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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 63-year-old female presented with the extremely rare occurrence of an aldosterone-secreting adrenocortical adenoma as part of the syndrome of multiple endocrine neoplasia type 1 (MEN1). Only two other MEN1 patients were reported in the literature with hyperaldosteronism. The patient's MEN1 syndrome consisted of the association of primary hyperparathyroidism due to parathyroid adenoma, a prolactinoma, and a toxic multinodular goiter. Elevated basal and meal-stimulated serum PP levels without demonstrable pancreatic tumor were also found. Genetic analysis of the aldosterone-secreting adenoma with DNA markers localized on chromosome 11 showed loss of heterozygosity in tumor DNA. Since the MEN1 syndrome is caused by loss of the tumor suppressor gene on chromosome 11 in the 11q13 region, it is probable that the same mechanism is associated with the formation of the adrenocortical adenoma.
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PMID:Aldosterone-secreting adrenal adenoma as part of multiple endocrine neoplasia type 1 (MEN1): loss of heterozygosity for polymorphic chromosome 11 deoxyribonucleic acid markers, including the MEN1 locus. 163 57

Radiation methods were used for examining 176 patients with hormonal-active tumors and 12 patients with hormonal-nonactive tumors. The correct diagnosis of tumor of the adrenals was established with the help of oxysuprarenography in 51.9%. Ultrasonic examination was used in 78.8% and roentgen computed tomography--in 93.5%. Differential diagnostics of the Itsenko--Cushing disease and Cushing syndrome, due to corticosteroma is possible on the basis of the whole complex of findings of USI, RCT and venography with determination of the level of cortisol, aldosterone, catecholamine in blood flowing from the adrenals.
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PMID:[Radiological diagnosis of tumors of the adrenal glands]. 165 27

A 25-year-old female was admitted for evaluation of hypertension and hypokalemia. Plasma renin activity was suppressed and plasma aldosterone level was higher than normal. The CT scan of adrenal gland revealed a 2.5cm in size low density tumor mass over right adrenal area, and NP-59 adrenal scan showed early and persistent uptake of radioactivity in the right adrenal gland. Interestingly, the plasma aldosterone level was elevated, decreased and unchanged to postural change on three different occasions. After right adrenalectomy, the plasma aldosterone level decreased to 4.77ng/dl, blood pressure, serum potassium, and plasma aldosterone returned to normal response to postural change. Histologically, it was compatible with the picture of cortical adenoma. However, the tumor cell may not have reached autonomous function yet, since different responses of plasma aldosterone to postural change were observed clinically.
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PMID:Aldosterone-producing adenoma--variable serum aldosterone response to postural change: a case report. 165 41

We have isolated and characterized two isozymes of mouse steroid 11 beta-hydroxylase (11 beta-OHase), designated 11 beta-OHase and aldosterone synthase (AS). Physical mapping of overlapping cosmid and phage isolates defined two genes (designated Cyp11b-1 and Cyp11b-2 in the standard nomenclature for cytochrome P450 genes) that are oriented in the same direction and separated by approximately 8 kilobase pairs of DNA. The two genes are highly homologous in their coding regions, with 84% nucleotide identity and 86% predicted amino acid identity. In regions where the sequences of the rat 11 beta-OHase and AS genes diverged most widely, the mouse sequences also differed significantly, thereby identifying putative mouse 11 beta-OHase and AS genes. Both genes were mapped to chromosome 15 by analyzing restriction fragment length variations in a panel of DNA samples from an interspecific cross. To determine the functional properties of the 11 beta-OHase and AS proteins, we transfected COS-7 cells with plasmids that expressed the proteins encoded by the 11 beta-OHase and AS genes. When expressed in transfected COS-7 cells, the 11 beta-OHase protein converted deoxycorticosterone to corticosterone but did not produce aldosterone. Consistent with its postulated role in mineralocorticoid biosynthesis, the product of the AS gene efficiently synthesized aldosterone. We next studied the expression of these two isozymes in Y1 adrenocortical tumor cells and in the intact mouse adrenal gland. Although Y1 cells otherwise resemble zona fasciculata cells and express the 11 beta-OHase gene at high levels, transcripts encoded by the AS gene were detected at levels approximately 10-fold lower than the 11 beta-OHase transcripts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different isozymes of mouse 11 beta-hydroxylase produce mineralocorticoids and glucocorticoids. 168 70

A gene encoding steroid 18-hydroxylase (P-450C18) was isolated from a human genomic DNA library. It was identified as CYP11B2, which was previously postulated to be a pseudogene or a less active gene closely related to CYP11B1, the gene encoding steroid 11 beta-hydroxylase (P-45011 beta) [Mornet, E., Dupont, J., Vitek, A. & White, P. C. (1989) J. Biol. Chem. 264, 20961-20967]. The nucleotide sequence of the promoter region of the P-450C18 gene is strikingly different from that of the P-45011 beta gene, although the sequences of their exons are 93% identical. The transient expression in Y-1 adrenal tumor cells of CAT constructs with a series of deletion mutants of promoter regions of both genes indicated that the two genes are regulated differently. P-450C18 as expressed in COS-7 cells exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta-hydroxylase activity as well. In contrast, P-45011 beta as expressed in the cultured cells exhibits steroid 11 beta-hydroxylase activity exclusively but fails to catalyze the synthesis of aldosterone and 18-oxocortisol. These results indicate that P-45011 beta and P-450C18 are products of two different genes and that the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.
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PMID:Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans. 174

Similar to growth factors aldosterone stimulates Na+/H+ exchange in renal target cells leading to cytoplasmic alkalinization. An alkaline intracellular pH reduces the H+ bonds between repressor proteins and DNA leading to the destabilization of the nuclear chromatin. We observed that sustained alkaline stress "per se" can lead to malignant transformation of Madin-Darby canine kidney (MDCK) cells. Cells grown for two weeks in alkaline culture medium (pH 7.8) developed multiple "foci" composed of spindle-shaped pleomorphic cells lacking contact inhibition and exhibiting poor adhesion to the culture support, typical characteristics of dedifferentiated tumor cells. "Focus" cells were cloned and grown in standard medium (pH 7.4). Cells maintained their abnormal growth pattern, indicating stable pH-induced genetic transformation. Cells were fused with polyethylene glycol to giant cells and impaled with microelectrodes. In contrast to non-transformed giant MDCK cells the plasma membrane potential showed spontaneous oscillations that could be virtually abolished by the omission of extracellular Ca2+ or by the addition of the K+ channel blocker Ba2+. We conclude that sustained alkaline stress can induce malignant transformation in MDCK cells indicated by an abnormal growth pattern and by membrane potential oscillations most likely due to Ca2+ activated K+ channels in the plasma membrane.
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PMID:Alkaline stress transforms Madin-Darby canine kidney cells. 174 13

Tumors of the female genital tract may be associated with a variety of unusual clinical manifestations. Uncommon endocrine and paraendocrine syndromes include production of human chorionic gonadotropin by tumors other than those of germ cell origin, hyperthyroidism associated with struma ovarii and gestational trophoblastic disease, the carcinoid syndrome, the Zollinger-Ellison syndrome, hypercalcemia, Cushing's syndrome, hypoglycemia, hypertension related to renin or aldosterone production, hyperprolactinemia, inappropriate secretion of antidiuretic hormone, and virilization associated with Nelson's syndrome and placental site trophoblastic tumor. Paraneoplastic syndromes associated with gynecological tumors include disorders of the nervous system, connective tissue, and skin, as well as hematologic abnormalities and the nephrotic syndrome. Heritable and other congenital syndromes associated with these tumors are the Peutz-Jeghers syndrome, the nevoid basal-cell carcinoma syndrome, Ollier's disease and Maffucci's syndrome, hereditary leiomyomatosis, ataxia-telangiectasia, von Hippel-Lindau's disease, thyroid abnormalities associated with Sertoli-Leydig cell tumors, and Carney's complex. Other syndromes associated with tumors of the female genital tract include Meigs' syndrome, hyperamylasemia, uveal melanocytic lesions, and pyrexia.
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PMID:Clinical syndromes associated with tumors of the female genital tract. 175 57

The steroid 11 beta-hydroxylase (P450c11) enzyme is responsible for the conversion of 11-deoxycortisol to cortisol in the zona fasciculata of the adrenal cortex. Animal studies have suggested that this enzyme or a closely related isozyme is also responsible for the successive 11 beta- and 18-hydroxylation and 18-oxidation of deoxycorticosterone required for aldosterone synthesis in the zona glomerulosa. There are two distinct 11 beta-hydroxylase genes in man, CYP11B1 and CYP11B2, which are predicted to encode proteins with 93% amino acid identity. We used a sensitive assay based on the polymerase chain reaction to analyze the expression of the CYP11B1 and B2 genes. Transcripts of CYP11B1 were detected at high levels in surgical specimens of normal adrenals and also in an aldosterone-secreting adrenal tumor. Transcripts of CYP11B2 were found at low levels in normal adrenals, but at a much higher level in the aldosterone-secreting tumor. CYP11B2 mRNA levels were increased in cultured zona glomerulosa cells by physiological levels of angiotensin-II. The entire coding regions of both CYP11B1 and B2 cDNAs were cloned from the tumor mRNA. Expression of these cDNAs in cultured COS-1 cells demonstrated that the CYP11B1 product could only 11 beta-hydroxylate 11-deoxycortisol or deoxycorticosterone, whereas the CYP11B2 product could also 18-hydroxylate cortisol or corticosterone. A small amount of aldosterone was synthesized from deoxycorticosterone only in cells expressing CYP11B2 cDNA. These data demonstrate that the product of CYP11B2 is required for the final steps in the synthesis of aldosterone.
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PMID:The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. 177 35

Specific renin has been identified in the outer layers of the adrenal of rat, mouse and human. Nephrectomy causes a marked elevation of adrenal renin, presumably through hyperkalemia. The subcellular distribution of adrenal renin was investigated by Percoll density gradient. The renin activity in the dense granules from the capsules of nephrectomized rats was 15 times greater than that of intact rats. Most of the active form renin was found in the dense renin granules. Immunohistochemical studies revealed that the dense granules increased in number after bilateral nephrectomy. Immunogold staining of these granules showed unequivocally the presence of renin therein. Adrenal capsules in organ culture were found to release renin at a steady rate. Renin release from bilaterally nephrectomized rat adrenals was 4.6 times greater than from the organs of intact animals. Further, adrenal slices from human adrenocortical tumor tissues which contained specific renin in a sizable quantity were found to release renin in a similar fashion to rats. The mechanism of the control of renin secretion from the adrenal gland was different from the kidney in that the release was stimulated by potassium chloride or angiotensin II but not by ACTH, suggesting stimulation by intracellular calcium. These results provide convincing evidence that the adrenal synthesizes renin, stores it in specific secretory granules, and secretes it in a regulated manner. It is most likely that the adrenal renin plays a role in the production of aldosterone in the adrenal cortex or in the secretion of catecholamines from the adrenal medulla through intra- and/or extracellular formation of angiotensin II.
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PMID:Renin in adrenal: an overview of its synthesis, subcellular localization, and functions. 182 83

A 55-year-old woman with bilateral multiple adenomas showed hypertension, muscle weakness, hypokalemia, moon-like face and truncal obesity. Increased serum and urinary levels of aldosterone were observed. Serum cortisol level did not show a normal circadian rhythm. Microscopic examination of the resected tumors showed two types of adenoma cells; one (golden yellow tumor) was a large clear cell with foamy cytoplasm which possibly secreted aldosterone and the other (dark brown tumor) was an acidophilic cell with lipofuscin which might have produced cortisol. This is a very rare case of primary aldosteronism with Cushing's syndrome due to multiple bilateral adrenal adenomas.
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PMID:Primary aldosteronism with cortisol overproduction from bilateral multiple adrenal adenomas. 186 73


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