Serum thyroglobulin by mass spectrometry versus immunoassay in thyroid cancer patients with anti-thyroglobulin antibodies: an interim analysis — ASN Events
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Serum thyroglobulin by mass spectrometry versus immunoassay in thyroid cancer patients with anti-thyroglobulin antibodies: an interim analysis (#301)

Sarah C Brennan 1 2 , Shejil Kumar 1 2 3 , Stephen Ludgate 2 , Magdalena Bolek 4 , Venessa HM Tsang 1 2 , Ayanthi Wijewardene 2 , Lyndal Tacon 1 2 , Cameron Wood 4 , Bruce G Robinson 1 2 , Roderick J Clifton-Bligh 1 2 5 , Lucy Ding 2 4 , Matti L Gild 1 2 5
  1. Faculty of Medicine & Health, University of Sydney, Camperdown, NSW, Australia
  2. Department of Diabetes & Endocrinology,, Royal North Shore Hospital, Sydney, NSW, Australia
  3. Department of Diabetes & Endocrinology, Westmead Hospital, Westmead, NSW, Australia
  4. Department of Chemical Pathology, NSW Health Pathology, St Leonards , NSW, Australia
  5. Cancer Genetics Lab, Kolling Institute, St Leonards, NSW, Australia

Anti-thyroglobulin antibodies (TgAb) can interfere with thyroglobulin immunoassay (Tg-IA), producing falsely low results; mass spectrometry (Tg-MS) may overcome this¹. Contemporary Tg-IA methods have improved functional sensitivity, so the magnitude of residual interference is unclear.

Adults with differentiated thyroid cancer were prospectively enrolled. Serum Tg was measured by immunoassay and by an in-house LC-MS/MS method; both have functional sensitivity 0.1 ng/mL, below which Tg was classified undetectable. Discordance was defined as detectable Tg by one method and undetectable by the other; agreement among concordantly detectable samples was assessed by Bland–Altman. Patients also had TgAb measured via immunoassay and were stratified as TgAb-negative (<4 IU/mL) or TgAb-positive (≥4 IU/mL), with Wilson 95% CIs and Fisher's exact test.

Thirty-seven patients, all post-total-thyroidectomy, contributed 40 evaluable paired samples (25 female; median age 48 years, range 20–84). Histology was papillary (32), oncocytic (3) and poorly differentiated (2) thyroid cancer. Twenty-seven received radioactive iodine and five had distant metastases.

Fourteen samples were TgAb-negative and 26 TgAb-positive (range <1 to >1000 IU/mL). Tg was detectable by both methods in 14 and undetectable by both in 25, giving concordance in 39/40 (discordance 2.5%; 95% CI 0.4–12.9%). The single discordant sample was TgAb-positive (titre 157 IU/mL), detectable by Tg-IA only (0.40 ng/mL, at the detection limit); none was detectable by Tg-MS alone. Discordance did not differ by TgAb status (1/26 versus 0/14; p=1.0).

Among concordantly detectable samples (Tg-IA median 2.40 ng/mL, range 0.10–55.4) the methods agreed closely (median Tg-MS:Tg-IA ratio 1.00, range 0.67–1.16; mean bias +0.48 ng/mL, 95% CI −0.62 to +1.57).

Contemporary Tg-IA showed near-complete concordance with Tg-MS irrespective of TgAb status, with no instance of Tg-MS detecting thyroglobulin missed by immunoassay. The role of Tg-MS remains to be defined; this sample size cannot exclude clinically relevant interference at high titre².

  1. Verburg FA, Luster M, Cupini C, et al. Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid. 2013;23(10):1211-25.
  2. Azmat U, Porter K, Senter L, et al. Thyroglobulin Liquid Chromatography-Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies. Thyroid. 2017;27(1):74-80.