Indirect Basal Metabolism Estimation in Tailoring Recombinant Human TSH Administration in Patients Affected by Differentiated Thyroid Cancer: A Hypothesis-Generating Study.

Agnese Barnabei,Laura Rizza,Maddalena Barba,Marialuisa Appetecchia,Aurora De Leo,Claudia Annoscia,Agnese Persichetti,Giovanni Cigliana,Lidia Strigari,Roberto Baldelli,Francesco Torino,Rosa Lauretta

doi:10.3389/fendo.2018.00037

Abstract

Recombinant human TSH (rhTSH) is currently used in follow-up of patients affected by differentiated thyroid cancer (DTC). Age, sex, weight, body mass index, body surface area (BSA) and renal function are known factors affecting serum TSH peak levels, but the proper rhTSH dose to deliver to single patient remains elusive. In this study, the correlations of basal metabolic rates with serum TSH peak following rhTSH administration were investigated. We evaluated 221 patients affected by thyroid cancer that received a standard dose rhTSH. Blood samples were collected at pre-established time points. Data on body weight, height, and BSA were collected. The Mifflin-St Jeor and Fleisch equations were used to assess basal metabolism. The median value (range) of serum TSH peaks was 142 ± 53 μU/ml. Serum TSH peaks were significantly lower in males than in females (p = 0.04). TSH values also increased with age. Data showed a significant decrease of TSH peak levels at day 3 from the administration of rhTSH when basal metabolic rates increased (p = 0.002 and p = 0.009, respectively). Similar findings were observed at day 5 (p = 0.004 and p = 0.04, respectively). A multivariate analysis of several factors revealed that patients' basal metabolism (obtained using the Mifflin-St Jeor but not Fleisch equation) predicts serum TSH level peak at day 3 (p < 0.001). These results were used to generate a new formula based on Mifflin-StJeor equation which reveals as a promising tool in tailoring rhTSH dose. Basal metabolism appears an improving factor in tailoring diagnostic rhTSH dose in patients affected by DTC.

Highlights

In patients diagnosed with early or locally advanced differentiated thyroid cancer (DTC), total thyroidectomy is currently the primary treatment and levothyroxine (LT4) at suppressive dose is required to prevent TSH-induced growth of potentially residual cancer cells [1].In some patients, an ablative dose of radioiodine (RAI) is delivered to kill residual cancer cells, reducing risk of recurrence
A still challenging issue is the tailored dosing of drugs delivered for therapeutic, and for diagnostic purpose. This is the case of recombinant human TSH (rhTSH), a hydrophilic drug delivered at fixed dose, having a key role in the follow-up of patients affected by DTC
In patients affected by DTC, several factors have been shown to affect serum TSH peak levels following rhTSH administration, including body weight, body mass index (BMI), body surface area (BSA), lean body mass, and serum creatinine concentration [4, 9, 10]

Summary

Introduction

In patients diagnosed with early or locally advanced differentiated thyroid cancer (DTC), total thyroidectomy is currently the primary treatment and levothyroxine (LT4) at suppressive dose is required to prevent TSH-induced growth of potentially residual cancer cells [1]. An ablative dose of radioiodine (RAI) is delivered to kill residual cancer cells, reducing risk of recurrence. In DTC patients, follow-up is based on serum thyroglobulin (TSH stimulated or during l-tiroxine therapy) and neck ultrasound. Diagnostic 131-radioiodine whole-body scan (131-I WBS) is not routinely used during follow-up, but may be required in specific conditions [1]. Elevated serum TSH are needed to RAI therapy and 131-I WBS execution, as well as to evaluate stimulated thyroglobulin during follow-up. Elevated serum TSH are obtainable either through LT4 withdrawal or by the administration of recombinant human TSH (rhTSH), a hydrophilic drug, which is metabolized and eliminated by the kidney [2,3,4,5]

Methods

Results

Conclusion