MON-443 - Refractory Hypothyroidism Due to Levothyroxine Malabsorption Despite Negative Workup-Case Report and Literature Review .

Background: Refractory hypothyroidism, defined as persistently elevated thyroid-stimulating hormone (TSH) despite adequate oral levothyroxine (LT4) therapy, is uncommon and is most often associated with nonadherence, drug interactions, or gastrointestinal disorders. True LT4 malabsorption is rare and represents a diagnosis of exclusion after ruling out pseudomalabsorption and identifiable gastrointestinal disease, frequently requiring confirmation by supervised absorption testing. To date, only a few cases have been reported in the Gulf region, including one case from Saudi Arabia attributed to diabetic gastroparesis. Cases occurring despite a normal gastrointestinal evaluation have not previously been described in the region.

Case: A 34-year-old woman with primary hypothyroidism presented with persistent fatigue, cognitive slowing, weight gain, cold intolerance, and menstrual irregularities despite escalating doses of oral LT4, multiple formulations, and a trial of liothyronine. Laboratory testing revealed a TSH of 229 mU/L with markedly low free T4 and T3. Comprehensive gastrointestinal evaluation, including celiac serology, upper endoscopy, and duodenal biopsies, was normal. A supervised six-hour LT4 absorption test demonstrated no rise in free T4. Intravenous LT4 resulted in rapid biochemical normalization, confirming true malabsorption.
Management: The patient was transitioned to parenteral LT4 with significant clinical and biochemical improvement. The limited local availability of alternative oral formulations posed additional challenges in the long-term management of confirmed malabsorption.

Discussion: This case represents, to our knowledge, the first report from Saudi Arabia of LT4 malabsorption occurring despite a normal gastrointestinal evaluation. Unlike the only previously documented regional case, which was secondary to diabetic gastroparesis, this patient exhibited complete failure of LT4 absorption without identifiable structural or serologic abnormalities. This underscores the importance of supervised LT4 absorption testing in distinguishing true malabsorption from pseudomalabsorption and highlights the need to consider rare physiologic absorption defects in patients with persistent biochemical hypothyroidism despite escalating oral therapy.

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