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Subclinical hypothyroidism is a common finding when serum thyrotropin and thyroid hormones are measured, but the benefits of treating such patients with levothyroxine remain unproven. During the 14th International Thyroid Congress, a debate and discussion relating to three different clinical case scenarios of subclinical hypothyroidism was held. The audience consisted predominantly of members of the European Thyroid Association. Participants (n = 380) voted using an electronic system to express their opinion about the treatment of the 3 cases. For a 53-year-old woman with fatigue and difficulty losing weight, who has a serum TSH of 6.8 mU/l, 49% would treat with levothyroxine. Whereas, for an 84-year-old woman with a serum TSH of 6.8 mU/l, only 8% of participants would treat with levothyroxine. In contrast, for a 39-year-old woman who is trying to become pregnant, with a serum TSH of 4.5 mU/l and strongly positive thyroid peroxidase antibodies, 95% of respondents would treat with levothyroxine. This article details the clinical case scenarios and the results of the thyroidologists’ opinions on treatment. It forms a snapshot of the range of accepted clinical practice in this common condition.
Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Queen Elizabeth Hospital, Gateshead, UK
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Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroid-stimulating hormone (TSH) level: mildly increased TSH levels (4.0-10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT<sub>4</sub> within reference range, should be investigated with a repeat measurement of both serum TSH and FT<sub>4</sub>, along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with <smlcap>L</smlcap>-thyroxine is recommended for younger patients (<65-70 years) with serum TSH >10 mU/l. In younger SCH patients (serum TSH <10 mU/l) with symptoms suggestive of hypothyroidism, a trial of <smlcap>L</smlcap>-thyroxine replacement therapy should be considered. For such patients who have been started on <smlcap>L</smlcap>-thyroxine for symptoms attributed to SCH, response to treatment should be reviewed 3 or 4 months after a serum TSH within reference range is reached. If there is no improvement in symptoms, <smlcap>L</smlcap>-thyroxine therapy should generally be stopped. Age-specific local reference ranges for serum TSH should be considered in order to establish a diagnosis of SCH in older people. The oldest old subjects (>80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. If the decision is to treat SCH, then oral <smlcap>L</smlcap>-thyroxine, administered daily, is the treatment of choice. The serum TSH should be re-checked 2 months after starting <smlcap>L</smlcap>-thyroxine therapy, and dosage adjustments made accordingly. The aim for most adults should be to reach a stable serum TSH in the lower half of the reference range (0.4-2.5 mU/l). Once patients with SCH are commenced on <smlcap>L</smlcap>-thyroxine treatment, then serum TSH should be monitored at least annually thereafter.
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Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Queen Elizabeth Hospital, Gateshead, UK
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Department of Pediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK
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Wellcome Trust-MRC Institute of Metabolic Sciences, University of Cambridge, Cambridge, UK
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Department of Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK
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Objective
Patients with thyrotoxicosis are treated with anti-thyroid drug (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT).
Design
A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the biochemical response to BR/DT in the first 6 months of therapy.
Methods
Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with randomisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change.
Results
There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There was no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had higher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31.7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0.57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentrations.
Conclusions
DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT therapy.