A prospective study of thyrotropin (TSH) response to Levothyroxine dose change in patients with primary hypothyroidism

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 437-470-Non-neoplastic Thyroid Disorders
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-437
Mehdi Mirzazadeh*1, Brian Shine1, Claudia Worth1, Helen Tyrrell1, Tim James1 and John A. H. Wass2
1John Radcliffe Hospital, Oxford, United Kingdom, 2Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, United Kingdom

Hypothyroidism is common and has a significant impact on health care resources. 1-2  The main treatment for all types of hypothyroidism remains levothyroxine (L-T4) and is mainly done in primary care. While different tests have been suggested for monitoring treatment 3-5, FT4 and TSH remain the recommended tests and the target for TSH is the reference range. 6-7 Although the optimum time interval for monitoring TSH level after a change in dose is considered to be 6 to 8 weeks 8, it lacks supporting evidence. In this prospective study, we examined the kinetics of change in plasma TSH in patients who had recently started on or changed their dosage of L-T4.


We recruited male and female patients aged 18 to 80 years with hypothyroidism.  Pregnant women, and patients with history of thyroid cancer or pituitary disease were excluded.  We identified the potential volunteers through the clinical biochemistry laboratory information system and information from the general practitioner or hospital database.  TSH, FT4, FT3 were analysed weekly for 12 weeks. If the TSH did not normalise after 8 weeks, the family doctor adjusted the dose . A stable TSH was defined as a change in consecutive TSH measurement of less than 20%. This was derived from studies on Least Significant Difference in bone density change following therapy.9


We recruited 63 patients, of whom 56 (8 males, 14.3%) completed the study. The median age was 56 (range 21-77) years. There were 91 dose changes overall of which 46 were of 25 micrograms. Thirty patients (48%) had at least one TSH result within the reference interval, after a mean of 2.96±1.71 (median 3) weeks. 21 patients had a stable TSH during the study after a mean of 2.72±1.53 (median 3) weeks. TSH was stable in the majority of patients (80%) after less than 4 weeks.


TSH concentration depends on many variables, including the bioavailability of levothyroxine, volume of distribution, biological and analytical variability of TSH. To minimise the effect of above factors , we compared each patient’s TSH levels with their other levels. Patients who completed the study were metabolically stable with no acute illness. The results of this study could have major clinical implications for dose adjustment in patients with hypothyroidism. Since TSH stabilises earlier in most patients than has been assumed, it is possible to adjust LT4 replacement doses at shorter intervals and thus reduce the time required to obtain optimum replacement. These results may also apply to special groups of patients not examined in this study, such as pregnant women and those who have had thyroid cancer.


This prospective study of 63 patients shows that most patients with hypothyroidism reach a stable TSH within 4 weeks after a change in L-T4 dose. This finding has financial and clinical implications for hypothyroid patients in general and also for specialised groups of patients.

1.  The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Vanderpump MP - Clin Endocrinol (Oxf) - 01-JUL-1995; 43(1): 55-68 2. Hypothyroidism ,  Lindsar RS, Toft AD Lancet 1997;349; 413-417 3. Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? W D Fraser, E M Biggart, D S O'Reilly, H W Gray, J H McKillop, J A Thomson M Br Med J (Clin Res Ed) 1986;293:808-810 (27 September) 4.  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. D Carr, DT McLeod, G Parry Clin Endocrinol (Oxf). 1988 Mar;28(3):325-33. 5. Treatment guidelines for patients with hyperthyroidism and hypothyroidism Singer PA, Cooper DS Levy EG, et al. JAMA 1995; 273:808-812 6. Thyroxine therapy. Toft AD. N Engl J Med 1994; 331: 174-180 7. American Thyroid Association Guidelines for detection of thyroid dysfunction. Ladenson PW, Singer PA, Ain KB, et al. Arch Int Med 2000; 160: 1573-1575 8. UK guidelines for the Use of Thyroid Function Tests; ACB, BTA, BFT June 2006 9. Reproducibility of bone mineral density measurement in daily practice. M C Lodder, W F Lems, H J Ader, A E Marthinsen, S C C M van Coeverden, P Lips, J C Netelenbos, B A C Dijkmans, J C Roos. Ann Rheum Dis 2004;63:285–289.

Nothing to Disclose: MM, BS, CW, HT, TJ, JAHW

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