Thyroid

Position Paper on Thyroid

Written by Knafo Henri, MD, MSc, BSc   

Introduction 

     Hypothyroidism is a common disorder, affecting about 5% of people over the age of 60 yr (1). Hormonal replacement therapy is a fundamental part in the management of this disease. There are two main categories of hormones available for treatment: synthetic and desiccated natural hormones. Levothyroxine, the most commonly used synthetic thyroxin form, is a stereoisomer of physiological thyroxin, which is metabolized more slowly and hence usually only needs once-daily administration. Natural desiccated thyroid hormones, also under the commercial name Armour Thyroid in the US and Thyroid® in Canada is derived from porcine thyroid glands, it is a "natural" hypothyroid treatment containing around 20% T3 and traces of T2, T1 and calcitonin. Also available are synthetic combinations of T3/T4 in different ratios (such as Thyrolar) and pure-T3 medications (Cytomel). When prescribing hormonal therapy we have therefore the choice between a natural base drug versus a synthetic one.  More and more patients are being aware of different drugs available in the market and physician should therefore be informed on the different options available. There is interesting evidence showing that natural hormone replacement could be beneficial in certain subset of patients, therefore it should be kept in mind when treatment with levothyroxine is suboptimal.

    The recommended therapy for hypothyroidism is levothyroxine, and the medication is now at least the fifth most commonly dispensed drug in the United States (2). Levels of serum T4 and T3 are relatively constant after oral administration of levothyroxine, given the relative long 6-day half-life of T4. Stable serum levels of these hormones facilitate titration of the levothyroxine dose to achieve preassigned ranges of thyroid hormones. Because of such advantage, synthetic hormones are being used as a first line treatment for hypothyroidism. Although many clinician feel that strict T4 dosage is necessary in order to achieve adequate clinical response a randomize trial demonstrated that small changes in T₄ dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life, despite the expected changes in serum TSH and markers of thyroid hormone action (3).  If such argument holds true, it would be of interest to further assess if scrutinious dosage adjustment while using synthetic hormonotherapy is of real relevance. 

   In a recent paper Grozinsky-Glasberg  et al (4) performed a systematic review and meta-analysis comparing the effectiveness of T4 –T3 combination therapy vs. T4 monotherapy for the treatment of clinical hypothyroidism in adults. They concluded that T4 monotherapy should remain the treatment of choice for clinical hypothyroidism. This statement is generally accepted among most endocrinologists. While many excellent studies have compared combination therapy to T4 monotherapy, almost none have really compared natural versus synthetic treatment. Since most patients treated with levothyroxine do well, it is improbable that such a study be initiated in the near future. Nevertheless, in patients taking levothyroxine replacement with a normal range serum TSH concentration, symptoms consistent with hypothyroidism may persist and have been documented. Successful observational studies have described the use of desiccated thyroid to treat hypothyroidism in such patients (5).

    Recently, there has been recognition that the currently available regimens for the treatment of hypothyroidism may not adequately address the needs of all patients (6). There may be a subgroup of patients responding and feeling better with natural desiccated thyroid. In decades past, desiccated thyroid was successfully employed for the treatment of hypothyroidism and still accounts for a small fraction of the prescriptions written for thyroid replacement in the United States and Canada. Anecdotal cases of over dosage using desiccated thyroid supplement have long let the scientific community believe that natural hormonotherapy could be potentially harmful (7).  Many efforts have been made since then to ensure that extracts comply with very strict pharmaceutical criterions and specific dosage of both T3 and T4 are rea™dily available. This ensures an adequate follow up of TSH lab values by physicians.

     Synthetic levothyroxine holds an undisputed literature pertaining to its beneficial usage in hypothyroidism. Most clinicians are well trained in prescribing and managing such drugs. It is important nevertheless to acknowledge the fact that natural hormonotherapy with Armour in the US and Thyroid in Canada, benefits some subgroup of patient that is yet to be defined. It is important to recognize that hormonal replacement therapy requires an ideal collaboration between the patient and its physician in order to have a favorable therapeutic outcome and one should keep in mind, that natural hormonotherapy with desiccated thyroid is becoming more and more an important part in the treatment of central hypothyroidism (8).  

(1) Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Evans JG, Hasan DM, Rodgers H, Tunbridge F, Young ET 1995 The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 43:55–68  

(2) Simonsen LP. 1994 Top 200 drugs of 1993. Pharm Times (Hosp Ed). 60:18-32.

(3) Walsh JP, Ward LC, Burke V, Bhagat CI, Shiels L, Henley D, Gillett MJ, Gilbert R, Tanner M, Stuckey BG.Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial.J Clin Endocrinol Metab. 2006 Jul;91(7):2624-30. Epub 2006 May 2

(4) Grozinsky-Glasberg S - Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab - 01-JUL-2006; 91(7): 2592-9

(5) Basier VW, Hertoghe J, and Eeekhaut W. Thyroid Insufficiency. Is Thyroxine the Only Valuable Drug? J Nutr Environ Med 2001;11:159-166.

(6) Danzi S, Klein I. Recent considerations in the treatment of hypothyroidism. Curr Opin Investig Drugs. 2008 Apr;9(4):357-62

(7) Eliason BC, Doenier JA, Nuhlicek DN.Desiccated thyroid in a nutritional supplement. J Fam Pract. 1994 Mar;38(3):287-8.

(8) Oppenheimer JH, Braverman LE, Toft A, Jackson IM, Ladenson PW. A therapeutic controversy. Thyroid hormone treatment: when and what? J Clin Endocrinol Metab. 1995 Oct;80(10):2873-83.