PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “ADRENAL CORTEX NEOPLASMS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2000

Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression.

Steroidogenic acute regulatory (StAR) protein plays a critical role in the movement of cholesterol from the outer to the inner mitochondrial membrane. Steroidogenic factor 1 (SF-1) controls basal and cAMP-stimulated transcription of the StAR gene. The 1.3-kb StAR promoter has three SF-1 binding sites, and two consensus transcription factor Spl binding sequences near the two most distal SF-1 binding sites. Spl mediates cAMP-dependent transcription of steroidogenic P450 enzyme genes, raising the possibility of Sp1 involvement in cAMP regulation of the StAR gene. However, the mechanism of Spl-mediated, cAMP-stimulated responsiveness is not known. In this study, we elucidated the roles of Sp1 and SF-1 in the regulation of the human StAR gene promoter. We found that there was negligible promoter activity in a pGL2 StAR construct (-235 to +39) in which Spl and SF-1 binding sites were mutated in Y-1 adrenal tumor cells. An Sp1 binding site mutation (pGL2Sp1M) did not support promoter activity, suggesting that Spl cooperates with SF-1 in regulating StAR promoter function. In gel shift assays, the SF-1 binding site formed a complex with an SF-1-GST fusion protein and Spl. Coimmunoprecipitation cross-linking experiments indicated that SF-1 physically interacts with Sp1 in vitro. Finally, a mammalian two-hybrid system was employed to demonstrate that Spl and SF-1 associate in vivo. In conclusion, our data indicate that Spl and SF-1 physically interact and cooperate in the regulation of human StAR promoter activity.

Adrenal Cortex Neoplasms↗
PubMed2004

The clinically inapparent adrenal mass: update in diagnosis and management.

Clinically inapparent adrenal masses are incidentally detected after imaging studies conducted for reasons other than the evaluation of the adrenal glands. They have frequently been referred to as adrenal incidentalomas. In preparation for a National Institutes of Health State-of-the-Science Conference on this topic, extensive literature research, including Medline, BIOSIS, and Embase between 1966 and July 2002, as well as references of published metaanalyses and selected review articles identified more than 5400 citations. Based on 699 articles that were retrieved for further examination, we provide a comprehensive update of the diagnostic and therapeutic approaches focusing on endocrine and radiological features as well as surgical options. In addition, we present recent developments in the discovery of tumor markers, endocrine testing for subclinical disease including autonomous glucocorticoid hypersecretion and silent pheochromocytoma, novel imaging techniques, and minimally invasive surgery. Based on the statements of the conference, the available literature, and ongoing studies, our aim is to provide practical recommendations for the management of this common entity and to highlight areas for future studies and research.

Adrenal Cortex Neoplasms↗
PubMed2003

Primary pigmented nodular adrenocortical disease: paradoxical responses of cortisol secretion to dexamethasone occur in vitro and are associated with increased expression of the glucocorticoid receptor.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent adrenal Cushing's syndrome (CS), which is often associated with Carney complex (CNC). We have recently described a paradoxical increase in cortisol excretion after dexamethasone administration in most patients with PPNAD. In the present study we investigated the hypothesis that this phenomenon is due to a primary abnormality of the tissues affected by PPNAD, rather than a defect of the patients' hypothalamic-pituitary-adrenal axis; as such it should be replicated in vitro by adrenal slices exposed directly to dexamethasone. We were able to study adrenal tissues from eight patients with CS caused by PPNAD; two patients were also studied in vivo according to a protocol first described in ACTH-independent macronodular adrenal hyperplasia (AIMAH) for the clinical detection of aberrant hormone receptor expression. Their DNA has been previously screened for inactivating mutations of the PRKAR1A gene, the most frequent molecular defect leading to PPNAD and/or CNC. We also investigated whether glucocorticoid receptor (GR) expression underlies paradoxical dexamethasone responses in PPNAD by immunohistochemistry and semiquantitative PCR, and we correlated GR expression with that of other markers for PPNAD (e.g. synaptophysin). Indeed, we demonstrated that dexamethasone induced cortisol secretion in vitro in five of these tumors; no such increase was seen in adenomatous or AIMAH tissues that were treated in the same manner. GR mRNA was expressed, and GR immunoreactivity was detected in PPNAD nodular cells. Staining for GR was not seen in surrounding cortical cells, and hence, it correlated with synaptophysin, which also stains PPNAD in a similar manner. In normal adrenal tissue, GR was detected mostly in medullary areas, whereas GR immunoreactivity was weak in adenomatous and AIMAH tissues. We conclude that 1) dexamethasone produces an increase in glucocorticoid synthesis by PPNAD adrenal slices in vitro, suggesting a direct effect on adrenocortical tissue, and 2) this phenomenon is accompanied by increased expression of the GR in PPNAD nodules. PPNAD and/or CNC patients with and without mutations leading to protein kinase A activation demonstrated in vitro and/or in vivo paradoxical dexamethasone responses and GR expression, indicating that PRKAR1A alterations are not necessary for these phenomena.

Actins↗
PubMed2004

Thiazolidinediones inhibit growth and invasiveness of the human adrenocortical cancer cell line H295R.

Thiazolidinediones (TZDs) are a new class of antidiabetic drugs that have also been shown to possess antitumoral properties in different human cancers. TZDs bind and activate the peroxisome proliferator-activated receptor (PPAR)-gamma, which is a nuclear receptor acting as a transcription factor in several tissues. In the present study, we evaluated PPARgamma mRNA and protein expression in tissue samples of human adrenocortical carcinomas (ACCs), normal adrenal glands, and the human ACC cell line H295R. PPARgamma mRNA was expressed in six of eight ACC, two of three normal adrenal glands and the H295R cells. These results were confirmed by immunohistochemistry. PPARgamma transcriptional activity in H295R cells, monitored by a reporter gene assay, was induced 2- to 3-fold by TZDs, such as rosiglitazone (RGZ) and pioglitazone, whereas in PPARgamma-transfected cells RGZ alone or RGZ plus 9-cis retinoic acid further increased reporter activity. TZDs inhibited both the proliferation and invasiveness of H295R cells in a dose-dependent manner. Thymidine incorporation was reduced by about 60% by 20 mum of both TZDs. Cotreatment with the retinoic X receptor ligand 9-cis retinoic acid had an additive effect. TZDs increased the number of cells in the G(0)/G(1) phase and decreased them in the S phase. Western blot analysis showed that TZDs increased the expression of the cell cycle inhibitors p21 and p27 and reduced the expression of cyclin D1. Twenty micromoles of RGZ and pioglitazone reduced H295R invasiveness through Matrigel by about 85%. Zymography and ELISA tests showed that TZD inhibited metalloproteinase-2 secretion by H295R cells in a dose-dependent manner. These data suggest that TZDs reduce the malignant potential of the H295R ACC cell line and, therefore, might potentially constitute a novel tool in the medical treatment of human ACCs.

Adrenal Cortex Neoplasms↗
PubMed2005

AKT is highly phosphorylated in pheochromocytomas but not in benign adrenocortical tumors.

CONTEXT: Activation of AKT plays a major role in a variety of human neoplasias. In mice, a heterozygous deletion of the Pten gene is associated with increased activation of AKT and with development of pheochromocytomas. OBJECTIVE: The objective of this study was the investigation of the role of AKT in the pathogenesis of pheochromocytomas and adrenocortical tumors. DESIGN, SETTING, AND PARTICIPANTS: Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas, nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In addition, in pheochromocytomas PTEN protein expression and PTEN loss of heterozygosity were analyzed. MAIN OUTCOME MEASURES: Determination of pAKT/total AKT ratio in adrenal tissues was the main outcome. RESULTS: In comparison to normal adrenals, total AKT expression was elevated in both pheochromocytomas (193 +/- 22%) and ACC (176 +/- 36%). The pAKT/AKT ratio was significantly increased in pheochromocytomas (338 +/- 49% vs. 100 +/- 11%) but not in ACC, aldosterone-producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of PTEN and no decrease in PTEN protein was detected in pheochromocytomas. Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in pheochromocytomas and focal staining in ACC. CONCLUSION: Our findings provide evidence for increased activation of AKT in pheochromocytomas but not in adrenocortical adenomas.

Adrenal Cortex Neoplasms↗
PubMed2005

Hereditary leiomyomatosis associated with bilateral, massive, macronodular adrenocortical disease and atypical cushing syndrome: a clinical and molecular genetic investigation.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder caused by mutations in the fumarate hydratase (FH) gene on chromosome 1q42.3-43. Massive macronodular adrenocortical disease (MMAD) is a heterogeneous condition associated with Cushing syndrome (CS) and bilateral hyperplasia of the adrenal glands. In MMAD, cortisol secretion is often mediated by ectopic, adrenocortical expression of receptors for a variety of substances; however, to date, no consistent genetic defects have been identified. In a patient with HLRCC caused by a germline-inactivating FH mutation, we diagnosed atypical (subclinical) CS due to bilateral, ACTH-independent adrenocortical hyperplasia. A clinical protocol for the detection of ectopic expression of various hormone receptors was employed. Histology was consistent with MMAD. The tumor tissue harbored the germline FH mutation and demonstrated allelic losses of the 1q42.3-43 FH locus. We then searched the National Institutes of Health (NIH) databases of patients with MMAD or HLRCC and found at least three other cases with MMAD that had a history of tumors that could be part of HLRCC; among patients with HLRCC, there were several with some adrenal nodularity noted on computed tomography but none with imaging findings consistent with MMAD. From two of the three MMAD patients, adrenocortical tumor DNA was available and sequenced for coding FH mutations; there were none. We conclude that in a patient with HLRCC, adrenal hyperplasia and CS were due to MMAD. The latter was likely due to the FH germline mutation because in tumor cells, only the mutant allele was retained. However, other patients with MMAD and HLRCC, or HLRCC patients with adrenal imaging findings consistent with MMAD, or MMAD patients with somatic FH mutations were not found among the NIH series. Although a fortuitous association cannot be excluded, HLRCC may be added to the short list of monogenic disorders that have been reported to be associated with the development of adrenal tumors; FH may be considered a candidate gene for MMAD.

Adrenal Cortex Neoplasms↗
PubMed2005

Elevated expression of luteinizing hormone receptor in aldosterone-producing adenomas.

CONTEXT: The mechanisms driving steroid production in aldosterone-producing adenomas (APAs) are poorly defined. However, previous studies have shown that steroid production in some cortisol-producing adenomas is regulated by aberrant expression of G protein-coupled receptors. Aberrant adrenal expression of LH receptors has been shown to cause Cushing's syndrome, but the role of LH receptors in Conn's disease (hyperaldosteronism) has not been studied. OBJECTIVE: The objective of the study was to determine whether APAs express elevated LH receptor, compared with normal adrenal (NA). DESIGN: Pools of RNA from NA and APAs were hybridized to oligonucleotide microarrays. Data were confirmed using real-time RT-PCR analysis of RNA derived from NA (n = 20) and APAs (n = 18). Aldosterone synthase transcription was studied in H295R adrenocortical cells transfected with an LH receptor expression construct and reporter constructs prepared from CYP11B2 5'-flanking DNA. PATIENTS: The patient population consisted of 20 normal control adrenals and 18 adenomas from patients with APAs. MAIN OUTCOME MEASURE: Regulation of CYP11B2 gene expression by aberrant LH receptor expression in aldosterone-producing adrenal adenoma was measured. RESULTS: LH/choriogonadotropin receptor gene and CYP11B2 are indicated as having greater than 25-fold expression in one pool of APA mRNA samples over NA using microarray analysis. Real-time RT-PCR analyses indicated that one APA sample (APA-LH receptor) exhibited more than 2400-fold elevation in LH receptor expression over NA. Examination of LH receptor mRNA levels in 18 independent APA samples indicated elevated expression in nine samples when compared with NA. In H295R cells transfected with LH receptor, LH treatment caused a concentration-dependent increase in CYP11B2 reporter activity. CONCLUSION: LH receptor expression is elevated in many APAs, which makes LH a potential cause of the excessive production of aldosterone in a subset of these adrenal tumors.

Adenoma↗
PubMed1975

Selective hypoaldosteronism despite prolonged pre- and postoperative hyperreninemia in primary aldosteronism.

In a prospective study of 7 patients with aldosterone-producing adenoma (APA), long-term (6-72 months) preoperative stimulation of plasma renin activity (PRA) by diuretic therapy (spironolactone plus hydrochlorothiazide) did not prevent selective aldosterone deficiency postoperatively. In all patients aldosterone excretion rate (AER) fell to subnormal values (from a mean of 97 to 2.6 mug/24 h) following removal of APA, although PRA remained elevated. Generalized adrenocortical insufficiency was excluded by the demonstration of normal baseline plasma cortisol and urinary 17-OHCS and the appropriate response to ACTH stimulation. In 6 of 7 patients studied 1-3 months postoperatively, short-term (4 days) sodium deprivation evoked normal increases in PRA, but AER response was blunted (except in 1). Restudy of 3 of 6 patients after 6-12 months revealed that aldosterone production had returned to normal. These results indicate that renin deficiency is not the principal cause of postoperative selective hypoaldosteronism in these patients. On the other hand, they appear to substantiate the possibility raised by in vitro and in vivo studies that spironolactone can directly inhibit aldosterone biosynthesis.

Adenoma↗
PubMed1976

Dual sites of inhibition by metyrapone of human adrenal steroidogenesis: correlation of in vivo and in vitro studies.

In a patient with pituitary ACTH-dependent adrenal hyperplasia (AH), the standard oral metyrapone test resulted in a decrease in "apparent 11beta-hydroxylase activity" (-48%) accompanied by an increase in "apparent cholesterol cleavage activity" (+318%). When incubated adrenal mitochondria from this patient were studied, metyrapone inhibited both 11beta-hydroxylation of labeled 11-deoxycorticosterone and cleavage of labeled cholesterol, although at 0.1 and 1.0 mM metyrapone concentrations, depression of cholesterol cleavage (23 and 54%, respectively) was less than that of 11beta-hydroxylation (62 and 84%, respectively). The inhibition of cholesterol cleavage by metyrapone (26 and 62%, at 0.1 and 1.0 mM concentrations, respectively) was also demonstrable in adrenal mitochondria from a patient with hypercorticism resulting from an ACTH-independent adrenal adenoman (AA). Metyrapone administration to AA resulted in a significant depression of both 11beta-hydroxylase (-62%) and cholesterol cleavage (-36%) "apparent activities"; when metyrapone and ACTH were given together to this patient, however, only 11beta-hydroxylase "apparent activity" diminished (-26%), while cholesterol cleavage "apparent activity" was greatly augmented (+231%), thereby simulating the results of the standard metyrapone test in AH. These data demonstrate that metyrapone inhibits both mitochondrial reactions involved in cortisol synthesis--initial cholesterol cleavage and final 11beta-hydroxylation; these effects probably result from interference by this agent with the interaction between substrate and related cytochrome P - 450. Since ACTH has a major stimulatory effect on cholesterol cleavage but not on 11beta-hydroxylation, the outcome of metyrapone administration is thus determined by whether a change in ACTH level ensues: while 11beta-hydroxylation is inhibited by metyrapone under any circumstances, total steroid output rises when a compensatory ACTH increase overcomes metyrapone inhibition of cholesterol conversion into pregnenolone and falls when metyrapone inhibition of this reaction is unopposed.

Adenoma↗
PubMed1976

A testosterone-producing adrenal cortical adenoma in an elderly woman.

A 76-year-old woman with virilization had menopausal levels of circulating LH and FSH, and a markedly elevated concentration of plasma testosterone (9130 pg/ml) into the range for adult men. Plasma cortisol and androstenedione levels andurinary 17-ketosteroid secretion were normal. Ethinyl estradiol suppressed plasma testosterone, LH, and FSH levels into the normal range for premenopausal women, but the testosterone concentration was unaffected by the administration of dexamethasone or ACTH. Retrograde venous sampling and angiography localized a right adrenal adenoma preoperatively. Following adrenalectomy, there was a prompt fall in testosterone, but there was no change in the LH concentration. Thus, this patient had an adrenal adenoma which secreted only testosterone and appeared to be gonadotropin-responsive. Testosterone levels in the adult male range failed to suppress gonadotropins. The significance of these findings is discussed.

Adenoma↗
PubMed1977

Studies of the diurnal pattern of plasma corticosteroids and gonadotropins in two cases of feminizing adrenal carcinoma: measurements of estrogen and corticosteroid production.

Two adult men with feminizing adrenal cortical carcinoma had measurements of their 24-h plasma corticosteroid and gonadotropin patterns as well as 24-h mean hormone levels of estradiol, estetrol, 11-desoxycortisol, DHEA-S, DHEA and testosterone. Cortisol, 11-desoxycortisol and estrogen production rates were also measured. The 24-h corticosteroid patterns showed preservation of the normal 24-h episodic and circadian patterns, albeit at higher levels. The cortisol production rates were markedly elevated despite only moderate elevation of the 24-h mean cortisol level. There were elevated plasma 11-desoxycortisol levels and a markedly elevated 11-desoxycortisol production rate in one patient and THS excretion in the other. The plasma estradiol levels, urinary excretion and production rates were markedly elevated. In addition, there was a decrease in the specific activity of estriol compared with estrone and estradiol as well as measurable levels of estetrol in both patients. These latter observations coupled with the urinary immunoassayable hCG in one patient suggest that these tumors may be functioning like trophoblastic tissue. The possibility that estetrol may serve as an additional marker for tumors of trophoblastic origin is of additional interest.

Adrenal Cortex Hormones↗
PubMed1977

Adenosine 3'5'-cyclic monophosphate dependent protein kinase in human adrenocortical tumors.

Protein kinase activity has been studied in four human adrenocortical tumors and compared to the one of the normal human adrenal. In two cases where the lack of action of ACTH was related to an anomaly of ACTH receptor, the protein kinase activity was normal. In the other two cases the ACTH receptor was normal, but the protein kinase activity was different from that of the normal adrenal. In one of these cases where the steroidogenesis response of isolated tumor cells to ACTH and DcAMP was higher than in normal adrenal, basal and cAMP stimulated protein kinase activities were significantly higher than those of the normal adrenal, but the activation constants of both nucleotides were similar to those of the normal gland. In the other case, the basal and the cAMP stimulated protein kinase activities were significantly lower, as well as the activation constant of cAMP. However, the binding affinity of 3H-cAMP was normal. Normal adrenal cytosol contains three protein kinases, as resolved by DEAE-cellulose, two of which designated I and II, are cAMP-dependent. The DEAE-cellulose chromatography of the last tumor showed a loss of isoenzyme II. In addition, the protein kinase eluted at the same molarity as that of isoenzyme I of the normal adrenal was not activated by cAMP. Therefore, the lack of response to ACTH of some adrenocortical human tumors may be attributed either to an anomaly of the ACTH receptor or to some defect of the cAMP-dependent protein kinase.

Adrenal Cortex Neoplasms↗
PubMed1977

A new and superior adrenal imaging agent, 131I-6beta-iodomethyl-19-nor-cholesterol (NP-59): evaluation in humans.

We have reported tissue distribution studies in rats and dogs with a new adrenal imaging agent. 131I-6beta-iodomethyl-19-nor-cholesterol (NP-59). This agent concentrated five times higher in the adrenal cortex than 131I-19-iodocholesterol without increased concentration in non-adrenal tissues. We now report in 34 patients, the findings on scintigraphy with NP-59 compared with angiograms and/or adrenal vein hormone levels and histopathology, including 13 patients with hypercortisolism, 12 with primary aldosteronism, 2 with low renin hypertension, 5 with catecholamine excess, 1 with a liver metastasis from an aldosterone producing adrenal cortical carcinoma, and 1 with anaplastic adrenal cortical carcinoma. NP-59 adrenal cortical uptake was more rapid and intense and background activity was less prominent, allowing earlier and more definite interpretation of images than was possible with 131I-19-iodocholesterol.

Adrenal Cortex Neoplasms↗