Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo.
(17/1819)
Progranulin is a 593-amino acid glycoprotein, the mRNA of which is expressed by many epithelial cells both in vitro and in vivo, but the biological significance of this expression is unclear. In this study, we demonstrate that overexpression of the progranulin gene in SW-13 adrenal carcinoma cells and MDCK nontransformed renal epithelia results in the transfection-specific secretion of progranulin, acquired clonogenicity in semisolid agar, and increased mitosis in monolayer culture, whereas diminution of progranulin gene expression impairs growth of these cells. Purified recombinant progranulin reproduces the effects of forced progranulin expression, being clonogenic in soft agar and mitogenic in monolayer culture to SW-13 and MDCK cells and other epithelia of various origins such as GPC16 colonic epithelium and A549 lung carcinoma cells. Progranulin overproduction in SW-13 cells markedly increases its tumorigenicity in nude mice, demonstrating that it can regulate epithelial proliferation in vivo. We propose that the rate of growth for some epithelia, such as SW-13 and MDCK, is proportional to the level of intrinsic progranulin gene expression, and that elevated progranulin gene expression confers a transformed phenotype on epithelial cells including anchorage independence in vitro and growth as tumors in nude mice. (+info)
A case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.
(18/1819)
Unilateral or bilateral non-Hodgkin's lymphomas arising primarily in the adrenal glands are extremely rare. These lymphomas are usually present with large, bilateral adrenal masses with or without lymphadenopathy, and may be accompanied by adrenal insufficiency in some cases. A review of the literature indicates that patients with primary lymphoma of the adrenal glands usually do not have disease elsewhere, and if present, it is frequently extranodal. We report here an unusual case of primary bilateral adrenal lymphoma with partial adrenal insufficiency. (+info)
Prenatal diagnosis of adrenal neuroblastoma by ultrasound: a report of two cases and review of the literature.
(19/1819)
Prenatal diagnosis of neuroblastoma is a rare event. Two cases diagnosed at 32 and 34 weeks are reported together with a description of the various ultrasound appearances of this tumor. Both cases had a favorable outcome and surgery was necessary in only one case. The management options are discussed in the light of the current literature. The role of ultrasound in the detection and follow-up of this tumor in the third trimester of pregnancy is discussed. (+info)
Vimentin-dependent utilization of LDL-cholesterol in human adrenal tumor cells is not associated with the level of expression of apoE, sterol carrier protein-2, or caveolin.
(20/1819)
SW-13 adrenal tumor cells that lack detectable intermediate filaments (IF-free) exhibit an impaired capacity to esterify lipoprotein-derived cholesterol compared with cells that contain vimentin filaments. IF-free cells were found to synthesize and secrete significant amounts of apoE, while apoE secretion was nearly undetectable in cell lines that spontaneously express vimentin. However, stable transfectants that express a mouse vimentin cDNA exhibited elevated levels of cholesterol esterification and apoE secretion compared with untransfected IF-free cells, indicating that apoE secretion is not directly related to the capacity of these cells to esterify cholesterol. Some of the cell lines that differed in the level of apoE synthesis and secretion had similar levels of apoE mRNA, suggesting that the differences in expression involve a post-transcriptional mechanism. Treatment of these cells with forskolin and IBMX, 8br-cAMP, or TPA had no effect on apoE secretion. The level of sterol carrier protein-2 (SCP(2)) synthesis and the distribution of SCP(2) between membrane and soluble cellular fractions was not observably different in cells that contained or lacked vimentin. SW-13 cell lines contained little or no detectable caveolin-1 or caveolin-2. These studies demonstrate that the difference in the capacity of these adrenal tumor cells that contain or lack vimentin filaments to esterify low density lipoprotein-cholesterol is not obviously associated with the level of expression or distribution of apoE, SCP(2), or caveolins. (+info)
Maximizing efficacy of endocrine tests: importance of decision-focused testing strategies and appropriate patient preparation.
(21/1819)
The efficacy of endocrine tests depends on the choice of tests, the preparation of the patients, the integrity of the specimens, the quality of the measurements, and the validity of the reference data. Close dialogue among the clinicians, the laboratory, and the patients is a key factor for optimal patient care. The characteristics of urine and plasma samples and the advantages and limitations of paired test measurements are presented. The importance of test sequence strategies, provocative or inhibitory procedures, and elimination of drug interferences is illustrated with four cases involving Cushing syndrome, pheochromocytoma, primary aldosteronism, and hypercalcemia. For each of these scenarios, key clinical issues are highlighted, along with discussions of the best test strategies, including which medications are likely to interfere. The importance of targeting laboratory tests to answer well-focused clinical decisions is emphasized. The roles of some time-honored provocative procedures are questioned in light of more sensitive and specific analytic methods. The importance of decision-focused analytical tolerance limits is emphasized by demonstrating the impact of analytic bias on downstream medical resource utilization. User-friendly support systems to facilitate the implementation of test strategies and postanalytic tracking of patient outcomes are presented as essential requirements for quality medical practice. (+info)
A probable relationship between an endogenous digitalis-like substance and concentric cardiac hypertrophy in primary aldosteronism.
(22/1819)
A 44-year-old woman was admitted to our hospital due to severe hypertension. An electrocardiogram (ECG) and an echocardiogram showed severe left ventricular hypertrophy. Her plasma aldosterone level was elevated. Magnetic resonance imaging revealed a small mass in the right adrenal gland. Before removal of the tumor, plasma endogenous digitalis-like substance (EDLS) levels were elevated. After removal of the tumor, EDLS levels quickly returned to the normal level. A series of echocardiograms and ECGs over a 6- year period after removal of the tumor showed marked regression of cardiac hypertrophy. These findings suggest that EDLS may be closely related to the development of concentric cardiac hypertrophy in primary aldosteronism. (+info)
Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas.
(23/1819)
OBJECTIVE: An increased response of 17-hydroxyprogesterone to ACTH stimulation has been observed in adrenal incidentaloma and linked to an impairment of either 21-hydroxylase or of 11beta-hydroxylase activity. To analyse this question further, we investigated the steroidogenic pathways in a series of 17 adrenal incidentalomas. DESIGN AND PATIENTS: 17 patients (7 women, 10 men; mean age, 62 +/- 12 years) with non-histologically analyzed adrenal incidentalomas were prospectively evaluated. METHODS: The following variables were investigated: 24-h urinary methanephrines and free cortisol excretion; plasma levels of ACTH and dehydroepiandrosterone; overnight dexamethasone suppression test; 1-24 ACTH stimulation test with measurement of: cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, 11-deoxycorticosterone, progesterone, 17-hydroxypregnenolone, Delta4-androstenedione, dehydroepiandrosterone and 21-deoxycortisol. RESULTS: Discordant features of subclinical hypercorticism were noted in one case. No patient had dehydroepiandrosterone sulfate levels in the normal range for his or her age. Peak 17-hydroxyprogesterone and peak 21-deoxycortisol disclosed impairment of 21-hydroxylase in 11 and 10 cases respectively. An increased 11-deoxycortisol/cortisol ratio identified reduced activity of 11beta-hydroxylase in 11 patients. Eight patients displayed features of mild 17,20-lyase impairment, which was related to 21-hydroxylase dysfunction. Whereas only 2 patients showed no enzyme modification, 9 displayed alterations of at least two pathways. CONCLUSION: In our hands, a combination of enzyme dysfunction was frequently observed. Shared biochemical mechanisms could explain combined 17,20-lyase and 21-hydroxylase alterations, whereas coexistence of 21-hydroxylase (particularly when based on peak 21-deoxycortisol) and 11beta-hydroxylase is more puzzling. (+info)
Aldosterone-producing adenoma without hypertension: a report of two cases.
(24/1819)
Normotensive primary hyperaldosteronism is exceedingly rare. We report two new cases of this syndrome in two middle-aged women, one of Asian origin. The presenting signs were tetany in one case and an adrenal mass in the other. Neither patient had hypertension, despite repeated measurements with a manual armlet. A typical biological profile of primary hyperaldosteronism was demonstrated in both patients, including hypokalemia with inappropriate kaliuresis, elevated resting plasma aldosterone, and undetectable plasma renin activity. The circadian rhythm of blood pressure was studied by ambulatory monitoring pre- and post-operatively. It confirmed the lack of hypertension, but the circadian rhythm of blood pressure was lost before surgery in one patient. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia. The main finding in these two patients was spontaneously low blood pressure in the post-operative period. This suggests that excess aldosterone induced relative hypertension in these patients whose blood pressure was spontaneously very low. Genetic screening for dexamethasone-sensitive hyperaldosteronism was negative in both patients. (+info)