From the FDA Drug Label
Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of levothyroxine sodium may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of levothyroxine sodium Instruct patients to take levothyroxine sodium tablets as a single dose, preferably on an empty stomach, one-half to one hour before breakfast with a full glass of water to avoid choking or gagging. Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine Instruct patients not to take levothyroxine sodium tablets within 4 hours of these agents.
To rule out thyroid hormone malabsorption in a patient taking levothyroxine and persistently elevated TSH, the following steps can be taken:
- Assess compliance: Verify that the patient is taking the medication as directed.
- Evaluate dose and administration: Check the dose of medication administered and the method of administration.
- Check for drug interactions: Identify any potential drug interactions that may be affecting levothyroxine absorption, such as iron and calcium supplements and antacids.
- Adjust administration: Instruct the patient to take levothyroxine on an empty stomach, one-half to one hour before breakfast, and avoid taking it within 4 hours of agents that can decrease absorption. 1 1
From the Research
To rule out thyroid hormone malabsorption in a patient taking levothyroxine with persistently elevated TSH, I recommend performing a supervised levothyroxine absorption test, as supported by the most recent study 2, which suggests that this test is a valuable tool to confirm the diagnosis of pseudomalabsorption.
Protocol for Supervised Levothyroxine Absorption Test
This involves administering a weight-based oral loading dose of levothyroxine (typically 600 mcg or 1000 mcg) to the fasting patient in the clinic, followed by serial measurements of serum free T4 and TSH at baseline, 2,4, and 6 hours after administration.
- Normal absorption is indicated by at least a 2.5-fold increase in free T4 levels from baseline, as suggested by 2.
- Before conducting this test, ensure the patient has been fasting for at least 8 hours and has not taken any medications known to interfere with levothyroxine absorption.
- Additionally, prior to the test, verify medication adherence through pill counts or pharmacy refill records, and rule out common causes of malabsorption such as celiac disease, H. pylori infection, and drug interactions (particularly with calcium, iron supplements, proton pump inhibitors, and antacids), as recommended by 3.
Importance of the Test
The test works because a significant rise in free T4 after a supervised dose indicates that the gastrointestinal tract can absorb the medication properly, suggesting that other factors like non-adherence or drug interactions may be responsible for the persistently elevated TSH, as noted in 4.
Considerations
It is also important to consider that some patients may have pseudomalabsorption, which is characterized by poor adherence, as discussed in 4, and that the LT4 loading test can help confirm this diagnosis.
- The study 5 also highlights the importance of considering drug interactions, such as those with calcium or iron supplements, which can affect levothyroxine absorption.
- However, the most recent and highest quality study 2 provides the strongest evidence for the supervised levothyroxine absorption test as the best approach to rule out thyroid hormone malabsorption.