Does Radioiodine Treatment Prevent Atrial Fibrillation and Bone Loss in Endogenous Subclinical Hyperthyroidism?

Subclinical Hyperthyroidism "To Treat or Not to Treat?" A Dutch Multicenter Trial

Subclinical hyperthyroidism is defined as the presence of serum free thyroxine (T4) and triiodothyronine (T3) levels within the reference range and a reduced serum thyrotrophin (TSH) level. Evidence is accumulating that it has important clinical effects. The SUBstudy is a randomised, Dutch multicenter trial to study whether radioiodine treatment prevents the development of atrial fibrillation and prevents decreases in bone mineral density in patients with endogenous subclinical hyperthyroidism.

Study Overview

• Status: Unknown
• Conditions: Hyperthyroidism
• Intervention / Treatment: Procedure: treatment with 131I

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth Hoogendoorn, MD; Phone Number: ++31243614599; Email: e.hoogendoorn@endo.umcn.nl
• Study Contact Backup: Name: Ad Hermus, MD, Prof; Phone Number: ++31243614599

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Academical Medical Centre Amsterdam
    • Contact: W. Wiersinga, MD, Prof
  • Groningen, Netherlands
    • Recruiting
    • Martini Ziekenhuis Groningen
    • Contact: K. van Tol, MD, PhD
    • Principal Investigator: K. van Tol, MD, PhD
  • Groningen, Netherlands
    • Recruiting
    • University Hospital Groningen
    • Contact: G. van den Berg, MD, PhD; Phone Number: ++31-5036161616
    • Principal Investigator: G. van den Berg, MD, PhD
  • Nijmegen, Netherlands, 6500HB
    • Recruiting
    • Radboud University Medical Centre Nijmegen
    • Contact: Elizabeth Hoogendoorn, MD; Phone Number: ++31-243614599
    • Principal Investigator: Elizabeth Hoogendoorn, MD
  • Veldhoven, Netherlands
    • Recruiting
    • Maxima Medisch Centrum
    • Contact: H. Haak, MD, PhD
    • Principal Investigator: H. Haak, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subclinical hyperthyroidism [TSH ≤ 0.1 mU/L, fT4 and T3 within the normal range of the own laboratory (determined 2 times in own laboratory) with an interval of at least 2 months].
• Endogenous cause of subclinical hyperthyroidism limited to autonomous adenoma or multinodular goiter (diagnosis made by the attending physician, based on palpation and the result of a thyroid scintigram).
• Informed consent.

Exclusion Criteria:

• Medication with anti-thyroid drugs in the last 3 months (also not allowed during follow-up); thyroid hormone in the last 3 months (allowed during follow-up, but TSH levels should be kept between 0.1 mU/L and the upper limit of normal in the own laboratory); and oral glucocorticoids in the last 3 months (allowed during follow-up when absolutely necessary, but patients in whom glucocorticoids are started cannot be evaluated with respect to changes in bone mineral density [BMD]).
• Radioiodine therapy in the past.
• Iodine-induced subclinical hyperthyroidism.
• Pituitary or hypothalamic insufficiency.
• Pregnancy.
• Age <= 40 years.
• Severe non-thyroidal illness.
• Drug abuse.
• Unstable angina pectoris, (history of) atrial fibrillation, (history of) congestive heart failure.
• (History of) osteoporotic fracture(s).
• Patients younger than 70 years of age with a bone mineral density T-score < - 2.5 standard deviations (SD), or older than 70 years of age with a bone mineral density Z-score < 1.0 SD. (These patients can be randomized but in case it is decided to treat them with anti-osteoporotic drugs they cannot be evaluated with respect to changes in BMD.)
• Use of betablockers in the last three months. (These patients can be randomised but cannot be evaluated with respect to general and cardiac symptoms. The same applies to patients in whom betablockers are started during follow up.)
• Other symptoms or signs of hyperthyroidism or obstruction of vital structures which, in the opinion of the attending physician, require active treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To provide evidence that restoration of euthyroidism (normal TSH) improves thyrotoxic symptoms and signs and quality of life and lowers the risk of subsequent atrial fibrillation and bone loss in subjects with endogenous subclinical hyperthyroidism

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Ad Hermus, MD, Prof, Radboud University Medical Center

Publications and helpful links

General Publications

• Hoogendoorn EH, Wiersinga WM, Prummel MF, den Heijer M, Corstens FH, Hermus AR. [Subclinical hypothyroidism; the start of a clinical trial into the usefulness of treatment with radioactive iodine]. Ned Tijdschr Geneeskd. 2004 May 8;148(19):953-4. Dutch.

Study record dates

Study Major Dates

• Study Start: April 1, 2004

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (Estimate): September 9, 2005

Study Record Updates

• Last Update Posted (Estimate): July 18, 2007
• Last Update Submitted That Met QC Criteria: July 17, 2007
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Keywords: endogenous subclinical hyperthyroidism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hyperthyroidism
• Other Study ID Numbers: SUBstudie