Defining a rational step-care algorithm for managing thyroid carcinoma patients with elevated thyroglobulin and negative on radioiodine scintigraphy (TENIS): considerations and challenges towards developing an appropriate roadmap

Abstract

One of the most challenging clinical situations in patients with differentiated thyroid cancer (DTC) is an elevated serum thyroglobulin (Tg) level with negative radioiodine scintigraphy (commonly termed BTENIS^). The diagnostic and therapeutic approaches adopted by attending physicians in day-to-day routine vary quite widely. The main reason for this variation is the rarity of the condition (2 -13 % from various series reported in literature), and its management, especially therapeutic strategies, continues to be imperfect in the absence of a clear-cut understanding and lack of evidence of its aetiology, as observed by various authorities [1]. In this editorial, we discuss the different therapeutic strategies that have been explored and the associated pitfalls in interpretation of clinical findings, and propose a logical step-wise algorithmic approach to care to follow in routine clinics in this particular group of patients. Our views are supported by an overview of the evidence in the literature (with respect to both efficacy and adverse effects) and by practical experience. In addition, we critically review and analyse the steps needed in the immediate future to enhance and rationalize patient care. We believe that such endeavours to identify and prioritize the challenges will further the roadmap to the development of a systematic and scientific approach to the management of patients with TENIS.

Incremental diagnostic value of [18F]tetrafluoroborate PET-CT compared to [131I]iodine scintigraphy in recurrent differentiated thyroid cancer

“…Respectively, contrast enhanced foci were retrospectively detected in prior CT acquisitions (c, e) [9]. This constellation is known as TENIS or flip-flop phenomena [3,8,9]. However, [ 18 The present retrospective study faces some limitations.…”

“…Riemann et al argued that this is partly caused by the tumor biology of DTC [3]: In case of recurrent DTC, a dedifferentiation of tumor cells might occur that decreases hNIS expression but increases [ 18 F]FDG metabolism in turn Recurrence of DTC was histologically validated. Respectively, contrast enhanced foci were retrospectively detected in prior CT acquisitions (c, e) [9]. This constellation is known as TENIS or flip-flop phenomena [3,8,9].…”

“…The detection of local recurrence or metastases of DTC by iodine imaging is of great relevance for the planning of localized therapies, like surgery or radiation therapy [2]. Moreover, negative iodine imaging despite elevated tumor marker levels is a prerequisite for diagnosing the "Thyroglobulin Elevated and Negative Iodine Scintigraphy" (TENIS) syndrome, which requires fundamentally different diagnostic and therapy concepts [8][9][10]. Therefore, a failure in detecting hNISexpressing local recurrences or metastases of DTCs might result both in a missed opportunity for localized therapy and an erroneously assumed TENIS syndrome.…”

Grouping of Metastatic Thyroid Carcinoma by Molecular Imaging Features to Allow for Individualized Treatment, with Emphasis on the TENIS Syndrome

“…The therapies for metastatic thyroid carcinoma and TENIS syndrome currently provided in the field are far from ideal, with various approaches being suggested, including those by our group (4). We have reported here on a gamut of representative cases in which molecular functional imaging was used to characterize metastatic lesions, group them into classes, and apply the best treatment for each class-this being the basis for individualization of treatment regimens.…”

“…The management of patients with thyroglobulin elevation and negative iodine scintigraphy (TENIS syndrome) has been a topic of considerable interest and debate among attending physicians and has been emphasized in recent years, particularly in view of poor outcomes, the associated challenges, and the absence of a definitive consensus on management (1)(2)(3)(4). Management continues to evolve, with several routine and investigational therapeutic approaches being explored with respect to their place and efficacy in this challenging clinical situation, including empiric 131 I therapy and whether it is justified (1)(2)(3)(4). It is imperative that with a more critical look into this entity, an individualized treatment approach be adopted, with the broad group being divided into various smaller segments based on both clinicopathologic and molecular imaging lesional characteristics.…”