Abstract
Introduction
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.
Key Points
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone (TSH).
Thyrotoxicosis is the clinical effect of high levels of thyroid hormones, whether or not the thyroid gland is the primary source.
The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma.
About 20 times more women than men have hyperthyroidism.
There is consensus that antithyroid drugs (carbimazole, propylthiouracil, and thiamazole) are effective in treating hyperthyroidism, although we found no evidence comparing them with placebo or with each other.
We found no evidence that antithyroid drugs plus thyroxine (block-replace regimens) improved relapse rates compared with titration regimens.
Higher-dose antithyroid drugs work better when taken for longer (greater than 18 months) than for a shorter time (6 months).
The doses of antithyroid drugs reported in the studies we found are higher than are generally used in practice.
There is also consensus that radioactive iodine (radioiodine) is effective for hyperthyroidism.
We don't know whether radioactive iodine increases risk of thyroid and extrathyroid cancer.
Radioactive iodine can worsen ophthalmopathy in people with Graves' disease.
Giving antithyroid drugs to people having radioiodine may increase the proportion of people with persistent or recurrent hyperthyroidism or who need further treatment.
There is consensus that thyroidectomy is effective for hyperthyroidism.
Total thyroidectomy is more effective than subtotal thyroidectomy for hyperthyroidism.
Replacement thyroxine will need to be given to people who become hypothyroid after thyroidectomy.
There may be some improvement in bone mineral density and TSH levels after treatment with antithyroid treatment in women who have subclinical hyperthyroidism.
About this condition
Definition
Hyperthyroidism is characterised by high levels of serum thyroxine (T4), high levels of serum triiodothyronine (T3), or both, and low levels of thyroid-stimulating hormone (TSH, also known as thyrotropin). Subclinical hyperthyroidism is characterised by decreased levels of TSH (<0.1 mU/L) but with levels of T4 and T3 within the normal range (total T4: 60–140 nanomol/L; total T3: 1.0–2.5 nanomol/L, depending on assay type). The terms hyperthyroidism and thyrotoxicosis are often used synonymously; however, they refer to slightly different conditions. Hyperthyroidism refers to overactivity of the thyroid gland leading to excessive production of thyroid hormones. Thyrotoxicosis refers to the clinical effects of unbound thyroid hormones, whether or not the thyroid gland is the primary source. Secondary hyperthyroidism due to pituitary adenomas, thyroiditis, iodine-induced hyperthyroiditis, and treatment of children and pregnant or lactating women are not covered in this review. Hyperthyroidism can be caused by Graves' disease (diffusely enlarged thyroid gland on palpation, ophthalmopathy, and dermopathy), toxic multinodular goitre (thyrotoxicosis and increased radioiodine uptake with multinodular goitre on palpation), or toxic adenoma (benign hyperfunctioning thyroid neoplasm presenting as a solitary thyroid nodule). We have not included treatment of Graves' ophthalmopathy in this review, although we do report on worsening of Graves' ophthalmopathy with radioiodine. We have also not included euthyroid sick syndrome (a condition seen in people with, for example, pneumonia, MI, cancer, and depression — it is characterised by low levels of TSH and T3). Diagnosis: The diagnosis of hyperthyroidism is established by a raised serum total or free T4 or T3 hormone levels, reduced TSH level, and high radioiodine uptake in the thyroid gland along with features of thyrotoxicosis. The usual symptoms are irritability, heat intolerance and excessive sweating, palpitations, weight loss with increased appetite, increased bowel frequency, and oligomenorrhoea. People with hyperthyroidism also often have tachycardia, fine tremors, warm and moist skin, muscle weakness, and eyelid retraction or lag.
Incidence/ Prevalence
Hyperthyroidism is more common in women than in men. One study (2779 people in the UK, median age 58 years, 20 years' follow-up) found an incidence of clinical hyperthyroidism of 0.8/1000 women a year (95% CI 0.5/1000 women/year to 1.4/1000 women/year). The study reported that the incidence was negligible in men. The incidence of hyperthyroidism is higher in areas of low iodine intake than in areas with high iodine intake, because suboptimal iodine intake induces nodular goitre, and, by time the nodules become autonomic, hyperthyroidism develops. In Denmark, an area characterised by moderate iodine insufficiency, the overall incidence of hyperthyroidism (defined as low levels of TSH) is 9.7%, compared with 1.0% in Iceland, an area of high iodine intake. The prevalence in this Danish study was 38.7/100,000 a year in women and 2/100,000 a year in men.
Aetiology/ Risk factors
Smoking is a risk factor, with an increased risk of both Graves' disease (OR 2.5, 95% CI 1.8 to 3.5) and toxic nodular goitre (OR 1.7, 95% CI 1.1 to 2.5). In areas with high iodine intake, Graves' disease is the major cause, whereas, in areas of low iodine intake, the major cause is nodular goitre. A correlation between diabetes mellitus and thyroid dysfunction has been described. In a Scottish population with diabetes, the overall prevalence of thyroid disease was found to be 13%, highest in women with type 1 diabetes (31%). As a result of screening, new thyroid disease was diagnosed in 7% of people with diabetes (hyperthyroidism in 1%).
Prognosis
Clinical hyperthyroidism can be complicated by severe cardiovascular or neuropsychiatry manifestations requiring admission to hospital or urgent treatment. Mortality: One population-based 10-year cohort study of 1191 people aged 60 years and over found a higher mortality among people who had a low initial TSH level. The excess in mortality was attributable to CVD. However, the people in this study who had a low TSH level may have had a higher prevalence of other illnesses, and adjustment was done only for age and sex, not for comorbidity. We found another population-based study evaluating 3888 people with hyperthyroidism. No increase was found in all-cause mortality or serious vascular events in people whose hyperthyroidism was treated and stabilised, but an increased risk of dysrhythmias was found in people treated for hyperthyroidism compared with standard population (standardised incidence ratio 2.71, 95% CI 1.63 to 4.24). Atrial fibrillation in people with overt hyperthyroidism: We found one cohort study evaluating the incidence of atrial fibrillation in people aged >60 years with low serum TSH concentrations (up to 0.1 mU/L). It found that low serum TSH concentrations were associated with an increased risk of atrial fibrillation (diagnosed by ECG) at 10 years (61 people with low TSH, 1576 people with normal TSH; incidence of atrial fibrillation: 28/1000 person-years with low TSH values v 11/1000 person-years with normal TSH values; 13/61 [21%] with low TSH values v 133/1576 [8%] with normal TSH values; RR 2.53, 95% CI 1.52 to 4.20; RR calculated by Clinical Evidence). A population-based study including 40,628 people diagnosed with hyperthyroidism in Denmark from 1977 to 1999 found that 8.3% were diagnosed with atrial fibrillation or flutter within ±30 days from the date of diagnosis of hyperthyroidism. Quality of life: Left untreated, thyroid problems can adversely effect quality of life in many ways, which can continue in the long term. In a long-term follow-up (179 people, treated for 14–21 years before investigation), people with Graves' disease, compared with a large Swedish reference population, had diminished vital and mental quality-of-life aspects even after years of treatment. Fracture rate and bone mineral density (BMD): Hip and spine BMD levels can decrease if hyperthyroidism is untreated. However, when treated, BMD can increase to normal levels. The risk of hip fracture is also higher in people with hyperthyroidism. Progression from subclinical to overt hyperthyroidism is seen in people with nodular goitre, but not in people found by screening to be without other signs of thyroid disease. A meta-analysis (search date 1996) based on data from screening studies estimated that each year 1.5% of women and 1.0% of men who had a low TSH level and normal free T4 and T3 levels developed an elevated free T4 or free T3 level. Ophthalmopathy is a complication of Graves' hyperthyroidism. Treatment can be problematic and usually involves topical corticosteroids and external radiation of the eye muscles. Thyroid volume and the nodularity of the gland influence the cure rate of hyperthyroidism: In a controlled study (124 people with newly diagnosed hyperthyroidism), remission rates were calculated after treatment with a combined antithyroid drug plus T4 for about 2 years. People with Graves' disease with no goitre or a small goitre had a significantly better outcome compared with people with Graves' disease with a medium-sized or large goitre. Most people with multinodular goitre had a relapse within the first year after stopping medication.
Aims of intervention
To eliminate the symptoms of hyperthyroidism and maximise quality of life, with minimum adverse effects of treatment.
Outcomes
Treatment success (levels of T4, T3, TSH); relapse; changes in thyroid function (including change of state from hyperthyroid to euthyroid/hypothyroid); quality of life and neuropsychological impairments (evaluated by cognitive function tests, memory tests, reaction time, self-rating mood scales, and depression scores); CVD (episodes of atrial fibrillation and ischaemic events); cardiac function (evaluated by echocardiography); changes in body composition (obesity and BMD measured by osteodensitometry or bioimpedance); prevention of progression from subclinical to overt hyperthyroidism; adverse effects of treatments (bone mass, fracture rate, development of hyperparathyroidism); ophthalmopathy.
Methods
Clinical Evidence search and appraisal February 2010. The following databases were used to identify studies for this review: Medline 1966 to February 2010, Embase 1980 to February 2010, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2010, Issue 1. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using predetermined criteria to identify relevant studies. Study-design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing >20 individuals, no lower percentage of individuals followed up, but a minimum length of follow-up of 12 months. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We also searched for prospective cohort studies with a control group for the question on surgical treatments, and did a specific harms search for thyroid ophthalmopathy worsened by radioiodine or surgery. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Hyperthyroidism (primary).
| Important outcomes | Changes in thyroid function, CVD, Neuropsychological impairments, Ophthalmopathy, Quality of life, Relapse rates, Treatment success | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of drug treatments for primary hyperthyroidism? | |||||||||
| 4 (390) | Relapse rates | Different durations of antithyroid treatment versus each other | 4 | 0 | 0 | –2 | 0 | Low | Consistency point deducted for different results at different end points, but added for dose response. Directness points deducted for not defining outcome and for using higher doses than would be used in practice |
| 1 (309) | Relapse rates | Different doses of antithyroid treatment versus each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for using higher doses than would normally be used in practice |
| 1 (309) | Changes in thyroid function | Different doses of antithyroid treatment versus each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for using higher doses than would normally be used in practice |
| 3 (870) | Ophthalmopathy | Radioactive iodine versus antithyroid drugs | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (114) | Ophthalmopathy | Radioactive iodine versus surgery | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 14 (1306) | Treatment success | Antithyroid drugs plus radioactive iodine versus radioactive iodine alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for poor methodology and uncertainty about randomisation/concealment |
| 14 (1306) | Changes in thyroid function | Antithyroid drugs plus radioactive iodine versus radioactive iodine alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for poor methodology and uncertainty about randomisation/concealment |
| 14 (1306) | CVD | Antithyroid drugs plus radioactive iodine versus radioactive iodine alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for poor methodology and uncertainty about randomisation/concealment |
| 12 (1250) | Relapse rates | Antithyroid drugs plus thyroxine (block-replace) versus antithyroid drugs alone (titration) | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for not defining outcome |
| 4 (566) | Relapse rates | Initial antithyroid drugs followed by either thyroxine or no treatment | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for not defining outcome |
| What are the effects of surgical treatments for primary hyperthyroidism? | |||||||||
| 35 (7241) | Treatment success | Total thyroidectomy versus subtotal thyroidectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for no intention-to-treat analysis |
| 35 (7241) | Changes in thyroid function | Total thyroidectomy versus subtotal thyroidectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for no intention-to-treat analysis |
| 1 (150) | Ophthalmopathy | Total thyroidectomy versus subtotal thyroidectomy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| What are the effects of treatments for subclinical hyperthyroidism? | |||||||||
| 1 (28) | Treatment success | Radioactive iodine | 2 | –1 | 0 | 0 | 0 | Very low | Quality point deducted for sparse data |
| 1 (28) | CVD | Radioactive iodine | 2 | –1 | 0 | 0 | 0 | Very low | Quality point deducted for sparse data |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Block-replace treatment
Combination of antithyroid treatment and concomitant thyroid-replacement therapy.
- High-quality evidence
Further research is very unlikely to change our confidence in the estimate of effect.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
References
- 1.Singhal T, Bal CS, Chandra P. Adjunctive antithyroid drugs in radioiodine therapy for hyperthyroidism (protocol). In: The Cochrane Library, Issue 2, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2004. [Google Scholar]
- 2.Lee SL, Ananthakrishnan S. Hyperthyroidism. eMedicine 18 July 2006. Available online at: http://www.emedicine.com/MED/topic1109.htm (last accessed 9 June 2010). [Google Scholar]
- 3.Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorder in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55–68. [DOI] [PubMed] [Google Scholar]
- 4.Laurberg P, Pedersen KM, Vestergaard H, et al. High incidence of multinodular toxic goitre in elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J Intern Med 1991;229:415–420. [DOI] [PubMed] [Google Scholar]
- 5.Laurberg P, Bulow Pedersen I, Pedersen KM, et al. Low incidence rate of overt hypothyroidism compared with hyperthyroidism in an area with moderately low iodine intake. Thyroid 1999;9:33–38. [DOI] [PubMed] [Google Scholar]
- 6.Vestergaard P, Rejnmark L, Weeke J, et al. Smoking as a risk factor for Graves' disease, toxic nodular goiter, and autoimmune hypothyroidism. Thyroid 2002;12:69–75. [DOI] [PubMed] [Google Scholar]
- 7.Perros P, McCrimmon RJ, Shaw G, et al. Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med 1995;12:622–627. [DOI] [PubMed] [Google Scholar]
- 8.Parle JV, Maisonneuve P, Sheppard MC, et al. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001;358:861–865. [DOI] [PubMed] [Google Scholar]
- 9.Flynn RW, McDonald TM, Jung RT, et al. Mortality and vascular outcomes in patients treated for thyroid dysfunction. J Clin Endocrinol Metab 2006;91:2169–2164. [DOI] [PubMed] [Google Scholar]
- 10.Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994;331:1249–1252. [DOI] [PubMed] [Google Scholar]
- 11.Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med 2004;164:1675–1678. [Erratum in: Arch Intern Med 2005;165:307] [DOI] [PubMed] [Google Scholar]
- 12.Abraham-Nordling M, Torring O, Hamberger B, et al. Graves' disease: a long-term quality-of-life follow up of patients randomized to treatment with antithyroid drugs, radioiodine, or surgery. Thyroid 2005;15:1279–1286. [DOI] [PubMed] [Google Scholar]
- 13.Vestergaard P, Mosekilde L. Hyperthyroidism, bone mineral, and fracture risk – a meta-analysis. Thyroid 2003;13:585–593. Search date 2002. [DOI] [PubMed] [Google Scholar]
- 14.Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: an update. Ann Intern Med 1998;129:144–158. Search date 1996. [Erratum in: Ann Intern Med 1999;130:246] [DOI] [PubMed] [Google Scholar]
- 15.Laurberg P, Buchholtz Hansen PE, Iversen E, et al. Goitre size and outcome of medical treatment of Graves' disease. Acta Endocrinol (Copenh) 1986;111:39–43. [DOI] [PubMed] [Google Scholar]
- 16.Prakash A, Avenell A, McGeoch SC, et al. Antithyroid drug regimen for treating Graves' hyperthyroidism. In: The Cochrane Library: Issue 1, 2010. Chichester UK: John Wiley & Sons, Ltd. Search date 2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis: special reference to normal white blood cell count agranulocytosis. Thyroid 2004;14:459–462. [DOI] [PubMed] [Google Scholar]
- 18.Reinwein D, Benker G, Lazarus JH, et al. A prospective randomized trial of antithyroid drug dose is Graves' Disease Therapy. J Clin Endocrinol Metab 1993;76:1516–1521. [DOI] [PubMed] [Google Scholar]
- 19.British National Formulary. Antithyroid drugs. BNF 62, September 2006, section 6.2.2. Available online at: http://www.bnf.org/bnf/bnf/current/4242.htm?q=%22carbimazole%22#_hit (last accessed 10 June 2010). [Google Scholar]
- 20.Cooper DS. Antithyroid drugs. N Engl J Med 2005;352:905–917. [DOI] [PubMed] [Google Scholar]
- 21.Hall P, Berg G, Bjelkengren G, et al. Cancer mortality after iodine-131 therapy for hyperthyroidism. Int J Cancer 1992;50:886–890. [DOI] [PubMed] [Google Scholar]
- 22.Franklyn JA, Maisonneuve P, Sheppard M, et al. Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study. Lancet 1999;353:2111–2115. [DOI] [PubMed] [Google Scholar]
- 23.Nygaard B, Faber J, Veje A, et al. Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131 I therapy. Thyroid 1999;9:477–481. [DOI] [PubMed] [Google Scholar]
- 24.Tallstedt L, Lundell G, Torring O, et al. Occurrence of ophthalmopathy after treatment for Graves' hyperthyroidism. New Engl J Med 1992;326:1733–1738. [DOI] [PubMed] [Google Scholar]
- 25.Bartelena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. New Engl J Med 1998;338:73–78. [DOI] [PubMed] [Google Scholar]
- 26.Träisk F, Tallstedt L, Abraham-Nordling M, et al. Thyroid-associated ophthalmopathy after treatment for Graves' hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009;94:3700–3707. [DOI] [PubMed] [Google Scholar]
- 27.Jarlov AE, Hegedus L, Kristensen LO, et al. Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while? Clin Endocrinol (Oxf) 1995;43:325–329. [DOI] [PubMed] [Google Scholar]
- 28.Walter MA, Briel M, Christ-Crain M, et al. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials. BMJ 2007;334:514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Abraham P, Avenell A, Park CM, et al. A systemic review of drug therapy for Graves' hyperthyroidism. Eur J Endocrinol 2005;153:489–498. Search date 2004. [DOI] [PubMed] [Google Scholar]
- 30.Palit TK, Miller CC, Miltenburg DM. The efficacy of thyroidectomy for Graves' disease: a meta-analysis. J Surg Res 2000;90:161–165. Search date 1998. [DOI] [PubMed] [Google Scholar]
- 31.Witte J, Goretzki PE, Dotzenrath C, et al. Surgery for Graves' disease: total versus subtotal thyroidectomy – result of a prospective randomized trial. World J Surg 2000;24:1303–1311. [DOI] [PubMed] [Google Scholar]
- 32.Faber J, Jensen IW, Petersen L, et al. Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women. Clin Endocrinol (Oxf) 1998;48:285–290. [DOI] [PubMed] [Google Scholar]