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Prolactin Secreting Renal Cell Carcinoma
0022-534 7/86/1361-0085$02.00
Vol. 136, July Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1986 by The Williams & Wilkins Co.
PROLACTIN SECRETING RENAL CELL CARCINOMA THOMAS H. STANISIC*
AND
JOHN DONOVAN
From the Department of Surgery/Urology, Arizona Health Sciences Center, Tucson, Arizona
ABSTRACT
We report a case of hyperprolactinemia and long-standing gynecomastia associated with a hypernephroma. After radical nephrectomy serum prolactin returned to normal and remained so for 4 years without evidence of tumor recurrence. Potential explanations for the observed concurrent findings and the literature are discussed. Renal cell carcinoma commonly is associated with paraneoplastic syndromes owing to ectopic hormone production by the tumor. Renal neoplasms have been demonstrated to produce parathormone, erythropoietin, renin, gonadotropins, placental lactogen and enteroglucagon. 1• 2 However, ectopic prolactin production by a neoplasm is rare, being reported only once previously in renal cell carcinoma3 and twice in bronchogenic carcinoma. 3·4 We report a case of a prolactin-secreting hypernephroma associated with long-standing gynecomastia.
the left kidney and a filling defect in the left renal pelvis suggestive of a blood clot (part A of figure). Arteriography showed a somewhat hypovascular lesion (part B of figure). Renal sonography suggested the mass to be solid. A chest x-ray and bone scan were within normal limits. Preoperatively, serum luteinizing hormone and follicle-stimulating hormone were within normal limits but serum prolactin measured 138 ng./ml. (normal 5 to 15) by radioimmunoassay. Left radical nephrectomy was performed through a left flank
A, nephrotomogram illustrates left renal mass. B, arteriogram shows corresponding hypovascular left renal mass
incision, and the patient was discharged from the hospital 8 days postoperatively. Pathological examination revealed renal cell carcinoma of the granular cell variety. A prolactin level drawn on postoperative day 7 was 5.6 ng./ml. Follicle-stimulating hormone, luteinizing hormone, testosterone, thyroid-stimulating hormone and cortisol levels also were within normal limits. The patient has been followed for 4 years postoperatively. Prolactin levels have been consistently within normal limits as have been bone scans and chest x-rays performed semiannually. Gynecomastia has persisted unchanged, and the patient is considering reduction mammoplasty. He has respectfully declined photographic documentation of the breast lesion.
CASE REPORT
J. N., a 42-year-old Mexican American man, presented to our emergency room in 1981 with a 2-day history of dark urine and dull left flank ache. History was unremarkable except for mild asthma since childhood and the presence of gynecomastia, which began when he was about 11 years old and progressed through adolescence but then remained stable. The patient stated that libido had always been "normal". At presentation he was not taking medications and had never taken estrogens, L-dopa, chlorpromazine, haloperidol or other drugs associated with elevated prolactin levels. Physical examination revealed mild left flank tenderness and generous gynecomastia but without galactorrhea. Laboratory studies 1 day preoperatively revealed white blood count 8,300 and hematocrit 42.5 per cent. Electrolytes, blood urea nitrogen, creatinine and glucose were within normal limits. Urinalysis showed red blood cells too numerous to count. Excretory urography revealed an 8.5 cm. spherical mass in the lower pole of
DISCUSSION
Our patient presented with documented hyperprolactinemia in the absence of a pituitary pathological condition, use of drugs that elevate prolactin, or any history of chest wall disease or hypothyroidism. Because the prolactin levels decreased to normal and have remained so postoperatively, the most likely explanation for the elevated serum prolactin is ectopic hormone production by the renal cell carcinoma. Although the presence of gynecomastia prompted our deter-
Accepted for publication February 14, 1986. * Requests for reprints: Department of Surgery/Urology, Arizona Health Sciences Center, 1501 N. Campbell, Tucson, Arizona 85724. 85
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STANISIC AND DONOVAN
mination of the serum prolactin level preoperatively, it is impossible to ascertain whether the hyperprolactinemia and gynecomastia were causally related or simply represented the simultaneous occurrence of 2 separate rare events. Frantz,5 and Carter and associates 6 have published extensive reviews on the physiology of prolactin, and the symptoms and signs associated with hyperprolactinemia. According to these authors, most men with gynecomastia do not have hyperprolactinemia. Conversely, only 14 per cent of the 22 cases with hyperprolactinemia reported by Carter and associates had gynecomastia and/ or galactorrhea. 6 Although prolactin may well be involved in human breast development physiologically and pathologically its precise mammotropic role in human beings is yet to be defined. The biological behavior of hypernephroma is varied and often unusual. The literature is replete with references to long-term spontaneous regression and delayed occurrence of metastasis even after 2 to 3 decades. 7 If the gynecomastia in our patient is secondary to hyperprolactinemia, then one must speculate that the tumor produced prolactin ectopically for more than 30 years. Whether such long-term ectopic hormone production can occur first in a cortical adenoma that later "evolves" into a hypernephroma8 or in a hypernephroma with a usually slow growth rate is moot. Whichever series of hypotheses one accepts
to explain the unusual combination of events in our patient, this case serves again to illustrate the unpredictable biological behavior and potential for unusual clinical presentation of this most interesting neoplasm. REFERENCES
1. Altaffer, L. F., III and Chenault, 0. W., Jr.: Paraneoplastic endocrinopathies associated with renal tumors. J. Urol., 122: 573, 1979. 2. Sufrin, G., Mirand, E. A., Moore, R. H., Chu, T. M. and Murphy, G. P.: Hormones in renal cancer. J. Urol., 117: 433, 1977. 3. Ozarda, A. T.: Prolactin-secreting tumors. J. Surg. Oncol., 22: 9, 1983. 4. Turkington, R. W.: Ectopic production of prolactin. New Engl. J. Med., 285: 1455, 1971. 5. Frantz, A. G.: Prolactin. New Engl. J. Med., 298: 201, 1978. 6. Carter, J. N., Tyson, J.E., Tolis, G., Van Vliet, S., Faiman, C. and Friesen, H. G.: Prolactin-secreting tumors and hypogonadism in 22 men. New Engl. J. Med., 299: 847, 1978. 7. Glenn, J. F.: Renal tumors. In: Campbell's Urology, 4th ed. Edited by J. H. Harrison, R. F. Gittes, A. D. Perlmutter, T. A. Stamey and P. C. Walsh. Philadelphia: W. B. Saunders Co., vol. 2, sect. IX, chapt. 27, pp. 1004-1005, 1979. 8. Trinkle, A. J.: The origin and development of renal adenomas and their relation to carcinoma of the renal cortex (hypernephroma). Amer. J. Cancer, 27: 676, 1936.
Vol. 136, July Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1986 by The Williams & Wilkins Co.
PROLACTIN SECRETING RENAL CELL CARCINOMA THOMAS H. STANISIC*
AND
JOHN DONOVAN
From the Department of Surgery/Urology, Arizona Health Sciences Center, Tucson, Arizona
ABSTRACT
We report a case of hyperprolactinemia and long-standing gynecomastia associated with a hypernephroma. After radical nephrectomy serum prolactin returned to normal and remained so for 4 years without evidence of tumor recurrence. Potential explanations for the observed concurrent findings and the literature are discussed. Renal cell carcinoma commonly is associated with paraneoplastic syndromes owing to ectopic hormone production by the tumor. Renal neoplasms have been demonstrated to produce parathormone, erythropoietin, renin, gonadotropins, placental lactogen and enteroglucagon. 1• 2 However, ectopic prolactin production by a neoplasm is rare, being reported only once previously in renal cell carcinoma3 and twice in bronchogenic carcinoma. 3·4 We report a case of a prolactin-secreting hypernephroma associated with long-standing gynecomastia.
the left kidney and a filling defect in the left renal pelvis suggestive of a blood clot (part A of figure). Arteriography showed a somewhat hypovascular lesion (part B of figure). Renal sonography suggested the mass to be solid. A chest x-ray and bone scan were within normal limits. Preoperatively, serum luteinizing hormone and follicle-stimulating hormone were within normal limits but serum prolactin measured 138 ng./ml. (normal 5 to 15) by radioimmunoassay. Left radical nephrectomy was performed through a left flank
A, nephrotomogram illustrates left renal mass. B, arteriogram shows corresponding hypovascular left renal mass
incision, and the patient was discharged from the hospital 8 days postoperatively. Pathological examination revealed renal cell carcinoma of the granular cell variety. A prolactin level drawn on postoperative day 7 was 5.6 ng./ml. Follicle-stimulating hormone, luteinizing hormone, testosterone, thyroid-stimulating hormone and cortisol levels also were within normal limits. The patient has been followed for 4 years postoperatively. Prolactin levels have been consistently within normal limits as have been bone scans and chest x-rays performed semiannually. Gynecomastia has persisted unchanged, and the patient is considering reduction mammoplasty. He has respectfully declined photographic documentation of the breast lesion.
CASE REPORT
J. N., a 42-year-old Mexican American man, presented to our emergency room in 1981 with a 2-day history of dark urine and dull left flank ache. History was unremarkable except for mild asthma since childhood and the presence of gynecomastia, which began when he was about 11 years old and progressed through adolescence but then remained stable. The patient stated that libido had always been "normal". At presentation he was not taking medications and had never taken estrogens, L-dopa, chlorpromazine, haloperidol or other drugs associated with elevated prolactin levels. Physical examination revealed mild left flank tenderness and generous gynecomastia but without galactorrhea. Laboratory studies 1 day preoperatively revealed white blood count 8,300 and hematocrit 42.5 per cent. Electrolytes, blood urea nitrogen, creatinine and glucose were within normal limits. Urinalysis showed red blood cells too numerous to count. Excretory urography revealed an 8.5 cm. spherical mass in the lower pole of
DISCUSSION
Our patient presented with documented hyperprolactinemia in the absence of a pituitary pathological condition, use of drugs that elevate prolactin, or any history of chest wall disease or hypothyroidism. Because the prolactin levels decreased to normal and have remained so postoperatively, the most likely explanation for the elevated serum prolactin is ectopic hormone production by the renal cell carcinoma. Although the presence of gynecomastia prompted our deter-
Accepted for publication February 14, 1986. * Requests for reprints: Department of Surgery/Urology, Arizona Health Sciences Center, 1501 N. Campbell, Tucson, Arizona 85724. 85
86
STANISIC AND DONOVAN
mination of the serum prolactin level preoperatively, it is impossible to ascertain whether the hyperprolactinemia and gynecomastia were causally related or simply represented the simultaneous occurrence of 2 separate rare events. Frantz,5 and Carter and associates 6 have published extensive reviews on the physiology of prolactin, and the symptoms and signs associated with hyperprolactinemia. According to these authors, most men with gynecomastia do not have hyperprolactinemia. Conversely, only 14 per cent of the 22 cases with hyperprolactinemia reported by Carter and associates had gynecomastia and/ or galactorrhea. 6 Although prolactin may well be involved in human breast development physiologically and pathologically its precise mammotropic role in human beings is yet to be defined. The biological behavior of hypernephroma is varied and often unusual. The literature is replete with references to long-term spontaneous regression and delayed occurrence of metastasis even after 2 to 3 decades. 7 If the gynecomastia in our patient is secondary to hyperprolactinemia, then one must speculate that the tumor produced prolactin ectopically for more than 30 years. Whether such long-term ectopic hormone production can occur first in a cortical adenoma that later "evolves" into a hypernephroma8 or in a hypernephroma with a usually slow growth rate is moot. Whichever series of hypotheses one accepts
to explain the unusual combination of events in our patient, this case serves again to illustrate the unpredictable biological behavior and potential for unusual clinical presentation of this most interesting neoplasm. REFERENCES
1. Altaffer, L. F., III and Chenault, 0. W., Jr.: Paraneoplastic endocrinopathies associated with renal tumors. J. Urol., 122: 573, 1979. 2. Sufrin, G., Mirand, E. A., Moore, R. H., Chu, T. M. and Murphy, G. P.: Hormones in renal cancer. J. Urol., 117: 433, 1977. 3. Ozarda, A. T.: Prolactin-secreting tumors. J. Surg. Oncol., 22: 9, 1983. 4. Turkington, R. W.: Ectopic production of prolactin. New Engl. J. Med., 285: 1455, 1971. 5. Frantz, A. G.: Prolactin. New Engl. J. Med., 298: 201, 1978. 6. Carter, J. N., Tyson, J.E., Tolis, G., Van Vliet, S., Faiman, C. and Friesen, H. G.: Prolactin-secreting tumors and hypogonadism in 22 men. New Engl. J. Med., 299: 847, 1978. 7. Glenn, J. F.: Renal tumors. In: Campbell's Urology, 4th ed. Edited by J. H. Harrison, R. F. Gittes, A. D. Perlmutter, T. A. Stamey and P. C. Walsh. Philadelphia: W. B. Saunders Co., vol. 2, sect. IX, chapt. 27, pp. 1004-1005, 1979. 8. Trinkle, A. J.: The origin and development of renal adenomas and their relation to carcinoma of the renal cortex (hypernephroma). Amer. J. Cancer, 27: 676, 1936.