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      Levothyroxine malabsorption or pseudomalabsorption? A question in the management of refractory hypothyroidism

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          Abstract

          Purpose

          The levothyroxine absorption test (LT4AT) is an important tool for distinguishing hypothyroidism due to malabsorption from ‘pseudomalabsorption’ conditions. Our aim was to review our institution’s LT4AT results and assess its role in the management of patients with refractory hypothyroidism.

          Methods

          We performed a retrospective study of all patients evaluated for refractory hypothyroidism who underwent LT4AT in our tertiary center between 2014 and 2020. Its results and the impact on thyroid function management during follow-up were assessed.

          Results

          Ten female patients were included with a mean age of 40 years (min-max: 26–62). Mean weight was 72 kg (min–max: 43–88) and baseline LT4 dosage ranged from 2.5 to 5.3 µg/kg/day. The most common causes of hypothyroidism were postsurgical in 50% ( n  = 5) and autoimmune in 20% ( n  = 2). During LT4AT, normal LT4 absorption was found in all but one individual (mean FT4 increase of 231%, min–max: 85–668). The only patient with objective LT4 absorption impairment (maximal increase of 48% by hour 5) presented also Helicobacter pylori gastritis and prior history of ‘intestinal surgery’ during childhood. No adverse events were reported during any of the LT4ATs. During follow-up (median 11.5 months (IQR 23)), three patients obtained euthyroidism and six had improved their hypothyroidism state.

          Conclusions

          The LT4AT is an effective and safe way to assess refractory hypothyroidism and provides valuable information to distinguish LT4 malabsorption from ‘pseudomalabsorption’. Our data suggest that most patients with suspicious LT4 malabsorption perform normally during LT4AT. This test provides relevant information for better management of patients with refractory hypothyroidism.

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          Most cited references27

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          Prevalence of and factors associated with primary medication non‐adherence in chronic disease: A systematic review and meta‐analysis

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            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.
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              Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review.

              Levothyroxine (LT4) is a drug with a narrow therapeutic index, applied in small amounts (micrograms), which makes interactions in the absorption phase clinically significant. The main aim of this article was to review and present the latest information on factors that affect the gastrointestinal absorption of this drug.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                01 November 2022
                01 December 2022
                : 11
                : 12
                : e220355
                Affiliations
                [1 ]Division of Endocrinology , Diabetes and Metabolism. Department of Medicine, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal
                [2 ]Department of Clinical Pathology , Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar Porto, Portugal
                Author notes
                Correspondence should be addressed to S Santos Monteiro: u12698@ 123456chporto.min-saude.pt
                Author information
                http://orcid.org/0000-0003-2198-6668
                Article
                EC-22-0355
                10.1530/EC-22-0355
                9716372
                36318199
                5b306361-ae51-4836-bd32-0e192458c202
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 04 October 2022
                : 01 November 2022
                Categories
                Research

                levothyroxine absorption test,refractory hypothyroidism,thyroid-stimulating hormone,thyroxine

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