Two months after the surgery, the patient visited the hospital because of lumbar and leg pain. The physical examination revealed pain when pressure was applied to lumbar vertebrae and a sciatic pain. He was admitted to the hospital. On his radiologic evaluation, the CT scan showed bone, right suprarenal and lung metastases as well as multiple intraabdominal lymph nodes. Also asymptomatic hyponatremia was observed on his blood biochemistry examination. The serum sodium level was 125 mMol/L while it was previously within the normal limits. Other parameters of the blood biochemistry and blood counts were normal. A systemic evaluation of the patient did not reveal clinical syndromes such as vomiting or diarrhea which could cause a gastrointestinal loss, nor a history of use of any medication such as diuretics which could influence changes in the Na+ level. He was euvolemic in clinical examination. Spot urine analysis was normal with a density of 1.015 and sodium level of 70 mMol/L. The urine osmolality was higher than blood osmolality being 258 mOsm/kg and 367 mOsm/kg H₂O, respectively. The thyroid function tests were within normal limits. An ACTH stimulation test was performed to rule out adrenal insufficiency and the cortisol level was able to increase adequately. No infection was found. Cranial and hypophysis MRI scans were normal. After all these procedures, SIADH was considered to be the cause of persisting hyponatremia after ruling out all other possibilities. An 800 ml/day water restriction was performed and the serum sodium was observed to rise to 132 mMol/L.

The patient was put on a chronic water restriction diet with 1-1.5 L of oral water intake per day. A chemotherapy regimen consisting of 3 weekly cycles of carboplatin AUC 5 on day 1 and gemcitabine 1250 mg/m² on day 1 and 8 was started for his metastatic cancer. Six cycles were completed with some delay due to recurrent urinary infections. His disease remained stable during the treatment and the pain was controlled with low doses of fentanyl patches. The serum sodium level remained within normal limits at the follow-up except for one occasion. At the completion of the chemotherapy, the patient tried voluntarily to stop the water restriction and the somnolence recurred when the sodium level decreased to 124 mMol/L. This was corrected easily with the return to water restriction.

His tumoral disease was stable at the end of chemotherapy. He was on supportive care after the chemotherapy. He did not receive further chemotherapy because of persisting hematologic toxicity. He was dead four months later because of rapid progression of his cancer.

SIADH was first described by Schwartz et al.[1], in two patients with bronchogenic carcinoma of the lung. Since that time it has been realized as the etiology of most hyponatremic cases observed in cancer patients.

Essential diagnostic criteria for SIADH are reduced effective extracellular volume osmolality (Plasma osmolality <275 mOsm/kg H₂O); inappropriate urine concentration (Urine osmolality >100 mOsm/kg H₂O) in the presence of normal renal function; euvolemia; increased sodium excretion; exclusion of any other potential conditions which can cause euvolemic hypoosmolality such as hypothyroidism, hypocortisolism and diuretic use. Water restriction test is not essential for the diagnosis. However it can provide supporting information[2].

All the above mentioned criteria were met by the patient and the water restriction confirmed the diagnosis of SIADH. SIADH can be induced by various pulmonary and central nervous system diseases or it can be caused by ectopic secretion of ADH by tumors. Small cell lung cancer is the most frequent cause of paraneoplastic SIADH. SIADH was also reported with pancreatic carcinomas and rarely with other cancers such as neuroblastoma and lymphoma.

To our knowledge, only one case of SIADH related to the bladder cancer was reported in the literature[3]. In this report, SIADH was diagnosed twenty months prior to the emergence of bladder cancer and as an early finding.

However, in our case, hyponatremia was not observed during the initial diagnosis and it appeared when the tumor recurred with systemic metastases. Our report has some similarities with the case of Andersen and Sorensen[4], who observed the appearance of SIADH during disease progression in a patient with breast cancer.

We can hypothesize that the SIADH in our patient is secondary to an ectopic ADH secretion and it reached significant levels with clinical consequences following an increase of the tumor mass. The systemic chemotherapy failed to decrease the tumor mass as well as to correct the SIADH. A simple measure such as chronic water restriction was able to maintain the serum sodium within normal levels.

The SIADH can be frequently observed in neoplasms such as bladder or other cancers, but missed often because of complicated clinical situations of patients with extensive metastatic diseases. Serum electrolytes should be evaluated carefully in such patients, because a simple hyponatremia can alert on the possibility of SIADH which can cause some neurologic damages in the absence of adequate treatment or with rapid correction of the hyponatremia.

1) Schwartz WB, Bennett W, Curelop S, et al. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 1957;23:529-42.

2) Verbalis JG. Disorders of body water homeostasis. Best Pract Clin Endocrinol Metab 2003;17:471-503.

3) Sugama T, Iseki K, Sesoko S, et al. A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with low plasma concentrations of antidiuretic hormone. Intern Med 1992;31:246-50.

4) Andersen MK, Sorensen JB. Development of syndrome of inappropriate secretion of antidiuretic hormone during progression of metastatic breast cancer. Acta Oncol 1997;36:535-7.