REFRACTORY HYPOTHYROIDISM POST-CHOLECYSTECTOMY SUCCESSFULLY TREATED WITH SOFTGEL CAPSULE THYROXINE

Abstract

INTRODUCTION
Refractory hypothyroidism has been increasingly identified globally and its management can be challenging. Primary hypothyroidism is considered refractory when there is persistent elevation of TSH despite escalating doses of levothyroxine >1.9 µg/kg/day. Physicians should rule out non-compliance and pursue further evaluation to identify aetiologies for increased dose requirements.

CASE
We present a case of a 44-year-old female with Hashimoto's thyroiditis well-replaced with levothyroxine 100 µg/ day (1.6 µg/kg/day). After cholecystectomy, her TSH was persistently high despite increasing levothyroxine to 500 µg/ day, good compliance and no concurrent drug interference. She developed progressive hypothyroid symptoms with elevated TSH levels >100 mIU/L. Thyroxine absorption test confirmed poor enteral absorption. Extensive evaluation failed to reveal any evidence of malabsorption where her esophagogastroduodenoscopy finding shows mild antral erosion. Further tests excluded H. pylori infection, coeliac disease and exocrine pancreatic insufficiency. She was hospitalized multiple times for severe symptomatic hypothyroidism and responded well with intravenous thyroxine. After extensive diagnostic measures, she was started on levothyroxine 300 µg/day in soft gel capsules. Her TSH and FT4 normalized following 8 weeks of treatment.

CONCLUSION
Various gastrointestinal disorders that lead to malabsorption or loss of intestinal secretions may result in higher requirements of levothyroxine. Our case highlights the malabsorption of oral levothyroxine in tablets after cholecystectomy. Hypothesized causes include intestinal malabsorption of levothyroxine due to reduction in bile salts after cholecystectomy and altered intestinal microbiota. An empirical switch to soft gel capsule formulation may resolve this treatment-refractory issue. This formulation has been shown to have the most consistent dissolution pattern, resulting in a more reliable bioavailability than the tablet form.