Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal growth retardation is associated with decreased postnatal growth, resulting in a lower adult height. In addition, a low birth weight is associated with an increased risk of developing diseases during adulthood, such as insulin resistance, type 2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular diseases. Children with persistent postnatal growth retardation, i.e., incomplete catch-up growth, can be treated with human GH. The GH/IGF-I axis is involved in the regulation of carbohydrate and lipid metabolism. The question of whether treatment with GH in children born small for gestational age (SGA) has long-term implications with respect to glucose/insulin and lipid metabolism has not been answered yet. In this article, the available data are reviewed.
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PMID:Metabolic implications of GH treatment in small for gestational age. 1778 97

Acromegalic patients present with volume expansion and arterial hypertension, but the renal sites and molecular mechanisms of direct antinatriuretic action of GH remain unclear. Here, we show that acromegalic GC rats, which are chronically exposed to very high levels of GH, exhibited a decrease of furosemide-induced natriuresis and an increase of amiloride-stimulated natriuresis compared with controls. Enhanced Na(+),K(+)-ATPase activity and altered proteolytic maturation of epithelial sodium channel (ENaC) subunits in the cortical collecting ducts (CCDs) of GC rats provided additional evidence for an increased sodium reabsorption in the late distal nephron under chronic GH excess. In vitro experiments on KC3AC1 cells, a murine CCD cell model, revealed the expression of functional GH receptors and IGF-I receptors coupled to activation of Janus kinase 2/signal transducer and activator of transcription 5, ERK, and AKT signaling pathways. That GH directly controls sodium reabsorption in CCD cells is supported by: 1) stimulation of transepithelial sodium transport inhibited by GH receptor antagonist pegvisomant; 2) induction of alpha-ENaC mRNA expression; and 3) identification of signal transducer and activator of transcription 5 binding to a response element located in the alpha-ENaC promoter, indicative of the transcriptional regulation of alpha-ENaC by GH. Our findings provide the first evidence that GH, in concert with IGF-I, stimulates ENaC-mediated sodium transport in the late distal nephron, accounting for the pathogenesis of sodium retention in acromegaly.
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PMID:Epithelial sodium channel is a key mediator of growth hormone-induced sodium retention in acromegaly. 1838 93

Numerous case reports of pregnancy in acromegaly exist, however detailed descriptions of changes in placental and pituitary GH and IGF-I throughout gestation are rare. A 19-yr-old female presented to this institution with signs and symptoms of a GH-secreting pituitary adenoma. Following transphenoidal hypophysectomy, she had 3 unplanned pregnancies, despite ongoing active disease. No pregnancy was complicated by glucose intolerance or hypertension and 3 healthy newborns were delivered near or at term. Clinical improvement was observed during each pregnancy, accompanied by IGF-I levels lower than in the non-pregnant state, the majority lying within the normal range. This was despite increasing placental GH levels, and was not consistent with previous reports in the literature. Further surgical and medical therapies for acromegaly failed to normalize nonpregnant GH or IGF-I levels in this woman. Estrogen is known to alter GH signaling via its interaction with Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. We hypothesize that increasing concentrations of estrogen or other pregnancy-related hormones resulted in her clinical and biochemical improvement during pregnancy. This may be used for future therapeutic benefit.
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PMID:Clinical and biochemical improvement in acromegaly during pregnancy. 1840 Dec 9

Epidemiological studies link intrauterine growth restriction (IUGR) to arterial hypertension in adulthood. We compared umbilical arteries from IUGR (n=12, <5th weight percentile) vs. appropriate for gestational age (AGA) infants (n=12) using structural and functional analyses. The vessel wall area of umbilical arteries in the IUGR group was significantly smaller than in the AGA group (2.8 vs. 3.8mm(2), P<0.05). Myographic measurements showed that maximal tension [mN/mm] as well as maximal force [mN] were both significantly increased in IUGR arteries compared with AGA arteries (P<0.05). Serum levels of IGF-I, a regulator of elastin synthesis, were significantly lower in IUGR cord blood (P<0.01) than in AGA cord blood. These IGF-I serum levels correlated significantly with maximum tension in umbilical arteries (P<0.01). Low intrauterine IGF-I serum levels may account for thinner and stiffer umbilical arteries in IUGR infants in comparison to AGA infants thereby providing a potential link to arterial hypertension in adulthood.
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PMID:Decreased umbilical artery compliance and igf-I plasma levels in infants with intrauterine growth restriction - implications for fetal programming of hypertension. 1907 Aug 92

The secondary occurrence of type 2 diabetes with various hormonal diseases (e.g. pituitary, adrenal and/or thyroid diseases) is a recurrent observation. Indeed, impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with acromegaly and hypercortisolism (Cushing syndrome). The increased cardiovascular morbidity and mortality associated with acromegaly and Cushing syndrome may partly be a consequence of increased insulin resistance that normally accompanies hormone excess. Acromegalic patients are insulin resistant, both in the liver and in the periphery, displaying hyperinsulinemia and increased glucose turnover in the basal post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is reported to range 16-56%, whereas the degree of glucose tolerance seems correlated with circulating growth hormone (GH) levels, age, and disease duration. Moreover, a family history of diabetes and concomitant presence of arterial hypertension have been found to predispose to diabetes as well. GH has physiological effects on glucose metabolism, stimulating gluconeogenesis and lipolysis, which results in increased blood glucose and free fatty acid levels. Conversely, insulin-like growth factor 1 (IGF-I) enhances insulin sensitivity primarily on skeletal muscles. However, in acromegaly, increased IGF-I levels are unable to counteract the insulin-resistance status determined by GH excess. Therapy with somatostatin analogues (SSAs) induce control of GH and IGF-I excess in the majority of patients, but their inhibitory effect on pancreatic insulin secretion might complicate the overall effect of this treatment on glucose tolerance. Hypercortisolism produces visceral obesity, insulin resistance, and dyslipidemia that together with hypertension, hypercoagulability, and ventricular morphologic and functional abnormalities increase cardiovascular risk, and persist up to 5 years after resolution of hypercortisolism. Hypercortisolism leads to hyperglycaemia and reduced glucose tolerance, determines insulin resistance, stimulates hepatic gluconeogenesis and glicogenolisis. In Cushing syndrome the prevalence of diabetes varies between 20 and 50%, but probably this prevalence is underestimated, as not always an oral glucose tolerance test is performed in the presence of an apparently normal fasting glycaemia. Again, disease duration, rather than hormone levels, seems to be the major determinant in the occurrence of systemic complications in Cushing syndrome. Due to the impact they have on mortality and morbidity in both acromegaly and Cushing syndrome, these complications should be treated aggressively. In patients with neuroendocrine tumours (NETs) the occurrence of altered glucose tolerance may be due to a decreased insulin secretion, like it happens in patients who underwent pancreatic surgery and in those with pheochromocytoma, or to an altered counterbalance between hormones, such as in patients with glucagonoma and somatostatinoma. Moreover, SSAs represent a valid therapeutic choice in the symptomatic treatment of NETs, and also in this case the medical therapy of the primary disease, may have a significant impact on the prevalence of glucose metabolism imbalance. In thyroid disorders, an abnormal glucose tolerance may be principally encountered in hyperthyroidism. The pathogenesis is complex and scant data on prevalence and severity are found in the literature. Adequate treatment for glucose imbalance is mandatory in these peculiar patients in line with the American Diabetes Association and the European Association for the Study of Diabetes consensus statement. In particular, since traditional insulins have two features that may complicate therapy (absorption profiles, delayed onset of action and peak activity), the new insulin analogues could be of particular interest in the management of the secondary diabetes associated with endocrinopathies, considering the frailty of these patients. Indeed, it has been demonstrated that insulin glargine, given once daily, reduces the risk of hypoglycaemia compared with other formulations, and can facilitate a more aggressive insulin treatment in this class of patients.
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PMID:Secondary diabetes associated with principal endocrinopathies: the impact of new treatment modalities. 1932 13

We report a 59-year-old acromegalic woman, who presented with generalized bone pain, weakness, fatigue and foamy urine, who was found to have multiple myeloma (MM); and a 60-year-old acromegalic woman with dizziness, vomiting and abdominal pain, high blood pressure and splenomegaly that was posteriorly diagnosed as having Waldenstrom's macroglobulinemia (WM). Acromegaly is an uncommon disease and epidemiological studies have provided increasingly debated evidence that elevated IGF-I levels might enhance the neoplastic risk, and that cancers constitute the third leading cause of mortality in acromegaly. It is known that GH and IGF-I can activate B cell lymphocytes, and that IGF-I receptor is universally expressed in MM cells. Although the complication of acromegaly with WM or MM in patients has rarely been reported until now, we described two case reports of acromegalic patients with those hematological neoplasias, which allow a discussion about this controversial issue.
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PMID:Hematologic neoplasias and acromegaly. 1933 40

Acromegaly is a disease characterized by chronic growth hormone (GH) excess. Since hypertension is a common finding in patients with acromegaly, interactions between GH and the renin-angiotensin-aldosterone system (RAAS) are under controversial debate. We examined GH, IGF-I, aldosterone, and renin in a well-defined group of acromegalic patients before and after cure by surgery. In addition, we analyzed the impact of chronic GH excess on the RAAS in mouse models over-expressing GH alone (G) or in combination with insulin-like growth factor-binding protein-2 (IGFBP-2; GB). Normalization of GH secretion after cure by surgery was accompanied by significant decreases of serum aldosterone in acromegalic patients (pre-op: 96.5 +/- 37.1 pg/mL, post-op: 41.3 +/- 28.2 pg/ mL; P < 0.001; n = 13), but renin concentrations were unaffected. In addition, aldosterone concentrations were positively correlated to GH levels (Spearman r = 0.39; P = 0.025; n = 26). To further study this association, we analysed two transgenic mouse models and found a similar relationship between GH and aldosterone in G mice, which showed about 3-fold elevated serum aldosterone levels in comparison to non-transgenic controls (males: 442 +/- 331 pg/mL vs. 151 +/- 84 pg/mL; P = 0.002; n > or = 12; females: 488 +/- 161 pg/mL vs. 108 +/- 125 pg/mL; P = 0.05; n > or = 4). Expression of aldosterone synthase was similar in adrenal glands of C and G mice. Aldosterone levels in G and GB mice of both genders were not different, indicating that the elevated aldosterone was due to GH excess and not caused by elevated IGF-I, which is known to be blocked by IGFBP-2 overexpression. Also in the mouse models, changes in aldosterone were independent from renin. In summary, we show that chronic GH excess is associated with increased aldosterone in humans and mice. GH-induced increases of aldosterone potentially contribute to the increased cardiovascular risk in acromegalic patients. The underlying mechanism is likely to be independent of renin, excess IGF-I, or adrenal aldosterone synthase expression.
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PMID:Chronic growth hormone excess is associated with increased aldosterone: a study in patients with acromegaly and in growth hormone transgenic mice. 1949 73

Milk intake is widely recommended for a healthy diet. Recent evidences suggest that milk/dairy products are associated with a lower risk of type 2 diabetes and hypertension. On the other hand, high calcium intake has been associated with a higher risk of prostate cancer. The calcium and vitamin D content in dairy foods could have beneficial effects on glucose metabolism and renin/angiotensin system as well regulates body weight. The association between high dairy/calcium consumption and prostate cancer risk are related to the presence of estrogens and insulin like growth factor (IGF-I) in milk. Based on the current evidence, it is possible that milk/dairy products, when consumed in adequate amounts and mainly with reduced fat content, has a beneficial effect on the prevention of hypertension and diabetes. Its potential role in the pathogenesis of prostate cancer is not well supported and requires additional study.
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PMID:Milk intake and the risk of type 2 diabetes mellitus, hypertension and prostate cancer. 1976 59

Assessment of coronary calcium deposits (CCD) by coronary computed tomography (CT) was recently introduced for evaluation of risk to develop events related to coronary heart disease (CHD). We investigated occurrence of CCD in 19 hypopituitary patients (patients), 34 healthy (H) subjects (H controls) and 36 patients with a similar rate of diabetes mellitus and hypertension (morbid, M), but without pituitary diseases (M controls). Patients were replaced with L-thyroxine, cortone acetate, sex hormones and/or desmopressin, but never with GH. Unenhanced coronary CT was performed by 16-row multislice scanner. Framingham score (FS) was calculated and CCD were measured by Agatston score (AS) in all subjects. AS>10 indicates increased CHD risk. CCD and AS >10 were detected in 50% and 33% of patients, respectively. Prevalence of CCD and mean AS were higher in patients than in H and M controls. In patients, AS was negatively dependent on IGF-I levels (p<0.01) and IGF-I SD (p<0.05), and AS >10 was associated with occurrence of hypertension (p<0.02) and hyperinsulinism (p<0.05). Men and women showed the same prevalence of AS >10 (25 vs 31%). FS and AS correlated significantly (rs=0.33, p<0.001), but CCD were detected also in 3/11 patients with low FS. In conclusion, 58% of patients were at CHD risk on the basis of increased FS and/or AS, above all if they were hypertensive and/or showed hyperinsulinism. CCD were detected also in patients with low FS. CHD risk is higher in women. Risk of CCD is increased in patients with low IGF-I levels.
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PMID:High prevalence of coronary calcifications and increased risk for coronary heart disease in adults with growth hormone deficiency. 2051 26

The approach to a patient with acromegaly and persistent disease after surgery requires a complex diagnostic assessment. Acromegaly is a chronic and insidious disease that is associated with multisystem comorbidities, including cardiovascular disease, hypertension, sleep apnea syndrome, colon polyposis, arthropathy, and metabolic complications including glucose intolerance and type 2 diabetes mellitus. Patients also have a variety of signs and symptoms, including headache, arthralgias, carpal tunnel syndrome, sweating, fatigue, and psychological issues that impact significantly on quality of life. The recommended approach to the evaluation of the postoperative patient includes a biochemical assessment, with measurement of serum IGF-I along with a glucose-suppressed GH value, radiological assessment to determine location of residual tumor and presence of mass effects, a physical examination for evidence of skeletal and soft tissue overgrowth and related signs of acromegaly, and a thorough clinical assessment for the presence of comorbidities. Repeat surgery is indicated if there is residual tumor that is surgically accessible and there may be a chance for surgical cure, or if there are persistent mass effects upon the optic chiasm. Otherwise, medical therapy is indicated, utilizing somatostatin analogs, dopamine agonists, and pegvisomant, a GH receptor antagonist. Radiation therapy is usually relegated to situations where medical therapy is ineffective or poorly tolerated or where patients would prefer not to sustain the cost of long-term medical therapy. The choice of therapy requires close dialog among endocrinologists, neurosurgeons, radiation therapists, and neuroophthalmologists for optimal care of patients.
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PMID:Approach to the patient with persistent acromegaly after pituitary surgery. 2082 64


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