Opioid dysregulation in anorexia nervosa: Naloxone effects on preprandial and postprandial growth hormone response to growth hormone-releasing hormone

Previously, we have shown that in the opposite extremes of nutritional status, obesity and anorexia nervosa (AN), growth hormone (GH) response to growth hormone-releasing hormone (GH-RH) is not inhibited by the ingestion of a normal 800-cal meal consumed at lunch time (1 pm), which is at variance with results in normal subjects. However, in obese patients the postprandial increase in GH response to GH-RH is inhibited by an infusion of naloxone (NAL). In this study we have tested anorectic patients, performing the following tests at 1 pm: GH-RH test (50 μg IV) or, in a different day session, NAL (1.6 mg/h, starting 30 minutes before GH-RH) + GH-RH test (50 μg IV). The tests were performed in the following three different experimental conditions: (1) short-term fasting studies (lasting from breakfast), (2) long-term fasting studies (from midnight of the day before) and (3) postprandial studies (after a standard meal consumed 1 hour before the test). In AN, the GH response to GH-RH was not influenced by NAL infusion at 1 pm, in both short-and long-term fasting studies (short-term fasting: peak values after GH-RH alone, 26.5 ± 6.5 ng/mL, duirng NAL, 28.0 ± 3.3 ng/mL; long-term fasting: peak values after GH-RH alone, 32.2 ± 6.8 ng/mL, during NAL, 30.6 ± 4.0 ng/mL). A partial NAL-inhibitory effect was instead observed in postprandial studies, as evidenced by the calculation of areas under the curve ([AUCs] 1,662.1 ± 90.0 after GH-RH alone v 1,090.5 ± 245.4 ng/mL/h during NAL). These findings indicate that NAL exerts differential effects in AN before and after a meal. Comparison to the results previously obtained in normal and obese subjects seems to suggest a differential opioid modulation of GH response to GH-RH in AN patients versus normal subjects or patients with obesity.