Originally published June 1994 The Townsend Letter for Doctors

Hemochromatosis Deadly and Undiagnosed Condition

Leslie N. Johnston, D.V.M.

Editor, Heredity hemochromatosis (HH) was once thought to be rare and if you consider 5 out of 1,000 people who have the double recessive genes to develop the diseases that this condition will lead to, then you can say that it is still a rare condition. Let us think of HH as a condition rather than a disease for if HH is not properly managed, it will lead to all kinds of diseases.

Like the wind on the ocean, just enough is needed to keep the waves choppy enough to keep the water aerated for the sea animals and just strong enough to gracefully make our ships sail across the water. What we dont need is enough wind to make the waves high enough to capsize our ships or to wash our shore lines away. The same goes for iron and our body, we need just enough iron to make and maintain our red blood cells and other vital processes, and to make them properly function and that is all. The amount of iron necessary to maintain the body is 3 to 5 grams and volume-wise, this is only about one half cc of ml. Something else to relate to is that 3 to 5 grams would be the volume of about one fifth of the last joint of your little finger. Very little more iron than this is necessary, and if
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more iron is absorbed it goes into storage and this is where iron overload problems begin. We now have the technology to measure the amount of iron in our bodies, and if we properly stain the tissues, iron can even be seen. The problem is that until the last 20 or so years, the amount of iron that we had in our bodies was not measured and it is not measured enough even today and the deadly diseases that iron overload leads to are what we have. Iron testing today is an absolute must; not so much of iron deficiency, but for iron overload.

It is not just the one and a quarter million people who have the double genes to develop HH, but it is also the 25 to 35 million who have the single gene or are carriers of HH that we have to deal with. Those with the double genes are the ones who absorb too much iron and those with the single gene absorb more than the normal person. Once iron is absorbed into the body, it is not lost unless the person bleeds; one milligram lost daily for normal body functions excepted.

No one knows just how much storage iron or iron overload is necessary to cause disease problems, but rest assured it is not near as much as it was once thought to be. The idea is to avoid the deadly iron buildup and to make the diagnosis before full blown HH; have the patients excess iron removed before this.

As far as this paper is concerned, hemochromatosis (H) means too much iron in the body. There are two types of hemochromatosis: heredity and acquired. Those with the double genes would probably eventually develop full-blown H from a normal non-iron fortified diet and the acquired type of H is because too much iron in the diet, too much medication with iron
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supplements, or from too many blood transfusions or disease conditions which are iron loading in nature.

Which doctors should be informed about H? Not just the Family Practice and Internal Medicine doctors, but all of these and more: Endocrinology, Gynecolory, Obstetrics, Psychiatry, Urology, Gastroenterology, General Surgery, Dermatology, Cardiology, Orthopedics, Rheumatology, Thoracic Surgery, Hematology, Pathology, Infectious Disease and all specialties. Look for this to be published in the practice parameter for HH by the College of American Pathologists.

Iron overload is holistic in that it affects the entire body. Lets start at the top.

Hair loss is caused by iron overload. This in itself is no big deal and may only be embarrassing to the patient, but dont forget this minor problem for the clue to a diagnosis.

With H, the skin may turn to a bronze or slate color: the further you go north, the more slate, and the further south you go, the more bronze the color. Dont be fooled by this, for the skin does not always change in color with H.

In those people with H, the brain is involved in that some of the people may have a sense of vertigo and a loss of memory. Evidence is now pointing to Alzheimers disease, Parkinsons and Tardive Dyskinesia being connected with iron overload. If iron overload can be connected with the heart attack, then it can be also connected with strokes caused by cholesterol problems
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in the blood vessels of the brain. Findlay, S., Podolsky, D., Silbemer, J., Iron and Your Heart, U.S. News and World Report, Sept. 21, 1992, pages 61-68. The pituitary gland is a very delicate piece of tissue and is very much involved with iron overload. Of course, this is the master gland and if you knock it out of commission, so goes other glands, namely the thyroid, parathyroid, adrenal, pancreas, and the gonads.

The heart is very much involved with H. That little bundle of nerve tissue that transmits the electrical impulses gets damaged so that your heart will misfire and run like a four cylinder engine with the timing chain out of it. The heart muscle takes up excessive iron and this makes it degenerate into cardiomyopathy. And then, there is strong, if not absolute proof, that iron acts on cholesterol in such a way that it makes cholesterol be deposited in the linings of the arteries of the heart.

Next, the liver is very much involved with H. All of the cells of the liver take up and store excess iron. This leads to an enlarged liver and an elevation in liver enzymes in the plasma. An elevation in liver enzymes is a very good reason to consider H as the cause. The pain that comes from the upper right quadrant of the abdomen, with some H patients, probably is associated with the liver. There is no double that cancer of the liver will develop in most of those patients improperly managed for H. Hepatoma is rare, but it sure is not rare in H patients about 219 to 240 times more so than in normal people. Cirrhosis will develop if the H patient is not properly managed.

The pancreas is also greatly involved. Remember that the pancreas is a dual action gland: secreting insulin into the bloodstream and digestive enzymes into the gut. Probably 50% of untreated H patients go on to
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develop diabetes, hence another name for H bronze diabetes. An increased incidence of pancreatic cancer is also associated with iron overload. Is there not a connection between Irritable Bowel Syndrome (IBS) and iron overload of the pancreas? Im sure this will be proven factual before too much longer. Even duodenal ulcers may be connected with this. How many more problems are associated with pancreatic unsufficiency?

Patients with H complain of very severe and explosive diarrheas and some with constipation. Iron is stored in the epithelial lining of the bowel and shedding of these cells is one way the body has to de-iron itself. However, shed off enough of these cells and what do you have bleeding ulcers. Acute abdominal pain cannot be ruled out as being caused by iron overload. The dumping syndrome is also associated with H. How many people have had their stomach operated on to correct this condition when the simple treatment of blood donations would have taken care of the problem? This could be the reason they are throwing away the books on gastric surgery having to do with the dumping syndrome and other diarrheas, because the end results did not take care of the problems.

Why does the aspirin a day work? Aspirin causes problems with the clotting process and also irritates the bowel so that it bleeds, therefore the person bleeds, loses iron and the curing of iron overload occurs.

Loss of function of the gonads is the result of insufficiency of the pituitary gland. This is too often overlooked by the physician in the case of impotence and the cessation of menstruation. Once that gonad part of the pituitary is damaged by iron overload, the sexual functions do not return to normal in a lot of the cases: but diagnose and treat the patients early enough and all is well.
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The joints, bones and related tissues are very much and painfully involved with iron overload. Iron overload causes a precipitation of calcium pyrophosphates in the joint spaces, the cartilage of the joint and the surrounding tissues of the joint. Calcium pyrophosphates are insoluble and will be with the patient until death. This arthritis cant even be cured; it may be stabilized by early diagnosis and proper management of iron overload. The hand joints, next the hips and knees and then the sternum and feet thrown in somewhere along the way is probably how this arthritis will progress. Acute gout or even chronic gout should be reason enough to test for iron overload.

Closely related to the joint involvement are the connective tissues extending from the joints and even into the muscles. A survey of fibromyalgia (also diagnosed as fibrositis, myofascial syndrome, fibromyositis, lumbago, neck spasm, pleurodynia and aches and charley horses) support group is now being done to see if there is a connection between iron overload and this condition. There is enough evidence now to prove that this is true in at least some cases. Acute, explosive and chronic diarrheas, also known as IBS, are associated with this fibromyalgia syndrome in some cases, to further confirm the iron overload connection with this multiplicity of conditions.

Infections just love people or animals with iron overload. Shell fish poisoning or infection caused by the mean bug Vibrio Vulnificus is probably the best example of how tragic and deadly this can be to people with iron overload. One with this infection who has H would be lucky to make it to the hospital and even if he recovered from this infection, his quality of life may be shattered. The physician must be very aggressive toward treating this infection and test this patient for iron overload. It has been proven that Bangs disease, tuberculosis and malaria, after being cured or arrested
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will relapse into active infection in at least some of those patients who are supplemented with iron. Nearly every infection we have is enhanced by iron overload.

There is no doubt that iron overload does enhance most cancers and does cause some cancers. People with untreated H are 219 to 240 times more likely to develop hepatoma than the normal person. There are any number of references that show that the incidence of liver, colon, pancreatic, and lung cancers, is increased by higher iron readings or excess iron found in these tissues. If the cancer is not directly caused by iron overload, iron is necessary for the growth of cancer cells, and iron overload is just the sauce that makes these cancer cells grow and prosper and overwhelm your body. Two brilliant papers by E. D. Weinberg, Ph.D. of Indiana University are given for reference: Cellular Iron Metabolism in Health and Disease, Drug Metabolism Reviews, 22(5); 531-579 (1990), and a Defense Against Infection and Neoplasia, Physiological Reviews, Vol. 64, No. 1, Jan. 1984, 65-102.

There is no doubt about this as seen in the AIDS patient. The iron readings will be reversed from the H patient. The serum iron and percent of saturation of transferrin will go way down and the amount of ferritin will go way up. This is the body withholding iron from infection and cancer and it does such a good job in that the body withholds iron from the making of red blood cells, resulting in anemia and the patient dies from suffocation among other things. This is like water, water everywhere and not a drop to drink and iron, iron everywhere and not an atom to use. Would you give this patient iron? Ref: conversation with Harry Bates, Ph.D., MethPath Labs, June 1992.

The diagnosis is simple and easy in most cases. You are told that to make a diagnosis a triad of disease processes are needed from heart, diabetic,
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liver, arthritic and skin problems. You are also told that the serum iron reading should be over about 150, the transferrin saturation over 50% for women and 60% for men, and that the ferritin reading should be over about 400. The idea is that these findings may be used for the diagnosis of fullblown H, but all of these high readings and the disease conditions that iron overload, will lead to, are to be avoided rather than to be used for a diagnosis. The literature and the labs that you are using will probably tell you that a normal reading for serum iron would be from about 50 to 150 and a normal transferring saturation of 25 to 50 or 60%. They will tell you that the ferritin reading can go up to about 300 to 400.

If you have patients with readings above 100 for serum iron, 35% saturation for transferrin, and 50 for ferritin, then this is the time to tell these patients to start donating blood to get these readings back down to at least these numbers especially for relatives of those patients who have been diagnosed with full blown H.

The tests to be run are: serum iron, transferrin, total iron binding capacity (TIBC), and ferritin. Unsaturated iron binding capacity (UIBC) could and is used in the place of TIBC. The percentage of saturation of transferrin can be obtained by dividing the serum iron reading by the TIBC; it is different using UIBC.

The liver biopsy is one of the best tests for H, but it sure isnt always the best test for the patient. This procedure is dangerous and one out of 1,000 patients aint going back home. I wouldnt want to be the physician in this case, and I sure wouldnt want to be the patient. Dont forget to stain the liver tissue with Prussian blue. Stay away from the liver biopsy if at all possible, especially from those relatives of the person who has already gone through the diagnostic experience of full blown H. You can go ahead and start the patient donating blood on the basis of the blood tests, and if
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the patient does not have hemochromatosis, the hematocrit or hemoglobin will drop like a lead balloon after four or five donations. Donating blood has to be one of the most healthful things an otherwise healthy person can do!

Today, any blood profile you have run on a patient should have at least serum iron and TIBC tests included. If these readings are high, then the lab should go ahead and run a ferritin test.

Deferoxamine sold under the trade name of Desferal (CIBA), can be used in the diagnosis and treatment of H, but stay away from the use of this drug if possible.

If you dont test for iron overload (H), it may cost you. Actually, these suits cost all of us, not just doctors. This is already a reality; a $2.2 million outof-court settlement was made to a woman for the doctor not testing and treating her for H. (Palm Beach Woman Wins $2.2 Million from Doctor, The Palm Beach Post, June 25, 1993.) You dont want to test for iron to avoid suits, you want to test for iron deficiency or overload, for the benefit of the patient and your own satisfaction. Remember that hemoglobin or hematocrit tests are not iron tests and if you use them as such, you are in deep trouble.

The treatment for iron overload (H) is the simple donating of blood, usually weekly one pint at a time for as long as it takes. As 70% of the normal persons iron is naturally chelated in the red blood cells, when a pint of blood is removed so is from 200 to 250 mgs of iron. To replace this pint of blood, the body draws both from normal and abnormal storage of iron and a little from the gut and this is the secret of the treatment. Prediction of how many blood donations it will take to de-iron the patient can be made for each 20 to 25 points of the ferritin reading; one pint of blood must be
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donated to reduce the ferritin reading by that much. This is a guide. Monitoring of hematocrit or hemoglobin and specific iron tests along the course of treatment are necessary; the hematocrit every time and the iron tests after about the fourth donation and towards the end of the treatment.

When the patient is made anemic and the iron test readings are at normal, establish a periodic donation schedule of say about 3 or 4 times yearly to keep the readings at normal. Have the patients iron readings checked afterwards about every 6 months to every 2 years.

The diet of the patient should be a good one and the patient should not try to avoid those foods high in iron except iron fortified foods. Tell the patient to eat a delicious diet and if he needs to, give another pint of blood to correct the situation.

Other iron loading conditions besides HH are: Sideroblastic anemia, Porphyria Cutanea Tarda, Transfusional Iron Overload, B-thalassemia, Xlinked Iron Loading Anemia, Pyriodoxine-responsive Anemia, Pyruvate Kinase Deficiency, Heredity Atransferrinemia, Neonatal Hemochromatosis, African Iron Overload, Post Portocaval Shunt, Chronic Hemodialysis, Sickle Cell Anemia, and Medicinal Iron Overload.

The fortification (adulteration would be a better term), of our foods with iron should be stopped now! Germany, France, Belguim, and Italy never have allowed their food companies to add iron to their foods and England has since lifted the requirement, so I understand. This should tell us something. The more iron there is in the diet, the more that is absorbed, and this practice is contraindicated in well over 30 million of our people. Ref. the Weinberg papers given above.
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Test for iron in your blood profiles!

Other Selected References: Crawford, Roberta, The Iron Elephant, Glyndon, MD; Vida Publishing, Inc., 1992; Emery, Thomas F., Iron and Your Health: Facts and Fallacies, Boca Raton, Boston, and Ann Arbor; CRC Press, Inc., 1991; Lauffer, Randall B., Iron Balance, New York, St. Martins Press, 1991; Practice Parameter for Hemochromatosis, this is a very good booklet: College of Am. Pathologists, 325 Waukegan Road, Northfield, IL 60093-2750.

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