Normalization of high plasma level of ouabain-like immunoreactivity in primary aldosteronism after removal of adenoma.

Plasma ouabain-like immunoreactivity, which has been supposed to be associated with hypertension, was significantly higher in five patients with primary aldosteronism than in age-matched normotensive subjects. High plasma levels of ouabain-like immunoreactivity decreased to normal after removal of adenoma. Extracts of adenoma tissue did not contain any apparent ouabain-like immunoreactivity. Anti-ouabain antibody used in this study did not cross-react with aldosterone, cortisol, corticosterone, arachidonic acid or lysophosphatidylcholine. Hypertension, hypokalemia, a high plasma aldosterone level and low plasma renin activity were also normalized after surgery. These results indicate that hyperaldosteronism induces the high plasma level of ouabain-like immunoreactivity and this is associated in part with high blood pressure (BP) in primary aldosteronism.

In vitro adrenal cortex lesions characterization by NMR spectroscopy.

Percentage of lipid content of 22 adrenal cortex lesions and their water proton longitudinal relaxation time were measured in vitro at 60 MHz. Although water relaxation times obtained on benign and malignant samples overlap each other, measurements of the percentage of lipids performed on the same tissues allow us to distinguish the two pathologies. The specific tool of characterization should be possible to obtain through in vivo spectroscopic imaging techniques.

Flow cytometric analysis of adrenal cortical tumor DNA. Relationship between cellular DNA and histopathologic classification.

Nuclear DNA contents of 22 paraffin-embedded adrenal cortical tumors (16 adenomas and 6 carcinomas) were determined by flow cytometric analysis. While all of the sixteen adenomas had a diploid pattern, 83.3% (5/6) of the carcinomas were aneuploid. Three of the six patients with carcinomas (50%) developed metastases and died of their disease; all had aneuploid tumors. The three living patients with carcinoma included two children, with aneuploid tumors, and one adult, with a diploid tumor. Large tumor size correlated with aneuploidy. This study indicated that flow cytometric analysis of nuclear DNA content complements conventional histopathologic methods in the diagnosis of malignancy in adrenal cortical tumors. It may also prove to be a valuable tool in predicting the prognosis of patients with adrenal cortical carcinomas.

Biochemical and immunological characterization of estrogen binding components in human neoplastic adrenocortical tissues.

The estrogen binding components in human adrenocortical tissues were examined. Two adrenocortical cancer cytosols were found to contain the binder with a relative low affinity (Kd 5 X 10(-9) M) for estradiol. The association of [3H]estradiol to these cytosols was inhibited by a large dose of unlabeled estrone, estradiol or estriol, but neither by diethylstilbestrol nor by dihydrotestosterone. Incubation of cultured cells derived from these cancers with [3H]estradiol also showed the presence of this low-affinity estradiol binder. The addition of bovine serum albumin into these cytosols surprisingly resulted in a marked increase in estradiol binding capacity in a concentration-dependent manner. This component sedimented at 5 S in the low salt sucrose density gradient. This binding ability was found to be heat-labile in the absence of estradiol, but preformation of complexes with estradiol markedly stabilized its binding ability against thermal inactivation. In addition, experiments using monoclonal antibodies to human estrogen receptor revealed that the estrogen binder from one adrenocortical cancer cytosol shared antigenic determinants with human estrogen receptor. These results suggest that the unique estrogen binder in some adrenocortical cancer has the characteristics similar to estrogen receptors in terms of thermal stability and immunological cross-reactivity to antibodies.

Purification and biochemical characterization of alpha 2-adrenergic receptor from the rat adrenocortical carcinoma.

The alpha 2-adrenergic receptor was purified from rat adrenocortical carcinoma 494 by an affinity chromatographic step using a novel para-aminoclonidine-sepharose resin followed by a gel-permeation high performance liquid chromatographic step. The iodinated receptor protein was homogeneous as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by high performance liquid chromatography. Both SDS-PAGE and high performance liquid chromatographic studies revealed that Mr of the protein was 64,000, suggesting the monomeric nature of the receptor protein. The purified protein showed the typical binding characteristics of alpha 2-adrenergic receptor.

Immunofluorescence microscopic evaluation of the intermediate filament expression of the adrenal cortex and medulla and their tumors.

Normal adrenal glands (10 specimens) and adrenal gland tumors (58 cases) were immunohistochemically evaluated for different types of intermediate filament (IF) proteins. Some of the normal cortical cells showed cytokeratin positivity, and no positivity was seen for epidermal keratin or other types of IF. In the adrenal medulla, neurofilament positivity was seen in nerve axons, some ganglion cells, and chromaffin cells; and cytokeratin-positive cells could not be detected. Only the vascular and connective tissue elements showed vimentin positivity in both cortical and medullary areas. In half of the cortical carcinomas (13/25), cytokeratin-positive tumor cells were found. Furthermore, vimentin-positive tumor cells were present in 10 of 25 cases, in some of them together with cytokeratin-positive cells. Thus, the results show heterogeneity among the adrenal cortical carcinomas. Interestingly, many benign adrenal cortical tissues and some carcinomas lacked immunoreactivity for all types of IF, suggesting a poorly developed IF system in these tissues. In contrast to adrenal cortical tumors, pheochromocytomas contained neurofilamentlike immunoreactivity. These results reflect the different cellular nature of adrenal cortical and medullary tumors, which apparently can be distinguished from each other with antibodies to intermediate filament proteins.

[Adrenocortical carcinoma with feminization: "in vivo" and "in vitro" study (author's transl)]. / Un cas de corticosurrénalome féminisant chez l'homme: etude "in vivo" et "in vitro".

A 31 year-old man with adrenocortical carcinoma is presented. Clinically he had a recidiving gynecomastia. The levels ddhydro-épi-androstérone (D.H.E.A.) and his ester Sulfate (D.H.E.A.S.), delta-4-androsténédione (A), estrone (Et), estradiol (E2) in urines, serum and tumor were very high. The cortisol production rate was in normal values. The serum levels or cortisol, D.H.E.A., D.H.E.A.S. and A were not increased by A.C.T.H. injection. In vitro, steroidogenesis in the tumor cells was not influenced by A.C.T.H. or prostaglandin E1, but stimulated by dibutyryl cyclic 3'5' adenosine monophosphate. Unresponsiveness of A.C.T.H. was related to an alteration of cells membranes receptors.

Rat adrenocortical carcinoma 494: an integrated structural, stereological, and biochemical analysis.

Snell adrenocortical tumor 494 was implanted into male Sprague-Dawley rats and recovered 7, 14, 21, 28 or 35 days following initial detection by palpation (7-10 days following transplantation). Electron microscopic, stereological and biochemical analyses of the tumor were compared to adrenals of normal animals to serve as a baseline for further studies of the effects of chemotherapeutic agents on tumor cells. Tumor cells possessed oval or elongated mitochondrial profiles with tubular cristae, one or two very large (greater than 5 micrometer) lipid droplets, abundant ribosomes and coated vesicles, and sparse rough and smooth endoplasmic reticulum. Stereologic evaluation revealed that tumor lipid volume was 41% and mitochondrial volume 29% that of the normal adrenal controls. Tumor nuclei were 2.5 times larger than adrenocortical nuclei while cellular volumes were similar. On a net weight basis, tumor cholesterol was 55%, cholesterol ester 2.2%, and lipid phosphate 25% of respective mean values for normal adrenal glands. The tumor cholesterol: cholesterol ester ratio progressively decreased with time but remained 18-fold greater than the normal adrenal. Plasma corticosterone levels in tumor-bearing rats were elevated 3-fold by 14 days and initial detection. The adrenals of the tumor-bearing host exhibited marked involution, the extent of which was directly related to tumor size.

Adrenal cortical tumors with low attenuation coefficients: a pitfall in computed tomography diagnosis.

Four cases of adrenal tumors with unusually low attenuation coefficients are reported. The tumors presented with values ranging from 8 to 17 EMI units (EU: 500 scale) instead of the expected 30 to 40 EU range of the remainder of our adrenal tumors. Two of these patients had primary aldosteronism and two had Cushing's syndrome. An unusually high lipid content may be responsible for the lucent appearance.