Hepatic steatosis, GH deficiency and the effects of GH replacement: a Liverpool magnetic resonance spectroscopy study

Gardner, Clarissa; Irwin, Andrew J.; Daousi, Christina; McFarlane, Ian A; Joseph, Franklin; Bell, Jimmy D.; Thomas, E. Louise; Adams, V.; Kemp, Graham J.; Cuthbertson, Daniel J.

doi:10.1530/eje-12-0002

Cited by 45 publications

(51 citation statements)

References 43 publications

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“…A further case report has also identified histological improvement in NAFLD following GH replacement therapy (62). Conversely, in a separate study in patients with GHD, GH replacement decreased subcutaneous and visceral but not hepatic fat (63). The causes of GHD in this study were variable and GH was typically not an isolated deficiency and therefore differences in other hormonal replacement regimes may be important.…”

Section: Oestrogensmentioning

confidence: 54%

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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Section: Oestrogensmentioning

confidence: 54%

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

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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“…These data suggest that NAFLD/NASH is one of the important comorbidities in adult hypopituitary patients with GHD. Recently, Gardner et al (26) reported that NAFLD is equally common in patients with GHD and age-and BMI-matched control subjects. Although the reason for the discrepancy is unknown, compared with the present study, the age of subjects was higher, the serum IGF1 levels were not severely impaired in the GHD group, and the unmatched sex in the study might influence the results.…”

Section: Discussionmentioning

confidence: 99%

Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy

Nishizawa

Iguchi

Murawaki

et al. 2012

European Journal of Endocrinology

134

126

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Background: Liver dysfunction in adult hypopituitary patients with GH deficiency (GHD) has been reported and an increased prevalence of nonalcoholic fatty liver disease (NAFLD) has been suggested. Objective: The objective of the present study was to elucidate the pathophysiology of the liver in adult hypopituitary patients with GHD. Patients and methods: We recruited 69 consecutive Japanese adult hypopituitary patients with GHD and examined the prevalence of NAFLD by ultrasonography and nonalcoholic steatohepatitis (NASH) by liver biopsy. Patients had been given routine replacement therapy except for GH. We compared these patients with healthy age-, gender-, and BMI-matched controls. We further analyzed the effect of GH replacement therapy on liver function, inflammation and fibrotic markers, and histological changes. Results: The prevalence of NAFLD in hypopituitary patients with GHD was significantly higher than in controls (77 vs 12%, P!0.001). Of 16 patients assessed by liver biopsy, 14 (21%) patients were diagnosed with NASH. GH replacement therapy significantly reduced serum liver enzyme concentrations in the patients and improved the histological changes in the liver concomitant with reduction in fibrotic marker concentrations in patients with NASH. Conclusions: Adult hypopituitary patients with GHD demonstrated a high NAFLD prevalence. The effect of GH replacement therapy suggests that the NAFLD is predominantly attributable to GHD.

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“…The GH/EGFR pathway downregulation is probably the mechanism responsible for liver regeneration deficiency associated with HS, which can be partially rescued in ob / ob mice by GH administration (25). Although GH treatment has a positive regenerative effect on the liver after hepatic resection (25), its efficacy in reducing NAFLD in hypopituitarism is controversial, with positive (26, 27) and negative (28) reports. Furthermore, IGF1 treatment does not improve NAFLD in individuals with Laron dwarfism, a known model of GH resistance (29).…”

Section: Discussionmentioning

confidence: 99%

Liver status in congenital, untreated, isolated GH deficiency

Diniz¹,

Souza²,

Salvatori³

et al. 2014

Endocrine Connections

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Nonalcoholic fatty liver disease (NAFLD) is known to be associated with insulin resistance, atherosclerosis, and low serum IGF1 levels. We have described a large cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G→A mutation in the GHRH receptor gene. These subjects have increased insulin sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized that, despite visceral obesity, NAFLD would be absent or mild due to the increased IS. To assess the prevalence and severity of NAFLD in adult subjects with lifetime, congenital, untreated IGHD, we studied 22 IGHD adults and 25 controls (COs) matched for age and sex. NAFLD was assessed by a comprehensive liver function panel, and ultrasonographic pattern (hyperechogenic pattern, HP) coded as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. Compared with COs, IGHD individual had lower serum IGF1 (P<0.0001), higher total cholesterol (P=0.027), lower prothrombin time (P=0.017), and similar activated partial thromboplastin time and fibrinogen values. Alanine transaminase (ALT) values were similar in the two groups, but aspartate transaminase was higher in IGHD (P=0.013). However, more IGHD subjects (7/22) than COs (3/23) had ALT above the upper limit of normal (P=0.044). The prevalence of NAFLD was higher in IGHD than COs (61 vs 29%, P=0.032), and the HP score was higher in IGHD than COs (P=0.041), but severe NAFLD was not observed in any IGHD (or CO) individual. Liver HP score is increased in lifetime, untreated, congenital IGHD, but the increase in transaminases is mild, suggesting a lack of advanced forms of NAFLD.

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Hepatic steatosis, GH deficiency and the effects of GH replacement: a Liverpool magnetic resonance spectroscopy study

Cited by 45 publications

References 43 publications

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

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

Nonalcoholic fatty liver disease in adult hypopituitary patients with GH deficiency and the impact of GH replacement therapy

Liver status in congenital, untreated, isolated GH deficiency

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