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Thyroid Disease in Hemochromatosis: Increased Incidence in Homozygous Men

Thyroid Disease in Hemochromatosis: Increased Incidence in Homozygous Men Abstract • The thyroid function of 49 patients homozygous for the hemochromatosis allele was studied by measurement of serum thyroxine and thyrotropin concentrations. Of 34 homozygous men, three were found to be hypothyroid (thyroxine, <3.0 μg/dL and thyrotropin, >40 ImU/mL) and one was hyperthyroid (thyroxine, 24 μg/dL). All 15 homozygous women had normal thyroid function. The hypothyroid patients had elevated titers of antithyroid antibodies. Histologic examination of the thyroid at autopsy of one hypothyroid patient showed notable iron accumulation and fibrosis with modest lymphocytic infiltration. The causative importance of iron deposition in thyroid diseases associated with hemochromatosis was suggested by the reversal of the usual sex ratio of thyroid dysfunction. Men with hemochromatosis had a much greater iron load than women, and they also had a surprisingly higher incidence of thyroid disease. Iron may have caused injury to the thyroid, followed by the development of antithyroid antibodies and hypothyroidism. The frequency of thyroid disorders in men with hemochromatosis is about 80 times that of men in the general population. (Arch Intern Med 1983;143:1890-1893) References 1. Edwards CQ, Dadone MM, Skolnick MH, et al: Hereditary haemochromatosis. Clin Haematol 1982;11:411-435. 2. Saddi R, Feingold J: Idiopathic haemochromatosis: An autosomal recessive disease. Clin Genet 1974;5:234-241.Crossref 3. McAllen PM, Coghill NF, Lubran M: The treatment of haemochromatosis with particular reference to the removal of iron from the body by repeated venesection. Q J Med 1957;26:251-276. 4. Darnall JR: Hemochromatosis: Review of the literature and report of three cases. Ann Intern Med 1935;8:1121-1137.Crossref 5. Stocks AE, Martin FIR: Pituitary function in haemochromatosis. Am J Med 1968;45:839-845.Crossref 6. Walsh CH, Wright AD, Williams JW, et al: A study of pituitary function in patients with idiopathic hemochromatosis. J Clin Endocrinol Metabol 1976;43:866-872.Crossref 7. Milder MS, Cook JD, Stray S, et al: Idiopathic hemochromatosis: An interim report. Medicine 1980;59:34-49.Crossref 8. Althausen TL, Kerr WJ: Hemochromatosis: A report of three cases with results of insulin therapy in one case. Endocrinology 1927;2:377-422.Crossref 9. Althausen TL, Kerr WJ: Hemochromatosis: II. A report of three cases with endocrine disturbances and notes on a previously reported case: Discussion of etiology. Endocrinology 1933;17:621-646.Crossref 10. Williams RS: Increased thyroid function in haemochromatosis. Br Med J 1959;1:1078-1080.Crossref 11. Herford MEM: Haemochromatosis, diabetes and hyperthyroidism. Br Med J 1969;3:359.Crossref 12. Friedland M, Schaefer P: Hemochromatosis, thrombocytopenic purpura, and multiple endocrine disturbances: An unusual association of uncommon disorders is reported. RI Med J 1980;63:342-344. 13. Edwards CQ, Carroll M, Bray P, et al: Hereditary hemochromatosis: Diagnosis in siblings and children. N Engl J Med 1977;297:7-13.Crossref 14. Edwards CQ, Skolnick MH, Kushner JP: Hereditary hemochromatosis: Contributions of genetic analyses. Prog Hematol 1981;12:43-71. 15. Chevrant-Breton J, Simon M, Bourel M, et al: Cutaneous manifestations of idiopathic hemochromatosis. Arch Dermatol 1977;113:161-165.Crossref 16. Tunbridge WMG, Evered DC, Hall R, et al: The spectrum of thyroid disease in a community: The Wickham survey. Clin Endocrinol 1977;7: 481-493.Crossref 17. Bahemuka M, Hodkinson HM: Screening for hypothyroidism in elderly inpatients. Br Med J 1975;2:601-603.Crossref 18. Wartofsky L, Burman KD: Alterations in thyroid function in patients with systemic illness: The 'euthyroid sick syndrome.' Endocr Rev 1982;3: 164-217.Crossref 19. Gregerman RI, Davis PJ: Effects of intrinsic and extrinsic variables on thyroid hormone economy , in Werner SC, Ingbar SH (eds): The Thyroid , ed 4. Hagerstown, Md, Harper & Row Publishers Inc, 1978, pp 223-246. 20. Edwards CQ, Cartwright GE, Skolnick MH, et al: Genetic mapping of the hemochromatosis locus on chromosome six. Hum Immunol 1980;1: 19-22.Crossref 21. Edwards CQ, Skolnick MH, Dadone MM, et al: Iron overload in hereditary spherocytosis: Association with HLA-linked hemochromatosis. Am J Hematol 1982;13:101-109.Crossref 22. Morris PJ, Vaughan H, Tait BD, et al: Histocompatibility antigens (HLA): Associations with immunopathic diseases and with responses to microbial antigens. Aust NZ J Med 1977;7:616-624.Crossref 23. Sheldon JH: Haemochromatosis . London, Oxford University Press, 1935. 24. Marble A, Bailey CC: Hemochromatosis. Am J Med 1951;11:590-599.Crossref 25. Kleckner MS, Baggenstoss AH, Weir JF: Iron-storage diseases. Am J Clin Pathol 1955;25:915-931. 26. MacDonald RA, Mallory GK: Hemochromatosis and hemosiderosis: Study of 211 autopsied cases. Arch Intern Med 1960;105:686-700.Crossref 27. Finch SC, Finch CA: Idiopathic hemochromatosis, an iron storage disease: A. Iron metabolism in hemochromatosis. Medicine 1955;34:381-430.Crossref 28. Bomford A, Williams R: Long-term results of venesection therapy in idiopathic haemochromatosis. Q J Med 1976;45:611-623. 29. Cartwright GE, Edwards CQ, Kravitz K, et al: Hereditary hemochromatosis: Phenotypic expression of the disease. N Engl J Med 1979;301:175-179.Crossref 30. Edwards CQ, Cartwright GE, Skolnick MH, et al: Homozygosity for hemochromatosis: Clinical manifestations. Ann Intern Med 1980;93:519-525.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Thyroid Disease in Hemochromatosis: Increased Incidence in Homozygous Men

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Publisher
American Medical Association
Copyright
Copyright © 1983 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1983.00350100052015
Publisher site
See Article on Publisher Site

Abstract

Abstract • The thyroid function of 49 patients homozygous for the hemochromatosis allele was studied by measurement of serum thyroxine and thyrotropin concentrations. Of 34 homozygous men, three were found to be hypothyroid (thyroxine, <3.0 μg/dL and thyrotropin, >40 ImU/mL) and one was hyperthyroid (thyroxine, 24 μg/dL). All 15 homozygous women had normal thyroid function. The hypothyroid patients had elevated titers of antithyroid antibodies. Histologic examination of the thyroid at autopsy of one hypothyroid patient showed notable iron accumulation and fibrosis with modest lymphocytic infiltration. The causative importance of iron deposition in thyroid diseases associated with hemochromatosis was suggested by the reversal of the usual sex ratio of thyroid dysfunction. Men with hemochromatosis had a much greater iron load than women, and they also had a surprisingly higher incidence of thyroid disease. Iron may have caused injury to the thyroid, followed by the development of antithyroid antibodies and hypothyroidism. The frequency of thyroid disorders in men with hemochromatosis is about 80 times that of men in the general population. (Arch Intern Med 1983;143:1890-1893) References 1. Edwards CQ, Dadone MM, Skolnick MH, et al: Hereditary haemochromatosis. Clin Haematol 1982;11:411-435. 2. Saddi R, Feingold J: Idiopathic haemochromatosis: An autosomal recessive disease. Clin Genet 1974;5:234-241.Crossref 3. McAllen PM, Coghill NF, Lubran M: The treatment of haemochromatosis with particular reference to the removal of iron from the body by repeated venesection. Q J Med 1957;26:251-276. 4. Darnall JR: Hemochromatosis: Review of the literature and report of three cases. Ann Intern Med 1935;8:1121-1137.Crossref 5. Stocks AE, Martin FIR: Pituitary function in haemochromatosis. Am J Med 1968;45:839-845.Crossref 6. Walsh CH, Wright AD, Williams JW, et al: A study of pituitary function in patients with idiopathic hemochromatosis. J Clin Endocrinol Metabol 1976;43:866-872.Crossref 7. Milder MS, Cook JD, Stray S, et al: Idiopathic hemochromatosis: An interim report. Medicine 1980;59:34-49.Crossref 8. Althausen TL, Kerr WJ: Hemochromatosis: A report of three cases with results of insulin therapy in one case. Endocrinology 1927;2:377-422.Crossref 9. Althausen TL, Kerr WJ: Hemochromatosis: II. A report of three cases with endocrine disturbances and notes on a previously reported case: Discussion of etiology. Endocrinology 1933;17:621-646.Crossref 10. Williams RS: Increased thyroid function in haemochromatosis. Br Med J 1959;1:1078-1080.Crossref 11. Herford MEM: Haemochromatosis, diabetes and hyperthyroidism. Br Med J 1969;3:359.Crossref 12. Friedland M, Schaefer P: Hemochromatosis, thrombocytopenic purpura, and multiple endocrine disturbances: An unusual association of uncommon disorders is reported. RI Med J 1980;63:342-344. 13. Edwards CQ, Carroll M, Bray P, et al: Hereditary hemochromatosis: Diagnosis in siblings and children. N Engl J Med 1977;297:7-13.Crossref 14. Edwards CQ, Skolnick MH, Kushner JP: Hereditary hemochromatosis: Contributions of genetic analyses. Prog Hematol 1981;12:43-71. 15. Chevrant-Breton J, Simon M, Bourel M, et al: Cutaneous manifestations of idiopathic hemochromatosis. Arch Dermatol 1977;113:161-165.Crossref 16. Tunbridge WMG, Evered DC, Hall R, et al: The spectrum of thyroid disease in a community: The Wickham survey. Clin Endocrinol 1977;7: 481-493.Crossref 17. Bahemuka M, Hodkinson HM: Screening for hypothyroidism in elderly inpatients. Br Med J 1975;2:601-603.Crossref 18. Wartofsky L, Burman KD: Alterations in thyroid function in patients with systemic illness: The 'euthyroid sick syndrome.' Endocr Rev 1982;3: 164-217.Crossref 19. Gregerman RI, Davis PJ: Effects of intrinsic and extrinsic variables on thyroid hormone economy , in Werner SC, Ingbar SH (eds): The Thyroid , ed 4. Hagerstown, Md, Harper & Row Publishers Inc, 1978, pp 223-246. 20. Edwards CQ, Cartwright GE, Skolnick MH, et al: Genetic mapping of the hemochromatosis locus on chromosome six. Hum Immunol 1980;1: 19-22.Crossref 21. Edwards CQ, Skolnick MH, Dadone MM, et al: Iron overload in hereditary spherocytosis: Association with HLA-linked hemochromatosis. Am J Hematol 1982;13:101-109.Crossref 22. Morris PJ, Vaughan H, Tait BD, et al: Histocompatibility antigens (HLA): Associations with immunopathic diseases and with responses to microbial antigens. Aust NZ J Med 1977;7:616-624.Crossref 23. Sheldon JH: Haemochromatosis . London, Oxford University Press, 1935. 24. Marble A, Bailey CC: Hemochromatosis. Am J Med 1951;11:590-599.Crossref 25. Kleckner MS, Baggenstoss AH, Weir JF: Iron-storage diseases. Am J Clin Pathol 1955;25:915-931. 26. MacDonald RA, Mallory GK: Hemochromatosis and hemosiderosis: Study of 211 autopsied cases. Arch Intern Med 1960;105:686-700.Crossref 27. Finch SC, Finch CA: Idiopathic hemochromatosis, an iron storage disease: A. Iron metabolism in hemochromatosis. Medicine 1955;34:381-430.Crossref 28. Bomford A, Williams R: Long-term results of venesection therapy in idiopathic haemochromatosis. Q J Med 1976;45:611-623. 29. Cartwright GE, Edwards CQ, Kravitz K, et al: Hereditary hemochromatosis: Phenotypic expression of the disease. N Engl J Med 1979;301:175-179.Crossref 30. Edwards CQ, Cartwright GE, Skolnick MH, et al: Homozygosity for hemochromatosis: Clinical manifestations. Ann Intern Med 1980;93:519-525.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Oct 1, 1983

References