High fibrinogen and plasminogen activator inhibitor activity in growth hormone-deficient adults.

The hemostatic balance is a complex system where the delicate equilibrium is regulated by several factors, including hormones. This review summarizes current knowledge of the effects of most frequent endocrine and metabolic diseases (such as hypothyroidism, hyperthyroidism, Cushing's syndrome, GH-related pituitary dysfunctions, pituitary prolactin-producing adenomas, polycystic ovary syndrome, primary hyperparathyroidism, and metabolic syndrome) on coagulation and fibrinolysis. Overt hypothyroidism appears to be associated with a bleeding tendency, whereas all other endocrine diseases appear to be associated with a thrombotic tendency. Globally, the disorders of coagulation and fibrinolysis usually range from mild to moderate, and, rarely, to severe laboratory abnormalities (for example, bleeding diathesis in overt hypothyroidism mainly due to an acquired von Willebrand's disease type 1). Further larger and high-quality studies are needed to provide more definitive information on the effects of endocrine disorders on coagulation and fibrinolysis.

Section: Gh Deficiencymentioning

confidence: 96%

Hemostatic abnormalities in endocrine and metabolic disorders

Franchini¹,

Lippi²,

Manzato³

et al. 2010

“…During the past two decades, evidence has emerged linking hypopituitarism with cardiovascular risk factors, including hyperlipidaemia (11,12,13,14), visceral adiposity (15,16), insulin resistance (17) and vascular endothelial dysfunction (18,19,20).…”

Section: Introductionmentioning

confidence: 99%

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

Gaillard

Mattsson²,

Åkerblad³

et al. 2012

117

108

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.

“…Much is made of the increased cardiovascular mortality in hypopituitary GH-deficient patients reported in two well-conducted epidemiological studies from Sweden (7,8). This, coupled with the finding of premature atherosclerosis (9), unfavourable lipid (10) and cardiovascular risk profile (11) together with favourable changes on GH replacement (5, 6, 11), has prompted some to suggest that GH replacement may lead to a lessening of the cardiovascular mortality in this patient group. However, there are concerns that GH replacement involves administration of an anabolic and potentially mitogenic substance to a patient group that contains many with previous or residual pituitary tumours.…”

Section: Introductionmentioning

confidence: 99%

Does GH replacement therapy in adult GH-deficient patients result in recurrence or increase in size of pituitary tumours?

Hatrick

Boghalo

Bingham

et al. 2002

Objective: Hypopituitary GH-deficient patients have an increased cardiovascular mortality and GH replacement in this population has resulted in considerable therapeutic benefit. GH replacement involves administration of a potentially mitogenic substance to patients with a previous or residual pituitary tumour. Our objective was to evaluate whether GH replacement results in an increase in the size of pituitary tumours. Methods: This was a non-randomised observational study on patients recruited from the endocrine clinic. All subjects had GH deficiency, proven on an insulin tolerance test and were divided into those who were or were not receiving long-term GH replacement. Comparison of change in pituitary size was made with interval radiological imaging of the pituitary. Results: Seventy-five patients (40 men and 35 women) were in the study, 47 were on long-term GH replacement and there were 28 controls. The average length of treatment for the treated group was 3.6 patient years. Thirty-nine patients in the treated group had at least 2 years of GH treatment between imaging studies of the pituitary. Two patients in the treated group had an increase in pituitary size (non-functioning adenomas) and two in the control group (one functioning and one nonfunctioning adenoma adenoma). None of these four patients required further treatment. There was no statistically significant difference between the two groups. Conclusion: Using a representative cohort of hypopituitary patients attending an endocrine clinic, GH replacement was not associated with an increased pituitary tumour recurrence rate. Although the results are not conclusive, in the period of observation GH had little adverse effect but longer studies are required to be certain.