Thyroxine Titration Study

Hypothyroidism Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00111735
• Other study ID #: 2003-015
• Status: Active, not recruiting
• Phase: Phase 4
• First received: May 24, 2005
• Last updated: June 23, 2005
• Start date: April 2003
• Est. completion date: March 2005

Study information

• Verified date: May 2005
• Source: Sir Charles Gairdner Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypothyroidism

Intervention

Drug:
• Thyroxine

Locations

Country	Name	City	State
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia

Sponsors (1)

Lead Sponsor	Collaborator
Sir Charles Gairdner Hospital

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual analog scales assessing wellbeing
Secondary	treatment satisfaction score
Secondary	treatment preference
Secondary	quality of life scores
Secondary	cognitive function tests
Secondary	clinical and biochemical markers of thyroid hormone action