Pseudomalabsorption of Levothyroxine: A Challenge for the Endocrinologist in the Treatment of Hypothyroidism

Abstract

Background: Hypothyroidism due to non-compliance with levothyroxine therapy (pseudomalabsorption) is rare. The diagnosis is considered in patients with persistent severe hypothyroidism despite treatment with large doses of levothyroxine. Intestinal malabsorption, drug and dietary interference with levothyroxine absorption and nephrotic syndrome should be excluded. The diagnosis of pseudomalabsorption can be demonstrated by using “an oral 1,000 µg of levothyroxine test” showing a rapid decrease in thyroid-stimulating hormone and increase in thyroxine. There are however few data on the sensitivity and specificity of the test in large cohorts of hypothyroid patients. Treatment of pseudomalabsorption is controversial, with reports using parenteral, intramuscular or single weekly oral dosing of levothyroxine. Cases: We report 3 patients who presented with persistent clinical and biochemical signs of hypothyroidism despite replacement therapy with high doses of levothyroxine. Pseudomalabsorption was diagnosed by a systematic approach, including prior exclusion of digestive, liver and kidney diseases. A peroral challenge test was positive in all cases. Patients denied non-compliance, and a psychiatric approach was elusive. Two of the patients were treated successfully with a single supervised weekly 1,000-µg administration of levothyroxine, while non-supervised weekly administration resulted in hypothyroidism confirming pseudomalabsorption. Conclusions: Non-compliance with medical therapy should be considered in patients with treatment-refractory hypothyroidism. Supervised once weekly levothyroxine treatment is a safe and well-tolerated treatment option, obviating the need for parenteral administration of the drug. Apart from the medical treatment, there is also a need for psychiatric evaluation and care.

Efficacy and Safety of Once-Weekly Thyroxine for Thyroxine-Resistant Hypothyroidism

“…Earlier studies considered 2-hour rapid levothyroxine testing as a marker for normal absorption [4, 6, 17]. In the current study we found that the response to OWT treatment could not be predicted based on the T4 or fT4 rise by >50% 2 hours after administration of the first dose of OWT.…”

“…In this study, a weight-related dose was used in each case, in contrast to many earlier studies where fixed doses were used [2, 3, 9]. Previous studies report that serum levels of levothyroxine are at or near their peak 2 hours after administration of an oral dose [3–6, 9–14]. This study showed that although the total T4 levels peak at 2 hours, the fT4 level is at maximum 24 hours after thyroxine ingestion.…”

Gastrointestinal Malabsorption of Thyroxine

“…Initially the clinician might suspect a decreased T4 gastrointestinal absorption (24), and an evaluation for diseases causing malabsorption, or drug interaction should be performed. Some authors suggest that an oral T4 absorption test (by giving a total amount of 600 to 2,000µg of thyroxine ) could be used to demonstrate pseudomalabsorption (4,25,26). The tablet formulations of levothyroxine contains a stable salt, sodium T4, together with a variety of excipients (27).…”

Levothyroxine absorption test in the management of a patient with persistent hypothyroidism

“…The daily use of oral LT4 is the most frequent treatment of hypothyroidism and is one of the most effective, inexpensive and safe hormone replacements in endocrinology. Although in some patients hypothyroidism persists despite therapy with high doses of levothyroxine 4 . In patients with persistently elevated TSH levels, there are a number of causes, which needs to be considered, including poor administration and pathological malabsorption conditions.…”