Background: Data suggest symptoms of hypothyroidism persist in 5–10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area. Methods: Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large. Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid patients who have persistent complaints despite serum TSH values within the reference range, provided they have previously received support to deal with the chronic nature of their disease, and associated autoimmune diseases have been excluded. Treatment should only be instituted by accredited internists/endocrinologists, and discontinued if no improvement is experienced after 3 months. It is suggested to start combination therapy in an L-T4/L-T3 dose ratio between 13:1 and 20:1 by weight (L-T4 once daily, and the daily L-T3 dose in two doses). Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13:1, and are not recommended. Close monitoring is indicated, aiming not only to normalize serum TSH and free T4 but also normal serum free T4/free T3 ratios. Suggestions are made for further research. Conclusion: L-T4 + L-T3 combination therapy should be considered solely as an experimental treatment modality. The present guidelines are offered to enhance its safety and to counter its indiscriminate use.

Objective: The most accurate way to measure urinary iodine excretion in epidemiological surveys is still debated. We propose a new principle of estimating iodine excretion based on casual urine samples. Material and methods: A total of 123 24 h urine samples and corresponding casual urine samples were collected from 31 subjects. Iodine excretion was expressed as 24 h iodine excretion and three different estimates: iodine concentration in the casual sample, iodine/gram creatinine in the casual sample, and the new principle—iodine/creatinine ratio in the casual sample, adjusted for expected creatinine excretion of the individual. Results: All three estimates based on casual urine samples correlated significantly to 24 h values with a r (Pearson) of 0.37 for iodine concentration, 0.61 for iodine/creatinine ratio and 0.62 for the age- and sex-adjusted iodine/creatinine ratio. The median iodine excretion in the entire group was 143 μg/day in 24 h samples, 87 μg/l as iodine concentration, 77 μg/g creatinine as iodine/creatinine ratio and 126 μg/day as age- and sex-adjusted iodine/creatinine ratio. Conclusion: Age- and sex-adjusted iodine/creatinine ratio is a more accurate and unbiased estimate of iodine excretion in epidemiological surveys of adults than the two most frequently used estimated: iodine concentration and iodine/gram creatinine, as these two estimates may introduce a bias depending on the composition of the investigated group. The adjusted iodine/creatinine ratio is superior to the other estimates, especially when individual estimates of 24 h iodine excretion is required or cohorts of selected groups are investigated. Sponsorship: This work was supported by grants from the Medical Research Foundation Region Greater Copenhagen, Faroe Islands and Greenland; the Wedell-Wedellsborg Foundation; Musikforlæggerne Agnes and Knut Mørks Foundation. European Journal of Clinical Nutrition (2000) 54, 361–363

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Background: Treatment of hypothyroidism with 3,5,3′-triiodothyronine (T₃) is controversial. A recent meta-analysis concludes that no evidence is present in favour of using T₃. However, the analysis included a mixture of different patient groups and dose-regimens.Objective: To compare the effect of combination therapy with thyroxine (T₄) and T₃ versus T₄ monotherapy in patients with hypothyroidism on stable T₄ substitution.Study design: Double-blind, randomised cross-over. Fifty micrograms of the usual T₄ dose was replaced with either 20 μg T₃ or 50 μg T₄ for 12 weeks, followed by cross-over for another 12 weeks. The T₄ dose was regulated if needed, intending unaltered serum TSH levels.Evaluation: Tests for quality of life (QOL) and depression (SF-36, Beck Depression Inventory, and SCL-90-R) at baseline and after both treatment periods.Inclusion criteria: Serum TSH between 0.1 and 5.0 mU/l on unaltered T₄ substitution for 6 months.Results: A total of 59 patients (55 women); median age 46 years. When comparing scores of QOL and depression on T₄ monotherapy versus T₄/T₃ combination therapy, significant differences were seen in 7 out of 11 scores, indicating a positive effect related to the combination therapy. Forty-nine percent preferred the combination and 15% monotherapy (P=0.002). Serum TSH remained unaltered between the groups as intended.Conclusion: In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T₃ 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.

OBJECTIVE--To investigate the long term effect of radioactive iodine on thyroid function and size in patients with non-toxic multinodular goitre. DESIGN--Consecutive patients with multinodular non-toxic goitre selected for radioactive iodine treatment and followed for a minimum of 12 months (median 48 months) after an intended dose of 3.7 MBq/g thyroid tissue corrected to a 100% uptake of iodine-131 in 24 hours. PATIENTS--69 patients with a growing multinodular non-toxic goitre causing local compression symptoms or cosmetic inconveniences. The treatment was chosen because of a high operative risk, previous thyroidectomy, or refusal to be operated on. MAIN OUTCOME MEASUREMENTS--Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 1, 2, 3, 6, and 12 months after treatment and then once a year. RESULTS--56 patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose and remaining euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (23-48) ml at 24 months in the 39 patients in whom this was measured during follow up. The median reduction was 40 (22-48) ml (60% reduction, p < 0.0001), half of which occurred within three months. Patients treated with two doses as well as those developing hypothyroidism and hyperthyroidism had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%, 95% confidence interval 4.8% to 38.4%). Side effects were few: three cases of hyperthyroidism and two cases of radiation thyroiditis. Only one patient was dissatisfied with the result; she was referred for operation six months after treatment. CONCLUSIONS--A substantial reduction in thyroid volume accompanied by a low incidence of hypothyroidism and few side effects makes the use of radioactive iodine an attractive alternative to surgery in selected cases of non-toxic multinodular goitre.