Discussion
Refractory hypothyroidism, a condition where the thyroid gland does not respond adequately to treatment, can arise from a multitude of factors. Non-pathological reasons include patient non-compliance, often due to poor adherence to medication schedules, leading to reduced treatment absorption
. Certain medications, such as proton-pump inhibitors (PPI), histamine receptor blockers, and cholestyramine, along with conditions like irritable bowel syndrome, lactose intolerance, and gastroesophageal reflux disease, can interfere with gastrointestinal absorption. Pregnancy also necessitates specific adjustments in medication dosage across different trimesters. Pathologically, gastrointestinal disorders like inflammatory bowel disease, H. pylori infection, and the effects of gastric bypass surgery can contribute to the condition. Furthermore, individual factors such as body mass, gender, and genetic variations specifically in deiodinase D2 can influence the effectiveness of levothyroxine therapy. It is essential to differentiate true malabsorption from pseudo-malabsorption, which is linked to poor treatment adherence. Idiopathic causes, where the reason remains unknown, account for 10-20% of cases. Understanding these diverse factors is crucial for the effective management of refractory hypothyroidism. (3)(4).
The management of refractory hypothyroidism requires a meticulous and structured approach. Confirming patient adherence to prescribed treatment and proper medication administration techniques is crucial. A thorough review of the patient’s medication history is essential to rule out drug interactions that may affect thyroxine levels. Subsequently, conducting tests to investigate potential thyroxine malabsorption is advised, which may include assessing gastrointestinal function and health. For women of childbearing age, a pregnancy test is imperative as pregnancy can alter thyroid hormone levels. Finally, a thyroxine absorption test should be performed to distinguish between pseudo-malabsorption where the issue is not actual malabsorption but perhaps non-compliance or interference, and true levothyroxine (LT4) malabsorption (4).
Treatment in cases of refractory hypothyroidism is achieved by different methods as proposed in different studies of soft gel and liquid LT4 showing potential in specific groups such as pediatric patients, bariatric surgery patients, patients on PPI, and patients unwilling to delay breakfast \RL (5). Parenteral administration is another suggested treatment. This includes subcutaneous (SQ), intramuscular (IM), and intravenous (IV) routes. Hays’ mathematical model \RL (6)(7) is used to figure out the doses, and the rates of absorption are twice as high with intramuscular and intravenous administration compared to SQ administration. Moreover, intramuscular administration was reported in multiple cases and favored due to the ability to safely adjust the dose once or twice weekly, which proved to be an acceptable alternative in cases of resistant hypothyroidism to achieve euthymic state in reported patients \RL (7)(8)(9).
Only a limited number of studies in the outpatient setting reported the IV administration of LT4. This was primarily due to its use in hospitalized patients and patients with myxedema. However, given that the IV dose is 75% of the enteral dose and can be administered weekly, it serves as a great substitute for the oral form as evidenced in our study to achieve an euthymic state. This method effectively addresses pseudo-malabsorption and overcomes the factors associated with levothyroxine malabsorption in the GI tract \RL (10)(11)(12)(13)