Efficacy and Safety of Once-Weekly Thyroxine for Thyroxine-Resistant Hypothyroidism

Chellama Jayakumari; Abilash Nair; Jabbar Puthiyaveettil Khadar; Darvin V. Das; Nandini Prasad; S.J. Jessy; Anjana Gopi; Padmanabhan Guruprasad


J Endo Soc. 2019;3(12):2184-2193. 

In This Article

Abstract and Introduction


Context: Noncompliance with thyroxine therapy is the most common cause of poor control of hypothyroidism. An open-label prospective study to compare once-weekly thyroxine (OWT) with standard daily thyroxine (SDT) was undertaken.

Design: Patients taking thyroxine doses of >3 μg/kg/d, with or without normalization of TSH, were included and administered directly observed OWT or nonobserved SDT according to patient preference based on their weight for 6 weeks. Furthermore, patients on OWT were advised to continue the same at home without supervision.

Results: Twenty six of 34 patients on OWT and 7 of 18 patients on SDT achieved a TSH <10 μIU/mL (P < 0.05), and 2 patients from the SDT arm were lost to follow-up. During home treatment, 15 of 25 at 12 weeks and 19 of 23 contactable patients at a median follow-up of 25 months maintained TSH below target. Thyroxine absorption test was unable to predict normalization of TSH at 6 weeks of OWT therapy. No adverse events were seen with OWT-treated patients over the 12-week follow-up period. OWT has significantly higher efficacy (OR = 5.1) than SDT for patients with thyroxine-resistant hypothyroidism and is not associated with side effects.

Conclusion: OWT benefits a majority of patients in the long-term treatment of thyroxine-resistant hypothyroidism, in the real-world setting.


The most common reason for poor control of hypothyroidism is noncompliance to thyroxine, attributed to the inconvenience of taking the medication in a fasting state, waiting for 60 minutes for the next meal or beverage, and avoiding other medications that may interfere with absorption of thyroxine.[1] Directly observed treatment for 5 to 6 weeks is one method to ensure compliance and rule out malabsorption as the cause of poor control of hypothyroidism.[2] Once-weekly thyroxine (OWT) with doses <3 mg/d have been shown to be a safe treatment alternative to standard daily thyroxine (SDT) therapy for treating hypothyroid patients.[3–7] OWT has been recommended by the American Thyroid Association for older adults and patients dependent on caregivers for thyroxine therapy.[8] Still, there are few data regarding performance of OWT for patients who are not able to maintain normal TSH levels with daily therapy. Moreover, very few studies have evaluated the long-term treatment with OWT outside an institution. The current study intended to evaluate the effectiveness of OWT for patients with thyroxine-resistant hypothyroidism and its outcome for patients taking it over the long term at home.