Cystic Fibrosis as a Cause of Malabsorption and Increased Requirement of Levothyroxine

Abstract

Cystic fibrosis (CF), a monogenic disease from mutations in the CFTR gene, causes pancreatic and biliary insufficiency with impaired absorption of nutrients and drugs. Unlike other malabsorption disorders, no data are available in literature on levothyroxine (L-T4) absorption in these patients. Herein we report L-T4 malabsorption and increased requirement in two hypothyroid patients with CF. Both patients (patient #1, a 44-years-old female; patient #2, a 39-years-old male), affected by post-surgical hypothyroidism, were unable to reach adequate TSH levels despite a daily L-T4 dosage largely exceeding their weight-estimated values, even after multiple increases. They did not take medications altering L-T4 absorption or metabolism. In both patients an L-T4 absorption test was performed, under clinical control. Serum concentrations of TSH, total (T4) and free-thyroxine (FT4) were measured before ingestion of L-T4, then every hour for 4 h and 24 h later. Area under the curve (AUC) for T4 and FT4 was calculated. After L-T4 load, T4 and FT4 values remained below the lower reference range limit in patient #1; a slight increase towards normal levels, but under a 2.5-fold cut-off was observed in patient #2, thus confirming a true malabsorption in both subjects. The AUC were similar in the two tests. Both patients were then shifted towards liquid L-T4 formulation, reaching stable target TSH ranges. CF should be included among the digestive diseases causing L-T4 malabsorption, likely due to the combination of pancreatic insufficiency, chronic intestinal inflammation and reduced biliary salts production. L-T4 oral liquid formulation allows to overcome the reduced absorption of L-T4 in these patients, in which L-T4 absorption test can confirm a real malabsorption, leading to more tailored choices for hypothyroidism management.