The diagnosis of GH deficiency in obese patients: a reappraisal with GHRH plus arginine testing after pharmacological blockade of lipolysis

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.

Download Full-text

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

Acta Endocrinologica ◽

10.1530/eje.1.01967 ◽

2005 ◽

Vol 153 (2) ◽

pp. 257-264 ◽

Cited By ~ 217

Author(s):

Ginevra Corneli ◽

Carolina Di Somma ◽

Roberto Baldelli ◽

Silvia Rovere ◽

Valentina Gasco ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Gh Deficiency ◽

Pituitary Hormone ◽

Obese Patients ◽

Releasing Hormone ◽

Gh Secretion ◽

Control Subjects ◽

Optimal Separation ◽

And Control

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.

Download Full-text

The levels of leptin, adiponectin, and free fatty acids in the patients of different body weight presenting with myocardial infarction and elevated ST segment

Problems of Endocrinology ◽

10.14341/probl20135938-12 ◽

2013 ◽

Vol 59 (3) ◽

pp. 8-12

Author(s):

L V Kvitkova ◽

D A Borodkina ◽

O V Gruzdeva ◽

O L Barbarash ◽

A A Silonova ◽

...

Keyword(s):

Myocardial Infarction ◽

Body Mass Index ◽

Fatty Acids ◽

Waist Circumference ◽

Free Fatty Acids ◽

Reference Values ◽

Obese Patients ◽

Group 3 ◽

Group 2 ◽

Group 1

The present study involed the patients (n=100) presenting with myocardial infarction (MI). Based on the body mass index, they were allocated to three groups: those with normal body mass index (BMI) (18.5≤BMI< 25 kg/m2; n=32; group 1), overweight patients (25≤BMI <30 kg/m2; n=42; group 2), and obese patients (BMI≤30 kg/m2; n=27; group 3). The laboratory studies included the measurement of serum adipocytokine levels (leptin, adiponectin, and free fatty acids (FFA)) in conjunction with the evaluation of insulin resistance (IR). All the patients regardless of BMI had the waist circumference in excess of the upper limit of the normal gender-specific values. Deviations from the reference values of leptin, adiponectin, and FFA levels were observed in 65.6% of the patients with normal BWI, in 69.0% of the overweight patients, and in 70.3% of the obese patients. In the patients of all the three groups, significant correlation was documented between waist circumference and the levels of leptin (group 1: r=0.3100, p=0.00; group 2: r=0.32, p=0.00; group 3: r=0.37, p=0.03) and adiponectin (group 1: r=-0.43, p=0.00; group 2: r=-0.35, p=0.04; group 3: r=-0.18, p=0.01). Moreover, the waist circumference significantly correlated with the occurrence of IR (group 1: r=0.11, p=0.04; group 2: r=0.45, p=0.00, group 3: r=0.34, p=0.03). It is concluded that the observed deviations of the parameters of interest from the respective reference values suggest disturbances in the metabolic and secretory functions of the visceral adipose tissue associated with the enlargement of its volume).

Download Full-text

Body Mass Index Determines Evoked Growth Hormone (GH) Responsiveness in Normal Healthy Male Subjects: Diagnostic Caveat for Adult GH Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2003-032213 ◽

2004 ◽

Vol 89 (7) ◽

pp. 3397-3401 ◽

Cited By ~ 83

Author(s):

Vivien S. Bonert ◽

Janet D. Elashoff ◽

Philip Barnett ◽

Shlomo Melmed

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Gh Deficiency ◽

Healthy Male ◽

Gh Secretion ◽

Adult Gh Deficiency ◽

Igf I ◽

Obese Subjects ◽

Male Subjects

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 < 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.

Download Full-text

Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.6.2711 ◽

1993 ◽

Vol 74 (6) ◽

pp. 2711-2717 ◽

Cited By ~ 33

Author(s):

D. A. MacLean ◽

T. E. Graham

Keyword(s):

Fatty Acids ◽

Amino Acid ◽

Free Fatty Acids ◽

Amino Acid Supplementation ◽

Placebo Administration ◽

Branched Chain Amino Acid ◽

Placebo Trial ◽

The Mean ◽

Branched Chain ◽

Exercise In Humans

This study examined the effects of branched-chain amino acid (BCAA) supplementation on amino acid and ammonia (NH3) responses during prolonged exercise in humans. Seven men cycled for 60 min at 75% of maximal O2 uptake after 45 min of either placebo (dextrose, 77 mg/kg) or BCAA (leucine + isoleucine + valine, 77 mg/kg) supplementation. Plasma samples (antecubital vein) were collected at rest and during exercise and analyzed for plasma NH3 and amino acids, whole blood glucose and lactate, and serum free fatty acids and glycerol. After BCAA administration, plasma BCAA levels increased from 375 +/- 22 to 760 +/- 80 microM (P < 0.05) by the onset of exercise and remained elevated throughout the experiment. Plasma NH3 concentrations increased continually during exercise for both trials and were higher (P < 0.05) after BCAA supplementation than after placebo administration. The mean plasma NH3 increase from rest to 60 min was 79 +/- 10 and 53 +/- 4 microM for BCAA and placebo trials, respectively. Plasma alanine and glutamine concentrations were elevated (P < 0.05) during exercise for both treatments. However, only glutamine concentrations were greater (P < 0.05) for BCAA trial than for placebo trial during exercise. There were no significant differences between treatments for glucose, lactate, free fatty acids, and glycerol or any other plasma amino acid. These data suggest that increased BCAA availability before exercise, when initial muscle glycogen is normal, results in significantly greater plasma NH3 responses during exercise than does placebo administration.

Download Full-text

Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

Acta Endocrinologica ◽

10.1530/acta.0.1220385 ◽

1990 ◽

Vol 122 (3) ◽

pp. 385-390 ◽

Cited By ~ 16

Author(s):

R. C. Castro ◽

J. G. H. Vieira ◽

A. R. Chacra ◽

G. M. Besser ◽

A. B. Grossman ◽

...

Keyword(s):

Growth Hormone ◽

Acetylcholinesterase Inhibitor ◽

Random Order ◽

Normal Subjects ◽

Obese Patients ◽

Releasing Hormone ◽

Gh Secretion ◽

Obese Subjects ◽

Higher Doses ◽

Hormone Responsiveness

Abstract Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1–29) NH2 100 μg iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 ± 4 vs 44 ± 16 μg/l; mean ± sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 ± 5 vs 77 ± 20 μg/l, respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.

Download Full-text

P373Arterial stiffness changes in patients with obesity and atrial fibrillation

EP Europace ◽

10.1093/europace/euaa162.336 ◽

2020 ◽

Vol 22 (Supplement_1) ◽

Author(s):

A Tarzimanova ◽

V I Podzolkov ◽

A E Bragina ◽

M V Pisarev ◽

R G Gataulin ◽

...

Keyword(s):

Atrial Fibrillation ◽

Body Mass Index ◽

Arterial Stiffness ◽

Sinus Rhythm ◽

Body Mass ◽

Paroxysmal Atrial Fibrillation ◽

Obese Patients ◽

Waist To Hip Ratio ◽

Group I ◽

The Mean

Abstract Objective To study the changes in arterial stiffness in patients with obesity and paroxysmal atrial fibrillation (AF). Materials and methods The study included 82 obese patients. Forty-two of them (group I) had paroxysmal AF, their mean age was 60.9 ± 6.2 years. The control group (group II) included 40 obese patients in sinus rhythm with the mean age of 57.2 ± 6.5 years. We studied arterial stiffness using cardio-ankle vascular index (CAVI) measured by the VaSera device (VS-1000) in all the patients. Patients from group I were evaluated after 3 days of sinus rhythm restoration and maintenance. We also measured the anthropometric indicators which included body mass index, waist circumference, abdominal sagittal diameter, waist-to-hip and waist-to-height ratios. Results There were no significant differences in body mass index between 2 groups. The waist-to-hip ratio was significantly higher in patients with obesity and paroxysmal atrial fibrillation than in obese patients in sinus rhythm and was 1.37 ± 0.09 and 0.84 ± 0.06, respectively (p = 0.002). The mean value of CAVI was 9.61 ± 1.51 and 6.42 ± 0.18 in group I and group II respectively; this difference was significant (p = 0.001). There was a strong positive correlation between CAVI and waist-to-hip ratio in the group I patients (p = 0.02). The results show that vascular stiffness is significantly higher in obesity patients with paroxysmal form AF. Conclusion Positive correlations between increased arterial stiffness and anthropometric indicators confirm the role of visceral obesity in the development of AF.

Download Full-text

Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.81.11.8923850 ◽

1996 ◽

Vol 81 (11) ◽

pp. 3998-4001 ◽

Cited By ~ 2

Author(s):

A E Pontiroli ◽

M F Manzoni ◽

M E Malighetti ◽

R Lanzi

Keyword(s):

Fatty Acids ◽

Growth Hormone ◽

Free Fatty Acids ◽

Releasing Hormone ◽

Plasma Free Fatty Acids ◽

Obese Subjects

Download Full-text

Restoration of growth hormone (GH) response to GH-releasing hormone in elderly and obese subjects by acute pharmacological reduction of plasma free fatty acids

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.81.11.3998 ◽

1996 ◽

Vol 81 (11) ◽

pp. 3998-4001 ◽

Cited By ~ 9

Author(s):

A. E. Pontiroli

Keyword(s):

Fatty Acids ◽

Growth Hormone ◽

Free Fatty Acids ◽

Releasing Hormone ◽

Plasma Free Fatty Acids ◽

Obese Subjects

Download Full-text

Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00335.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. E296-E303 ◽

Cited By ~ 55

Author(s):

Polyxeni Koutkia ◽

Gary Meininger ◽

Bridget Canavan ◽

Jeff Breu ◽

Steven Grinspoon

Keyword(s):

Fatty Acids ◽

Growth Hormone ◽

Free Fatty Acids ◽

Metabolic Regulation ◽

Fat Distribution ◽

Visceral Adiposity ◽

Control Groups ◽

Pulse Area ◽

Gh Secretion ◽

Hiv Lipodystrophy

Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 ± 0.6, 4.7 ± 0.8, and 4.5 ± 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 ± 0.27 vs. 4.67 ± 1.24 ng·ml–1·min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 ± 0.27 vs. 3.18 ± 0.92 ng·ml–1·min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 ± 46 vs. 514 ± 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 ± 46 vs. 546 ± 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy.

Download Full-text