title: The emergence of levothyroxine as a treatment for hypothyroidism.
abstract: OBJECTIVE
  To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies.
  
  
  METHODS
  A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified.
  
  
  RESULTS
  Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines.
  
  
  CONCLUSIONS
  The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.
authors.affiliation: Harvard Medical School, Division of Endocrinology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Gryzmish 619, Boston, 02215, MA, USA. jhenness@bidmc.harvard.edu.
authors.forename: James V
authors.initials: JV
authors.lastname: Hennessey
mesh_terms: D000818:Animals; D004339:Drug Compounding / Q000266:history / Q000639:trends; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000266:history; D004704:Endocrinology / Q000266:history / Q000379:methods / Q000639:trends; D019317:Evidence-Based Medicine; D049673:History, 20th Century; D049674:History, 21st Century; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000266:history*; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000266:history; D017410:Practice Guidelines as Topic; D057285:Precision Medicine; D012958:Societies, Scientific; D013810:Therapeutic Equivalency; D013962:Thyroid (USP) / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use; D013974:Thyroxine / Q000009:adverse effects / Q000266:history / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014481:United States
chemical_list: D013962:Thyroid (USP); D013974:Thyroxine
keywords: Levothyroxine; Levothyroxine bioequivalence; Levothyroxine mono therapy; Thyroid hormone history; Thyroid hormone replacement