More than 90% of hypothyroidism cases are caused by primary hypothyroidism. Because this illness is chronic, the majority of these patients will require levothyroxine therapy for the rest of their lives. Adherence to levothyroxine, on the other hand, gradually decreases over time. Early detection and proper counseling, as well as modifying the regimen as needed, are required to reverse the potential complications and prevent the life-threatening myxedema coma [
8].
In our case, the patient had hypothyroidism for 20 years and was treated with levothyroxine. She was referred to the endocrine department due to her persistently elevated TSH despite taking levothyroxine on a daily basis. By responding to the following questions, the common causes of TSH elevation even after daily levothyroxine administration can be addressed. Firstly, the biggest challenge is to ensure adherence to levothyroxine medication, as in a majority of cases noncompliance to medication is the main reason behind failure to achieve euthyroid status [
8]. Second, it is prudent to inquire about any over-the-counter medications that the patient may be taking concurrently and that may have interfered with levothyroxine absorption [
2]. Notably these medications are multivitamins, iron and calcium supplements, rifampin, anti-epileptics, proton pump inhibitors, cholestyramine, imatanib, and sucralfate [
8]. Third, thyroxine should be taken on an empty stomach for maximum absorption, and no other medication or food should be taken for at least 30–60 minutes after levothyroxine ingestion [
2]. Fourth, investigations regarding malabsorption should be done to exclude any chance of levothyroxine malabsorption from gastrointestinal tract because levothyroxine is usually absorbed from small intestine especially jejunum and ileum. In this context, a levothyroxine absorption test can be performed to distinguish between those who have true malabsorption and those who have raised TSH due to medication nonadherence or pseudo-malabsorption. Because there is no gold standard method for the LT4 absorption test, different protocols have been advocated in the literature. The majority of centers use 4- and 6-hour sampling to determine the trend of total T4 and FT4. Some have also tested for rapid inhibition of TSH. When all published pseudo-malabsorption cases are considered, it has been stated that at least two to three times increase in the basal FT4 levels may exclude malabsorption [
9]. Similarly, in certain medical conditions like nephrotic syndrome, large amounts of albumin are excreted, which may increase levothyroxine requirements due to binding of T4 to the excreted albumin. This creates a milieu of protein malnourishment that may be difficult to differentiate from malabsorption syndromes [
10]. Finally, potential side effects of giving higher doses of thyroxine should be kept in mind, such as once-weekly dose, especially in the elderly and those with prior ischemic heart disease, as they may develop or precipitate tachyarrhythmia; therefore, DOTS therapy should not be used in this group of patients.
Our patient already had two autoimmune conditions; therefore, it was critical to consider celiac disease as one of the possible autoimmune absorptive diseases causing impaired levothyroxine absorption. Despite the fact that the celiac serology was negative, the question arose as to whether we should still refer the patient for a duodenal biopsy. We deferred this step because the history and laboratory workup revealed no significant malabsorption and our patient’s TSH remained in the normal range on follow-up.