Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly.

Objective: To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome.

Patients And Methods: Seventeen patients (6 women), mean age 46·3 years (range: 23·2-76·2), were studied. For each patient, four hospital visits were identified including 'active disease' (no treatment) and last follow-up.

Cotreatment with pegvisomant and a somatostatin analog (SA) in SA-responsive acromegalic patients.

Context: Cotreatment of acromegaly with pegvisomant and a somatostatin analog (SA) has proven feasible. Previous studies in the field have focused on patients with an insufficient response to SA monotherapy in whom pegvisomant was added without changing the SA dose.

Objective: The objective of the study was to study whether patients sufficiently controlled on SA monotherapy can be transferred to combination therapy with low-dose pegvisomant and a reduced SA dose.

Sustained low-dose growth hormone therapy optimizes bioactive insulin-like growth factor-I level and may enhance CD4 T-cell number in HIV infection.

High-dose recombinant human growth hormone (rhGH) (2-6 mg/day) regimes may facilitate T-cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose rhGH regimens increase insulin-like growth factor-I (IGF-I) to supra-physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T-cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.

Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.

Objectives: Growth hormone (GH) reduces the catabolic side effects of steroid treatment via effects on the amino-nitrogen metabolism. Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on selected hepatic measures of alpha-amino-nitrogen conversion during steroid-induced catabolism.

Elevated free IGF2 levels in localized, early-stage breast cancer in women.

Objective: Epidemiological studies imply an association between circulating IGF1 and breast cancer, whereas the role of IGF2, which also acts on the IGF1 receptor, is less settled. This study investigates the association between IGF2 and breast cancer in patients with localized disease.

Design: The participants were women with well-characterized, early stage, localized breast cancer (n=43) and matched healthy women (n=38), from whom fasting serum levels of IGF-related peptides were measured.

[Medical co-treatment af acromegaly with a somatostatin analogue and a growth hormone receptor antagonist].

We tested the effect of co-treatment of acromegaly with a somatostatin analogue (SA) and a growth hormone receptor antagonist (GHA). Eleven patients underwent: 1) conventional treatment with SA, 2) discontinued treatment, 3) 6 weeks treatment with GHA (10 mg), 4) 6 weeks treatment with GHA (15 mg), 5) 3 months combined SA and GHA. Circulating IGF-I was lowered by GHA and more so with combined treatment.

The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly.

Context: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described.

Patients And Methods: We assessed basal and insulin-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design.

Kinetics and secretion of placental growth hormone around parturition.

Objective: During pregnancy, placental growth hormone (PGH) is secreted into the maternal circulation, replacing pituitary GH. It is controversial whether PGH levels decline during vaginal birth. After placental expulsion, PGH is eliminated from the maternal blood.

Growth factors, glucose and insulin kinetics after low dose growth hormone therapy in HIV-lipodystrophy.

Objectives: Low-dose growth hormone (GH) administration has been suggested as a treatment for HIV-lipodystrophy.

Methods: Postglucose GH-secretion, kinetics of insulin-like growth factors (IGFs), insulin, and glucose metabolism were examined in six male HIV-infected lipodystrophic patients (two normal-weight patients with normal glucose-tolerance (NGT), two normal-weight with impaired glucose-tolerance (IGT), and two obese patients with diabetes (DM)) during a 16 weeks open-labelled pilot-study of low-dose GH, 0.7 mg/day.

Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist.

Context: Pegvisomant is a GH receptor antagonist that blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin (SMS) analogs, does not suppress the activity of the GH-producing adenoma.

Objective: We assessed the effects of cotreatment with pegvisomant and SMS in acromegaly on GH secretion, IGF-I levels, and glucose tolerance.

Effects of 2 wk of GH administration on 24-h indirect calorimetry in young, healthy, lean men.

The present study was designed as a randomized, double-blind placebo (Plc)-controlled study to determine the effect of 2 wk of growth hormone administration (GH-adm.) on energy expenditure (EE) and substrate oxidation in healthy humans. Sixteen young healthy men were divided into two groups.

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men.

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/- S.E.

Continuous glucose monitoring in interstitial subcutaneous adipose tissue and skeletal muscle reflects excursions in cerebral cortex.

Continuous glucose monitoring (CGM) is being explored using several types of glucose sensors. Some are designed for subcutaneous adipose tissue. It is important to determine to which extent these glucose fluctuations in different tissues reflect changes taking place in the central nervous system, where glucose sensing is thought to occur.

Different growth hormone sensitivity of target tissues and growth hormone response to glucose in HIV-infected patients with and without lipodystrophy.

Growth hormone (GH)-secretion in HIV-lipodystrophy is impaired; however, GH-sensitivity of GH-target tissues remains to be evaluated. We measured overnight fasting concentrations of GH-sensitive insulin-like growth-factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) including GH binding protein (GHBP), a marker of GH-receptor sensitivity, in antiretroviral treated HIV-infected patients with (LIPO) and without lipodystrophy (NONLIPO) and antiretroviral naive HIV-infected patients (NAIVE). Three h GH-suppression tests using oral glucose were undertaken to determine dynamics of GH-secretion.

Testosterone and estradiol regulate free insulin-like growth factor I (IGF-I), IGF binding protein 1 (IGFBP-1), and dimeric IGF-I/IGFBP-1 concentrations.

The present study tests the clinical postulate that elevated testosterone (Te) and estradiol (E2) concentrations modulate the effects of constant iv infusion of saline vs. recombinant human IGF-I on free IGF-I, IGF binding protein (IGFBP)-1, and dimeric IGF-I/IGFBP-1 concentrations in healthy aging adults. To this end, comparisons were made after administration of placebo (Pl) vs.

Increasing urine albumin excretion is associated with growth hormone hypersecretion and reduced clearance of insulin in adolescents and young adults with type 1 diabetes: the Oxford Regional Prospective Study.

Hypothesis: We previously described lower insulin-like growth factor I (IGF-I) levels in association with increased microalbuminuria (MA) risk in type 1 diabetic subjects followed from diabetes diagnosis through puberty into adulthood. By inference lower IGF-I levels may be associated with higher GH levels and changes in insulin sensitivity.

Methods: To test this hypothesis, microalbuminuric subjects (MA+, n = 14) from the same cohort had overnight GH levels measured during euglycaemia (5 mmol/l, 01:00-07:30 h) maintained by a variable rate insulin infusion followed by a 2-step hyperinsulinaemic, euglycaemic clamp study using [6.

Residual beta-cell function more than glycemic control determines abnormalities of the insulin-like growth factor system in type 1 diabetes.

The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual beta-cell function. Patients with hemoglobin A1c (HbA1c) less than 6% (reference range, 3.

Insulin-like growth factors, insulin-like growth factor-binding proteins, insulin-like growth factor-binding protein-3 protease, and growth hormone-binding protein in lipodystrophic human immunodeficiency virus-infected patients.

Human immunodeficiency virus (HIV)-lipodystrophy is associated with impaired growth hormone (GH) secretion. It remains to be elucidated whether insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), IGFBP-3 protease, and GH-binding protein (GHBP) are abnormal in HIV-lipodystrophy. These parameters were measured in overnight fasting serum samples from 16 Caucasian males with HIV-lipodystrophy (LIPO) and 15 Caucasian HIV-infected males without lipodystrophy (NONLIPO) matched for age, weight, duration of HIV infection, and antiretroviral therapy.

Fasting unmasks a strong inverse association between ghrelin and cortisol in serum: studies in obese and normal-weight subjects.

Administration of ghrelin, the endogenous ligand for the GH secretagogue receptor, stimulates not only GH secretion but also appetite and food intake in humans. Endogenous ghrelin levels display a distinct circadian rhythm, which is reciprocal to that of insulin and presumed to be meal dependent and not associated with GH secretion. We tested the hypothesis that food deprivation could impact circadian serum ghrelin levels and unmask meal-independent regulatory mechanisms.

Free rather than total circulating insulin-like growth factor-I determines the feedback on growth hormone release in normal subjects.

Pituitary GH secretion is feedback regulated by circulating IGF-I. However, it remains to be determined whether the feedback control is mediated through circulating free or total IGF-I. To study this, we compared the temporal changes in circulating levels of GH vs.

Free IGF-I, IGFBP-1, and the binary complex of IGFBP-1 and IGF-I are increased during human pregnancy.

Background/aims: To investigate changes in free insulin-like growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP-1) complexed IGF-I during human pregnancy.

Methods: Overnight fasting serum was obtained in a longitudinal design from 11 women with non-complicated pregnancy at gestation weeks 6-10, 16-20, 24-28 and 35-38 and, for comparison, 5 weeks post-partum. All samples were analyzed for total and free IGF-I and IGF-II, IGFBP-3 and IGFBP-3 proteolysis, total and non-phosphorylated (np-) IGFBP-1, and IGFBP-1 complexed IGF-I.

Gene expression of the GH receptor in subcutaneous and intraabdominal fat in healthy females: relationship to GH-binding protein.

Objective: Circulating GH-binding protein (GHBP) is produced by proteolytical cleavage of the extracellular part of the GH receptor (GHR) and is positively correlated to the amount of body fat. To test the hypothesis that adipose tissue may contribute to the production of circulating GHBP, we compared gene expression of two GHR isoforms in adipose tissue with serum GHBP concentrations in healthy females.

Design: Twenty-two healthy females undergoing surgery for benign gynecological conditions were included in the study.

Acute hyperinsulinemia restrains endotoxin-induced systemic inflammatory response: an experimental study in a porcine model.

Background: Intensive insulin therapy in critically ill patients reduces morbidity and mortality. The current study elucidates whether acute hyperinsulinemia per se could attenuate the systemic cytokine response and improve neutrophil function during endotoxin (lipopolysaccharide)-induced systemic inflammation in a porcine model.

Methods: Pigs were anesthetized, mechanically ventilated, randomized into four groups, and followed for 570 min: group 1 (anesthesia solely, n = 10), group 2 (hyperinsulinemic euglycemic clamp [HEC], n = 9), group 3 (lipopolysaccharide, n = 10), group 4 (lipopolysaccharide-HEC, n = 9).