R – script

To be used after you have installed R and R-Studio

How hypothyroid can it be

I would like to know how hypothyroid the model can get when the different parameters from fig. 6. A in Principles, Hoermann et al 2022.

Recap text from fig. 6. A: FT4 levels (blue curve) decline, but the mechanisms in system (sys. 10) protect FT3 levels (green curve), keeping them in a range close to the original level, as the percentage of the estimate of FT4 production rate constant (k32 = 0.4 to 1.1) decreases – as typical at the onset of hypothyroidism in patients suffering from autoimmune thyroiditis and progressive thyroid destruction. Other parameters are chosen within ranges, k423 = 0.2-0.3, k43 = 0.7-0.8 and k42 = 0.1-0.2, to approximate the relative contributions to FT3 production according to (32).

The figures shows the most hypothyroid state the model can achieve under the given conditions.

Trying to change the k42 parameter which results in a slight decrease of TSH

Adding drug4 = 0.8 to the most hypothyroid state. We see FT3 is not returning to the level in the perfect homeostasis. See sys1 below. Apart from that FT3 drops with lower k32.

Here I have tried to show the pattern following perfect homeostasis plus drug4. Mimicing the situation where a patient gets unnecessary LT-4 treatment. Will it be possible to identify the pattern and use it to get the patient off LT-4? Is the pattern disguised by the transformation to real hormone values?

Scenarios – observations 1

Pilo (1) and Kobuta (2) are different scenarios and here we have looked into TSH, FT3 and FT4 from the Simthyr model.

Below you find the description of the Pilo scenarios (The Kubota scenarios will follow later in the text) – The last entry is the figures for the standard scenario in SimThyr:

Case No. 1 from Pilo et al. showing slight hyperdeiodination and high conversion rate
The FT3 value is 6,97 a little higher than the standard value (5,36)
The FT4 value is lower than the standard value (17,76) – Pilo 1 (13,72)
The TSH value is 1,36 and the standard value is 1,96
Pilo 1 GH < (lower than) standard. See the effect of GH here
Pilo 1 LS > (higher than) standard. See the effect of LS here
Pilo 1 SS > standard. See the effect of SS here
Pilo 1 GT < standard. See the effect of GT here
Pilo 1 GD1 > standard. See the effect of GD1 here
(Diagram)
Case No. 2 from Pilo et al. showing slight hyperdeiodination
The FT3 value is 9,13 a little higher than the standard value (5,36)
The FT4 value is lower than the standard value (17,76) – Pilo 2 (14,08)
The TSH value is 1,57 and the standard value is 1,96
Pilo 2 LS > standard. See the effect of LS here
Pilo 2 GT < standard. See the effect of GT here
Pilo 2 GD1 > standard. See the effect of GD1 here
(Diagram)
Case No. 6 from Pilo et al. with low secretion rate for T4
The FT3 value is 5,46 a little higher than the standard value (5,36)
The FT4 value is lower than the standard value (17,76) – Pilo 6 (11,84)
The TSH value is 1,70 and the standard value is 1,96
Pilo 6 LS > (higher than) standard. See the effect of LS here
Pilo 6 SS > standard. See the effect of SS here
Pilo 6 GT < standard. See the effect of GT here
Pilo 6 GD1 > standard. See the effect of GD1 here
(Diagram)
Case No. 11 from Pilo et al. with high secretion rate for T4
The FT3 value is 6,11 a little higher than the standard value (5,36)
The FT4 value is lower than the standard value (17,76) – Pilo 11 (11,84)
The TSH value is 1,23 and the standard value is 1,96
Pilo 11 GH < standard. See the effect of GH here
Pilo 11 dH < standard. See the effect of GH here
Pilo 11 LS > standard. See the effect of LS here
Pilo 11 SS > standard. See the effect of SS here
Pilo 11 GT < standard. See the effect of GT here
Pilo 11 GD1 > standard. See the effect of GD1 here
(Diagram)
Case No. 12 from Pilo et al. with high production rate for T3
The FT3 value is 6,64 a little higher than the standard value (5,36)
The FT4 value is lower than the standard value (17,76) – Pilo 12 (14,1)
The TSH value is 1,47 and the standard value is 1,96
Pilo 12 GH < standard. See the effect of GH here
Pilo 12 LS > standard. See the effect of LS here
Pilo 12 SS > standard. See the effect of SS here
Pilo 12 GT < standard. See the effect of GT here
Pilo 12 GD1 > standard. See the effect of GD1 here
(Diagram)
Case No. 14 from Pilo et al. with low production rate for T3 Coming soon
Case No. 10 from Pilo et al. with normal values for SPINA-GT and SPINA-GD
Case No. 1 from Kubota et al. showing latent (subclinical) hypothyroidism
Case No. 2 from Kubota et al. showing overt hypothyroidism
Case No. 5 from Kubota et al. showing overt hypothyroidism

Look hypophyseal secretory capacity (GH) up – LINK

  1. Pilo A, Iervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R. Thyroidal and peripheral production of 3,5,3′-triiodothyronine in humans by multicompartmental analysis. Am J Physiol. 1990 Apr;258(4 Pt 1):E715-26. PubMed PMID: 2333963.
  2. Kubota S, Fujiwara M, Hagiwara H, Tsujimoto N, Takata K, Kudo T, Nishihara E, Ito M, Amino N, Miyauchi A. Multiple thyroid cysts may be a cause of hypothyroidism in patients with relatively high iodine intake. Thyroid. 2010 Feb;20(2):205-8. doi: 10.1089/t