The diagnosis of GH deficiency in obese patients: what help from pharmacological blockade of lipolysis?
Federica Orsini, Agnese Cattaneo, Alice Grasso, Barbara Filippini, Maria Letizia Fatti, Mirella Moro, Massimo Scacchi & Francesco Cavagnini
The diagnostic approach to GH deficiency (GHD) in obese patients is complicated by the reduced spontaneous and stimulated GH secretion associated with overweight. A GH response to GHRH+arginine lower than 4.2 μg/l is currently considered indicative of GHD in obesity (Corneli et al., Eur J Endocrinol 2005). Aim of the study was to verify the diagnostic validity of this cut-off value by investigating the effect of acute pharmacological blockade of lipolysis on the GH response to GHRH + arginine in obese patients.
Patients and methods: Two groups of patients were studied: 12 obese patients with proven GHD and 14 patients with essential obesity. On separate occasions two tests were carried out in each patient: GHRH+arginine, and GHRH+arginine preceded by acipimox 250 mg, given orally at −270 and −60 min. IGF1 and FFA values were measured on serum samples collected at baseline; FFA were also assayed after acipimox administration.
Results: The mean GH peak in response to GHRH+arginine was significantly lower in obese hypopituitary patients than in subjects with essential obesity (1.63±1.37 vs 5.99±4.38 μg/l, P<0.01). Acipimox pretreatment significanly increased the GH response to the combined test in patients with essential obesity (mean GH peak from 5.99±4.38 to 9.31±3.86 μg/l, P<0.05), but not in hypopituitary subjects (mean GH peak from 1.63±1.37 to 2.20±1.70 μg/l, NS). Seven out of 14 patients with essential obesity GH peaks lower than 4.2 μg/l after GHRH +arginine. The GH response clearly increased after acipimox premedication in five of them. Baseline circulating FFA were superimposable in patients with essential obesity and in hypopituitary subjects with a comparable decrease in both groups after acipimox administration. All IGF SDS values were normal in both groups of subjects.
Conclusions: Our study has demonstrated that the acipimox-induced acute reduction of circulating FFA levels increases mean somatotropin response to GHRH+arginine in patients with essential obesity, whereas it has no effect in hypopituitary subjects. Additional large studies revising GH cut-off values following GHRH+arginine according to different BMI groups within the population of obese patients are needed, in order to avoid the possibility that subjects affected by severe obesity are erroneously classified as really GH-deficient.