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)

A case of adrenocorticotropic hormone independent bilateral adrenocortical macronodular hyperplasia (AIMAH) is reported. A 59 year old male was admitted to hospital because of hypertension. Subsequently, hypercortisolism, low plasma adrenocorticotropic hormone (ACTH), loss of diurnal rhythm of ACTH, lack of suppression with high dose dexamethasone were found and bilateral adrenal enlargement was detected by abdominal computerized tomography and adrenal scintigraphy. Bilateral total adrenalectomy was performed under a diagnosis of bilateral adrenal hyperplasia associated with Cushing's syndrome. Both adrenal glands were enlarged in size and weight. Bulging nodules were found at the cut section. Microscopically, a variegated histologic pattern including trabecular, adenoid and zona glomerulosa-like (ZG-like) structures was revealed in the nodules. Immunohistochemical examination disclosed positive staining of cytochrome P-450 17 alpha, negative of 3 beta-HSD in the ZG-like structure. Ultrastructurally, the cells composing the ZG-like structure were similar to those of the ZG in normal adrenal cortex. The authors agree that AIMAH is one of the entities causing Cushing's syndrome, and advise pathologists to keep this disorder in mind when they examine the adrenals in Cushing's syndrome.
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PMID:Adrenocorticotropic hormone-independent bilateral macronodular adrenocortical hyperplasia associated with Cushing's syndrome. 778 95

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary cause of human hypertension in which aldosterone secretion is regulated by adrenocorticotropin (ACTH). A genetic mutation which causes GRA has recently been identified in our laboratory, a hybrid or chimeric gene fusing nucleotide sequences of the 11 beta-hydroxylase and aldosterone synthase genes. The finding that these chimeric gene duplications are sensitive and specific markers for GRA allows for a simple, direct genetic test for this disorder. In preliminary studies, we found a wide range of blood pressure levels (including normotension) in affected GRA subjects. Studies to data indicate that this is not related to environmental factors such as sodium intake. Another possibility is that chimeric gene expression is variable, with low blood pressure subjects having reduced gene expression. However, the data have not demonstrated differences in steroid levels in subjects with severe versus mild hypertension. In fact, it is likely that the wide range in blood pressure levels in affected subjects involves interaction of other systems which control blood pressure. Preliminary data in two kindreds suggest that blood pressure levels are reciprocally related to levels of urinary kallikrein excretion, supporting the notion that GRA is a hypertension-predisposing syndrome, with the resultant blood pressure the interaction of the gene mutation with other blood pressure regulatory systems. Although GRA is a mineralocorticoid excess state, as evidenced by profoundly suppressed levels of plasma renin activity, we have observed (contrary to the reported literature) that normokalemia is a typical finding. In one large normokalemic pedigree, preliminary findings indicate that these subjects have a normal capacity to excrete potassium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoid-remediable aldosteronism (GRA): diagnosis, variability of phenotype and regulation of potassium homeostasis. 779 15

In an attempt to locate biochemical markers specific for fetal distress we measured the amniotic concentrations of beta-endorphin, ACTH, cortisol, dopamine, norepinephrine and epinephrine with its major metabolite metanephrine (MN) in pregnancies with documented fetal well-being and pregnancies complicated by hypertension and fetal distress. While higher levels of cortisol and MN were found only in a selected subgroup of highly compromised subjects (p < 0.001 and p < 0.005, respectively), beta-endorphin increased significantly under conditions of moderate or severe intrauterine sufferance (p < 0.001 in both cases). Due to higher levels of the opioid even during the initial stage of fetal discomfort we evaluated its characteristics as a possible clinical marker. Specificity was 88.5%, whereas the sensitivity of 65.6% in the moderately compromised subgroup increased to 88.9% in severely suffering fetuses. Although more accurate and mainly real-time information on the fetal health status is obtained by means of biophysical methods, the determination of amniotic fluid beta-endorphin might be of clinical usefulness in prenatal diagnosis.
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PMID:Stress mediators in the amniotic compartment in relation to the degree of fetal distress. 781 78

Infantile spasms is a refractory seizure disorder for which a number of different treatment regimens are available. No information is available on which treatment regimens are most widely used and which would be of practical importance in designing clinical trials to determine efficacy of new treatments. We proceeded to gather data on the most commonly employed methods of treating infantile spasms. A survey was mailed in 1991 to all junior, active, and emeritus members of the Child Neurology Society asking details about the treatment of infantile spasms. Telephone follow-up on a random sample of nonresponders was made. The total response rate was 58.3%. Most respondents who treat infantile spasms use corticotropin (ACTH) as their drug of first choice (88%). The most frequently used dosage was 40 IU per day, and the most frequent duration of treatment was 1 to 2 months. The most frequently reported side effects of ACTH or oral corticosteroid treatment were cushingism, behavior changes or irritability, hypertension, topical infections, and systemic infections. Of those not using ACTH, valproic acid was the next most commonly employed agent, followed by oral corticosteroids. The results were similar for all respondents regardless of age, sex, type of practice, number of cases of infantile spasms seen, location (United States or abroad) or whether the survey was completed by mail or telephone. These data suggest that there is a relative uniformity among child neurologists in the management of infantile spasms despite the publication of many alternative treatment strategies.
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PMID:The treatment of infantile spasms by child neurologists. 782 38

Familial glucocorticoid resistance (FGR) is a rare hereditary disorder characterized by hypercortisolism and the absence of stigmata of Cushing's syndrome. The inability of glucocorticoids to exert their effects on target tissues is compensated for by increases in circulating corticotropin (ACTH) and cortisol, the former causing excess secretion of both adrenal androgens and adrenal steroid-biosynthesis intermediates with salt-retaining activity. There is considerable variability in the clinical presentations of FGR ranging from asymptomatic, to isolated chronic fatigue and to hypertension with or without hypokalemic alkalosis or to hyperandrogenism, or both. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men it may lead to infertility and in children to precocious puberty. The reported molecular defects in FGR, such as point mutations and a microdeletion of the glucocorticoid receptor (GR) gene, cause partial resistance by, respectively, compromising the function of the GR or decreasing its intracellular concentration in glucocorticoid target tissues. Complete glucocorticoid resistance is believed to be incompatible with life in humans. Hence, the glucocorticoid resistance cases reported have been partial and of variable degree. The extreme variability in the clinical manifestations of the disorder can, additionally, be explained by differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps by different biochemical defects of the glucocorticoid receptor, causing selective resistance of certain glucocorticoid responses in specific tissues. Isolated tissue-resistance from a somatic mutation of the GR in a corticotropinoma from a patient with Nelson's syndrome was also found, suggesting that this may be a mechanism of tumorigenesis. There is additional evidence that defects of GR function can appear surreptitiously in a variety of clinical conditions, suggesting that glucocorticoid resistance in humans may be involved in the pathogenesis and/or clinical picture of a plethora of disease states, of which FGR is the archetype.
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PMID:Glucocorticosteroid resistance in humans. Elucidation of the molecular mechanisms and implications for pathophysiology. 782 90

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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PMID:Weaning of immunosuppression in long-term liver transplant recipients. 783 42

The zona glomerulosa cells of the adrenal gland have an intrinsic renin-angiotensin system that appears to modulate the aldosterone response to potassium and corticotropin. The actions of circulating angiotensin II (Ang II) are mediated by the activation of the Ang II type 1 (AT1) receptor on the adrenal cortex. In this study we examined the effects of the AT1 receptor antagonist DuP 753 and other antagonists on aldosterone secretion in cultured bovine zona glomerulosa cells. Zona glomerulosa cells were cultured in PFMR-4 medium containing 10% fetal calf serum for 72 hours, and the medium was replaced with serum-free medium for the next 24-hour experimental period. DuP 753 (10 mumol/L) inhibited basal aldosterone secretion (from 88.6 +/- 7.1 to 54.8 +/- 9.6 pg/10(6) cells per hour; 38% inhibition). EXP 3174, an active metabolite of DuP 753, also inhibited aldosterone dose dependently (from 88.6 +/- 7.1 to 55.9 +/- 8.4 at 1 mumol/L and 88.6 +/- 7.1 to 21.7 +/- 3.3 at 100 mumol/L; 37% and 75% inhibition, respectively). Another and more potent AT1 receptor antagonist, L158,809, showed significant inhibition at 100 nmol/L, and at 10 mumol/L it inhibited basal aldosterone secretion (from 144.7 +/- 18.2 to 83.4 +/- 17.1 pg/10(6) cells per hour; 42% inhibition). DuP 753 inhibited Ang II (100 nmol/L)-stimulated aldosterone production in a dose-dependent fashion, with a 30% reduction at 100 nmol/L and complete inhibition at 100 mumol/L. DuP 753 also inhibited potassium (12 nmol/L) and corticotropin (1 nmol/L) stimulation of aldosterone in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Mar
PMID:Locally generated angiotensin II in the adrenal gland regulates basal, corticotropin-, and potassium-stimulated aldosterone secretion. 787 70

To study the relationship between somatostatin (SS), atrial natriuretic peptide (ANP), beta-endorphin (beta-EP), aldosterone (Aldo) and pregnancy induced hypertension (PIH), blood was collected from 69 cases, including non-pregnant women, normal pregnant women, patients with PIH and their newborns (umbilical arteries) and plasma levels of ANP, SS, beta-EP, Aldo were measured by radioimmunoassay. Results indicated that ANP, SS beta-EP and Aldo levels either during normal pregnancy or at delivery were significantly higher than those in non-pregnant women. ANP, SS and beta-EP levels in last trimester of patients with PIH, particular in severe cases, were significantly higher than those in normal pregnancy or moderate PIH whereas Aldo levels were lower in PIH when compared with normal pregnancy. A positive correlation between ANP, SS levels and the severity of PIH was observed. Levels of ANP, SS, beta-EP and Aldo in newborns were higher than those in mothers at delivery. Levels of ANP and SS in neonates born to mother of PIH were much higher, whereas beta-EP and Aldo were lower as compared with normal pregnancy. The conclusion is that high levels of ANP and Aldo during pregnancy may play an important role in stabilizing blood pressure and maintaining the balance of water and electrolyte. Therefore it could be used as an index for prediction of PIH.
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PMID:[Relation between somatostatin, atrial natriuretic peptide, beta-endorphin, aldosterone and pregnancy induced hypertension]. 790 29

A number of mechanisms may be involved in the protective effect of low ethanol (ETOH) consumption on the development of the age-dependent hypertension in both human and experimental animals. It was the objective of the present study to test the hypothesis that acute administration of low doses of ETOH would increase the plasma content of atrial natriuretic peptide (ANP), a hormone known to decrease blood pressure. Plasma ANP levels were increased significantly within 15 min after the i.p. injection of 1 or 2 g of ETOH/kg b.wt. The increase in plasma ANP was more pronounced and longer lasting after the i.p. injection of 2 rather than 1 g of ETOH/kg b.wt. This increase in plasma ANP level was associated with a rapid decrease of atrial ANP, but not of ventricular ANP which on the contrary was significantly elevated at 120 min postinjection. It has been suggested that opioids could play a significant role in controlling ANP release. In fact, circulating levels of beta-endorphin were also rapidly increased after the ETOH injection, with a time-course pattern similar to that of ANP. Furthermore, a highly positive correlation was found between the ETOH-induced changes of plasma ANP and beta-endorphin contents. Significant increases in plasma corticosterone and adrenocorticotropic hormone, but not aldosterone contents, were observed after the i.p. injection of 2 g of ETOH/kg b.wt., whereas plasma arginine vasopressin levels were significantly decreased at 15 but not at 120 min postethanol. There was no significant elevation in blood pressure during the 120-min experimental period, although a small tachycardia did develop in the ETOH-treated animals. Thus, acute in vivo administration of ETOH increased plasma ANP content in a dose-dependent manner and may play a role in the "protective" effect of low ETOH consumption in the development of the age-dependent hypertension.
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PMID:Increased plasma atrial natriuretic peptide after acute injection of alcohol in rats. 799 81

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 micrograms/kg per day) were examined in conscious sheep (n = 8). Mean arterial pressure increased from 81 +/- 2 to 93 +/- 3 mm Hg (P < .001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13 +/- 0.19 to 6.06 +/- 0.33 L/min (P < .01) because of an increase in stroke volume from 65 +/- 4 to 79 +/- 8 mL per beat (P < .01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8 +/- 0.2 to a minimum of 4.9 +/- 0.3 (mL/min)/mm Hg (P < .05), and renal conductance increased from 3.5 +/- 0.3 to 4.6 +/- 0.3 (mL/min)/mm Hg (P < .001). There was a small increase in iliac conductance (P < .05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278 +/- 18 to 403 +/- 23 mL/min (P < .001); mesenteric blood flow was unchanged; there was a small increase in iliac blood flow (P < .01); and coronary blood flow increased (P < .05), paralleling the change in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jul
PMID:Differential regional hemodynamic effects of corticotropin in conscious sheep. 802 Oct 7


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