Cystatin C, a Controversial Biomarker in Hypothyroid Patients under Levothyroxine Therapy: THYRenal, a Pilot Cohort Observational Study

Background: Cystatin C (Cys-C) is recognized as one of the most reliable renal function parameters in the general population, although it might be biased by thyroid status. Herein, we tested Cys-C and conventional renal parameters in a cohort of hypothyroid patients treated with Levothyroxine. Methods: Eighty-four hypothyroid patients were recruited and subgrouped according to their serum thyroid-stimulating hormone (TSH) values as a paradigm for therapeutic targeting (n = 54, optimal TSH range = 0.5-2 mu IU/mL; n = 30, TSH > 2 mu IU/mL). Serum Cys-C, creatinine, measured and estimated glomerular filtration rates (mGFR and eGFR) were assessed. Results-mGFR and eGFR were comparable among the two subgroups, whereas Cys-C was significantly higher in patients with suboptimal TSH values (>2 mu IU/mL) (p < 0.0001). TSH significantly correlated with Cys-C in the overall patient group, and in the subgroup with TSH above the target value (>2 mu IU/mL). Out of 20 patients with abnormal Cys-C, 19 had suboptimal TSH levels. Receiver operating characteristic (ROC) analysis indicated Cys-C as a moderately accurate diagnostic tool (AUC = 0.871) to assess Levothyroxine replacement efficacy in hypothyroid patients (63% sensitivity, and 98% specificity). Conclusions: The observation of increased serum Cys-C in patients with suboptimal TSH would suggest the importance of a careful interpretation by clinicians of this biomarker in the case of hypothyroid patients.