Related Experiment Video
Updated: Feb 26, 2026

Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets
Salvatore Benvenga1,2,3, Giampaolo Papi4, Alessandro Antonelli5
1Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Rome, Italy.
Context:
A not negligible part of hypothyroid patients on levothyroxine therapy do not normalize serum thyrotropin (TSH) concentrations. "Refractory hypothyroidism," i.e., a condition characterized by persistently abnormal serum TSH levels despite adequate titration of l-T4 substitution therapy, requires biochemical and instrumental investigation, but no definite etiology is found in up to 15% of cases.
Objective:
To report patients presenting with refractory hypothyroidism with proven improper storage of levothyroxine tablets.
Design:
Patients on l-T4 substitution therapy referred to three Italian outpatient Clinics of Endocrinology between January 2013 and December 2015 for refractory hypothyroidism were investigated for levothyroxine tablet exposure to humidity, light, and high temperature.
Results:
We report eight patients, accounting for approximately 1% of all hypothyroid patients and 5% of those with refractory hypothyroidism in our series. Careful anamnesis disclosed that these patients stored levothyroxine tablets inappropriately. Normalization of serum TSH concentrations was obtained in all cases by simply recommending to store the new levothyroxine tablets away from heat, light, and humidity.
Conclusion:
Refractory hypothyroidism linked to improper storage of l-T4 tablets does exist and might be an underrecognized entity. In addition to proper modalities of ingestion of l-T4 tablets, patients need to be instructed on proper modalities of storage, as well.
Related Concept Videos
Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Desensitization and Tachyphylaxis
Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
Long-term Depression
Long-term Depression
Calcium Ion Concentration Mechanism
If over...
Drug Distribution: Tissue Binding
For...

