Luca Giovanella

Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement

BACKGROUNDnEven though the presence of antithyroglobulin antibodies (TgAbs) represents a significant problem in the follow-up of patients with differentiated thyroid cancer (DTC), the current guidelines on the management of DTC that have been published in recent years contain no text concerning the methods to be used for detecting such antibody-related interference in thyroglobulin (Tg) measurement or how to manage TgAb-positive patients in whom Tg cannot be used reliably as a tumor marker.nnnAIMnAn international group of experts from the European Thyroid Association Cancer Research Network who are involved in the care of DTC patients met twice to form a consensus opinion on how to proceed with treatment and follow-up in TgAb-positive DTC patients based on the available evidence in the literature. Here we will report on the consensus opinions that were reached regarding technical and clinical issues.nnnRESULTSnThis clinical opinion article provides an overview of the available evidence and the resulting consensus recommendations. The current literature does not provide sufficient data for giving evidence-based answers to many questions arising in the care of TgAb-positive DTC patients. Where insufficient evidence was available, a thorough discussion by a group of physician-scientists, all of whom have a distinguished track record in thyroid cancer care, was held to arrive at a consensus expert opinion. The questions and answers discussed were then summarized into an algorithm for the management of TgAb-positive patients.nnnCONCLUSIONnWe were able to define 26 consensus expert recommendations and a resulting algorithm for the care of TgAb-positive DTC patients.

Circulating Mucins and Cytokeratins in Aggressive Thyroid Cancers

Follicular cell-derived and medullary thyroid carcinomas constitute a biological continuum progressing from the highly curable well-differentiated forms to the rare aggressive and undifferentiated forms. A progressive dedifferentiation translates in a more aggressive tumor behavior and worse prognosis especially in patients with locally advanced or metastatic disease.

Thyroglobulin and Thyroglobulin Antibodies

Differentiated thyroid cancer (DTC) is the most common endocrine cancer, and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131 depending on post-operative risk stratification. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up of DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous thyrotropin (TSH) is suggested to detect occult disease with maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has been incorporated into more recent clinical guidelines; thus, the cornerstone in current guidelines for long-term follow-up is by measuring serum basal (i.e. unstimulated) Tg, and most patients can be followed by this method. However, some thyroid cancer patients have serum anti-thyroglobulin antibodies (TgAb), both at diagnosis and after treatment, when follow-up is started. As these antibodies interfere technically in the immunological methods measuring Tg, current guidelines cannot be implemented in the follow-up of TgAb-positive patients. However, many studies have indicated that following the concentration of TgAb in serum could serve as a “surrogate marker” for recurrence of the thyroid carcinoma. Additionally, in recent years, complementary laboratory methods such as Tg mini-recovery test and Tg measurement by tandem mass liquid spectrometry were proposed to overcome interferences when measuring Tg. The present chapter reviews the biological basis, advances and challenges in Tg and TgAb measurement techniques, as well as their impact on clinical management of DTC patients.

Radionuclide Imaging of Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumour originating from the neural crest-derived parafollicular C cells of the thyroid gland. This chapter describes the current diagnostic approach in patients with MTC. In particular the role of radionuclide imaging in recurrent MTC is emphasised.

Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis.

PURPOSE: Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours (NETs). on the other hand, only a few studies have evaluated the detection rate (DR) of this imaging method in recurrent medullary thyroid carcinoma (MTC). We aimed to perform a systematic review and a meta-analysis of the DR of somatostatin receptor PET or PET/CT in patients with recurrent MTC to add evidence-based data to this setting. METHODS: A comprehensive computer literature search of studies published in PubMed/MEDLINE and the Cochrane Library Database through may 2017 and regarding somatostatin receptor PET or PET/CT in patients with recurrent MTC was carried out. DR was determined on a per patient-basis. A sub-analysis considering serum calcitonin (Ctn) values was also performed. RESULTS: Nine studies on the diagnostic performance of somatostatin receptor PET or PET/CT in detecting recurrent MTC were discussed in the systematic review. The meta-analysis of these selected studies provided the following DR on a per patient-based analysis: 63.5% [95% confidence interval (95%CI): 49–77]. Heterogeneity among the selected studies was found. DR of somatostatin receptor PET or PET/CT increased in patients with higher serum Ctn levels (83% for Ctn >500 ng/L). CONCLUSIONS: In patients with recurrent MTC, somatostatin receptor PET or PET/CT demonstrated a non-optimal DR which increased in patients with higher serum Ctn values. The diagnostic performance of somatostatin receptor PET or PET/CT in recurrent MTC is lower compared to that of the same imaging method in the majority of NETs.

Nuclear Medicine Techniques

This chapter provides an introduction to nuclear medicine technique useful for evaluating head and neck endocrine diseases. Different radiotracers can be used for thyroid imaging and they can be classified in two groups: a) radiotracers describing the function of follicular cells and b) radiotracers mapping the proliferative activity of follicular cells. The first group includes technetium-99m-pertechnetate (99mTcO4–) and radioiodine; the second group includes Tc99m-methoxyisobutylisonitrile (99mTc-MIBI) and fluorodeoxyglucose (18F-FDG).

Anaplastic Carcinoma and Other Tumors

This chapter provides a brief summary on more rare thyroid tumors, including anaplastic thyroid carcinoma and thyroid lymphomas. Some diagnostic images of these thyroid tumors including ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography are discussed.

Atlas of Head and Neck Endocrine Disorders

This atlas draws on a multidisciplinary approach to provide a comprehensive overview on endocrine disorders of the head and neck, with particular emphasis on the role of imaging and image-guided procedures. The first section discusses the basic characteristics of the imaging methods and other techniques used for evaluation and diagnosis. The remainder of the book focuses on application of these methods in thyroid, parathyroid, and other endocrine disorders of the head and neck. The coverage is wide ranging, encompassing Graves’ disease, toxic multinodular goiter, toxic adenoma, thyroiditis, non-toxic goiter, benign nodules, and the different forms of thyroid carcinoma, as well as parathyroid adenoma, hyperplasia, and carcinoma and paragangliomas. Informative, high-quality images are provided by international experts in endocrine disorders, including endocrinologists, pathologists, radiologists, nuclear medicine physicians, and surgeons, who also discuss sample cases and provide syntheses of the relevant scientific literature.

Other Neuroendocrine Tumors of Head and Neck Region

The aim of this chapter is to introduce other neuroendocrine tumors (NETs) of the head and neck region beyond medullary thyroid carcinoma and paragangliomas. NETs of the head and neck are rare neoplasms and can be of epithelial or non-epithelial differentiation. Anatomical and functional imaging can be complementary for the diagnosis, staging, and monitoring of treatment response of these tumors. This chapter briefly describes the imaging methods used to evaluate these tumors and illustrates the imaging features of some NETs of the head and neck region.

Differentiated Thyroid Carcinoma

Differentiated thyroid cancer (DTC), arising from thyroid follicular epithelial cells, is the most common endocrine malignancy. DTC is characterized by low morbidity and mortality because its clinical course is generally indolent.