METASTATIC RENAL CELL CARCINOMA: UNUSUAL CAUSE OF ADDISON DISEASE
S. L. GOLDENBERG, M.D.
J. E. WRIGHT, M.D., F.R.C.S. M. G. McLOUGHLIN, M.D., F.R.C.S.
From the Division of Urology, Department of Surgery, University of British Columbia, Vancouver
ABSTRACT-We report a case of adrenocortical insufficiency presenting thirty months after radi- cal nephrectomy for renal cell carcinoma. Removal of the remaining contralateral adrenal gland revealed metastatic disease.
Metastatic spread to the adrenal glands, result- ing in Addison disease, is rare.1 Sixteen bio- chemically confirmed cases have been re- ported,2-4 and the implicated primary sites are listed in Table I.
Herein, we report a case of renal cell car- cinoma metastatic to and obliterating the soli- tary contralateral adrenal gland thirty months after radical nephrectomy.
Case Report
A fifty-three-year-old man presented in March, 1978, with hematuria and left flank pain. Radiologic investigations revealed a solid hypovascular tumor in the left kidney, with a normal right kidney and adrenal gland. A metastatic workup was negative, and the pa- tient underwent an enbloc left radical nephrec- tomy and adrenalectomy. Microscopic ex- amination of the specimen demonstrated a well-differentiated adenocarcinoma with a papillary configuration that infiltrated the perinephric fat. There was no evidence of lym- phatic or venous involvement, and a normal adrenal gland was present. His convalescence was uneventful.
Two years later, progressive symptoms of fa- tigue, anorexia, weight loss, and light headed-
ness developed. He continued with his daily ac- tivities until a sudden syncopal episode brought him to the emergency room. Physical examina- tion revealed increased skin pigmentation in his surgical scar, and postural hypotension. Serum potassium was 7.7 mEq/L.
Soon after his admission, a corticotropin stimulation test was performed. This was con- sistent with primary adrenal insufficiency, with a baseline cortisol of 6.0 µg/100 ml and no elevation upon intravenous administration of 25 units of ACTH (Cortrosyn). He was given cortisone and fludrocortisone (Florinef) with marked subjective and objective improvement. Serum electrolytes returned to normal.
Ultrasound examination of the abdomen demonstrated a 4-cm solid mass in the right adrenal gland. CT scan and angiography con- firmed the presence of a 5 to 6-cm hypovascular
| Site | Number of Cases |
|---|---|
| Bronchus | 12 |
| Stomach | 1 |
| Pancreas | 1 |
| Breast | 1 |
| Occult seminoma | 1 |
adrenal tumor with a normal right kidney. Metastatic workup was again negative.
In January, 1981, the patient underwent a right thoraco-abdominal adrenalectomy and had an unremarkable postoperative course. Mi- croscopic examination of the specimen showed poorly differentiated tumor cells with marked pleomorphism and prominent eosinophilic nu- cleoli. Many cells had a granular cytoplasm. Fat staining with oil red “O” demonstrated neu- tral fat in occasional cells, and Sudan black stain was positive for large amounts of phospho- lipid. Electron-microscopy confirmed the pres- ence of fat vacuoles, and helped to establish the diagnosis of metastatic renal cell carcinoma. Several months later, widespread lung metas- tases developed, and he succumbed.
Comment
Guttman1 estimates that less than 1 per cent of cases of primary Addison disease is due to metastatic tumor to the adrenals. There are several factors that may account for this low in- cidence. First, the clinical presentation is rare because there needs to be obliteration of over 90 per cent of functioning adrenal tissue prior to the onset of symptoms.3 Also, the symptoms of
advanced cancer may mimic those of adrenal insufficiency, resulting in a failure to make the proper diagnosis. Often, many cases may be masked by coincidental steroid treatment, and there is a general lack of effort to establish any secondary diagnoses in the terminally ill pa- tient.
Renal cell carcinoma metastasizes to the ipsi- lateral or contralateral adrenal gland in 19 per cent of cases.5 We report the first case of total ablation of adrenal tissue from renal adenocar- cinoma, with resultant medical emergency.
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References
1. Guttman PH: Addison’s disease-a statistical analysis of 566 cases and a study of pathology, Arch Pathol 10: 742 (1930).
2. Hill JG, and Brownell-Wheeler H: Adrenal insufficiency due to metastatic carcinoma of the lung, Cancer 18: 1467 (1965).
3. Vieweg WVR, Reitz RE, and Weinstein RL: Addison’s dis- ease secondary to metastatic carcinoma, an example of adreno- cortical and adrenomedullary insufficiency, ibid 5: 1240 (1975).
4. Henson JC: Addison’s disease secondary to occult metastatic seminoma, ibid 19: 1754 (1966).
5. Bennington JL, and Beckwith JB: Tumors of the Kidney, Re- nal Pelvis and Ureter, Atlas of Tumor Pathology, Washington, D.C., Armed Forces Institute of Pathology, 1975, p 168.