P296 - ECE_3232 - The third phenotype: high preoperative serum IGF-1 imprints post-surgical discordant trajectory in acromegaly

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Abstract Introduction The 2024 consensus on acromegaly remission relies on biochemical concordance, yet a gray zone of discordant growth hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) levels still exists. We postulate this represents a distinct “Third Phenotype”—neither cured nor classically active—and investigated the characteristics of this discordant group and biological predictors in a large single-center surgical cohort. Methods We performed a longitudinal analysis of 103 patients (1994-2019) treated at a dedicated Pituitary Center of Excellence. The final cohort (n = 82) had complete postoperative Oral Glucose Tolerance Test and IGF-1 data. Discordance was rigorously defined as one parameter (GH nadir or IGF-1) indicating remission while the other remained elevated. Phenotypic stability was tracked across three assay eras (RIA/Immulite/iSYS). Results Biochemical discordance manifested in 20% (16/82) of patients, predominantly as the High-IGF1/Normal-GH pattern (88%). The median age of discordant patients was 44 (range:30-75 years), 75% of discordant patients were men. Most patient (81%) presented with a macroadenoma at diagnosis of acromegaly and 47% had an invasive tumour. Hypertension was observed in 38%, and diabetes mellitus in 19% of patients. The phenotype demonstrated remarkable stability (94% retention of discordance type over a decade), arguing against transient assay variability. While tumor size and invasiveness were non-predictive, high preoperative IGF-1 was the defining predictor: median IGF-1 at diagnosis was significantly higher in discordant vs concordant-controlled patients (3.1 vs 2.5 × ULN, P = .01). Conclusions Biochemical discordance represents a stable biological entity rather than a methodological artifact. Approximately one fifth of patients exhibited postoperative discordance, most commonly elevated IGF-1 with a normal GH nadir. The majority of discordant patients had macroadenomas. Higher IGF-1 levels at diagnosis predicted postoperative discordance. These patients remain in a gray zone between remission and active disease, requiring careful and individualized follow-up.

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