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