Impaired Growth Hormone Responses to Growth Hormone–Releasing Factor in Obesity A Pituitary Defect Reversed with Weight Reduction

• Published in: The New England journal of medicine Vol. 311; no. 22; pp. 1403 - 1407
• Main Authors: Williams, Timothy, Berelowitz, Michael, Joffe, Stephen N, Thorner, Michael O, Rivier, Jean, Vale, Wylie, Frohman, Lawrence A
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 29.11.1984
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood Glucose - analysis; Body Weight; Digestive System Surgical Procedures; Female; Growth Hormone - secretion; Growth Hormone-Releasing Hormone; Humans; Insulin - pharmacology; Male; Medical sciences; Metabolic diseases; Middle Aged; Obesity; Obesity - physiopathology; Obesity - therapy; Pituitary Gland - physiopathology; Human; Protein hormone; Obesity; Pituitary hormone; Diet therapy; STH; Weight loss; Metabolic diseases; Hormonal investigation; STH-RH
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198411293112203

To investigate whether the impaired growth hormone secretion associated with obesity is a result of a hypothalamic or a pituitary disorder and whether it is a cause or a consequence of obesity, we studied plasma growth hormone responses to growth hormone–releasing factor in morbidly obese patients before gastrointestinal surgical therapy, in formerly obese subjects who had lost considerable weight postoperatively, and in non-obese controls. Growth hormone secretion was also assessed in response to insulin-induced hypoglycemia (in seven patients preoperatively and four postoperatively). In patients studied preoperatively, growth hormone responses to growth hormone–releasing factor were markedly impaired (P<0.001 as compared with controls), whereas in patients studied postoperatively they were partially restored to normal (P<0.05 as compared with those studied preoperatively). Growth hormone responses to insulin-induced hypoglycemia were similarly diminished in obese patients studied before operation (P<0.02). The growth hormone response to growth hormone–releasing factor was inversely correlated with the percentage of ideal body weight (P<0.01) and directly correlated with the growth hormone response to insulin (P<0.01). The impaired responsiveness to growth hormone–releasing factor suggests that the diminished response to insulin hypoglycemia is mediated by an impaired pituitary response to endogenous growth hormone–releasing factor. The reversibility of the defect after weight reduction suggests that it is a consequence rather than a cause of obesity. (N Engl J Med 1984; 311:1403–7.) OBESE subjects characteristically have blunted responses to all stimuli of growth hormone release and, after successful weight reduction, they have partial or complete restoration of normal growth hormone responsiveness. 1 2 3 4 5 6 7 Since all the stimuli that have previously been used act within the central nervous system, it has not been possible to determine whether the secretory abnormality has a hypothalamic or a pituitary origin. A primary hypothalamic defect has been suggested by the intimate involvement of nutrients in the control of growth hormone secretion and the proximity of the hypothalamic loci controlling such secretion as well as neurometabolic regulation and nutrient homeostasis. . . .