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

60,000 women in France have received RU 486 and a prostaglandin to induce abortion. In the late 1980's, clinical researchers assessed the safety and effectiveness of 600 mg of oral RU 486 in 2040 French women. 2 days later, health workers either injected 0.25-0.5mg of sulprostone or inserted a 1mg vaginal suppository of gemeprost in 1964 women who had not yet aborted. 96% experienced complete abortions. Physicians needed to conduct either a vacuum aspiration of dilation and curettage on the other 4%. RU 486 was most successful with 0.5mg of sulprostone, but these women also experienced considerable vaginal bleeding and pain. Overall uterine bleeding occurred for 8.9 days. The researchers recommended that adequate medical facilities be accessible to women using this method. Mild side effects were nausea, vomiting, and diarrhea. Efficacy and safety matched those of other early abortion methods. In April 1991, a grand multiparous women who smoked heavily and received RU 486 and a prostaglandin died--the 1st reported RU 486 related death. RU 486 may be able to treat fibroids, endometriosis, premenstrual syndrome, meningioma, hypertension, adrenal cancer, glaucoma, some forms of Cushing's syndrome, and breast cancer. The US Food and Drug Administration forbade the commercial import of RU 486 in 1989, even though it deemed RU 486 safe and effective. FDA considered the antiabortion view of the Bush Administration when making this decision. It made this decision despite the fact that abortion was still legal. RU 486 should be available soon for use as an abortifacient in the UK, the Netherlands, Sweden, Norway, Denmark, and Finland. These countries do not intent providing it to US women, however. Further the manufacturer is not willing to provide it to US researchers because it is afraid of antiabortion repercussions which may jeopardize WHO's approval of RU 486.
 ...
PMID:The RU 486 story: the French experience. 173 8

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.
 ...
PMID:[Current therapy of endocrine organ tumors (adrenal and parathyroid glands)]. 334 84

Recent increased use of ultrasonography and computed tomography (CT) has detected a substantial number of incidentally discovered adrenal tumor (incidentaloma). In our institute the discovery rate of adrenal incidentaloma per number of abdominal CT examinations was 0.43%. Those incidentalomas were incidentally found during examination for abdominal discomfort and lumbar pains or evaluation of the cause of hypertension. In the group study by the research committee on "Disorders of Adrenal Steroid Hormones" under the sponsorship of the Ministry of Health and Welfare of Japan, in 53 of 149 patients with incidentaloma, surgical resection was done during 5 years between 1983 and 1989. The pathological examination of those tumors revealed 67.9% of non-hyperfunctioning adrenocortical adenoma, 9.4% of adrenal cancer, 9.4% of ganglioneuroma, 5.7% of pheochromocytoma, 5.7% of adrenal cyst and 1.9% of myelolipoma. The criteria for resection of adrenal incidentaloma have not been established. However, tumors having a diameter of over 5 cm are generally excised in most institutes. Tumors having a diameter of between 3 cm and 5 cm are usually resected if the shape of the tumor is ambiguous and the margin of the tumor is irregular. Tumors having a diameter of less than 3 cm should be carefully followed up by abdominal CT examination every 6 months.
 ...
PMID:[Adrenal incidentaloma]. 833 Jun 54

As a potent antagonist of glucocorticoid and progesterone receptors, mifepristone (RU-486) has potential use in the treatment of Cushing's syndrome. Initial research in this area has demonstrated that RU-486 acts as an anti-glucocorticoid by antagonizing the negative feedback on the pituitary of endogenous and exogenous glucocorticoids. Since 1985, the literature has reported four studies of the feasibility of RU-486 treatment in Cushing's syndrome patients. In the largest of these studies, 11 patients with inoperable adrenal cancer or ectopic adrenocorticotrophic hormone-secreting neoplasms received 5-22 mg/kg/day of RU-486 for 1-12 months. In seven of these patients, treatment resulted in marked improvement in the Cushingoid phenotype, psychiatric status, hypertension, and carbohydrate intolerance. Three patients discontinued RU-486 because of clinical manifestations of adrenal insufficiency. The most common side effect was nausea. Titration of RU-486 dosing remains imprecise due to the lack of an acceptable rapid biochemical measurement to monitor glucocorticoid action. Regrettably, further research in this area has been hindered by the political controversy regarding RU-486's use as an abortifacient agent.
 ...
PMID:Mifepristone: treatment of Cushing's syndrome. 873 15

Patients with malignant lesions of the adrenal gland may present with a syndrome of excess mineralocorticoids. Both primary hyperaldosteronism and excess mineralocorticoids other than aldosterone resulting from adrenal carcinoma have rarely been reported. In most patients with adrenal tumors secreting mineralocorticoids other than aldosterone, distant metastasis had already occurred at the time of diagnosis and the prognosis was poor. We present a rare case of adrenal cancer with hypertension in a patient with low plasma renin activity and a low plasma aldosterone concentration. The patient's blood pressure returned to normal after removal of the tumor. The patient is still alive and without recurrence 6 years after surgery. This case illustrates the value of thorough evaluation of hypertension and prompt surgical treatment for patients with adrenal cancer.
 ...
PMID:Adrenal cancer with hypertension but low plasma renin and aldosterone. 1006 79

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.
 ...
PMID:Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling. 1188 72

The genetic and histopathological backgrounds of adrenocortical tumorigenesis remain poorly characterized. In other tissues, there is conclusive evidence that hyperplasia and adenomas precede cancer. In the adrenal, there are few clinical cases of either hyperplasia or adenoma associated with later development of cancer, and there are few biological studies that attempt to characterize this process molecularly. Current research focuses on the early lesions of the adrenal cortex because of their possible molecular link with carcinogenesis, and evidence of their frequent association with atypical forms of Cushing's and Conn's syndromes, obesity, hypertension and/or diabetes. These studies indicate a model for oncogenesis that is the same as that in other tissues. The rarity of adrenal cancer compared to benign lesions could be a clue to unique features of adrenocortical cells. It might also highlight the function of genes that are associated with endocrine tumors in the context of which the concept of gene 'conductors' is introduced here.
 ...
PMID:Genetics of adrenocortical tumors: gatekeepers, landscapers and conductors in symphony. 1458 Jul 59

Our prior phase I study of the combination of vascular endothelial growth factor (VEGF) antibody, bevacizumab, and VEGF receptor (VEGFR) inhibitor, sunitinib, in advanced solid tumors identified an encouraging response evaluation. An expansion phase of this study was thus undertaken to obtain further safety data, response assessment and characterization of pharmacodynamic biomarkers in melanoma, renal, and adrenal carcinoma patients. Patients with metastatic solid tumors received sunitinib (37.5 mg/d, 4 wk on/2 wk off) and bevacizumab (5 mg/kg intravenously every 2 wk). Responses were assessed every 2 cycles. Serum levels of angiogenic molecules were measured using ELISA assays. Twenty-two patients were enrolled, including 11 melanoma, 5 renal cell carcinoma (RCC), 5 adrenal cancer, and 1 angiosarcoma. Grade 3 or higher adverse events were observed in 15 patients, including hypertension (41%), thrombocytopenia (23%), and fatigue (14%). Three RCC patients, and 1 melanoma patient developed thrombotic microangiopathy (TMA). Partial response (PR) occurred in 21% patients, including melanoma (2), adrenal (1), and renal (1) carcinomas. Overall, 6 patients demonstrated some reduction in their tumor burden. Serum VEGF and several other proangiogenic proteins declined over the first 4 wk of treatment whereas the putative VEGF-resistant protein, prokineticin-2, increased over 10-fold. Occurrence of TMA related to dual VEGF/VEGFR inhibition can result from systemic or nephron specific injury even in non-renal malignancies. While the combination of sunitinib and bevacizumab was clinically efficacious in renal cell carcinoma and melanoma, the observance of microangiopathy, even in non-RCC patients, is a significant toxicity that precludes further clinical development.
...
PMID:Dual VEGF/VEGFR inhibition in advanced solid malignancies: clinical effects and pharmacodynamic biomarkers. 2484 48