The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency

Deepak, Doddabele Srinivasa; Daousi, Christina; Javadpour, Mohsen; Clark, D.; Perry, Y. S.; Pinkney, JH; MacFarlane, I. A.

doi:10.1016/j.ghir.2010.02.002

Cited by 54 publications

(39 citation statements)

References 62 publications

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“…In 2006, the KIMS group reported that 2589 adults with GH deficiency who participated in this observational study had elevated total cholesterol and LDL cholesterol. 134 High-density lipoprotein cholesterol and triglycerides were found to be normal as previously reported by de Boer et al 135 Fasting LDL cholesterol was also found to decrease after 6 months of GH replacement in a recent study by Deepak et al 136 There is a growing literature supporting a true improvement in lipid parameters after GH replacement in deficient patients, but more clinical data is necessary to assess a true benefit to patients.…”

Section: Lipid Abnormalities In Gh Deficiencysupporting

confidence: 59%

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Growth Hormone and the Cardiovascular System

Palmeiro

Anand

Dardi

et al. 2012

Cardiology in Review

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Growth hormone (GH) exerts its effects through insulin-like growth factor-1, and although ubiquitous in human tissues, it has a significant role in cardiovascular function. In recent years, there has been a great deal of interest in GH as an etiologic factor in many cardiovascular disease states. Acromegaly, a state of endogenous GH excess, results in myocardial hypertrophy and decreased cardiac performance with increased cardiovascular mortality. Additional insight into the role of excess GH on the cardiovascular system has been gained from data collected in athletes doping with GH. Likewise, GH deficiency is associated with increased mortality, possibly from the associated increase in atherosclerosis, lipid abnormalities, and endothelial dysfunction. However, further research is required to clarify the benefit of GH treatment in both deficient states and in heart failure patients.

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Section: Lipid Abnormalities In Gh Deficiencysupporting

confidence: 59%

“…148 For the majority of published trials, investigations continue to report worsening insulin resistance. Recently, Deepak et al 136 …”

Section: Insulin Resistancementioning

confidence: 99%

Growth Hormone and the Cardiovascular System

Palmeiro

Anand

Dardi

et al. 2012

Cardiology in Review

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“…Moreover, one study in active acromegaly reported increased levels of fibrinogen together with reduced CPR, in agreement with our observations (47). In untreated GHD, increased baseline CRP has been observed with subsequent reductions during GH replacement therapy (15,48,49). However, in patients with long-term GH disturbances, changes in levels of APPs may not be solely dependent on direct effects of GH and IGF1.…”

Section: Discussionmentioning

confidence: 99%

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Andreassen

Frystyk

Faber

et al. 2012

European Journal of Endocrinology

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Introduction: The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro-and anti-inflammatory effects have been demonstrated. Methods/design: Twelve healthy volunteers (mean age 36, range 27-49 years) were treated in random order with increasing doses of GH for 3 weeks (first week 0.01 mg/kg per day, second week 0.02 mg/kg per day, and third week 0.03 mg/kg per day) or a GH receptor antagonist (pegvisomant; first week 10 mg/day and last two weeks 15 mg/day), separated by 8 weeks of washout. Circulating levels of the pro-inflammatory cytokines tumor necrosis factor a (TNFa (TNFA)), interleukin 6 (IL6), and IL1b (IL1B) and the acute phase proteins (APPs) C-reactive protein (CRP), haptoglobin, orosomucoid, YKL40 (CHI3L1), and fibrinogen were measured. Conclusions: GH/IGF1 action appears to modulate the initial stage of the inflammatory response as well as downstream processes elucidated by levels of APPs. The data suggest a complicated relationship not allowing any simple conclusions as to whether GH/IGF1 actions have mainly pro-or antiinflammatory effects in vivo.

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“…Although actions of GH are often described as anti-inflammatory [84], GH-deficient and GH-resistant mice are characterized by reduced expression of pro-inflammatory cytokines in the adipose tissue, in the hypothalamus and in other brain regions [82, 85–87], reduced NLRP3 inflammasome activation [88], reduced hypothalamic astrogliosis [86] and increased adiponectin levels [80, 89]. This shift from a pro- to an anti-inflammatory profile almost certainly contributes to healthy aging and the extended longevity of these mutants.…”

Section: What Mechanisms Link Reduced Somatotropic Signaling With Slomentioning

confidence: 99%

GH and ageing: Pitfalls and new insights

Bartke

Darcy

2017

Best Practice & Research Clinical Endocrinology & Metab

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Interrelationships of growth hormone (GH) actions and aging are complex and incompletely understood. The very pronounced age-related decline in GH secretion together with benefits of GH therapy in individuals with congenital or adult GH deficiency (GHD) prompted interest in GH as an anti-aging agent. However, the benefits of treatment of normal elderly subjects with GH appear to be marginal and counterbalanced by worrisome side effects. In laboratory mice, genetic GH deficiency or resistance leads to a remarkable extension of longevity accompanied by signs of delayed and/or slower aging. Mechanisms believed to contribute to extended longevity of GH-related mutants include improved anti-oxidant defenses, enhanced insulin sensitivity and reduced insulin levels, reduced inflammation and cell senescence, major shifts in mitochondrial function and energy metabolism and greater stress resistance. Negative association of the somatotropic signaling and GH/insulin-like growth factor 1 (IGF-1)-dependent traits with longevity was also shown in other mammalian species. In humans, syndromes of GH resistance or deficiency have no consistent effect on longevity, but can provide striking protection from cancer, diabetes and atherosclerosis. More subtle variations in various steps of GH and IGF-1 signaling are associated with reduced old-age mortality, particularly in women and with improved chances of attaining extremes of lifespan. Epidemiological studies raise a possibility that the relationship of IGF-1 and perhaps also GH levels with human healthy aging and longevity may be biphasic. However, the impact of somatotropic signaling on neoplastic disease is difficult to separate from its impact on aging and IGF-1 levels exhibit opposite associations with different chronic, age-related diseases.

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The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency

Cited by 54 publications

References 62 publications

Growth Hormone and the Cardiovascular System

Growth Hormone and the Cardiovascular System

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

GH and ageing: Pitfalls and new insights

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