PRESERVATION OF GROWTH-HORMONE PULSATILITY DESPITE PITUITARY PATHOLOGY, SURGERY, AND IRRADIATION

Detailed assessment of physiological and pathophysiological GH secreti on has, until recently, been limited by the poor sensitivity of the av ailable assays. We have used an ultrasensitive chemiluminescence GH as say (sensitivity, 0.002 mu g/L) to study 24-h GH profiles (20-min samp ling) from 24 patients who had been treated for hypothalamic-pituitary disease with surgery and irradiation and from 24 healthy control subj ects matched for age, sex, and body mass index. Twenty-three of the 24 patients demonstrated pulsatile GH secretion, determined by Cluster. The median (range) area under the curve for GH, mean pulse area, mean pulse height, average valley mean level, and mean interpeak nadir were lower in the patients than in the controls [119.25 (7.273-843.600) vs . 968.539 (227.200-4625.000) min/mu g.L (P < 0.00001); 3.777 (0.288-30 .850) vs. 61.390 (12.880-224.210) min/mu g.L (P < 0.00001), 0.107 (0.0 10-0.958) vs. 1.408 (0.368-5.050) mu g/L (P < 0.00001), 0.074 (0.006-0 .415) vs. 0.348 (0.048-2.350) mu g/L (P < 0.00001), and 0.066 (0.003-0 .270) vs. 0.205 (0.021-1.838) mu g/L (P = 0.0004), respectively]. The median (range) number of pulses, mean pulse duration, and mean interva l between pulses did not differ between the patients and controls [10 (4-15) vs. 10 (7-15;P = 0.36), 96.4 (68.0-220.0) vs. 104.0 (72.0-151.4 ) min (P = 0.65) and 128.0 (92.8-255.0) vs. 126.2 (90.0-180.0) min (P = 0.73), respectively]. The diurnal rhythm of GH secretion was present in the controls, but there was only limited evidence of residual diur nal rhythm in the patients. This study has demonstrated that GH secret ion remains pulsatile in GH-deficient patients despite the mass effect of hypothalamic-pituitary pathology, pituitary surgery, and radiother apy. With the development of potent GH secretagogues that are active o rally, our findings may have important implications for the future man agement of GH-deficient subjects.