Diagnosing growth hormone deficiency: the value of short-term hypocaloric diet

In the attempt to define possible causes of false positive GH deficiency, the role of caloric intake on GH determination was explored. The serum GH responses to insulin-induced hypoglycemia or arginine were assessed before and after 3 days of a hypocaloric diet in 23 prepubertal children of normal weight, aged 6.7-11.9 yr. Seventeen had short stature and a GH response to insulin and arginine below 10 micrograms/L, and 6 controls had normal stature and a GH peak above 10 micrograms/L in response to arginine. After diet, the serum peak GH and the area under the curve increased in both the patients (P < 0.0005 and P < 0.0005) and the controls (P < 0.005 and P < 0.025) with a GH peak greater than 10 micrograms/L in 11 of 17 patients. The patients with a persistent GH response below 10 micrograms/L also had lower mean 12-h overnight GH levels (P < 0.0005), whereas those with a normal GH response after diet had an overnight GH level greater than 3 micrograms/L. In the patients, the mean nighttime GH concentrations correlated with the serum GH peak (r = 0.85; P < 0.005) and with the area under the curve after the diet (r = 0.65; P < 0.025). The diet induced changes in plasma insulin-like growth factor-I, GH-releasing hormone levels, basal blood sugar and the nadir level obtained during insulin stimulation, total T3, and rT3. Height increased significantly during 1 and 2 yr (P < 0.005) of GH treatment only in patients with a GH response below 10 micrograms/L after the diet. These data are consistent with the hypothesis that the GH response to stimulation is strongly calorie dependent and that 3 days of a hypocaloric diet can increase the number and height of GH peaks and the total GH responses to insulin and arginine. The clear correlation of the GH response to stimulation after a hypocaloric diet with the mean nighttime GH and also with the growth response to GH treatment indicates that GH deficiency may be overdiagnosed in many children with short stature.