Fat Content in Liver and Skeletal Muscle Changes in a Reciprocal Manner in Patients with Acromegaly during Combination Therapy with a Somatostatin Analog and a GH Receptor Antagonist: A Randomized Clinical Trial

Madsen, Mette; Krusenstjerna-Hafstrøm, Thomas; Møller, Louise; Christensen, Britt; Vendelbo, Mikkel Holm; Pedersen, Steen B.; Frystyk, Jan; Jessen, Niels; Hansen, Troels Krarup; Stødkilde-Jørgensen, Hans; Flyvbjerg, Allan; Jørgensen, Jens Otto Lunde

doi:10.1210/jc.2011-2681

Cited by 44 publications

(29 citation statements)

References 40 publications

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“…A total of 20 normal-weight subjects (meanGS.E.M., BMI: 25G2) comprising ten 'young' subjects (5F/5M) with a mean (range) age of 25 (20)(21)(22)(23)(24)(25)(26)(27)(28) years and ten 'old' subjects (5F/5M) with a mean age of 65 (60-72) years participated in this study. None were smokers or receiving prescribed drugs, and none of the females received estrogen supplementation.…”

Section: Subjectsmentioning

confidence: 99%

“…MR spectroscopy was performed using a Signa Excite 1.5 tesla twin-speed scanner (GE Medical Systems) to quantify fat in muscle (IMCL) and liver (IHL) as described previously (22,23). The spectra were quantified using the LC model software package (LCModel6.2; Stephen Provencher, Oakville, ON, Canada) by means of dedicated muscle and liver spectroscopy fitting models.…”

Section: Body Composition and Physical Fitnessmentioning

confidence: 99%

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GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

Vestergaard

Vendelbo

Pedersen

et al. 2014

European Journal of Endocrinology

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Objective: The mechanisms underlying the impact of age and gender on the GH-IGF1 axis remain unclear. We tested the hypothesis that age and gender have impacts on GH signaling in human subjects in vivo. Design: A total of 20 healthy non-obese adults ('young group' !30 years (5F/5M) and 'old group' O60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline. Methods: Muscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO 2max , and muscle strength were measured. Results: In the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (PZ0.002) and fat (PZ0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced in women when compared with men (PZ0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; rZK0.56, PZ0.01) and positively with the CISH mRNA response (rZ0.533, PZ0.05). Conclusion: i) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact of sex steroid administration and physical training on GH signaling in human subjects in vivo are required.

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Section: Subjectsmentioning

confidence: 99%

Section: Body Composition and Physical Fitnessmentioning

confidence: 99%

GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

Vestergaard

Vendelbo

Pedersen

et al. 2014

European Journal of Endocrinology

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“…However, untreated acromegaly is associated with raised serum TGs (64) and IR and a high visceral adiposity index (65). Perhaps unexpectedly, a single study has shown that co-treatment of acromegaly with a somatostatin analogue and the GH receptor antagonist, pegvisomant, increases intrahepatic lipid (66), but further studies are clearly warranted.…”

Section: Oestrogensmentioning

confidence: 99%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation worldwide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, GH deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. While in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition among common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarise the clinical data endorsing these observations.

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“…55 A transient increase in liver transaminases is observed in 25% of patients. 70 The mechanism is currently unknown, but a cross-sectional study recently found an association between the risk of hepatocellular injury and genetic polymorphisms associated with Gilbert's disease. 71 A more severe transaminitis (greater than three times the upper limit of normal) can be seen in 2.5% of patients and seems to be more prevalent in patients concurrently treated with somatostatin analogs.…”

Section: Pegvisomant: Metabolic and Cardiac Effectsmentioning

confidence: 99%

“…60 Cotreatment with pegvisomant and somatostatin analogs was recently shown to increase intrahepatic lipid and decrease intramyocellular lipid compared to somatostatin analog therapy alone, which may serve as a possible explanation. 70 …”

Section: Pegvisomant: Metabolic and Cardiac Effectsmentioning

confidence: 99%

An update on the treatment of acromegaly

Edling¹,

Heaney²

2013

RRED

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Acromegaly is caused by pituitary somatotroph hypersecretion of growth hormone leading to elevated hepatic-derived and local levels of insulin-like growth factor-1. It is associated with increased morbidity and mortality due primarily to cardiovascular disease and diabetes mellitus. Normalization of growth hormone and insulin-like growth factor-1 levels has been associated with decreased morbidity from metabolic and cardiovascular effects, as well as reduced overall mortality in epidemiologic studies. Many patients experience a delay in obtaining a diagnosis, have pituitary macroadenomas at presentation, and accordingly, a significant number will not be cured by tumor surgical resection alone. Adjunctive radiation therapy cannot always offer biochemical and clinical disease control and carries a 40% risk of partial or total pituitary failure in the medium term. Several monotherapies or combination medical therapies are currently available for both primary and adjuvant acromegaly treatment, and include long-acting somatostatin analogs, the growth hormone receptor antagonist pegvisomant, and dopamine agonists. Next generation somatostatin analogs and new drug delivery methods of existing agents are in ongoing clinical studies. This paper will review current and novel therapies under development for acromegaly.

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Fat Content in Liver and Skeletal Muscle Changes in a Reciprocal Manner in Patients with Acromegaly during Combination Therapy with a Somatostatin Analog and a GH Receptor Antagonist: A Randomized Clinical Trial

Abstract: Cotreatment with pegvisomant and a reduced SA dose increase IHL and decrease IMCL compared with SA monotherapy. The clinical implications remain unclear, but increased IHL may be causally linked to the transient elevations in liver enzymes observed during pegvisomant treatment.

Cited by 44 publications

References 40 publications

GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

An update on the treatment of acromegaly

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