VALUE AND LIMITS OF PHARMACOLOGICAL AND PHYSIOLOGICAL TESTS TO DIAGNOSE GROWTH-HORMONE (GH) DEFICIENCY AND PREDICT THERAPY RESPONSE - FIRSTAND 2ND RETESTING DURING REPLACEMENT THERAPY OF PATIENTS DEFINED AS GH DEFICIENT

There is currently a debate about the use of pharmacological and physi ological tests to define GH deficiency and predict response to GH ther apy. In addition, a good response to therapy has also been described i n subjects without GH deficiency. For further information, we reevalua ted GH secretion during replacement therapy in a group of children def ined as GH deficient and examined response to therapy in the subjects subdivided according to secretion. One hundred eighty four children (1 13 boys and 71 girls) initially diagnosed with GH deficiency by means of pharmacological (peak <8 mu g/L after arginine and L-dopa tests) an d physiological tests (mean nocturnal concentration less than or equal to 3.3 mu g/L during sleep test) underwent the same tests 2.8 +/- 1.1 yr after start of GH therapy. Sixty eight patients were retested 1.5 +/- 0.4 yr after first retesting. At diagnosis 122 subjects had pathol ogical pharmacological and physiological tests (group A), 30 subjects normal sleep test with pathological pharmacological tests (group B), a nd 32 subjects pathological sleep test with normal pharmacological tes ts (group C). At diagnosis 140 subjects were prepubertal and 44 pubert al. To evaluate response to therapy in relation to GH secretion at dia gnosis and at both retestings, a number of auxological parameters were calculated during treatment. At first retesting, 107 subjects (58.1%) changed initial group of diagnosis, 34 of whom (18.5%) presented norm al secretion in both pharmacological and physiological tests (group D) . At second retesting, 31 of the 68 subjects reexamined (45.6%) change d first test results, and 33 (48.5%) reverted to the initial group of diagnosis; none of the 6 subjects of group D maintained normal secreti on. Although the percentage of normalized subjects was higher in the p ubertal subjects (36.4%; P = 0.0003) than prepubertal subjects (8.9%), puberty did not prevent a reduction of secretion in some subjects. Re sponse to treatment during the first year of therapy was similar in th e various groups. GH secretion seems to change in both prepubertal and pubertal children diagnosed with GH deficiency when pharmacological a nd physiological tests are repeated over time. Moreover, such tests ma y not represent a reliable tool for predicting response to treatment. GH secretion normalization at retesting may not necessarily represent the end of a transient secretory defect.