BACKGROUND
Hypothyroidism is a common condition in which the thyroid gland does not make enough thyroid hormone to meet the body’s needs. This is diagnosed by high levels of thyroid-stimulating hormone (TSH) and low levels of thyroxine (T4). Hypothyroidism can be due to numerous causes including destruction by antibodies (autoimmune thyroid disease), surgical removal, destruction after radioactive iodine therapy, inflammation (thyroiditis), pituitary disease, and medications. It is more common in women than men. Hypothyroidism is usually treated by starting thyroid hormone replacement therapy in the form of levothyroxine. Starting doses of levothyroxine are often calculated based on body weight. In patients with the most common types of hypothyroidism, therapy is guided by TSH levels with a typical goal to return the TSH level to the normal range.

If the treatment of hypothyroidism over-shoots and causes the TSH level to be low with high normal or increased T4, then the patient can be made hyperthyroid. This is called “iatrogenic hyperthyroidism,” meaning that it is caused but taking too much levothyroxine. Hyperthyroidism is associated with symptoms of thyroid overactivity (weight loss, heat intolerance, elevated heart rate, anxiety, tremor, insomnia) as well as bone loss and abnormal heart rhythms, especially atrial fibrillation. For these reasons, over-replacement of hypothyroidism with thyroid hormone should be avoided in most cases.

It has been reported that over-replacement with thyroid hormone occurs more frequently in women. This study sought to identify the potential factors that contribute to the increased risk of iatrogenic hyperthyroidism in women.

THE FULL ARTICLE TITLE
Adams, R and Mammen JS. Sex Differences in Risk for Iatrogenic Thyrotoxicosis Among Older Adults: An Analysis from Real-World Clinical Data. Thyroid. 2025;35(5):485-493; doi: 10.1089/thy.2024.0604. PMID: 40117123.

SUMMARY OF THE STUDY
The study looks at data from a review of the electronic medical record. The study included 20,734 patients with hypothyroidism over the age of 50 that received healthcare in the John Hopkins Health System between January 2014 and February 2024.

Patients had to have at least two visits and data available for a variety of different measures including gender, height, weight, levothyroxine dose, medications, and other medical conditions. Severity of hypothyroidism over-treatment was classified as moderate (TSH low – ≥0.1 and < lower normal limit or <0.45mIU/L) or severe (TSH suppressed – <0.1 mU/L) based on the degree of TSH suppression. Thyroid cancer patients were excluded from the analysis as sometimes TSH suppression is recommended to reduce risk of cancer recurrence.

Overall, 34% of patients had a low TSH with 14% having a suppressed TSH (severe). As expected, higher rates of TSH suppression were seen with higher doses of levothyroxine treatment. Women (36.7%) were more likely than men (23.9%) to have a suppressed TSH and these differences remained when controlling for several variables such as levothyroxine dose per actual body mass, demographics, use of the health care system and comorbidities. However, the gender differences in risk of iatrogenic hyperthyroidism went away when the levothyroxine dose was adjusted by lean body mass instead of body weight. When men and women were receiving comparable levothyroxine doses per lean body mass, there were no differences in risk of iatrogenic hyperthyroidism. This suggests that using body weight to calculate the required thyroid hormone dose in women may overestimate thyroid hormone needs. Using lean body mass to calculate thyroid hormone dose in women may lead to prescribing lower doses and result in fewer cases of iatrogenic hyperthyroidism.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Over-replacement of hypothyroidism with levothyroxine results in iatrogenic hyperthyroidism and should usually be avoided due to its association with multiple negative health consequences. Iatrogenic hyperthyroidism is more common in women compared to men. Using lean body mass, instead of actual body mass, to estimate thyroid hormone dose requirements may reduce the risk of iatrogenic hyperthyroidism in women.

— Whitney W. Woodmansee MD

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