Cushing's syndrome by left adrenocortical adenoma synchronously associated with primary aldosteronism by right adrenocortical adenoma: report of a case.

Synchronous associations of Cushing's syndrome (CS) and primary aldosteronism (PA) with multiple adrenocortical adenomas secreting each hormone independently have rarely been reported. Herein, we describe a unique case of PA associated with CS with detailed clinical and pathological investigations. Bilateral adrenal masses with clinical symptoms of CS and PA were found in a 43-year-old woman. Venous sampling demonstrated excess secretion of cortisol, and aldosterone from right, and left tumor, respectively. A bilateral laparoscopic partial adrenalectomy was undergone. The right adrenal tumor (3 cm) was yellow in color with abundant lipofuscin granules, and was composed of both eosinophilic compact cells and clear cells. In situ hybridization showed that both mRNAs for HSD3B2 and CYP17A1 were strongly expressed in the tumor, suggesting cortisol synthesis. Left adrenal tumor (2.4 cm) was golden-yellow in color, and composed of clear cells only. Expression of HSD3B2 and CYP11B mRNAs were observed in the tumor compatible with the aldosterone synthesis. Furthermore, minute nodules were found at the surface of normal-appearing cortex on both sides of the adrenal glands, and the expression of HSD3B2 and CYP11B mRNAs was clearly demonstrated within the nodules, indicating aldosterone synthesis. We diagnosed that the present case had 1) cortisol-producing right adrenocortical adenoma, 2) aldosterone producing left adrenocortical adenoma, and 3) cortical minute nodules with aldosterone production in both adrenal glands compatible with idiopathic adrenal hyperplasia. We reviewed the cases reported, and discussed the significance of the minute nodules in the adrenal cortex, often found in association with the adrenocortical adenoma.

Inhibition of nuclear factor-kappaB activation by pyrrolidine dithiocarbamate prevents chronic FK506 nephropathy.

BACKGROUND: Chronic tacrolimus (FK506) nephrotoxicity is characterized by renal fibrosis with interstitial inflammation. Since nuclear factor-kappaB (NF-kappaB) plays a key role in chronic inflammatory diseases including renal disease, the present study was conducted to elucidate the role of NF-kappaB in the pathogenesis of chronic FK506-induced nephropathy. METHODS: FK506 (1 mg/kg/day, SC) was administered daily to rats maintained on low sodium diet for 42 days. Some rats were treated with a putative NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC; 100, 200 mg/kg/day, by gavage). The renal function, renal histology, renal NF-kappaB-DNA binding activity and gene expression profile were examined. RESULTS: FK506 caused a decline in glomerular filtration and induced characteristic renal morphologic changes including arteriolopathy, tubular atrophy and interstitial fibrosis. FK506 markedly activated renal cortical NF-kappaB-DNA binding. PDTC administration inhibited NF-kappaB-DNA binding activity in a dose dependent manner. With higher dose, NF-kappaB-DNA binding activity was decreased to a control level. PDTC had little effect on FK506-induced renal dysfunction. Renal cortical monocyte/macrophage infiltration observed in FK506-treated rats was dramatically suppressed by PDTC. FK506 up-regulated renal cortical gene expression of chemoattractant proteins, monocyte chemoattractant protein-1 (MCP-1) and osteopontin. PDTC significantly blocked MCP-1 gene expression but had no effect on osteopontin gene expression. Tubular atrophy and tubulointerstitial fibrosis, but not arteriolopathy, were significantly attenuated by PDTC. FK506 increased renal mRNA expression of fibrogenic molecules and extracellular matrices that also were attenuated by PDTC treatment. CONCLUSIONS: NF-kappaB plays an important role in mediating cortical monocyte/macrophage infiltration and in the pathogenesis of tubular injury and interstitial fibrosis in experimental FK506-induced chronic nephropathy.

Role of renin-angiotensin system and nuclear factor-kappaB in the obstructed kidney of rats with unilateral ureteral obstruction.

The present study was conducted to elucidate the role of oxidative stress and nuclear factor-kappaB (NF-kappaB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-kappaB. Both an AT(1) antagonist, candesartan, and a NF-kappaB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-kappaB activation in obstructive nephropathy.

[Two cases of systemic lupus erythematosus accompanied by antiphospholipid syndrome nephropathy without immune complex nephritis].

We report here two interesting cases of systemic lupus erythematosus(SLE) accompanied by antiphospholipid syndrome nephropathy(APSN). These cases satisfied the criteria for SLE established by the American College of Rheumatology 1997 and also satisfied the criteria for antiphospholipid syndrome (APS) established by the Sapporo International Workshop of APS 1998. Both cases had high blood pressure with elevated plasma renin activity, proteinuria and renal dysfunction. Their biopsied renal specimens showed the characteristic findings for APSN, such as mesangial proliferation, double contours, thickening of the capillary loops, and intimal hyperplasia, but there was no evidence for immune complexes in the glomeruli, which were examined by the indirect immunofluorescence methods and the electron microscopy method. These results indicated that their renal dysfunction was caused by APSN, but not by immune complex nephritis. In addition to treatment with prednisolone, they were administered anticoagulants(warfarin, or aspirin, or heparin) for APSN and an angiotensin II receptor blocker, candesartan, for the hypertension. Subsequently, their conditions recovered with the improvement of renal function and hypertension. Our experiences suggest that anticoagulant therapy in addition to corticosteroids offers advantages in the treatment of patients with SLE accompanied by APSN and renal dysfunction.