Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report

There is a frequently encountered subset of hypothyroid patients who are refractory to standard thyroid hormone replacement treatment and require unexpectedly high doses of levothyroxine. In addition to clinical situations where hypothyroid patients are non-compliant, or where there is the possibility of excipient-induced disease exacerbation (gluten/celiac disease), therapeutic failure may be due to impaired absorption of the administered drug. The common approach to managing patients with unusual thyroxine needs is to escalate the dose of levothyroxine until targeted TSH levels are achieved. This approach can increase the risk for prolonged exposure to supratherapeutic doses of levothyroxine, which increase the chances of adverse outcomes. Repeated adjustments of levothyroxine can also escalate the costs of treatment, as frequent office visits and laboratory tests are required to determine and maintain the desired dose. Clinicians should take a systematic approach to managing patients whom they suspect of having treatment-refractory hypothyroidism. This may include searching for, and adjusting, occult medical conditions and/or other factors that may affect the absorption of levothyroxine, before up-titrating the dose of traditional levothyroxine therapy. Depending on the underlying pathology, another approach that may be considered is to try alternative formulations of levothyroxine that are less susceptible to intolerance issues related to excipients, or, in some cases, to malabsorption. The early discovery of these factors via a thoughtful patient work-up may avoid unnecessary thyroid medication adjustments and their consequences for both patients and clinicians

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Drug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice

Background and Objectives : Several drugs may interact with levothyroxine and reduce its bioavailability. The aim of this study was to analyse the Italian general practice patients with hypothyroidism from 2002â2011, in terms of variation of thyroid-stimulating hormone (TSH) levels, number of levothyroxine prescriptions and dose of levothyroxine before and during potential drugâdrug interactions (DDIs).Methods: Data were extracted from the Italian general practice Health Search CSD Longitudinal Patient Database (HSD). Analysis was limited to individuals aged 18 years and older with at least one levothyroxine prescription from 2002 to 2011 and at least one year of clinical history recorded in HSD. A quasi-experimental pre-post analysis was carried out using a self-controlled study design, on an intention-to-treat basis.Results: Overall, 5,426 levothyroxine users (7.5 % of population in HSD) were included in the study. The incidence rate ratio comparing the TSH trend before and during the period of exposure to potential DDI showed a significant increase of TSH levels during initial exposure to potential DDI, which decreased over time. The number of prescriptions and dose of levothyroxine decreased before the potential DDI and increased symmetrically during the period of exposure to potential DDI.Conclusions: The co-prescription of levothyroxine and potentially interacting drugs results in an increased use of levothyroxine. Clinicians should carefully consider adjusting levothyroxine therapy in presence of concomitant drugs, such as proton-pump inhibitors, which may reduce levothyroxine bioavailability