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Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis
Abstract
Hyperthyroidism is a common condition with a global prevalence of 0·2-1·3%. When clinical suspicion of hyperthyroidism arises, it should be confirmed by biochemical tests (eg, low TSH, high free thyroxine [FT4], or high free tri-iodothyonine [FT3]). If hyperthyroidism is confirmed by biochemical tests, a nosological diagnosis should be done to find out which disease is causing the hyperthyroidism. Helpful tools are TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy. Hyperthyroidism is mostly caused by Graves' hyperthyroidism (70%) or toxic nodular goitre (16%). Hyperthyroidism can also be caused by subacute granulomatous thyroiditis (3%) and drugs (9%) such as amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors. Disease-specific recommendations are given. Currently, Graves' hyperthyroidism is preferably treated with antithyroid drugs. However, recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. Being younger than 40 years, having FT4 concentrations that are 40 pmol/L or higher, having TSH-binding inhibitory immunoglobulins that are higher than 6 U/L, and having a goitre size that is equivalent to or larger than WHO grade 2 before the start of treatment with antithyroid drugs increase risk of recurrence. Long-term treatment with antithyroid drugs (ie, 5-10 years of treatment) is feasible and associated with fewer recurrences (15%) than short-term treatment (ie, 12-18 months of treatment). Toxic nodular goitre is mostly treated with radioiodine (131I) or thyroidectomy and is rarely treated with radiofrequency ablation. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases. Specific attention is given to patients with hyperthyroidism who are pregnant, have COVID-19, or have other complications (eg, atrial fibrillation, thyrotoxic periodic paralysis, and thyroid storm). Hyperthyroidism is associated with increased mortality. Prognosis might be improved by rapid and sustained control of hyperthyroidism. Innovative new treatments are expected for Graves' disease, by targeting B cells or TSH receptors.
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“Third, the proximal predominant weakness with greater functional impairment in the upper extremities (2/5 proximally) on formal neurological examination differs from the classic lower limb predominant or ascending pattern typically described in TPP, expanding the recognized clinical spectrum of this condition [9].”
From Iatrogenic Thyrotoxicosis and Corticosteroid-Triggered Hypokalemic Periodic Paralysis in a Patient With Treated Hypothyroidism (2026) · cites this paper as [9]
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Metadata
- Authors
- Wiersinga, W. M., Poppe, K. G., & Effraimidis, G.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Université Libre de Bruxelles (BE)
- University of Thessaly (GR)
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 11
- Issue
- 4
- Pages
- 282-298
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W4321766463
- Semantic Scholar
- f3b4164bc2bb48249a703dd0658e104ae5a4fcfb
- Cited by
- 254
- References
- 154
- Citations by year
- 2026: 76 · 2025: 85 · 2024: 75 · 2023: 18
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Ophthalmology › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- hyperthyroidism, Graves' disease, etiology, pathogenesis, diagnosis, antithyroid drug therapy, thyroidectomy, radiofrequency ablation, thyrotoxicosis, thyroid storm, thyrotoxic periodic paralysis, atrial fibrillation, pregnancy, COVID-19 pandemic, prognosis, mortality, B cell-targeted therapy
- MeSH terms
- COVID-19, COVID-19 Testing, Female, Goiter, Nodular, Graves Disease, Humans, Hyperthyroidism, Iodine Radioisotopes, Pregnancy, Prognosis, Antithyroid Agents, Thyrotropin
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