Supplementary file 1_Surveillance intensity influences the observed incidence of delayed hyponatremia after microscopic transsphenoidal pituitary surgery: early sodium and sex as risk stratifiers.docx

An apparent two-decade increase largely disappeared once surveillance was held constant: under the assumptions of a direct-standardization analysis, approximately 83% of the observed temporal increase was explained by differences in surveillance intensity. Early postoperative hyponatremia (any sodium below 135 mmol/L on days 0–2) showed the largest univariable association among bedside-available variables: 46.9% of affected patients later developed delayed hyponatremia versus 12.4% without it (relative risk 3.77; odds ratio 6.14), although this did not reach significance after multivariable adjustment within the surveillance-complete subgroup (odds ratio 2.83; 95% CI 0.86–9.33).

Female sex was independently associated with the outcome (adjusted odds ratio 2.73), and a significant age-by-sex interaction (p = 0.010) showed consistently elevated risk in women of all ages and risk rising with age in men; age was analyzed continuously. A secondary, exploratory risk-stratification model reached an optimism-corrected area under the curve of 0.645, adequate for hypothesis generation but not clinical deployment.

Even within a single surgical team, apparent incidence varied more than threefold with surveillance intensity, suggesting that much of the reported heterogeneity may reflect differences in how the outcome is ascertained rather than between patients. Whether early sodium, sex, and age can direct day 5–7 surveillance instead of screening every patient requires prospective evaluation.</p>