Thyroid Hormone Requires Iron, Cortisol, Selenium, Iodine

Iron Deficiency Anemia

Low iron, or more specifically, low ferritin, is one of the most overlooked causes of low thyroid function. [1]  Ferritin is the stored form of iron that is used by the cells and a better measure of available iron levels than serum iron.  Iron is a component of multiple enzymes involved with cellular metabolism, so low iron means poorly functioning enzymes, and less than optimal metabolism.  Those with low iron also have low T4 and even lower T3 levels. [12]  Iron deficiency also lowers thyroid peroxidase (TPO) activity.  TPO is an iron-containing enzyme that initiates the first two steps in thyroid hormone synthesis. [2]

Low ferritin can cause negative reactions like palpitations, nervousness, and anxiety in someone starting thyroid hormone replacement.  Someone described it like being shot out of a cannon.  It is therefore imperative that ferritin not be at the bottom of the range before starting thyroid hormone medication. [3]  The following are just a few reasons why someone’s ferritin could be low:

  • poor gut absorption of iron from celiac disease (another autoimmune disease)
  • the use of antacids (acid is necessary to digest foods) [4]
  • poor gut absorption from low digestive acids/enzymes due to hypothyroidism [5]
  • not eating enough red meat
  • being vegetarian
  • excessive blood loss from heavy periods, another hypothyroid symptom
  • donating blood too frequently (more than 3x/year) [22]
  • intestinal bleeding from something as simple as too much aspirin, or something as serious as colon cancer.

Hereditary hemochromatosis (HH) is a genetic disorder that can cause the body to retain excess iron.  This can damage organs like the heart, thyroid, testes, etc.  It is possible to have low ferritin with this disease, so a full iron panel should be run to rule it out.  Iron supplementation would obviously be contraindicated with hemochromatosis.  If one does not have hemochromatosis, consumption of high iron foods such as red meat, the elimination of gluten from one’s diet for a trial period, or probiotics/yogurt to restore gut health may help raise ferritin levels.  A non-constipating supplement form of iron, ferrous bisglycinate, is highly recommended by several forums.  Liver pills are another option.  Iron infusions have some serious drawbacks that one should be aware of, including fatal allergic reactions. [6]

Iron Deficiency Anemia (IDA) vs. Anemia of Chronic Disease (ACD)

Iron deficiency anemia should be verified with blood tests before anyone supplements iron.  Because iron is used by bacteria and cancer cells for their growth, it is imperative that one have a full iron panel to rule out something called anemia of chronic disease, which can also cause a low serum iron reading, low transferrin saturation percent, and low hemoglobin. [19]  Supplementing iron in this case amounts to feeding the pathogens, which is not a good idea.  It also defeats the body’s protective mechanism of limiting available iron when pathogens are present.  The body is purposely shunting available iron to ferritin to get it out of circulation and out of the pathogens’ reach. [21]

Iron deficient patients will have low hemoglobin/hematocrit, low ferritin, low iron, low transferrin iron saturation percent, low MCH [20], and high total iron binding capacity (TIBC).[19]  A good chart that compares Iron Deficiency Anemia (IDA) with Anemia of Chronic Disease (ACD) is available from

Ferritin levels can rise when infection, inflammation, or cancer is present, appearing normal or high in a state of iron deficiency.  Because someone can have both Iron Deficiency Anemia and Anemia of Chronic Disease simultaneously, multiple tests are looked at to confirm a diagnosis.  An elevated CRP is a marker of inflammation [20], and would be another diagnostic for Anemia of Chronic Disease.  In Anemia of Chronic Disease, there will be a slight drop in hemoglobin to low normal levels, along with a normal or high ferritin. Serum iron and transferrin saturation percent will also be low. Total iron binding capacity (TIBC) is low in Anemia of Chronic Disease because even though there are ample iron stores, they are not easily mobilized. [19]

Iron Deficiency Anemia, once confirmed, should be treated by supplementing iron.  On the other hand, iron should not be supplemented in Anemia of Chronic Disease, but the underlying condition should be addressed.  This can be as benign as a urinary tract infection, a head or chest cold, mononucleosis, tonsillitis or strep, stomach or intestinal flu, and bacterial infections such as H. pylori.  But Anemia of Chronic Disease can also indicate something more serious such as kidney disease, hepatitis, tumors, or cancer, so it should be investigated. [19]

If iron lab results don’t point to Iron Deficiency Anemia or Anemia of Chronic Disease but still seem unusual, further research into unusual iron disorders might be warranted.  Apparently iron overload or anemia is a consequence of certain disease states, and managing the disease state can positively impact the iron dysfunction.  Some are mentioned here, and a visit with a hematologist for further testing might not be out of order.


Cortisol levels must be sufficient for someone to tolerate thyroid hormone.  Flat-lined cortisol levels (found in Addison’s disease) require supplemental hydrocortisone before thyroid can be taken, or symptoms as severe as vomiting (that requires hospitalization) can occur. [7,8]  For others who are low, but not flat-lined, supporting the adrenals and raising very slowly has often worked.  Thyroid and corticosteroid binding globulin (CBG) have an inverse relationship, so as thyroid is raised, CBG goes down, leaving more cortisol free.  Thyroid and cortisol levels usually rise and fall in tandem. [9]

Other Cofactors

Iodine, iron, selenium, zinc, and Vitamin A are all essential for normal thyroid hormone metabolism [12,13,14], and can be obtained from diet or daily multi-vitamins.  Iron works in conjunction with iodine and has reduced goiters in those who were anemic, when iodine alone did not work.[14]  Selenium is a component of the deiodinase enzymes that convert T4 to T3.  It also protects the thyroid gland from damage by excessive iodide exposure. [14]  Zinc appears to be involved in thyroid conversion and a deficiency correlates with reverse T3 production. [10,11,14,15]  But zinc should not be supplemented without the guidance of a nutritionist or physician, because a balance needs to be maintained between zinc and copper.  People in the autistic spectrum tend to be low in zinc and high in copper.  But if one is not autistic, supplementing zinc without copper can create a copper deficiency, and create unintended side effects. [16,17]

One hypothesis is that the standard American diet (high in carbs and low in protein) contributes to a deficiency of essential nutrients such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune function and autoimmunity.  These nutrients, along with methionine, cysteine, and arginine (amino acids obtained from protein in the diet), are necessary for the synthesis and maintenance of sufficient amounts of glutathione, nitrogen monoxide, and metallothionein (a storage molecule for metal ions such as zinc and copper), which help regulate immune responses to antigens. [18]


Recommended Labwork


  1. Junta Takamatsu, Motoko Majima, Kyoko Miki, Kanji Kuma And Toshiji Mozai. Serum Ferritin as a Marker of Thyroid Hormone Action on Peripheral Tissues. The Journal of Clinical Endocrinology & Metabolism Vol. 61, No. 4 672-676, 1985.
  2. Sonja Y. Hess, Michael B. Zimmermann, Myrtha Arnold, Wolfgang Langhans and Richard F. Hurrell. Iron Deficiency Anemia Reduces Thyroid Peroxidase Activity in Rats.  The Journal of Nutrition. July 1, 2002,vol. 132,no. 7,1951-1955.
  3. K M Shakir, D Turton, B S Aprill, A J Drake, 3rd and J F Eisold. Anemia: a cause of intolerance to thyroxine sodium.  Mayo Clinic Proceedings. February 2000vol. 75no. 2189-192.  Available from:
  4. Jason W. Harper, Stephen F. Holleran, Rajasehkar Ramakrishnan, Govind Bhagat, Peter H.R. Green. Anemia in celiac disease is multifactorial in etiology. American Journal of Hematology.  Volume 82, Issue 11, pages 996–1000, November 2007.
  5. Madeleine J Ball and Melinda A Bartlett. Dietary intake and iron status of Australian vegetarian women.  American Journal of Clinical Nutrition, Vol. 70, No. 3, 353-358, September 1999.
  6. Steven Fishbane. Safety in Iron Management.  Am J Kidney Dis 41(S5):S18-S26, 2003.
  7. Jonathan Stephen Murray,Rubaraj Jayarajasingh,Petros Perros. Deterioration of symptoms after start of thyroid hormone replacement.  BMJ 2001;323:332.
  8. I A Osman, Peter Leslie. Adrenal insufficiency should be excluded before thyroxine replacement is started (Letter to the Editor).  BMJ Volume 313, 17August 1996.
  9. Sonia C Dumoulin, Bertrand P Perret, Antoine P Bennet and Philippe J Caron. Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans. European Journal of Endocrinology, Vol 132, Issue 5, 594-598, 1995.
  10. S. Nishiyama, Y. Futagoishi-Suginohara, M. Matsukura, T. Nakamura, A. Higashi, M. Shinohara and I. Matsuda. Zinc supplementation alters thyroid hormone metabolism in disabled patients with zinc deficiency.  Journal of the American College of Nutrition, Vol 13, Issue 1 62-67, 1994.
  11. Christy Maxwell, Stella Lucia Volpe. Effect of Zinc Supplementation on Thyroid Hormone Function A Case Study of Two College Females.  Ann Nutr Metab 2007;51:188-194.
  12. Triggiani V, Tafaro E, Giagulli VA, Sabbà C, Resta F, Licchelli B, Guastamacchia E. Role of iodine, selenium and other micronutrients in thyroid function and disorders.  Endocrine Metabbolic & Immune Disorders Drug Targets. 2009 Sep;9(3):277-94.
  13. Zhang XK, Pfahl M. Hetero- and homodimeric receptors in thyroid hormone and vitamin A action.  Receptor. 1993 Fall;3(3):183-91.
  14. Michael B. Zimmermann, Josef Köhrle. The Impact of Iron and Selenium Deficiencies on Iodine and Thyroid Metabolism: Biochemistry and Relevance to Public Health. Thyroid. October 2002, 12(10): 867-878.
  15. Fujimoto S, Indo Y, Higashi A, Matsuda I, Kashiwabara N, Nakashima I. Conversion of thyroxine into tri-iodothyronine in zinc deficient rat liver. J Pediatr Gastroenterol Nutr. 1986 Sep-Oct;5(5):799-805.
  16. Hoogenraad TU, Dekker AW, van den Hamer CJ. Copper responsive anemia, induced by oral zinc therapy in a patient with acrodermatitis enteropathica.  Sci Total Environ. 1985 Mar 15;42(1-2):37-43.
  17. Hoffman HN 2nd, Phyliky RL, Fleming CR. Zinc-induced copper deficiency. Gastroenterology. 1988 Feb;94(2):508-12.
  18. J.E. Sprietsma. Modern diets and diseases: NO–zinc balance.  Medical Hypotheses.  Volume 53,Issue 1, Pages 6-16 (July 1999).
  19. Iron Disorders Institute, Anemia of Chronic Disease,
  20. Manuel Munoz, Jose Antonia Garcia-Erce, Angel Francisco Remacha. Disorders of Iron Metabolism. Part II:  iron deficiency and iron overload.  Journal of Clinical pathology Online First, Dec 20, 2010.
  21. Fredric M. Pieracci and Philip S. Barie. Iron and the Risk of Infection. Surgical Infections. June 2005, 6(s1): s41-s46.
  22. Brittenham, G. M., Iron deficiency in whole blood donors. Transfusion, 51: 458–461. March 2011.