Thyroglobulin and thyroglobulin autoantibodies: interpret with care

Abstract

A middle-aged lady with a past history of hyperlipidemia presented to our institution with worsening of a lower back pain that has been present for a year. The back pain radiated down her left lower limb and was associated with left foot numbness and nocturnal pain. On examination, a mass was palpated in the left iliac fossa. A full body CT scan revealed a soft tissue lesion with central necrosis and bony destruction of the left iliac bone, a similar bony lesion in the left 6th rib, and a thyroid mass. An ultrasound of thyroid gland showed a cystic nodule with interrupted calcified rim. A biopsy of the left iliac fossa mass was reported as metastatic follicular thyroid carcinoma. She underwent total thyroidectomy and was given four courses of radioiodine after a failed debulking surgery. During follow up, she was comanaged with another institution where she received the radioiodine therapy. Her thyroglobulin autoantibodies (TgAb) and thyroglobulin (Tg) concentrations were measured by both institutions. Interestingly, at our institution, her TgAb were always undetectable and her Tg showed rapidly decreasing trend (both Immulite 2000, Siemens). At the other institution, her TgAb were strongly positive and her Tg concentrations showed a different trend and were closely mirrored by TgAb concentrations (both Kryptor, B R A H M S) (Fig. 1). The Immulite 2000 TgAb method employs a chemiluminescence sequential immunometric format. On the other hand, the Kryptor TgAb method is a fluorescence competitive immunoassay. This report was exempted from local institutional board review. This case illustrated several important points about interpretation of Tg and TgAb. Tg is produced by the thyroid gland and is a tumor marker for differentiated thyroid cancers (DTC). TgAb are autoantibodies that may develop in autoimmune thyroid diseases or DTC. TgAb must be simultaneously measured with Tg as they may interfere with and falsely lower Tg measurements. When TgAb are positive, the Tg results should be interpreted with care and the TgAb may be used as surrogate tumor marker, as detailed in this clinical review [1]. Rising or stable TgAb trends are associated with increased risk of residual disease, metastasis, or recurrence, while a declining trend suggests the risks are low [1]. This approach remains controversial and more evidence is needed to establish its role in routine clinical care. An emerging and promising alternative is the use of mass spectrometric methods to measure Tg that may avoid the interference from TgAb. TgAb have been shown to be heterogeneous and have different epitopes between individuals, and are associated with histologic features of lymphocytic thyroiditis [2]. They are detected variably using different laboratory assays and may be classified differently in nearly 40 % of patients with papillary thyroid cancer with lymphocytic thyroiditis [3]. In patients with lymphocytic thyroiditis, it is probably prudent to confirm a negative TgAb with an alternate assay when Tg is unexpectedly undetectable [2, 3]. This patient did not have histologic evidence of lymphocytic thyroiditis yet showed highly discrepant TgAb results. The discrepancy may be accounted for by the use T. P. Loh (&) Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, 119074 Singapore, Singapore e-mail: lohtp@yahoo.com