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

2005 ◽  
Vol 153 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Ginevra Corneli ◽  
Carolina Di Somma ◽  
Roberto Baldelli ◽  
Silvia Rovere ◽  
Valentina Gasco ◽  
...  

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/m2), overweight (BMI ≥25 and <30 kg/m2) and obese (BMI ≥30 kg/m2). 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 μg/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 μg/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 μg/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.

2011 ◽  
Vol 164 (5) ◽  
pp. 685-693 ◽  
Author(s):  
Fausto Bogazzi ◽  
Luca Manetti ◽  
Martina Lombardi ◽  
Clara Giovannetti ◽  
Valentina Raffaelli ◽  
...  

ObjectiveTo evaluate the impact of different peak GH cut-off limits after GHRH-Arg test, IGF1 measurement, or their combination in identifying patients with GH deficit (GHD).Design and patientsTotally, 894 normal subjects (used for determining IGF1 normative limits) and 302 patients with suspected GHD were included. Different peak GH cut-off limits (used by European (depending on body mass index (BMI)) or North American (4.1 μg/l) Endocrine Societies, by HypoCCs (2.5 μg/l), or with 95% specificity (based on BMI), Method 1, 2, 3, or 4 respectively) and IGF1 were considered.MethodsPeak GH after GHRH-Arg and IGF1.ResultsDifferent peak GH cut-off limits recognized different proportions of GHD (range, 24.8–62.9%). Methods 1 and 2 with high sensitivity recognized a higher proportion (95.5 and 92.5% respectively) of GHD among patients with three (T) pituitary hormone deficits (HD), whereas Method 4 (with high specificity) identified 96.7% normal subjects among those without pituitary HD; on the contrary, Method 4 identified only 75% GHD among patients with THD, whereas Method 1 recognized a high proportion (40%) of GHD among subjects without HD. Of the total patients, 82% with THD and 84.5% without HD were recognized as GHD or normal respectively by IGF1. Among the remaining patients with THD and normal IGF1, 75% was recognized as GHD by Method 1; among patients without HD and abnormal IGF1, 87.5% was identified as normal by Method 4. Overall, combination of IGF1 and Method 1 or Method 4 identified 95.5% GHD among patients with THD and 98.1% normal subjects among those without HD.ConclusionsSingle peak GH cut-offs have limits to sharply differentiate GHD from normal subjects; IGF1 may be used for selecting patients to be submitted to the GHRH-Arg test; the peak GH cut-off limits to be used for identifying healthy or diseased patients depend mainly on the clinical context.


2010 ◽  
Vol 162 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Marinella Tzanela ◽  
Dimitra Zianni ◽  
Kalliopi Bilariki ◽  
Alexandros Vezalis ◽  
Nikos Gavalas ◽  
...  

ObjectivesDiminished GH response to stimulation has been demonstrated in obesity, leading to erroneous diagnosis of GH deficiency. The aim of this study was to evaluate the influence of body mass index (BMI) on GH responsiveness in patients at risk for pituitary function deficits.MethodsA total of 59 healthy subjects and 75 patients with a pituitary insult underwent insulin tolerance test or pyridostigmine+GHRH test in order to assess GH secretory reserve. Normal subjects and patients were classified as normal weight (BMI <24.9 kg/m2), overweight (BMI 25–29.9 kg/m2), and obese (BMI >30 kg/m2).ResultsAll normal individuals with BMI <24.9 kg/m2 demonstrated adequate GH responses, while three of the 21 overweight (14.3%) and nine of the 28 obese subjects (32.1%) did not respond to GH stimulation. Among patients, four of 14 (28.6%) with BMI <24.9 kg/m2, 18 of 22 (81.8%) who were overweight, and 28 of 39 (71.7%) who were obese did not respond to GH stimulation. Of the 46 nonresponder patients with increased BMI, nine (19.6%) had normal insulin-like growth factor 1 (IGF1) values and no other pituitary hormone deficits, raising questions about the accuracy of somatotroph function assessment, while all nonresponders with BMI <24.9 kg/m2 had low IGF1 values and panhypopituitarism.ConclusionsOur results indicate that BMI >25 kg/m2 has a negative effect on GH response not only in normal healthy subjects but also in patients at risk for pituitary function deficit as well. Parameters such as IGF1 levels and anterior pituitary deficits should be taken into account to accurately assess GH status in these patients.


1994 ◽  
Vol 77 (5) ◽  
pp. 2231-2236 ◽  
Author(s):  
D. Gozal ◽  
R. Arens ◽  
K. J. Omlin ◽  
S. L. Ward ◽  
T. G. Keens

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.


2004 ◽  
Vol 89 (7) ◽  
pp. 3397-3401 ◽  
Author(s):  
Vivien S. Bonert ◽  
Janet D. Elashoff ◽  
Philip Barnett ◽  
Shlomo Melmed

Abstract GH secretion is decreased in obese subjects, whereas age-adjusted IGF-I concentrations are normal. This study was undertaken to rigorously delineate the extent of obesity [elevated body mass index (BMI)] associated with decreased somatotrope secretory function resulting in apparent adult GH deficiency. The peak GH response evoked by combined arginine (0.5 g/kg infused iv over 30 min) and GHRH (1 μg/kg iv bolus) was measured in 59 healthy male subjects with BMIs ranging from normal to obese. BMI correlated with the peak evoked GH response (Pearson r = −0.59; P &lt; 0.01), and the percentage of subjects exhibiting an abnormal evoked GH response, i.e. less than 9 ng/ml, increased from 5% for those with a BMI less than 25 (normal), to 13% for those with a BMI of 25–26.9 (mildly overweight), to 33% for those with a BMI of 27–29.9 (moderately overweight), and to 64% for those with a BMI of 30 or more (obese). BMI is a major determinant of evoked adult GH response to provocative testing. The diagnosis of adult GH deficiency using the evoked GH response in patients with even mild BMI elevation does not accurately distinguish normal from deficient responses and may result in the erroneous classification of obese subjects as GH deficient and thus unnecessarily requiring GH replacement.


2006 ◽  
Vol 154 (3) ◽  
pp. 459-466 ◽  
Author(s):  
Emanuel R Christ ◽  
Michael H Cummings ◽  
Michael Stolinski ◽  
Nicola Jackson ◽  
Peter J Lumb ◽  
...  

Background: Epidemiological studies suggest that hypopituitary patients have an increased risk for cardiovascular mortality. The dyslipidaemia associated with this condition is often characterised by an increase in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol (LDL-C) and may contribute to these findings. The underlying mechanisms are not fully elucidated. Materials and Methods: LDL apolipoprotein B (apoB) production rate and metabolic clearance rate were measured in seven patients with hypopituitarism (including GH deficiency) under stable conventional replacement therapy (three males and four females; age 40–16.1 years; body mass index 29.0–6.1 kg/m2 (means ± s.d.)) and seven age-, gender- and body mass index-matched control subjects with an infusion of 1-13C-leucine. Fasting lipid profile and lipid composition of LDL were also measured. Results: Fasting TC, triglycerides (TG), high-density lipoprotein-C, LDL-C and free fatty acid concentrations were not different between hypopituitary patients and control subjects. LDL-TG (P < 0.006) and LDL-TG/LDL apoB ratio (P < 0.02) were significantly increased in hypopituitary patients. LDL apoB pool size was not statistically different between patients and control subjects. In the hypopituitary patients, LDL apoB metabolic clearance rate (P < 0.05) and LDL apoB production rate (P < 0.02) were lower than in the control subjects. Conclusions: The present results suggest that LDL apoB turnover and LDL composition is altered in hypopituitary patients. Whether these findings explain the increased risk for cardiovascular disease in hypopituitary patients remains to be established.


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.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
K Giesinger ◽  
JM Giesinger ◽  
DF Hamilton ◽  
J Rechsteiner ◽  
A Ladurner

Abstract Background Total knee arthroplasty is known to successfully alleviate pain and improve function in endstage knee osteoarthritis. However, there is some controversy with regard to the influence of obesity on clinical benefits after TKA. The aim of this study was to investigate the impact of body mass index (BMI) on improvement in pain, function and general health status following total knee arthroplasty (TKA). Methods A single-centre retrospective analysis of primary TKAs performed between 2006 and 2016 was performed. Data were collected preoperatively and 12-month postoperatively using WOMAC score and EQ-5D. Longitudinal score change was compared across the BMI categories identified by the World Health Organization. Results Data from 1565 patients [mean age 69.1, 62.2% women] were accessed. Weight distribution was: 21.2% BMI < 25.0 kg/m2, 36.9% BMI 25.0–29.9 kg/m2, 27.0% BMI 30.0–34.9 kg/m2, 10.2% BMI 35.0–39.9 kg/m2, and 4.6% BMI ≥ 40.0 kg/m2. All outcome measures improved between preoperative and 12-month follow-up (p < 0.001). In pairwise comparisons against normal weight patients, patients with class I-II obesity showed larger improvement on the WOMAC function and total score. For WOMAC pain improvements were larger for all three obesity classes. Conclusions Post-operative improvement in joint-specific outcomes was larger in obese patients compared to normal weight patients. These findings suggest that obese patients may have the greatest benefits from TKA with regard to function and pain relief one year post-op. Well balanced treatment decisions should fully account for both: Higher benefits in terms of pain relief and function as well as increased potential risks and complications. Trial registration This trial has been registered with the ethics committee of Eastern Switzerland (EKOS; Project-ID: EKOS 2020–00,879)


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