Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity

Ghigo, Ezio; Procopio, Massimo; Boffano, G. M.; Arvat, Emanuela; Valente, Francesca; Maccario, Mauro; Mazza, Enrico; Camanni, F.

doi:10.1016/0026-0495(92)90220-5

Cited by 77 publications

(60 citation statements)

References 31 publications

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“…A hypothalamic pathogenesis for reduced somatotrope activity in obese patients has been proposed A somatostatinergic hyperactivity has been suggested by some authors 10 but it is not supported by other data. 3,5,34 Also our present data showing that GHRH combined with a substance likely acting via inhibition of hypothalamic somatostatin, such as arginine, 28,29 fails to elicit a normal GH response in obesity, agree with other data 38 against the existence of an exaggerated somatostatinergic activity.…”

Section: Discussionsupporting

confidence: 88%

“…GH reserve in obesity M Maccario et al of impaired GHRH activity 5 while there is evidence indicating that hyperinsulinism and/or elevated free fatty acid levels, which are usually elevated in obesity 15,19,20 could play a major role in causing hyposomatotropinism acting via the hypothalamus or, more likely, at the pituitary level. 12,13,17,18,21,23,40 Con®rm-ing the metabolic pathogenesis of GH de®ciency in obesity there is the well known evidence that spontaneous and stimulated GH secretion are restored by weight loss 2,6 and that a clear inverse relationship exists between GH secretion and body mass.…”

Section: Discussionmentioning

confidence: 99%

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Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

et al. 1997

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OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH de®ciency. DESIGN: Stimulation with GHRH. (1 mg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH ARG was evaluated in a second session. SUBJECTS: Forty-®ve patients with simple obesity (OB 11 male and 34 female, age 40.5 AE AE 1.8 y, BMI 38.8 AE AE 1.1 kg/m 2 ), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6 AE AE 2.4 y, 24.7 AE AE 0.7 kg/m 2 ) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 AE AE 1.0 y, 21.6 AE AE 0.3 kg/m 2 ) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at 7 60 and 0 min, and than every 15 min up to 120 min. Basal IGF±I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF±I levels in OB were lower (P`0.005) than those in NS but higher (P`0.005) than those in GHD. Mean peak GH response to GHRH ARG in OB was clearly lower than that in NS (P`0.005) and higher (P`0.005) than that in GHD. Sixty±percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 mg/l) while 4% OB and only 53% GHD with GH responses lower than 3 mg/l, the limit under which GH replacement therapy of severe de®ciency is allowed. Good intraindividual reproducibility of the GH response to GHRH arginine test was present in all groups (OB: r 0.78, P`0.0001; GHD: r 0.57, P`0.003; NS: r 0.74, P`0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH de®ciency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH de®ciency.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

et al. 1997

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“…In the diagnostic approach for GH deficiency obesity presents a great limitation since it is characterized by a low response to all provocative stimuli for GH secretion (26)(27)(28)(29)(30)(31)(32)(33). In obesity reduction in the half-life of GH (43) as well as a significant decrease in the production and secretion of the hormone have been reported (44).…”

Section: Discussionmentioning

confidence: 99%

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

et al. 2005

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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. Design and 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 $ 25 and , 30 kg/m 2 ) and obese (BMI $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 mg/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 mg/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 mg/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.European Journal of Endocrinology 153 257-264

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“…This discrepancy may be due to differences in physique and body composition between patient populations in different countries. GH responses to stimulation tests are known to be influenced by obesity [21][22][23], BMI [24,25], and waist circumference [24]. Obesity is associated with a state of chronic somatostatin hypersecretion [23], and free fatty acids block GHRH stimulation [26,27], suppressing the GH peak in the stimulation tests.…”

Section: Disclosure Statementmentioning

confidence: 99%

“…Obesity is associated with a state of chronic somatostatin hypersecretion [23], and free fatty acids block GHRH stimulation [26,27], suppressing the GH peak in the stimulation tests. The ARG test is also affected by obesity [22,23], and free fatty acids reduce stimulated GH secretion [28]. Moreover, the ARG was generally given by intravenous infusion of 0.5 g/kg with a maximum of 30 g, so larger patients tended to have weaker stimulation with the ARG.…”

Section: Disclosure Statementmentioning

confidence: 99%

The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: A comparison

et al. 2013

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Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity

Cited by 77 publications

References 31 publications

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: A comparison

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