Somatostatin pretreatment enhances growth hormone (GH) responsiveness to GH-releasing hormone: a potential new diagnostic approach to GH deficiency.

Abstract

Despite the availability of numerous testing procedures to evaluate GH secretion in short children, there is still controversy about the most reliable test in the diagnosis of GH deficiency. We have recently demonstrated that in normal short children, priming with the long-acting somatostatin analog. SMS 201-995 (SMS), significantly potentiates their GH response to subsequent GHRH challenge. In the present study, we used the combined SMS + GHRH test in patients with GH deficiency to validate the hypothesis that this test would better discriminate between normal short children and those with truly diminished GH secretion. We studied 24 children classified into three groups according to their GH peak response to up to four conventional tests: 1) children with normal short stature and normal GH response (NSSA: GH peak > or = 10 micrograms/L, n = 6); 2) children with normal short stature with borderline GH response (NSSB: GH peak > or = 7 micrograms/L but < 10 micrograms/L, n = 4); and 3) GH-deficient children (GHD: GH peak < 7 micrograms/L, n = 14). Two study protocols were performed in all subjects: SMS (1 microgram/kg, sc) was randomly administered or omitted (control test) a 0800 h and GHRH (1 microgram/kg, iv) was given 5 h later. Plasma GH levels were measured every 30 min from 0800 h until 2 h after the GHRH injection. Pretreatment with SMS significantly augmented the GH peak response and the GH area under the GH concentration curve over 2 h after GHRH injection in the NSSA group, compared with control tests, but had no effect in the other two groups. While there was wide overlap of individual peak GH values to both the conventional tests and to the GHRH injection in the control test among the three groups of children, pretreatment with SMS resulted in complete discrimination between GHD and normal short children; the mean GH peak response to GHRH after SMS pretreatment was 8- to 9-fold lower in the GHD subjects (5.2 +/- 0.8 micrograms/L) compared with both the NSSA (44.0 +/- 14.3 micrograms/L; P < 0.01) and NSSB (42.9 +/- 5.0 micrograms/L; P < 0.01) groups and, more importantly, there was no overlap in the individual GH responses between GHD and normal short children. These results demonstrate that the combined SMS + GHRH test clearly discriminates normal short children from those with GHD. In view of its testing economy, safety, and accuracy, this combined test could become the test of choice to establish a diagnosis of GH deficiency in the slowly growing child.