Hyponatremic Natriuretic Syndrome in Tuberculous Meningitis

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Abstract
HYPONATREMIA HAS BEEN reported in up to one third of patients with intracranial disease and has frequently been associated with tuberculous meningitis, often complicated by hydrocephalus. The lowered plasma sodium levels were previously attributed to the syndrome of inappropriate secretion of antidiuretic hormone. A controlled prospective study of 24 patients with tuberculous meningitis and hydrocephalus was carried out. Analyses of serum electrolytes and cerebrospinal fluid were performed. Plasma and cerebrospinal fluid levels of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured by radioimmunoassay. Fifteen patients were found to be hyponatremic (plasma sodium < 130 mmol/L) and ANP levels of 12 to 1,488 pg/ml were present (median, 26 pg/ml). The remaining 9 patients had normal plasma sodium values between 130 and 145 mmol/L, and in these, plasma ANP values varied between 12 and 21.7 pg/ml (median, 12 pg/ml). The difference between these two groups was not statistically significant. (Control values from patients undergoing myelography were established to range between 12 and 40 pg/ml; median, 14.4 pg/ml.) ANP levels were undetectable in the cerebrospinal fluid in all. Plasma ADH levels in the hyponatremic group were between 7 and 159 pg/ml (median, 40 pg/ml). In the normonatremic group, plasma ADH levels of 25 to 250 pg/ml (median, 29 pg/ml) were obtained. (The controls ranged between 3.6 and 35 pg/ml; median, 10.4 pg/ml). In the hyponatremic group, there was a moderate negative correlation (r = −0.683) between plasma ANP and plasma sodium (P = 0.02). No correlation between plasma ADH and plasma sodium was found (r = −0.168; P = 0.62). It therefore appears that plasma ANP accounted for 65% of the variation in plasma sodium (P = 0.0085), while ADH accounted for only 3% (P = 0.489). These findings suggest that elevations in plasma ANP account for the major proportion of the hyponatremic states in tuberculous meningitis with hydrocephalus, while ADH, initially thought to be important, seems to play a negligible role. A more accurate and useful description of the hyponatremic state in tuberculous meningitis would be “hyponatremic natriuretic syndrome.”