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.

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.