ENDOCRINE SYSTEM and DIABETES

The endocrine system is affected by HH & the pancreas is one part of this system that is vulnerable to the effects of too much iron.  Some studies indicate that 10% of diabetes is caused by underlying iron overload in the pancreas.  Certainly, it would be prudent for all diabetics to have an iron profile done & all HH patients should have their pancreatic function evaluated!   Click on the titles to read more regarding diabetes with HH.

• A 24-year-old patient with decreased libido and erectile dysfunction as initial manifestations of hemochromatosis  Dtsch Med Wochenschr. 2000 Dec 1: In subfertility from an endocrine disorder primary hemochromatosis should be considered in the differential diagnosis. Only early diagnosis and prompt iron depletion may improve the prognosis of these patients.

• ABC of diseases of liver, pancreas, and biliary system Other causes of parenchymal liver disease  BMJ 2001;322:290-292 ( 3 February ) Haemochromatosis is the commonest inherited liver disease in the United Kingdom. It affects about 1 in 200 of the population and is 10 times more common than cystic fibrosis.

• Abnormalities in estrogen, androgen, and insulin metabolism in idiopathic hemochromatosis.  
  Ann N Y Acad Sci 1988  We have concluded that hypogonadism and carbohydrate intolerance are caused by the specific distribution pattern of excess iron in the organism, accompanied by functional impairment of affected parenchymal cells.

• A history of phlebotomy therapy for hemochromatosis.  Crosby WH. Chapman Cancer Center, Joplin, MO Am J Med Sci 1991 Jan  The earlier the disease is discovered, the less risk of morbidity and mortality. Screening tests (serum iron, total iron-binding capacity, serum ferritin) are recommended for all blood relatives of index cases of this hereditary disease and for all clinics where complications of hemochromatosis may be treated: liver disorder however mild, diabetes mellitus, heart disease, arthropathies, sterility, impotence, premature menopause, and abnormal pigmentation of the skin.

• A middle aged man with diabetes mellitus and a liver mass. Steven Eliason, M.D., Elizabeth M. Brunt, M.D., Bruce R. Bacon, M.D., Leonard E. Grosso, M.D., Ph.D.  SLUCARE PathLab Case of the Month  

• Annals of Internal Medicine SUPPLEMENT DIAGNOSIS AND MANAGEMENT 
  Diagnosis of Hemochromatosis, Annals of Internal Medicine, 1 December 1998. 129:925-931.Lawrie W. Powell, MD; D. Keith George, MD; Sharon M. McDonnell, MD; and Kris V. Kowdley, MD

• Association of increased ferritin with premature coronary stenosis in men
  Clin Chem 2001 Sep, Ferritin was significantly higher in diabetic male patients

• Body iron stores are associated with serum insulin and blood glucose concentrations.
  Diabetes Care 1997. Mildly elevated body iron stores are associated with statistically significant elevations in glucose homeostasis indexes.

• C282Y and H63D mutations of the haemochromatosis gene in patients with iron overload
  Rev Esp Enferm Dig 2001 [a pdf file]

• Cardiac dysfunction because of secondary hemochromatosis caused by congenital non-spherocytic hemolytic anemia. Jpn Circ J. 2001 Feb Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure.

• Cardiomyopathy as the cause of death in genetic hemochromatosis-.
  Z Gastroenterol. 1996 Mar [article in German] The reports of these two cases underline that hemochromatosis-associated cardiomyopathy is often irreversible if severe congestive heart failure is present. In cardiac decompensation heart transplantation has to be considered as early as possible.

• Chronic iron overload and toxicity: clinical chemistry perspective.
  Clin Lab Sci 2001 Summer; This toxicity involves many organs leading to a variety of serious diseases such as liver disease, heart disease, diabetes mellitus, hormonal abnormalities, dysfunctional immune system, etc. The tissue damage associated with iron overload is believed to result primarily from free radical reactions mediated by iron.

• Clinical Consequences of New Insights in the Pathophysiology of Disorders of Iron and Heme Metabolism Hematology 2000  The American Society of Hematology The screening strategy could be based on the assessment of serum transferrin saturation in adults aged 18 or more. Genetic testing testing for C282Y would be confined to individuals with transferrin saturation > 45%. This strategy would then avoid the ethical, logistical, and financial problems raised by systematic genetic testing as well as the societal impact of discovering a genetic mutation in asymptomatic persons without a disease. It is, in fact, essential that major changes occur in the attitudes towards unexpressed or slightly expressed HFE homozygosity, especially by insurers and health care administrators, to avoid any adverse genetic discrimination.

• Clinical Features of Genetic Hemochromatosis in Women Compared with Men 
  Abstracts - August 19, 1997 ANNALS OF INTERNAL MEDICINE  Recognizing the nonspecific nature of presenting symptoms in women is essential for early diagnosis and treatment.

• Clinical management of iron overload.
  Gastroenterol Clin North Am. 1998 Sep HHC is a common inherited disorder, characterized by iron accumulation in the liver, heart, pancreas, and other organs. The clinical consequences of systemic iron loading are diverse and not always improved with iron reduction therapy.

• Clinical spectrum and management of haemochromatosis 
  Baillieres Clin Haematol 1994 Dec Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.

• Clinical Studies of Haemochromatosis  Queensland Institute of Medical  Research, Hepatocellular Cancer Laboratory, Professor Lawrie Powell   Knowledge of haemochromatosis, its prevention, the type and severity of symptoms it causes, the availability and nature of treatment, ability of sufferers to participate in normal activities, and longevity are relevant issues for community education. Members of an informed public can mobilise support for the early diagnosis of haemochromatosis, encourage people to be tested for the disorder and influence the debate about screening.

• Clinico-morphologic characteristics of primary hemochromatosis
   Arkh Patol. 1995 Nov-Dec 12 autopsy cases of primary hemochromatosis were studied.

• Current concepts in rational therapy for haemochromatosis.  
  Drugs. 1991 Jun . Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years).
  
• Current diagnosis: hereditary metabolic diseases of the liver (primary hemochromatosis, Wilson disease] Schweiz Rundsch Med Prax 1996 Nov [article in German]

• Deferoxamine therapy in high-ferritin diabetes.
  Cutler P.  Diabetes 1989 Oct  Data show that lowering elevated ferritin levels correlated well with diabetes control and improved fasting glucose, triglyceride, and HbA1c in 8 of 9 patients with high ferritin levels. This study shows there is a need to study iron metabolism in poorly controlled diabetes and demonstrates the value of DFO in controlling high-ferritin diabetes.

• Dermatology and the Liver and the Pancreas:  Hemochromtaosis  Section 6 of 10.  Emedicine journal Sept. 27, 2001.  Hemochromatosis is a disorder of increased iron uptake leading to excess deposition in multiple body organs. The dermatologic manifestation of the disease involves skin hyperpigmentation, which is present in more than 90% of patients at the time of diagnosis. This discoloration has a characteristic metallic gray or bronze-brown color that is generally diffuse, but it may be increased in areas of scars or on the face, neck, extensor surfaces of the arms, or genitalia. Approximately 20% of patients also have pigmentation of the buccal mucosa or the conjunctiva.

• Diabetes and haemochromatosis: current concepts, management and prevention.
  Diabete Metab 1995 Dec Diabetes, a serious complication of haemochromatosis, is frequently associated with cirrhosis which reduces life expectancy.

• Diabetes and serum ferritin concentration among U.S. adults.  Diabetes Care. 1999 Dec  Elevated serum ferritin concentration was associated with an increased risk of diabetes.

• Diabetes mellitus and a liver mass
  August 1999, Eliason, Brunt, Bacon, Grosso.  Case report of a middle-aged man

• Diabetes mellitus in hemochromatosis Z Gastroenterol. 1999 Jun  [Article in German] The degree of glucose intolerance and diabetes mellitus in hemochromatosis is closely associated with the stage of iron overload and thus also the stage of the accompanying liver disease. Similar to other liver diseases glucose intolerance due to insulin resistance precedes diabetes mellitus also in hemochromatosis.

• Diabetic ketoacidosis and hypogonadotropic hypogonadism in association with transfusional hemochromatosis in a man with beta-thalassemia major, J Formos Med Assoc 2001 Jul

• Diabetic Pancreas: Hemochromatosis, slides & pictures  Michigan State University

• Diagnosis and management of hemochromatosis
  by Dr. Anthony Tavill, Director of the Maurice and Sadie Friedman Center For Digestive Diseases and Liver Disorders, Mathile and Morton J. Stone Professor of Digestive Diseases and Liver Disorders at the Mt. Sinai Medical Center, Professor of Medicine and Nutrition at Case Wetern Reserve University. [Excellent & thorough article of diagnosis & treatment.  This is a pdf file] 

• Diagnosis and treatment of genetic hemochromatosis Rev Prat. 2000 May 1 [Article in French]
  Moirand R, Guillygomarc'h A, Brissot P, Deugnier Y. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.

• Dietary Iron Supplements - Use or not to use?
  Nutrition Today James R. Connor John L. Beard 05-06-1997 There is little reason to support a general need for iron supplementation in the diet at any age. Perhaps this article and review of supplementation pros and cons should conclude with a new interpretation of an old saying: "It is better to wear out than to rust out;" don't expose your system to more iron than it needs.

• DIGESTIVE TRACT AND REGULATION
  REGULATION OF METABOLISM & ENERGY BALANCE   November 13, 1998 (Chap. 17; pp. 602-607)

• Dr. Rose's Peripheral Brain--HEMOCHROMATOSIS

• Effects of Iron Overload Harvard University 1999

• "Effect of phlebotomy treatment on diabetes mellitus and impaired glucose tolerance."  
  Excerpt from the "Barton" book  pg. 272-273. 

• Endocrine abnormalities in idiopathic haemochromatosis.  Q J Med. 1983 Winter  Impairment of anterior pituitary function occurs in idiopathic haemochromatosis but is selective; gonadotrophin and prolactin deficiencies are common. Clinical hypogonadism is usually hypogonadotrophic in origin.

• Endocrine complications of genetic hemochromatosis
  Acta Clin Belg   1999 Dec  Impairment of anterior pituitary function occurs in idiopathic haemochromatosis but is selective; gonadotrophin and prolactin deficiencies are common.

• Epidemiology, clinical spectrum and prognosis of hemochromatosis,
  abnormality in liver function tests (75%), weakness and lethargy (74%), skin hyperpigmentation (70%), diabetes mellitus (48%), arthralgia (44%), impotence (45% in males), and ECG abnormalities (31%) were the most frequent findings and symptoms at diagnosis.  Adv Exp Med Biol 1994

• Factors affecting glucose tolerance in hereditary hemochromatosis
  Clin Invest Med 1997 Apr; These results suggest that iron overload can impair insulin secretion and glucose tolerance early in hereditary hemochromatosis, before cirrhosis occurs.
• Ferritin Physiology Overview of the function of ferritin with a section on hemochromatosis.

• FINAL DIAGNOSES:  A case of Hereditary Hemochromatosis with dilated cardiomyopathy, micronodular cirrhosis, history of chronic alcoholism from Department of Pathology, University of Pittsburgh School of Medicine.

• Genetic Haemochromatosis:   A guideline on Diagnosis & Therapy compiled on behalf of the Clinical Task Force of the  British Committee for Standards in Haemotology  2/2000 [a pdf file]

• Genetic Health-What Is Hemochromatosis? By Amanda Ewart Toland, PhD  Reviewed by Chris Friedrich, MD, PhD Last updated September 1, 2000

• Haemochromatosis and Diabetes– By Paul Steel.  Paul Steel is a diabetes educator with Manningham Community Health Service in Victoria. He has both a personal and professional interest in haemochromatosis, the most common genetic disorder in Australia, occurring in about one in 300 people.

• Haemochromatosis as an endocrine cause of subfertility. 
  BMJ 1998;316:915-916 ( 21 March ) Clinical review.  Lesson of the week.   Haemochromatosis is well established as a cause of infertility in both men and women, usually because iron deposition in the pituitary or the gonads leads to hypogonadism.  As haemochromatosis is a fairly common disorder it should be considered when subfertility from an endocrine disorder is being investigated.

• Haemochromatosis may present as exercise related joint pains without arthropathy, early treatment improving outcome, Case reports including x-ray pictures of hips, hands, knees. CLINICAL REVIEW Lesson of the week: Ian McCurdie and J David Perry BMJ 1999

• Haemoglobin AIc in patients on venesection therapy for haemochromatosis
  [Article in French] Diabete Metab 1982 Jun Thus, the decreased HbAIc rates observed in haemochromatosis patients may be ascribed to the venesection therapy, which induces an increased turnover of red cells, and consequently a decrease of the time available for their glycosylation.

• Hemochromatosis can now be appropriately defined as the presence of two hemochromatosis alleles with or without organ injury, and with or without the presence of iron overload. [I have not been able to retrieve the url to the website from where this came, so if anyone locates it, please let me know!]

• Hemochromatosis eMedicine Journal, December 7 2001, Volume 2, Number 12, Authored by Sandor Joffe, MD, Section Chief of Abdominal Imaging, Department of Radiology, Beth Israel Medical Center  This article covers the pathophysiology of hemochromatosis as well as the techniques in using ULS, CT & MRI to identify iron deposition in the organs. Pictures & descriptions from scans of the abdomen are shown. The pancreas also is commonly involved by primary hemochromatosis. Patients with early hemochromatosis (noncirrhotic) frequently have insulin resistance, while patients with cirrhosis and hemochromatosis often have insulin-dependent diabetes mellitus (IDDM).

• Hemochromatosis  Gale Encyclopedia of Medicine The symptoms of hemochromatosis include fatigue, weight loss, weakness, shortness of breath, heart palpitations, chronic abdominal pain, and impaired sexual performance. The patient may also show symptoms commonly connected with heart failure, diabetes or cirrhosis of the liver. Changes in the pigment of the skin may appear, such as grayness in certain areas, or a tanned or yellow (jaundice) appearance.

• Hemochromatosis: A Common, Rarely Diagnosed Disease
  By Vincent J. Felitti, MD, FACP  Commentary by David Baer, MD, FACP.  Hemochromatosis is the most common, life-threatening genetic disorder in North America, yet most physicians have never personally diagnosed a case: all see an unrecognized case in their offices every two weeks.

• Hemochromatosis: a review.  Clin J Oncol Nurs 2001 Nov-Dec;5(6):257-60   Dolbey CH. Fletcher Allen Health Care, UHC Campus, Arnold 2, 1 South Prospect Avenue, Burlington, VT, 05401, USA. This disorder affects the liver, pancreas, heart, and endocrine systems, and if undetected and untreated, organ damage and death can result.

• Hemochromatosis, A simple genetic trait, Dr. Richard D. Press, Oregon Health Sciences University With the discovery of the causative gene, the disorder stands revealed as America's single most common mendelian disease. Unlike other genetic diseases, it is already curable. Indeed, genetic screening makes it potentially preventable.

• Haemochromatosis as an endocrine cause of subfertility, case report BMJ 1998

• Hemochromatosis at the intersection of classical medicine and molecular biology.
  C R Acad Sci III 2001 Sep, Brissot P

• Hemochromatosis:  Conemaugh Health System  
  Hemochromatosis is a condition that develops when too much iron builds up in the body. Excess iron is stored in the organs, such as the kidneys, liver, and heart, and in the joint tissues.

• Hemochromatosis, Cooley Dickinson Hospital  Editor: George R Bowers MD CDH Oncology  January 2000 Volume 4: No. 1.   Hemochromatosis is a common, genetically transmitted disease. The diagnosis of hemochromatosis is sometimes difficult and frequently missed. This issue will review the pathogenesis, diagnosis and treatment of this fascinating disease. Ms. Kathy Fleming will review the management of a most troubling complication of therapy---lymphedema. 

• Hemochromatosis, Front Range Gastroenterology Associates, P.C.  
  2030 Mountain View Avenue, Suite 300, Longmont, CO.  Basic statistics on HH.

• Hemochromatosis: Gastrointestinal Health Hemochromatosis, the most common genetic disease in the United States, results in iron overload and, if left untreated, severe organ damage. 

• Hemochromatosis: genetics helps to define a multifactorial disease 
  Clin Genet, 54(1):1-9 1998 Jul University of Washington, Seattle 98105 wburke@u.washington.edu  Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder.

• Hemochromatosis:  Genetics, Pathophysiology, Diagnosis and Treatment, "Introduction to Hemochromatosis"  Part I,  by Barton & Edwards.  Except from their book, [a pdf file] This is a large & excellent book covering all areas of hemochromatosis.  Published in 2000, $215.00
  [***According to Barton & Edwards, "diabetes is now the second most common cause of death in hemochromatosis cases."]

• HEMOCHROMATOSIS; HFE Mercier et al. (1997) urged strongly that the symbol HFE be used for the hemochromatosis gene rather than 'HLA-H' as used by Feder et al. (1996)

• Hemochromatosis in Ireland and HFE. Blood Cells Mol Dis. 1998  The allele frequency of 14% for the C282Y mutation in our control population is the highest reported and supports the hypothesis of a Celtic origin for the hereditary hemochromatosis gene.[pdf file]

• Hemochromatosis:  Life Extension Foundation website.  Disease, Prevention & Treatment 3rd editon.  Dietary & Vitamin recommendations listed here including calcium for blocking of iron absorption.

• Hemochromatosis Mutation Detection, Cys282Tyr and His63Asp  
  Guide to Clinical Laboratory Testing &  Interpretation of genetic testing. 

• Hemochromatosis Special  American Liver Foundation newsletter,  ALF Progress, Vol. 21 No. 1, Summer 1999 The ALF newsletter created three scenarios based on the real life ethical, economic and medical quandaries posed by hemochromatosis, and asked three experts from divergent fields to respond with their opinions. The experts are: Bruce R. Bacon, MD [Director, Div. of Gastroenterology & Hepatology, Saint Louis University School of Medicine, St. Louis, M0]; medical ethicist Mark A. Rothstein, Esq. [Director, University of Houston Law Center, Health Law & Policy Institute, Houston, TX] and hemachromatosis patient Gayle Hoffman.

• Hepatic injury in chronic iron overload. Role of lipid peroxidation.   Chem Biol Interact. 1989 Bacon BR, Britton RS. Excess deposition of iron in the parenchymal tissues of several organs (e.g. liver, heart, pancreas, joints, endocrine glands) results in cell injury and functional insufficiency.

• Hereditary Hemochromatosis and Cancer risk:  More fuel to the fire?  Gastroenterology Vol. 121, No. 5, November 2001  Pg. 1253 [a pdf file]  These data suggest an involvement of iron in carcinogenesis even in heterozygotes for HFE mutations. 

• Hereditary Haemochromatosis and Iron Metabolism, Carlson J, Olsson S, eJIFCC vol 13 no 2, THE JOURNAL OF THE INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY

• Hereditary hemochromatosis.  Ann Clin Lab Sci. 1998 Sep-Oct   Patients at risk for genetic hemochromatosis should be screened, identified, and treated as early as age 20 to prevent or minimize the deadly complications of hemochromatosis. Population screening should include measurements of serum iron concentration, total iron binding capacity (TIBC), percent saturation of transferrin, and serum ferritin concentrations.  Early diagnosis and treatment will reduce the population of aging individuals with severe, complicated hemochromatosis and dramatically reduce medical costs (billions of U.S. dollars per annum) associated with the management of this disease.

• Hereditary Hemochromatosis--A Risk Factor for Cardiovascular Disease The HH mutation is a human genetic model of disturbed iron metabolism, which facilitates research to the mechanism of HH and iron involved in cardiovascular disease. We expect that in the near future, the mechanism of disturbed iron metabolism leading to cardiovascular disease in human will be better understood.

• Hereditary Hemochromatosis 
  CME Activity, Release Date: 2/28/2000 Expiration Date: 2/28/2002 From the February 2000 Issue of Physician Assistant  Objectives: After reading the article, the reader should be able to:
  1. describe the pathophysiology of hereditary hemochromatosis;
  2. recognize the clinical symptoms and signs of hereditary hemochromatosis;
  3. outline screening and evaluation testing; and
  4. provide accurate diagnosis, management, and treatment.

• Hereditary hemochromatosis: diagnosis and treatment in primary care
  Tenn Med 1999 Nov With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.

• Hereditary Hemochromatosis FamilyPractice.com  Robert B. Hash, MD, Department of Family Medicine, Mercer University School of Medicine, Macon, Ga. [J Am Board Fam Pract Dec. 2000] Considering the prevalence of the disease, it is important for physicians to consider it in the differential diagnosis when patients complain of the common signs and symptoms. For most patients hereditary hemochromatosis can be successfully treated in the physician's office. Early diagnosis and treatment, before signs of iron toxicity, if possible, can result in improved quality and quantity of life for many patients.

• Hereditary hemochromatosis: impact of molecular and iron-based testing on the diagnosis, treatment, and prevention of a common, chronic disease.  Arch Pathol Lab Med. 1999 Nov, Press RD.  Department of Pathology, Oregon Health Sciences University, Portland 97201, USA. pressr@ohsu.edu This direct HFE mutation test can now be used not only to confirm the diagnosis of HH in those with symptomatic disease, but also, perhaps more importantly, to detect those with presymptomatic iron overload in whom future disease manifestations may be prevented (with phlebotomy therapy).

• Hereditary hemochromatosis in children, adolescents, and young adults. 
  Am J Pediatr Hematol Oncol. 1988 Spring  Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.

• Hereditary Hemochromatosis, J Am Board Fam Pract 14(4):266-273, 2001, Robert B. Hash, MD, Department of Family Medicine, Mercer University School of Medicine, Macon, Ga

• Hereditary hemochromatosis. J Fam Pract, 44(3):304-8 1997 Mar  Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.

• Hereditary hemochromatosis: Preventing chronic effects of this underdiagnosed disorder
  Sharon M. McDonnell, MD, MPH; David Witte, MD, PhD VOL 102 / NO 6 / DECEMBER 1997 / POSTGRADUATE MEDICINE.  In this article, Drs McDonnell and Witte discuss the diagnosis and management of this under-recognized problem as well as the various issues involved in screening. An illustrative case of hemochromatosis is also included.

• Hereditary Hemochromatosis Since Discovery of the HFE Gene  Clinical Chemistry 2001 [a pdf file] Includes an algorithm for screening and diagnosis of hemochromatosis. This review provides a comprehensive discussion of known mutations in the HFE gene and their phenotypic expression

• HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology
  Am J Epidemiol 2001 Aug 1

• HFE gene knockout produces mouse model of hereditary hemochromatosis Proc Natl Acad Sci U S A. 1998 Mar.  Xiao Yan Zhou, Shunji Tomatsu, Robert E. Fleming, Seppo Parkkila, Abdul Waheed, Jinxing Jiang, Ying Fei, Elizabeth M. Brunt, David A. Ruddy, Cynthia E. Prass, Randall C. Schatzman, Rosemary O'Neill, Robert S. Britton, Bruce R. Bacon, and William S. Sly  The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload.

• HFE mutations in insulin resistance-associated hepatic iron overload.J Hepatol. 2000 Sep;33;33(3):515-6. No abstract available.

• HFE-PROTEIN IN HEREDITARY HEMOCHROMATOSIS
  Hereditary hemochromatosis is the most common known autosomal recessive disorder in Caucasians

• Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients.
  Am J Clin Pathol. 2001 Aug The aim of the present study was to describe histologic features of the liver in insulin resistance-associated hepatic iron overload (IR-HIO), defined as the association of metabolic disorders and hepatic iron overload.

• Homozygosity for hemochromatosis: clinical manifestations.  Ann Intern Med. 1980 Oct; Diagnosis of asymptomatic hemochromatosis is important because organ damage may be prevented by early therapy.

• How Do I Know If I've Got Too Much Iron?  "The Protein Power Lifeplan" by Michael R. Edes, MD and Mary Dan Eades, MD.  How much iron should you have in storage?  Probably around 500 mg or a little less, which corresponds to a serum ferritin of 50 or lower.

• Hypogonadism and sexual dysfunction in hemochromatosis: the effects of cirrhosis and diabetes.
  J Clin Endocrinol Metab. 1989 Jul  Sexual dysfunction was a common early complaint in hemochromatosis patients, but these symptoms were frequently overlooked, leading to diagnostic delay.

• Idiopathic hemochromatosis in a 45-year-old infertile man. Andrologia. 1987 Sep-Oct The clinical manifestations of primary or idiopathic hemochromatosis include mainly hepatomegaly, diabetes mellitus, and hypogonadism.

• Idiopathic hemochromatosis in a young female. A case study and review of the syndrome in young people Gastroenterology 1979 Jan;76(1):178-83  The case presented here describes a 26-yr-old woman with problems presenting heart failure, insulin-dependent diabetes, hepatomegaly, and secondary amenorrhea.

• Idiopathic hemochromatosis presenting as amenorrhea and arthritis 
  Am J Med 1987 May A young woman with idiopathic hemochromatosis is described.

• Insulin resistance-associated hepatic iron overload Gastroenterology 1999 Nov; This study shows that patients with unexplained hepatic iron overload are characterized by a mild to moderate iron burden and the nearly constant association of an IRS irrespective of liver damage.

• Investigating Anaemia and Iron Storage Disease
  Discussion of the different types of anemia, as well as the effects of iron overload.  

• Iron catalyzed oxidative damage, in spite of normal ferritin and transferrin saturation levels and its possible role in Werner's syndrome, Parkinson's disease, cancer, gout, rheumatoid arthritis, etc.
  Med Hypotheses 2000 Sep the disease is often overlooked by physicians, until several organs have been damaged permanently (heart, liver, brain, pancreas, kidneys, spleen, etc.). Moreover, since ferritin, transferrin saturation and hematocrit levels are not directly related to cellular iron levels, and since excess iron can wreak havoc in the cell, we can conclude that there is a need for a better way to evaluate intracellular iron levels and especially the intracellular free iron levels by a non-invasive technique.

• Iron is Hot:  An Update on the Pathophysiology of Hemochromatosis:  Blood Journal Sept. 15, 1998  Genetic iron overload disorders are prevalent yet poorly understood. [A pdf file.]

• Iron Loading and Disease Surveillance
  Eugene D. Weinberg   Indiana University, Bloomington, Indiana   Emerging Infectious Diseases Journal, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Excessive iron in specific tissues and cells (iron loading) promotes development of infection, neoplasia, cardiomyopathy, arthropathy, and various endocrine and possibly neurodegenerative disorders.

• IRON OVERLOAD AND INSULIN RESISTANCE: Hyperferritinemia with normal transferrin saturation.   The increased iron burden should presumably be treated as in genetic hemochromatosis. Whether morbidity and mortality from the associated conditions is modified by such a measure remains to be determined.

• Iron overload and public health
  Bull Acad Natl Med. 2000  Genetic hemochromatosis, due to its frequency (about 300,000 cases in France) and to its severity, must be considered as a public health burden. Its curability--insofar as its diagnosis has been made early--and the disposal of non invasive and reliable phenotypic (transferrin saturation) and genotypic (HFE C282Y mutation) tests make its diagnosis easy.

• Iron Loading and Disease Surveillance Eugene D. Weinberg, Indiana University, Bloomington, Indiana, USA Emerging Infectious Diseases

• Iron Overload Disease due to Hereditary Hemochromatosis  CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection and treatment for this genetic condition can lessen morbidity and mortality, and in some cases prevent the onset of disease. Therefore, early detection of hemochromatosis represents a major chronic disease prevention opportunity.

• Iron Overload Disorder Common and Increases Risk for Heart Attacks
  Full Health Nutrition Canada ArterialHealth e-News^© October 1999 A genetic defect that causes iron overload disease is the most common inherited disorder among whites, affecting one in 188 people of northern European descent.

• Iron Overload (Hemosiderosis; Hemochromatosis) The Merck Manual of Diagnosis and Therapy Section 11. Hematology And Oncology Chapter 128. Hemochromatosis is often diagnosed late in the course of disease after significant tissue injury is present because the clinical symptoms are insidious and the extent of organ involvement varies; thus, the full clinical picture evolves slowly.

• Liver disease and diabetes, MayoClinic.com questions and answers section

• Long-term survival analysis in hereditary hemochromatosis.
  Gastroenterology. 1991 Aug Early diagnosis and treatment of hemochromatosis in the precirrhotic stage can lead to long-term survival similar to that in the general population. The presence of cirrhosis significantly increases mortality and is the major clinical factor affecting survival.

• Long-term survival in patients with hereditary hemochromatosis Gastroenterology, Vol 110, 1107-1119, 1996 by American Gastroenterological Association   Prognosis of hemochromatosis and most of its complications, including liver cancer, depend on the amount and duration of iron excess. Early diagnosis and therapy largely prevent the adverse consequences of iron overload.

• Management of hereditary hemochromatosis. Blood Rev. 1994 Dec Phatak PD, Cappuccio JD. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening.

• Management of hemochromatosis. Hemochromatosis Management Working Group.
  Ann Intern Med. 1998 Dec 1  Barton JC, McDonnell SM, Adams PC, Brissot P, Powell LW, Edwards CQ, Cook JD, Kowdley KV.  The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management.

• Molecular genetics of hemochromatosis 
  Ann Endocrinol (Paris) 1999 Sep Hemochromatosis is a recessive disorder of iron metabolism characterized by progressive iron loading of parenchymal organs, which accounts for clinical complications such as cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions and arthropathy.

• Most People Get Too Much Not Too Little Iron   Optimal Wellness Center Issue 200 March 7, 2001 Dr. Joseph Mercola.  DR. MERCOLA'S COMMENT: I have warned about the dangers of iron many times before in this newsletter. It is a potentially dangerous supplement and it needs to be used very cautiously, especially in those with an increased risk of heart disease.

• Nonalcoholic fatty liver disease: a feature of the metabolic syndrome: Diabetes 2001 Aug;  There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis.

• Overview on Iron Overload and Hemochromatosis CDC website, National Center for Chronic Disease Prevention and Health Promotion.  Early detection of hemochromatosis is essential because the disease’s potentially serious complications can be prevented by early therapy.

• Pathology Cases for Diagnosis: A 37 year old male is referred to the liver clinic for evaluation of abnormal liver related enzymes.  Includes pictures of biopsy slides. Case 96-19: Liver II Contributed by D. Robert Dufour, M.D., CAPT, MC, USNR-R Date Available: July 22, 1996 - December 31, 1996 

• Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene The C282Y gene mutation is a potential genetic marker for type 2 diabetes. It, or a closely linked gene, may be associated with greater than 20% of cases of type 2 diabetes.

• Population screening in hereditary hemochromatosis   Annu Rev Public Health 2000

• Practice guideline development task force of the College of American Pathologists. Hereditary hemochromatosis. Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA. College of American Pathologists Clin Chim Acta 1996 Feb. In view of the high prevalence in the American population (prevalence varies with ethnic background), the low cost of diagnosis and treatment, the efficacy of treatment if begun early, and, on the other hand, high costs and low success rate of late diagnosis and treatment, systematic screening for hemochromatosis is warranted for all persons over the age of 20.

• Preventing manifestations of hereditary haemochromatosis through population based screening.
  To evaluate the efficacy of identifying presymptomatic hereditary haemochromatosis through population based screening.  J Med Screen 1994 Jan

• Protect Yourself: Only Eat Fish That's Been Thoroughly Cooked  Important Health Information For People With Diabetes Mellitus   DEPARTMENT OF HEALTH AND HUMAN SERVICES   PUBLIC HEALTH SERVICE  U.S. FOOD AND DRUG ADMINISTRATION  This brochure is to inform people with diabetes mellitus of the hazards they face if they eat raw molluscan shellfish-- oysters, mussels, clams, and whole scallops.

• PubMed Search for Diabetes mellitus in hemochromatosis resulting in 342 articles

• PULLING IRON OUT OF THE FIRE by Shelly Morrow.  This article appeared in the Sept/Oct 2000 issue of Arthritis Today, published by the Arthritis Foundation, Inc.,

• Recognition and management of hereditary hemochromatosis.   Am Fam Physician 2002 Mar 1 65:853-60 Brandhagen DJ, Fairbanks VF, and Baldus W Mayo Medical School, Rochester, Minnesota, USA. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations and resolving ambiguities concerning iron overload.

• Recognizing genetic hemochromatosis.  J La State Med Soc. 1994 Dec  This article reviews the disease process hemochromatosis, which is now recognized as one of the most common genetic disorders.  It is imperative that physicians learn to recognize early signs and symptoms of hemochromatosis so that treated patients can expect a normal life span with minimal medical intervention.

• Reduced chromium retention in patients with hemochromatosis, a possible basis of hemochromatotic diabetes, Metabolism 1979 Jan

• Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis 
  Rev Port Cardiol 1994 Oct   It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.

• Relating Genomic Research to Patient Care JAMA 11/2000 Educating health care professionals about the complexities of the genetics of adult disease (in addition to congenital illness) is an important goal, and one disease model that is useful for this purpose involves hemochromatosis.

• Relation between iron stores and non-insulin dependent diabetes in men: case-control study 
  Non-insulin dependent diabetes mellitus is a common complication of diseases of iron overload such as haemochromatosis; 53-80% of patients with haemochromatosis develop diabetes. The development of diabetes in haemochromatosis is related to the magnitude of the excess iron. 1998, British Medical Journal BMJ 1998;317:727,730 (12 September)

• Response to repeated phlebotomies in patients with non-insulin-dependent diabetes mellitus.
  Metabolism. 1994 May Bleeding produced a significant decrease in serum glucose, cholesterol, triglyceride, and apoprotein B concentration in diabetic patients.  Moreover, three nonrespondent diabetic patients with poor glycemic control responded normally 6 to 13 months later, in a second operation, when glycemic control had improved significantly.

• Risk of disease in siblings of patients with hereditary hemochromatosis Digestion 2001

• Risk of neoplastic and other diseases among people with heterozygosity for hereditary hemochromatosis.  Cancer. 1995 Sep 1 . Heterozygosity for HH is associated with increased risk for colorectal neoplasia, diabetes, hematologic malignancy, and gastric cancer.

• Role of C282Y mutation in haemochromatosis gene in development of type 2 diabetes in healthy men: prospective cohort study. British Medical Journal BMJ 2000 (24 June) As the incidence of diabetes in northern Europe is among the highest in the world and rising, screening for C282Y mutation by DNA analysis, monitoring of iron status, and iron depleting treatment could potentially constitute new important measures in the primary prevention of diabetes.

• Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy: Diabetes Care 2001 Jul

• Safety aspects of iron in food. 
  Ann Nutr Metab 2001;  There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects.

• Screening for genetic haemochromatosis in blood samples with raised alanine aminotransferase
  Gut 2000;46:707-710 ( May )

• Screening for Iron Overload due to Hereditary Hemochromatosis 
  CDC website, Reyes, Michele, PhD and Muin J. Khoury, MD, PhD,  National Center for Chronic Disease Prevention and Health Promotion  Identifying people early with evidence of iron overload represents a major chronic disease prevention opportunity.

• Should all patients with diabetes mellitus be screened for hemochromatosis?   Department of Family Medicine University of California, Los Angeles 924 Westwood Blvd, Suite 650 Los Angeles, CA 90095-1628  West J Med 2002;176:110-114  Enhanced case finding becomes the first stage in a public health response when evidence has emerged for an effective early treatment of a disorder. It means the detection of HHC at the time of early symptoms, and it allows patients to benefit from early phlebotomy.  The implementation of this approach would include adding fasting serum transferrin saturation to the usual workup of patients with newly diagnosed diabetes mellitus, arthritis, and impotence.  The CDC recommends such iron-overload testing in anyone with possible symptoms of hemochromatosis, which includes patients with newly diagnosed diabetes mellitus.

• Successful treatment using iron depletion phlebotomy combined with recombinant erythropoietin after allogeneic bone marrow transplantation for myelodysplastic syndrome complicated by secondary hemochromatosis, Rinsho Ketsueki 2001 Jul

• The articular damage of hemochromatosis. A little known aspect Recenti Prog Med 1999 Apr The aim of this report is to underline that the patients with premature osteoarthritis or unexplained chondrocalcinosis must be screened for genetic haemochromatosis in order to formulate the correct diagnosis before the development of severe internal organ involvement

• Survival and causes of death in hemochromatosis.   Observations in 163 patients.
  Ann N Y Acad Sci. 1988  Life expectancy was reduced in patients who presented with cirrhosis or diabetes compared to patients who presented without these complications at the time of diagnosis. Patients who could be depleted of iron during the first 18 months of venesection therapy had a markedly better prognosis compared to those patients who could not be depleted during this time period.

• The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology. 1997 Jan The nonspecific nature of the presenting features in patients and the presence of significant clinical symptoms in patients discovered through family investigations underscore the importance of family and population screening for hemochromatosis.  The prevalence of cirrhosis, diabetes, cardiac disease, pigmentation, and fatigue increased as liver iron concentration increased. The most common presentations at diagnosis were fatigue.

• The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans Am J Gastroenterol 2001 Aug.  Diabetes mellitus (DM) has been reported to increase the risk of hepatocellular carcinoma (HCC). We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC

• Too Much Iron Can Cause Problems  What's New, from the 8th Conference on Retroviruses and Opportunistic Infections March 27, 2001

• Too much iron can hurt joints, body organs 
  The Albuquerque Tribune. By John Crowe The Associated Press 1/11/00

• Ultrastructural changes in the pancreas of carbonyl iron-fed rats.  
  Iancu TC, Ward RJ, Peters TJ. Division of Clinical Cell Biology, MRC Clinical Research Centre, Harrow, Middlesex, U.K.    J Pediatr Gastroenterol Nutr 1990 Jan   Diabetes mellitus is found with increased frequency in patients with both primary and secondary hemochromatosis.

• Use of HFE Mutation Analysis for Hereditary Hemochromatosis:  The Need for Physician Education in the Translation of Basic Science to Clinical Practice  Manish Kohli, MB, ChB, Steven A. Schichman, MD, PhD, Louis Fink, MD, Clive S. Zent, MB, BCh, Department of Internal Medicine, Division of Hematology/Oncology and the Department of Pathology, John L. McClellan Memorial Veteran's Hospital and University of Arkansas for Medical Sciences, Little Rock.  Southern Medical Journal

• Venesection therapy of insulin resistance-associated hepatic iron overload
  J Hepatol 2001 Sep The association of hepatic iron overload with metabolic disorders has been coined as the insulin resistance-associated hepatic iron overload syndrome (IR-HIO).

• What's new in hemochromatosis.  Curr Opin Hematol 2001 Mar  The high correlation of HFE to HHC has caused it to be considered as a candidate gene for population-based genetic testing for diagnosis and detection of predisposition to HHC. 

• Why concentration of serum ferritin does not in all circumstances reflect storage iron but is still of value in its estimation.
  Rajantie J, Siimes MA. We describe a 10-year-old girl with familial haemochromatosis which is associated with a normal concentration of S-ferritin, myocardial disease and diabetes mellitus. We speculate that iron is accumulated primarily in the heart and pancreas as such isoferritins are not detected by the routine assay of serum ferritin based on antispleen or placenta ferritin.

Click on this link to read about HH. Discussion of a liver biopsy is also here: 

 

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