Refractory hypothyroidism: Diagnostic evaluation and management strategies

The term refractory hypothyroidism is used to describe the condition in which patients require levothyroxine doses higher than expected for their age and weight (> 1.9-2.5μg/kg/day). Its prevalence is not well defined. Refractory hypothyroidism is not related to thyroid hormone resistance, while most common causes include non-compliance (also known as pseudo-malabsorption) and malabsorption. Malabsorption can be caused by food and/or medication interactions as well as digestive pathologies such as gastritis, coeliac disease, lactose intolerance, or a history of digestive surgery. Less commonly, refractory hypothyroidism is caused by increased thyroid hormone degradation due to elevated expression of type 3 deiodinase, typically related to hemangiomatous tumors or tyrosine kinase inhibitors treatment. Medical history and clinical examination will help to guide the diagnosis and etiological investigations. Screening for associated deficiencies and digestive auto immune diseases can direct the diagnosis towards a digestive pathology. A levothyroxine absorption test may be performed to confirm true malabsorption and avoid more invasive tests such as digestive endoscopies.