Ms. Sarah Chen, aged 45, is adherent to her levothyroxine 100 mcg daily for hypothyroidism. She reports to your pharmacy complaining of persistent fatigue, despite reporting good adherence. She recently started taking a calcium supplement 500 mg twice daily, approximately 1 hour before her levothyroxine, because she was concerned about her bone health. What is the most likely explanation for Ms. Chen's persistent fatigue?

Question: Ms. Sarah Chen, aged 45, is adherent to her levothyroxine 100 mcg daily for hypothyroidism. She reports to your pharmacy complaining of persistent fatigue, despite reporting good adherence. She recently started taking a calcium supplement 500 mg twice daily, approximately 1 hour before her levothyroxine, because she was concerned about her bone health. What is the most likely explanation for Ms. Chen's persistent fatigue?

Answer options:

• The calcium supplement is increasing the metabolism of levothyroxine, leading to lower thyroid hormone levels. ✅ The calcium supplement is interfering with levothyroxine absorption, leading to uncorrected hypothyroidism.
• Ms. Chen is experiencing new onset depression, presenting as fatigue.
• The calcium supplement is causing constipation, which manifests as fatigue.

Correct answer: The calcium supplement is interfering with levothyroxine absorption, leading to uncorrected hypothyroidism.

Explanation: Calcium supplements, along with other polyvalent cations (e.g., iron, aluminum, magnesium), can chelate levothyroxine in the gastrointestinal tract, forming insoluble complexes that reduce its absorption. This leads to lower levothyroxine levels and persistent hypothyroid symptoms like fatigue. Patients should separate levothyroxine and calcium intake by at least 4 hours.