Increase in serum pregnancy-associated plasma protein-A is correlated with increase in cardiovascular risk factors in adult patients with growth hormone deficiency.
ABSTRACT Adult Growth Hormone Deficiency (AGHD) is correlated to many adverse effects on metabolism and increased cardiovascular risk. Pregnancy-associated plasma protein-A (PAPP-A) is a protease that promotes IGF-I availability in vascular tissues in recent study, and PAPP-A levels have been proposed as an early predictor of cardiac events. The aim of our study was to compare PAPP-A levels in AGHD patients with that of healthy adult subjects to determine if there is a relationship between serum PAPP-A and glucose and lipid metabolism. Twenty AGHD patients and 20 healthy, age-matched and weight-matched persons were chosen for the study. Their weight, height, blood pressure, body mass index (BMI), body fat percentage, waist and hip circumference, and waist-hips ratio were assessed. An oral glucose tolerance test was performed and venous blood was collected from the each patient's cubital vein for biochemical analysis. Serum PAPP-A level in AGHD patients was significantly higher than that of the control group [(7.62 ± 1.62 vs. 6.54 ± 1.31) p < 0.05], and PAPP-A was positively correlated to age, BMI, waist circumference and so on. After adjusting for the waist circumference, waist-hip ratio, 2 h postprandial blood glucose, triglycerides, the serum PAPP-A in AGHD patients was positively correlated to the BMI (r = 0.728, p < 0.05) and fasting insulin (r = 0.433, p < 0.05). In a multiple step-wise regression analysis, BMI, 2 h postprandial glucose, fasting insulin, HOMA-IR were independently associated with serum PAPP-A in AGHD patients. The increase in serum PAPP-A levels is associated with abnormal glucose metabolism and increased risk of atherosclerosis in AGHD patients.
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ABSTRACT: Four retrospective studies have reported premature mortality in patients with hypopituitarism with standard mortality ratios (SMRs) varying between 1.20 and 2.17. Patients with hypopituitarism have complex endocrine deficiencies, and the mechanisms underpinning any excess mortality are unknown. Furthermore, the suggestion has emerged that endogenous growth-hormone deficiency might account for any excess mortality. We aimed to clarify these issues by doing a large prospective study of total and specific-cause mortality in patients with hypopituitarism. We followed up 1014 UK patients (514 men, 500 women) with hypopituitarism from January, 1992, to January, 2000. 573 (57%) patients had non-functioning adenomas, 118 (12%) craniopharyngiomas, and 93 (9%) prolactinomas. SMRs were calculated as the ratio of observed deaths to the number of deaths in an age-matched and sex-matched UK population. The number of observed deaths was 181 compared with the 96.7 expected (SMR 1.87 [99% CI 1.62-2.16], p<0.0001). Univariate analysis indicated that mortality was higher in women (2.29 [1.86-2.82]) than men (1.57 [1.28-1.93], p=0.002), in younger patients, in patients with an underlying diagnosis of craniopharyngioma (9.28 [5.84-14.75] vs 1.61 [1.30-1.99], p<0.0001), and in the 353 patients treated with radiotherapy (2.32 [1.71-3.14] vs 1.66 [1.30-2.13], p=0.004). Excess mortality was attributed to cardiovascular (1.82 [1.30-2.54], p<0.0001), respiratory (2.66 [1.72-4.11], p<0.0001), and cerebrovascular (2.44 [1.58-4.18], p<0.0001) causes. There was no effect of hormonal deficiency on mortality, except for gonadotropin deficiency, which, if untreated was associated with excess mortality (untreated 2.97 [2.13-4.13] vs treated 1.42 [0.97-2.07], p<0.0001). Multiple regression analyses identified age at diagnosis, sex, a diagnosis of craniopharyngioma, and untreated gonadotropin deficiency as independent significant factors affecting mortality. Patients with hypopituitarism have excess mortality, predominantly from vascular and respiratory disease. Age at diagnosis, female sex, and above all, craniopharyngioma were significant independent risk factors. Specific endocrine-axis deficiency, with the exception of untreated gonadotropin deficiency, does not seem to have a role.The Lancet 03/2001; 357(9254):425-31. · 39.06 Impact Factor
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ABSTRACT: Data regarding gender-specific efficacy of GH on critical endpoints are lacking. There are no randomized, placebo-controlled studies of physiological GH therapy solely in women. Our objective was to determine the effects of physiological GH replacement on cardiovascular risk markers and body composition in women with GH deficiency (GHD). This was a 6-month, randomized, placebo-controlled, double-blind study. The study was conducted at the General Clinical Research Center. 43 women with GHD due to hypopituitarism were included in the study. Study participants were randomized to receive GH (goal mid-normal serum IGF-1) or placebo. Cardiovascular risk markers, including high-sensitivity C-reactive protein, tissue plasminogen activator, and body composition, including visceral adipose tissue by cross-sectional computed tomography, were measured. Mean daily GH dose was 0.67 mg. The mean IGF-1 sd score increased from -2.5 +/- 0.3 to -1.4 +/- 0.9 (GH) (P < 0.0001 vs. placebo). High-sensitivity C-reactive protein decreased by 38.2 +/- 9.6% (GH) vs.18.2 +/- 6.0% (placebo) (P = 0.03). Tissue plasminogen activator and total cholesterol decreased, and high-density lipoprotein increased. Homeostasis model assessment-insulin resistance and other markers were unchanged. Body fat decreased [-5.1 +/- 2.0 (GH) vs. 1.9 +/- 1.0% (placebo); P = 0.002] as did visceral adipose tissue [-9.0 +/- 5.9 (GH) vs. 4.3 +/- 2.7% (placebo); P = 0.03]. Change in IGF-1 level was inversely associated with percent change in visceral adipose tissue (r = -0.61; P = 0.002), total body fat (r = -0.69; P < 0.0001), and high-sensitivity C-reactive protein (r = -0.51; P = 0.003). Low-dose GH replacement in women with GHD decreased total and visceral adipose tissue and improved cardiovascular markers, with a relatively modest increase in IGF-1 levels and without worsening insulin resistance.Journal of Clinical Endocrinology & Metabolism 07/2008; 93(6):2063-71. · 6.43 Impact Factor
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ABSTRACT: We recently described a novel mouse model that combines resistance to lactogenic hormones with GH deficiency (GHD). The GHD/lactogen-resistant males develop obesity and insulin resistance with age. We hypothesized that altered production of pancreatic hormones and dysregulation of adipocytokine secretion and action contribute to the pathogenesis of their insulin resistance. Double-mutant males (age 12-16 months) had fasting hyperinsulinemia, hyperamylinemia, hyperleptinemia, and a decreased ratio of adiponectin to leptin. Adiponectin receptor 1 and 2 (AdipoR1 and R2) mRNA levels in liver and skeletal muscle were normal but hepatic insulin receptor mRNA was increased. Relative to double-mutant males, GHD males had lower levels of insulin, amylin, and leptin, higher levels of adiponectin, and higher expression of hepatic AdipoR1 and insulin receptor mRNAs. Lactogen-resistant mice had reduced hepatic adipoR2 mRNA. In response to stress the plasma concentrations of MCP-1 and IL-6 increased in double-mutant males but not GHD or lactogen-resistant males. Our findings suggest that the insulin resistance of GHD/lactogen-resistant males is accompanied by dysregulation of pancreatic hormone and adipocytokine secretion and receptor expression. Phenotypic differences between double-mutant and GHD males suggest that lactogens and GH exert differential but overlapping effects on fat deposition and adipocytokine secretion and action.Endocrine 11/2007; 32(2):182-91. · 2.25 Impact Factor