title: Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults.
abstract: There is now wide consensus that, within an appropriate clinical context, GH deficiency (GHD) in adults must be shown biochemically by provocative testing of GH secretion and that appropriate cut-off limits have to be defined for each provocative test. Insulin-induced hypoglycemia (ITT) is indicated as the test of choice, and severe GHD, to be treated with recombinant human GH replacement, is defined by a GH peak response to ITT of less than 3 micrograms/L. GHRH + arginine (GHRH + ARG) is one of the most promising tests in alternative to ITT. In fact, it has been reported as a potent, reproducible, and age-independent test and that it is able to distinguish between GHD and normal adults. The aim of the present study was to compare the GH response to ITT and GHRH + ARG in a large group of hypopituitary adults (n = 40; 29 male and 11 female; age: 36.4 +/- 2.1 yr). The third centile limit of the peak GH response to ITT has been reported as 5 micrograms/L, whereas in our lab, that to GHRH + ARG is 16.5 micrograms/L. In hypopituitary adults, the mean peak GH response to ITT (1.5 +/- 0.2 micrograms/L, range: 0.1-8.5 micrograms/L) was lower (P < 0.001) than that to GHRH + ARG (3.0 +/- 0.4 micrograms/L, range 0.1-12.0 micrograms/L), though there was positive correlation (r = 0.61, P < 0.001) between the GH responses to the 2 tests. The peak GH response to GHRH + ARG, but not that to ITT, was positively (though weakly) associated with insulin-like growth factor-I levels (r = 0.35, P < 0.03). Childhood and adult onset GHD patients, as well as patients with single and multiple pituitary insufficiencies, had similar peak GH responses to ITT or GHRH + ARG. Analyzing individual GH responses, 4/40 (10%) of the hypopituitary patients had GH peaks higher than 5 micrograms/L after ITT; moreover, 3 other patients (7%) had GH peaks, after ITT, higher than 3 micrograms/L. On the other hand, after GHRH + ARG, all patients had GH peaks lower than 16.5 micrograms/L, whereas 21/40 (52.5%) had GH peaks higher than 3 micrograms/L. Because 3 micrograms/L is the arbitrary cut-off for ITT, the third centile limit of which is 5 micrograms/L, we arbitrarily considered 9 micrograms/L as the cut-off point for GHRH + ARG. It is noteworthy that 37/40 (92.5%) patients had a GH peak, after GHRH + ARG, below this limit. In conclusion, our present results confirm that the ITT test is a reliable provocative test for the diagnosis of adult GHD, whereas they show that the GHRH + ARG test is, at least, as sensitive as the ITT test (provided that appropriate cut-off limits are considered). Note that even the arbitrary cut-off point below which severe GHD is demonstrated has to be appropriate to the potency of the test.
authors.affiliation: Department of Internal Medicine, University of Turin, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Aimaretti
authors.forename: G
authors.initials: G
authors.lastname: Corneli
authors.forename: P
authors.initials: P
authors.lastname: Razzore
authors.forename: S
authors.initials: S
authors.lastname: Bellone
authors.forename: C
authors.initials: C
authors.lastname: Baffoni
authors.forename: E
authors.initials: E
authors.lastname: Arvat
authors.forename: F
authors.initials: F
authors.lastname: Camanni
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000328:Adult; D001120:Arginine; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000009:adverse effects; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007018:Hypopituitarism / Q000503:physiopathology; D007328:Insulin / Q000009:adverse effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male
chemical_list: D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine