http://repub.eur.nl/res/aut/49510/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33278/ 2011-10-01T00:00:00Z Context: Adults with GH deficiency (GHD) have a decreased life expectancy. The effect of GH treatment on mortality remains to be established. Objective: This nationwide cohort study investigates the effect of GH treatment on all-cause and cause-specific mortality and analyzes patient characteristics influencing mortality in GHD adults. Design, Setting, and Patients: Patients in the Dutch National Registry of Growth Hormone Treatment in Adults were retrospectively monitored (1985-2009) and subdivided into treatment (n =2229), primary (untreated, n = 109), and secondary control (partly treated, n = 356) groups. Main Outcome Measures: Standardized mortality ratios (SMR) were calculated for all-cause, malignancy, and cardiovascular disease (CVD) mortality. Expected mortality was obtained from cause, sex, calendar year, and age-specific death rates from national death and population counts. Results: In the treatment group, 95 patients died compared to 74.6 expected [SMR 1.27 (95% confidence interval, 1.04-1.56)]. Mortality was higher in women than in men. After exclusion of high-risk patients, the SMR for CVD mortality remained increased in women. Mortality due to malignancies was not elevated. In the control groups mortality was not different from the background population. Univariate analyses demonstrated sex, GHD onset, age, and underlying diagnosis as influencing factors. Conclusions: GHD men receiving GH treatment have a mortality rate not different from the background population. In women, after exclusion of high-risk patients, mortality was not different from the background population except for CVD. Mortality due to malignancies was not elevated in adults receiving GH treatment. Next to gender, the heterogeneous etiology is of influence on mortality in GHD adults with GH treatment. Copyright http://repub.eur.nl/res/pub/33969/ 2011-04-01T00:00:00Z Objective: The Dutch National Registry of GH Treatment in Adults was established in 1998 as an initiative of the Ministry of Health. The main goals were to gain more insight into long-term efficacy, safety, and costs of GH therapy (GHT) in adult GH-deficient (GHD) patients in The Netherlands. Methods: Baseline patient characteristics and diagnostic test procedures were evaluated. Results: Until January 2009 in roughly 10 years, 2891 patients (1475 men and 1416 women, mean age 43.5±16.5 years) were registered. GHD was of childhood-onset (CO) in over 20% of the patients and of isolated in 11%. The most common causes of GHD were pituitary tumors and/or their treatment, craniopharyngiomas, and idiopathic GHD. In 85% of the patients, a GH stimulation test was performed, in the majority an insulin tolerance test (ITT) (49%) or a combined GHRH-arginine test (25%). In 12% of the patients, IGF1 levels were ≤-2 S.D. combined with two or more additional pituitary hormone deficits, and in 2%, it concerned patients with CO-GHD continuing GHT in adulthood. Over the years, the test of first choice shifted from ITT toward GHRH-arginine test. Conclusion: Nearly, 2900 patients were included in the nationwide surveillance database of the Dutch National Registry of GH Treatment in Adults until January 2009. Baseline patient characteristics are comparable to that reported previously. In 85% of these patients, the diagnosis of GHD was established by provocative testing, particularly an ITT or a combined GHRH-arginine test, with an evident increase in the percentage of GHRH-arginine tests being performed in the last years. http://repub.eur.nl/res/pub/39392/ 1993-09-15T00:00:00Z The renin-angiotensin system (RAS) plays an important role in the regulation of arterial blood pressure and water and salt regulation. Until recently this system was considered to be exclusively a circulating endocrine system. Circulating renin, released by the renal juxtaglomerular cells, reacts with hepatically derived angiotensinogen (renin substrate) to form the inactive decapeptide angiotensin I (Ang 1). Ang I, in turn, is converted to the biologically active octapeptide angiotensin II (Ang II) by angiotensin converting enzyme (ACE) which is bound to the endothelial cell membrane. Ang II formed in the circulation diffuses to the tissues where it stimulates specific receptors on the surface of vascular smooth muscle cells as well as on the surface of the aldosterone-producing cells in the adrenal glands. More recent evidence, however, suggests that, in addition to the circulating endocrine RAS, there exist local or tissue renin-angiotensin systems in which Ang I and Ang II are formed in the tissues ratherthan in the circulation. Tissue production of these peptides may be catalyzed either by locally synthesized renin and renin substrate or by renin and renin substrate that are taken up from the plasma. Local renin-angiotensin systems have both autocrine and paracrinefunctions. Messenger RNA (mRNA) for renin has been demonstrated not only in the kidney but also in such organs as the adrenals, ovaries, testes, and brain, and mRNA for angiotensinogen has been found in all of these tissues as well. On the other hand, renin in the heart and blood vessel wall probably originates mainly in the kidneys and is then taken up from the circulation. Human plasma contains not only renin but also its enzymatically inactive precursor prorenin. Virtually all plasma renin is derived from the kidney, as evidenced by the observation that circulating renin levels are extremely low or not demonstrable in anephric patients. The kidney is also an important source of circulating prorenin. However the finding that anephric patients have plasma prorenin levels that are 30-40% of normal indicates that a proportion of circulating prorenin is clearly of extrarenal origin. It is likely that such organs as the adrenals, testes, and ovaries release not renin but prorenin into the circulation. For example, the increased plasma prorenin levels seen in pregnant women are largely derived from the ovaries. Unlike plama renin, plasma prorenin is increased in patients with diabetes mellitus who have microvascular complications. The mechanisms that account for the elevations in plasma prorenin levels seen in these patients are yet unknown. In patients receiving a beta-adrenoreceptor antagonist (beta-blocker), plasma renin levels fall and plasma prorenin levels rise. Thus, it has been proposed that the development of autonomic neuropathy in patients with diabetes mellitus may be responsible for the increase in plasma pro renin. Loss of sympathetic stimulation ofthe beta-adrenoreceptors on the juxtaglomerular cells might result in diminished secretion of renin and, as a compensatory mechanism, the synthesis and secretion of prorenin in the juxtaglomerular apparatus might be augmented According to an alternative hypothesis, when the juxtaglomerular cells are affected by diabetic micrangiopathy, conversion of prorenin to renin in these cells decreases and secretion of prorenin consequently increases