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Electrolyte and Hormonal Disorders / Autoimmune Neurological Disorders and Treatments · Journal article
Endocrine Connections · August 14, 2026
Early or partial results. Treat as a signal, not a conclusion.
This evidence mapping examined 194 published reports on ICI-associated hyponatremia and reclassified 144 case-level records into diagnostic categories. The analysis found that adrenal-axis immune-related adverse events dominated the classifiable literature (88.2%), while strictly supported SIADH was rare (0.7%), with a substantial proportion of cases (11/144, 7.6%) reflecting mixed, confounded, or non-endocrine mechanisms.
Systematic evidence mapping with structured case reclassification. Published reports (case reports, case series, population studies) describing patients with hyponatremia during ICI therapy; setting and geographic origin not specified.. Intervention: Immune checkpoint inhibitor therapy (type and dosing not specified in this extract). n = 144.
127/144 cases (88.2%) classified as confirmed/probable adrenal-axis irAEs 1/144 cases (0.7%) classified as confirmed/probable SIADH 3/144 cases (2.1%) classified as SIADH-like phenotypes with incomplete endocrine exclusion
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This evidence mapping reveals that published cases of ICI-associated hyponatremia are heavily skewed toward adrenal-axis irAEs rather than SIADH, and that true SIADH is rare when strict diagnostic criteria are applied. Clinicians should be aware that many published SIADH labels may represent adrenal insufficiency and should apply the proposed diagnostic algorithm to distinguish mechanisms, though the study does not provide an incidence estimate or prospective outcome data to guide practice directly.
This is a systematic evidence mapping and reclassification study of case reports and small series, not a primary clinical trial or high-quality meta-analysis; it documents diagnostic patterns in published literature rather than prospective outcomes.
As stated by the source record.
Quoted from the source exactly as published.
This evidence mapping reveals that published cases of ICI-associated hyponatremia are heavily skewed toward adrenal-axis irAEs rather than SIADH, and that true SIADH is rare when strict diagnostic criteria are applied. Clinicians should be aware that many published SIADH labels may represent adrenal insufficiency and should apply the proposed diagnostic algorithm to distinguish mechanisms, though the study does not provide an incidence estimate or prospective outcome data to guide practice directly.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
OBJECTIVE: Severe 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. METHODS: PubMed, Embase, Web of Science Core Collection, Scopus, and the Cochrane Library were searched through 24 May 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. RESULTS: All 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. CONCLUSIONS: Published 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 standalone practice guideline.
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