Hyponatremia with intracranial disease: not often cerebral salt wasting.

The degree to which hyponatremia occurs primarily as a result of natriuresis has remained controversial for many years. Cerebral salt wasting (CSW) was first proposed by Peters et al (1) in 1950 as an explanation for the natriuresis and hyponatremia that sometimes accompany intracranial disease, particularly subarachnoid hemorrhage (SAH), in which up to one-half of patients often develop hyponatremia. After the first clinical description of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 1957, such patients were generally assumed to have hyponatremia secondary to nonosmotic arginine vasopressin (AVP) secretion with a secondary natriuresis (2). However, bothclinical andexperimentaldata have suggested that some patients with SAH and other intracranial diseases may actually have a primary natriuresis leading to extracellular fluid (ECF) volume contraction rather than SIADH (3, 4), in which case the elevated measured plasma AVP levels may actually be physiologically appropriate for the degree of volume contraction present. The major clinical question as to the frequency of CSW as a primary or contributory cause of hyponatremia is critically dependent on the criteria used to assess the ECF volume status of these patients; opponents argue that there is insufficient evidence of true hypovolemia despite ongoing natriuresis (5), whereas proponents argue that the combined measures that have traditionally been used to estimate ECF volume do, in fact, support the presence of hypovolemia in many such cases (6). Noticeably lacking from this ongoing debate has been carefully done clinical research that critically assesses the cause of hyponatremia in neurological diseases such as SAH. The article by Hannon et al (7) in this issue of the JCEM addresses this deficiency by carefully studying 100 patients with acute nontraumatic aneurysmal SAH with serial assessments of clinical ECF volume status by a single experienced clinician and measurements of plasma cortisol, AVP, and brain natriuretic peptide (BNP). Their results demonstrated the expected high incidence of hyponatremia in 49% of the patients; but when all analyses were considered, the cause of the hyponatremia was attributable to SIADH in 71.4% of patients and acute glucocorticoid deficiency in 8.2%, with the remaining cases caused by incorrect iv fluid administration or hypovolemia. Most significantly, no cases were found that met historically accepted criteria for a diagnosis of CSW. Thus, as opposed to the current trend to diagnose CSW with a relatively high frequency in neurological cases, this careful analysis indicates that CSW is an exceedingly rare cause of the hyponatremia in SAH and, by analogy, likely in other intracranial disorders as well. Since the original cases studied by Schwartz and Bartter, increased renal sodium excretion has been viewed as one of the cardinal manifestations of SIADH, indeed one that later became embedded in the requirements for its diagnosis (8). However, next to the use of the term “inappropriate,” probably no other aspect of SIADH has been so widely misinterpreted. Demonstration that the natriuresis accompanying administration of antidiuretic hormone is not due to AVP itself, but rather is due to the volume expansion produced as a result of water retention, was unequivocally shown by Leaf et al (9) even before the description of the clinical occurrence of SIADH. Subsequent metabolic balance studies demonstrated that excess urinary sodium excretion and a negative sodium balance occurred during the development of hyponatremia in patients with SIADH, but eventually urinary sodium excre-