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Drug-induced thyroid dysfunction
Published in David S. Cooper, Jennifer A. Sipos, Medical Management of Thyroid Disease, 2018
Victor Bernet, Robert C. Smallridge
There are also medications that distort in vitro tests of thyroid function, with particular reference to estimates of serum free thyroxine (109). Displacement of thyroid hormone from serum-binding proteins has been noted with heparin, aspirin, carbamazepine, furosemide, phenytoin, and salsalate therapy (110–114). Non-esterified fatty acids (NEFA) in a concentration of >3 mmol/l can increase the displacement of T4 from TBG. In patients receiving heparin, lipoprotein lipase becomes mobilized in vivo, which during sample storage or incubation can lead to rising NEFA levels which stimulate disassociation of T4 and T3 from thyroid-binding proteins resulting in spuriously high results in FT4 and FT3 assays. Heparin does not appear to impact TSH measurements nor total T4 and T3 levels (115). Furosemide has been found to inhibit T4 binding and appears to impact measurement in free T4 assays which involve less sample dilutions than others (109). Phenytoin and carbamazepine can displace T4 and T3 from thyroid-binding proteins leading to an increase in free hormone concentrations and a concomitant decrease in total T4 and T3 levels. As FT4 and FT3 assays tend to yield spuriously low levels in these circumstances, TSH levels, which are not impacted, should be relied on to guide therapy (116). The impact of aspirin, salsalate, and nonsteroidal anti-inflammatory drugs (NSAIDs) vary by drug and length of exposure. A single-dose or 1 week of salsalate therapy was found to decrease both free and total T4 and T3 levels while TSH remained unchanged after a lone dose and decreased after 1 week while remaining in the normal range (112). In the same study, acute TH changes noted with aspirin included lower TT3 and FT3 with stable TT4 and FT4 and TSH levels; after 1 week TSH, TT4, TT3, and FT3 all dropped but FT4 remained stable. Testing with the NSAID meclofenamate revealed an acute rise in TT4, TT3, FT3 with no change in TSH and FT4 and stability in all these levels after 1 week.
Disease-modifying therapies for tauopathies: agents in the pipeline
Published in Expert Review of Neurotherapeutics, 2019
Francesco Panza, Bruno P. Imbimbo, Madia Lozupone, Antonio Greco, Davide Seripa, Giancarlo Logroscino, Antonio Daniele, Carlo Colosimo
Salsalate is an old salicylate derivative with anti-inflammatory properties. The drug blocks activation of the NF-κB pathway. Recent studies have shown that salsalate inhibits acetylation of tau. In the PS19 transgenic mouse model of FTD, salsalate oral treatment lowered brain levels of acetylated tau (Lys174) and total tau [96]. Interestingly, the drug prevented hippocampal atrophy and reversed memory deficits [96]. In a mouse model of traumatic brain injury (controlled cortical impact), salsalate treatment was shown to significantly improve functional recovery [97]. A 6 month, safety and tolerability study of salsalate (2,250 mg/day) in 10 patients with PSPS is expected to be completed by March 2019 (ClinicalTrials.gov identifier: NCT02422485). Although the study is uncontrolled, brain volume, motor functioning, cerebrospinal fluid (CSF) biomarkers, and cognition are being measured in the study as exploratory efficacy variables. This study may give indications of whether targeting tau acetylation may have therapeutic potential in primary tauopathies, although doubts remain due to the poor brain penetration of salsalate (<3%). Indeed, the encouraging results obtained by the Gladstone Institute group in a transgenic mouse model of FTD were not replicated by other independent groups.