iThyroid.com

Iron is a very critical mineral for persons with thyroid disease.  There is a high association between hyperthyroidism and anemia and while most of those cases of anemia are from copper deficiency, it is possible that some of them are from iron deficiency.  

Many hypos also seem anemic and it's possible that in hypothyroidism, anemia stems more often from iron deficiency than from copper deficiency.

The balance of the three minerals, copper, zinc, and iron, is critically important in preventing and correcting thyroid diseases.  Each of these three minerals antagonizes and can deplete the other two.  Many times the antagonistic and depletion effects are not due to competition in absorption, but because these minerals work together.  

We can think of these three minerals as corners of a triangle.  Each one affects the other two.  If any one of the three is ingested in large amounts it depletes the other two.  Likewise if one of the three gets deficient, then the other two may not be utilized and therefore build up in the liver, hair, or other tissues.

For example, if zinc gets too high in the body, copper and iron will get depleted with the result of anemia and (probably) hyperthyroidism.  If two of the three minerals are high, then the third mineral will get very depleted.  For example, high intake of both iron and copper could deplete zinc and cause hypothyroidism.

An interesting pair to look at is copper and iron.  Copper and iron work together to form hemoglobin, the oxygen-carrying molecule in the red blood cell.  The two minerals have to be present is a balanced amount, usually about 5:1, and if one of the two is supplied in higher amounts it can cause the other to be depleted.  

We see this when people take large amounts of iron to correct anemia.  Anemia can be caused by iron deficiency or copper deficiency (or B-12 or other vitamin deficiencies), but most people and doctors assume that anemia is always caused by iron deficiency.

Taking large amounts of iron when it is copper that is deficient will cause copper to be further depleted and lead to a worsening of the anemia.  I believe this is one practice that can lead to hyperthyroidism. It's possible that the addition of  nutritional supplements like iron to foods may also contribute to thyroid disease. For example, iron is added to many food products, especially breakfast cereals, breads, and other grain products. We know that excess iron will deplete copper, so it's possible that eating iron fortified foods is a contributing factor to hyperthyroidism. 

If one of the pair gets deficient then the other will not be able to be used effectively and will build up in the liver or other tissues. For example, if iron gets deficient, then copper may build up in the liver, hair, and appear as rings or spots in the iris of the eyes.  These accumulations of copper occur in Wilson's Disease, a disease which is described as a hereditary disease of copper buildup.  Whether Wilson's disease is caused by iron or zinc deficiencies is unknown but many Wilson's patients take zinc to keep copper levels low (often along with a copper chelator).

There is one subset of hyperthyroids who have high copper levels in the hair and presumably also have high copper accumulations in the liver.  These people often manifest schizophrenic or manic-depressive symptoms.  In fact one of the characteristics of these psychiatric symptoms is high copper levels which can be detected in the hair.  Also these conditions are highly associated with hyperthyroidism.  

One of the hypotheses that I'm working on is that this subset of hyperthyroidism, where the person has high copper levels, may be caused by iron deficiency, with a "functional" copper deficiency caused because the lack of iron is preventing the copper that is present from being effectively used.  I don't think zinc is deficient in these people because if that were true, the person would probably be hypothyroid.

What happens when copper and zinc are high and iron gets depleted?  I can tell you from personal experience that bad things happen.  I just went through this through a serious oversight on my part and my failure to supplement iron along with copper and zinc.  I'd like to relate the story so that others don't have to go through the same problems. Here's what happened:

At Christmas time I got the flu and it was quite severe.  To mitigate the symptoms and hopefully get over it, I did what I tell people not to do:  I stopped taking iron, because viruses and bacteria need iron to live, just as we do.  This is an effective but unwise strategy for stopping a cold or flu.  Many people do this inadvertently when they stop eating red meat and then go for years without getting sick.  They think they have become very healthy because they are no longer getting sick, but what they've actually done is make their body so depleted in iron and copper that even viruses can't live there.  They usually go along happily until they get hyperthyroidism.  I've done this very thing.

When I stopped taking iron, I started developing pains in my abdomen that concentrated on the left side (left side pain that some people have reported?).  The pains migrated around my left side, sometimes higher, sometimes lower, sometimes in the front and sometimes in the back.  They seemed to be pains in the liver, pancreas, and kidneys.  In addition, I had pains in the ribs, mostly in the left side but sometimes in the right side, which seemed to be caused by calcium deficiency, but yet calcium or magnesium didn't correct the problem.  On top of all this I couldn't sleep well and started getting nighttime rapid heart beat.

These pains got worse and worse over the following months and on the occasions when I did try iron, I had negative symptoms immediately afterward.  However, after I started looking at iron, I discovered that the following day is when I got the benefits, while at the time I was concentrating on the immediate negative effects.

I tried just about every combination of vitamins and minerals except taking iron but could not figure out what was wrong. I  fasted, went on raw foods, and tried a vegetable only diet.  Nothing helped.  Also I noticed that every high copper food was making it worse.  Nuts, beans, chocolate, and beer increased the symptoms so I discontinued them. 

I finally got a critical clue when I went to the mountains snowboarding.  I got out of breath frequently and it reminded me of years ago when I was anemic.  In fact I was anemic.  Then I started getting dizzy and feeling I might faint.  The clues were hitting me in the head, but for some reason I was not paying attention.  I think it's because I'm male and males are not supposed to need iron like females.  What I didn't take into consideration was that I was supplementing copper, about 5 mgs. per day.

A couple days after returning from the mountains, I had a dream that all my relatives were coming to visit me because I was dying.  As you can imagine that is a disturbing dream! That morning I got up and the inspiration came to me to take iron.  Within one hour of taking 25 mgs. I started feeling better, so I took another 25 mgs.  I continued to improve so I took another 50 mgs.  

By that night 50% of my symptoms were gone.  I slept through the whole night without waking once, which hadn't happened in many months.  After another day of taking 100 mgs. of iron, 75% of my symptoms were gone and I again slept the whole night without waking.  I was back to life.

This was a good lesson for me.  I recalled that through the last 20 years whenever I have serious, chronic health problems they always turn out to be mineral deficiencies.  I always think I have some vitamin deficiency or feel like I'm being poisoned. 

 I would try all different kinds of vitamins, fast, eat raw foods, eat only vegetables, eat only potatoes, etc. trying to find the answer.  Then after months of getting worse despite all my efforts I would discover it's a mineral deficiency.  I would take the mineral, feel much better in only a few hours, and then recover completely over the next couple weeks. It's taken me a very long time to learn this lesson.  

Minerals are the key to health and just about every disease is the result of mineral deficiencies.  When you take the right mineral, you might feel better in hours or you might feel worse immediately.  However, usually within the next day or two you feel significantly better.  It always amazes me how fast health returns once the right nutrient is supplied to the body.  When we have a mineral deficiency we deteriorate slowly, but when it is corrected, we improve very fast.  Underneath our sickness is a body crying for nutrients!

ABSORBING IRON

Getting enough iron is difficult for many people. This is probably why iron deficiency is still the number one nutritional deficiency world-wide.

Iron absorption from foods is very limited. The Nutrition Almanac states that only 2 to 10% of the iron in beans, fruits, and vegetables is absorbed. Animal sources of iron are better absorbed. While the body can use several forms of iron, such as ferric or ferrous iron (ferrous is better), the best form is heme iron. Actually heme iron makes other forms of iron more absorbable, so it's probably best to take an iron supplement with a meal of red meat.

Some things can interfere with iron absorption. Lack of hydrochloric acid in the stomach is a big reason. Person on a low salt diet might not be getting enough chlorine (the Cl in NaCl) and therefore not able to produce enough HCl. Taking a good digestive enzyme with the iron supplement should assist the absorption.

Too high an alkaline diet might interfere since iron needs an acid environment. Eat more acid foods with your iron. Too much roughage in the diet can speed up intestinal transit time and reduce iron absorption. Too much coffee, tea, phytates (from grains), oxalates (spinach, rhubarb), and phosphates can all interfere with iron absorption.

There are nutrients which need to be present for iron absorption: B-12 (try a high potency, 3000 mcg); folic acid (400-800 mcg); vitamin C (1000 mgs); vitamin A; copper; calcium; manganese; molybdenum; and other of the B complex vitamins.

Excessive intake of vitamin E and zinc can interfere with iron absorption. Vitamin E in amounts like 800-1000 IU per day can cause iron deficiency (causing ear aches). Don't take more zinc than iron, since that can also deplete iron.

If all else fails, you might want to experiment with different levels of the B vitamins. It may be that you need more B vitamins and need to get up the the 200 mgs per day quantity. However, I'd try the other things first.

IRON STUDIES

Hemochromatosis is a disease of iron accumulation with resultant damage to the liver, pancreas, heart, and pituitary.  Premenopausal women are protected from getting it because of menstrual blood loss.  While many people believe it is a hereditary disease, I believe it is a disease of copper deficiency.   When copper gets deficient, the body can't use iron so it accumulates and causes damage.  The disease is also called siderosis, which is characterized by a gray pallor to the skin from iron accumulation in the tissue.

The first study concludes "The frequency of thyroid disorders in men with hemochromatosis is about 80 times that of men in the general population."  What this means is that when men get copper deficient, they get iron accumulation and thyroid disorders.

I've also seen information that links hemochromatosis to a deficiency of selenium and copper.

Title
    Thyroid disease in hemochromatosis. Increased incidence in homozygous men.

Author
    Edwards CQ; Kelly TM; Ellwein G; Kushner JP

Source

Arch Intern Med, 143(10):1890-3 1983 Oct

Abstract

The following study indicates that iron helps to reduce goiter size. This is excellent evidence that iron is critical for thyroid function and that iron-deficiency anemia is often an important factor in causing hypothyroidism.

Eur J Endocrinol 2000 Mar;142(3):217-223

Iron supplementation in goitrous, iron-deficient children improves their response to oral iodized oil.

Zimmermann M, Adou P, Torresani T, Zeder C, Hurrell R.

Human Nutrition Laboratory, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland. michael.zimmermann@ilw.agrl.ethz.ch

OBJECTIVE: In developing countries, many children are at high risk for both goiter and iron-deficiency anemia. Because iron deficiency may impair thyroid metabolism, the aim of this study was to determine if iron supplementation improves the response to oral iodine in goitrous, iron-deficient anemic children. DESIGN: A trial of oral iodized oil followed by oral iron supplementation in an area of endemic goiter in the western Ivory Coast. METHODS: Goitrous, iodine-deficient children (aged 6-12 years; n=109) were divided into two groups: Group 1 consisted of goitrous children who were not anemic; Group 2 consisted of goitrous children who were iron-deficient anemic. Both groups were given 200mg oral iodine as iodized oil. Thyroid gland volume using ultrasound, urinary iodine concentration (UI), serum thyroxine (T(4)) and whole blood TSH were measured at baseline, and at 1, 5, 10, 15 and 30 weeks post intervention. Beginning at 30 weeks, the anemic group was given 60mg oral iron as ferrous sulfate four times/week for 12 weeks. At 50 and 65 weeks after oral iodine (8 and 23 weeks after completing iron supplementation), UI, TSH, T(4) and thyroid volume were remeasured. RESULTS: The prevalence of goiter at 30 weeks after oral iodine in Groups 1 and 2 was 12% and 64% respectively. Mean percent change in thyroid volume compared with baseline at 30 weeks in Groups 1 and 2 was -45.1% and -21.8% respectively (P<0.001 between groups). After iron supplementation in Group 2, there was a further decrease in mean thyroid volume from baseline in the anemic children (-34.8% and -38.4% at 50 and 65 weeks) and goiter prevalence fell to 31% and 20% at 50 and 65 weeks. CONCLUSION: Iron supplementation may improve the efficacy of oral iodized oil in goitrous children with iron-deficiency anemia.

[Changes in brain monoamine neurotransmitter in iron deficiency nonanemic rats].

[Article in Chinese]

Hu R, Wei M, Ding X

Iron, thermoregulation, and metabolic rate.

Rosenzweig PH, Volpe SL

 

Redox Rep 1999;4(5):243-50

Derangement of Kupffer cell functioning and hepatotoxicity in hyperthyroid rats subjected to acute iron overload.

Boisier X, Schon M, Sepulveda A, Basualdo A, Cornejo P, Bosco C, Carrion Y, Galleano M, Tapia G, Puntarulo S, Fernandez V, Videla LA

Programas de Farmacologia Molecular y Clinica, Facultad de Medicina, Universidad de Chile, Santiago.

[Medline record in process]

Liver oxidative stress, Kupffer cell functioning, and cell injury were studied in control rats and in animals subjected to L-3,3',5-tri-iodothyronine (T3) and/or acute iron overload. Thyroid calorigenesis with increased rates of hepatic O2 uptake was not altered by iron treatment, whereas iron enhanced serum and liver iron levels independently of T3. Liver thiobarbituric acid reactants formation increased by 5.8-, 5.7-, or 11.0-fold by T3, iron, or their combined treatment, respectively. Iron enhanced the content of protein carbonyls independently of T3 administration, whereas glutathione levels decreased in T3- and iron-treated rats (54%) and in T3Fe-treated animals (71%). Colloidal carbon infusion into perfused livers elicited a 109% and 68% increase in O2 uptake in T3 and iron-treated rats over controls. This parameter was decreased (78%) by the joint T3Fe administration and abolished by gadolinium chloride (GdCl3) pretreatment in all experimental groups. Hyperthyroidism and iron overload did not modify the sinusoidal efflux of lactate dehydrogenase, whereas T3Fe-treated rats exhibited a 35-fold increase over control values, with a 54% reduction by GdCl3 pretreatment. Histological studies showed a slight increase in the number or size of Kupffer cells in hyperthyroid rats or in iron overloaded animals, respectively. Kupffer cell hypertrophy and hyperplasia with presence of inflammatory cells and increased hepatic myeloperoxidase activity were found in T3Fe-treated rats. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of iron, which seems to be related to the development of a severe oxidative stress status in the tissue, thus contributing to the concomitant liver injury and impairment of Kupffer cell phagocytosis and particle-induced respiratory burst activity.

PMID: 10731099, UI: 20193365

 

 

 

: J Basic Clin Physiol Pharmacol 1999;10(4):315-25

Evaluation of antioxidant status in liver tissues: effect of iron supplementation in experimental hyperthyroidism.

Seymen HO, Seven A, Civelek S, Yigit G, Hatemi H, Burcak G

Department of Physiology, Cerrahpasa Medical Faculty, Istanbul University, Turkey. seymano@yahoo.com

The antioxidant defense system in liver tissue in experimental hyperthyroidism and/or in iron supplementation was investigated. Thyroid hormones (T3, T4, TSH), ferritin (marker of iron status), antioxidant status components (glutathione [GSH], glutathione peroxidase [GSH-Px], superoxide dismutase [SOD]), and serum transaminases (GOT and GPT, both of which are known to be released from damaged hepatocytes), were measured. Hyperthyroidism in rats, induced by L-thyroxine administration, significantly raised SOD activity (p < 0.05), but significantly decreased GSH-Px activity and GSH values (p < 0.001) in the liver. In the L-thyroxine administered and iron supplemented (TI) group, GSH and GSH-Px values of liver tissues were significantly lower than those of control rats (p < 0.05). GSH-Px levels of the TI group were higher (p < 0.001), and SOD levels significantly lower (p < 0.001) than those of the L-thyroxine administered group. We conclude that hyperthyroidism induces SOD activity in liver; ferritin levels increase in hyperthyroidism, contributing to the antioxidant defense system; GSH-Px and GSH levels are decreased significantly in hyperthyroidism either due to inactivation due to increased oxidative stress or to insufficient synthesis; iron supple- and GPT analysis); iron decreases the effect of T4. This must be taken into consideration during iron supplementation.

PMID: 10631595, UI: 20097170

 

: South Med J 1997 Jun;90(6):637-9

Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism.

Shakir KM, Chute JP, Aprill BS, Lazarus AA

Department of Internal Medicine, National Naval Medical Center, Bethesda, MD 20889-5600, USA.

Recent studies have shown that under experimental conditions ferrous sulfate may reduce the gastrointestinal absorption of orally administered levothyroxine sodium in patients with primary hypothyroidism. We describe a patient who became hypothyroid while taking ferrous sulfate. The hypothyroid status was corrected by increasing the dose of levothyroxine. Subsequently, when ferrous sulfate was discontinued, the patient became hyperthyroid while taking the higher dose of thyroid hormone preparation. Since both hypothyroidism and iron deficiency anemia may coexist, additional thyroid function testing is recommended in patients treated concurrently with ferrous sulfate and L-thyroxine.

PMID: 9191742, UI: 97335076

 

: J Biol Chem 1996 May 17;271(20):12017-23

Thyroid hormone modulates the interaction between iron regulatory proteins and the ferritin mRNA iron-responsive element.

Leedman PJ, Stein AR, Chin WW, Rogers JT

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

The cytoplasmic iron regulatory protein (IRP) modulates iron homeostasis by binding to iron-responsive elements (IREs) in the transferrin receptor and ferritin mRNAs to coordinately regulate transferrin receptor mRNA stability and ferritin mRNA translational efficiency, respectively. These studies demonstrate that thyroid hormone (T3) can modulate the binding activity of the IRP to an IRE in vitro and in vivo. T3 augmented an iron-induced reduction in IRP binding activity to a ferritin IRE in RNA electrophoretic mobility shift assays using cytoplasmic extracts from human liver hepatoma (HepG2) cells. Hepatic IRP binding to the ferritin IRE also diminished after in vivo administration of T3 with iron to rats. In transient transfection studies using HepG2 cells and a human ferritin IRE-chloramphenicol acetyltransferase (H-IRE-CAT) construct, T3 augmented an iron-induced increase in CAT activity by approximately 45%. RNase protection analysis showed that this increase in CAT activity was not due to a change in the steady state level of CAT mRNA. Nuclear T3-receptors may be necessary for this T3-induced response, because the effect could not be reproduced by the addition of T3 directly to cytoplasmic extracts and was absent in CV-1 cells which lack T3-receptors. We conclude that T3 can functionally regulate the IRE binding activity of the IRP. These observations provide evidence of a novel mechanism for T3 to up-regulate hepatic ferritin expression, which may in part contribute to the elevated serum ferritin levels seen in hyperthyroidism.

PMID: 8662626, UI: 96216126

The following study describes a 62-year old male with sideroblastic anemia, which is anemia with excessive iron deposition in the liver and other cells of the body, and hyperthyroidism.  My analysis of this is that the man had a copper deficiency which created the iron build-up and the hyperthyroidism.

 

Medicina (B Aires) 1995;55(6):693-6

[Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol].

[Article in Spanish]

Mamianetti A, Munoz A, Ronchetti RD, Maccione E, Poggi U, Mugnolo R, Gallo O

Departamento de Medicina Interna, Hospital Aeronautico Central, Buenos Aires, Argentina.

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

PMID: 8731582, UI: 96340505

Ferritin is a combination of iron and apoferritin, which is an iron-transporting protein. In the following study it is noted that serum ferritin levels increase in hyperthyroidism, meaning that there is excess iron.  In fact, the serum ferritin levels of four anemic patients were significantly higher than those of nine nonanemic patients.  (I'll bet the researchers couldn't figure that one out!) 

 

I believe that ferritin levels are high because of a copper deficiency and that once the thyroid hormone levels are decreased (through antithyroid medication), copper is not being used up to de-activate the hormones, and copper levels increase.  This decreases the ferritin level and increases hemoglobin (because the iron now has copper to combine with to form hemoglobin).

 

Clin Investig 1993 Dec;72(1):26-9

Evaluation of increased serum ferritin levels in patients with hyperthyroidism.

Kubota K, Tamura J, Kurabayashi H, Shirakura T, Kobayashi I

Department of Medicine, Kusatsu Branch Hospital, Gunma, Japan.

To further elucidate the mechanism of increased serum ferritin levels in hyperthyroidism, the changes in erythrocytes and serum iron and total iron-binding capacity levels were examined in addition to serum ferritin levels in 13 hyperthyroid patients. The mean values of hemoglobin, red blood cells, and packed cell volume were increased by antithyroid therapy. While the serum levels of iron did not change, those of total iron-binding capacity increased significantly after achieving a euthyroid state. Increased serum ferritin levels returned to normal through antithyroid therapy. Furthermore, the serum ferritin levels of four anemic patients were significantly higher than those of nine nonanemic patients. Thus it is concluded that the increase in serum ferritin levels in patients with hyperthyroidism may be due to the direct action of thyroid hormones on its synthesis, while in some cases complicated with anemia impaired iron utilization by erythropoietic cells may also be involved.

PMID: 8136612, UI: 94184112

The following study shows that liver ferritin synthesis is not elevated in hypothyroidism as it is in hyperthyroidism.  This indicates that copper is not made deficient by experimental hypothyroidism induced by PTU.

 

: Thyroidology 1992 Dec;4(3):93-7

Relation between thyroid status and ferritin metabolism in rats.

Deshpande UR, Nadkarni GD

Radiation Medicine Centre, B.A.R.C., Bombay, India.

Rats were made hypo and 'hyperthyroid' with propylthiouracil (PTU) and L-Thyroxine (L-T) respectively. The hypo and hyperthyroid status in these rats were confirmed by serum level of T4 and T3. Liver iron was significantly increased in both the hypo and hyperthyroid animals. However, liver ferritin synthesis rate was reduced by 36% in hypothyroid rats, and elevated by 38% in hyperthyroid ones. A similar trend was seen in liver ferritin concentration. Further, serum transaminases were elevated only in animals of the hyperthyroid group. It appears from the present data that ferritin metabolism is influenced by thyroid hormone as well as by iron. Thus, the raised serum ferritin in hyperthyroid patients may be partially attributed to increased ferritin synthesis in the liver and its possible leakage into circulation.

Iron is used for staining tissue for the demonstration of glycosaminoglycan (GAG) deposition in the skin, which is seen in pretibial myxedema of Graves' Disease.  I'm not sure exactly what this means at this point but hope to fit this in at some time.

 

J Histochem Cytochem 1984 Oct;32(10):1121-4

Histochemical evaluation of glycosaminoglycan deposition in the skin.

Kupchella CE, Matsuoka LY, Bryan B, Wortsman J, Dietrich JG

Histologic demonstration of glycosaminoglycan (GAG) deposition in the skin has been based on the use of either colloidal iron or alcian blue. To define the best technique for the determination of skin GAG content we undertook a prospective study comparing the two stains and evaluating the use of cetylpyridinium chloride (CPC) to enhance fixation. Slides were prepared from skin biopsies obtained from five patients with cutaneous mucinoses. The preparations were coded and examined by three observers. Colloidal iron staining gave a higher intensity for GAG deposits in papillary and reticular dermis. Digestion by specific enzymes identified similar GAGs with either colloidal iron, or alcian blue; however, colloidal iron made GAGs more obvious, partly due to the contrast afforded by the yellow background stain. The addition of CPC to the fixative appreciably enhanced GAG fixation without interfering with the action of enzymes. Experimentally, we confirmed this effect of CPC by determining a pronounced decrease in GAG leakage into the fixative from CPC treated human umbilical cord. We conclude that the combination of CPC fixation and colloidal iron staining gives the best definition of skin GAGs in clinical specimens.

The following study concludes "that during thyrotoxicosis the supply of iron into erythroblasts is greater than the amount used for haemoglobin synthesis."  Since hemoglobin production also requires copper, this is indicative of a copper deficiency in hyperthyrodism.

 

Scand J Haematol 1980 Sep;25(3):237-43

Sideroblasts and haemosiderin in thyrotoxicosis.

Lahtinen R

Bone marrow sideroblasts and haemosiderin were studied in 19 thyrotoxic patients before therapy and in the euthyroid state. The proportion of sideroblasts and the amount of haemosiderin were significantly higher in the hyperthyroid than in the euthyroid phase. Pathological sideroblasts with coarse perinuclear iron granules were found before therapy but not in the euthyroid phase. It is concluded that during thyrotoxicosis the supply of iron into erythroblasts is greater than the amount used for haemoglobin synthesis.

Because aluminum interferes with iron metabolism, studies have found that people who eat food cooked in aluminum pots get anemia.  Getting these people to switch to iron cookware greatly reduces the rate of anemia.

 

Lancet 1999 Feb 27;353(9154):712-6

Effect of consumption of food cooked in iron pots on iron status and growth of young children: a randomised trial.

Adish AA, Esrey SA, Gyorkos TW, Jean-Baptiste J, Rojhani A

School of Dietetics and Human Nutrition, McGill University, St Anne-de-Bellevue, Quebec, Canada.

BACKGROUND: In less-developed countries, novel strategies are needed to control iron-deficiency anaemia, the most common form of malnutrition. METHODS: We undertook a community-based randomised controlled trial to assess the effects of iron or aluminium cooking pots in young Ethiopian children. Analysis was by intention-to-treat. The primary outcomes were change in children's haemoglobin concentration, weight, or length over the study period. We also did a laboratory study of total and available iron in traditional Ethiopian foods cooked in iron, aluminium, and clay pots. FINDINGS: 407 children, one per household, entered the study. The change in haemoglobin concentration was greater in the iron-pot group than in the aluminium-pot group (mean change to 12 months 1.7 [SD 1.5] vs 0.4 [1.0] g/dL; mean difference between groups 1.3 g/dL [95% Cl 1.1-1.6]). The mean differences between the groups in weight and length gain to 12 months (adjusted for baseline weight or length) were 0.6 cm (95% CI 0.1-1.0) and 0.1 kg (-0.1 to 0.3). The laboratory study showed that total and available iron was greatest in foods cooked in iron pots, except for available iron in legumes for which there was no difference between types of pot. INTERPRETATION: Ethiopian children fed food from iron pots had lower rates of anaemia and better growth than children whose food was cooked in aluminium pots. Provision of iron cooking pots for households in less-developed countries may be a useful method to prevent iron-deficiency anaemia.

Iron deficiency may be a factor in anemia, hypothyroidism, and myxedema (pretibial myxedema is a swelling of the front of the shin from fibroblast proliferation, a condition associated with thyroid disease and thyroid eye disease).   There are not many studies which have looked at iron levels in myxedema, but the following study is suggestive.

 

Lik Sprava 1999 Jun;(4):148-50

[Iron-deficiency anemia as a hematological mask of myxedema].

[Article in Ukrainian]

Vydyborets' SV

An atypical course of myxedema manifested by iron-deficiency anemia is described that proved to be a diagnostic challenge. Pathogenetic mechanisms of origination are analyzed.

 

Eur J Endocrinol 2000 Mar;142(3):217-23

Iron supplementation in goitrous, iron-deficient children improves their response to oral iodized oil.

Zimmermann M, Adou P, Torresani T, Zeder C, Hurrell R

Human Nutrition Laboratory, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland. michael.zimmermann@ilw.agrl.ethz.ch

OBJECTIVE: In developing countries, many children are at high risk for both goiter and iron-deficiency anemia. Because iron deficiency may impair thyroid metabolism, the aim of this study was to determine if iron supplementation improves the response to oral iodine in goitrous, iron-deficient anemic children. DESIGN: A trial of oral iodized oil followed by oral iron supplementation in an area of endemic goiter in the western Ivory Coast. METHODS: Goitrous, iodine-deficient children (aged 6-12 years; n=109) were divided into two groups: Group 1 consisted of goitrous children who were not anemic; Group 2 consisted of goitrous children who were iron-deficient anemic. Both groups were given 200mg oral iodine as iodized oil. Thyroid gland volume using ultrasound, urinary iodine concentration (UI), serum thyroxine (T(4)) and whole blood TSH were measured at baseline, and at 1, 5, 10, 15 and 30 weeks post intervention. Beginning at 30 weeks, the anemic group was given 60mg oral iron as ferrous sulfate four times/week for 12 weeks. At 50 and 65 weeks after oral iodine (8 and 23 weeks after completing iron supplementation), UI, TSH, T(4) and thyroid volume were remeasured. RESULTS: The prevalence of goiter at 30 weeks after oral iodine in Groups 1 and 2 was 12% and 64% respectively. Mean percent change in thyroid volume compared with baseline at 30 weeks in Groups 1 and 2 was -45.1% and -21.8% respectively (P<0.001 between groups). After iron supplementation in Group 2, there was a further decrease in mean thyroid volume from baseline in the anemic children (-34.8% and -38.4% at 50 and 65 weeks) and goiter prevalence fell to 31% and 20% at 50 and 65 weeks. CONCLUSION: Iron supplementation may improve the efficacy of oral iodized oil in goitrous children with iron-deficiency anemia.

 

The following study sheds light on the situation faced when the patient cannot tolerate taking thyroid replacement hormone.  The person experiences rapid heart beat and palpitations.  This indicates that the person is probably anemic from iron deficiency and will tolerate thyroxin when the anemia is corrected. 

 

Mayo Clin Proc 2000 Feb;75(2):189-92

Anemia: a cause of intolerance to thyroxine sodium.

Shakir KM, Turton D, Aprill BS, Drake AJ 3rd, Eisold JF

Department of Internal Medicine, National Naval Medical Center, Bethesda, Md., 20889-5600, USA.

Usual causes of intolerance to thyroxine sodium include coronary artery disease, advanced age, untreated adrenal insufficiency, and severe hypothyroidism. We describe 4 patients with iron deficiency anemia and primary hypothyroidism. After treatment with thyroxine sodium, these patients developed palpitations and feelings of restlessness, which necessitated discontinuation of the thyroid hormone. After the anemia was treated with ferrous sulfate for 4 to 7 weeks, they were able to tolerate thyroxine sodium therapy. Iron deficiency anemia coexisting with primary hypothyroidism results in a hyperadrenergic state. In such patients, we postulate that thyroid hormone administration causes palpitations, nervousness, and feelings of restlessness. Correction of any existing pronounced anemia in hypothyroid patients who are intolerant to thyroxine sodium therapy may result in tolerance to this agent.

 

J Nutr 1998 Aug;128(8):1401-8

Plasma thyroid hormone kinetics are altered in iron-deficient rats.

Beard JL, Brigham DE, Kelley SK, Green MH

Nutrition Department, The Pennsylvania State University, University Park, PA 16802, USA.

Iron deficiency anemia is associated with lower plasma thyroid hormone concentrations in rodents and, in some studies, in humans. The objective of this project was to determine if plasma triiodothyronine (T3) and thyroxine (T4) kinetics were affected by iron deficiency. Studies were done at a near-thermoneutral temperature (30 degrees C), and a cool environmental temperature (15 degrees C), to determine plasma T3 and T4 kinetics as a function of dietary iron intake and environmental need for the hormones. Weanling male Sprague-Dawley rats were fed either a low Fe diet [iron-deficient group (ID), <5 microg/g Fe] or a control diet [control group (CN), 35 microg/g Fe] at each temperature for 7 wk before the tracer kinetic studies. An additional ID group receiving exogenous thyroid hormone replacement was also used at the cooler temperature. For T4, the disposal rate was >60% lower (89 +/- 6 vs. 256 +/- 53 pmol/h, P < 0.001) in ID rats than in controls at 30 degrees C, and approximately 40% lower (192 +/- 27 vs. 372 +/- 26 pmol/h, P < 0.01) in ID rats at 15 degrees C. Exogenous T4 replacement in a cohort of ID rats at 15 degrees C normalized the T4 concentration and the disposal rate. For T3, the disposal rate was significantly lower in ID rats in a cool environment (92 +/- 11 vs. 129 +/- 11 pmol/h, P < 0.01); thyroxine replacement again normalized the T3 disposal rate (126 +/- 12 pmol/h). Neither liver nor brown fat thyroxine 5'-deiodinase activities were sufficiently different to explain the lower T3 disposal rates in iron deficiency. Thus, plasma thyroid hormone kinetics in iron deficiency anemia are corrected by simply providing more thyroxine. This suggests a central regulatory defect as the primary lesion and not peripheral alterations.

 

Gartner R, Dugrillon A.

[From iodine deficiency to goiter. Pathophysiology of iron deficiency goiter].
Internist (Berl). 1998 Jun;39(6):566-73. Review. German. No abstract available.
PMID: 9677510; UI: 98342474

 

Am J Clin Nutr 2000 Jan;71(1):88-93

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Persistence of goiter despite oral iodine supplementation in goitrous children with iron deficiency anemia in Cote d'Ivoire.

Zimmermann M, Adou P, Torresani T, Zeder C, Hurrell R

Human Nutrition Laboratory, Swiss Federal Institute of Technology, Zurich, Switzerland. michael.zimmermann@ilw.agrl.ethz.ch

BACKGROUND: In developing countries, many children are at high risk of goiter and iron deficiency anemia. Because iron deficiency can have adverse effects on thyroid metabolism, iron deficiency may influence the response to supplemental iodine in areas of endemic goiter. OBJECTIVE: The aim of this study was to determine whether goitrous children with iron deficiency anemia would respond to oral iodine supplementation. DESIGN: A trial of oral iodine supplementation was carried out in an area of endemic goiter in western Cote d'Ivoire in goitrous children (n = 109) aged 6-12 y. Group 1 (n = 53) consisted of goitrous children who were not anemic. Group 2 (n = 56) consisted of goitrous children who had iron deficiency anemia. At baseline, thyroid gland volume and urinary iodine, thyrotropin, and thyroxine were measured by using ultrasound. Each child received 200 mg I orally and was observed for 30 wk, during which urinary iodine, thyrotropin, thyroxine, hemoglobin, and thyroid gland volume were measured. RESULTS: The prevalence of goiter at 30 wk was 12% in group 1 and 64% in group 2. The mean percentage change from baseline in thyroid volume 30 wk after administration of oral iodine was -45.1% in group 1 and -21.8% in group 2 (P < 0.001). Among the anemic children, there was a strong correlation between the percentage decrease in thyroid volume and hemoglobin concentration (r(2) = 0.65). CONCLUSION: The therapeutic response to oral iodine was impaired in goitrous children with iron deficiency anemia, suggesting that the presence of iron deficiency anemia in children limits the effectiveness of iodine intervention programs.

 

WESTPORT, May 08 (Reuters Health) - Bolus injection of deferoxamine decreases serum ferritin concentrations in patients with iron overload, researchers in Italy report in the May 1st issue of Blood.

Dr. Massimo Franchini, of Ospedale Policlinico in Verona, and colleagues studied 27 adults with iron overload due to various conditions or treatments. Initial comparison of two doses of deferoxamine, given subcutaneously 12 hours apart, and a 12-hour subcutaneous infusion of deferoxamine showed that mean 48-hour urinary iron excretion was similar for both types of administration.

Twenty-six patients continued therapy with bolus injection, and the researchers measured serum ferritin concentrations at various times up to a mean of about 20 months. Overall, ferritin concentrations dropped from an average of 1631.5 micrograms/L to below 1,000 micrograms/L in 73% of patients, below 500 micrograms/L in 42% of patients, and to normal levels in 26% of patients.

Dr. Franchini's group notes that patients who did not receive blood transfusions during deferoxamine therapy had a significantly larger decrease in mean serum ferritin concentration compared with patients who regularly had transfusions. Ferritin concentrations did not reach normal levels in any patients who had transfusions.

The authors caution that measuring serum ferritin is not an accurate way of measuring iron stores, and that the two methods of administering deferoxamine should be compared with respect to levels of free iron.

However, they believe that the results "support the need for a prospective, randomized controlled trial in a larger and more homogenous population of patients in which hepatic, cardiac, and endocrine functions are systematically assessed."

Blood 2000;95:2776-2779.

The following study offers support for a copper deficiency in hyperthyroidism since iron has enhanced toxicity to the liver in hyperthyroidism. Low copper allows free iron which is uncoupled to copper to be more toxic.

Redox Rep 1999;4(5):243-50

Derangement of Kupffer cell functioning and hepatotoxicity in hyperthyroid rats subjected to acute iron overload.

Boisier X, Schon M, Sepulveda A, Basualdo A, Cornejo P, Bosco C, Carrion Y, Galleano M, Tapia G, Puntarulo S, Fernandez V, Videla LA

Programas de Farmacologia Molecular y Clinica, Facultad de Medicina, Universidad de Chile, Santiago.

Liver oxidative stress, Kupffer cell functioning, and cell injury were studied in control rats and in animals subjected to L-3,3',5-tri-iodothyronine (T3) and/or acute iron overload. Thyroid calorigenesis with increased rates of hepatic O2 uptake was not altered by iron treatment, whereas iron enhanced serum and liver iron levels independently of T3. Liver thiobarbituric acid reactants formation increased by 5.8-, 5.7-, or 11.0-fold by T3, iron, or their combined treatment, respectively. Iron enhanced the content of protein carbonyls independently of T3 administration, whereas glutathione levels decreased in T3- and iron-treated rats (54%) and in T3Fe-treated animals (71%). Colloidal carbon infusion into perfused livers elicited a 109% and 68% increase in O2 uptake in T3 and iron-treated rats over controls. This parameter was decreased (78%) by the joint T3Fe administration and abolished by gadolinium chloride (GdCl3) pretreatment in all experimental groups. Hyperthyroidism and iron overload did not modify the sinusoidal efflux of lactate dehydrogenase, whereas T3Fe-treated rats exhibited a 35-fold increase over control values, with a 54% reduction by GdCl3 pretreatment. Histological studies showed a slight increase in the number or size of Kupffer cells in hyperthyroid rats or in iron overloaded animals, respectively. Kupffer cell hypertrophy and hyperplasia with presence of inflammatory cells and increased hepatic myeloperoxidase activity were found in T3Fe-treated rats. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of iron, which seems to be related to the development of a severe oxidative stress status in the tissue, thus contributing to the concomitant liver injury and impairment of Kupffer cell phagocytosis and particle-induced respiratory burst activity.

IRON DEFICIENCY AND THERMOREGULATION

The following studies offer evidence that the inability to maintain body temperature (feeling cold when others are warm) is due to iron deficiency. Most hypos experience this, indicating that iron deficiency is usually a factor in hypothyroidism.

IRON DEFICIENCY AND SUPPLEMENTATION IMPACT THERMOREGULATION AND BROWN ADIPOSE TISSUE (BAT) MITOCHONDRIAL MORPHOLOGY OF RATS EXPOSED TO COLD

Author(s):

MICHELSEN KIM G HALL CLINTON B NEWMAN JR SAMUEL M DROKE ELIZABETH A SLEEPER MARY E LUKASKI HENRY C

Interpretive Summary:

The role that iron (Fe) plays in regulating whole-body temperature is not well defined. Fe-deficient rats have reduced concentrations of thyroid hormones and altered body temperature. Because thyroid hormones act at the mitochondria level of brown adipose tissue to produce heat, Fe status may affect the structural characteristics of mitochondria, a cell component that produces energy to maintain body temperature. To examine the relationships among dietary iron, body temperature, thyroid hormones, and brown adipose tissue mitochondria, young male rats were fed diets containing adequate or deficient amounts of Fe. Some of the rats fed the low-Fe diets then were given the diet containing an adequate amount of Fe. When exposed to cold air for four hours, the rats fed the Fe-deficient diet had a greater decline in body temperature than the rats fed the Fe- adequate diet. The rats initially fed the Fe-deficient diet then fed the Fe-adequate diet had similar body temperatures as the animals fed the Fe- adequate diet. Plasma thyroid hormone concentrations were less in the rats fed the Fe-deficient, as compared to the Fe-adequate and Fe-deficient supplemented with adequate Fe diets. The structure of mitochondria suggests that Fe deficiency produced changes that indicate impaired heat production; this change was ameliorated with Fe supplementation. These findings indicate that Fe deficiency reduces the capability of rats to maintain body temperature during short-term cold exposure. Biological impairments of Fe deficiency lie in the production of adequate amounts of thyroid hormones and adverse changes in the mitochondria that inhibit the production of heat. This information will be useful to scientists who seek to understand how mineral elements regulate energy utilization.

See also:
http://www.nap.edu/books/0309054842/html/248.html


IRON DEFICIENCY

Several key observations have stimulated interest in the relationship
between iron deficiency and thermoregulation. Iron-deficient anemic rats
were found to be unable to maintain normal body temperature when exposed to
cold (39°F [4°C]) (Beard et al., 1982, 1984; Dillmann et al., 1979, 1980).
Accompanying the impairment in thermoregulation were a decrease in the rate
of thyroid hormone turnover and an increase in the rate of norepinephrine
turnover, as compared to those observed in noniron-depleted cold-exposed
(control) rats. Iron-deficient humans are unable to maintain their body
temperature during exposure to cool water (82°F [28°C]) (Beard et al.,
1990a; Martinez-Torres et al., 1984) or cool air (61°F [16°C]) (Lukaski et
al., 1990), compared to subjects with normal iron status and equivalent body
composition. Additionally, the iron-deficient subjects had lower thyroid
hormone (Beard et al., 1990a) and higher catecholamine responses to cold
(Lukaski et al., 1990; Martinez-Torres et al., 1984), similar to the
response of iron-deficient rats. After repletion with iron supplements, the
previously iron-deficient human subjects showed improved ability to maintain
body temperature in the cold. These observations clearly demonstrate the
link between iron deficiency and poor thermoregulation.

Anemia vs. Tissue Iron Deficiency

Iron deficiency may exert its effects on thermoregulation through two
distinct, yet related, mechanisms, one involving anemia and the other
involving tissue iron deficiency. Iron-deficiency anemia results in
decreased oxygen transport from the lungs to tissues, and this reduction in
oxygen availability inhibits physiological responses to cold, including
peripheral vasoconstriction, a heat-conserving process, and increased
metabolic rate, a heat-generating process. Hypoxia, created by reducing the
oxygen content or the pressure of inspired air, results in hypothermia in
rodents (Gautier et al., 1991). The inability to conserve and produce body
heat properly accounts for hypoxia-induced hypothermia (Wood, 1991). Lack of
oxygen availability for aerobic metabolism causes a decrease in metabolic
rate and, subsequently, a decrease in heat production. Hypoxic rats
demonstrate decreased shivering and nonshivering thermogenesis (Gautier et
al., 1991) and a decrease in body temperature set-point (Gordon and
Fogelson, 1991). Impaired neural control of these processes may also account
for the effects of hypoxia on thermoregulation (Mayfield et al., 1987).
Tissue iron deficiency, apart from anemia, decreases the ability of muscles
to utilize energy for muscular contraction, presumably via a decrease in the
activity of mitochondrial iron-containing enzymes required for the oxidative
production of ATP (Davies et al., 1984).