Iron deficiency is shown to significantly reduce T4 to T3 conversion, increase reverse T3 levels, and block the thermogenic (metabolism boosting) properties of thyroid hormone (238-242). Thus, iron deficiency, as indicated by an iron saturation below 25 or a ferritin below 70, will result in diminished intracellular T3 levels. Additionally, T4 should not be considered adequate thyroid replacement if iron deficiency is present (238,239,241,242).
Inflammation associated with common conditions
The inflammatory cytokines IL-1, Il-6, C-reactive protein (CRP), and TNF-alpha will significantly decrease D1 activity and reduce tissue T3 levels (105-113). Any person with an inflammatory condition — including physical or emotional stress (243-248), obesity (248-252), diabetes (248,249,253), depression (254-257), menopause (surgical or natural) (258), heart disease (248,259,260), autoimmune disease (lupus, Hashimoto’s, multiple sclerosis, arthritis, etc) (114,115,164,265), injury (266), chronic infection (261,262) or cancer (267-269) — will have a decreased T4 to T3 conversion in the body and a relative tissue hypothyroidism. The inflammatory cytokines will, however, increase the activity of D2 and suppress the TSH despite reduced peripheral T3 levels; again, making a normal TSH an unreliable indicator of normal tissue thyroid levels (105-113)
There is a direct inverse correlation between CRP and reduced tissue T3 (112,270), so individuals with elevated CRP (greater than 3 mg/l) or other inflammatory cytokines will have a significant reduction in cellular T3 levels. The suppression of intracellular T3 levels correlates with the degree of elevation of CRP, despite serum thyroid tests being “normal” (112,270). Thus, if any inflammation is present, which is found in numerous clinical and subclinical conditions (as above), the body will have lower cellular T3 levels that are often inadequate for optimal functioning; but the pituitary will have increased levels of T3, resulting in a lowering of the TSH that would potentially be inappropriately interpreted as an indication of “normal” thyroid levels.
My GP ignored my symptoms and didn't even inform me TSH was 7.5 then 8 for over 7 years. As not over 10, she wasn't bothered, but I understand that over 5 with symptoms should be offered help. But yes you would help the endocrinologist is knowledgeable enough not to need the print out. He was recommended on Louise's good NHS endo's list. They tried to make me see another endo (who has had bad feedback on this site) but I insisted on the good one.
Thank you, that is so informative. I have always been anaemic and now without a thyroid gland I imagine it is even more important to have optimum levels.
I've been using this website as a reference for the past few months. I think everyone should bookmark it as the information in it is invaluable. Thanks for posting it.
Sometimes, thyroid patients don’t even know where the inflammation exists in their body, except that their high ferritin reveals it, or their C-Reactive Protein or ESR (erythrocyte sedimentation rate or sed rate) lab tests reveal it. Other times, it’s obvious by the pain they notice in their bodies. .... Many thyroid patients take supplements to help lower that inflammation, which range from Astaxanthin to Ginger to NAC to Curcumin/Turmeric…and/or a combination of them all.
It has been well known and understood for years that inflammation is harmful. Inflammation essentially kills. .... To put it simply, inflammation causes undesirable reactions on the inner lining of blood vessels. The combination of inflammation and circulating lipids is a dangerous recipe that produces something called “foam cells”. Foam cells attach to the endothelial lining of our blood vessels, such as the arteries that feed our heart and brain, and once they mature over months to years form arterial plaques. These plaques narrow the blood vessels making it an eventual challenge for oxygen carrying blood cells to pass. ....
Chronic physiologic stress results in decreased D1 activity (11,12,13-17,234) and an increase in D3 activity (1,195,196), decreasing thyroid activity by converting T4 into reverse T3 instead of T3 (1,195,196,216,234). Conversely, D2 is stimulated, which results in increased T4 to T3 conversion in the pituitary and reduced production of TSH (11,16,18-22,234). The increased cortisol levels seen with stress also contribute to physiologic disconnect between the TSH and peripheral tissue T3 levels (16,18-20). This stress induced reduced tissue T3 level and increased reverse T3 results in tissue hypothyroidism and potential weight gain, fatigue, and depression (12,13,194,217-219).
***This vicious cycle of weight gain, fatigue, and depression that is associated with stress can be prevented with supplementation with timed-released T3 (25,26,52,121-124,199,201-215,220,221) but not T4 (52,197-199,201,222,223).*****
Great paper. Thanks for posting, feel better informed to see Endo. this week who ordered TSH & FT4 only ("within range", but they don't give the range). Have asked GP for FT3 test, Ferritin, B12, Folate, they refused.
Great site, Graves & Thyroid issues are really very confusing. Many thanks to everyone who posts their research on here & in giving their support to others.
Hi Silver pony, can't understand why GP would refuse you iron, Ferritin, B12, Folate, vit d test, if you have been experiencing fatigue as low ranges on these can explain fatigue symptoms. GP/lad only do FT3 when TSH over 10, or suppressed, ie under 1. Very odd that endo didn't order FT3 though. Perhaps he will after your appt? and you can ask him for the iron, Ferritin, B12, Folate, vit d test as well. You must get all blood tests in printed form (from GP and Endo) so you can see ranges and post up on here for advice.
Have you had your antibodies checked, again attain print out and post on here : )
Good morning & thank you for your kind reply. Am off to Endo today & feel a little more prepared. Will ask for the above tests & ranges which they have thus far refused to give. I fatigue very quickly after any activity & recovery is taking longer & longer. The muscle & bone pain is extraordinary, can't understand why. But the above paper goes some way in explaining that, so many thanks for the posting.
St Mary's & Imperial PCT (as was) are particularly stubborn about giving the ranges for their diagnostics tests to patients but have found some (not thyroid function) on their website after a lot of digging. But when & if I get them will post on here.
I did I have TP ab test in Oct & June 2014 & 9th Jan 2015 which were negative (down from 134 [<75 ] in July 14) & TSH receptor ab in July 2015; 4.0, Sept 2014; 3 .7 & most recently in October 2014;3.2 all above range of <0.4.
Endo won't test for TSH Abs again, don't know why.
May I ask, from your well informed perspective, do you feel it's good practice to base treatment on TSH & FT3 (the blood test Endo ordered)? Am in month 6 of 18 on carbimazole and have aged about 40 years in that time! Started on 20mg now down to 10mg & TSH wavering between 5.73 (high ) on 7.1.15 & 2.92 (normal) on 9.1.15. FT3 at 10. No ranges given on readout, will ask for them today but Imperial (that is both St Mary's, GP & blood lab) are very stubborn about not giving those ranges to patients. Might have to be more assertive or 'creative' on the the phone.
Sorry for the long message, but thank you very much again for your reply & all the effort you put into this site.
Hope you're enjoying good health. With much gratitude, Andrea
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T4 to T3 conversion ratio
T4 to T3 conversion troubles 
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