Hyponatremia and anti-diuretic hormone in Legionnaires' disease

Background: Medical textbooks often list Legionnaires' disease as a differential diagnosis of the syndrome of inappropriate secretion of anti-diuretic hormone (ADH) (SIADH), but evidence supporting this association is largely lacking. We tested the hypothesis whether hyponatremia in patients with Legionnaires' disease would be caused by increased CT-ProVasopressin. Methods: We measured CT-ProVasopressin and sodium levels in a prospective cohort of 873 pneumonia patients from a previous multicentre study with 27 patients having positive antigen tests for Legionella pneumophila. Results: Patients with Legionnaires' disease more frequently had low sodium levels (Na < 130 mmol/L) (44.4% vs 8.2%, p < 0.01), but similar mean CT-ProVasopressin levels (pmol/l) (39.4 [+/- 7] vs 51.2 [+/- 2.7], p = 0.43) as compared to patients with pneumonia of other etiologies. In patients with Legionnaires' disease, CT-ProVasopressin levels showed a positive correlation with sodium (r = 0.42, p < 0.05). Independent of pneumonia etiology, CT-ProVasopressin correlated significantly with the pneumonia severity index (r = 0.56, p < 0.05), ICU admission (adjusted odds ratio per decile, 95% CI) (1.6, 1.2 - 2.0), and 30-day-mortality (1.8, 1.3 - 2.4). Conclusion: While Legionnaires' disease was associated with hyponatremia, no concurrent increase in CT-ProVasopressin levels was found, which argues against elevated ADH levels as the causal pathway to hyponatremia. Rather, Vasopressin precursors were upregulated as response to stress in severe disease, which seems to overrule the osmoregulatory regulation of ADH.