The syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with metastatic malignant melanoma

ARTICLE

ejd.2012.1738

Auteur(s) : Miho Ueda, Yuichiro Endo, Yo Kaku, Hideaki Tanizaki, Hiroaki Fujisawa, Miki Tanioka mtanioka@kuhp.kyoto-u.ac.jp, Yoshiki Miyachi

Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawara-cho Sakyo, Kyoto 606-8507, Japan

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a state where excess vasopressin is secreted from hypophysis in conditions when sufficient water is sustained in the body [1]. Although SIADH occurs in association with a variety of tumors, few papers have reported the association of SIADH with malignant melanoma. We report a case of SIADH associated with metastatic malignant melanoma.

An 84-year-old woman presented with a 27 × 25 mm pigmented lesion on the toe of the left foot. Histological examination showed malignant melanoma. The result of a sentinel lymph node biopsy was negative. Surgical excision was performed, followed by six courses of subcutaneous injections of interferon beta. Two years and four months later, a routine computed tomography (CT) showed metastases of malignant melanoma to lung, bone, abdominal cavity, liver, urinary bladder, adrenal gland and diaphragm. The patient's staging was T4bN1bM1c, Stage IV. Monthly subcutaneous injection of interferon beta was restarted.

One month after the final injection of interferon beta, the patient complained of muscle weakness, loss of appetite and insomnia. CT examination of the brain showed no abnormality. Laboratory works revealed that the serum sodium level was 112 mEq/L (136-144 mEq/L) and creatinine, 1.0 mg/dL (0.4-0.8 mg/dL). The urine sodium level was 88 mEq/L. The serum and urine osmolality was 243 mOsm/kgH₂O, 548 mOsm/kgH₂O, respectively. In SIADH, the urine sodium level is ≥20 mEq/L, the serum osmolality is <280 mOsm/kgH₂O and the urine osmolality is > 300 mOsm/kgH₂O. Serum arginine vasopressin level was 2.53 pg/mL. This means that the impaired water excretion was caused by a high level of ADH secretion. Thyroid, parathyroid and adrenal cortex function tests were within normal ranges. These results satisfied the criteria for SIADH diagnosis.

After a few days, she became drowsy and unable to walk. Administration of isotonic sodium chloride solution with additional salt led to a transient clinical improvement and elevation of the serum sodium level to 131 mEq/L. However, the patient died one month later after the diagnosis of SIADH.

The causes of SIADH can be classified as follows: (1) tumors, (2) non-neoplastic pulmonary disease, (3) central nervous system disease, (4) drugs and (5) others (hypothermia, positive pressure ventilation, etc) [2]. To the best of our knowledge, five causes of SIADH in association with melanoma have been documented [2-4]. Two cases had metastases in the brain, and one in the lung. In the present case, cerebral and pulmonary lesions were absent. As our patient did not take any medication at the time of diagnosis, we concluded that this case was melanoma-related SIADH.

The most common cancer associated with vasopressin production is carcinoma of the lung, predominantly oat cell carcinoma. Pancreatic, prostatic, duodenal and adrenal cortical carcinoma, lymphosarcoma, reticulum cell sarcoma, Hodgkin's lymphoma and thymoma have been reported as causes for tumor-related SIADH [2]. The occurrence of SIADH in the absence of pulmonary and cerebral metastasis suggests that melanoma may produce ADH-like hormone or that drugs such as interferon may trigger SIADH.

Chemotherapy and interleukin are known to be causes of SIADH. SIADH has been associated with the administration of some cytotoxic drugs, including cyclophosphamide, vincristine and cisplatinum. Indeed the aforementioned five cases with SAIDH, three received chemotherapy. However, no report has described the association of SIADH with dacarbazine [2], which is usually included in chemotherapy for melanoma in Japan. As for interleukin, there was a report of SIADH in patients with metastatic melanoma who received high-dose bolus interleukin-2 therapy [5].

To summarize, when a patient with melanoma presents clouding of consciousness, SIADH should be ruled out.

Disclosure

Financial support: none. Conflict of interest: none.

References

1. Rose, BD, Post, TW, Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York, 2001, 703-11.

2. Sanghera P, El-Modir A. Malignant melanoma and SIADH. Clin Oncol(R Coll Radiol) 2005 ; 17 : 3199-200.

3. Lo Scocco G, Di Lernia V, Bisighini G. Syndrome of inappropriate secretion of antidiuretic hormone in a patient affected by metastatic melanoma. Melanoma Res 1998 ; 8 : 4367-9.

4. Kefford RF MD, Milton GW MD. Fatal inappropriate ADH secretion in melanoma. Med J Aust 1986; 144(6):333-4.

5. Myke R. Green, BS, PharmD, et al. Syndrome of inappproproate antidiuretic hormone secretion caused by high-dose bolus Interleukin-2 therapy for metastatic melanoma. Am J Therapeutics 2011 ;18(5):159-61.