SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC-HORMONE (SIADH) IN MALIGNANT DISEASE

The first clinical case of a patient with the syndrome of inappropriat e secretion of antidiuretic hormone (SIADH) was presented by Schwartz et al. in 1957 (Am J Med 1957; 23: 529-42), describing two patients wi th lung cancer who developed hyponatraemia associated with continued u rinary sodium loss. They postulated that the tumours led to the inappr opriate release of antidiuretic hormone (ADH), later discovered to con sist of arginine-vasopressin (AVP). This suggestion was later confirme d in several studies. The clinical description of the syndrome has cha nged little since the original observation, and the cardinal findings of SIADH are as follows: (i) hyponatraemia with corresponding hypo-osm olality of the serum and extracellular fluid, (ii) continued renal exc retion of sodium, (iii) absence of clinical evidence of fluid volume d epletion, (iv) osmolality of the urine greater than that appropriate f or the concomittant osmolality of the plasma, i.e. urine less than max imal diluted, and (v) normal function of kidneys, suprarenal glands an d thyroid glands. Measurement of AVP in plasma is not a part of the de finition of SIADH, SIADH may be caused by a variety of malignant tumou rs, but may also be caused by various other conditions, such as disord ers involving the central nervous system, intrathoratic disorders such as infections, positive pressure ventilation and conditions with decr ease in left atrial pressure. Also, a large number of pharmaceutical a gents have been shown to produce SIADH, including a number of cytotoxi c drugs such as vincristine, vinblastine, cisplatin, cyclophosphamide, and melphalan. A broad spectrum of malignant tumours has been reporte d to cause SIADH; however, most of these observations have been in cas e reports including very few patients. This includes a number of prima ry brain tumours, haematologic malignancies, intrathoracic non-pulmona ry cancers, skin tumours, gastrointestinal cancers, gynaecological can cer, breast-and prostatic cancer, and sarcomas. Larger series of patie nts have revealed that SIADH occurs in 3% of patients with head and ne ck cancer (47 cases out of 1696 patients), in 0.7% of patients with no nsmall-cell lung cancer (three cases out of 427 patients), and in 15% of cases of small-cell lung cancer (214 cases out of 1473 patients). T he optimal therapy for SIADH is to treat the underlying malignant dise ase, If this is not possible, or if the disease has become refractory, other treatment methods are available such as water restriction, deme clocycline therapy, or, in severe cases, infusion of hypertonic saline together with furosemide during careful monitoring.