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Thyroxine Titration Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00111735
Recruitment Status : Unknown
Verified May 2005 by Sir Charles Gairdner Hospital.
Recruitment status was:  Active, not recruiting
First Posted : May 25, 2005
Last Update Posted : June 24, 2005
Information provided by:
Sir Charles Gairdner Hospital

Brief Summary:
The aim of the study is to examine the effects of fine titration of thyroxine dosage on symptoms of hypothyroidism, wellbeing and quality of life. The hypothesis is that symptoms of hypothyroidism, wellbeing and quality of life will be improved in thyroxine-treated subjects when serum thyrotropin (TSH) is suppressed and/or in the lower reference range, compared to when TSH is in the upper reference range.

Condition or disease Intervention/treatment Phase
Hypothyroidism Drug: Thyroxine Phase 4

Detailed Description:

Primary hypothyroidism is a common disorder, affecting 2% of the Australian population. The standard treatment is with thyroxine (T4), and conventionally, a serum thyrotropin (TSH) concentration within the laboratory range is taken as indicating adequacy of thyroxine dosage.

Some patients with hypothyroidism complain of persistently impaired well-being, despite taking thyroxine in a dose which normalises serum TSH concentrations. It is not clear whether this is because of comorbidity or because standard thyroxine replacement is in some way inadequate for some individuals.

The reference range for serum TSH is wide (currently 0.34-4.8 mU/L at PathCentre). The distribution of serum TSH concentrations in the population is skewed, with the mean and median in the lower reference range at approximately 1.0 mU/L. This has led some to argue that a serum TSH in the lower reference range should be the usual therapeutic target. Anecdotal evidence suggests that some thyroxine-treated patients do feel better if the thyroxine dose is adjusted so that serum TSH is in the lower reference range rather than the upper reference range. The National Academy for Clinical Biochemistry of the United States now recommends, that for thyroxine-treated patients, that serum TSH should be less than 2.0 mU/L. There is, however, no evidence from properly conducted studies that aiming for a serum TSH concentration in the lower reference range improves symptoms of hypothyroidism or general wellbeing, and this proposal has not been generally adopted.

Only one study examining the effects of fine titration of thyroxine dosage on wellbeing has been published. In this study, patients had significantly improved wellbeing if they took a dose of thyroxine which was 50 μg greater than their biochemically optimal dose as determined by a thyrotropin-releasing hormone test. In most cases, serum TSH was suppressed to below 0.2 mU/L (the limit of sensitivity of the assay) on the thyroxine doses which improved wellbeing. This study was open-label and non-randomised, and the results therefore may have been affected by bias.

A well-designed, double blind study of the effects of fine titration of thyroxine dosage on symptoms of hypothyroidism, wellbeing and quality of life is required to determine if a serum TSH in the lower reference range, rather than simply TSH within the reference range, should indeed be the usual therapeutic target for thyroxine therapy in primary hypothyroidism. It is also desirable to confirm the findings of Carr et al., that patients have improved wellbeing if TSH is suppressed to below normal levels.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 55 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: What is the Optimal Serum TSH Concentration During Thyroxine Treatment for Primary Hypothyroidism? Effects of Fine Titration of Thyroxine Dosage on Wellbeing, Quality of Life and Cognitive Function
Study Start Date : April 2003
Study Completion Date : March 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothyroidism

Primary Outcome Measures :
  1. Visual analog scales assessing wellbeing

Secondary Outcome Measures :
  1. treatment satisfaction score
  2. treatment preference
  3. quality of life scores
  4. cognitive function tests
  5. clinical and biochemical markers of thyroid hormone action

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male or female subjects >18 years of age
  • Primary hypothyroidism ≥6 months duration arising from autoimmune hypothyroidism, thyroidectomy or radioiodine treatment
  • Thyroxine dose ≥100 mcg/day
  • No change in thyroxine dose in past 2 months
  • Serum TSH of 0.1-4.8 mU/L
  • Adequate contraceptive measures for women of childbearing age

Exclusion Criteria:

  • Major systemic illness affecting quality of life or likely to affect participation in the study
  • Treatment with T3 currently or in past 2 months
  • History of thyroid cancer requiring suppression of TSH secretion by thyroxine
  • Ischaemic heart disease – previous myocardial infarction, angina or coronary artery revascularisation
  • Renal failure: serum creatinine >135 micromol/L
  • Known liver disease with alkaline phosphatase or ALT >2x upper limit of reference range
  • Bony fracture in past 3 months or Paget’s disease of bone
  • Secondary (central) hypothyroidism or hypopituitarism

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00111735

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Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
Sir Charles Gairdner Hospital

Layout table for additonal information Identifier: NCT00111735     History of Changes
Other Study ID Numbers: 2003-015
First Posted: May 25, 2005    Key Record Dates
Last Update Posted: June 24, 2005
Last Verified: May 2005
Additional relevant MeSH terms:
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Thyroid Diseases
Endocrine System Diseases