Assessment of Levothyroxine Therapy Adequacy in Low-Risk Differentiated Thyroid Carcinoma: A Multicenter Cohort Study (REVISED VERSION R3)

Juan Díez^1*ANDA EMMA²VICTORIA ALCÁZAR LÁZARO³Juan Carlos Galofre⁴Cristina Familiar⁵María J. Pamplona-Civera⁶Silvia González-Martínez⁷Ana Herrero-Ruiz⁸María R. Alhambra⁹Alejandra Planas¹⁰Cecilia Sánchez Ragnarsson¹¹Tomás Martín¹²Beatriz Rodríguez Jiménez¹²Mireia Mora Porta¹³Aida Orois¹³Reinaldo Sánchez-Barrera¹⁴Julia Sastre¹⁵

• ¹Puerta de Hierro University Hospital Majadahonda, Madrid, Spain
• ²Hospital Universitario de Navarra, Pamplona, Spain
• ³Hospital Universitario Severo Ochoa, Leganés, Spain
• ⁴Clinica Universidad de Navarra, Pamplona, Spain
• ⁵Hospital Clinico San Carlos, Madrid, Spain
• ⁶Hospital Royo Villanova, Zaragoza, Spain
• ⁷Hospital de Cabuenes, Gijón, Spain
• ⁸Hospital Universitario de Salamanca, Salamanca, Spain
• ⁹Hospital Universitario Reina Sofia, Córdoba, Spain
• ¹⁰Hospital Universitari Vall d'Hebron, Barcelona, Spain
• ¹¹Hospital Universitario Central de Asturias, Oviedo, Spain
• ¹²Hospital Universitario Virgen Macarena, Seville, Spain
• ¹³Hospital Clinic de Barcelona, Barcelona, Spain
• ¹⁴Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain
• ¹⁵Hospital Universitario de Toledo, Toledo, Spain

Objective. This study aimed to evaluate the adequacy of levothyroxine therapy, assessed by serum thyrotropin (TSH) levels, in patients with low-risk differentiated thyroid carcinoma (DTC). Methods. We conducted a multicenter, retrospective cohort study including patients with low-risk DTC. Dynamic risk stratification was performed 12 months after initial treatment and at the last follow-up visit according to the 2015 American Thyroid Association (ATA) guidelines. Patients were categorized based on treatment response as excellent, indeterminate, biochemical incomplete, and structural incomplete. Levothyroxine adequacy was determined according to ATA-recommended TSH target values. Results. A total of 1016 patients (median age, 48 years; 80.7% women; 91.4% papillary thyroid carcinoma) were followed for a median of 6.6 years. Total thyroidectomy was performed in 935 (92.0%) (plus radioiodine in 667), while 81 (8.0%) underwent lobectomy. An excellent response was observed in 633 (62.3%) at 12 months and in 761 (77.8%) at the last follow-up. Treatment adequacy increased from 264 (26.0%) at 12 months to 387 (39.5%) at the final visit (P<0.001). Among patients with excellent response, treatment adequacy rose from 25.8% to 44.3% (P<0.001). At the last visit, inadequacy was primarily due to excessive levothyroxine in patients with excellent response (30.5%), and insufficient dosing in those with indeterminate or biochemical incomplete response (62.2% and 50.0%, respectively). Levothyroxine dose instability correlated significantly with treatment inadequacy (P<0.001). Conclusion. The low rate of treatment adequacy highlights the need of personalized levothyroxine dosing to optimize therapeutic outcomes and minimize the risks of under-or overdosing in patients with low-risk DTC.