Thyroid Hormone replacement therapy – "This house believes that thyroxine is not an adequate form of thyroid hormone replacement in everyone…."

C M Dayan

Consultant Senior Lecturer, University of Bristol

Endocrine Nurses Training Course 9-11 September 2004
Wills Hall, Stoke Bishop, Bristol, BS9 1AE

There are over 500,000 people taking thyroid hormone therapy in the UK. The vast majority apppear happy with their replacement therapy, but a subpopulation, which we have recently estimated at around 5%¹ appear psychological dissatisfied despite TSH levels in the reference range. This has been assumed to be due to coincident psychological morbidity (independent of thyroid status). However, recent developments in thyroid hormone physiology indicate that there are multiple levels at which differences between individuals might results in differential sensitivity to replacement with T4 alone, titrated to "reference range TSH levels". These include variations in the 3 deoidinase enzymes, recently recognised cell membrane thyroid hormone transporters and transcription factors associated with thyroid hormone action. It is possible that variations in these elements means that replacement with T4 alone is not adequate in some individuals. Recent studies use a combination of T4 and T3 have produced conflicting results but we argue that the possibility that a subgroup of patients need combination therapy has not been excluded.

¹Saravanan P, Chau WF, Roberts N, Vedhara K, Greenwood R & Dayan CM. (2002) Psychological well-being in patients on 'adequate' doses of L-thyroxine: results of a large, controlled community-based questionnaire study. [Article]. Clinical Endocrinology 57, 577-585.

Bianco AC, Salvatore D, Gereben B, Berry MJ & Larsen PR. (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr.Rev. 23, 38-89.

Bunevicius R, Kazanavicius G, Zalinkevicius R & Prange AJ, Jr. (1999) Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N.Engl.J.Med. 340, 424-429.

Carr D, McLeod DT, Parry G & Thornes HM. (1988) Fine adjustment of thyroxine replacement dosage: comparison of the thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment. Clin.Endocrinol.(Oxf) 28, 325-333.

Clyde PW, Harari AE, Getka EJ & Shakir KMM. (2003) Combined Levothyroxine Plus Liothyronine Compared With Levothyroxine Alone in Primary Hypothyroidism: A Randomized Controlled Trial. JAMA: The Journal of the American Medical Association 290, 2952-2958.

Cooper DS. (2003) Combined T4 and T3 therapy--back to the drawing board. JAMA: The Journal of the American Medical Association 290, 3002-3004.

Hennemann G, Docter R, Visser TJ, Postema PT & Krenning EP. (2004) Thyroxine plus low-dose, slow-release triiodothyronine replacement in hypothyroidism: proof of principle. Thyroid 14, 271-275.

Saravanan P, Simmons DJ, Greenwood R, Peters TJ & Dayan CM. (2003) Weston Area T4/T3 (Thyroid Hormone Replacement) Study: Psychological Effects of Combined T4/T3 Therapy. Thyroid 13, 697.

Sawka AM, Gerstein HC, Marriott MJ, MacQueen GM & Joffe RT. (2003) Does a combination regimen of thyroxine (T4) and 3,5,3'-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. J.Clin.Endocrinol.Metab 88, 4551-4555.

Siegmund W, Spieker K, Weike AI, Giessmann T, Modess C, Dabers T, Kirsch G, Sanger E, Engel G, Hamm AO, Nauck M & Meng W. (2004) Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14:1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism. Clin.Endocrinol.(Oxf) 60, 750-757.

Walsh JP. (2002) Dissatisfaction with thyroxine therapy - could the patients be right? Curr.Opin.Pharmacol. 2, 717-722.

Walsh JP, Shiels L, Lim EM, Bhagat CI, Ward LC, Stuckey BG, Dhaliwal SS, Chew GT, Bhagat MC & Cussons AJ. (2003) Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J.Clin.Endocrinol.Metab 88, 4543-4550.

The opinions expressed in this paper are those of the speaker and do not necessarily reflect the views of the Society