Papillary Thyroid Carcinoma Intertwined with Hashimoto’s Thyroiditis: An Intriguing Correlation

Abstract

Illustrating the ancient link connecting inflammation with cancer, the correlation of papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT) has long been pursued as intersection of autoimmunity-induced chronic inflammation and tumor-induced immunity. The dramatic rise of the incidence of PTC οver the last decades-the main culprit for "thyroid cancer (TC) epidemic"-parallels the increasing incidence of HT, potentially reflecting a pathogenetic link that could be harnessed in diagnostics and therapeutics. Prompted by this perspective, in the present chapter, we dissect the hitherto elusive interrelationship of PTC with HT, focusing on four issues: firstly, an unresolved conundrum is whether PTC emerges due to or notwithstanding immune response or mirrors the "tumor defense-induced autoimmunity." Secondly, the interrelationship of HT with PTC may be merely epiphenomenon of selection bias inherent in thyroidectomy series. Thirdly, the impact of HT on coexistent PTC is equivocal-host protective versus tumor protective. Fourthly, translating serum concentrations of thyroid autoantibodies and thyroidstimulating hormone (TSH) into predictive and prognostic PTC biomarkers dichotomizes, till now, the researchers. In the era of precision medicine, illuminating whether HT precipitates PTC or vice versa is awaited with anticipation in order to refine the preventive and therapeutic policy counteracting "TC epidemic."

Spectrum of thyroid disease in a single patient: A case of papillary thyroid carcinoma in a patient with Graves' disease and Hashimoto's thyroiditis

“…This represents the shortest reported time interval in current literature regarding transformation from hypothyroidism to hyperthyroidism. In addition, this patient was incidentally diagnosed with papillary thyroid carcinoma following thyroidectomy, which provides further evidence to suggest papillary thyroid carcinoma may be associated with Hashimoto's thyroiditis and Graves' disease 17,21–23 . This case depicts the unique spectrum of thyroid disease in a single patient: conversion of hypothyroidism to hyperthyroidism and presence of papillary thyroid carcinoma, all in the same gland.…”

“…In addition, this patient was incidentally diagnosed with papillary thyroid carcinoma following thyroidectomy, which provides further evidence to suggest papillary thyroid carcinoma may be associated with Hashimoto's thyroiditis and Graves' disease. 17,[21][22][23] This case depicts the unique spectrum of thyroid disease in a single patient: conversion of hypothyroidism to hyperthyroidism and presence of papillary thyroid carcinoma, all in the same gland. Future studies investigating this distinct conversion can provide further insight into the association between autoimmune thyroid disease and thyroid malignancy…”

Charting the Unknown Association of COVID-19 with Thyroid Cancer, Focusing on Differentiated Thyroid Cancer: A Call for Caution

“…Third, the hypothalamus–pituitary–thyroid axis is a well-documented target of SARS-CoV-2 [ 65 ], and of the related cytokine storm, resulting in a wide spectrum alterations to thyroid function [ 66 ]. Fourth, the long-pursued, yet not clarified, inflammatory and immunological background of DTC, discussed by two of the authors of this review (M.V.D, D.T.T) elsewhere [ 67 ], can interact with the immune-inflammatory reactions triggered by SARS-CoV-2 [ 68 ]. Fifth, there are convincing data sustaining the critical role of oxidative stress—a key player of COVID-19—in DTC, namely: (i) the exposure of follicular thyroid cells to a great amount of H 2 O 2 (a landmark member of non-radical ROS), which is essential for synthesis of thyroid hormones; (ii) the detection of oxidative stress and DNA damage across the continuum of thyroid carcinogenesis from thyroid adenomas to advanced stages of thyroid cancer; and (iii) the upregulation of two main ROS-generating systems, the NADPH oxidases DUOX1 and NOX4, by ionizing radiation and mutated oncogenes RAS and BRAF—the most well-described carcinogenic factors for DTC [ 62 ].…”