ArticleEndocrine connections2026
Immune checkpoint inhibitor-associated severe hyponatremia: evidence mapping of SIADH-like phenotypes and endocrine immune-related adverse events.
Article in Endocrine connections, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveSevere or symptomatic hyponatremia during immune checkpoint inhibitor (ICI) therapy may reflect syndrome of inappropriate antidiuresis (SIADH), endocrine immune-related adverse events (irAEs), cancer-related factors, or mixed mechanisms. We mapped the evidence and reclassified diagnostically extractable cases to distinguish SIADH-like phenotypes from endocrine irAEs.
methodsPubMed, Embase, Web of Science Core Collection, Scopus, and the Cochrane Library were searched through May 24, 2026. Reports were assigned to A1 case-level, A2 population-level, or A3 diagnostic-framework layers. A1 summaries used patient/case denominators after a report-versus-patient audit. Diagnostic categories were reviewer-derived. Reporting completeness was described using six prespecified domains. We performed source-label and full-length-only sensitivity analyses.
resultsAll 194 reports sought for retrieval were assessed, and 146 were included: 127 A1 reports describing 144 patients/cases, 16 A2 reports, and 3 A3 reports. Strict classification identified 127/144 (88.2%) confirmed/probable adrenal-axis irAEs, 1/144 (0.7%) confirmed/probable SIADH, 3/144 (2.1%) SIADH-like phenotypes with incomplete endocrine exclusion, 2/144 (1.4%) thyroid-related cases, and 11/144 (7.6%) mixed, confounded, or non-endocrine mechanisms. Ten patients/cases carried an explicit source-level SIADH label; strict review classified six as adrenal-axis irAEs, one as SIADH, and three as SIADH-like with incomplete endocrine exclusion. After exclusion of 81 abstract/database-only A1 reports, 46 full-length reports described 59 patients: 52 adrenal-axis irAEs, 1 SIADH, and 6 mixed/confounded or non-endocrine cases.
conclusionPublished classifiable A1 cases were dominated by adrenal-axis irAEs. Strictly supported SIADH occurred but was rare in this selected evidence base, and the direction of findings persisted in the full-length-only analysis. These proportions are not incidence estimates. The proposed algorithm supports diagnostic sequencing and transparent reporting; it is not a stand-alone practice guideline.
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