A Case of Adrenocortical Carcinoma With Severe Hypertension and Hypokalemia

Case: 70 years old woman was pointed out for hypertension at a medical checkup and visited a primary physician. Severe hypokalemia (2.4 mmol/L) was noted, and abdominal CT scan revealed a right 99 mm diameter adrenal tumor adjacent to a 80 mm diameter liver tumor. She was referred to our hospital for further management. Despite treatment with antihypertensive agents, including ARB, MRB, and CCB, her blood pressure remained around 170/90 mmHg. In the meantime, 120 meq of potassium chloride treatment was needed to keep her serum potassium levels around 3.5 mmol/L. Both her plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were high (6.4 ng/mL/h and 376 pg/mL), indicating renin-dependent hypertension. Since CT angiography revealed the right renal artery compressed downward by the adrenal tumor, renovascular hypertension was suspected. Moreover, both early morning plasma ACTH levels and serum cortisol levels were suppressed (8.5 pmol/L and 5.3 μg/dL), despite elevated urinary free cortisol levels (350 μg/day). Urinary steroid profile analysis detected various elevated precursor steroid metabolites, including deoxycorticosterone (DOC) and corticosterone. DOC levels were 5 folds more than the upper normal limit, suggesting one of the causes of her hypertension with hypokalemia, while elevated corticosterone levels were thought to be contributed to suppressing ACTH. After the right adrenalectomy and hepatic segmentectomy, both of her hypertension and hypokalemia rapidly improved with declining PRA and PAC levels to 0.2 ng/mL/h and < 0.7 pg/mL, respectively. Urinary DOC levels also fell into the normal range. From the pathological findings, she was diagnosed with adrenocortical carcinoma (ACC) infiltrating the liver (pT4N0M0, stage IV). The immunohistochemistry analysis showed disorganized expression of steroidogenic enzymes, including CYP11B1, CYP11B2, and 3β-HSD, supporting a variety production of steroid metabolites from the ACC. Although mitotane was initiated as a adjuvant chemotherapy, multiple metastasis was found at her lung, liver, and vertebrae, 6 months after the operation. Along with that, hypertension and hypokalemia recurred gradually with both of PRA and PAC elevation. However, CT angiography detected no apparent renovascular stenosis. We performed renin immunostaining of ACC specimen revealed partially positive, demonstrating renin production from this ACC. Conclusion: Although juxtaglomerular cell tumor is the most common renin-producing tumor, some cases of renin secreting ACC have been reported as a quite rare case. In the present case, renin secretion from ACC might be contributed to severe hypertension and hypokalemia, and both renal artery stenosis and DOC secretion induced by the ACC are considered to be a major cause.