bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of growth hormone administration on protein dynamics and substrate metabolism during 4 weeks of dietary restriction in obese women
Authors: Nørrelund Helene , Børglum Jens , Jørgensen Jens Otto Lunde , Richelsen Bjørn , Møller Niels , Sreekumaran Nair  , Christiansen Jens Sandahl 
Published: March 2003

OBJECTIVETreatment of obesity with very low calorie diet (VLCD) is complicated by protein loss. We evaluated the effects of coadministration of GH on protein turnover, substrate metabolism, and body composition in VLCD treated obesity.DESIGN AND PATIENTSFifteen obese women underwent 4 weeks of very low calorie diet (VLCD) in parallel with GH treatment (n = 7) or placebo (n = 8).MEASUREMENTSProtein metabolism and total glucose turnover were isotopically assayed. Plasma concentrations of amino acids were determined by an HPLC system. Estimated rates of lipid and glucose oxidation were obtained by indirect calorimetry. Fat free mass was determined by DEXA‐scan.RESULTSProtein breakdown decreased in both groups (tyrosine flux μmol/h): −12% ± 3 (GH) vs. − 9% ± 3 (placebo)). Phenylalanine degradation in relation to phenylalanine concentration decreased by 9% in the GH group, whereas an increase of 8% was observed in the placebo group (P = 0.1). Plasma concentrations of several amino acids were significantly decreased in the placebo group, while urea excretion decreased in the GH group. A decrease in FFM was found in placebo treated patients (2.14% ± 1.9 (GH) vs. − 3.54% ± 1.6 (placebo), P < 0.05). Rates of lipid oxidation tended to be increased by GH treatment (lipid oxidation (mg/minutes): 79.7 ± 5.9 (GH) vs. 64.6 ± 5.9 (placebo), P = 0.1).CONCLUSIONDuring dietary restriction GH primarily seems to conserve protein by a reduced hepatic degradation of amino acids.
Pre‐treatment IGF‐I level is the major determinant of GH dosage in adult GH deficiency
Authors: Murray R. D. , Howell S. J. , Lissett C. A. , Shalet S. M. 
Published: March 2003

OBJECTIVESevere GH deficiency in adults is a definite clinical entity, the effects of which can be reversed by administration of subcutaneous recombinant GH. The ideal dosing regimen and determinants of the maintenance dose have, however, yet to be elucidated.PATIENTSIn an open study of GH replacement we treated 65 GH‐deficient adults of mixed adult‐ and childhood‐onset, of mean age 35.5 (range 17–72) years, and comprising 38 females and 27 males, using an individualized low‐dose titration regimen aimed at normalization of the serum IGF‐I and induction of clinical improvement.RESULTSBefore initiation of GH therapy, median IGF‐I SD was significantly lower in female than male patients (− 3.3 vs. − 1.9, P = 0.007) and in childhood‐onset compared with adult‐onset patients (− 3.9 vs. − 2.0, P < 0.001). Once maintenance dosage had been achieved, the median GH requirement was significantly greater in female than male patients (1.6 vs. 0.8 IU/day, P = 0.013) and childhood‐onset compared with adult‐onset patients (1.6 vs. 0.8 IU/day, P = 0.019). The median maintenance GH dose for the cohort overall was 1.2 (range 0.4–2.4) IU/day. By univariate analysis a significant negative correlation was observed between the maintenance GH dose and baseline IGF‐I SD (r = ‐ 0.63, P < 0.001). No significant correlation was demonstrated between maintenance GH dose and either age or weight. Multiple linear regression analysis using age, gender, weight, time of onset of GH deficiency, peak GH to the insulin tolerance test (ITT) and baseline IGF‐I SD as independent variables demonstrated baseline IGF‐I SD to account for 51% of the variation in GH dose required to normalize the IGF‐I SD (P < 0.001). Those patients with the lower IGF‐I SD at initiation of GH therapy required the greater GH dose. None of the other variables studied significantly influenced the maintenance dose.CONCLUSIONWe have demonstrated that the GH dose required in an individual is dependent on the serum IGF‐I SD before commencement of replacement. In contrast, the severity of GH deficiency as judged by the peak GH response to an ITT was unrelated to the maintenance GH requirement. The effect of age, gender and age at onset of GH deficiency on the final GH dose are accounted for by the lower pretreatment IGF‐I SD in young, female and childhood‐onset patients relative to older, male and adult‐onset patients, respectively.
Soluble interleukin‐1 receptor antagonist concentration in patients with Graves' ophthalmopathy is neither related to cigarette smoking nor predictive of subsequent response to glucocorticoids
Authors: Bartalena Luigi , Manetti Luca , Tanda Maria Laura , Dell'Unto Enrica , Mazzi Barbara , Rocchi Roberto , Barbesino Giuseppe , Pinchera Aldo , Marcocci Claudio 
Published: March 2003

OBJECTIVEThe aim of the present study was to evaluate serum soluble interleukin‐1 receptor antagonist (sIL‐1RA) concentration and its relationship with the degree of cigarette smoking in patients with Graves' ophthalmopathy (GO).DESIGN AND SUBJECTSTwenty‐two consecutive GO patients (20 women, two men; age range 25–68 years, mean 48 years; 12 smokers, 10 non‐smokers) submitted to IV glucocorticoid pulses over a 3‐month period.MEASUREMENTSsIL‐1RA levels were measured by an immunoenzymatic assay (sensitivity, 4 ng/l; normal range, 50–290 ng/l) before glucocorticoid treatment, after two months of therapy, and 3 months after drug withdrawal.RESULTSThirteen patients responded to treatment (59%; five smokers and eight non‐smokers), nine were non‐responders (41%; seven smokers and two non‐smokers). Baseline median sIL‐1RA concentration did not differ in smokers and non‐smokers (222 and 173 ng/l, respectively; P = 0.69). Likewise, no significant differences were found between the two groups during treatment (537 and 389 ng/l, respectively; P = 0.28); sIL‐1RA concentration after treatment was higher in smokers (258 vs. 94 ng/l; P = 0.02). There was no correlation between basal sIL‐1RA levels and the degree of cigarette smoking. Likewise, there was no difference in sIL‐1RA levels in responders and non‐responders, either at baseline (186 vs. 216 ng/l; P = 0.83), during or after treatment.CONCLUSIONOur study suggests that circulating soluble interleukin‐1 receptor antagonist levels, both at baseline and during glucocorticoid treatment, are neither influenced by cigarette smoking nor predictive of subsequent response to glucocorticoid treatment.
Adrenal responsiveness to high, low and very low ACTH 1–24 doses in obesity
Authors: Maccario M. , Grottoli S. , DiVito L. , Rossetto R. , Tassone F. , Ganzaroli C. , Oleandri S. E. , Arvat E. , Ghigo E. 
Published: March 2003

OBJECTIVETo investigate adrenal activity in visceral obesity in which adrenal hyperactivity has been hypothesized. This could reflect hypothalamus–pituitary alterations leading to slight hyperfunction of the adrenal. Primary adrenal hypersensitivity to ACTH drive in obesity has also been suggested. However, it has also been reported that dehydroepiondrosterone (DHEA) levels in obesity are reduced and it has been hypothesized that this could play a role in the increased cardiovascular risk in obese patients.SUBJECTSWe have studied seven obese women with visceral adiposity (OB, age: 33.6 ± 3.3 years, BMI: 33.8 ± 1.3 kg/m2, WHR: 0.88 ± 0.01). The results in OB were compared with those recorded in a group of age‐matched normal women (NS, age: 30 ± 1.3 years, BMI: 19.9 ± 0.4 kg/m2, WHR: 0.76 ± 0.02).METHODSWe have studied the cortisol (F), aldosterone (A) and DHEA responses to ACTH 1–24 administered at low (LD, 0.5 μg/m2) or very low (VLD, 0.125 μg/m2) dose followed by a second challenge with supramaximal dose (HD, 250 μg).RESULTSBasal F, A and DHEA levels in OB were similar to those in NS. The peak F responses to ACTH were dose‐related in both groups. At each dose the F peaks in OB (VLD: 495.6 ± 43.9 nmol/l, HD: 722.3 ± 67.7 nmol/l; LD: 519.2 ± 46.0 nmol/l, HD: 729.6 ± 44.7 nmol/l) were similar to those in NS (VLD: 556.7 ± 45.9 nmol/l, HD: 704.8 ± 20.7 nmol/l; LD: 511.8 ± 22.8 nmol/l, HD: 726.7 ± 26.5 nmol/l). The peak A responses to ACTH were dose‐related in both groups. At each dose, the A peaks in OB (VLD: 0.55 ± 0.03 pmol/l, HD: 0.79 ± 0.09 pmol/l; LD: 0.63 ± 0.04 pmol/l, HD: 0.78 ± 0.09 pmol/l) were similar to those in NS (VLD: 0.8 ± 0.10 pmol/l, HD: 0.86 ± 0.09 pmol/l; LD: 0.8 ± 0.10 pmol/l, HD: 0.95 ± 0.12 pmol/l). The peak DHEA responses to ACTH were dose‐related in both groups. At each dose the DHEA peaks in OB (VLD: 58.6 ± 13.3 nmol/l, HD: 61.9 ± 13.1 nmol/l; LD: 55.18 ± 6.4 nmol/l, HD: 72.3 ± 9.8 nmol/l) were similar to those in NS (VLD: 54.3 ± 8.2 nmol/l, HD: 57.8 ± 8.2 nmol/l; LD: 42.2 ± 3.7 nmol/l, HD: 56.9 ± 4.3 nmol/l).CONCLUSIONSThis study shows that the cortisol, aldosterone and dehydroepiondrosterone responses to high, low and very low ACTH doses in obese women overlap with those in age‐matched lean controls; these findings suggest normal sensitivity of the different zones of the adrenal cortex to ACTH in obesity.
Cholinergic modulation of growth hormone responses to growth hormone‐releasing hormone in uraemic patients on peritoneal dialysis
Authors: Díez Juan J. , Iglesias Pedro , Selgas Rafael , Bajo María A. , Aguilera Abelardo 
Published: March 2003

BACKGROUNDHypothalamic cholinergic neurotransmission plays a major role in the regulation of GH secretion. Pyridostigmine, a cholinesterase inhibitor, is able to decrease hypothalamic somatostatinergic tone and release GH in normal subjects. Blockade of muscarinic receptor with pirenzepine blunts the GH release in several clinical situations. However, little information is available on the role played by central cholinergic pathways in GH regulation in uraemic patients.OBJECTIVEWe aimed to assess GH responses to GHRH after pretreatment with pyridostigmine and pirenzepine in a group of uraemic patients undergoing peritoneal dialysis (PD). GH responses of the patients treated with recombinant human erythropeitin (rhEPO) were compared to patients without treatment.DESIGNWe studied 14 male patients on PD and nine control subjects. All subjects underwent three endocrine test in random order after an overnight fast. Each subject received GHRH (100 μg, i.v. in bolus at 0 minutes). Sixty minutes before the injection of GHRH subjects were given oral placebo, pyridostigmine (120 mg), or pirenzepine (100 mg).MEASUREMENTSBlood samples for GH were collected at −60, 0, 15, 30, 45, 60 and 90 minutes The hormonal secretory responses were studied by a time‐averaged (area under the curves, AUC) and time‐independent (peak values) analysis.RESULTSBaseline GH concentrations were similar in patients and controls. GH responses to placebo plus GHRH were also comparable in patients and controls (peak 26.6 ± 3.8 vs. 33.2 ± 4.4 mU/l, AUC 28.2 ± 3.4 vs. 27.8 ± 4.6 mU/h/l). Pyridostigmine administration induced a significant potentiation of GH responses to GHRH both in patients (peak 43.2 ± 5.2 mU/l, AUC 47.6 ± 6.0 mU/h/l; P < 0.01) and in control subjects (peak 79.2 ± 8.6 mU/l, AUC 78.0 ± 9.4 mU/h/l; P < 0.01). However, the increment in GH peak and AUC was significantly (P < 0.05) greater in controls in relation to values found in patients. Pirenzepine administration induced an abolishment of GH release after GHRH stimulation both in PD patients (peak 5.4 ± 2.6 mU/l, AUC 6.0 ± 2.4 mU/h/l; P < 0.01) and in healthy controls (peak 3.8 ± 0.6 mU/l, AUC 4.0 ± 0.4 mU/h/l; P < 0.05). Responses to pyridostigmine plus GHRH and pirenzepine plus GHRH were similar in patients on chronic therapy with recombinant human erythropeitin and in patients without rhEPO therapy.CONCLUSIONThese results suggest that the cholinergic regulation of GH release is preserved in uraemic patients on peritoneal dialysis. The significantly lower increase in GH response to GHRH induced by pyridostigmine suggests that cholinergic stimulatory tone is attenuated in patients in relation to control subjects. Long‐term therapy with rhEPO seems not to affect GH responses to cholinergic stimulation or blockade.
Long‐term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia
Authors: Newfield Ron S. , Spitz Irving M. , Isacson Christina , New Maria I. 
Published: March 2003

Mifepristone (RU486) is a potent antiprogestagen, and at high doses it also acts as an antiglucocorticoid drug. Mifepristone, administered as a single 600 mg dose, is commonly employed to induce medical abortion in conjunction with prostaglandins. The long‐term safety profile of mifepristone, especially at high doses, is less well‐established. Long‐term mifepristone is considered efficacious in treating uterine myomas, endometriosis (25–100 mg/day), and possibly in inoperable meningiomas (200 mg/day), as well as inoperable Cushing's syndrome. Many animal studies document an antiproliferative effect (antioestrogenic), as do some reports in humans. However, there are also data to suggest that, as an antiprogestagen, mifepristone may promote an unopposed oestrogen milieu, and thus have a proliferative effect upon the endometrium.We hereby describe the first reported case of an adolescent female with Cushingoid features and morbid osteoporosis who was treated with mifepristone for its antiglucocorticoid effect (400 mg/day) in an attempt to prevent further bone loss. The patient's striae, weight gain, and buffalo hump markedly improved, and further bone loss was halted. However, with each of the two 6‐month courses of mifepristone (9 months apart) she developed massive simple endometrial hyperplasia and a markedly enlarged uterus. This reversed to normal after cessation of mifepristone treatment.In conclusion, High doses of the antiprogestagen mifepristone over a prolonged period of time may promote an unopposed oestrogen milieu leading to endometrial hyperplasia. Therefore, interval pelvic imaging in women who receive long‐term mifepristone may be prudent.
Elevated inferior petrosal sinus levels of PTHrP in a patient with Cushing's disease
Authors: Höfle G. , Gasser R. W. , Buchfelder M. , Fahlbusch R. , Waldenberger P. , Finkenstedt G. 
Published: March 2003

PTHrP has been found in various tissues, including prolactinomas and growth hormone producing adenomas. The function and clinical importance of PTHrP are poorly understood.We report the case of a 25‐year‐old female patient with hirsutism. Autonomous ACTH‐dependent hypercortisolism was documented by endocrine testing. Magnetic resonance imaging (MRI) revealed a 3‐mm intrasellar hypointense lesion in the left side of the pituitary gland. The inferior petrosal sinus sampling disclosed a gradient of ACTH left central/peripheral of 30·5 and right central/peripheral of 2·0 and suggested the diagnosis of a left‐sided pituitary ACTH secreting microadenoma.Interestingly, we found elevated PTHrP levels in the left inferior petrosal sinus with a gradient of 4·7 compared to peripheral venous blood and of 3·6 compared to the right sinus.Our results fit very well to the concept of a para‐/autocrine secretion of PTHrP which has been proposed recently and suggest a role in the regulation of cell growth of pituitary adenomas.
Smaller LDL particle size in women with polycystic ovary syndrome compared to controls
Authors: Dejager S. , Pichard C. , Giral P. , Bruckert E. , Federspield M.C. , Beucler I. , Turpin G. 
Published: March 2003

OBJECTIVE Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. The contribution of lipid abnormalities to this higher risk, in particular atherogenic modifications of low density lipoprotein (LDL) such as a shift towards smaller LDL, has not been properly explored. We aimed to examine LDL size variation in relation to androgens and other risk factors in women with PCOS.DESIGN Comparison of clinical and biochemical measurements in women with PCOS and women with normal ovarian function, of similar age and body mass index (BMI).PATIENTS Thirty‐one women with PCOS and 27 controls were studied. Patients were recruited from the outpatient endocrine clinic.MEASUREMENTS Fasting total cholesterol, triglycerides (TG), high density lipoprotein (HDL), LDL, glucose, insulin, gonadotrophins, androgens, oestradiol, 17 OH progesterone and SHBG were measured. LDL particle diameter was calculated based on distance travelled in polyacrylamide native gels. Recumbent blood pressure was measured automatically.RESULTS LDL particle size appeared to be significantly smaller in hyperandrogenic PCOS as compared to regularly cycling women (P = 0006), independent of variations in lipid levels. SHBG was the only independent predictor of LDL size in this population, with a strong correlation, which persisted after adjustment for all confounding variables.CONCLUSIONS Our results suggest that androgen excess and mild insulin‐resistance (both responsible for lower SHBG) may have an early modifying effect on low density lipoprotein size in polycystic ovary syndrome women. The denser pattern observed in polycystic ovary syndrome women could by itself constitute a higher cardiovascular risk, even in the absence of overt dyslipidaemia, and contribute to the excess risk of cardiovascular disease reported in this syndrome.
Effect of acute pharmacological modulation of plasma free fatty acids on GH secretion in acromegalic patients
Authors: Cordido Fernando , Peñalva Angela , Martinez Teresa , Casanueva Felipe F. , Dieguez Carlos 
Published: March 2003

OBJECTIVES In acromegaly GH secretion is markedly increased due in most cases to a GH secreting pituitary adenoma. GH secretion is modulated by variations in the levels of free fatty acids (FFA). Recent studies in different clinical situations, have shown that reduction in FFA with acipimox (A) modifies somatotroph cell responsiveness. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on both basal GH levels and GHRH‐mediated GH secretion in acromegalic patients.PATIENTS Six acromegalic patients (four female, two male) aged 57 ± 4 years., with active disease due to pituitary adenomas were studied. Four of the patients had been treated previously by surgery and/or radiotherapy. The diagnosis of active acromegaly was established by clinical assessment, increased serum IGF‐I and impaired GH supression after oral glucose.MEASUREMENTS Four tests were performed: placebo, A (250 mg, orally, − 210 minutes and − 60 minutes), GHRH (100 µg, iv, 0 minutes) and GHRH plus A. The different tests on each subject were performed in random order one week apart, each subject served as their own control. Serum GH was measured by RIA at appropriate intervals. The area under the curve (AUC) was calculated by the trapezoidal method. Statistical analysis was performed by Wilcoxon test. P < 0·05 was considered significant.RESULTS The administration of A induced a FFA reduction during the entire test both when administered with placebo and with GHRH: AUC (mmol/l × 90 minutes): placebo plus placebo: 88·2 ± 7·3. Placebo plus A: 23·2 ± 4·6 (P < 0·05). Placebo plus GHRH: 85·4 ± 6·9. A plus GHRH: 21·8 ± 3·8 (P < 0·05). Mean peak GH level (µg/l) after placebo plus placebo was 5·0 ± 1·8 not significantly different than after placebo plus A with a mean peak of 6·2 ± 2 (P = ns). Mean peak GHRH‐induced GH secretion was 26·0 ± 15·4 and was not modified by previous A administration with mean peak of 24·4 ± 11·8 (P = ns).CONCLUSIONS In acromegalic patients acute pharmacological reduction of FFA with acipimox did not modify basal GH levels or GHRH‐induced GH secretion, suggesting that the adenomatous somatotroph cell is unresponsive to physiological signals such as FFA which act at a pituitary level. These data support the hypothesis of an intrinsic neoplastic pituitary defect for the pathogenesis of acromegaly.
Urate and arteriosclerosis in primary hyperparathyroidism
Authors: Westerdahl J. , Valdemarsson S. , Lindblom P. , Bergenfelz A. 
Published: March 2003

OBJECTIVEAn increased mortality due to cardiovascular disease has been reported in patients with primary hyperparathyroidism (pHPT). An association between urate and cardiovascular disease has been suggested. Metabolic abnormalities in pHPT may include urate. We therefore evaluated the metabolic arteriosclerotic risk profile in pHPT with special focus on the role of urate.DESIGNRetrospective analysis of data before and 1 year after surgery for pHPT.PATIENTS130 consecutive patients, over the age of 44 years, who underwent surgery for pHPT.MEASUREMENTSBiochemical variables known to reflect risk of arteriosclerotic disease (AD) and renal function tests including measurement of glomerular filtration rate (GFR) were investigated before and 1 year after surgery.RESULTSpHPT patients with AD (n = 40) were older and had higher serum levels of urate and triglyceride, and more impaired renal function in comparison with patients without AD. PTH and calcium values did not differ. Multiple logistic regression analysis indicated that urate was an independent risk factor for AD in pHPT (P < 0·01). Three variables were shown to be positively associated with urate; male gender (P < 0·01), fasting blood glucose (P < 0·05) and serum level of triglyceride (P < 0·05).CONCLUSIONSUrate was found to be an independent risk factor for arteriosclerotic disease in primary hyperparathyroidism. Serum level of urate could (in addition to gender) be associated with a metabolic disorder comprising increased glucose and triglyceride levels.
The influence of growth hormone replacement on heart rate variability in adults with growth hormone deficiency
Authors: Leong King S. , Mann Paul , Wallymahmed Maureen , MacFarlane Ian A. , Wilding John P.H. 
Published: March 2003

OBJECTIVE Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. Abnormalities in heart rate variability (HRV), a surrogate marker of cardiac autonomic tone, have also been found in untreated growth hormone deficient (GHD) patients. Similar abnormalities have been found in patients with complications postmyocardial infarction.DESIGN AND MEASUREMENTS This study was designed to investigate whether GH treatment leads to normalization of cardiac autonomic tone.HRV measurements were obtained from 15 minute resting ECG recordings in 11 untreated adult GHD patients (7 females; mean age 39·2 years), 10 GHD patients (6 females; mean age 46·2 years) reCENving GH replacement (mean duration, 52·7 months) and 12 healthy controls (7 females; mean age 44·6 ± 2·9 years) who were all of similar age, weight and BMI. The untreated GHD patients were then commenced on GH and HRV measurements repeated after 3 and 6 months of treatment.RESULTS In accord with our previous findings, HRV analysis using Fast Fourier Transform (FFT) showed a distinct pattern of abnormality in GHD patients compared with controls. Specifically, there was an increase in nHF power (P = 0·04) and a reduction in nLF power (P = 0·04) (representing parasympathetic and sympathetic activity, respectively), a reduction in nVLF power (P = 0·03) and a 50% reduction in LF/HF ratio (P = 0·02) (a measure of sympathovagal balance) in GHD patients when compared with controls. HRV results in patients who have been on long‐term GH replacement were indistinguishable from controls. After 3 months GH replacement in the untreated GHD patient group, nVLF power had increased by 28% (P = 0·03) at 3 months and this was sustained at 6 months. However, no significant changes in LF and HF power were seen.CONCLUSIONS These results suggest that abnormalities of the cardiac autonomic system in GHD patients may be correctable. Longer duration of prospective follow‐up will be required to determine at what time point improvements in the other frequency bands occur.