A study of serum antidiuretic hormone and atrial natriuretic peptide levels in a series of patients with intracranial disease and hyponatremia

Patients with intracranial disease are at risk of developing clinical deterioration due to a hyponatremic syndrome associated with an inappropriate degree of natriuresis, the 'syndrome of inappropriate secretion of anti-diuretic hormone (ADH)' or SIADH. To investigate the hypothesis that atrial natriuretic peptide (ANP) is related to the natriuresis in SIADH, serum samples were obtained from 8 neurosurgical patients with intracranial disease seen consecutively who fulfilled the traditional clinical and laboratory criteria for SIADH. In one patient with a hemorrhagic cerebral infarction an elevation of serum ADH (5.7 pg/ml; normal = 1 to 5 pg/ml) in association with a normal level of serum ANP (49.8 pg/ml; normal = 10 to 60 pg/ml) was seen. Six patients (2 with intracerebral hemorrhage and 1 with hemorrhagic cerebral infarction, 1 with aneurysmal subarachnoid hemorrhage, 1 with glioblastoma multiforme, and 1 with Creutzfeldt-Jakob disease) had elevated serum ANP levels (197.0, 112.0, 92.0, 432.0, 97.5, and 138.0 pg/ml, respectively) associated with either normal or low ADH levels (1.3, 2.5, 1.2, 0.7, 2.3, and 0.5 pg/ml, respectively). Another patient with an intracerebral hemorrhage had a normal serum ANP level (37.0 pg/ml) and undetectable ADH level (<0.5 pg/ml). In the 7 patients in whom either ADH or ANP alone was elevated, a reciprocal relationship was observed between serum ADH and ANP levels, which could be expressed in logarithmic form (correlation coefficient, r = 0.727). In the 6 patients in whom serum ANP level alone was elevated, a near linear relationship was observed between serum ANP levels and urine sodium excretion (r = 0.851). No such relationship was observed between serum ADH levels and urine sodium excretion (r = 0.249). The finding of elevated serum ANP with normal or low serum ADH and a correlation between serum ANP and urinary sodium excretion is more consistent with the original concept of cerebral salt washing than with SIADH. The term, SIADH, describes at least three subtypes of the hyponatremic-natriuretic syndrome in intracranial disease based on serum levels of ADH and ANP.