Biomedical subjects

Felix Beuschlein

Publications and source records attributed to Felix Beuschlein.

23 records · Page 2Linked to original sources

PubMed2004

Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication.

OBJECTIVE: The aim of this study was to investigate the utility of different screening techniques for primary aldosteronism (PA), including serum aldosterone (SA), plasma renin activity (PRA) and the SA/PRA ratio in hypertensive patients of a tertiary-care centre. Furthermore, the influence of antihypertensive medication on SA and the SA/PRA ratio were studied. DESIGN: Clinical records of 425 hypertensive patients who had SA and PRA measurements over a 27-month period were analysed retrospectively. Eighty patients were excluded from further analysis because of incomplete data. The remaining 345 patients were classified into the following groups: patients with essential hypertension (EH) (n=260, 75.4%), patients with PA (n=49, 14.2%) and patients with secondary hypertension other than PA (n=36, 10.4%). Diagnosis of PA was made in accordance with established laboratory criteria (including measurements of SA, PRA, urinary excretion of aldosterone and metabolites, imaging techniques and response to treatment). RESULTS: Although mean serum potassium values were significantly lower (P<0.001) in the PA group compared with the EH group, 61% of PA subjects were normokalaemic (3.4-5.2 mmol/l). The SA/PRA ratio alone identified 94% of the patients with PA, but was false positive in 30% of the patients with EH. The SA/PRA ratio together with SA>150 g/ml increased the diagnostic accuracy, led to the correct identification of 84% of the patients with PA, and decreased the false-positive rate to 3%. A multivariate binary logistic regression analysis based on SA and PRA was performed, which identified PA with 90% sensitivity and 91% accuracy. The SA(2)/PRA or the SA(3)/PRA ratio was found useful for simplification of the regression analysis. Antihypertensive medication influenced SA, PRA and the SA/PRA ratio only in EH patients. In EH patients taking beta-adrenoceptor antagonists PRA tended to be lower, leading to a significantly higher SA/PRA ratio and therefore increasing the false-negative rate. CONCLUSION: To reduce false-positive results in screening for PA, and thereby avoid unnecessary and cost-intensive diagnostic procedures, SA should be taken into account in addition to the SA/PRA ratio as a second screening criterion. Alternatively, the SA(2)/PRA or the SA(3)/PRA ratio is more accurate screening tests than the SA/PRA ratio. Beta-blockers should be avoided whilst screening for PA.

Aldosterone↗

PubMed2003

Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice.

Inhibin and activin are members of the transforming growth factor beta (TGF-beta) family of ligands produced and secreted primarily by the gonads and adrenals. Inhibin-null (INH(-/-)) mice develop gonadal tumors and-when gonadectomized-adrenocortical carcinoma. The mechanisms leading to adrenal tumorigenesis have been proposed to involve the lack of a gonadal factor and/or a compensatory increase in gonadotropins. In order to achieve elevation of gonadotropins without the concomitant loss of a gonadal hormone, we crossed INH(-/-) mice with a transgenic mouse strain that has chronically elevated luteinizing hormone (LH) levels (LH-CTP). Compound INH(-/-)-LH-CTP mice die within 6 weeks of age from severe cancer cachexia induced by large, activin-secreting ovarian tumors. Unexpectedly, INH(-/-)-LH-CTP mice not only fail to develop adrenal tumors but have smaller adrenals, with a regressed x zone, indicating that elevated LH levels are not sufficient to induce adrenal tumor formation. However, following gonadectomy, INH(-/-)-LH-CTP mice develop large, sex steroid-producing adrenal tumors that arise from the x zone, indicating a growth-promoting effect of high levels of LH on the adrenal cortex in the absence of ovarian tumors. In addition, in vivo and in vitro data indicate that activin induces apoptosis specifically in the adrenal x zone. The restricted expression of activin receptor subunits and Smad2 in cells of the adrenal x zone, together with the elevated activin levels in INH(-/-)-LH-CTP mice, supports the conclusion that activin inhibits adrenal tumor growth by inducing x-zone regression.

Activins↗

PubMed2002

Ectopic pro-opiomelanocortin syndrome.

Ectopic POMC syndrome remains one of the most challenging differential diagnoses in endocrinology. Recent progress in the understanding of the tissue specific regulation of POMC gene expression and new insights into the processing of the POMC peptide in nonpituitary tissues has helped elucidate some of the molecular events leading to ectopic expression and secretion of POMC peptides. Corticotropin and other POMC-derived peptides have diverse effects on adrenal steroidogenesis, growth, and extra-adrenal tissues. Differences in POMC gene regulation in the corticotrope versus ectopic POMC-producing tumors provides a scientific framework for the clinical distinction between eutopic and ectopic Cushing's syndrome. In an attempt to revisit recent basic and clinical advances in the diagnosis of ectopic POMC syndrome the authors undertook an extensive literature review of 530 cases in 197 published papers and provided a molecular biologic, demographic and diagnostic update. According to this review, the four most common causes of ectopic POMC syndrome are the small cell carcinoma of the lung (27%), bronchial carcinoids (21%), islet cell tumor of the pancreas (16%), and thymic carcinoids (10%). Although the clinical features of patients with ectopic POMC syndrome are similar to those with Cushing's disease, subgroup analysis reveals a broad spectrum of severity and progression of signs and symptoms of hypercortisolism. The endocrine workup of a patient with suspected ectopic POMC syndrome includes the establishment of pathologic hypercortisolism, diagnosis of corticotropin dependency, and the differential diagnosis of corticotropin-dependent Cushing's syndrome. The use of a variety of baseline endocrine values, dynamic endocrine testing, and invasive procedures leads to the correct diagnosis in the majority of patients with ectopic POMC syndrome. Diagnostic imaging, including conventional radiological techniques and somatostatin receptor scintigraphy, aids in the correct localization and eventual treatment of ectopic POMC production.

Adenoma, Islet Cell↗

PubMed2002

Interaction between Dax-1 and steroidogenic factor-1 in vivo: increased adrenal responsiveness to ACTH in the absence of Dax-1.

Two nuclear receptors, dosage-sensitive sex reversal adrenal hypoplasia congenita, critical region on the X chromosome gene-1 (Dax-1) and steroidogenic factor-1 (SF-1), are required for adrenal development and function. In vitro assays suggest that Dax-1 represses SF-1 mediated transcription. In this study, we generated SF-1(+/-): Dax-1(-/Y) mice to examine the role of Dax-1 in SF-1-dependent steroidogenesis in vivo. While the SF-1 expression was impaired in SF-1(+/-) mice, there was no change in Dax-1 expression in SF-1(+/-) mice and no change in SF-1 expression in Dax-1(-/Y) mice. SF-1(+/-) mice had small adrenal glands with adrenal hypoplasia and cellular hypertrophy. The loss of Dax-1 in SF-1(+/-): Dax-1(-/Y) mice reversed the decreased adrenal weight and histological abnormalities observed in SF-1(+/-) mice. SF-1(+/-) mice had elevated ACTH and the lowest corticosterone following restraint stress. In contrast, Dax-1(-/Y) mice had elevated corticosterone and decreased ACTH. Adrenal responsiveness (ACTH/corticosterone) was highest in Dax-1(-/Y) mice, intermediate in WT and SF-1(+/-): Dax-1(-/Y) mice, and lowest in SF-1(+/-) mice. In accordance with these findings, ACTH stimulation testing resulted in the highest levels of corticosterone in the Dax-1(-/Y) mice. Protein levels of P450c21 and the ACTH receptor were increased in Dax-1(-/Y) mice and intermediate in SF-1(+/-): Dax-1(-/Y) mice following chronic food deprivation. These results are consistent with a model in which Dax-1 functions to inhibit SF-1-mediated steroidogenesis in vivo.

Adrenal Cortex↗

PubMed2002

Steroidogenic factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy.

While the orphan nuclear receptor steroidogenic factor-1 (SF-1) has been shown to function as an induction factor to define adrenocortical cell lineage, it remains unclear whether SF-1 plays an additional role as a growth promoting agent in the adult adrenal cortex. The proliferative potential of the adrenal cortex in adult SF-1(+/-) mice was examined using the model of compensatory adrenal growth following unilateral adrenalectomy (uADX). While the right adrenal gland of wild-type (wt) mice grew significantly after uADX, the adrenal of SF-1(+/-) mice exhibited a blunted, statistically nonsignificant weight increase. Accordingly, a profound increase in the proliferation marker proliferating cell nuclear antigen could be detected only in wt mice after uADX but not in the SF-1(+/-) mice. The proposed key regulator in adrenal compensatory growth, the recently cloned adrenal secretory serine protease was up-regulated in the remaining adrenal of wt mice, whereas this increase was blunted in SF-1(+/-) mice. While no differences in preadipocyte factor-1, the presumed marker of primitive adrenocortical cells, were detectable in the adrenals of wt and SF-1(+/-) mice, an increase in the ACTH receptor as well as agouti-related protein was observed only in wt animals but not in the SF-1(+/-) mice following uADX. Taken together, these results reflect a primary inability of adrenal cortical cells of SF-1(+/-) mice to undergo compensatory adrenal growth in response to uADX.

Adrenal Glands↗