Malignant Disease and Cardiovascular Morbidity in Hypopituitary Adults with or without Growth Hormone Replacement Therapy

Svensson, Johan; Bengtsson, Bengt‐Åke; Rosén, Thord; Odén, Anders; Johannsson, Gudmundur

doi:10.1210/jc.2003-031601

Cited by 211 publications

(217 citation statements)

References 38 publications

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“…In contrast to these previous studies, no increased SMR for deaths from cardiovascular diseases or malignancies were observed. The elevated SMR noted in the studied cohort and the excess mortality seen in female patients confirm the results of earlier studies (1,2,3,4,6,8). That said, the present study revealed a lower SMR in the KIMS study cohort as a whole compared with mortality studies reported in the literature, and an SMR close to 1 in males.…”

Section: Discussionsupporting

confidence: 91%

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Overall and cause-specific mortality in GH-deficient adults on GH replacement

Gaillard

Mattsson²,

Åkerblad³

et al. 2012

European Journal of Endocrinology

118

108

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Objective: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. Design: In KIMS (Pfizer International Metabolic Database) 13 983 GH-deficient patients with 69 056 patient-years of follow-up were available. Methods: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P!0.05. Results: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at followup, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (PZ0.017) and malignancies (PZ0.044). Conclusions: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.

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Section: Discussionsupporting

confidence: 91%

“…It is well-established that mortality is increased in patients with hypopituitarism (1,2,3,4,5,6,7,8,9). Recently, an extensive review was devoted to this subject (10).…”

Section: Introductionmentioning

confidence: 99%

Overall and cause-specific mortality in GH-deficient adults on GH replacement

Gaillard

Mattsson²,

Åkerblad³

et al. 2012

European Journal of Endocrinology

118

108

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“…Therefore, it remains to be established whether quantitative and qualitative changes of lipids are the main cause for the increased cardiovascular mortality and morbidity found in hypopituitary patients with GHD (39,40). Similarly, the lack of effect of GHRT on LDL size in the present study does not support the concept that a possible effect of GHRT on cardiovascular mortality, as recently suggested (41), is related to the effect of GH on lipid metabolism.…”

Section: Ghd Versus Controls (Pz)contrasting

confidence: 87%

Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy

Rizzo

Trepp²,

Berneis³

et al. 2007

eur j endocrinol

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Objective: Patients with growth hormone deficiency (GHD) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein (HDL) cholesterol concentrations, two lipid abnormalities usually accompanied by increased small dense LDL in the 'atherogenic lipoprotein phenotype' (ALP). In the present study, we directly investigated (1) whether hypopituitary patients with GHD have increased small dense LDL; (2) whether growth hormone replacement therapy (GHRT) beneficially impact on such particles; (3) the prevalence of ALP in GHD and GHRT patients. Design and methods: In 14 hypopituitary patients with GHD (44G13 years, body mass index (BMI) 27G3) before and after 4 months of GHRT, and in 11 healthy age-and BMI-matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis. Results: Compared with controls, GHD showed increased triglycerides (PZ0.0024), similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations (PZ0.0894). GHRT reduced total and LDL cholesterol levels (PZ0.0303 and 0.0120 respectively), but no effect was found on triglycerides and HDL cholesterol levels. LDL size was unchanged in GHD versus controls (269G9 vs 274G6 Å , PZns), but LDL subclass analysis revealed a shift towards more dense particles (PZ0.0046). GHRT had no significant impact on LDL size and subclasses. The prevalence of ALP was 14% in GHD and 7% in GHRT. Conclusions: In GHD patients, individual features of ALP (including increased small dense LDL) may be common, but complete ALP is relatively uncommon. Short-term replacement therapy seems to be ineffective on such lipid alterations, but the effect of a longer GHRT remains to be assessed.

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“…Abnormally low GH was also deleteriously associated with higher fasting insulin, lower IGF-1, and higher HOMA index. Large waist circumference is a strong independent risk factor for insulin resistance, 38,39 and untreated GH deficiency is associated with an array of unfavorable cardiovascular risk factors and outcomes 23,24,[40][41][42][43] and may also be a risk factor for insulin resistance. 13,23,44,45 The risk profile for diabetes that we observed in ALL survivors with GH deficiency is notable.…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia

Gurney

Ness

Sibley

et al. 2006

Cancer

234

188

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BACKGROUND. The purpose of the study was to determine the prevalence of metabolic syndrome, growth hormone deficiency, and cardiovascular risk factors among adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with or without cranial irradiation. METHODS. Follow‐up was undertaken of 75 randomly selected long‐term childhood ALL survivors. Testing included fasting insulin, glucose, lipids, and growth hormone (GH) releasing hormone plus arginine stimulation test. The prevalence of metabolic syndrome was compared with population norms from 1999–2002 National Health and Nutrition Examination Study (NHANES) data, and internally between those with and without past cranial irradiation and those with normal (>16.5 μg/L) versus insufficient (9–16.5 μg/L) versus deficient (<9 μg/L) peak GH secretion. RESULTS. The mean subject age was 30 years and the mean time since ALL diagnosis was 25 years. The prevalence of metabolic syndrome did not differ statistically (P = .87) between study subjects (16.6%) and same‐age, same‐sex population norms (17.5%). However, 60% of subjects treated with cranial irradiation, compared with 20% of those who were not, had 2 or more of the 5 components of metabolic syndrome. Untreated abnormally low GH was present in 64% of subjects overall and 85% of those who received past cranial irradiation. Cranial irradiation was strongly related to GH deficiency, and in turn lower insulin‐like growth factor 1 (IGF‐1), higher fasting insulin, abdominal obesity, and dyslipidemia, particularly in women. CONCLUSIONS. Hematologists who treat childhood ALL patients, and particularly those who provide primary care to adult survivors, should be aware of the potential for long‐term GH deficiency and adverse cardiovascular and diabetes risk profiles as a consequence of leukemia treatment. Cancer 2006. © 2006 American Cancer Society.

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Malignant Disease and Cardiovascular Morbidity in Hypopituitary Adults with or without Growth Hormone Replacement Therapy

Cited by 211 publications

References 38 publications

Overall and cause-specific mortality in GH-deficient adults on GH replacement

Overall and cause-specific mortality in GH-deficient adults on GH replacement

Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy

Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia

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