Human-AI Co-reasoning for Clinical Diagnosis with Evidence-Integrated Language Agent

Abstract: We present PULSE, a medical reasoning agent that combines a domain-tuned LLM with scientific literature retrieval to support diagnostic decision-making in complex real-world cases. To evaluate its capabilities, we curated a benchmark of 82 authentic endocrinology case reports encompassing a broad spectrum of disease types and incidence levels. In controlled experiments, we compared PULSE's performance against physicians with varying levels of expertise-from residents to senior specialists-and examined how AI assistance influenced human diagnostic reasoning. PULSE attained expert-competitive accuracy, outperforming residents and junior specialists while matching senior specialist performance at both Top@1 and Top@4 thresholds. Unlike physicians, whose accuracy declined with disease rarity, PULSE maintained stable performance across incidence tiers. The agent also exhibited adaptive reasoning, increasing output length with case difficulty in a manner analogous to the longer deliberation observed among expert clinicians. When used collaboratively, PULSE enabled physicians to correct initial errors and broaden diagnostic hypotheses, but also introduced risks of automation bias. The study explores both serial and concurrent collaboration workflows, revealing that PULSE offers robust support across common and rare presentations. These findings underscore both the promise and the limitations of LLM-based agents in clinical diagnosis, and offer a framework for evaluating their role in real-world decision-making.