Impact of Renal Function and Demographic/Anthropomorphic Variables on Peak Thyrotropin After Recombinant Human Thyrotropin Stimulation: A Stepwise Forward Multiple-Regression Analysis

Abstract

When applying the recommended standard doses of recombinant human thyrotropin (rhTSH) in the diagnostic/therapeutic management of patients with differentiated thyroid cancer (DTC), the resulting peak TSH levels vary extensively. Previous studies applying multivariate statistics identified patient-inherent variables influencing the rhTSH/peak TSH relation. However, those results were inconclusive and partly conflicting. Notably, no independent role of renal function was substantiated, despite the fact that the kidneys are known to play a prominent role in TSH clearance from blood. Therefore, the study's aim was to investigate the impact of renal function on the peak TSH concentration after the standard administration of rhTSH used in the management of thyroid cancer. The second objective was to calculate a ranking regarding the effect sizes of the selected variables on the peak TSH. There were 286 patients with DTC included in the study. Univariate and multivariate analyses were performed, testing the correlation of serum creatinine and glomerular filtration rate (GFR) as surrogate parameters of renal function, age, sex, weight, height, and body surface area (BSA) with the peak TSH level. In six additional patients, the subsequent TSH pharmacokinetics after the TSH peak were measured and qualitatively compared. By univariate analyses, TSH correlated negatively with BSA, GFR, weight, and height, and positively with age, female sex, and serum creatinine (p<0.001). On the multivariate analysis, the stepwise forward multiple linear regression revealed BSA and renal function as the two most influential independent variables, followed by age, sex, and height. The pharmacokinetic datasets indicated that these identified parameters also influence the TSH decline over time. Identifying those patients with a favorable combination of parameters predicting a high-peak TSH is the first step toward an individualization of rhTSH dosing. Additionally, the subsequent TSH decrease over time needs to be taken into account. A complete understanding of the interrelation of the identified key parameters and both the TSH peak and subsequent TSH pharmacokinetics might allow for a more personalized rhTSH dosage strategy to achieve sufficient TSH levels instead of the fixed dosing procedure used at present.