Dr. Bianco: Office out-of Endocrinology and you can Metabolic process, Rush School Healthcare facility, 1735 West Harrison Roadway, Cohn Building, Area 212, Chi town, IL 60612.
Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (Tcuatro) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l -thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l -thyroxine mono-therapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l -thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l -thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism.
Big diagnostic and you can healing advancements during the early twentieth century considerably altered the fresh new prognosis out-of hypothyroidism regarding an incredibly morbid updates to help you the one that will be successfully managed which have safer, energetic therapy. This type of advancements determined medication trend having contributed to the newest adoption of l -thyroxine monotherapy, given within amounts so you can normalize gel thyroid gland-revitalizing hormonal (TSH), just like the modern level of proper care ( Figure ). Really customers do just fine using this means, hence one another normalizes gel TSH profile and you may contributes to symptomatic remission (1).
The historical past and you can Way forward for Therapy of Hypothyroidism
Initial strategies for thyroid hormone replacement included thyroid transplantation, but efficacious pharmacologic strategies soon won favor. Natural thyroid preparations containing T4 and T3, such as desiccated thyroid, thyroid extracts, or thyroglobulin, were the initial pharmacologic agents. Synthetic agents were synthesized later. Early clinical https://datingmentor.org/italy-deaf-dating/ trials demonstrated the efficacy of synthetic and natural agents, but concerns arose regarding consistency of natural thyroid preparations and adverse effects associated with T3-containing preparations (natural or synthetic). With the demonstration of peripheral T4-to-T3 conversion and the availability of the serum TSH radioimmunoassay in the early 1970s, there was a major trend in prescribing preference toward l -thyroxine monotherapy. BMR = basal metabolic rate; DT = desiccated thyroid; IV = intravenous; RIA = radioim-munoassay; T3 = triiodothyronine; T4 = thyroxine; TG = thyroglobulin; TSH = thyroid-stimulating hormone.
Despite these successes, authors have questioned the efficacy of l -thyroxine monotherapy because about 10% to 15% of patients are dissatisfied as a result of residual symptoms of hypothyroidism (1, 2), including neurocognitive impairment (3), and about 15% of patients do not achieve normal serum triiodothyronine (T3) levels (4). Studies of several animal models indicate that maintaining normal serum T3 levels is a biological priority (5). Although the clinical significance of relatively low serum T3 in humans is not well-defined (1), evidence shows that elevating serum T3 through the administration of both l -thyroxine and l -triiodothyronine has benefited some patients (6, 7). However, this has not been consistently demonstrated across trials (1). Novel findings highlight the molecular mechanisms underlying the inability of l -thyroxine monotherapy to universally normalize measures of thyroid hormone signaling (8, 9), and new evidence may lay the foundation for a role of personalized medicine (10). Understanding the historical rationale for the trend toward l -thyroxine monotherapy allows us to identify scientific and clinical targets for future trials.