Jb. Sorensen et al., SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC-HORMONE (SIADH) IN MALIGNANT DISEASE, Journal of internal medicine, 238(2), 1995, pp. 97-110
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.