Stress, Thyroid Dysregulation, and Thyroid Cancer in Children and Adolescents: Proposed Impending Mechanisms

Abstract

Stress is a potential catalyst for thyroid dysregulation through cross-communication of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid (HPT) axes. Stress and stressors exposure motivates molecular mechanisms affecting compound feedback loops of the HPT axis. Whilst, there is evidence of connection between stress and thyroid dysregulation, the question whether this connection is implicated in the development of thyroid cancer (TC) remains unanswered. In view of the rising incidence of TC in both adults and children alongside the increasing stress in our modern society, there is a need to understand possible interrelations between stress, thyroid dysregulation and TC. Prolonged glucocorticoid secretion due to stress, interferes with immune system response by altering the cytokines, inducing low-grade chronic inflammation, and suppressing function of immune-protective cells. Chronic inflammation is a risk factor linked to TC. The role of autoimmunity has been a matter of controversy. However, there is epidemiological connection between autoimmune thyroid disease (AITD) and TC; patients with AITD show increased incidence in papillary thyroid carcinoma (PTC) and those with TC show a high prevalence of intrathyroidal lymphocyte infiltration and thyroid autoantibodies. Timing and duration dependent exposure to specific endocrine disrupting chemicals (EDCs) has an impact on thyroid development, function and proliferation leading to thyroid disease and potentially cancer. Thyroid hormone imbalance, chronic inflammation and EDCs are potential risk factors for oxidative stress. Oxygen free radicals are capable of causing DNA damage via stimulation of the mitogen activating protein (MAP) kinase or phosphatidylinositol-3-kinase (PI3K/Akt) and/or nuclear factor kB (NFkB) pathways resulting in TC-associated-gene mutations such as RET/PTC, AKAP9–BRAF, NTRK1, RAASF, PIK3CA, and PTEN. Stressful events during the critical periods of prenatal and early life can influence neuroendocrine regulation and induce epigenetic changes. Aberrant methylation of tumour suppressor genes such as P16INK4A, RASSF, PTEN is associated with PTC; histone H3 acetylation is shown to be higher in TC, and thyroid specific non-coding-RNAs are downregulated in PTC. This review focuses on the above proposed mechanisms that potentially lead to thyroid tumorigenesis with the aim to help in the development of novel prognostic and therapeutic strategies for TC.

Recent insights into the role of hormones during development and their functional regulation

“…Just as with GH supplementation, deficiencies of iodine are treated with iodine supplementation ( 29 ). Recent research into developmental thyroid disorders include uncovering potential mechanisms by which stress alters the hypothalamic-pituitary-thyroid (HPT) axis as a source of inflammation that leads to thyroid cancer ( 30 ).…”

Multidimensional Prediction Method for Thyroid Cancer Based on Spatiotemporally Imbalanced Distribution Data

“…However, both groups should pay more attention to their thyroid health if they have a family history of diabetes or hypertension, sleep too much or have an abnormal body mass index (BMI) [33], and increase the frequency of medical check-ups. The incidence of thyroid cancer is also due to the accumulation of bad habits over time, and many studies have shown an association between stress and the development of thyroid cancer [36], [37], [38]. Therefore, it is important to maintain a happy mood and an optimistic and positive attitude towards life and good lifestyle habits.…”

Pathogenesis of the crosstalk between reproductive function and stress in animals – part 2: Prolactin, thyroid, inflammation and oxidative stress

“…Thyroid system has also been largely involved in the immune dysregulation observed during chronic stressful conditions (Cremaschi et al, 2000). In addition, prolonged thyroid dysregulation during stress has been suggested to be linked to child and adolescent thyroid cancers, in particular through their effects on the immune system (Kyriacou et al, 2023). The mechanisms linking thyroid and immune functions are well-identified.…”