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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenomas of the adrenal cortex which produce aldosterone (APA) are among the surgically correctible causes of hypertension accounting for 0.5 to 1.0% of all hypertensive etiologies. The adenomas have a 5:1 predilection for women and generally present with hypertension or profound hypokalemia. A low plasma renin activity completes the triad for primary hyperaldosteronism which could be caused by adrenocortical cancer, a neoplasm with an average diameter of 12 cm, or idiopathic hyperaldosteronism (IHA), a bilateral hyperplasia of the zona glomerulosa of the adrenal cortex which responds poorly to surgical resection. The adenomas are small (2 cm) but can be localized by imaging or selective venous sampling. Resection has a high success rate with minimal morbidity.
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PMID:Aldosterone-producing tumors (Conn's syndrome). 218 43

Since the adrenal or parathyroid cancer is a clinically rare entity. We often have difficulty in its diagnosis and treatment. The adrenocortical cancer is usually classified into two categories--endocrinologically functioning or non-functioning. The incidence is not different between them. It is often found in an advanced stage as it does not show clinical manifestation before it has grown up to a large tumor. Only an effective agent for the adrenal cancer is op'-DDD so far. Recently, cisplatin, VP-16 (etoposide) and others are administered as trial use. Most of malignant pheochromocytomas are endocrinologically active and they often cause hypertension leading to death. Therefore it is important to control hypertension in malignant pheochromocytoma. Chemotherapy and irradiation are not effective for it. Recently, 131I-MIBG (metaiodobenzylguanidine) is found to be useful not only for diagnosis but also treatment of malignant pheochromocytoma. 131I-MIBG is accumulated specifically in the chromaffin cells and with helpful to find out metastatic foci. It is also used in a large amount as a specific irradiation therapy for this malignancy. Parathyroid cancer is found in approximately 3 percent of primary hyperparathyroidism. Clinically it usually reveal serum calcium level higher than 14 mg/dl, bone lesions and renal dysfunction in addition to palpable cervical tumors adhering with skin. Sometimes it is difficult to differentiate malignancy from adenoma in histology. Most cases develop local recurrences and distant metastases in due course and dies of hypercalcemia. It is very important to control hypercalcemia in inoperable cases. As both chemotherapy and radiation therapy render no effect on this malignancy. Surgery is a sole strategy for it.
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PMID:[Current therapy of endocrine organ tumors (adrenal and parathyroid glands)]. 334 84

Inhibitors of steroid synthesis such as o,p'-DDD, aminoglutethimide, metyrapone, trilostane and ketoconazole are usually used for treatment of Cushing's syndrome in order to reduce the steroid production in the patients showing several complications, including severe hypertension and diabetes mellitus, and also an incomplete remission after the surgical treatment. o,p'-DDD and metyrapone are recommended to use for treatment of adrenocortical cancer and rapid reduction of cortisol levels, respectively. Aminoglutethimide and trilostane do not always have any side effects, although ketoconazole which is commonly used for treatment of Cushing's disease shows severe hepatic damage. RU 486 is effective for inhibiting the activity of glucocorticoid receptor, and will be used for treatment of Cushing's syndrome in near future.
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PMID:[Clinical usefulness of pharmacological treatment of Cushing's syndrome]. 816 84

230 patients with arterial hypertension of adrenal origin were treated. 205 of them underwent adrenalectomy with surrounding paranephral fat. There were no lethal outcomes. Endogenic adrenocorticism was diagnosed in 134 patients. Cushing's syndrom was in 96 patients, Cushing's disease--in 34, ACTH-ectopic syndrome--in 2, adrenocortical cancer--in 2. Primary hyperaldosteronism was diagnosed in 42 cases: idiopathic hyperaldosteronism in 23 patients, aldosteronproducing adenoma (Conn's syndrome)--in 19. Tumors of chromaffine tissue were defected in 30 patients. All the patients underwent complex examination (hormonal profile, US, CT, MRT, angiography if it was necessary). Symptomatic arterial hypertension of adrenal origin was diagnosed during one year in 10% patients only because of absence of typical clinical picture. Use of complex examination has permitted to make a correct topical diagnosis and to choose optimum treatment policy in all the cases.
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PMID:[Diagnosis and surgical treatment of arterial hypertension of adrenal origin]. 1121 Mar 11

Systemic cortisol plays an important role in the metabolism of glucose, lipids and proteins, as well as in the regulation of electrolyte balance. It is well known that the development of the microvascular disease of various organs such as the heart and kidney, in patients with diabetes mellitus, hyperlipidemia and hypertension of which disorders are frequently associated with Cushing's syndrome. Thus, we should treat Cushing's syndrome as soon as possible, since many complications, including cardiovascular diseases and infections, will soon occur when the definite diagnosis is delayed. Adrenalectomy is essential for treatment for Cushing's syndrome even in the patients with pituitary or ectopic ACTH-producing tumor. Some case can not be treated with surgical procedures because of worsened conditions with several complications of infection and diabetes. Then we choose medical treatment. Medical adrenalectomy is achieved by using with mitotane which is usually used for adrenocortical cancer. We commonly treat the patients with Cushing's syndrome due to adrenal tumor and pituitary or ectopic ACTH producing tumor by using metyrapone which mainly inhibits 11-hydroxylase. Metyrapone is also recommended to treat the patients who are not well differentiated Cushing's disease from ectopic ACTH syndrome. We rarely use trilostane which is an inhibitor against 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Replacement therapy with hydrocortisone should be considered if adrenal failure will occur during treatment with those drugs.
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PMID:[Medical treatment for Cushing's syndrome]. 1818 63

Endothelial cells have been shown to induce adrenal steroidogenesis and to enhance aldosterone secretion via angiotensin II and endothelin 1-independent mechanisms. It has been demonstrated that endothelial cells and adrenocortical cells are capable of producing interleukin-6 (IL-6) and IL-6 is a factor known to stimulate adrenal cortisol secretion. We therefore asked whether endothelial cells have an effect on adrenal IL-6 generation and whether IL-6 mediates biosynthesis of aldosterone as is observed after exposure of adrenocortical cells to endothelial cell-conditioned medium (ECCM). Cells from the adrenocortical cancer cell line NCI-H295R were incubated with ECCM produced from human umbilical vein endothelial cells at increasing concentrations. As detected by an enzyme-linked immunosorbent assay, pure ECCM significantly increased IL-6 protein secretion by cultured adrenocortical cells in a dose-dependent fashion, to a 18.0+/-2.0 pg/mL (mean+/-SEM). This was paralleled by an enhanced IL-6 promoter activity as determined with the transfection of an IL-6-promoter-luciferase reporter gene construct. Pure ECCM also induced aldosterone secretion by adrenocortical cells more than three times that of controls with serum-free medium. ECCM PER SE contains significant amounts of IL-6 protein. However, blockade of IL-6 signal transduction did not interfere with aldosterone synthesis. These data suggest that endothelial cells secrete IL-6 and that endothelial cell-derived factors regulate adrenal IL-6 synthesis which does not alter adrenal aldosterone secretion. Our findings support the hypothesis that the endothelium and the adrenal gland may play a role in the development of some forms of hypertension and - more speculative - inflammation.
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PMID:The endothelium secretes interleukin-6 (IL-6) and induces IL-6 and aldosterone generation by adrenocortical cells. 1877 60

We recently demonstrated that a recurrent gain-of-function mutation in a T-type calcium channel, CACNA1H(M1549V), causes a novel Mendelian disorder featuring early-onset primary aldosteronism and hypertension. This variant was found independently in five families. CACNA1H(M1549V) leads to impaired channel inactivation and activation at more hyperpolarized potentials, inferred to cause increased calcium entry. We here aimed to study the effect of this variant on aldosterone production. We heterologously expressed empty vector, CACNA1H(WT) and CACNA1H(M1549V) in the aldosterone-producing adrenocortical cancer cell line H295R and its subclone HAC15. Transfection rates, expression levels, and subcellular distribution of the channel were similar between CACNA1H(WT) and CACNA1H(M1549V). We measured aldosterone production by an ELISA and CYP11B2 (aldosterone synthase) expression by real-time PCR. In unstimulated cells, transfection of CACNA1H(WT) led to a 2-fold increase in aldosterone levels compared with vector-transfected cells. Expression of CACNA1H(M1549V) caused a 7-fold increase in aldosterone levels. Treatment with angiotensin II or increased extracellular potassium levels further stimulated aldosterone production in both CACNA1H(WT)- and CACNA1H(M1549V)-transfected cells. Similar results were obtained for CYP11B2 expression. Inhibition of CACNA1H channels with the T-type calcium channel blocker Mibefradil completely abrogated the effects of CACNA1H(WT) and CACNA1H(M1549V) on CYP11B2 expression. These results directly link CACNA1H(M1549V) to increased aldosterone production. They suggest that calcium channel blockers may be beneficial in the treatment of a subset of patients with primary aldosteronism. Such blockers could target CACNA1H or both CACNA1H and the L-type calcium channel CACNA1D that is also expressed in the adrenal gland and mutated in patients with primary aldosteronism.
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PMID:CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil. 2725 46

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation. Because APA diagnosis requires a difficult invasive procedure, patients often remain undiagnosed and inadequately treated. Inhibitors of KCNJ5MUT could allow noninvasive diagnosis and therapy of APAs carrying KCNJ5 mutations. Here, we developed a high-throughput screen for rescue of KCNJ5MUT-induced lethality and identified a series of macrolide antibiotics, including roxithromycin, that potently inhibit KCNJ5MUT, but not KCNJ5WT. Electrophysiology demonstrated direct KCNJ5MUT inhibition. In human aldosterone-producing adrenocortical cancer cell lines, roxithromycin inhibited KCNJ5MUT-induced induction of CYP11B2 (encoding aldosterone synthase) expression and aldosterone production. Further exploration of macrolides showed that KCNJ5MUT was similarly selectively inhibited by idremcinal, a macrolide motilin receptor agonist, and by synthesized macrolide derivatives lacking antibiotic or motilide activity. Macrolide-derived selective KCNJ5MUT inhibitors thus have the potential to advance the diagnosis and treatment of APAs harboring KCNJ5MUT.
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PMID:Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma. 2860 87