Hypertension in Acromegaly: Hereditary Hypertensive Factor Produces Hypertension by Enhancing IGF-I Production.

Ohtsuka, Hideyuki; Komiya, Ichiro; Aizawa, Toru; Yamada, Takashi

doi:10.1507/endocrj.42.781

Cited by 36 publications

(27 citation statements)

References 31 publications

(45 reference statements)

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“…Neither GH nor IGF-I concentrations correlated with high blood pressure. This is in accordance with Ohtsuka et al [17]who found that IGF-I levels positively correlate with blood pressure only in acromegalic patients with a family history of hypertension. More recently, a close association has been found between abnormalities in glucose metabolism and both systolic and diastolic blood pressure as well as left ventricular hypertrophy in patients with acromegaly [5, 18].…”

Section: Discussionsupporting

confidence: 93%

Clinical-Biochemical Correlations in Acromegaly at Diagnosis and the Real Prevalence of Biochemically Discordant Disease

Mercado

Monteros²,

Sosa³

et al. 2004

Horm Res Paediatr

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Objective: To analyze clinical-biochemical correlations in newly diagnosed acromegaly, focusing in particular on patients with discrepant parameters. Design: Retrospective study. Methods: Data from 164 patients with acromegaly seen between 1995 and 2003. Patients were reviewed for the presence of headaches, arthralgias, hypertension, menstrual abnormalities, impotence, glucose intolerance or diabetes. Biochemical evaluation consisted of age- and gender-adjusted IGF-I levels and glucose-suppressed GH. Results: Magnetic resonance imaging (MRI) revealed macroadenoma in 127 patients and microadenoma in 37. Patients with macroadenomas were younger than those with microadenomas and the disease was more frequent in females. Excluding acral enlargement, which was present in all the patients, the most commonly reported complaints were headaches (66%) and arthralgias (52%). Hypertension was present in 37% of patients, whereas the prevalence of glucose intolerance and diabetes was 27 and 32%, respectively. Hyperprolactinemia was present in 20% of patients with microadenomas and in 40% of patients with macroadenomas. Hypogonadism was demonstrated in more than half of the patients and was not related to tumor size or prolactin level. Of all the clinical and metabolic abnormalities of acromegaly, only the presence of diabetes correlated with both basal and nadir post-glucose GH levels. Only 4 patients (2.4%) had glucose-suppressed GH values of <1 ng/ml in the presence of clinical evidence of acromegaly, an elevated IGF-I level and a pituitary adenoma on MRI. Conclusions: Clinical features of acromegaly correlate poorly with indices of biochemical activity. The prevalence of biochemically discordant acromegaly is considerably lower than recently reported.

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Section: Discussionsupporting

confidence: 93%

Clinical-Biochemical Correlations in Acromegaly at Diagnosis and the Real Prevalence of Biochemically Discordant Disease

Mercado

Monteros²,

Sosa³

et al. 2004

Horm Res Paediatr

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“…In another study, a reduction in serum IGF-I level in relation to bezafibrate treatment in post-myocardial infarction patients was independently associated with angiographic measures of coronary artery disease regression (30). Furthermore, in acromegaly, a human model of IGF-I excess (where World Health Organization criteria indicate that 37.5% patients have hypertension), blood pressure positively correlates with IGF-I concentration (31). These findings strongly support an endocrine effect of IGF-I in vivo.…”

Section: Discussionmentioning

confidence: 96%

Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes

et al. 2002

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The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically developed immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which is predominantly highly phosphorylated, was significantly lower in subjects with known macrovascular disease triglycerides, and nonesterified fatty acids. In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration ( ‫؍‬ 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n ‫؍‬ 29) than for any other group. This effect persisted after adjustment of tIGFBP-1 levels for BMI, C-peptide, age, and sex (F ‫؍‬ 6.5, P < 0.001, ‫؍‬ ؊0.46). Such an effect was not apparent for lpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas lpIGFBP-1 isoforms are associated with glycemic control, suggesting a dual role for IGFBP-1 in the regulation of IGF actions in type 2 diabetes. Our data suggest that high circulating concentrations of highly phosphorylated IGFBP-1 may protect against the development of hypertension and cardiovascular disease by reducing the mitogenic potential of IGFs on the vasculature.

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“…Acromegaly, which leads to enhanced release of IGF1, is a well-known cause of hypertension, and the IGF1 gene locus demonstrates linkage to blood pressure in twins. 25,26 Only a subpopulation of acromegalic patients develop hypertension. In view of the present data, it is tempting to speculate that the acromegalic patients who remain normotenEffect of the polymorphisms on blood pressure in the twin sample and the replication sample.…”

Section: Discussionmentioning

confidence: 99%

Serum- and Glucocorticoid-Regulated Kinase (SGK1) Gene and Blood Pressure

et al. 2002

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Abstract-The serum-and glucose-regulated kinase (SGK1) gene has recently been identified as an important aldosterone-induced protein kinase that mediates trafficking of the renal epithelial Na ϩ channel (ENaC) to the cell membrane. Thus, SGK1 is an appealing candidate for blood pressure regulation and possibly essential hypertension. To test this hypothesis, we recruited monozygotic (126 pairs) and dizygotic (70 pairs) normotensive twin subjects and parents of dizygotic twins. Blood pressure was measured in a controlled fashion: recumbent, sitting, and upright. We documented genetic variance on blood pressure in all positions. We then relied on microsatellite markers at the SGK1 gene locus (D6S472, D6S1038, and D6S270) and 2 single nucleotide polymorphisms within the SGK1 gene. We found significant linkage of the SGK1 gene locus to diastolic blood pressure (PϽ0.0002) and suggestive evidence for linkage for systolic blood pressure (PϽ0.04), documenting the locus as a quantitative trait locus for blood pressure. We next performed association, using all dizygotic twins and a monozygotic member from each pair. We found significant associations between both single nucleotide polymorphism variants and blood pressure, as well as a significant interaction between the single nucleotide polymorphisms enhancing the effect. This combined effect of the polymorphisms was confirmed in an independent sample of 260 young normotensive men. We conclude that the SGK1 gene is relevant to blood pressure regulation and probably to hypertension in man.

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Hypertension in Acromegaly: Hereditary Hypertensive Factor Produces Hypertension by Enhancing IGF-I Production.

Cited by 36 publications

References 31 publications

Clinical-Biochemical Correlations in Acromegaly at Diagnosis and the Real Prevalence of Biochemically Discordant Disease

Clinical-Biochemical Correlations in Acromegaly at Diagnosis and the Real Prevalence of Biochemically Discordant Disease

Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and Hypertension in Type 2 Diabetes

Serum- and Glucocorticoid-Regulated Kinase (SGK1) Gene and Blood Pressure

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