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Potential Therapeutic Uses of Thyroid Hormone

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Thyroid Disorders with Cutaneous Manifestations

Editorial Perspective

At the outset, I must admit my bias and conflict of interest on this topic as I have US Patent Number 5,951,989 for the use of topical thyroid hormone in treating xerosis. Regardless of that fact, it is clear that the therapeutic use of thyroid hormone has been considered a neglected stepchild compared to hormones of the same nuclear receptor subfamily: corticosteroids, retinoids, and vitamin D. Indeed, a PubMed search performed on Independence Day (July 4th) 2007 revealed 10,081 references for topical corticosteroids and only 69 for topical thyroid hormone. As explained in this chapter, thyroid hormone has profound effects on the skin and its appendages and has the potential to treat myriad conditions, including disorders of keratinization, alopecia, wound healing, xerosis, and chronic idi-opathic urticaria. This subject was chosen for the concluding chapter of this text because I hope the reader will have already come to the realization that not only are thyroid–cutaneous interactions important in health and disease but also that further research in this discipline may foster novel concepts and therapies utilizing thyroid hormone to alleviate human suffering.

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References

  1. Ord WM. On myxoedema, term proposed to be applied to an essential condition in the “cretinoid” affection occasionally observed in middle-aged women. Med Chir Trans Lond 1878;61:57–78.

    CAS  Google Scholar 

  2. Horsley V. The thyroid gland: its relation to the pathology of myxoedema and cretinism, to the question of surgical treatment of goitre, an to the general nutrition of the body. Br Med J 1885;1:111–115.

    Article  PubMed  CAS  Google Scholar 

  3. Fisher C, Blumenberg M, Tomic-Canic M. Retinoid receptors and keratinocytes. Crit Rev Oral Biol Med 1995;6:284–301.

    Article  PubMed  CAS  Google Scholar 

  4. Holick MF. McCollum award lecture, 1994: vitamin D—new horizons for the 21st century. Am J Clin Nutr 1994;60:619–630.

    PubMed  CAS  Google Scholar 

  5. Warthin TA, Boshell BR. Pretibial myxedema treated with local injection of triiodothyronine. Arch Int Med 1957;100:319–321.

    Article  CAS  Google Scholar 

  6. Gabrilove JL, Alavarez AS, Churg J. Generalized and localized (pretibial) myxedema: effect of thyroid analogues and adrenal glucocorticoids. J Clin Endocrine Metab 1960;20:825–832.

    Article  CAS  Google Scholar 

  7. Gimlette TMD. Pretibial myxedema. Br Med J 1960;2:348‱351.

    Article  PubMed  CAS  Google Scholar 

  8. Cohen BD, Benua RS, Rawson RW. Localized myxedema involving the upper extremities. Arch Intern Med 1963;111:641–646.

    Article  PubMed  CAS  Google Scholar 

  9. Berman A. Peripheral effects of L-thyroxine on hair growth and coloration in cattle. J Endocrinol 1960;20:288–292.

    Article  CAS  Google Scholar 

  10. Abulkadir J, Besrat A, Abraham G, et al. Thyrotoxicosis in Ethiopian patients—a prospective study. Trans R Soc Trop Med Hyg 1982;76:500.

    Article  Google Scholar 

  11. Tibaldi JM, Barzel US, Albin J, et al. Thyrotoxicosis in the very old. Am J Med 1986;81:619.

    Article  PubMed  CAS  Google Scholar 

  12. Holt PJA. In vitro responses of the epidermis to trii-odothyronine. J Invest Dermatol 1978;71:202–204.

    Article  PubMed  CAS  Google Scholar 

  13. Ahsan MK, Urano Y, Kato S, Oura H, Arase S. Immunohistochemical localization of thyroid hormone nuclear receptors in human hair follicles and in vitro effect of L-triiodothyronine on cultured cells of hair follicles and skin. J Med Invest 1998;44:179–184.

    PubMed  CAS  Google Scholar 

  14. Safer JD, Crawford TM, Fraser LM, et al. Thyroid hormone action on skin: diverging effects of topical versus intraperitoneal administration. Thyroid 2003;3:159–165.

    Article  Google Scholar 

  15. Safer JD. The skin in thyrotoxicosis. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the Thyroid. 9th ed. Philadelphia: Lippincott Williams and Wilkins; 2005:553–558.

    Google Scholar 

  16. Reuter MJ. Histopathology of the skin in myxedema. AMA Arch Derm Syphil 1931;24:55–71.

    Article  Google Scholar 

  17. Gabrilove JL, Ludwig AW. The histogenesis of myxe-dema. J Clin Endocrinol Metabol 1957;17:925–932.

    Article  CAS  Google Scholar 

  18. Fink CW, Ferguson JL, Smiley JD. Effect of hyper-thyroidism and hypothyroidism on collagen metabolism. J Lab Clin Med 1967;69:950–959.

    PubMed  CAS  Google Scholar 

  19. Kivirikko KI, Laitinen O, Aer J, Halme J. Metabolism of collagen in experimental hyperthyroidism and hypothy-roidism in the rat. Endocrinology 1967;80:1051–1061.

    Article  PubMed  CAS  Google Scholar 

  20. Torma H, Rollman O, Vahlquist A. Detection of mRNA transcripts for retinoic acid, vitamin D3, and thyroid hormone (c-erb-A) nuclear receptors in human skin using reverse transcription and polymerase chain reaction. Acta Derm Venereol 1993;73:102–107.

    PubMed  CAS  Google Scholar 

  21. Billoni N, Buan B, Gautier B, Gaillard O, Mahe YF, Bernhard BA. Thyroid hormone receptor β1 is expressed in the human hair follicle. Br J Dermatol 2000;142:645–652.

    Article  PubMed  CAS  Google Scholar 

  22. Torma H, Karlsson T, Michaelsson G, Rollman O, Vahlquist A. Decreased mRNA levels of retinoic acid receptor a, retinoid X receptor a and thyroid hormone receptor a in lesional psoriatic skin. Acta Derm Venereol 2000;80:4–9.

    Article  PubMed  CAS  Google Scholar 

  23. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endo Rev 2002;23:38–89.

    Article  CAS  Google Scholar 

  24. Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest 2006;116:2571–2579.

    Article  PubMed  CAS  Google Scholar 

  25. Refetoff S, Matalon R, Bigazzi M. Metabolism of L-thyroxine (T4) and L-triiodothyronine (T3) by human fibroblasts in tissue culture: evidence for cellular binding proteins and conversion of T4 to T3. Endocrinology 1972;91:934–947.

    Article  PubMed  CAS  Google Scholar 

  26. Huang TS, Chopra IJ, Beredo A, Solomon DH, Chua Teco GN. Skin is an active site for the inner ring monodeiodination of thyroxine to 3,3′,5′-triiodothy-ronine. Endocrinology 1985;117:2106–2113.

    Article  PubMed  CAS  Google Scholar 

  27. Kaplan MM, Pan C, Gordon PR, Lee JK, Gilchrest BA. Human epidermal keratinocytes in culture convert thyroxine to 3,5,3′-triiodothyronine by type II iodothy-ronine deiodination: a novel endocrine function of skin. J Clin Endocrinol Metab 1988;66:815–822.

    Article  PubMed  CAS  Google Scholar 

  28. Villar D, Nichols F, Arthur JR, et al. Type II and type III monodeiodinase activities in the skin of untreated and propylthiouracil-treated cashmere goats. Res Vet Sci 2000;68:119–123.

    Article  PubMed  CAS  Google Scholar 

  29. Schroder-van der Elst JP, van der Heide D, de Escobar GM, Obregon MJ. Iodothyronine deiodinase activities in fetal rat tissues at several levels of iodine deficiency: a role for the skin in 3,5,3′-triiodothyronine economy? Endocrinology 1998;139:2229′2234.

    Article  PubMed  CAS  Google Scholar 

  30. Santini F, Vitti P, Chiovato L, et al. Role for inner ring deiodination preventing transcutaneous passage of thyroxine. J Clin Endocrinol Metab 2003;88:2825–2830.

    Article  PubMed  CAS  Google Scholar 

  31. Dumitrescu AM, Liao X-H, Abdullah MSY, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat Genet 2005;37:1247–1252.

    Article  PubMed  CAS  Google Scholar 

  32. Tomic M, Jiang CK, Epstein HS, Freedberg IM, Samuels HH, Blumenberg M. Nuclear receptors for retinoic acid and thyroid hormone regulate transcription of keratin genes. Cell Regul 1990;1:965–973.

    PubMed  CAS  Google Scholar 

  33. Ohtsuki M, Tomic-Canic M, Freedberg IM, Blumenberg M. Regulation of epidermal keratin expression by retinoic acid and thyroid hormone. J Dermatol 1992;19:774–780.

    PubMed  CAS  Google Scholar 

  34. Thompson CC. Thyroid hormone-responsive genes in developing cerebellum include a novel synaptotagmin and a hairless homolog. J Neurosci 1996;16:7832–7840.

    PubMed  CAS  Google Scholar 

  35. Thompson CC, Bottcher MC. The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors. Proc Natl Acad Sci U S A 1997;94:8527–8532.

    Article  PubMed  CAS  Google Scholar 

  36. Miyazaki T, Kanou Y, Murata Y, et al. Molecular cloning of a novel thyroid hormone responsive gene, ZAKI-4, in human skin fibroblasts. J Bio Chem 1996;271:14567–14571.

    Article  CAS  Google Scholar 

  37. Safer JD, Crawford TM, Holick MF. A role for thyroid hormone in wound healing through keratin gene expression. Endocrinology 2004;145:2357–2361.

    Article  PubMed  CAS  Google Scholar 

  38. Safer JD, Fraser LM, Ray S, Holick MF. Topical triiodothyronine stimulates epidermal proliferation, dermal thickening, and hair growth in mice and rats. Thyroid 2001;11:717–724.

    Article  PubMed  CAS  Google Scholar 

  39. Safer JD. The skin and connective tissue in hypothy-roidism. In: Braverman LE, Utiger RD, eds. Werner and Ingbar's the Thyroid. 9th ed. Philadelphia: Lippincott Williams and Wilkins; 2005:769–773.

    Google Scholar 

  40. Faergemann J, Sarnhult T, Hedner E, et al. Dose-response effects of tri-iodothyroacetic acid (Triac) and other thyroid hormone analogues on glucocorti-coid-induced skin atrophy in the haired mouse. Acta Derm Venereol 2002;82:179–183.

    Article  PubMed  CAS  Google Scholar 

  41. Yazdanparast P, Carlsson B, Oikarinen A, Risteli J, Faergemann J. A thyroid hormone analogue, trii-odothyroacetic acid, corrects corticosteroid downregu-lated collagen synthesis. Thyroid 2004;14:345–353.

    Article  PubMed  CAS  Google Scholar 

  42. Safer JD, Crawford TM, Holick MF. Topical thyroid hormone accelerates wound healing in mice. Endocrinology 2005;146:4425–4430.

    Article  PubMed  CAS  Google Scholar 

  43. Lindenbaum ES, Har Shai Y, Ullmann Y, et al. Stimulated healing of recalcitrant wounds by topical application of enriched cell culture medium: a clinical report. Plast Reconstr Surg 2001;108;104–113.

    Article  PubMed  CAS  Google Scholar 

  44. Zamick P, Mehregan AH. Effect of l-tri-iodothyro-nine on marginal scars of skin grafted burns in rats. Plast Reconstr Surg 1973;51:71–75.

    Article  PubMed  CAS  Google Scholar 

  45. Mehregan AH, Zamick P. The effect of triiodothyro-nine in healing of deep dermal burns and marginal scars of skin grafts. A histologic study. J Cutan Pathol 1974;1:113–116.

    Article  CAS  Google Scholar 

  46. Lennox J, Johnston IDA. The effect of thyroid status on nitrogen balance and the rate of wound healing after injury in rats. Br J Surg 1973;60:309.

    PubMed  CAS  Google Scholar 

  47. Pirk FW, El Attar MA, Roth GD. Effect of analogues of steroid and thyroxine hormones on wound healing in hamsters. J Periodontal Res 1974;9:290–297.

    Article  PubMed  CAS  Google Scholar 

  48. Ashton IK, Dekel S. Fracture repair in the snell dwarf mouse. Br J Exp Pathol 1983;64:479–486.

    PubMed  CAS  Google Scholar 

  49. Alexander MV, Zajtchuk JT, Henderson RL. Hypothyroidism and wound healing: occurrence after head and neck radiation and surgery. Arch Otolaryngol 1982;108:289–291.

    Article  PubMed  CAS  Google Scholar 

  50. Talmi YP, Finkelstein Y, Zohar Y. Pharyngeal fistulas in postoperative hypothyroid patients. Ann Otol Rhinol Laryngol 1989;98:267–268.

    PubMed  CAS  Google Scholar 

  51. Cannon CR. Hypothyroidism in head and neck cancer patients: experimental and clinical observations. Laryngoscope 1994;104:1–22.

    Article  PubMed  CAS  Google Scholar 

  52. Ladenson, PW, Levin AA, Ridgeway EC, Daniels GH. Complications of surgery in hypothyroid patients. Am J Med 1984;77:261–266.

    Article  PubMed  CAS  Google Scholar 

  53. Hale PA, Ebling FJ. The effect of a single epilation on successive hair eruptions in normal and hormone-treated rats. J Exp Zool 1979;207:49ȁ72.

    Article  PubMed  CAS  Google Scholar 

  54. Schell H, Kiesewetter F, Seidel C, et al. Cell cycle kinetics of human anagen scalp hair bulbs in thyroid disorders determined by DNA flow cytometry. Dermatologica 1991;182:23.

    Article  PubMed  CAS  Google Scholar 

  55. Puchala R, Prieto I, Banskalieva V, Goetsch AL, Lachica M, Sahlu T. Effects of bovine somatotropin and thyroid hormone status on hormone levels, body weight gain, and mohair fiber growth of angora goats. J Anim Sci 2001;79:2913–2919.

    PubMed  CAS  Google Scholar 

  56. Lindenbaum ES, Feitelberg AL, Tendler M, et al. Pilot study of a novel treatment for androgenetic alopecia using enriched cell culture medium: clinical trials. Dermatol Online J 2003;9:4.

    PubMed  CAS  Google Scholar 

  57. Heymann WR. Cutaneous manifestations of thyroid disease. J Am Acad Dermatol 1992;26:885.

    Article  PubMed  CAS  Google Scholar 

  58. Freinkel RK. Cutaneous manifestations of endocrine disease. In: Freedberg IM, Jisen AZ, Wolff K, et al., eds. Dermatology in General Medicine. 4th ed. New York: McGraw-Hill; 1993:2113.

    Google Scholar 

  59. Hodak E, David M, Feuerman EJ. Palmoplantar keratoderma in association with myxedema. Acta Derm Venereol (Stockh) 1986;66:354.

    CAS  Google Scholar 

  60. Isseroff RR, Chun KT, Rosenberg RM. Triiodothyronine alters the cornification of cultured human keratinoc-ytes. Br J Dermatol 1989;120:503–510.

    Article  PubMed  CAS  Google Scholar 

  61. Rosenberg RM, Isseroff RR, Ziboh VA, et al. Abnormal lipogenesis in thyroid hormone-deficient epidermis. J Invest Dermatol 1986;86:244.

    Article  PubMed  CAS  Google Scholar 

  62. Hanley K, Jiang Y, Katagiri C, et al. Epidermal steroid sulfatase and cholesterol sulfotransferase are regulated during late gestation in the fetal rat. J Invest Dermatol 1997;108:871.

    Article  PubMed  CAS  Google Scholar 

  63. Heymann WR, Gans EH, Manders SM, Green JJ, Haimowitz JE. Xerosis in hypothyroidism: a potential role for the use of topical thyroid hormone in euthyroid patients. Med Hypotheses 2001;57:736–739.

    Article  PubMed  CAS  Google Scholar 

  64. Heymann WR. Chronic idiopathic urticaria and angioedema associated with thyroid autoimmunity: review and therapeutic implications. J Am Acad Dermatol 1999;40:229.

    Article  PubMed  CAS  Google Scholar 

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Safer, J.D., Holick, M.F. (2008). Potential Therapeutic Uses of Thyroid Hormone. In: Heymann, W.R. (eds) Thyroid Disorders with Cutaneous Manifestations. Springer, London. https://doi.org/10.1007/978-1-84800-187-9_14

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  • DOI: https://doi.org/10.1007/978-1-84800-187-9_14

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