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Serial post-surgical stimulated and unstimulated highly sensitive thyroglobulin measurements in low- and intermediate-risk papillary thyroid carcinoma patients not receiving radioactive iodine

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Abstract

The purpose of this study was to determine the natural temporal trends of serial thyroglobulin (Tg) among low/intermediate-risk PTC patients not receiving radioactive iodine (RAI) using TSH-stimulated Tg (Stim-Tg) and unstimulated highly sensitive Tg (u-hsTg). We prospectively analyzed serial Stim-Tg measurements after total thyroidectomy ± therapeutic central neck dissection among 121 consecutive low/intermediate-risk PTC patients who did not receive RAI, of whom 104 also had serial u-hsTg measurements available. Median follow-up was 6.5 years with Stim-Tg measurements commencing 3 months after surgery and u-hsTg commencing 1.8 years after surgery (when the assay became available). TSH stimulation was performed with 9-day T3 withdrawal, 22-day T4 withdrawal, or using recombinant human TSH (rhTSH). To account for within-patient correlations of repeated Tg measurements, temporal trends in Stim-Tg and u-hsTg were assessed using Generalized Estimating Equations. Stim-Tg models were adjusted for the method of TSH stimulation, whereas the u-hsTg models were adjusted for concurrent TSH level. Linear regression modeling was used to assess the trend in serial Stim-Tg and u-hsTg measurements as a function time from time of surgery throughout the duration of follow-up. The main outcome measured was the change in u-hsTg and Stim-Tg measurements over time. A total of 337 Stim-Tg (2.8/patient) and 602 u-hsTg (5.8/patient) measurements were analyzed. Among the 337 Stim-Tg measurements, Stim-Tg was assessed using rhTSH in 202 (60 %), T4 withdrawal in 41 (12 %), and T3 withdrawal in 94 (28 %) measurements. The overall mean ± 1SD for Stim-Tg and u-hsTg measured was 1.0 ± 1.2 and 0.2 ± 0.1 μg/L, respectively. When adjusted for method of TSH stimulation, serial Stim-Tg measurements did not significantly change over time (all p = NS). The estimated changes in Stim-Tg per year for rhTSH, T4 withdrawal, and T3 withdrawal were 0.01, −0.08, and 0.04 μg/L, respectively. Upon exclusion of 73 patients with an initial undetectable Stim-Tg (n = 48), serial Stim-Tg measurements did not change significantly over time (all p = NS). For these patients, the estimated changes in Stim-Tg per year for rhTSH, T4 withdrawal, and T3 withdrawal were −0.09, −0.10, and 0.01 μg/L, respectively. Serial u-hsTg measurements did not significantly change over time after adjusting for TSH level (p = NS). The estimated change in u-hsTg per year was −0.003 μg/L. No patients had any clinical or imaging evidence of a recurrence during the duration of their follow-up. Among low/intermediate-risk PTC patients not treated with RAI, serial post-surgical Stim-Tg and u-hsTg measurements do not change significantly over a median follow-up of 6.5 years.

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Acknowledgments

This study was supported in part by unrestricted educational grants from Abbott/Mylan Laboratories Limited Canada; the Mount Sinai Hospital Foundation of Toronto Da Vinci Gala Fundraiser; the George Knudson Oakdale Pro-Am Charity Golf Tournament; the Mount Sinai Hospital Department of Medicine Research Fund; and the Alex and Simona Shnaider Research Chair in Thyroid Oncology to PGW.

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Authors and Affiliations

  1. Department of Medicine, Endocrine Division & Department of Otolaryngology-Head & Neck Surgery Program, Joseph & Mildred Sonshine Family Centre for Head & Neck Diseases, Mount Sinai Hospital, University of Toronto Medical School, Toronto, ON, M5G 1X5, Canada

    Lawrence Kashat, Steven Orlov, David Orlov, Jasmeet Assi, Farnaz Salari & Paul G. Walfish

  2. Senior Endocrine Consultant, Alex and Simona Shnaider Research Chair in Thyroid Oncology, Mount Sinai Hospital, Toronto, ON, Canada

    Paul G. Walfish

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  1. Lawrence Kashat
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  2. Steven Orlov
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  3. David Orlov
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  4. Jasmeet Assi
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  5. Farnaz Salari
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  6. Paul G. Walfish
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Correspondence to Paul G. Walfish.

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Conflict of interest

PGW receives consulting fees from Genzyme Canada, a Sanofi company and a shareholder in Protoecyte Diagnostics Inc. LK, SO, DO, JA, JC, and FS have no relevant disclosures of interest.

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Kashat, L., Orlov, S., Orlov, D. et al. Serial post-surgical stimulated and unstimulated highly sensitive thyroglobulin measurements in low- and intermediate-risk papillary thyroid carcinoma patients not receiving radioactive iodine. Endocrine 54, 460–466 (2016). https://doi.org/10.1007/s12020-016-0989-3

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