The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in large compressive goitres. While some patients decline surgery others may have contraindications due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine (131I) therapy has been used for two decades as an effective and safe alternative to surgery in the treatment of symptomatic non-toxic MNG. Since much higher activities of 131I are employed when treating non-toxic rather than toxic MNG, there has been reluctance in many countries to use this treatment modality. Frequently, the 131I -uptake in a non-toxic MNG is low, which makes 131I therapy less feasible. Another challenge is the negative correlation between the initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid 131I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR by 35–56% at the expense of up to fivefold higher rate of permanent hypothyroidism. An alternative strategy is to reduce the administered 131I-activity with a factor corresponding to the rhTSH induced increase in 131I-uptake. Hereby, the extrathyroidal irradiation can be reduced without compromising efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented 131I therapy may profoundly alter the non-surgical treatment of benign non-toxic MNG.
Søren Fast, Viveque Egsgaard Nielsen, Steen Joop Bonnema and Laszlo Hegedüs
Helle Døssing, Finn Noe Bennedbæk, Steen Joop Bonnema, Peter Grupe and Laszlo Hegedüs
Objective: To compare the efficacy of interstitial laser photocoagulation (ILP) with radioiodine in hot thyroid nodules.
Design: Thirty consecutive outpatients with subclinical or mild hyperthyroidism and a scintigraphically solitary hot nodule with extraglandular suppression were randomized to either one ILP session or one radioiodine (131I) dose.
Methods: ILP was performed under continuous ultrasound-guidance and with an output power of 2.5–3.5 W. 131I was given as a single dose based on thyroid volume and a 24-h thyroid 131I uptake. Thyroid function and nodule volume were evaluated at inclusion and at 1, 3 and 6 months after treatment.
Results: Normalization of serum TSH was achieved in 7 out of 14 patients in the ILP group and in all 15 patients in the 131I group (P=0.0025). In the ILP group, mean thyroid nodule volume reduction was 44±5% (s.e.m.; P<0.001), and in the 131I group 47±8% (P<0.001), within 6 months, without between-group difference (P=0.73). The mean reduction of total thyroid volume was 7±5% in the ILP group (P=0.20) and 26±8% (P=0.006) in the 131I group (P=0.06 between-group). Two patients in the 131I group developed hypothyroidism but no major side effects were seen.
Conclusions: This first randomized study, comparing ILP with standard therapy, demonstrates that ILP and 131I therapy approximately halves thyroid nodule volume within 6 months; but in contrast to 131I, extranodular thyroid volume is unaffected by ILP and no patient developed hypothyroidism. Using the present design, ILP seems inferior to 131I therapy in normalization of serum TSH. The potential value of ILP as a non-surgical alternative to 131I needs further investigation.
Kristian Hillert Winther, Steen Joop Bonnema, Frederik Cold, Birgit Debrabant, Mads Nybo, Søren Cold and Laszlo Hegedüs
Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake.
The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60–74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast or matching yeast-based placebo tablets (n=126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period.
Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT3), and free thyroxine (FT4) at baseline, and after 6 months, and 5 years of supplementation.
Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio.
In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved.
Torquil Watt, Mogens Groenvold, Åse Krogh Rasmussen, Steen Joop Bonnema, Laszlo Hegedüs, Jakob Bue Bjorner and Ulla Feldt-Rasmussen
The importance of patient-reported outcomes such as health-related quality of life (HRQL) in clinical research is increasingly acknowledged. In order to yield valid results, the measurement properties of HRQL questionnaires must be thoroughly investigated. One aspect of such a validation process is the demonstration of content validity, i.e. that the questionnaire covers all relevant aspects. We review studies reporting on consequences of thyroid disorders and present the frequency of identified aspects, both overall HRQL issues and classical thyroid symptoms, in order to evaluate which issues are relevant for patients with thyroid diseases. Furthermore, existing questionnaires for thyroid patients are reviewed. A systematic search was performed in the Medline, Cinahl and Psycinfo databases and the reference lists of the relevant articles were hand-searched. Seventy-five relevant studies were identified. According to these studies, patients with untreated thyroid disease suffer from a wide range of symptoms and have major impairment in most areas of HRQL. Furthermore, the studies indicate that impairments in HRQL are also frequent in the long term. Six HRQL questionnaires for thyroid patients were identified. Generally, data supporting the validity of these questionnaires were sparse. According to the available literature, the quality of life of thyroid patients is substantially impaired over a wide range of aspects of HRQL in the untreated phase and continues to be so in many patients also in the long term. Studies systematically exploring the relative importance of these various aspects to thyroid patients are lacking, as is a comprehensive, validated thyroid-specific HRQL questionnaire.
Torquil Watt, Laszlo Hegedüs, Mogens Groenvold, Jakob Bue Bjorner, Åse Krogh Rasmussen, Steen Joop Bonnema and Ulla Feldt-Rasmussen
Appropriate scale validity and internal consistency reliability have recently been documented for the new thyroid-specific quality of life (QoL) patient-reported outcome (PRO) measure for benign thyroid disorders, the ThyPRO. However, before clinical use, clinical validity and test–retest reliability should be evaluated.
To investigate clinical (‘known-groups’) validity and test–retest reliability of the Danish version of the ThyPRO.
For each of the 13 ThyPRO scales, we defined groups expected to have high versus low scores (‘known-groups’). The clinical validity (known-groups validity) was evaluated by whether the ThyPRO scales could detect expected differences in a cross-sectional study of 907 thyroid patients. Test–retest reliability was evaluated by intra-class correlations of two responses to the ThyPRO 2 weeks apart in a subsample of 87 stable patients.
On all 13 ThyPRO scales, we found substantial and significant differences between the groups expected to have high versus low scores. Test–retest reliability was above 0.70 (range 0.77–0.89) for all scales, which is usually considered necessary for comparisons among patient groups, but below 0.90, which is the usual threshold for use in individual patients.
We found support for the clinical validity of the new thyroid-specific QoL questionnaire, ThyPRO, and evidence of good test–retest reliability. The questionnaire is now ready for use in clinical studies of patients with thyroid diseases.