iThyroid.com

ANEMIA

ANEMIA--TYPES AND CAUSES

Many disease conditions are associated with thyroid diseases, but of all these diseases, the one with the highest association is anemia.  I read one study which indicated that about one half of all hyperthyroids had clinically diagnosed anemia.  It's possible, and to me quite likely, that the other half were also anemic but not diagnosed because they had copper-deficiency anemia and not iron-deficiency anemia.

Anemia is usually caused by a deficiency of hemoglobin which is the oxygen carrying molecule in the red blood cell.  While many minerals are important in the body's manufacture of hemoglobin, iron and copper are the most important.  A deficiency of either iron or copper will result in anemia, either iron-deficiency anemia or copper-deficiency anemia.

Anemia is often medically diagnosed by determining blood levels of  iron and the iron-carrying protein ferritin.  This test will determine anemia if the anemia is due to iron deficiency.  However, this test will not show if the person has copper-deficiency anemia.  

It seems that many doctors are unaware of copper-deficiency anemia and will try to correct all cases of anemia by prescribing very large doses of iron.  Since the majority of cases of anemia are probably the result of iron deficiency, then this procedure usually works.  However, in copper-deficiency anemia, taking excess amounts of iron will further deplete copper and cause the anemia to worsen.  This exact scenario has happened to more than one person in our group.

SYMPTOMS OF ANEMIA

The symptoms of anemia are: rapid heart beat, dizziness upon standing, reduced capacity to exercise, reduced endurance, elevated heart rate when exercising and failure of the heart to return to a normal rate in a reasonable time upon exercise cessation, low physical energy, low mental energy ("brain fog"), feeling of unease which is alleviated by a period of breathing deeply, inability to fall asleep or to sleep well (insomnia), waking up gasping for breath, and an increase of all these symptoms when traveling to a higher altitude (vacationing in the mountains).

All of these symptoms are related to a reduced amount of oxygen getting to the cells.  The most serious of these symptoms is the increase in heart rate.  Because each red blood cell carries less oxygen to the cells, the heart rate increases to increase the blood flow so that the cells will not be oxygen starved.

CONNECTION BETWEEN ANEMIA AND THYROID DISEASE

Keep in mind that there is no clear-cut proof of this, but I believe that the mineral deficiencies which lead to hypothyroidism and hyperthyroidism bear remarkable similarity to the mineral deficiencies which lead to the two main types of anemia.  

Iron-deficiency anemia and hypothyroidism are similar in that in both iron is more deficient than copper.    Copper-deficiency anemia and hyperthyroidism are similar in that in both copper is more deficient than iron.   

It is an easy step to postulate that anemia is the single most important pre-existing and causative condition in the etiology of hypothyroidism and hyperthyroidism.  Hypothyroidism may be the result of iron-deficiency anemia and hyperthyroidism may be the result of copper-deficiency anemia.  

Since iron is needed by the body in amounts approximately five times that of copper, then iron deficiency probably occurs more often than copper deficiency.  I've read that one-fifth of the world's population suffers from iron deficiency.  This may be one of the reasons that hypothyroidism is more common than hyperthyroidism.

WHO GETS ANEMIA AND THYROID DISEASE

Women in their child-bearing years need more iron and copper than  women at other ages and men at any age because of the monthly blood loss during menstruation.  Pregnancy, child-birth, and nursing place additional mineral drains on this group of women. This age group of women is the same group that is 8-10 times more likely to get thyroid diseases and autoimmune diseases.

When a otherwise healthy teenage girl gets hyperthyroidism right after beginning her period, then it has to be the result of a deficiency of minerals that are depleted by the blood loss.  What other explanation could there be?  When a woman develops hyperthyroidism during pregnancy or breast feeding, it also indicates a deficiency.

Who else gets anemic and gets thyroid disease?  People who exercise excessively like Olympic athletes and they often get anemia and hyperthyroidism.  Older men and women, especially if they don't eat much red meat (iron) or drink much beer (copper).  Also, people with poor digestion such as those with celiac disease.

WHAT ARE THE MAJOR DEFICIENCIES INVOLVED IN ANEMIA?

Following is a study from the US Dept of Agriculture, which seems to be doing some of the best nutritional research in the country.  The study clearly states that copper deficiency causes anemia and serious cardiovascular disease.

Biofactors 1999;10(4):359-75

Cardiovascular effects of dietary copper deficiency.

Saari JT, Schuschke DA

US Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, ND 58202-9034, USA. jsaari@gfhnrc.ars.usda.gov

Dietary copper deficiency may impair cardiovascular health by contributing to high blood pressure, enhancement of inflammation, anemia, reduced blood clotting and arteriosclerosis. The purpose of this review is to compile information on the numerous changes of the heart, blood and blood vessels that may contribute to these cardiovascular defects. These alterations include weakened structural integrity of the heart and blood vessels, impairment of the use of energy by the heart, reduced ability of the heart to contract, altered ability of blood vessels to control their diameter and to grow, and altered structure and function of circulating blood cells. The fundamental causes of these changes rest largely on reduced effectiveness of enzymes that depend on copper for their activity.

Zinc is essential for normal iron metabolism and prevention of anemia, but high levels of zinc can depress iron and lead to anemia.

 

J Am Coll Nutr 1998 Jun;17(3):291-5

Zinc status relates to hematological deficits in middle-aged women.

Nishiyama S, Irisa K, Matsubasa T, Higashi A, Matsuda I

Department of Pediatrics, Kumamoto University, School of Medicine, Japan.

OBJECTIVE: The objective of our study was to investigate zinc (Zn) status and the effects of Zn supplementation in relation to iron deficiency anemia in middle-aged women. It is important to define the role of Zn in hematologic abnormalities and to determine the frequency of Zn deficiency. METHODS: Fifty-two Japanese women, selected from a health examination survey on 6200 women, had hemoglobin concentrations below 12.0 g/dl, total iron binding capacity (TIBC) below 390 micrograms/dl and fairly normocytemia. These 52 were divided into three groups and we then compared the hematological status before and after iron (group A) or Zn (group B) or iron plus Zn (group C) supplementation. RESULTS: After treatment, concentrations of hemoglobin (Hb) increased slightly in groups A and B, but not statistically significant. In group C, Hb levels were significantly increased from 10.8 +/- 1.1 to 12.8 +/- 1.1 g/dl. Furthermore, numbers of RBC and reticulocytes, and concentrations of albumin were also increased significantly. Increased values over 1.0 g/dl of hemoglobin levels were noted in four women (26.6%) in group A, three women (14.2%) in group B and 13 women (81.2%) in group C. CONCLUSION: Zn status to some extent can account for hematological abnormalities in middle-aged women. At least 5.0% of middle-aged Japanese women may have Zn deficiency. Normocytic anemia with low TIBC levels may serve as a good indicator of a marginal Zn deficiency.

This study of a hyena which ingested high-zinc coins shows that excessive zinc can cause anemia

J Zoo Wildl Med 1999 Sep;30(3):431-4

Zinc toxicosis in a captive striped hyena (Hyaena hyaena).

Agnew DW, Barbiers RB, Poppenga RH, Watson GL

Detroit Zoological Institute, Royal Oak, Michigan 48068, USA.

An 11-yr-old captive-born female striped hyena (Hyaena hyaena) acutely developed lameness and swelling of the left front foot with anorexia, depression, and lethargy. Hematologic evaluation revealed regenerative anemia, azotemia, and other mild serum electrolyte and mineral abnormalities. Twenty radiographically visible coins and 10 coin fragments were removed by laparotomy and gastrotomy following unsuccessful medical therapy. The animal died during anesthetic recovery. Zinc serum levels were 41.0 ppm at first presentation and 36.0 ppm at the time of surgery, compared with concentrations of 1.78 ppm and 2.82 ppm for serum taken from this female and a male hyena 3 mo previously. Zinc toxicosis was diagnosed based on the similarity of clinical signs to those described in dogs, presence in the stomach of pennies minted after 1982 (when the zinc content of U.S. pennies was increased substantially), necropsy findings, and elevated serum and liver zinc values. The case highlights the risk posed by penny ingestion for subsequent zinc toxicosis in captive omnivores.

WHAT OTHER FACTORS MAY CAUSE ANEMIA?

We have seen that certain minerals like cadmium, aluminum, and mercury are involved in thyroid disease because they deplete copper, iron, zinc, and selenium.  Are they also involved in anemia?

Smokers get hyperthyroidism at a higher rate than nonsmokers and the reason is probably the high levels of cadmium in tobacco which depletes copper.  Do smokers have a higher rate of anemia than nonsmokers?  There are not a lot of studies which directly address this issue, but some that look at it indirectly.  The following study suggests that this hypothesis may be true:

Epidemiology 2000 May;11(3):285-91

Smoking and myelodysplastic syndromes.

Bjork J, Albin M, Mauritzson N, Stromberg U, Johansson B, Hagmar L

Department of Occupational and Environmental Medicine, Lund University Hospital, Sweden.

[Medline record in process]

The purpose of this case-control study was to investigate tobacco smoking as a risk factor for myelodysplastic syndromes, emphasizing karyotypic aberrations as markers for exposure and risk differentiation with respect to morphology. We obtained smoking history by interview of 330 cytogenetically investigated adult myelodysplastic syndrome cases and 337 controls, matched with respect to sex, year of birth, and county of living. Smoking for at least 1 year at some time 20 years or less before diagnosis was associated with an elevated relative risk (RR) for primary myelodysplastic syndromes (odds ratio (OR) 1.8; 95% confidence interval (CI) = 1.2-2.7). The results indicated a relation with intensity and duration of smoking as well as a decrease in risk a few years after cessation of smoking. Smoking was associated with an increased RR for primary myelodysplastic syndromes with chromosome 7 abnormalities (OR 5.0; 95% CI = 1.1-23). Elevated RRs were also seen for refractory anemia (OR 2.5; 95% CI = 1.2-5.6) and for refractory anemia with ringed sideroblasts (OR 3.2; 95% CI = 0.88-12). The findings suggest that smoking is a risk factor for myelodysplastic syndromes.

PMID: 10784245, UI: 20244831

Following is a very good review which states that cadmium and lead toxicity causes anemia.  Extremely interesting is the comment that "

Quoting the study, "Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++."  Does this "10 times" strike a bell for you as it does for me?  This is the factor by which women (high in estrogen) are more likely to get hyperthyroidism than men.  The evidence is clearly pointing to heavy metal toxicity from cadmium and mercury which is accelerated by estrogen as the causative factor for hyperthyroidism and hypothyroidism.

[The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children].

[Article in German]

Schumann K

Walther-Straub-Institut fur Pharmakologie und Toxikologie der Ludwig-Maximilians-Universitat, Munchen, FRG.

There are differences between young and adult organisms regarding toxokinetic aspects and clinical manifestations of heavy metal intoxications. Chronically, toxic Cd intake causes a microcytotic hypochromic anemia in young rats at lower exposure levels and after shorter exposure periods than in adult animals. Cd absorption is increased by co-administration of milk and in conjunction with iron deficiency. After long exposure periods toxic Cd concentrations accumulate in the kidney cortex; this process starts very early in life. In 3-year-old children Cd concentrations in the kidney can reach up to one-third of those found in adults. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers. Toxic Pb concentrations can lead to Pb encephalopathia. A high percentage of surviving children have seizures and show signs of mental retardation. Anemia and reduced intelligence scores were recently observed in children after exposure to very low levels of Pb. Pb absorption is increased in children and after co-administration of milk. There are no definite proofs for carcinogenesis or mutagenesis after oral exposure to Cd, Hg, and Pb in man. Heavy metal concentrations were found in the same order of magnitude in commercial infant formulas and in breast milk. When infant formulas are reconstituted with contaminated tap water, however, Pb and Cd concentrations can be much higher. The average heavy metal uptake from such diets exceeds the provisional tolerable weekly intake levels set by the WHO for adults, calculated on the basis of an average food intake and a downscaled body weight. These considerations do not even provide for differences in absorption and distribution or for the increased sensitivity of children to heavy metal exposure. However, dilution effects for essential heavy metals were observed in fast-growing young children; this effect might be extrapolated to toxic metals. These theoretical considerations are compared with epidemiological evidence. A health statistic from Baltimore shows a decline of Pb intoxications in infants. This observation correlates with a simultaneous decline in exposure to Pb which was due, for example, to decreased use of lead dyes in house paints and the abolition of tin cans for infant food.

 

What about aluminum?  Does high aluminum intake cause anemia?  The following study shows that aluminum can interfere with iron absorption and metabolism and contribute to anemia.

 

Toxicology 2000 Jan 3;142(2):97-109

Effect of dietary aluminum on tissue nonheme iron and ferritin levels in the chick.

Han J, Han J, Dunn MA

Department of Food Science and Human Nutrition, University of Hawaii, Honolulu 96822, USA.

Aluminum toxicity is well documented but the mechanism of action is poorly understood. In renal failure patients with aluminum overload, disturbances in iron metabolism leading to anemia are apparent. Few animal models, however, have been used to study the effects of dietary aluminum on iron metabolism. The purpose of this study was to determine if dietary aluminum exposure alters tissue iron and ferritin concentrations in the chick, as has been found in cultured human cells exposed to aluminum. Groups of day-old chicks were fed purified diets containing one of two levels of iron (control or high iron), and one of three levels of aluminum chloride in a 2 x 3 factorial design. Diets were consumed ad libitum for 1 week, then pair-feeding was initiated for 2 more weeks. A seventh group consumed a low iron diet ad libitum for comparative purposes. After the 3-week feeding period, samples of kidney, liver, and intestinal mucosa were analyzed for nonheme iron and ferritin concentrations by a colorimetric assay and SDS-PAGE, respectively. Results showed that dietary aluminum intake reduced iron stores in liver and intestine, but had no effect on nonheme iron levels in the kidney. Ferritin levels were reduced by aluminum intake in all tissues studied. The decreases in tissue ferritin levels were proportionately more than the decreases in tissue nonheme iron levels. This resulted in increased nonheme iron to ferritin ratios that amounted to as much as 140 and 525% in kidney and intestine, respectively. These findings are consistent with the interpretation that, in the growing chick, dietary aluminum can inhibit iron absorption, disrupt the regulation of tissue ferritin levels by iron, and potentially alter the compartmentalization and protective sequestration of iron within cells.

PMID: 10685509, UI: 20147936

The following study shows that aluminum inhibits iron metabolism, red blood cell production (

Acta Physiol Pharmacol Bulg 1998;23(1):27-31

Influence of aluminium on erythropoiesis, iron metabolism and some functional characteristics of erythrocytes in rats.

Ganchev T, Dyankov E, Zacharieva R, Pachalieva I, Velikova M, Kavaldjieva B

Medical Univesity of Varna, Department of Physiology, Bulgaria.

The increased aluminium (Al) levels in serum of patients with chronic renal failure on hemodialysis are associated with impaired erythropoiesis and iron metabolism. The long term Al loading of rats (20 to 90 days) has similar effect. Data are still lacking about the effects after short-term aluminium treatment. The 7 day's treatment with Al2(SO4)3 in a dose 67.5 mg/kg b. w., i. m. m. significantly decreased hemoglobin, hematocrit, incorporation of 59Fe in newly formed erythrocytes and increased reticulocytes in absolute and relative counts. We observed a mild degree hypochromic, ferropenic, microcytic anemia and polychromazia in the available macrocytes. The immature erythroblasts were predominant forms in the erythroblastogram while the number of mature erythroblasts was decreased. Index of maturation of erythroblasts was lower, indicating inhibited erythroblast maturation. Plasma iron, TIBC, transferrin saturation and 59Fe absorption in the experimental group were significantly decreased. Spontaneous and mechanical hemolysis of erythrocytes were lower while erythrocyte deformability was increased. Obviously, Al treatment inhibits erythropoiesis and iron metabolism, probably hinders hemoglobin synthesis and erythroid cell maturation but does not affect the studied functional characteristics of mature erythrocytes negatively.

PMID: 10347617, UI: 99276965

What about mercury from dental amalgam fillings?  Can mercury cause anemia?  The following study indicates that it does.

 

: Sci Total Environ 1990 Dec 1;99(1-2):23-35

The relationship between mercury from dental amalgam and the cardiovascular system.

Siblerud RL

Department of Physiology, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins 80523.

The findings presented here suggest that mercury poisoning from dental amalgam may play a role in the etiology of cardiovascular disorders. Comparisons between subjects with and without amalgam showed amalgam-bearing subjects had significantly higher blood pressure, lower heart rate, lower hemoglobin, and lower hematocrit. Hemoglobin, hematocrit, and red blood cells were significantly lower when correlated to increased levels of urine mercury. The amalgam subjects had a greater incidence of chest pains, tachycardia, anemia, fatigue, tiring easily, and being tired in the morning. The data suggest that inorganic mercury poisoning from dental amalgam does affect the cardiovascular system.

PMID: 2270468, UI: 91102526

Here's another study indicating that mercury intoxication causes anemia where the patient used Mercurochrome as a topical antiseptic.  No one uses Mercurochrome anymore, do they?  Anyone know if this product is still sold?  If you have this or any other mercury compound in your medicine chest, get rid of it now.

 

Acta Med Scand 1979;205(6):463-6

A case of merbromin (Mercurochrome) intoxication possibly resulting in aplastic anemia.

Slee PH, den Ottolander GJ, de Wolff FA

A patient is described who appeared to be suffering from mercury intoxication caused by local application of merbromin to an operation wound and who developed aplastic anemia, which we ascribed to merbromin.

PMID: 88168, UI: 79206133

 

As the following study states, a great many factors can affect the blood and lead to anemia.

Folia Med Cracov 1993;34(1-4):29-47

Immunotoxic and hematotoxic effects of occupational exposures.

Lisiewicz J

Department of Hematology, Collegium Medicum, Jagiellonian University, Krakow.

The toxic effects of environmental factors at work places on the hematopoietic and immune systems are of basic importance due to the time of exposure, lasting on average 8 hours daily during one week. Porphyrinurias and porphyrias have been observed after exposure to hexachlorobenzene, chlorinated dibenzodioxins, polychlorinated biphenyls, polybrominated biphenyls, vinyl chloride and lead. Aplastic anemia may occur after exposure to benzene, pesticides, arsenic, cadmium and copper compounds. Megaloblastic anemia has been noted in subjects exposed to arsenic, chlordane, benzene and nitrous oxide. Methemoglobinemia is induced by aromatic nitro and amino compounds. Hemolytic reactions caused by arsenic, methyl chloride, naphthalene, lead, cadmium and mercury compounds represent a separate problem. Immunodeficiencies resulting in decreased antitumor and antiinfectious immunity have been reported in subjects exposed to asbestos, ozone, dimethylsulphoxide, vinilidene chloride, and benzene homologues. Lymphocytopenia may be induced by manganese, lead, toluene and industrial noise. Neutropenia was marked after exposure to carbon disulphide, arsenic compounds, benzene and electromagnetic fields. Only a few reports concern the lymphocyte T3, T4 and T8 subpopulations. Electromagnetic fields (microwaves) cause an imbalance of that subpopulation, consisting of a decrease in the T8 cell count. The neutrophil enzymes, such as myeloperoxidase and alkaline phosphatase, decrease in their activity after exposure to polychlorinated biphenyls, carbon disulphide, chlorobenzene and DDT. A majority of agents cited include genotoxic effects reflected in chromosome aberrations and increased sister chromatid exchange and abnormal unscheduled DNA synthesis. Leukemia or lymphoma risk is increased after exposure to pesticides, electromagnetic fields, benzene and irradiation.

ANEMIA AND HYPERTHYROIDISM

What studies show that anemia is associated with hyperthyroidism?  In the following study, 38 out of 100 hyperthyroid patients were found to be have hypochromic anemia (low hemoglobin).  Also the 38 anemic patients had significantly higher levels of thyroid hormones than the 62 without anemia.  Additionally, the authors state that iron deficiency, B-12 deficiency, and folic acid deficiency could all be excluded as possible causes of the anemia.  This makes sense to me.  The conclusion, as I see it: copper-deficiency anemia.  Since copper gets used up in de-activating thyroid hormones, treating the hyperthyroidism normalized the anemia because the excessive drain on copper reserves produced by high thyroid hormones was ended.

 

Z Gesamte Inn Med 1981 Mar 15;36(6):203-8

[Hyperthyroidism and anemia].

[Article in German]

Hambsch K, Fischer H, Langpeter D, Muller P

In a random test of 100 patients with hyperthyroidism with clinical and paraclinical ascertainment of the diagnosis in 38 cases normo-hypochromic, normocytary anaemias of different expression were found. In the patients with anaemia the serum hormone values were statistically significantly higher than in the 62 patients without anaemia. Also cardiotoxic and hepatotoxic findings were more frequently to be proved in patients with anaemia. A causal iron deficiency, deficit of vitamin B12 or folic acid as well as a haemolytic component of the induction of anaemia could vastly be excluded. By means of the treatment of the basic disease and metabolic balance a normalisation of hemoglobin was achieved without additional medication. From the results of the examinations is concluded that above all a thyreotoxic damage is responsible for the development of the anaemia. In cases of oligo-symptomatic hyperthyroidism part from hepatotoxicity and cardiotoxicity also anaemias may become a leading symptom.

ANEMIA AND HYPOTHYROIDISM

The following study states that 20-60% of patients with hypothyroidism are anemic.  It also states that "Anemia is often the first sign of hypothyroidism."  Very important is the observation that anemia in hypothyroidism is often not diagnosed because hypothyroids have a lower volume of plasma which causes a false high estimation of the amount of hemoglobin in the blood.

 

Med Pregl 1999 Mar-May;52(3-5):136-40

[Anemia in hypothyroidism].

[Article in Serbo-Croatian (Roman)]

Antonijevic N, Nesovic M, Trbojevic B, Milosevic R

Poliklinika Vizim, Beograd.

INTRODUCTION: Anemias are diagnosed in 20-60% patients with hypothyroidism. Real values of the degree of anemia are estimated by radioisotopic analysis due to the lower volume of plasma in hypothyroidism causing false high levels of hemoglobin in blood. Anemia is often the first sign of hypothyroidism. Diagnosis of hypothyroidism should be considered in every case of anemia with uncertain etiology because sometimes signs of overt hypothyroidism needn't necessarily be evident. Microcytic, macrocytic and normocytic are regularly described anemias. CLASSIFICATION: Microcytic anemia is usually ascribed to malabsorption of iron and loss of iron by menorrhagia. Macrocytic anemia is caused by malabsorption of vitamin B12, folic acid, pernicious anemia and inadequate nutrition. Pernicious anemia occurs 20 times more frequently in patients with hypothyroidism than generally. Macrocytosis is found in up to 55% patients with hypothyroidism and may result from the insufficiency of the thyroid hormones themselves without nutritive deficit. Normocytic anemia, so-called uncomplicated anemia, arises due to thyroid hormones deficit itself not followed by nutritive deficit. This type of anemia is considered to be an adaptation to a decreased basal metabolism. Thyroid hormones directly or indirectly, through erythropoietin, stimulate growth of erythroid colonies (BFU-E, CFU-E). Normocytic anemia is characterized by reticulopenia, hypoplasia of erythroid lineage, decreased level of erythropoietin, mainly regular erythrocyte survival. Acanthocytosis findings in cytologic blood smear suggest hypothyroidism in about 90% of cases.

The following study shows that anemia is also present in congenital hypothyroidism (in infants born with hypothyroidism) just as it is found in adult hypothyroids.  Note that the authors of this study, as most researchers in the field, try to attribute the anemia to the effect of low thyroid hormones, despite the fact that the anemia persists even after thyroid hormone supplementation.  It seems that no one is seeing that the same mineral deficiencies which cause anemia  (iron and zinc), cause hypothyroidism.

 

J Endocrinol Invest 1996 Oct;19(9):613-9

Anemia in infants with congenital hypothyroidism diagnosed by neonatal screening.

Franzese A, Salerno M, Argenziano A, Buongiovanni C, Limauro R, Tenore A

Dipartimento di Pediatria, Universita di Napoli, Italy.

Although anemia is a common finding in adult hypothyroid patients, there are no studies on anemia in hypothyroid infants. The aim of this study, therefore, was to review the hematologic status during the first year of life in 50 infants with congenital hypothyroidism detected through the regional neonatal screening program. The mean age at diagnosis was 23.7 +/- 6.5 days and treatment was initially begun with a mean L-thyroxine dose of 6.8 +/- 1.3 micrograms/kg/day. Clinical and haematological assessments were performed at diagnosis, 3, 6 and 12 months of age. The patients were divided in 2 groups based on whether T4 serum concentration at diagnosis was < 3 micrograms/dl (Group A) or > or = 3 micrograms/dl (Group B). Data for hemoglobin (Hb), hematocrit (Ht), red cells count (RCC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), serum iron and ferritin were expressed as Standard Deviation Score (SDS). Although at diagnosis the mean value of Hb-SDS, Ht-SDS and RCC-SDS were in the low-normal range in both groups, at 3 months of age the values in Group A (Hb -1.9 +/- 0.79; Ht -2.34 +/- 1.02; RCC -1.56 +/- 1.25) were significantly lower than in Group B (Hb -1.14 +/- 0.78, p < 0.005; Ht -1.59 +/- 0.94, p < 0.05; RCC -0.55 +/- 1.32, p < 0.02). A rise of the Hb, Ht and RCC values was observed in both groups from 6 to 12 months. The mean values of MCV-SDS and MCH-SDS were in the normal range at diagnosis in both groups, decrease progressively at 3 and 6 months and returned to normal at 12 months of age; no differences were found between the 2 groups at any time. Mean Hb levels at 3 months of age were correlated with mean serum T4 at diagnosis (r = 0.30, p < 0.05). The present results indicate that anemia is a frequent finding in infants with congenital hypothyroidism and is depended on the degree of neonatal hypothyroidism and imply that hypothyroidism during development may produce persisting changes even after thyroid replacement has begun.

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.

There are numerous studies to suggest that both hypothyroidism and hyperthyroidism are diseases which stem from the same deficiencies which cause anemia.

Other studies indicate that the same metals which we have seen contribute to thyroid disease also contribute to anemia. It appears that toxicities from metals like cadmium, mercury, lead, and aluminum are involved in the etiologies of both diseases.

An understanding of anemia can be very important for the person suffering from thyroid disease.  The symptoms of anemia listed above should be watched for so that you can more closely monitor the effects of your supplement and eating programs on your thyroid disease.  By eating to correct anemia, you should be able to correct your thyroid disease.  

ADDENDUM--THALASSEMIA

Thalassemia is an inherited form of anemia and there are two main types: alpha-thalassemia in which there is a decreased rate of synthesis of the alpha chains of hemoglobin; and beta-thalassemia in which there is a decreased  rate of synthesis of the beta chains of hemoglobin.  

Cardiac arryhthmia (irregular heart rate) is a symptom of thalassemia induced anemia as it is of anemia caused by nutrient deficiencies.  Amiodarone is a potassium channel blocking drug which is used to control the cardiac arryhthmia caused by thalassemia.      

 

Amiodarone is known to induce hypothyroidism and hyperthyroidism.  Following is a study about thyroid dysfunction induced by Amiodarone treatment.   

 

 

 

 

J Endocrinol Invest 1999 Jan;22(1):55-63

 

High prevalence of thyroid dysfunction in adult patients with beta-thalassemia major submitted to amiodarone treatment.

Mariotti S, Loviselli A, Murenu S, Sau F, Valentino L, Mandas A, Vacquer S, Martino E, Balestrieri A, Lai ME

Dipartimento di Scienze Mediche M. Aresu, Universita di Cagliari, Italy.

Amiodarone may induce hyper- or hypothyroidism. Patients with beta-Thalassemia Major (beta-Thal) have an increased prevalence of primary hypothyroidism and often require amiodarone for hemosyderotic cardiomyopathy. Aim of this study was to retrospectively evaluate thyroid function in beta-Thal adult patients on long-term amiodarone. The study group consisted of twenty-two (21 males, 1 female; age: 23-36 yr) beta-Thal patients submitted to long-term (3-48 months) amiodarone therapy from January 1991 to July 1996. Controls included 73 beta-Thal patients (23 males and 50 females aged 25-35 yr) not treated with amiodarone. In all cases serum free thyroid hormones, thyrotropin and thyroid autoantibodies were evaluated. A higher prevalence of overt hypothyroidism (5/22 [22.7%]) as compared to controls (3/73 [4.1%], p=0.02) was found in beta-Thal patients < or = 3 months after starting amiodarone, while the prevalence of subclinical hypothyroidism was similar in amiodarone-treated (18.2%) and untreated (15%) beta-Thal patients. Overt hypothyroidism resolved spontaneously after amiodarone withdrawal in 1 case, while the remaining patients were maintained euthyroid on amiodarone by L-thyroxine administration. After 21-47 months of amiodarone therapy, 3 patients (13.6%) developed thyrotoxicosis (2 overt and 1 subclinical), which remitted shortly after amiodarone withdrawal. No case of hyperthyroidism was observed in beta-Thal controls (p=0.012 vs amiodarone-treated patients). In conclusion, amiodarone administration is often associated in adult beta-Thal patients to a rapid progression of the pre-existing subclinical hypothyroidism, but transient thyrotoxicosis may also be observed after a longer period of therapy. These findings should be carefully considered in the management of these patients.

The following study shows that anemia and iron deficiency cause tongue pain. Thus tongue abnormalities may be a useful indicator of anemia.

 

 

 

Am J Med Sci 1999 Nov;318(5):324-9

The pathophysiology of glossal pain in patients with iron deficiency and anemia.

Osaki T, Ueta E, Arisawa K, Kitamura Y, Matsugi N

Department of Oral Surgery, Kochi Medical School, Nankoku-city, Japan.

BACKGROUND: It is well known that prolonged anemia causes atrophy of tongue papillae, glossal pain, and dysphagia, but it is uncertain whether iron (Fe) deficiency induces glossal pain without any objective manifestation. To resolve this matter, the relationship between Fe deficiency and glossal pain was examined. METHODS: Eighteen patients with Fe deficiency and 7 anemic patients manifesting spontaneous irritation or pain of the tongue without any objective abnormalities participated in this study. To ascertain the cause of glossal pain and the oral pathophysiology in Fe deficiency and anemia, peripheral blood was examined and the glossal pain threshold and salivary flow rates (SFRs) were estimated along with Candida albicans cell culture tests. RESULTS: Compared with patients with Fe deficiency, those with anemia had a longer history of tongue pain. In patients with anemia, painful areas of the tongue were more numerous than in patients with Fe deficiency. Pain thresholds were decreased in the painful portions, and both nonstimulated and stimulated SFRs were suppressed. Each patient was treated with oral Fe; within 2 months, most patients exhibited increased serum ferritin level (P< 0.02, paired t-test), pain threshold (P < 0.05) and salivation (P < 0.05) and glossal pain subsided. CONCLUSIONS: Fe deficiency causes glossal pain and the degree of glossal pain increases as Fe deficiency advances to anemia, manifesting hyposalivation and abnormalities of glossal papillae.

 

Protein Discovery Leads Researchers to New Suspect in Iron Anemia

 

From: http://www.berkeley.edu/news/berkeleyan/1999/0224/protein.html

 

By Kathy Scalise, Public Affairs
Posted February 24, 1999

If you're slugging down iron pills but remain weak and anemic, the culprit may not be iron at all, but another metal: copper. A new genetic find explaining why is described by a Berkeley scientist and his colleagues in this month's issue of the journal Nature Genetics.

The researchers discovered a protein, hephaestin, that appears critical for moving iron to the bloodstream. This protein contains copper and cannot be produced in the absence of copper. Thus in some cases, having too little copper present even with an ample iron supply might cause anemia, said the lead author on the paper, Assistant Professor Christopher Vulpe of the Division of Nutrition and Toxicology in the College of Natural Resources.

The new protein may also help explain what Vulpe describes as the number one inherited disease in Caucasians, hemochromatosis. It results from too much iron in the body and can cause diabetes if it kills insulin-producing cells in the pancreas, or "iron heart" if too much of the metal accumulates in that organ and causes cardiac arrest.

Vulpe's collaborators on the project included researchers from UC San Francisco, the University of Utah and the University of Queensland in Australia.

Hephaestin was isolated from mice and named after the Greek god for metal-working, Hephaestus. The protein is produced by the gene Heph, also discovered by the researchers and reported in the Nature paper, and is tethered to the membrane of intestinal cells. The researchers suspect it is a "multi-copper ferroxidase" protein that contains copper and works on iron molecules.

Vulpe led the original study while a postdoctoral fellow in the laboratory of Professor Jane Gitschier of UCSF. Gitschier said in a recent UCSF statement that "more work needs to be done to determine if and how often genetic defects in iron transport occur in humans."

In describing the possible role of the new protein, Vulpe traced the path of iron through the body.

Iron, he said, usually originates in the food supply, either as "heme," a cage of iron that transports oxygen in blood and comes mainly from meats, or as "free" iron from other sources. Both kinds of iron are processed by the gut -- stomach and intestine -- where they are converted by means not well understood to a form of iron readily used by the body. Finally, the iron winds up in the intestinal epithelial cells, ready for export to red blood cells, muscle tissue and organs.

But somehow "it has to get out of the gut and into the bloodstream," said Vulpe.

This is particularly difficult, he said, because the so-called "hydrophobic" intestinal membrane wants to reject the charged iron molecule.

So hephaestin comes into play. Probably acting as a helper molecule forming a complex with a yet unknown transport protein, it allows iron to make its way through the membrane.

In fact, hephaestin may act like an "on/off" switch to control the flow of iron into the body, said Vulpe. Perhaps in the presence of hephaestin, more iron is pumped into the blood, and when hephaestin stops production, the pumping also soon halts.

While a certain amount of iron is vital for survival, about 10 percent of infants and women of childbearing age in the U.S. -- about 8.5 million people -- are iron deficient. Many other people suffer from having too much iron circulating in the body, a syndrome called hemochromatosis, which can also have toxic effects.

When the body functions correctly, excess iron remains trapped in the intestine and is harmlessly excreted. Disease results only after too much iron escapes from the intestine and into the blood.

The UC researchers plan to investigate whether hephaestin plays a role in hemochromatosis.

They suspect improper regulation of the Heph gene may result