function occur in bulimia in the absence of weight disturbance and suggest central activation of CRH and/or synergistic factors as well as alterations in signals from gut to brain in this syndrome.

^* This work was supported by the NIH NICHHD Center Grant HD-12303 and in part by the Andrew Mellon Foundation and UCSD General Clinical Research Center, NIH/Division of Research Resources Grant RR-00827. This research was conducted in part by the Clayton Foundation for Research.

Andrew Mellon Foundation Faculty Scholar.

Clayton Foundation investigator.

Received July 29, 1988.

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