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.

Outline: •Author's profiles and motivation for this analysis•The philosophical alternatives in science and medicine•Reductionism vs. systems approach in clinical thyroid disease guidelines•The entry into complexity: the involvement of the musculoskeletal system•Integrating 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 disease•Importance of iron, zinc and magnesium in relation to thyroid function•Putting together new concepts related to thyroid function for a systems approach•Expanding our model into general aspects of medicine.

Fig. 1

Imaging of the thyroid in power Doppler mode in a case of newly diagnosed hyperthyroidism. The 2D image allows the examiner to recognize dispersed areas that correspond to vessels. The 3D image shows the complex continuous structure of vessels. This picture is associated with low CoQ10 values.

Fig. 2

Magnetic resonance Imaging of the right knee of a healthy subject. The arrow on a round marker shows the location of acupoint stomach 36 or Zu San Li. Technical details of the imaging procedure have been described before , .

Fig. 3

Two years of follow up in a case of hyperthyroidism. The initial images are on the top row. They show markedly diminished echogenicity together with hyperperfusion. The lower row shows the current images with recovered echogenicity and normal perfusion. Two different machines were used in this evaluation, Siemens Antares (upper row) and GE Logiq E9 (lower row).

Fig. 4

Two years of follow up in a case of hyperthyroidism. Vascular structures are depicted using 2D power Doppler mode. The improvement of thyroid texture and perfusion can be seen by comparing the upper and the lower row of images. All images were done using a GE LOGIQ E9 ultrasound machine in power Doppler modus.

Fig. 5

Time relation between fT4 and magnesium levels observed during 10 follow-up time points. At time point 7 increased stress at work and an infection preceded a relapse of hyperthyroidism. At this time magnesium levels showed a concomitant drop from 0.82 to 0.67 mmol/l. Following supplementation with 8.4 mmol elemental magnesium fT4 normalized and magnesium rose to 0.76 mmol/l.

Fig. 6

Shows a simple example of B mode sonography of the thyroid during follow up. The initial diffuse hypoechogenic pattern disappeared after 3 years of specific supplementation.

Fig. 7

Shows fibrotic changes of the thyroid. In this condition recovery of thyroid morphology is not achievable.

Fig. 8

The magnesium deficiency syndrome 2017 by Moncayo and Moncayo.

Fig. 9

Basic thyroid diagnostics.

Fig. 10

Integrated systems approach to thyroid function. Abbreviations used: SREBPs: sterol regulatory element binding proteins; Mg-ATP: magnesium ATP, NIS: natrium iodide symporter, TPO: thyroid peroxidase, DUOX: dual oxidases, GPX: glutathione peroxidases, Tg: thyroglobulin. CII–CIII: complex II and III of the mitochondrial respiratory chain.