Thyroid : official journal of the American Thyroid Association
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Background: L-triiodothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer (TC) patients during the preparation for nuclear medicine procedures, and it is used in combination with LT4 in patients who do not respond to the standard treatment for hypothyroidism. This therapy is commonly done by using fixed doses, potentially resulting in supraphysiologic levels of triiodothyronine (T3). A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes that are able to maintain serum T3 levels within the reference range, but data on the PK of LT3 are conflicting. ⋯ PK modeling predicts that a twice-daily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the reference range. Conclusions: The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapies directed to maintain stable T3 serum levels.
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Background: Elevated postoperative serum calcitonin (Ctn) level indicates persistent/recurrent disease in patients with medullary thyroid carcinoma (MTC). Its location is a challenge. ⋯ The reference assessment localized disease in 24 (64%) patients with 74 lesions detected in the thyroid bed (8), in neck lymph nodes (15), mediastinal lymph nodes (6), lungs (1), liver (2), bones (3), and other site (1). At the patient level, the detection rates were 64% (CI 0.48-0.80) for F-18-Dopa PET/CT with early acquisitions, 40% (CI 0.24-0.56) for F-18-FDG PET/CT, 40% (CI 0.24-0.56) for WB MRI, and 48% (CI 0.31-0.66) for WB CT scan. Conclusions: In MTC patients with increased Ctn and no known distant metastases, F-18-Dopa PET/CT is more sensitive to detect structural disease than any other imaging modality, including WB MRI.
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Background: Some studies reported that among athyreotic patients on levothyroxine (LT4) after total thyroidectomy, patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum fT3 levels. The reduction of the thyroid volume (TV) after radioiodine treatment for Graves' disease is well known; however, a few studies evaluated thyroidal function including serum triiodothyronine (T3) levels of hypothyroid patients on LT4 after radioiodine treatment in detail. Methods: We retrospectively studied 446 patients treated with LT4 for radioiodine-induced hypothyroidism and who had undergone ultrasonography. ⋯ In 13 patients with TV more than 10 mL, serum fT3 levels were equivalent to those in controls (p = 0.844). Conclusions: Serum thyroid hormone balance in most patients on LT4 after radioiodine treatment for Graves' disease was similar to that in athyreotic patients on LT4. Mild TSH suppression with LT4 is needed to achieve normal fT3 levels in such patients.
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Background: High-mobility group box 1 (HMGB1) has been implicated in the pathogenesis of inflammatory autoimmune diseases. This study investigated the influence and mechanisms of HMGB1 in Graves' orbitopathy (GO). Methods: HMGB1 and its receptors (receptor for advanced glycation end products [RAGE], Toll-like receptor [TLR] 2, and TLR4) mRNA levels were evaluated by real-time polymerase chain reaction (RT-PCR) in GO and non-GO orbital tissues. The mRNA expressions of HMGB1 and its receptors were evaluated in primary cultured orbital fibroblasts from six GO patients and five healthy control subjects under interleukin (IL)-1β or tumor necrosis factor (TNF)-α stimulation using RT-PCR. ⋯ The plasma levels of HMGB1 were highly increased in patients with active GO, and were significantly correlated with the clinical activity score (r = 0.566, p = 0.002) and levels of thyrotropin binding inhibitory immunoglobulin (r = 0.506, p < 0.001). Conclusions: This study demonstrates an association of HMGB1 and its receptors in the inflammatory mechanisms of GO. HMGB1, RAGE, and TLR2 blockers reduced the production of pro-inflammatory molecules, providing a rationale for blocking the HMGB1 pathway to treat patients with GO. HMGB1 proteins were secreted further in the plasma of patients with active GO, suggesting that HMGB1 can be used as a biomarker of GO activity.
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Background: Medullary thyroid carcinoma (MTC) presents a disproportionate number of thyroid cancer deaths due to limited treatment options beyond surgery. Gain-of-function mutations of the human REarranged during Transfection (RET) proto-oncogene have been well-established as the key driver of MTC tumorigenesis. RET has been targeted by tyrosine kinase inhibitors (TKIs), such as cabozantinib and vandetanib. ⋯ Furthermore, combined treatment with miR-153-3p plus cabozantinib caused greater growth inhibition and appeared to reverse cabozantinib resistance. Mechanistically, miR-153-3p targets ribosomal protein S6 kinase B1 (RPS6KB1) of mTOR signaling and reduced downstream phosphorylation of Bcl-2 associated death promoter. Conclusion: This study provides evidence to establish systemic miRNA replacement plus TKIs as a novel therapeutic for patients with metastatic, progressive MTC.