The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index.
OBJECTIVE
The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population.


METHODS
The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI <25 kg/m(2)), overweight (BMI > or = 25 and <30 kg/m(2)) and obese (BMI > or =30 kg/m(2)). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency.


RESULTS
In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 mug/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 mug/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 mug/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion.


CONCLUSIONS
In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.
Corneli
Ginevra
G
Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, University of Turin, Italy.
Di Somma
Carolina
C
Baldelli
Roberto
R
Rovere
Silvia
S
Gasco
Valentina
V
Croce
Chiara Giulia
CG
Grottoli
Silvia
S
Maccario
Mauro
M
Colao
Annamaria
A
Lombardi
Gaetano
G
Ghigo
Ezio
E
Camanni
Franco
F
Aimaretti
Gianluca
G
D000328:Adult; D001120:Arginine; D015992:Body Mass Index; D003940:Diagnostic Techniques, Endocrine / Q000592:standards; D005260:Female; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000175:diagnosis*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine