Subclinical Hyperthyroidism 'To Treat or Not to Treat?' - A Dutch Multicentre Trial

ISRCTN	ISRCTN04337637
DOI	https://doi.org/10.1186/ISRCTN04337637
Protocol serial number	NTR75
Sponsor	University Medical Centre St Radboud (Netherlands)
Funder	University Medical Centre St. Radboud (Netherlands)

Submission date: 12/09/2005
Registration date: 12/09/2005
Last edited: 24/08/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr E.H. Hoogendoorn
Scientific

UMCN st Radboud
Dept Endocrinologie, huispost 531
P.O. Box 9101
Nijmegen
6500 HB
Netherlands

Phone	+31 (0)24 3614599
Email	E.Hoogendoorn@ENDO.umcn.nl

Study information

Primary study design	Interventional
Study design	Multicentre randomised single blind active controlled parallel group trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	SUBstudy / SUBstudie
Study objectives	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.
Ethics approval(s)	Received from local medical ethics committee
Health condition(s) or problem(s) studied	Thyrotoxic symptoms, nodular goiter, hyperthyroidism
Intervention	Randomised clinical trial comparing active treatment with 131I with no treatment in subjects with endogenous subclinical hyperthyroidism in a multicenter study.
Intervention type	Other
Primary outcome measure(s)	1. Progression to overt hyperthyroidism: TSH, fT4, T3 every year 2. Changes in (thyrotoxic) symptoms (null-hypothesis: radioiodine does not cause improvement): 2.1. Quality of life - short form 36 Health Survey: on T=0, T=2 and T=5 years 2.2. Modified hyperthyroid symptom scale: on T=0, T=2 and T=5 years 2.3. In the treatment group on T= 1 year: duration of admission to hospital for administration of I131 (if necessary) and signs or symptoms of iodine induced thyroiditis or Graves like disease following iodine treatment making medical treatment necessary 3. Cardiac changes (null-hypothesis: radioiodine does not prevent development of atrial fibrillation): 3.1. 12-lead ECG: on T=0, T=2 and T=5 years 3.2. Holter monitoring (24 hour): mean 24-hour heart rate, number of PAC and VES: on T=0, T=2 and T=5 years 4. Changes in bone mineral density (null-hypothesis: radioiodine does not prevent deterioration of BMD): DEXA (Hologic or Lunar) L1-L4 and (right) femoral neck): on T=0, T=2 and T=5 years
Key secondary outcome measure(s)	Not provided at time of registration
Completion date	01/06/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	192
Key inclusion criteria	1. 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) 2. 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) 3. Informed consent
Key exclusion criteria	1. 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 BMD). 2. Radioiodine therapy in the past 3. Iodine-induced subclinical hyperthyroidism 4. Pituitary or hypothalamic insufficiency 5. Pregnancy 6. Age <= 50 years and > 80 years 7. Severe non-thyroidal illness 8. Drug abuse 9. Unstable angina pectoris, (history of) atrial fibrillation, (history of) congestive heart failure. 10. (History of) osteoporotic fracture(s) 11. Patients younger than 70 years of age with a bone mineral density T-score <2.5 SD, or older than 70 years of age with a bone mineral density Z-score <-1.0 SD 12. These patients can be randomised but in case it is decided to treat them with antiosteoporotic drugs they cannot be evaluated with respect to changes in BMD. 13. 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. 14. Other symptoms or signs of hyperthyroidism or obstruction of vital structures which in the opinion of the attending physician urge to active treatment.
Date of first enrolment	01/06/2003
Date of final enrolment	01/06/2010

Locations

Countries of recruitment

Netherlands

Study participating centre

UMCN st Radboud

Nijmegen
6500 HB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan