Applying a systems approach to thyroid physiology: Looking at the whole with a mitochondrial perspective instead of judging single TSH values or why we should know more about mitochondria to understand metabolism

Abstract

Classical thinking in endocrine physiology squeezes our diagnostic handling into a simple negative feedback mechanism with a controller and a controlled variable. In the case of the thyroid this is reduced to TSH and fT3 and fT4, respectively. The setting of this tight notion has no free space for any additions. In this paper we want to challenge this model of limited application by proposing a construct based on a systems approach departing from two basic considerations. In first place since the majority of cases of thyroid disease develop and appear during life it has to be considered as an acquired condition. In the second place, our experience with the reversibility of morphological changes makes the autoimmune theory inconsistent.While medical complexity can expand into the era of OMICS as well as into one where manipulations with the use of knock-outs and -ins are common in science, we have preferred to maintain a simple and practical approach. We will describe the interactions of iron, magnesium, zinc, selenium and coenzyme Q10 with the thyroid axis. The discourse will be then brought into the context of ovarian function, i.e. steroid hormone production. Finally the same elemental players will be presented in relation to the basic mitochondrial machinery that supports the endocrine.We propose that an intact mitochondrial function can guard the normal endocrine function of both the thyroid as well as of the ovarian axis. The basic elements required for this function appear to be magnesium and iron. In the case of the thyroid, magnesium-ATP acts in iodine uptake and the heme protein peroxidase in thyroid hormone synthesis. A similar biochemical process is found in steroid synthesis with cholesterol uptake being the initial energy-dependent step and later the heme protein ferredoxin 1 which is required for steroid synthesis. Magnesium plays a central role in determining the clinical picture associated with thyroid disease and is also involved in maintaining fertility. With the aid of 3D sonography patients needing selenium and/or coenzyme Q10 can be easily identified. By this we firmly believe that physicians should know more about basic biochemistry and the way it fits into mitochondrial function in order to understand metabolism. Contemplating only TSH is highly reductionistic.OutlineAuthor's profiles and motivation for this analysisThe philosophical alternatives in science and medicineReductionism vs. systems approach in clinical thyroid disease guidelinesThe entry into complexity: the involvement of the musculoskeletal systemIntegrating East and West: teachings from Chinese Medicine and from evidence based medicine (EBM)Can a mathematical model represent complexity in the daily thyroid practice?How effective is thyroxine treatment?Resolving the situation of residual symptoms in treated patients with thyroid diseaseImportance of iron, zinc and magnesium in relation to thyroid functionPutting together new concepts related to thyroid function for a systems approachExpanding our model into general aspects of ...

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

“…Our clinical work on benign thyroid diseases over the past 15 years has avoided inaction by introducing an advanced ultrasound methodology with 3D power Doppler imaging [7] and has gone through a stepby-step inclusion of additional laboratory parameters related to the new aspects found in sonography [8] . Power Doppler examination has allowed us to characterize an inflammatory condition common to subacute thyroiditis, hypothyroidism or hyperthyroidism related to a compound deficiency state affecting magnesium, coenzyme Q 10 (CoQ 10 ) and selenium levels.…”

“…Our observational research results have allowed us to propose a model of acquired mitochondrial dysfunction as the central event in thyroid disease. Consequently, we designed a therapy concept aimed at clinical improvement of mitochondrial function [8,9] . This therapy can reverse the hypo-echogenic changes of the thyroid and also correct the inflammatory hyperperfusion of the gland [10] .…”

“…To provide relief, we will present our approach to diagnosing and treating thyroid disease based on our WOMED model of benign thyroid disease [8,9] .…”

“…Within a time period of 1-2 years, normalization of parenchymal and perfusion changes can be seen [9,10] . The following Figure 10 shows our practical clinical approach [7][8][9][10] as compared to the classical description made by Hashimoto [14] .…”

The interaction between lipid exchange and thyroid status in the conditions of prolonged influence of small doses of radiation

“…Селективні модулятори TRβ-рецепторів також беруть участь у зворотному транспорті холестерину та можуть знизити рівень холестерину в сироватці крові, незалежно від рецепторів до ліпопротеїнів низької щільності, за рахунок збільшення синтезу жовчних кислот у печінці (Kan-nisto et al, 2014;Lindemann et al, 2014). Вагому роль у зв'язку ліпідного обміну та тиреоїдного статусу відіграють певні хімічні елементи, зокрема, магній і залізо (Moncayo and Moncayo, 2017). Клінічні стани, пов'язані з дисрегуляцією метаболізму ліпідів у печінці, зокрема, неалкогольні жирові хвороби печінки та цукровий діабет ІІ типу, можуть зумовлюватися змінами внутрішньоклітинної дії тиреоїдних гормонів, особливо за вираженого гіпотиреозу (Sinha et al, 2014;van den Berg et al, 2016).…”