Hyperthyroidism and thyrotoxicosis

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Claire L Wood Department of Paediatric Endocrinology, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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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Niamh Morrison Department of Paediatric Endocrinology, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK

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Michael Cole Population Health Sciences Institute, Newcastle University, Baddiley-Clark Building, Newcastle upon Tyne, UK

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Malcolm Donaldson Department of Child Health, University of Glasgow School of Medicine, Glasgow, UK

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David B Dunger Department of Paediatrics, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
Wellcome Trust-MRC Institute of Metabolic Sciences, University of Cambridge, Cambridge, UK

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Ruth Wood Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK

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Simon H S Pearce Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK
Department of Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK

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Timothy D Cheetham Department of Paediatric Endocrinology, Great North Children’s Hospital, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
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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on behalf of the British Society for Paediatric Endocrinology and Diabetes (BSPED)

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.

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Laure Felix Univ. Grenoble Alpes, Department of Radiology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France

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Peggy Jacon Univ. Grenoble Alpes, Department of Cardiology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France

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Maxime Lugosi Univ. Grenoble Alpes, Department of Internal Medicine, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France

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Justine Cristante Univ. Grenoble Alpes, Department of Endocrinology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France

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Julie Roux Univ. Grenoble Alpes, Department of Nuclear Medicine, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France

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Olivier Chabre Univ. Grenoble Alpes, Department of Endocrinology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France

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Background and Objective

It has been reported recently in a cross sectional study that patients with amiodarone induced thyrotoxicosis (AIT) showed a ‘white’ thyroid on unenhanced computed tomography, due to intrathyroid iodine accumulation. However, the link between increase in thyroid radiologic density and amiodarone induced thyrotoxicosis remains unknown. We sought to analyze this link.

Methods

We present the case of a 34-year-old patient with severe sarcoidosis-related hypertrophic cardiomyopathy who was followed with successive unenhanced CT scans integrated with FDG PET scans. After the first CT scans the patient, who initially had a normal thyroid function, was exposed to amiodarone during 23 months and developed AIT, very likely by thyroiditis (AIT type 2). There were no thyroid antibodies, no evidence of thyroid sarcoidosis on FDG PET scan, while thyroid sonogram showed a homogenous 22 ml moderate goiter with normal echogenicity and no nodules.

Results

Analysis of the successive enhanced CT scans revealed that after initiation of amiodarone treatment, thyroid radiologic density steadily increased before detection of AIT, peaked after cessation of amiodarone and initiation of thyrotoxicosis treatment, before returning to normal as thyrotoxicosis receded. Thyroid volume also showed a moderate increase, peaking at the detection of thyrotoxicosis, before returning to normal.

Conclusion

This case suggests that AIT is preceded by a very high intrathyroid iodine accumulation before the ‘burst’ of thyroiditis occurs and that measurements of thyroid gland radiological density might predict the development and remission of AIT.

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Bruno Bouça Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Ana Cláudia Martins Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Paula Bogalho Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Lídia Sousa Cardiology Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Tiago Bilhim Interventional Radiology Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Filipe Veloso Gomes Interventional Radiology Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Élia Coimbra Interventional Radiology Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Ana Agapito Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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José Silva-Nunes Endocrinology, Diabetes and Metabolism Department, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal

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Introduction

Amiodarone-induced thyrotoxicosis (AIT) can sometimes lead to life-threatening complications, especially in patients with congenital heart disease (CHD). We report the case of a patient with refractory AIT that was successfully treated with thyroid arterial embolization (TAE).

Case report

A 34-year-old man with complex cyanotic CHD complicated with heart failure (HF), pulmonary hypertension, and supraventricular tachyarrhythmias, was treated with amiodarone since 2013. In March 2019, he presented worsening of his cardiac condition and symptoms of thyrotoxicosis that were confirmed by laboratory assessment. Thiamazole 30 mg/day and prednisolone 40 mg/day were prescribed, but the patient experienced worsening of his cardiac condition with several hospital admissions in the next 5 months, albeit increasing dosages of thionamide and glucocorticoid and introduction of cholestyramine and lithium. Thyroidectomy was excluded due to the severity of thyrotoxicosis, and plasmapheresis was contraindicated due to the cardiac condition. TAE of the four thyroid arteries was then performed with no immediate complications. Progressive clinical and analytical improvement ensued with gradual reduction and suspension of medication with the patient returning to euthyroid state and his usual cardiac condition previous to the AIT.

Conclusion

For patients with medication refractoriness and whose condition precludes thyroidectomy, embolization of thyroid arteries may be an effective and safe option.

Established facts

  • Amiodarone-induced thyrotoxicosis (AIT) can be refractory to a combination therapy of thionamides and glucocorticoids.

  • Restoration of euthyroidism is of paramount importance in heart failure (HF) patients.

  • Emergency thyroidectomy for AIT unresponsive to medical therapy is recommended in patients with severe underlying cardiac disease or deteriorating cardiac function.

Novel insights

  • Thyroid arterial embolization (TAE) appeared as a salvage therapy in this patient.

  • To the best of our knowledge, few case reports in the literature have described the embolization of the four thyroid arteries in AIT context.

  • Endovascular embolization techniques are a valuable therapeutic option and can be considered in cases where standard forms of treatment are ineffective or involve unacceptable risks.

Open access