Related Experiment Video
Updated: Dec 22, 2025
Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Levothyroxine prescribing and laboratory test use after a minor change in reference range for thyroid-stimulating
Christopher Symonds1, Gregory Kline1, Inelda Gjata1
1Department of Medicine/Endocrinology (Symonds, Kline), Physician Learning Program (Gjata), Department of Clinical Neurosciences (Cooke) and Department of Pathology and Laboratory Medicine (Naugler), Cumming School of Medicine, University of Calgary; Health Services Statistical & Analytic Methods (Rose) and Alberta Precision Laboratories (Guo), Alberta Health Services, Calgary, Alta.
Background:
Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory.
Methods:
Using provincial administrative data, we compared predicted volumes of TSH tests with actual TSH test volumes before and after a planned change in the TSH reference range. We also determined the number of new levothyroxine prescriptions for previously untreated patients and the rate of changes to the prescribed dose for those on previously stable, long-term levothyroxine therapy before and after the change in the TSH reference range.
Results:
Before the change in the TSH reference range, actual and predicted monthly volumes of TSH testing followed an identical course. After the change, actual test volumes exceeded predicted test volumes by 7.3% (95% confidence interval [CI] 5.3%-9.3%) or about 3000 to 5000 extra tests per month. The proportion of patients with newly "abnormal" TSH results almost tripled, from 3.3% (95% CI 3.2%-3.4%) to 9.1% (95% CI 9.0%-9.2%). The rate of new levothyroxine prescriptions increased from 3.24 (95% CI 3.15-3.33) per 1000 population in 2013 to 4.06 (95% CI 3.96-4.15) per 1000 population in 2014. Among patients with preexisting stable levothyroxine therapy, there was a significant increase in the number of dose escalations (p < 0.001) and a total increase of 500 new prescriptions per month.
Interpretation:
Our findings suggest that clinicians may have responded to mildly elevated TSH results with new or increased levothyroxine prescriptions and more TSH testing. Knowledge translation efforts may be useful to accompany minor changes in reference ranges.
Related Concept Videos
01:20Synthesis 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...
01:18Functions 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...
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
01:29Therapeutic Drug Monitoring: Affecting Factors
01:23The Thyroid Gland
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...
01:16Therapeutic Drug Monitoring: Overview and Classification