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Syndrome of Inappropriate Antidiuresis in Ovarian Serous Carcinoma with Neuroendocrine Differentiation
GYNECOLOGIC ONCOLOGY ARTICLE NO.
62, 400–404 (1996)
0256
CASE REPORT Syndrome of Inappropriate Antidiuresis in Ovarian Serous Carcinoma with Neuroendocrine Differentiation METIN TASKIN, M.D., BEL BARKER, M.D., ANTHONY CALANOG, M.D.,
AND
SUSAN JORMARK, M.D.
Departments of Pathology and Gynecology, Lenox Hill Hospital and New York University, New York, New York 10021 Received December 6, 1995
A 58-year-old postmenopausal woman with primary ovarian serous carcinoma presented with the syndrome of inappropriate antidiuresis (SIAD). Preoperative workup showed serum sodium level of 110 mEq/liter and antidiuretic hormone level of 3.3 pg/ml. The serum and urine osmolarity were 239 and 371, respectively. Antidiuretic hormone was demonstrated in tumor cells by immunohistochemistry. To the best of the authors’ knowledge, this represents the first case of SIAD due to primary ovarian tumor. q 1996 Academic Press, Inc.
INTRODUCTION
The syndrome of inappropriate antidiuretic hormone (SIADH) was described first by Schwartz et al. in 1957 [1] and named as such because of its similarity to the syndrome seen in patients who were given antidiuretic hormone (ADH). Recently, hormones other than ADH have also been shown to cause a similar syndrome [2]. Therefore, the name syndrome of inappropriate antidiuresis (SIAD) has been suggested to replace SIADH. More than one half of the patients with SIAD have an underlying malignancy. Small cell carcinoma of the lung is by far the most common cause, accounting for three-quarters of cancer-related cases of SIAD [3]. Other less common neoplasms include a wide variety of tumors ranging from malignant lymphoma to soft tissue sarcomas [4, 5]. In this case report, we present the first example of the SIAD due to a primary ovarian carcinoma along with the review of the current literature. CASE REPORT
A 58-year-old G0P0 postmenopausal woman presented to the emergency room with complaints of weakness, fatigue, nausea, and headache progressively worsening over the prior 3 days. The patient had no significant medical or surgical
Gyn 4414
/
6d10$$$261
PATHOLOGY
The ovarian tumor was partly cystic and measured 5 1 3 1 2 cm. The cystic portion was 3.2 cm in diameter and was
400
0090-8258/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
AID
history and a normal menstrual history with menopause at age 48. The patient was not on hormone replacement therapy. Admission laboratory values were sodium 110 mEq/ liter (normal, 136–145 mEq/liter); glucose 109 mg/dl (normal, 85–115 mg/dl); potassium 4.4 mEq/liter (normal, 3.5– 5.0 mEq/liter); chloride 81 mEq/liter (normal, 96–106 mEq/ liter); CO2 21 mEq/liter (normal, 24–30 mEq/liter); BUN 10 mg/dl (normal, 10–26 mg/dl); creatinine 0.7 mg/dl (normal, 0.5–1.5 mg/dl); and calcium 8.7 mg/dl (normal, 8.5– 10.5 mg/dl). Thyroid function tests were triiodothyronine (T3) uptake 41.2% (normal, 30–47%); thyroxine (T4) 8.3 mg/ dl (normal, 5–12 mg/dl); and thyroid-stimulating hormone (TSH) 1.43 mIU/ml (normal, 0.46–3.60 mIU/ml). In addition, serum osmolarity was 239 with a urine osmolarity of 371. Physical examination of the patient revealed a large left adnexal mass. The abdominal/pelvic CT scan showed 6.5cm solid left adnexal mass. The patient underwent exploratory laparatomy, total abdominal hysterectomy and bilateral salpingo-oopherectomy, tumor debulking, omentectomy, and appendectomy. The patient had an uneventful postoperative course and was discharged home on Postoperative Day 6 with a serum sodium of 139 mEq/liter. Preoperative antidiuretic hormone (ADH) level was found to be 3.3 pg/ml (normal, 0.4 – 2.4 pg/ml) and on Postoperative Day 3 was found to be 0.3 pg/ml. The patient was treated with one cycle of taxol and cisplatin, which was discontinued due to an anaphylactic reaction to taxol. The patient then received six cycles of cytoxan and cisplatin. She remained well 7 months later with a normal serum sodium.
08-16-96 18:41:12
goas
AP: Gyn Onc
401
CASE REPORT
FIG. 1. A papillary frond lined by highly atypical and mitotically active neoplastic serous epithelium. Hematoxylin–phloxine–saffron, medium power.
FIG. 2. Area of transition between solid undifferentiated component and poorly formed neoplastic glands. Hematoxylin–phloxine–saffron, medium power.
AID
Gyn 4414
/
6d10$$4414
08-16-96 18:41:12
goas
AP: Gyn Onc
402
TASKIN ET AL.
filled by yellow creamy material. The cyst lining was pink, granular, and fragile. The solid portion was tan and variably hemorrhagic. The left Fallopian tube was firm and diffusely thickened by tumor involvement. Microscopically, the tumor was a solid and cystic serous adenocarcinoma with dedifferentiation in the tubal component. The ovarian component was mostly cystic and lined by atypical papillary serous epithelium having a broad central core (Fig. 1). The solid areas in both ovary and Fallopian tube contained glands with varying degrees of differentiation and solid sheets of undifferentiated tumor cells. Areas of clear-cut transition between well-differentiated glandular and dedifferentiated solid areas were evident. The neoplastic cells in the solid areas were generally small and round or spindle-shaped with scant cytoplasm (Fig. 2). Occasional giant cells with bizarre pleomorphic nuclei were also present. The mitotic index was uniformly high throughout the tumor. On immunohistochemical evaluation, tumor cells were uniformly positive with neuron-specific enolase and focally positive with chromogranin, both of which are classic markers for neuroendocrine differentiation. Furthermore, there was focal immunopositivity with ADH antibody in solid areas and single-cell positivity in papillary fronds, proving that ADH was in fact produced by tumor cells (Fig. 3). In addition to neuroendocrine markers, low-molecular-weight keratin, a marker for epithelial differentiation, was positive in well-differentiated glandular component but negative in solid poorly differentiated areas. Electron microscopic examination performed on formalin-fixed paraffin-embedded tumor tissue revealed 70- to 100-nm, membrane-bound electron-dense cytoplasmic neurosecretory granules in small undifferentiated tumor cells (Fig. 4). A diagnosis of poorly differentiated papillary serous adenocarcinoma with neuroendocrine differentiation was made. DISCUSSION
Tumors of the ovary have been associated with paraendocrine syndromes. Sometimes the symptoms related to endocrine activity are the first manifestation of the disease. The endocrine activity is usually due to hormones released by the neoplasm. Paraendocrine syndromes have also been described following the treatment of the neoplasm [6]. The most commonly described paraendocrine syndrome of the ovary is hypercalcemia and it is usually due to small cell carcinoma of the ovary [7]. Other less common paraendocrine syndromes of ovarian malignancies include carcinoid, Zollinger–Ellison, and Cushing’s syndromes [8, 9]; however, SIAD has never been conclusively shown to be due to an ovarian tumor.
AID
Gyn 4414
/
6d10$$$262
08-16-96 18:41:12
The clinical diagnosis of SIAD relies on the demonstration of a decreased serum osmolarity and a decreased sodium along with an inappropriately increased urine osmolarity. Edema and volume depletion are not found with SIAD. Other clinical conditions that may be associated with hyponatremia, such as renal, thyroid, and adrenal disorders, should be ruled out before the diagnosis of SIAD can be made. Hormones other than ADH may cause the SIAD. In a recent paper, a subset of patients with hyponatremia (fitting the criteria for SIAD) were shown to have elevated atrial natriuretic hormone with normal or decreased ADH levels [2]. Furthermore, in a case of a patient with SIAD due to small cell carcinoma of the lung, Shimuzu et al. demonstrated presence of atrial natriuretic factor in tumor cells [10]. Several mechanisms have been proposed to explain inappropriately elevated ADH levels in SIAD. Some authors have suggested that resetting of the hypothalamic osmostat might be the reason for lower osmotic threshold for the release of ADH from the hypothalamus in cases of SIAD with normal or low ADH levels since not all SIAD cases have elevated ADH levels [11]. Others have suggested direct ADH synthesis and release from neoplastic cells. This idea has been supported by several authors demonstrating ADH in tumor cells by immunohistochemistry and in situ hybridization using mRNA for ADH [12, 13]. SIAD has rarely been reported with female genital tract cancers. Two patients with small cell carcinoma of the cervix were reported to have SIAD and elevated ADH in the serum [14, 15]; however, ADH was not demonstrated in the tumor cells. In another case report, SIAD developed in a patient with endometrioid carcinoma of the ovary 6 days after treatment with cisplatin [6]. The cause of SIAD in this patient seems to be cisplatin since she did not have SIAD prior to chemotherapy; however, chemotherapy-induced tumor lysis and ADH release from neoplastic cells cannot be ruled out. In our case, we were able to demonstrate ADH in tumor cells by immunohistochemistry and membrane-bound neurosecretory granules by electron microscopy. This supports the idea that elevated serum ADH levels prior to surgery were due to release of hormone from tumor cells. Furthermore, serum ADH dropped abruptly right after the surgery and serum sodium reached normal range. We believe that these findings are consistent with synthesis and release of ADH by a primary ovarian tumor. The treatment of SIAD in malignancy includes removal of the source of hormone if possible and appropriate fluid management which includes restriction of fluid intake and increase renal water excretion. In small cell carcinoma of the lung, chemotherapy is an effective treatment of SIAD as long as the tumor is in remission; however, as the carcinoma relapses, SIAD recurs and other forms of treatment may become necessary.
goas
AP: Gyn Onc
403
CASE REPORT
FIG. 3.
FIG. 4.
AID
Strong cytoplasmic immunostaining in neoplastic cells with antidiuretic hormone antibody. Immunoperoxidase stain, high power.
Electron micrograph shows membrane-bound electron-dense neurosecretory granules in the cytoplasm of the tumor cells. 118,200.
Gyn 4414
/
6d10$$4414
08-16-96 18:41:12
goas
AP: Gyn Onc
404
TASKIN ET AL.
REFERENCES 1. Schwartz, W. B., Bennet, W., Curelop, S., and Bartter, F. C. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone, Am. J. Med. 23, 529– 542 (1957). 2. Kamoi, K., Ebe, T., Hasegawa, A., Sato, F., Takato, H., Iwamoto, H., Kaneko, H., Ishibashi, M., and Yamaji, T. Hyponatremia in small cell lung cancer. Mechanisms not involving inappropriate ADH secretion, Cancer 60, 1089–1093 (1987). 3. Detroyer, A., and Demanet, J. C. Clinical, biological and pathogenetic features of the syndrome of inappropriate secretion of ADH, J. Med. 45, 521–531 (1976). 4. Miller, R., Ashkar, F. S., and Rudzinski, D. J. Inappropriate secretion of antidiuretic hormone in reticulum cell sarcoma, South. Med. J. 64, 763–764 (1971). 5. Yokokawa, T., Shigetomi, S., Takahashi, S., Ogawa, S., Fukuchi, S., and Miura, T. A case of epipharyngeal sarcoma associated with the syndrome of inappropriate secretion of antidiuretic hormone, Nippon Naika Gakkai Zasshi 70, 410–416 (1981). 6. Porter, A. T. Syndrome of inappropriate antidiuretic hormone secretion during cis-dichlorodiammineplatinum therapy in a patient with an ovarian carcinoma, Gynecol. Oncol. 21, 103–105 (1985). 7. Clement, P. B., Young, R. H., and Scully, R. E. Clinical syndromes associated with tumors of the female genital tract, Semin. Diagn. Pathol. 8, 204–233 (1991).
AID
Gyn 4414
/
6d10$$$262
08-16-96 18:41:12
8. Brown, H., and Lane, M. Cushing and malignant carcinoid syndromes from ovarian neoplasm, Arch. Intern. Med. 115, 490–494 (1965). 9. Cocco, A. E., and Conway, S. J. Zollinger–Ellison syndrome associated with ovarian mucinous cystadenocarcinoma, N. Engl. J. Med. 293, 485– 486 (1975). 10. Shimuzu, K., Nakano, S., Nakano, Y., Ando, M., Seki, K., and Kameda, N. Ectopic atrial natriuretic peptide production in small cell lung cancer with the syndrome of inappropriate antidiuretic hormone secretion, Cancer 68, 2284–2288 (1991). 11. Zerbe, R., Stropes, L., and Robertson, G. Vasopressin function in the syndrome of inappropriate antidiuresis, Annu. Rev. Med. 31, 315–327 (1980). 12. Yamaji, T., Ishibashi, M., and Katayama, S. Nature of the immunoreactive neurophysins in ectopic vaso-pressin producing oat cell carcinomas of the lung: Demonstration of a putative common precursor to vasopressin and neurophysin, J. Clin. Invest. 68, 388–398 (1981). 13. Kavanagh, B. D., Halperin, E. C., Rosenbaum, L., Shannon, E. M., and Nilaver, G. Syndrome of inappropriate secretion of antidiuretic hormone in a patient with carcinoma of nasopharynx, Cancer 69, 1315– 1319 (1992). 14. Pazdur, R., Bonomi, P., Slayton, R., Gould, V. E., Miller, A., Wellington, J., Dolan, T., and Wilbanks, G. Neuroendocrine carcinoma of the cervix: Implications for staging and therapy, Gynecol. Oncol. 12, 120– 128 (1981). 15. Kothe, M. J. C., Prins, J. M., DeWit, R., Velden, K. V. D., and Schellekens, P. T. A. Small cell carcinoma of the cervix with inappropriate antidiuretic hormone secretion: Case report, Br. J. Obstet. Gynecol. 97, 647–648 (1990).
goas
AP: Gyn Onc
62, 400–404 (1996)
0256
CASE REPORT Syndrome of Inappropriate Antidiuresis in Ovarian Serous Carcinoma with Neuroendocrine Differentiation METIN TASKIN, M.D., BEL BARKER, M.D., ANTHONY CALANOG, M.D.,
AND
SUSAN JORMARK, M.D.
Departments of Pathology and Gynecology, Lenox Hill Hospital and New York University, New York, New York 10021 Received December 6, 1995
A 58-year-old postmenopausal woman with primary ovarian serous carcinoma presented with the syndrome of inappropriate antidiuresis (SIAD). Preoperative workup showed serum sodium level of 110 mEq/liter and antidiuretic hormone level of 3.3 pg/ml. The serum and urine osmolarity were 239 and 371, respectively. Antidiuretic hormone was demonstrated in tumor cells by immunohistochemistry. To the best of the authors’ knowledge, this represents the first case of SIAD due to primary ovarian tumor. q 1996 Academic Press, Inc.
INTRODUCTION
The syndrome of inappropriate antidiuretic hormone (SIADH) was described first by Schwartz et al. in 1957 [1] and named as such because of its similarity to the syndrome seen in patients who were given antidiuretic hormone (ADH). Recently, hormones other than ADH have also been shown to cause a similar syndrome [2]. Therefore, the name syndrome of inappropriate antidiuresis (SIAD) has been suggested to replace SIADH. More than one half of the patients with SIAD have an underlying malignancy. Small cell carcinoma of the lung is by far the most common cause, accounting for three-quarters of cancer-related cases of SIAD [3]. Other less common neoplasms include a wide variety of tumors ranging from malignant lymphoma to soft tissue sarcomas [4, 5]. In this case report, we present the first example of the SIAD due to a primary ovarian carcinoma along with the review of the current literature. CASE REPORT
A 58-year-old G0P0 postmenopausal woman presented to the emergency room with complaints of weakness, fatigue, nausea, and headache progressively worsening over the prior 3 days. The patient had no significant medical or surgical
Gyn 4414
/
6d10$$$261
PATHOLOGY
The ovarian tumor was partly cystic and measured 5 1 3 1 2 cm. The cystic portion was 3.2 cm in diameter and was
400
0090-8258/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.
AID
history and a normal menstrual history with menopause at age 48. The patient was not on hormone replacement therapy. Admission laboratory values were sodium 110 mEq/ liter (normal, 136–145 mEq/liter); glucose 109 mg/dl (normal, 85–115 mg/dl); potassium 4.4 mEq/liter (normal, 3.5– 5.0 mEq/liter); chloride 81 mEq/liter (normal, 96–106 mEq/ liter); CO2 21 mEq/liter (normal, 24–30 mEq/liter); BUN 10 mg/dl (normal, 10–26 mg/dl); creatinine 0.7 mg/dl (normal, 0.5–1.5 mg/dl); and calcium 8.7 mg/dl (normal, 8.5– 10.5 mg/dl). Thyroid function tests were triiodothyronine (T3) uptake 41.2% (normal, 30–47%); thyroxine (T4) 8.3 mg/ dl (normal, 5–12 mg/dl); and thyroid-stimulating hormone (TSH) 1.43 mIU/ml (normal, 0.46–3.60 mIU/ml). In addition, serum osmolarity was 239 with a urine osmolarity of 371. Physical examination of the patient revealed a large left adnexal mass. The abdominal/pelvic CT scan showed 6.5cm solid left adnexal mass. The patient underwent exploratory laparatomy, total abdominal hysterectomy and bilateral salpingo-oopherectomy, tumor debulking, omentectomy, and appendectomy. The patient had an uneventful postoperative course and was discharged home on Postoperative Day 6 with a serum sodium of 139 mEq/liter. Preoperative antidiuretic hormone (ADH) level was found to be 3.3 pg/ml (normal, 0.4 – 2.4 pg/ml) and on Postoperative Day 3 was found to be 0.3 pg/ml. The patient was treated with one cycle of taxol and cisplatin, which was discontinued due to an anaphylactic reaction to taxol. The patient then received six cycles of cytoxan and cisplatin. She remained well 7 months later with a normal serum sodium.
08-16-96 18:41:12
goas
AP: Gyn Onc
401
CASE REPORT
FIG. 1. A papillary frond lined by highly atypical and mitotically active neoplastic serous epithelium. Hematoxylin–phloxine–saffron, medium power.
FIG. 2. Area of transition between solid undifferentiated component and poorly formed neoplastic glands. Hematoxylin–phloxine–saffron, medium power.
AID
Gyn 4414
/
6d10$$4414
08-16-96 18:41:12
goas
AP: Gyn Onc
402
TASKIN ET AL.
filled by yellow creamy material. The cyst lining was pink, granular, and fragile. The solid portion was tan and variably hemorrhagic. The left Fallopian tube was firm and diffusely thickened by tumor involvement. Microscopically, the tumor was a solid and cystic serous adenocarcinoma with dedifferentiation in the tubal component. The ovarian component was mostly cystic and lined by atypical papillary serous epithelium having a broad central core (Fig. 1). The solid areas in both ovary and Fallopian tube contained glands with varying degrees of differentiation and solid sheets of undifferentiated tumor cells. Areas of clear-cut transition between well-differentiated glandular and dedifferentiated solid areas were evident. The neoplastic cells in the solid areas were generally small and round or spindle-shaped with scant cytoplasm (Fig. 2). Occasional giant cells with bizarre pleomorphic nuclei were also present. The mitotic index was uniformly high throughout the tumor. On immunohistochemical evaluation, tumor cells were uniformly positive with neuron-specific enolase and focally positive with chromogranin, both of which are classic markers for neuroendocrine differentiation. Furthermore, there was focal immunopositivity with ADH antibody in solid areas and single-cell positivity in papillary fronds, proving that ADH was in fact produced by tumor cells (Fig. 3). In addition to neuroendocrine markers, low-molecular-weight keratin, a marker for epithelial differentiation, was positive in well-differentiated glandular component but negative in solid poorly differentiated areas. Electron microscopic examination performed on formalin-fixed paraffin-embedded tumor tissue revealed 70- to 100-nm, membrane-bound electron-dense cytoplasmic neurosecretory granules in small undifferentiated tumor cells (Fig. 4). A diagnosis of poorly differentiated papillary serous adenocarcinoma with neuroendocrine differentiation was made. DISCUSSION
Tumors of the ovary have been associated with paraendocrine syndromes. Sometimes the symptoms related to endocrine activity are the first manifestation of the disease. The endocrine activity is usually due to hormones released by the neoplasm. Paraendocrine syndromes have also been described following the treatment of the neoplasm [6]. The most commonly described paraendocrine syndrome of the ovary is hypercalcemia and it is usually due to small cell carcinoma of the ovary [7]. Other less common paraendocrine syndromes of ovarian malignancies include carcinoid, Zollinger–Ellison, and Cushing’s syndromes [8, 9]; however, SIAD has never been conclusively shown to be due to an ovarian tumor.
AID
Gyn 4414
/
6d10$$$262
08-16-96 18:41:12
The clinical diagnosis of SIAD relies on the demonstration of a decreased serum osmolarity and a decreased sodium along with an inappropriately increased urine osmolarity. Edema and volume depletion are not found with SIAD. Other clinical conditions that may be associated with hyponatremia, such as renal, thyroid, and adrenal disorders, should be ruled out before the diagnosis of SIAD can be made. Hormones other than ADH may cause the SIAD. In a recent paper, a subset of patients with hyponatremia (fitting the criteria for SIAD) were shown to have elevated atrial natriuretic hormone with normal or decreased ADH levels [2]. Furthermore, in a case of a patient with SIAD due to small cell carcinoma of the lung, Shimuzu et al. demonstrated presence of atrial natriuretic factor in tumor cells [10]. Several mechanisms have been proposed to explain inappropriately elevated ADH levels in SIAD. Some authors have suggested that resetting of the hypothalamic osmostat might be the reason for lower osmotic threshold for the release of ADH from the hypothalamus in cases of SIAD with normal or low ADH levels since not all SIAD cases have elevated ADH levels [11]. Others have suggested direct ADH synthesis and release from neoplastic cells. This idea has been supported by several authors demonstrating ADH in tumor cells by immunohistochemistry and in situ hybridization using mRNA for ADH [12, 13]. SIAD has rarely been reported with female genital tract cancers. Two patients with small cell carcinoma of the cervix were reported to have SIAD and elevated ADH in the serum [14, 15]; however, ADH was not demonstrated in the tumor cells. In another case report, SIAD developed in a patient with endometrioid carcinoma of the ovary 6 days after treatment with cisplatin [6]. The cause of SIAD in this patient seems to be cisplatin since she did not have SIAD prior to chemotherapy; however, chemotherapy-induced tumor lysis and ADH release from neoplastic cells cannot be ruled out. In our case, we were able to demonstrate ADH in tumor cells by immunohistochemistry and membrane-bound neurosecretory granules by electron microscopy. This supports the idea that elevated serum ADH levels prior to surgery were due to release of hormone from tumor cells. Furthermore, serum ADH dropped abruptly right after the surgery and serum sodium reached normal range. We believe that these findings are consistent with synthesis and release of ADH by a primary ovarian tumor. The treatment of SIAD in malignancy includes removal of the source of hormone if possible and appropriate fluid management which includes restriction of fluid intake and increase renal water excretion. In small cell carcinoma of the lung, chemotherapy is an effective treatment of SIAD as long as the tumor is in remission; however, as the carcinoma relapses, SIAD recurs and other forms of treatment may become necessary.
goas
AP: Gyn Onc
403
CASE REPORT
FIG. 3.
FIG. 4.
AID
Strong cytoplasmic immunostaining in neoplastic cells with antidiuretic hormone antibody. Immunoperoxidase stain, high power.
Electron micrograph shows membrane-bound electron-dense neurosecretory granules in the cytoplasm of the tumor cells. 118,200.
Gyn 4414
/
6d10$$4414
08-16-96 18:41:12
goas
AP: Gyn Onc
404
TASKIN ET AL.
REFERENCES 1. Schwartz, W. B., Bennet, W., Curelop, S., and Bartter, F. C. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone, Am. J. Med. 23, 529– 542 (1957). 2. Kamoi, K., Ebe, T., Hasegawa, A., Sato, F., Takato, H., Iwamoto, H., Kaneko, H., Ishibashi, M., and Yamaji, T. Hyponatremia in small cell lung cancer. Mechanisms not involving inappropriate ADH secretion, Cancer 60, 1089–1093 (1987). 3. Detroyer, A., and Demanet, J. C. Clinical, biological and pathogenetic features of the syndrome of inappropriate secretion of ADH, J. Med. 45, 521–531 (1976). 4. Miller, R., Ashkar, F. S., and Rudzinski, D. J. Inappropriate secretion of antidiuretic hormone in reticulum cell sarcoma, South. Med. J. 64, 763–764 (1971). 5. Yokokawa, T., Shigetomi, S., Takahashi, S., Ogawa, S., Fukuchi, S., and Miura, T. A case of epipharyngeal sarcoma associated with the syndrome of inappropriate secretion of antidiuretic hormone, Nippon Naika Gakkai Zasshi 70, 410–416 (1981). 6. Porter, A. T. Syndrome of inappropriate antidiuretic hormone secretion during cis-dichlorodiammineplatinum therapy in a patient with an ovarian carcinoma, Gynecol. Oncol. 21, 103–105 (1985). 7. Clement, P. B., Young, R. H., and Scully, R. E. Clinical syndromes associated with tumors of the female genital tract, Semin. Diagn. Pathol. 8, 204–233 (1991).
AID
Gyn 4414
/
6d10$$$262
08-16-96 18:41:12
8. Brown, H., and Lane, M. Cushing and malignant carcinoid syndromes from ovarian neoplasm, Arch. Intern. Med. 115, 490–494 (1965). 9. Cocco, A. E., and Conway, S. J. Zollinger–Ellison syndrome associated with ovarian mucinous cystadenocarcinoma, N. Engl. J. Med. 293, 485– 486 (1975). 10. Shimuzu, K., Nakano, S., Nakano, Y., Ando, M., Seki, K., and Kameda, N. Ectopic atrial natriuretic peptide production in small cell lung cancer with the syndrome of inappropriate antidiuretic hormone secretion, Cancer 68, 2284–2288 (1991). 11. Zerbe, R., Stropes, L., and Robertson, G. Vasopressin function in the syndrome of inappropriate antidiuresis, Annu. Rev. Med. 31, 315–327 (1980). 12. Yamaji, T., Ishibashi, M., and Katayama, S. Nature of the immunoreactive neurophysins in ectopic vaso-pressin producing oat cell carcinomas of the lung: Demonstration of a putative common precursor to vasopressin and neurophysin, J. Clin. Invest. 68, 388–398 (1981). 13. Kavanagh, B. D., Halperin, E. C., Rosenbaum, L., Shannon, E. M., and Nilaver, G. Syndrome of inappropriate secretion of antidiuretic hormone in a patient with carcinoma of nasopharynx, Cancer 69, 1315– 1319 (1992). 14. Pazdur, R., Bonomi, P., Slayton, R., Gould, V. E., Miller, A., Wellington, J., Dolan, T., and Wilbanks, G. Neuroendocrine carcinoma of the cervix: Implications for staging and therapy, Gynecol. Oncol. 12, 120– 128 (1981). 15. Kothe, M. J. C., Prins, J. M., DeWit, R., Velden, K. V. D., and Schellekens, P. T. A. Small cell carcinoma of the cervix with inappropriate antidiuretic hormone secretion: Case report, Br. J. Obstet. Gynecol. 97, 647–648 (1990).
goas
AP: Gyn Onc