ADRENAL
INSUFFICIENCY
UNILATERAL WILLIAM
RADICAL
L. HENRICH,
JAN GOLDBERG, MARK LUCAS,
AFTER
NEPHRECTOMY
M.D.
B.A. M.D.
PATRICIA GAB0 W, M. D. From the Division of Renal Diseases, Department of Medicine, and the Department of Urology, Denver General Hospital and the University of Colorado Medical Center, Denver, Colorado
ABSTRACT -A case of adrenal insufficiency occurring after unilateral radical nephrectomy presented. Recommendations for identification and treatment of this condition are discussed.
Renal cell carcinoma is a common tumor in which surgical therapy with radical nephrectomy affords a 57 per cent, five-year survival if metastases are not present at the time of operation.’ To our knowledge, adrenal insufficiency occurring after unilateral nephrectomy for renal cell carcinoma has not been described. The following case report describes a patient in whom acute adrenocortical insufficiency developed after radical nephrectomy for renal cell carcinoma. Case Report A sixty-six-year-old nondiabetic black male was admitted to Denver General Hospital for rectal bleeding. He recently had lost 6 pounds, but denied hematuria, fever, or flank pain. Initial blood pressure was 125/85 mm. Hg and the heart rate 82 without orthostatic changes. No hyperpigmentation was present; the stool was frankly bloody on inspection. A 15-cm. mass was palpable in the right upper abdominal quadrant. Initial laboratory values showed a hematocrit of 32, white blood cell count of 9,900 per cubic millimeter, and a platelet count of 10,000 per cubic millimeter. Electrolytes were sodium 140 mEq., potassium 3.8 mEq., chloride 108 mEq., and bicarbonate 25 mEq. per liter; blood urea nitrogen was 23 mg. and creatinine 1.1 mg. per 100 ml. Urinalysis revealed no protein, white cells, or casts. A chest
584
is
x-ray film was normal and purified protein derivative test negative. Thrombocytopenia evaluation revealed increased megakaryocytes in the bone marrow. Treatment with prednisone 15 mg. per day increased the platelet count to 77,000 per cubic millimeter by the third hospital day; glucocorticoids were continued throughout his hospital course. Excretory urogram, abdominal ultrasound, and angiography demonstrated a 15-cm., partially calcified, right renal cyst. Percutaneous cyst puncture was performed revealing very irregular walls and thick, brown fluid which was cytologically and microbiologically negative. At laparotomy, a large mass arising in the kidney and adherent to liver, right colon, and duodenum was encountered. Radical nephrectomy was performed, and renal cell carcinoma of the kidney was demonstrated pathologically. The accompanying right adrenal gland weighed 3 Gm. (normal is about 5 Gm.2) and was free of tumor. By the fourth postoperative day the patient had lost 12 pounds, had marked orthostatic hypotension (125/85 mm. Hg supine, 90/50 mm. Hg erect) and volume depletion. Electrolytes were sodium 130 mEq., potassium 5.3 mEq., chloride 100 mEq., and bicarbonate 26 mEq. per liter. Despite hypovolemia and hypotension the urine sodium concentration was 197 mEq. per liter; peripheral supine plasma renin activity was 4.1 ng. per milliliter (normal is 0.2 to 3.6 ng. per milliliter per hour);
UROLOGY
/ DECEMBER
1976 / VOLUME
VIII,
NUMBER 6
plasma aldosterone was 0 pg. per milliliter (normal is 32 to 200 pg. per milliliter); and urinary aldosterone was 0.5 pg. per day (normal is 5 to 20 pg. per day). An alpha l-24 ACTH (Cortrosyn)3,4 stimulation test showed no aldosterone increase at thirty minutes or one hour (values were 0 pg. per milliliter baseline and after the injection); serum cortisol values were 6 pg. per deciliter baseline (normal is i’ to 20 ng. per deciliter), and 8 pg. per deciliter at one hour (normal equals double baseline). Fludrocortisone (Florinef) 0.1 mg. was added to the 15 mg. of prednisone. One month later the patient had gained 6 pounds and had a blood pressure of 130/90 mm. Hg without orthostatic change. Repeat electrolytes were sodium 143 mEq., potassium 4.1 mEq., chloride 104 mEq., and bicarbonate 104 mEq. per liter. A subsequent bone scan and orbital tomograms show osteolytic lesions in the left orbital area.
sistent and profound volume depletion with salt wasting and hyperkalemia were clues to the diagnosis, which was confirmed by high renin and low aldosterone and cortisol values without ACTH responsiveness. Prednisone is measured in the assay of plasma cortisol and partly accounts for the levels obtainedeg In patients undergoing radical nephrectomy, adrenal insufficiency should be suspected in the setting of postoperative hypotension and weight loss. Prompt determination of urinary sodium concentration, plasma renin, and aldosterone should be obtained. Correction of volume depletion with intravenous saline solution and treatment for hyperkalemia as well as specific therapy with corticosteroids and mineralocorticoid should be promptly instituted. lo Such measures will prevent sudden postoperative insufficiency. death due to adrenal Division of Renal Diseases Department of Medicine Denver General Hospital Denver, Colorado 80203 (DR. GABOW)
Comment The differential diagnosis of Addison’s disease includes idiopathic atrophy, granulomatous disease, amyloid, destruction of the gland by metastatic tumor, adrenolytic drugs (0, p’ DDD), congenital aplasia, and sepsis with shock. In our patient, amyloid, granulomatous disease, intra-adrenal hemorrhage during the period of thrombocytopenia, and metastatic destruction of the contralateral adrenal gland are the most likely possibilities. Unilateral aplasia of the adrenal is exceedingly rare but is included as an etiologic possibility.5 Amyloidosis may occur in as many as 5 per cent of patients with hypernephroma;6 however, the exact incidence of adrenal involvement and insufficiency is not known. Evidence of systemic amyloid and amyloid involvement of the removed adrenal were absent in our case. Since there was no diagnostic evidence for miliary tuberculosis, intra-adrenal hemorrhage, and metastatic destruction of the remaining adrenal gland appear to be the most likely causes. Although adrenal metastases from hypernephroma occur relatively frequently,7 adrenal insufficiency has not been often recognized as a sequelae of the event. The symptoms and signs of adrenal insufficiency may be difficult to recognize in the context of postoperative recovery from major surgery, as has been recently noted by Hubay, Weckesser, and Levy. * In this patient, per-
UROLOGY /
ACKNOWLEDGMENT. To Fred Katz, M, D., and Miss Loretta Durkin for their assistance. References 1. SKINNER, D. G., VERMILLON, C. D., and COLVIN, R. B.: The surgical management of renal cell carcinoma, J. Urol. 107: 705 (1972). 2. LIDDLE, G. W.: The adrenals, in Williams, R. H., Ed.: Textbook of Endocrinology, 5th ed., Philadelphia, W. B. Saunders Co., 1974, p. 234. 3. SPECKART, P. F., NICOLOFF, J. T., and BETHUNE, J. E. : Screening for adrenocortical insufficiency with cosyntropin, Arch. Int. Med. 128: 761 (1971). 4. DLUHY, R. G., HIMATHONGKAM,T., and GREENFIELD, M.: Rapid ACTH test with plasma aldosterone levels. Improved diagnostic discrimination, Ann. Int. Med. 80: 693 (1974). 5. HUME, D. M.: Pituitary and adrenal, in Schwartz, S. I., Ed.: Principles of Surgery, New York, McGraw Hill Co., 1969, p. 1231. 6. GILLENWATER, J. Y.: Disorders of the kidney, in Wyker, A. W., and Gillenwater, J. Y., Eds.: Method of Urology, Baltimore, Williams and Wilkins Co., 1975, p. 159. 7. WRIGHT, F. W.: Adrenal metastases from renal carcinoma diagnosed by selective angiography, Br. J. Urol. 46: 472 (1974). 8. HUBAY, C. A., WECKESSER, E. C., and LEVY, R. P.: Occult adrenal insufficiency in surgical patients, Ann. Surg. 181:325 (1975). 9. BOWMAN, R. E., and DELUNA, R. F.: Assessment of a protein binding method for cortisol determination, Anal. Biochem. 26: 465 (1969). 10. LEVINSKY, N. G.: Management of emergencies VI: Hyperkalemia, N. Engl. J. Med. 274: 1076 (1966).
DECEMBER 1976 i VOLUME VIII, NUMBER 6
INSUFFICIENCY
UNILATERAL WILLIAM
RADICAL
L. HENRICH,
JAN GOLDBERG, MARK LUCAS,
AFTER
NEPHRECTOMY
M.D.
B.A. M.D.
PATRICIA GAB0 W, M. D. From the Division of Renal Diseases, Department of Medicine, and the Department of Urology, Denver General Hospital and the University of Colorado Medical Center, Denver, Colorado
ABSTRACT -A case of adrenal insufficiency occurring after unilateral radical nephrectomy presented. Recommendations for identification and treatment of this condition are discussed.
Renal cell carcinoma is a common tumor in which surgical therapy with radical nephrectomy affords a 57 per cent, five-year survival if metastases are not present at the time of operation.’ To our knowledge, adrenal insufficiency occurring after unilateral nephrectomy for renal cell carcinoma has not been described. The following case report describes a patient in whom acute adrenocortical insufficiency developed after radical nephrectomy for renal cell carcinoma. Case Report A sixty-six-year-old nondiabetic black male was admitted to Denver General Hospital for rectal bleeding. He recently had lost 6 pounds, but denied hematuria, fever, or flank pain. Initial blood pressure was 125/85 mm. Hg and the heart rate 82 without orthostatic changes. No hyperpigmentation was present; the stool was frankly bloody on inspection. A 15-cm. mass was palpable in the right upper abdominal quadrant. Initial laboratory values showed a hematocrit of 32, white blood cell count of 9,900 per cubic millimeter, and a platelet count of 10,000 per cubic millimeter. Electrolytes were sodium 140 mEq., potassium 3.8 mEq., chloride 108 mEq., and bicarbonate 25 mEq. per liter; blood urea nitrogen was 23 mg. and creatinine 1.1 mg. per 100 ml. Urinalysis revealed no protein, white cells, or casts. A chest
584
is
x-ray film was normal and purified protein derivative test negative. Thrombocytopenia evaluation revealed increased megakaryocytes in the bone marrow. Treatment with prednisone 15 mg. per day increased the platelet count to 77,000 per cubic millimeter by the third hospital day; glucocorticoids were continued throughout his hospital course. Excretory urogram, abdominal ultrasound, and angiography demonstrated a 15-cm., partially calcified, right renal cyst. Percutaneous cyst puncture was performed revealing very irregular walls and thick, brown fluid which was cytologically and microbiologically negative. At laparotomy, a large mass arising in the kidney and adherent to liver, right colon, and duodenum was encountered. Radical nephrectomy was performed, and renal cell carcinoma of the kidney was demonstrated pathologically. The accompanying right adrenal gland weighed 3 Gm. (normal is about 5 Gm.2) and was free of tumor. By the fourth postoperative day the patient had lost 12 pounds, had marked orthostatic hypotension (125/85 mm. Hg supine, 90/50 mm. Hg erect) and volume depletion. Electrolytes were sodium 130 mEq., potassium 5.3 mEq., chloride 100 mEq., and bicarbonate 26 mEq. per liter. Despite hypovolemia and hypotension the urine sodium concentration was 197 mEq. per liter; peripheral supine plasma renin activity was 4.1 ng. per milliliter (normal is 0.2 to 3.6 ng. per milliliter per hour);
UROLOGY
/ DECEMBER
1976 / VOLUME
VIII,
NUMBER 6
plasma aldosterone was 0 pg. per milliliter (normal is 32 to 200 pg. per milliliter); and urinary aldosterone was 0.5 pg. per day (normal is 5 to 20 pg. per day). An alpha l-24 ACTH (Cortrosyn)3,4 stimulation test showed no aldosterone increase at thirty minutes or one hour (values were 0 pg. per milliliter baseline and after the injection); serum cortisol values were 6 pg. per deciliter baseline (normal is i’ to 20 ng. per deciliter), and 8 pg. per deciliter at one hour (normal equals double baseline). Fludrocortisone (Florinef) 0.1 mg. was added to the 15 mg. of prednisone. One month later the patient had gained 6 pounds and had a blood pressure of 130/90 mm. Hg without orthostatic change. Repeat electrolytes were sodium 143 mEq., potassium 4.1 mEq., chloride 104 mEq., and bicarbonate 104 mEq. per liter. A subsequent bone scan and orbital tomograms show osteolytic lesions in the left orbital area.
sistent and profound volume depletion with salt wasting and hyperkalemia were clues to the diagnosis, which was confirmed by high renin and low aldosterone and cortisol values without ACTH responsiveness. Prednisone is measured in the assay of plasma cortisol and partly accounts for the levels obtainedeg In patients undergoing radical nephrectomy, adrenal insufficiency should be suspected in the setting of postoperative hypotension and weight loss. Prompt determination of urinary sodium concentration, plasma renin, and aldosterone should be obtained. Correction of volume depletion with intravenous saline solution and treatment for hyperkalemia as well as specific therapy with corticosteroids and mineralocorticoid should be promptly instituted. lo Such measures will prevent sudden postoperative insufficiency. death due to adrenal Division of Renal Diseases Department of Medicine Denver General Hospital Denver, Colorado 80203 (DR. GABOW)
Comment The differential diagnosis of Addison’s disease includes idiopathic atrophy, granulomatous disease, amyloid, destruction of the gland by metastatic tumor, adrenolytic drugs (0, p’ DDD), congenital aplasia, and sepsis with shock. In our patient, amyloid, granulomatous disease, intra-adrenal hemorrhage during the period of thrombocytopenia, and metastatic destruction of the contralateral adrenal gland are the most likely possibilities. Unilateral aplasia of the adrenal is exceedingly rare but is included as an etiologic possibility.5 Amyloidosis may occur in as many as 5 per cent of patients with hypernephroma;6 however, the exact incidence of adrenal involvement and insufficiency is not known. Evidence of systemic amyloid and amyloid involvement of the removed adrenal were absent in our case. Since there was no diagnostic evidence for miliary tuberculosis, intra-adrenal hemorrhage, and metastatic destruction of the remaining adrenal gland appear to be the most likely causes. Although adrenal metastases from hypernephroma occur relatively frequently,7 adrenal insufficiency has not been often recognized as a sequelae of the event. The symptoms and signs of adrenal insufficiency may be difficult to recognize in the context of postoperative recovery from major surgery, as has been recently noted by Hubay, Weckesser, and Levy. * In this patient, per-
UROLOGY /
ACKNOWLEDGMENT. To Fred Katz, M, D., and Miss Loretta Durkin for their assistance. References 1. SKINNER, D. G., VERMILLON, C. D., and COLVIN, R. B.: The surgical management of renal cell carcinoma, J. Urol. 107: 705 (1972). 2. LIDDLE, G. W.: The adrenals, in Williams, R. H., Ed.: Textbook of Endocrinology, 5th ed., Philadelphia, W. B. Saunders Co., 1974, p. 234. 3. SPECKART, P. F., NICOLOFF, J. T., and BETHUNE, J. E. : Screening for adrenocortical insufficiency with cosyntropin, Arch. Int. Med. 128: 761 (1971). 4. DLUHY, R. G., HIMATHONGKAM,T., and GREENFIELD, M.: Rapid ACTH test with plasma aldosterone levels. Improved diagnostic discrimination, Ann. Int. Med. 80: 693 (1974). 5. HUME, D. M.: Pituitary and adrenal, in Schwartz, S. I., Ed.: Principles of Surgery, New York, McGraw Hill Co., 1969, p. 1231. 6. GILLENWATER, J. Y.: Disorders of the kidney, in Wyker, A. W., and Gillenwater, J. Y., Eds.: Method of Urology, Baltimore, Williams and Wilkins Co., 1975, p. 159. 7. WRIGHT, F. W.: Adrenal metastases from renal carcinoma diagnosed by selective angiography, Br. J. Urol. 46: 472 (1974). 8. HUBAY, C. A., WECKESSER, E. C., and LEVY, R. P.: Occult adrenal insufficiency in surgical patients, Ann. Surg. 181:325 (1975). 9. BOWMAN, R. E., and DELUNA, R. F.: Assessment of a protein binding method for cortisol determination, Anal. Biochem. 26: 465 (1969). 10. LEVINSKY, N. G.: Management of emergencies VI: Hyperkalemia, N. Engl. J. Med. 274: 1076 (1966).
DECEMBER 1976 i VOLUME VIII, NUMBER 6
