Global view on the pathogenesis of benign thyroid disease based on historical, experimental, biochemical and genetic data, identifying the role of magnesium, selenium, coenzyme Q10 and iron in the context of the unfolded protein response and protein quality control of thyroglobulin

Abstract

We conducted a global review on the characteristics of benign thyroid disease beginning with the original clinical descriptions by Riedel, de Quervain and Hashimoto. A special section describes the attempts to fit human thyroid disease into animal models. The main emphasis is set on thyroglobulin including descriptions of isolation procedures and identification of molecular variations. The next element in this review describes the genetic knowledge about thyroglobulin synthesis and processing, showing that several mutations can result in a misfolded thyroglobulin molecule. This fact identifies the endoplasmic reticulum as a key element. Up to this point, thyroid disease still appears to be invincible. We proceeded to describe our own clinical experiences empirically aimed at improving mitochondrial function, i.e., ATP generation. We demonstrate several mechanisms, e.g., heat, stress and pregnancy, that can lead to an inflammatory thyroid condition. These changes can be reversed by supplementation with magnesium, selenium and coenzyme Q10. Finally, we reveal a functional relation between magnesium and anti-thyroglobulin antibody levels such that the antibodies disappear when magnesium levels normalize. We conclude that benign thyroid disease has the characteristics of an acquired mitochondrial dysfunction, which consequently compromises the function of the endoplasmic reticulum because of limited ATP supply. Altered thyroglobulin has the potential to change thyroid function on the basis of its autoregulatory thyroidal property. At the same time, it can be a stimulus for the production of anti-thyroglobulin antibodies. We propose a general applicability of this concept to beta-cell and ovarian function where compromised function of the endoplasmic reticulum can be expected.

Keywords

Thyroid diseases / thyroiditis / magnesium / selenium / coenzyme Q10 / power Doppler sonography / thyroglobulin

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