scholarly journals Comparison between Insulin-Induced Hypoglycemia and Growth Hormone (GH)-Releasing Hormone + Arginine as Provocative Tests for the Diagnosis of GH Deficiency in Adults1

1998 ◽  
Vol 83 (5) ◽  
pp. 1615-1618 ◽  
Author(s):  
G. Aimaretti ◽  
G. Corneli ◽  
P. Razzore ◽  
S. Bellone ◽  
C. Baffoni ◽  
...  

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 μg/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 μg/L, whereas in our lab, that to GHRH+ARG is 16.5 μg/L. In hypopituitary adults, the mean peak GH response to ITT (1.5 ± 0.2 μg/L, range: 0.1–8.5μ g/L) was lower (P < 0.001) than that to GHRH+ARG (3.0 ± 0.4 μg/L, range 0.1–12.0 μg/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 μg/L after ITT; moreover, 3 other patients (7%) had GH peaks, after ITT, higher than 3 μg/L. On the other hand, after GHRH+ARG, all patients had GH peaks lower than 16.5 μg/L, whereas 21/40 (52.5%) had GH peaks higher than 3 μg/L. Because 3 μg/L is the arbitrary cut-off for ITT, the third centile limit of which is 5μ g/L, we arbitrarily considered 9 μg/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.

1999 ◽  
Vol 84 (8) ◽  
pp. 2633-2637
Author(s):  
M. Gasperi ◽  
G. Aimaretti ◽  
G. Scarcello ◽  
G. Corneli ◽  
C. Cosci ◽  
...  

GH deficiency (GHD) in adults must be shown by provocative testing of GH secretion. Insulin-induced hypoglycemia (ITT) is the test of choice, and severe GHD, treated with recombinant human GH replacement, is defined by a GH peak response to ITT of less than 3 μg/L. GHRH plus arginine (ARG) is a more provocative test and is as sensitive as ITT provided that appropriate cut-off limits are assumed. GH secretagogues are a family of peptidyl and nonpeptidyl GH-releasing molecules that strongly stimulate GH secretion and, even at low doses, truly synergize with GHRH. Our aim was to verify the diagnostic reliability of the hexarelin (HEX; 0.25 μg/kg, iv) and GHRH (1 μg/kg, iv) test for the diagnosis of adult GHD. To this goal, in the present study we 1) defined the normal ranges of the GH response to GHRH+HEX in a group of normal young adult volunteers (NS; n = 25; 18 men and 7 women; age, 28.5 ± 0.6 yr) and in 11 of them verified its reproducibility in a second session, and 2) compared the GH response to GHRH+HEX with that to ITT in a group of normal subjects (n = 33; 12 men and 21 women; age, 34.1 ± 1.5 yr) and hypopituitaric adults with GHD (n = 19; 10 men and 9 women; age, 39.9 ± 2.2 yr; GH peak <5 μg/L after ITT). The GH response to GHRH+ARG was also evaluated in all GHD and in 77 normal subjects (40 men and 37 women; age, 28.1 ± 0.6 yr). The mean GH peak after GHRH+HEX in NS was 83.6 ± 4.5 μg/L; the third and first percentile limits of the normal GH response were 55.5 and 51.2 μg/L, respectively). The GH response to GHRH+HEX in NS showed good intraindividual reproducibility. In GHD the mean GH peak after GHRH+HEX (2.6 ± 0.7 μg/L) was similar to that after GHRH+ARG (3.6 ± 1.0 μg/L), and both were higher (P < 0.001) than that after ITT (0.6± 0.1 μg/L); the GH responses to GHRH+HEX were positively associated with those to ITT and GHRH+ARG. Analyzing individual GH responses, 100% had severe GHD after ITT (GH peak, <3 μg/L). After GHRH+HEX all GHD had GH peaks below the third percentile limit of normality appropriate for this test (i.e. 55.5 μg/L). Thirteen of 19 (68.4%) GHD subjects had GH peaks below 3 μg/L after GHRH+HEX but all 19 (100%) had GH peaks below the first percentile limit of normality (i.e. 51.2 μg/L). The GH responses to GHRH+HEX were highly concordant with those after GHRH+ARG. In conclusion, the present results define normal limits of the GH response to stimulation with low dose HEX+GHRH in normal adults and show that this test is as sensitive as ITT for the diagnosis of adult GHD provided that appropriate cut-off limits are considered.


2000 ◽  
pp. 347-352 ◽  
Author(s):  
G Aimaretti ◽  
C Baffoni ◽  
L DiVito ◽  
S Bellone ◽  
S Grottoli ◽  
...  

Classical provocative stimuli of GH secretion such as insulin-induced hypoglycaemia, arginine, clonidine, glucagon and levodopa have been widely used in clinical practice for approximately 30 years. On the other hand, in the last 10 years new potent stimuli of GH secretion have been proposed, but an extensive comparison with the classical ones has rarely been performed, at least in adults. In order to compare the GH-releasing activity of old and new provocative stimuli of GH secretion, and to define the normative values of the GH response, in 178 normal adults (95 males, 83 females; age range: 20-50 years, all within +/-15% of their ideal body weight), we studied the GH response to: insulin-induced hypoglycaemia (ITT, 0.1IU/kg i.v.), arginine (ARG, 0.5g/kg i.v.), clonidine (CLO, 300 microg/kg p.o.), glucagon (GLU, 1mg i.m.), pyridostigmine (PD, 120mg p.o.), galanin (GAL, 80pmol/kg per min), GH-releasing hormone (GHRH, 1 microg/kg i.v.), GHRH+ARG, GHRH+PD, hexarelin, a GH-releasing protein (HEX, 2 microg/kg i.v.) and GHRH+HEX (0.25 microg/kg i.v.). The mean (+/-s.e.m.) peak GH response to ITT (21.8+/-2.8, range: 3.0-84.0 microg/l) was similar to those to ARG (18.0+/-1.6, range: 2.9-39.5 microg/l) or GLU (20. 5+/-2.2, range: 10.6-36.9 microg/l) which, in turn, were higher (P<0. 001) than those to CLO (8.2+/-1.6, range: 0.3-21.5 microg/l), PD (9. 6+/-1.1, range: 2.2-33.0 microg/l) and GAL (9.3+/-1.1, range: 3.9-18. 3 microg/l). The GH response to GHRH (19.1+/-1.5, range: 2.7-55.0 microg/l) was similar to those after ITT, ARG or GLU but clearly lower than those after GHRH+ARG (65.9+/-5.5, range: 13.8-171.0 microg/l) and GHRH+PD (50.2+/-4.6, range: 17.7-134.5 microg/l) which, in turn, were similar. The GH response to HEX (55.3+/-5.5, range: 13.9-163.5 microg/l) was similar to those after GHRH+ARG and GHRH+PD but lower (P<0.001) than that after GHRH+HEX (86.0+/-4.3, range: 49. 0-125.0 microg/l) which was the most potent stimulus of GH secretion. In this adult population the third centile limits of peak GH response to various stimuli were the following: ITT: 5.3; ARG: 2.9; CLO: 1.5; GLU: 7.6; PD: 2.2; GAL: 4.0; GHRH: 5.0; GHRH+ARG: 17.8; GHRH+PD: 17.9; HEX: 21.6; GHRH+HEX: 57.1. These results confirm that, among classical provocative tests of GH secretion, ITT followed by ARG and GLU are the most potent ones and possess clear limits of normality. GHRH+ARG or PD and HEX are strong stimuli of GH secretion which, however, is maximally stimulated by a combination of GHRH and a low dose of HEX. It is recommended that each test is used with appropriate cut-off limits.


1989 ◽  
Vol 121 (2) ◽  
pp. 290-296 ◽  
Author(s):  
Izumi Sukegawa ◽  
Naomi Hizuka ◽  
Kazue Takano ◽  
Kumiko Asakawa ◽  
Reiko Horikawa ◽  
...  

Abstract. Nocturnal urinary growth hormone values were measured by a sensitive enzyme immunoassay in normal adults, patients with GH deficiency, patients with Turner's syndrome, normal but short children who had normal plasma GH responses to provocative tests, and patients with acromegaly. The mean nocturnal urinary GH values in patients with acromegaly were significantly greater than those in normal adults (1582.3 ± 579.8 vs 53.5 ± 8.6 pmol/mmol creatinine (± sem); p < 0.05). In the normal but short children and patients with Turner's syndrome, the mean nocturnal urinary GH values were 83.1 ± 5.2 and 79.8 ± 29.5 pmol/mmol creatinine, respectively. In patients with GH deficiency, the nocturnal urinary GH values were undetectable (< 5.3 pmol/mmol creatinine) except in one patient where the value was 6.3 pmol/mmol creatinine. The nocturnal urinary GH values of the patients with GH deficiency were significantly lower than those of the other groups (p < 0.05). In normal but short children, the nocturnal urinary GH values correlated significantly with mean plasma nocturnal GH concentrations (r = 0.76, p < 0.001), and 24-hour urinary GH values (r = 0.84, p < 0.001), respectively. In 4 patients with GH deficiency who had circulating anti-hGH antibody, the urinary GH values were also undectable. These data indicate that nocturnal urinary GH value reflects endogenous GH secretion during collection time, and that measurement of the nocturnal urinary GH values is a useful method for screening of patients with GH deficiency and acromegaly.


2000 ◽  
Vol 85 (10) ◽  
pp. 3693-3699
Author(s):  
G. Aimaretti ◽  
C. Baffoni ◽  
S. Bellone ◽  
L. Di Vito ◽  
G. Corneli ◽  
...  

Within an appropriate clinical context, severe GH deficiency (GHD) in adults has to be defined biochemically by provocative testing of GH secretion. Patients with childhood-onset GHD need retesting in late adolescence or young adulthood to verify whether they have to continue recombinant human GH treatment. GHRH + arginine (GHRH+ARG) is the most reliable alternative to the insulin-induced hypoglycemia test (ITT) as a provocative test for the diagnosis of GHD in adulthood, provided that appropriate cut-off limits are assumed (normal limits, 16.5 μg/L as 3rd and 9.0 μg/L as 1st centile). We studied the GH response to a single GHRH (1 μg/kg iv) + ARG (0.5 g/kg iv) test in 62 young patients who had undergone GH replacement in childhood, based on the following diagnosis: 1) organic hypopituitarism with GHD (oGHD)[ n = 18: 15 male (M), 3 female (F); age, 26.8 ± 2.2 yr; GH peak &lt; 10 μg/L after two classical tests]; 2) idiopathic isolated GHD (iGHD) [n = 23 (15 M, 8 F); age, 23.0 ± 1.5 yr; GH peak &lt; 10 μg/L after two classical tests]; and 3) GH neurosecretory dysfunction (GHNSD) [n = 21 (10 M, 11 F); age, 25.1 ± 1.6 yr; GH peak &gt; 10 μg/L after classical test but mGHc &lt; 3 μg/L]. The GH responses to GHRH+ARG in these groups were also compared with that recorded in a group of age-matched normal subjects (NS) [n = 48 (20 M, 28 F); age, 27.7 ± 0.8 yr]. Insulin-like growth factor I levels in oGHD subjects (61.5 ± 13.7μ g/L) were lower (P &lt; 0.001) than those in iGHD subjects (117.2 ± 13.1 μg/L); the latter were lower than those in GHNSD subjects (210.2 ± 12.9 μg/L), which, in turn, were similar to those in NS (220.9 ± 7.1 μg/L). The mean GH peak after GHRH+ARG in oGHD (2.8 ± 0.8 μg/L) was lower (P &lt; 0.001) than that in iGHD (18.6 ± 4.7μ g/L), which, in turn, was clearly lower (P &lt; 0.001) than that in GHNSD (31.3 ± 1.6 μg/L). The GH response in GHNSD was lower than that in NS (65.9 ± 5.5 μg/L), but this difference did not attain statistical significance. With respect to the 3rd centile limit of GH response in young adults (i.e. 16.5 μg/L), retesting confirmed GHD in all oGHD, in 65.2% of iGHD, and in none of the GHNSD subjects. With respect to the 1st centile limit of GH response (i.e. 9.0 μg/L), retesting demonstrated severe GHD in 94% oGHD and in 52.1% of iGHD. All oGHD and iGHD with GH peak after GHRH+ARG lower than 9 μg/L had also GH peak lower than 3 μg/L after ITT. In the patients in whom GHD was confirmed by retesting, the mean GH peak after GHRH+ARG was higher than that after ITT (3.4 ± 0.5 vs. 1.9 ± 0.4). In conclusion, given appropriate cut-off limits, GHRH+ARG is as reliable as ITT for retesting patients who had undergone GH treatment in childhood. Among these patients, severe GHD in adulthood is generally confirmed in oGHD, is frequent in iGHD, but never occurs in GHNSD.


2006 ◽  
Vol 154 (5) ◽  
pp. 659-666 ◽  
Author(s):  
S Pekic ◽  
M Doknic ◽  
D Miljic ◽  
M Joksimovic ◽  
J Glodic ◽  
...  

Objective: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly. Design and methods: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test - oral glucose tolerance test (OGTT) and the GH provocation test - ghrelin test (1 μg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects. Results: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 μg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 μg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (±s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 ± 0.2 μg/l vs 20.1 ± 2.4 μg/l vs 31.1 ± 2.5 μg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different. Conclusions: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.


1996 ◽  
Vol 135 (5) ◽  
pp. 568-572 ◽  
Author(s):  
Maria Rosa Valetto ◽  
Jaele Bellone ◽  
Claudia Baffoni ◽  
Paola Savio ◽  
Gianluca Aimaretti ◽  
...  

Valetto MR, Bellone J, Baffoni C, Savio P, Aimaretti G, Gianotti L, Arvat E, Camanni F, Ghigo E. Reproducibility of the growth hormone response to stimulation with growth hormone-releasing hormone plus arginine during lifespan. Eur J Endocrinol 1996;135:568–72. ISSN 0804–4643 The reliability and reproducibility of provocative stimuli of growth hormone (GH) secretion in the diagnosis of GH deficiency are still controversial both in childhood and in adulthood. The combined administration of GH-releasing hormone (GHRH) and arginine (ARG), which likely acts via inhibition of hypothalamic somatostatin release, is one of the most potent stimuli known so far and has been proposed recently as the best test to explore the maximal somatotrope capacity of somatotrope cells. However, it is well known that, usually, provocative stimuli of GH secretion suffer from poor reproducibility and that of the GHRH + ARG test has still to be verified. We aimed to verify the between- and within-subject variability of the GH response to the GHRH + ARG test in normal subjects during their lifespan as well as in hypopituitaric patients with GH deficiency (GHD). In 10 normal children (C: six male and four female, age 12.3 ± 0.9 years, body mass index (BMI) = 16.6 ± 0.7 kg/m2, pubertal stages I-III), 18 normal young adults (Y: ten male and eight female, age 31.1 ± 1.3 years, BMI = 21.4 ± 0.4 kg/m2), 12 normal elderly subjects (E: two male and ten female, age 74.4 ± 1.8 years, BMI= 22.6 ± 0.6 kg/m2) and 15 panhypopituitaric GH-deficient patients (GHD: nine male and six female, age 40.9 ± 4.1 years, BMI= 22.7 ± 1.0 kg/m2), we studied the inter- and intra-individual variability of the GH response to GHRH (1 μg/kg iv) + ARG (0.5 g/kg iv) in two different sessions at least 3 days apart. The GH responses to GHRH + ARG in C (1st vs 2nd session: 61.6 ± 8.1 vs 66.5 ± 9.4 μg/l), Y (70.4 ± 10.1 vs 76.2 ± 10.7 μg/l) and E (57.9 ± 14.8 vs 52.1 ± 8.0 μg/l) were similar and reproducible in all groups. The somatotrope responsiveness to GHRH + ARG also showed a limited within-subject variability (r = 0.71, 0.90 and 0.89 and p < 0.02, 0.0005 and 0.0005 for C, Y and E, respectively). Similarly in GHD, the GH response to the GHRH + ARG test showed a good inter- (1st vs 2nd session: 2.3 ± 0.5 vs 2.2 ± 0.6 μg/l) and intra-individual reproducibility (r = 0.70, p < 0.005). The GHRH + ARG-induced GH responses in GHD were markedly lower (p < 0.0005) than those in age-matched controls and no overlap was found between GH peak responses in GHD and normal subjects. In normal subjects, the GH response to GHRH + ARG is very marked, independent of age and shows limited inter- and intra-individual variability. The GH response to the GHRH + ARG test is strikingly reduced in panhypopituitaric patients with GHD, in whom the low somatotrope responsiveness is reproducible. Thus, these findings strengthen the hypothesis that GHRH + ARG should be considered the most reliable test to evaluate the maximal secretory capacity of somatotrope cells and to distinguish normal subjects from GHD patients in adulthood. E. Ghigo, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126, Torino, Italy


1985 ◽  
Vol 110 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Naomi Hizuka ◽  
Kazue Takano ◽  
Kazuo Shizume ◽  
Izumi Tanaka ◽  
Noriko Honda ◽  
...  

Abstract. Pituitary growth hormone (GH) responses during a 10-h iv infusion of saline or human GH-releasing factor (hGRF-44) at 500 ng/kg/h, followed by an iv bolus injection of hGRF-44 at 2 μg/kg body weight, were studied in 10 patients with GH deficiency. During saline infusion in 4 patients, small plasma GH increase were observed in 2 patients. However, during hGRF infusion in 6 patients, up to 4 or 13 pulses of GH secretion were observed. The mean integrated GH pulse area during hGRF infusion was 22.5 ± 5.2 (se) ng/ml × h, which was greater than that obtained during saline infusion. Plasma somatomedin C levels did not increase after hGRF infusion. After saline or hGRF infusion all patients responded to an iv bolus injection of the peptide. These results indicate that hGRF infusion augments GH secretion by increasing the number and amplitude of GH pulses and that the infusion does not cause pituitary somatotrophs to lose their capacity to respond to hGRF subsequently.


1989 ◽  
Vol 120 (1) ◽  
pp. 31-36 ◽  
Author(s):  
L. Lima ◽  
V. Arce ◽  
N. Lois ◽  
C. Fraga ◽  
M.J. Lechuga ◽  
...  

Abstract. The effects of changes in circulating gonadal steroids on GH secretion elicited by GHRH challenge (1 μg/kg) in normal adults volunteers (aged 18–24 years), were evaluated in 10 women and 10 men before and after gonadal blockade was achieved by a GnRH agonist (1500 μg/day by nasal spray for 40 days). To see if the effect of testosterone on GH secretion was dependent on its aromatization to estradiol (E2), GHRH tests were performed in 7 normal men prior to administration of testosterone enanthate (250 mg im), 8 days after this treatment had began, and again after E2 receptor blockade with tamoxifen (30 mg for 2 days plus 10 mg on the third day 2 h before the GHRH test, po) administered 8 days after testosterone enanthate. The study of the functional status of the somatotropes at the time of GHRH testing was made according to our previous postulate. Short-term gonadal blockade did not affect the parameters of GH response to GHRH in neither women nor men. Thus, the functional blockade of the gonads may be advisable as an adjunct therapy in the treatment of hypothalamic GH-deficiency during the peripubertal stage. In the other group of men, administration of testosterone enanthate significantly increased GHRH-elicited GH release, but this was reverted after E2 receptor blockade. Since the hypothalamic-somatotrope rhythm was altered by both these farmacological manipulations, it appears that testosterone acts on GH release mainly at the suprapituitary level, and that this action is secondary to its aromatization to E2


2012 ◽  
Vol 32 (2) ◽  
pp. 154-162 ◽  
Author(s):  
SK Kota ◽  
S Jammula ◽  
K Gayatri ◽  
SK Kota ◽  
PR Tripathy ◽  
...  

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. Serum IGF-I levels are monitored during GH replacement treatment in subjects with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GHrelated side-effects. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 hours and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. We hereby review the various literatures at disposal justifying the use of IGF-1 and IGBP3 for diagnosis of growth hormone deficiency.Data Source: We searched PUBMED and MEDLINE database for relevant articles including key words. References of each article were further reviewed for final synthesis of the manuscript.J Nepal Paediatr Soc 2012;32(2):154-162 doi: http://dx.doi.org/10.3126/jnps.v32i2.5342


2010 ◽  
Vol 163 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Massimo Scacchi ◽  
Federica Orsini ◽  
Agnese Cattaneo ◽  
Alice Grasso ◽  
Barbara Filippini ◽  
...  

BackgroundThe diagnosis of GH deficiency (GHD) in obese patients is complicated by the reduced 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. The aim of the study was to investigate the effect of acute pharmacological blockade of lipolysis on the GH response to GHRH+arginine in obese patients.Patients and methodsTwo 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.ResultsThe mean GH peak after GHRH+arginine was significantly lower in hypopituitary patients than in subjects with essential obesity. Acipimox significantly increased the mean GH response in patients with essential obesity, but not in hypopituitary subjects. All hypopituitary patients and 7/14 patients with essential obesity displayed GH peaks lower than 4.2 μg/l after GHRH+arginine: the GH response to the test increased after acipimox pretreatment in five of these seven essentially obese subjects. After acipimox administration, free fatty acids (FFAs) significantly fell in both groups with comparable mean absolute decreases. All IGF1 values were normal in both groups of subjects.ConclusionsOur 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. The current criterion for the diagnosis of GHD in obese patients may be misleading. Indeed, subjects affected by third degree obesity, like most of our patients, may be erroneously classified as really GH-deficient and started on an expensive unjustified treatment. It appears therefore that the current criteria for the diagnosis of GHD in obesity should be reconsidered in the light of further studies also taking into account different body mass index groups.


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