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A 60-year-old man with Parkinson's disease developed hyponatraemia with low plasma osmolarity, urine hyperosmolarity and an elevated urine sodium concentration. Plasma vasopressin (AVP) level was five times the upper normal limit and a diagnosis of the syndrome of inappropriate antidiuresis (SIAD) was made. Although the patient was treated with levodopa/carbidopa 500 mg/50 mg, entacapone 400 mg, seregiline 5 mg, cabergoline 1 mg, pergolide 250 μg and pramipexole 3 mg, SIAD resolved after the dose reduction of pramipexole. Dopamine is reported to facilitate AVP secretion through activation of D4 receptors. The hD4:hD2L pKi ratio calculated from published data is 0.017 for cabergoline, 0.44 for pergolide, 1.1 for ropinirole and 13 for pramipexole. The hD4:hD2 pKi ratio of dopamine is reported to be 1. Accordingly, pramipexole has a higher selectivity for D4 receptor than other dopamine agonists. Pramipexole is likely to increase AVP secretion, which is a prerequisite for developing SIAD.

Malignant pheochromocytomais a rare tumor with a poor prognosis because excess production of catecholamines leads to potentially lethal complications. Several chemotherapy regimens have been reported to be effective against this tumor, but a standard form of chemotherapy has not been established. Wetreated two patients with histologically confirmed pheochromocytoma after surgical removal of the primary lesion. Non-cardiogenic pulmonary edema was resolved and bone metastases were controlled by individualized chemotherapy that decreased the catecholamine levels, and the performance status was improved in both cases. Palliative chemotherapy should be designed to improve the quality of life of cancer patients. (Internal Medicine 38: 433-435, 1999) Key words: pulmonary edema, bone metastasis, cytosine arabinoside, individualized modification, quality of life Case Reports Case1A 35-year-old womanwith malignant pheochromocytoma was admitted with dyspnea, hypertensive attacks, constipation, and a sensation of impending doom in 1993. Her blood pressure was 176/118 mmHgand heart rate, 110 bpm. The oxygen saturation was 90%. Abdominal X-ray films showed constipation and computed tomography showed pulmonary edema. Echocardiography showed a normal ejection fraction. In 1988, she had undergone surgical treatment of a pheochromocytoma in the bladder wall and angiography had shown multiple lymph node metastases in the pelvis, indicating the malignancy of her disease. Investigations revealed elevated catecholamine levels and disease progression. However, no mass lesions were found except for equivocal swelling of lymph nodes in the pelvis. The plasma norepinephrine level was 41 ng/ml (normal: 0.05-0.40) and 24-hour urinary norepinephrine was 1 7, 100 |Hg/day (normal: 29-1 20).There was no uptake of 1 3 1 -metaiodobenzylguanidine (MIBG) on scanning, suggesting that MIBGtherapy was not indicated. Adrenergic blockade did not relieve her symptoms, so cytoreductive therapy was tried. The chemotherapeutic regimen, consisting of 750 mg/m2 of cyclophosphamide on day 1, 1.4 mg/m2 of vincristine on day 1, and 600 mg/m2 of dacarbazine on days 1 and 2 (CVD), has been reported to be effective against malignant pheochromocytoma (1 , 2). Due to her poor general condition, we modified the CVDregimen to VdsD;cyclophosphamide was not administered, 6 mg/m2of vindesine was given in place of vincristine on day 1, and dacarbazine was given according to the original schedule. She received chemotherapy at approximately 10-day intervals with careful observation of toxicity. Her pulmonary edema was resolved (Fig. 1A, B) and bowel function improved, with a decrease of 24-hour urinary catecholamines (Fig. 1C). The sensation of impending doom also diminished. According to the Eastern Cooperative Oncology Group, her performance status was improved from grade 3 to 1. She was discharged and continued to receive chemotherapy for 15 months as an outpatient. In 1995, seven years after the diagnosis of malignant pheochromocytoma, she died of cerebral hemorrhage...