Metabolic Co-Morbidities Revealed in Patients with Childhood-Onset Adult GH Deficiency after Cessation of GH Replacement Therapy for Short Stature

Izumi, Fujio; Hizuka, Naomi; Yasumoto, Kumiko; Morita, Junko; Kurimoto, Makiko; Takano, Kazue

doi:10.1507/endocrj.k08e-079

Cited by 22 publications

(14 citation statements)

References 21 publications

(27 reference statements)

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“…Total cholesterol and LDL-C increased in three studies but did not change in another study (27,29,31). An increase in hsCRP after discontinuation of rhGh therapy has been reported in two studies (28,29).…”

Section: Lipid Metabolism (Four Studies)mentioning

confidence: 89%

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Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature

Appelman‐Dijkstra

Rijndorp

Biermasz

et al. 2016

European Journal of Endocrinology

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Background: Recombinant human growth hormone (rhGH) replacement is advocated in adult growth hormonedeficient (GHD) patients to increase bone mass and improve lipid profile, body composition, and quality of life. The long-term effects of discontinuation of rhGh replacement are unknown. Methods: This cohort study and systematic review aim to evaluate the long-term metabolic effects of discontinuation of rhGh replacement in adult GHD patients, with a subgroup analyses according to age (< or > 60 years). Data on anthropometry, lipids, glucose, and bone mass density (BMD) were assessed for 3 years after discontinuation. Results: Cohort study included 64 patients who had discontinued rhGh replacement for >12 months. Fat percentage increased from 31.5 ± 9.5% to 33.8 ± 9.0% (mean difference 2.3, P = 0.003). BMI decreased only in subjects <60 years (P = 0.014). Glucose, total cholesterol, and LDL-cholesterol levels did not change; however, the percentage of patients on statins increased slightly from 39% to 44%. HDL-C concentration increased only in patients <60 years (mean difference 0.2, P = 0.043). Lumbar spine BMD did not change; however, femoral neck BMD and bone turnover markers decreased in subjects <60 years (P = 0.001). Systematic review included eight studies (n = 166 patients) with a follow-up duration of 6-18 months. Of the eight studies, three qualified as low risk of bias and five as having an intermediate risk of bias. None of the studies reported handling of statins, bisphosphonates, and glucose-lowering medication or excluded patients using these medications. Conclusions: In this study, discontinuation of rhGh replacement resulted in metabolic changes only in patients <60 years after 3 years. Further research warrants to determine the optimal strategies for (dis)continuation of rhGh replacement in adult patients with GHD.

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Section: Lipid Metabolism (Four Studies)mentioning

confidence: 89%

“…The mean duration of withdrawal was 3-18 months in all studies except one. Two studies did not clearly report the duration of rhGh replacement at the time of discontinuation; in the other studies, the duration of rhGh treatment before termination ranged from 6 months to 10 years (27,30).…”

Section: Study Characteristicsmentioning

confidence: 99%

Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature

Appelman‐Dijkstra

Rijndorp

Biermasz

et al. 2016

European Journal of Endocrinology

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“…Several reports have suggested that such hepatic impairment may be particularly related to GHD. For instance, adult hypopituitarism with GHD has been reported to be associated with liver dysfunction and hyperlipidemia (3,4). Ichikawa et al (5) showed that hepatic steatosis was more frequently observed in hypopituitary patients with GHD than in patients without GHD, with hepatic steatosis present in 54% of the patients with GHD.…”

Section: Introductionmentioning

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

140

132

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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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“…They suggested that lifelong GH replacement might be important for improving the overall metabolic profile 22) . There is a case report of an adult with hypopituitarism who suffered from NAFLD, which improved with GH treatment 9) .…”

Section: Discussionmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease in Children with Hypopituitarism

Yoon

Shin

et al. 2010

Korean J Pediatr Gastroenterol Nutr

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Purpose: It has been reported that children with hypopituitarism have features of metabolic syndrome, including obesity, impaired glucose tolerance, and dyslipidemia. The aim of this study was to investigate the clinical features and liver histology of pediatric non-alcoholic fatty liver disease (NAFLD) associated with hypopituitarism. Methods: We reviewed the clinical data of 11 children diagnosed with NAFLD among patients with hypopituitarism. Results:The mean age at the time of diagnosis of hypopituitarism was 10.4±3.2 years, and the mean age at the time of diagnosis of NAFLD was 13.1±2.7 years. A craniopharyngioma was the most common cause of pituitary dysfunction. At the time of diagnosis of NAFLD, 9 patients (82%) had a body mass index greater than the 85th percentile, 5 patients (45%) had elevated fasting blood glucose levels, and 9 patients (82%) had hypertriglyceridemia. The mean height SD score was significantly lower at the time of diagnosis of NAFLD than at the time of diagnosis of hypopituitarism. Of the six patients who were biopsied, one had cirrhosis, two had non-alcoholic steatohepatitis (NASH) with bridging fibrosis, two had NASH with mild portal fibrosis, and one had simple steatosis. Conclusion: Children with hypopituitarism are at risk of short stature, obesity, dyslipidemia, and NAFLD. The early diagnosis of NAFLD is important in children with hypopituitarism because advanced fibrosis is common. (Korean J Pediatr Gastroenterol Nutr 2010; 13: 51∼57)

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Metabolic Co-Morbidities Revealed in Patients with Childhood-Onset Adult GH Deficiency after Cessation of GH Replacement Therapy for Short Stature

Cited by 22 publications

References 21 publications

Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature

Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature

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

Nonalcoholic Fatty Liver Disease in Children with Hypopituitarism

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