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JAMA Oct 2023Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine... (Review)
Review
IMPORTANCE
Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality.
OBSERVATIONS
The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L.
CONCLUSIONS AND RELEVANCE
Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.
Topics: Adult; Female; Humans; Male; Pregnancy; Antithyroid Agents; Graves Disease; Hyperthyroidism; Iodine; Iodine Radioisotopes; Osteoporosis; Thyroid Neoplasms; Thyroid Nodule; Thyroiditis; Thyrotoxicosis; Thyrotropin; Thyroxine; Weight Loss
PubMed: 37847271
DOI: 10.1001/jama.2023.19052 -
Biochimica Et Biophysica Acta. Reviews... Jul 2023Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. Surgery, chemotherapy, radiotherapy, and radioactive iodine (RAI) therapy are the standard TC... (Review)
Review
Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. Surgery, chemotherapy, radiotherapy, and radioactive iodine (RAI) therapy are the standard TC treatment modalities. However, recurrence or tumor metastasis remains the main challenge in the management of anaplastic thyroid cancer (ATC) and radioiodine (RAI) radioactive iodine-refractory differentiated thyroid cancer (RR-DTC). Several multi-tyrosine kinase inhibitors (MKIs), or immune checkpoint inhibitors in combination with MKIs, have emerged as novel therapies for controlling the progression of DTC, medullary thyroid cancer (MTC), and ATC. Here, we discuss and summarize the molecular basis of TC, review molecularly targeted therapeutic drugs in clinical research, and explore potentially novel molecular therapeutic targets. We focused on the evaluation of current and recently emerging tyrosine kinase inhibitors approved for systemic therapy for TC, including lenvatinib, sorafenib and cabozantinib in DTC, vandetanib, cabozantinib, and RET-specific inhibitor (selpercatinib and pralsetinib) in MTC, combination dabrafenib with trametinib in ATC. In addition, we also discuss promising treatments that are in clinical trials and may be incorporated into clinical practice in the future, briefly describe the resistance mechanisms of targeted therapies, emphasizing that personalized medicine is critical to the design of second-line therapies.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Anilides; Thyroid Carcinoma, Anaplastic; Protein Kinase Inhibitors
PubMed: 37257629
DOI: 10.1016/j.bbcan.2023.188928 -
Clinical Cancer Research : An Official... Jul 2023To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with...
PURPOSE
To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.
PATIENTS AND METHODS
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.
RESULTS
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients.
CONCLUSIONS
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Proto-Oncogene Proteins B-raf; Thyrotropin Alfa; Prospective Studies; Pyridones; Pyrimidinones; Oximes; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Mutation
PubMed: 37074727
DOI: 10.1158/1078-0432.CCR-23-0046 -
The Malaysian Journal of Pathology Apr 2024Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical...
INTRODUCTION
Persistently elevated thyroid stimulating hormone (TSH) despite levothyroxine (LT4) treatment that exceeds the standard weight-adjusted dose is a common clinical presentation. This may lead to additional testing for LT4 malabsorption or poor LT4 adherence, the latter of which is challenging to confirm because it is predicated on accurate patient accountability.
CASE REPORT
A 35-year-old lady, post-radioactive iodine therapy for Graves' disease remained euthyroid for a year on oral LT4. Two years later, she was clinically and biochemically hypothyroid despite claiming LT4 compliance. As all laboratory investigations were within the reference range, pseudomalabsorption was suspected and a LT4 absorption test was done. During the test, her free thyroxine increased significantly at 4 hours, reaching a peak of more than 50% from baseline while TSH decreased appropriately from 0 minute to 360 minutes. This was followed by normalisation of TSH with LT4 treatment under direct observation.
DISCUSSION
The LT4 absorption test is a prompt and economical means to rule out true malabsorption, decrease unwarranted subspecialty referrals and validate the weight-adjusted LT4 dose reduction.
Topics: Humans; Adult; Hypothyroidism; Female; Thyroxine; Graves Disease; Thyrotropin
PubMed: 38682851
DOI: No ID Found -
Endocrine Reviews Jan 2024Radiation is an environmental factor that elevates the risk of developing thyroid cancer. Actual and possible scenarios of exposures to external and internal radiation... (Review)
Review
Radiation is an environmental factor that elevates the risk of developing thyroid cancer. Actual and possible scenarios of exposures to external and internal radiation are multiple and diverse. This article reviews radiation doses to the thyroid and corresponding cancer risks due to planned, existing, and emergency exposure situations, and medical, public, and occupational categories of exposures. Any exposure scenario may deliver a range of doses to the thyroid, and the risk for cancer is addressed along with modifying factors. The consequences of the Chornobyl and Fukushima nuclear power plant accidents are described, summarizing the information on thyroid cancer epidemiology, treatment, and prognosis, clinicopathological characteristics, and genetic alterations. The Chornobyl thyroid cancers have evolved in time: becoming less aggressive and driver shifting from fusions to point mutations. A comparison of thyroid cancers from the 2 areas reveals numerous differences that cumulatively suggest the low probability of the radiogenic nature of thyroid cancers in Fukushima. In view of continuing usage of different sources of radiation in various settings, the possible ways of reducing thyroid cancer risk from exposures are considered. For external exposures, reasonable measures are generally in line with the As Low As Reasonably Achievable principle, while for internal irradiation from radioactive iodine, thyroid blocking with stable iodine may be recommended in addition to other measures in case of anticipated exposures from a nuclear reactor accident. Finally, the perspectives of studies of radiation effects on the thyroid are discussed from the epidemiological, basic science, and clinical points of view.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Radioactive Hazard Release; Iodine
PubMed: 37450579
DOI: 10.1210/endrev/bnad022