Background
Goitre is an enlargement of the thyroid gland that can be classified as simple, diffuse goitre or multinodular goitre. Nodules (lumps) within the thyroid gland are common and usually benign. They are more frequent in women, the elderly, and in people who live in iodine-deficient areas. Thyroid nodules may occur as a single nodule or as multiple nodules (multinodular). Multinodular goitre can be 'toxic' (producing too much thyroid hormone), or non-toxic (normal thyroid function). Treatments for non-toxic multinodular goitre include surgery, thyroid hormone suppressive therapy, and radioiodine therapy. Usually, higher amounts of radioiodine are needed to enable an appropriate radioiodine uptake in the thyroid nodules. Genetically engineered recombinant human thyroid-stimulating hormone (rhTSH) has been used to increase radioiodine uptake.
We wanted to find out whether rhTSH-aided radioiodine treatment is better for people with non-toxic multinodular goitre compared with radioiodine treatment alone. The outcomes we were specifically interested in were health-related quality of life, underactive thyroid (hypothyroidism), side effects, reduction in thyroid volume, death from any cause, and costs.
What did we look for?
We searched medical databases for studies that:
— were randomised controlled trials (medical studies where participants are put randomly into one of the treatment groups);
— included people with non-toxic multinodular goitre;
— compared rhTSH-aided radioiodine treatment with radioiodine treatment alone;
— tracked participants (follow-up) for at least one year.
What did we find?
We found six studies that included a total of 321 participants. A single dose of radioiodine was administered 24 hours after the intramuscular injection of a single dose of rhTSH. Participants were followed up for 12 to 36 months.
Key results
One study with 85 participants showed there was not a clear beneficial or harmful effect on health-related quality of life for either intervention. Fewer people (53 to 377 of 1000 treated) receiving radioiodine alone experienced hypothyroidism compared with rhTSH-aided radioiodine therapy. It is possible that radioiodine alone resulted in fewer side effects, like discomfort and neck pain, than rhTSH-aided radioiodine, but we need more studies to confirm this finding. On the other hand, rhTSH-aided radioiodine reduced thyroid volume by, on average, 12% more than radioiodine treatment alone. One study, with 28 participants, reported one death in the radioiodine alone group. No study reported on costs.
Certainty of the evidence
We are moderately confident about the results for hypothyroidism and reduction of thyroid volume, mainly because there were only six studies with 268 to 321 participants. We are very uncertain about the results for health-related quality of life and death from any cause, because there was just one study, with 85 participants that reported these outcomes. We are uncertain about the results for adverse events, mainly because there were not enough studies or participants to reliably evaluate this outcome.
How up to date is this review?
This evidence is up to date to 18 December 2020.
RhTSH-aided radioiodine treatment for non-toxic multinodular goitre, compared to radioiodine alone, probably increased the risk of hypothyroidism but probably led to a greater reduction in thyroid volume. Data on QoL and costs were sparse or missing.
Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine therapy is the only non-surgical alternative for non-toxic multinodular goitre. However, a high amount of radioiodine is needed to enable the thyroid nodules to adequately take up the radioiodine, because the multinodular goitre takes up a low amount of iodine. Recombinant human thyrotropin (rhTSH) has been used to increase radioiodine uptake and reduce thyroid volume of the multinodular goitre. Whether the improved reduction of the goitre resulting from rhTSH-stimulated radioiodine therapy is beneficial to the person remains controversial.
To assess the effects of recombinant human thyrotropin-aided radioiodine treatment for non-toxic multinodular goitre.
We searched the CENTRAL, MEDLINE, Scopus as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 18 December 2020.
We included randomised controlled clinical trials (RCTs) comparing the effects of rhTSH-aided radioiodine treatment compared with radioiodine alone for non-toxic multinodular goitre, with at least 12 months of follow-up.
Two review authors independently screened titles and abstracts for relevance. Screening for inclusion, data extraction, and risk of bias assessment were carried out by one review author and checked by a second. Our main outcomes were health-related quality of life (QoL), hypothyroidism, adverse events, thyroid volume, all-cause mortality, and costs. We used a random-effects model to perform meta-analyses, and calculated risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We evaluated the certainty of the evidence using the GRADE approach.
We included six RCTs. A total of 197 participants were allocated to rhTSh-aided radioiodine therapy, and 124 participants were allocated to radioiodine. A single dose of radioiodine was administered 24 hours after the intramuscular injection of a single dose of rhTSH. The duration of follow-up ranged between 12 and 36 months.
Low-certainty evidence from one study, with 85 participants, showed uncertain effects for QoL for either intervention. RhTSH-aided radioiodine increased hypothyroidism compared with radioiodine alone (64/197 participants (32.5%) in the rhTSH-aided radioiodine group versus 15/124 participants (12.1%) in the radioiodine alone group; RR 2.53, 95% CI 1.52 to 4.20; 6 studies, 321 participants; moderate-certainty evidence in favour of radioiodine alone). A total of 118/197 participants (59.9%) in the rhTSH-aided radioiodine group compared with 60/124 participants (48.4%) in the radioiodine alone group experienced adverse events (random-effects RR 1.24, 95% CI 0.94 to 1.63; 6 studies, 321 participants; fixed-effect RR 1.23, 95% CI 1.02 to 1.49 in favour of radioiodine only; low-certainty evidence).
RhTSH-aided radioiodine reduced thyroid volume with a MD of 11.9% (95% CI 4.4 to 19.4; 6 studies, 268 participants; moderate-certainty evidence). One study with 28 participants reported one death in the radioiodine alone group (very-low certainty evidence). No study reported on costs.