Aim for Normal TSH Range in Hypothyroidism Treatment

3d render of TSH test blood tubes lying on clipboard over white background
Physicians warn against alternative levothyroxine formulations to achieve high or low TSH levels.

Recent evidence suggests the implementation of a levothyroxine-guided policy in the United States and Europe aimed at normalizing serum thyroid-stimulating hormone (TSH) could reduce the risk of mortality in 28.3 million patients with hypothyroidism, according to a paper published in the European Journal of Endocrinology.

Guidelines from the American Thyroid Association recommend the normalization of serum TSH in patients with hypothyroidism. Recommendations state that clinicians should aim for a serum TSH less than the upper limit of normal, given the evidence suggesting an increased risk of cardiovascular events and mortality in the presence of increased TSH.

Recent studies suggest that overtreatment with levothyroxine, which results in extremely low or suppressed TSH, can increase the risk of mortality. Conversely, high TSH levels as a result of under treatment may also increase mortality risk in patients with hypothyroidism. Normalization of TSH levels with levothyroxine, however, is not associated with any evidence of negative long-term outcomes in these patients.

In spite of this evidence, resources on the Internet from a minority of patient groups and purported “experts” continue to promote unproven methods of diagnosis and treatment based only on patient testimonies.

Population surveys have demonstrated the relatively high prevalence of low and high serum TSH levels among levothyroxine-treated patients with hypothyroidism. According to the authors of the European Journal of Endocrinology article, approximately 16.5 million patients in the United States and 37 million patients in Europe have hypothyroidism. Among these, approximately 53% have a serum TSH outside the normal range at any given time.

This suggests that up to 8.7 million hypothyroid patients in the United States and 19.6 million people in Europe are at risk of premature death resulting from under- or overtreatment. The authors wrote that “the societal burden of this is considerable and it takes a mere change in dosage of one of the cheapest medications known to mankind to reverse it.”

“A first step in the right direction is for dissemination of this message to all those who are involved in the care of patients with hypothyroidism: endocrinologists, internists, primary care physicians and above all hypothyroid patients themselves,” wrote the authors who were led by Petros Perros, MBBS, MD, of the University of Newcastle upon Tyne in England. “Professional and patient-led organizations have a responsibility to work towards changing perceptions and optimizing the treatment of hypothyroidism. For those patients who have a normal serum TSH, this message will be reassuring. For those who are outside the normal range, one hopes it will provide an incentive to normalize their serum TSH.”


Perros P, Nirantharakumar K, Hegedüs L. Recent evidence sets therapeutic targets for levothyroxine-treated patients with primary hypothyroidism based on risk of death. Eur J Endocrinol. 2021;184(2):C1-C3. doi:10.1530/EJE-20-1229