After Suramin therapy, a metastatic adrenal carcinoma switched from producing aldosterone to producing cortisol

CASE REPORT. Hypertension and hypokalemia appeared in a fifty-years old woman in 1990. On treatment with anti-hypertensive drugs, she consulted our Rheumatology Unit complaining muscle weakness at her legs and fatigue. Clinical chemistry showed hypokalemia, hypernatremia, alkaline urine pH, and a primary aldosteronism was supposed. Increase in plasma aldosterone concentration (619 pg/ml) and B-scan images confirmed diagnosis. Plasma renin, cortisol and ACTH levels were in normal values. Operative intervention with excision of the tumor was performed in February 1991, and the histological examination showed a macro-adenoma with a necrotic area inside. No enlargement or involvement of lymphnodes were seen. Despite operative intervention and histological diagnosis, liver metastases (confirmed by needle biopsy) occurred in May 1992. Suramin therapy was begun at a weekly dose of 800 mg/square meter. The drug was stopped in October 1992 for inefficacy and side effects. The patient presented brain and bone metastases and a serious dermatitis, too. She was hospitalized again and Cushingʹs syndrome with typical habitus, truncal obesity, hirsutism, purplish abdominal striae was seen. Plasma aldosterone concentration was in normal value but plasma cortisol was 548 microgram/ml and ACTH 4,04 pg/ml. The patient was treated with Cortone acetate and Aminoglutemide, a drug inhibiting gluco-and mineral-corticoids synthesis. Cortisol came back into normal value but aldosterone increased. CONCLUSIONS. Primary aldosteronism is an uncommon disease. It results from an aldosterone-producing adrenal adenoma or, rarely, adrenal carcinoma (less than 1%). Despite operative intervention, most patients with adrenal carcinoma die within 3 years of diagnosis. Our patient died in April 1994. Suramin is used in the treatment of adrenal cancer. The number of patients evaluated is small and more study is needed to prove its efficacy. We have not found any report about a switch of hormonal production by adrenal metastatic cells after Suramin therapy. Suramin possesses adrenocorticolytic properties. On human normal adrenocortical cells it has an inhibitory effect on the cytochrome P-450 enzymes. The drug might inhibit five adrenal steroidogenic enzymes decreasing the hormone production. It seems that Suramin acts on ACTH-receptors, too. To explain the inhibition of aldosterone synthesis and the very high increase of cortisol plasma level occurred in our patient, we suppose Suramin especially induced a block on an active, tumoral 18-Hydroxylase-enzyme so that the reaction from DOC to Aldosterone was shut and the accumulation of metabolic middle compounds led to cortisol biosynthesis increase. Other hypotheses could be possible.