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

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 to 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 72kg (min-max: 43-88) and baseline LT4 dosage ranged from 2.5 to 5.3µg/kg per day. Most common cause 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)], 3 patients obtained euthyroidism and 6 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.

Levothyroxine liquid oral substitution as an alternative treatment for refractory hypothyroidism due to gastrointestinal malabsorption: A case report

“…Questioning should screen the concomitant use of other drugs that affect LT4 absorption and bioavailability, particularly proton-pump inhibitors, calcium carbonate, iron salts, and laxatives. 3,11 LT4 absorption can also be compromised by several gastrointestinal diseases, including celiac disease, atrophic gastritis, H. pylori infection, gastroparesis, inflammatory bowel disease, short bowel syndrome, and lactose intolerance. 3,4 Identification and adequate treatment of these conditions generally lead to TSH level normalization.…”

“…Questioning should screen the concomitant use of other drugs that affect LT4 absorption and bioavailability, particularly proton-pump inhibitors, calcium carbonate, iron salts, and laxatives. 3,11…”

“…7 Orally administrated LT4 is absorbed through the small intestine mucosa with an absorption rate ranging from 60% to 82% during the first 3 h after ingestion. 3,8 However, oral substitution fails to achieve euthyroidism in some patients despite escalating dosages of LT4 beyond 1.9 μg/kg/day. This situation is not uncommon in clinical practice.…”

“…3,4 Therapeutic failure can be due to poor adherence to treatment or impaired LT4 absorption because of drug interactions or gastrointestinal diseases such as atrophic gastritis, Helicobacter pylori gastritis, celiac disease, inflammatory diseases, and lactose intolerance. [3][4][5][6] In such conditions, the management of hypothyroidism is challenging.…”

“…Most patients require approximately 1.6-1.8 µg/kg/day. 3 The treatment target is to reverse the clinical signs of hypothyroidism and to normalize TSH levels. In most cases, appropriate doses of LT4 restore euthyroidism.…”