Levothyroxine Requirement in a Patient with LRBA Deficiency and GVHD Induced Cholestasis

TL;DR

A child with LRBA deficiency and GVHD-induced cholestasis required higher levothyroxine doses due to impaired absorption.

Contribution

This case highlights the need for adjusted levothyroxine dosing in patients with GVHD-related cholestasis.

Findings

The patient showed severe hypothyroidism despite standard levothyroxine therapy.

Cholestasis from chronic GVHD was identified as the cause of poor thyroxine absorption.

Dosage adjustments were necessary to manage thyroid function in this complex case.

Abstract

Levothyroxine is a lipophilic hormone that is absorbed in the small intestine, mainly in the jejunum and ileum. The absorption of levothyroxine after oral administration averages 60–80%. We report a 7-year-old male patient who presented to a tertiary care hospital in Muscat, Oman, in 2020 at the age of three years with an early diagnosis of lipopolysaccharide beige-like anchor protein (LRBA) deficiency. LRBA deficiency is characterised by recurrent infections, autoimmune thyroid disease and autoimmune cytopenia. The patient was prescribed levothyroxine treatment (112.5 mcg daily) and underwent haematopoietic stem cell transplantation (HSCT) in March 2023; four months post-HSCT, he developed appendicitis followed by jaundice and elevation of liver enzymes. His physical examination revealed a distended abdomen with enlarged liver and spleen. Graft-versus-host disease (GVHD) was diagnosed and confirmed by a liver biopsy and treatment for GVHD was initiated. Despite ongoing levothyroxine therapy, he exhibited biochemically severe hypothyroidism with very low free-throxine and high thyroid-stimulating hormone, prompting a dosage increment. Investigations to determine the cause of his severe hypothyroidism were unremarkable, ultimately attributing the need for increased thyroxine to cholestasis induced by chronic GVHD. This case emphasises the complexities of managing thyroid function in patients with hepatic GVHD, highlighting the necessity for frequent monitoring and levothyroxine dosage adjustments.

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