ELSEVIER
CALCIFIED ALDOSTERONE-PRODUCING ADRENOCORTICAL ADENOMA
TOMISLAV M. JELIC, MD, PHD, WILLIAM TRIEST, MD, JOHN SHEILS, MD, DAVID PORTER, MD, DANIEL CHERRY, MD, RICHARD J. BALTARO, MD, PHD, WILLIAM SHEILS, JR., MD, HENRY K. DRISCOLL, MD, HARESH P. SOLANKI, MD, RAPHAEL MOLINA, MD, LOUIS MOLINA, MD, AND BRUCE S. CHERTOW, MD
We report the first case of benign aldosteronoma of an ordinary size with calcifications. We review the clini- cal, clinical imaging, histopathological, and labora- tory features of aldosterone-producing adrenal ade- noma versus carcinoma. We conclude that no single feature is diagnostic, and the full range of data must be considered. Calcifications may not necessarily be a distinguishing point.
KEY WORDS:
Adrenal calcifications; Aldosterone-secreting neoplasms.
INTRODUCTION
Primary hyperaldosteronism is a rare cause of hyper- tension, found in only 0.8% of all hypertensive patients (1). Usually it is caused by an adenoma or bilateral adre- nal hyperplasia in 64% and 32%, respectively (2) and very rarely by an adrenocortical carcinoma. Diagnos- ing hyperaldosteronism and identifying the nature of the lesion is a complex challenge involving endocrino- logical evaluation combined with multiple clinical im- aging procedures. Calcifications of a benign aldostero- noma are an exceptional finding but may frequently occur with malignancy. In our patient calcifications
of the adrenal gland tumor detected by computed tomography suggested carcinoma as a cause of primary hyperaldosteronism. However, endocrinological data, NP59-131I-iodocholesterol scans [NP-59 is assigned code name for I-131-iodo methyl-norcholesterol], and pathological findings indicated a benign calcified adre- nocortical adenoma.
CASE REPORT
A 24-year-old white woman presented with a 5-year his- tory of uncontrolled hypertension of about 190/125 mm Hg despite combinations of various antihypertensive drugs. She also had muscle weakness and severe hypokalemia (2.9 mEq/L). Plain X-ray studies of the ab- domen and intravenous urography showed calcifica- tions in the region of the right adrenal gland (Figure 1).
Endocrinological evaluation revealed a high serum aldosterone level and high urinary excretion of al- dosterone and potassium. Plasma renin activity did not increase with upright posture. Urinary excretion of cor- tisol and metanephrines was normal as well as plasma 11-deoxycortisol levels. Bilateral adrenal vein sampling showed a right-to-left aldosterone ratio of 27.5:1, sug- gesting a right-sided tumor. Computed tomography demonstrated marked calcifications within a 2.0 to 3.0- cm × 1.5-cm soft-tissue mass (Figure 2) in the right adrenal gland. NP59-131I-iodocholesterol scans after dexamethasone suppression showed persistent focal uptake of nuclide in the right adrenal gland on days 4 and 5 after injection (Figure 3). This finding was con- sistent with a right adrenal aldosteronoma.
Because all the above-mentioned data strongly
From the Departments of Radiology and Pathology, Cabell Hun- tington Hospital (W.T., J.S., D.P., W.S., R.M., L.M.); Department of Medicine, Marshall University School of Medicine (T.J., R.B., H.D., D.C., B.C.); and Nuclear Medicine Section, Medical Service (H.S., B.C.), VA Medical Center, Huntington, West Virginia.
Address reprint requests to: Haresh P. Solanki, MD, Section of Nuclear Medicine, VA Medical Center, 1540 Spring Valley Drive, Hun- tington, WV 25704.
Received January 15, 1995; accepted June 15, 1995.
pointed to an aldosterone-producing tumor of the right adrenal gland, the patient was explored through a posterior approach and the right adrenal gland was re- moved. The gland measured 4.0 x 2.8 x 2.7 cm and contained a nodule measuring 2.5 cm in greatest dimension. Toward the periphery of the nodule was a region of calcification measuring up to 0.8 cm in greatest dimension. The adrenal gland and tumor to- gether weighed 12 g. Microscopically the tumor was encapsulated and composed of mature, uniform cells resembling zona fasciculata for the most part (Figures 4 and 5). There were no mitoses. Some areas of the tu-
mor were calcified. Notably, calcifications were limited to the adenoma and its capsule and did not involve the adjacent normal adrenal gland (Figure 6). There was no evidence of capsular or vascular invasion. One year postoperatively off any medications, the patient’s blood pressure was 110/70 mm Hg, and the plasma potassium level was normal.
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DISCUSSION
Aldosterone-secreting adrenocortical adenomas and carcinomas may have characteristic features that may assist in their differentiation. This distinction is im- portant because of the dismal prognosis of carcinoma, different treatment, and different surgical approach. If carcinoma is preoperatively suspected, an anterior transabdominal approach is used to ensure an adequate surgical exploration and a complete excision. If a be-
nign adrenal adenoma is expected, a posterior lumbar approach is preferred, because it is associated with less postoperative morbidity and lower medical cost. Com- pared to adenomas, carcinomas are usually larger, may occur at any age including in children (adenomas usu- ally occur in adults), frequently are calcified, gener- ally secrete more than one steroid hormone, are not visualized by 131I-iodocholesterol scan, and may cause more pronounced hypokalemia. Microscopic exami- nation of adrenocortical carcinomas may show a high
mitotic rate, pleomorphism, vascular and capsular in- vasion, tumor cell necrosis, and broad fibrous bands traversing the tumor (3). To the best of our knowledge, this is the first published case of a benign calcified adrenal aldosterone-secreting adenoma that has usual dimensions. In only one other case have calcifications been reported in a benign adenoma (4). It was an aldosterone-producing gigantic adrenocortical ade- noma (75 g, 6.5 x 5.5 x 5.0 cm) with calcifications, hemorrhage, and cysts. Calcifications were limited to the cysts and were not present inside the parenchyma of the adenoma. It is notorious that calcification is a highly nonspecific sign and may be present in 85% of neuroblastomas, 75% of cysts, 50% of cases of histoplasmosis or hemorrhage, and 6% of cases of pheochromocytomas or metastasis in adrenals (5). Cal- cification may occur in up to 40% of adrenocortical carcinomas and in 14% of adrenal adenomas that do not secrete aldosterone (5). All reported aldosterone- secreting tumors that were calcified were found to be carcinomas (1, 6), except that found by Yoshida et al. (4).
Exceptions to all the previously cited characteristics of adrenocortical aldosterone-secreting adenomas and aldosterone-secreting carcinomas have been reported.
Aldosterone-secreting adenomas usually measure around 1.2 cm in diameter (7) while carcinomas mea- sure from 6 to 35 cm in greatest dimension (1). How- ever, 5.6% of the aldosterone-secreting adenomas reported by Conn et al. (9) measured between 6 and 7 cm in diameter (8) and aldosterone-secreting adreno- cortical carcinoma may measure 2 x 1.8 cm. Improved
CT technology with contiguous 5-mm collimation yields 82% sensitivity in detecting aldosterone-secret- ing adenomas, and can detect an aldosteronoma as small as 0.7 cm (10). However, CT alone cannot distin- guish whether an adrenal mass is benign or malignant, and sometimes it underestimates the actual size of the adrenal gland tumor (11).
Adrenocortical carcinomas are not usually visu- alized by 131I-iodocholesterol functional scanning. However, there are exceptions in which aldosterone- secreting carcinomas were (6) and aldosterone-secret- ing adenomas were not visualized on a functional scan (12).
Although aldosterone-secreting adrenocortical car- cinomas secrete precursors of aldosterone and other steroid hormones along with aldosterone, several cases have been reported in which these tumors secreted al- dosterone only (6, 13).
Differentiation between adenoma and carcinoma of the adrenal gland may be difficult on the basis of histo- logical features alone, and sometimes the only reliable criterion of malignancy is distant metastasis, usually to the liver and lungs (14).
Although in our patient the aldosterone-producing adenoma was calcified, we believe it is benign because of its histopathological appearance, hormonal pattern, and unilateral visualization by 1311-iodocholesterol scan. Absence of recurrence 1 year postoperatively supports this conclusion. We suggest that distinction between an aldosterone-producing adenoma and carcinoma may be made only by rational interpretation of all clinical, laboratory, and histopathological data. No one char-
acteristic has 100% diagnostic accuracy, and any one isolated finding may be misleading.
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