Early postoperative voice-change phenotypes after thyroid surgery: a prospective cohort study.

BACKGROUND

Post-thyroidectomy voice change is common, but early postoperative objective voice-change patterns and their short-term clinical relevance remain insufficiently characterized.

METHODS

In this single-center prospective cohort study, patients undergoing thyroid surgery were screened consecutively from October 2025 to November 2025. Standardized voice recordings were obtained at baseline and postoperative day 2 (POD2), and clinical voice outcomes were assessed at postoperative day 7 (POD7). Five POD2 spectral change features relative to baseline were used to derive phenotypes through a prespecified two-stage unsupervised clustering workflow based on partitioning around medoids, Manhattan distance, and silhouette-based cluster-number selection. Clinical validation used change in Voice Handicap Index-30 (VHI-30), the prespecified VHI-30 responder definition (Delta VHI-30 ≥ 13), and change in Grade within the Grade, Roughness, Breathiness, Asthenia, Strain scale. Robustness was evaluated using consensus clustering, proportion of ambiguous clustering, sample-level stability, and resampling-based adjusted Rand index reproducibility. Sensitivity analyses compared the primary workflow with one-step k = 3 and k = 4 clustering alternatives, and exploratory analyses evaluated operative and demographic factors in relation to POD7 outcomes.

RESULTS

Of 401 screened patients, 245 were included in the final analytic cohort. The final phenotypes were A/B/C = 59/56/130. All five spectral clustering features differed significantly across phenotypes (all P < 0.001). At POD7, phenotypes differed significantly in VHI-30 change (epsilon-squared = 0.641), VHI-30 responder rate (Cramér's V = 0.639), and Grade change (epsilon-squared = 0.203) (all P < 0.001). Phenotype B showed the greatest short-term burden, including a responder rate of 53.6% (30/56; exact 95% confidence interval, 39.7%-67.0%), compared with 1.7% (1/59; exact 95% confidence interval, 0.0%-9.1%) in phenotype A and 1.5% (2/130; exact 95% confidence interval, 0.2%-5.4%) in phenotype C. Sensitivity analyses did not support replacing the prespecified two-stage workflow with one-step k = 3 or k = 4 alternatives. Exploratory analyses suggested that the clinical profile of phenotype B was not simply explained by thyroidectomy extent, surgical approach, lateral neck dissection, or operative time.

CONCLUSIONS

Early postoperative objective voice changes after thyroid surgery can be organized into clinically interpretable short-term phenotypes associated with patient-reported and supportive perceptual outcomes. These phenotypes should be interpreted as early postoperative voice-change patterns rather than as nerve-injury phenotypes or persistent long-term voice categories.