JAMA: The Journal of the American Medical Association: July, 2019

Subclinical hypothyroidism, defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) affects up to 10% of the adult population.

Subclinical hypothyroidism may be categorized as grade 1 when thyrotropin levels are between the upper limit of the reference range and 9.9 mU/L and as grade 2 if serum thyrotropin levels are 10mU/L or higher.

TAKE HOME MESSAGE

This article provides a current review of the controversies related to the clinical significance, diagnosis, and therapeutic considerations related to subclinical hypothyroidism.

Subclinical hypothyroidism is most often caused by autoimmune (Hashimoto) thyroiditis. However, serum thyrotropin levels rise as people without thyroid disease age; serum thyrotropin concentrations may surpass the upper limit of the traditional reference range of 4 to 5 mU/L among elderly patients.

Approximately 90% of patients with subclinical hypothyroidism have serum thyrotropin levels lower than 10mU/L.

In patients who have circulating thyroid peroxidase antibodies, there is a greater risk of progression from subclinical to overt hypothyroidism.

Subclinical hypothyroidism may be associated with an increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease. In addition, middle-aged patients with subclinical hypothyroidism may have cognitive impairment, nonspecific symptoms such as fatigue, and altered mood.

Treatment Rationale

Treatment might be indicated for patients with subclinical hypothyroidism and serum thyrotropin levels of 10 mU/L or higher or for young and middle-aged individuals with subclinical hypothyroidism and symptoms consistent with mild hypothyroidism.

Normalization of serum thyrotropin is the goal of therapy in patients who are treated for subclinical hypothyroidism.

Levothyroxine is the treatment of choice. Because the degree of thyroid dysfunction is mild, small (eg, 25-75 μg) doses of levothyroxine are adequate to restore normal serum thyrotropin levels in the majority of nonpregnant patients.

Serum thyrotropin levels should be assessed 6 weeks after initiating the medication, and at 6-week intervals after subsequent changes in the medication dose.

Once the thyrotropin target has been achieved, annual thyroid function tests are recommended to document that serum thyrotropin is still within the target range.

Conclusions and Relevance 

Subclinical hypothyroidism is common and most individuals can be observed without treatment.

Possible indications for treating subclinical hypothyroidism include improvement in symptoms, prevention of overt hypothyroidism, and prevention of adverse events.

These potential benefits of thyroid hormone supplementation should be weighed against the risks of reducing thyrotropin values below the reference range and causing iatrogenic subclinical or overt hyperthyroidism.

In the absence of large randomized trials showing benefit from levothyroxine therapy, the rationale for treatment is based on the potential for decreasing the risk of adverse cardiovascular events and the possibility of preventing progression to overt hypothyroidism.

However, levothyroxine therapy may be associated with iatrogenic thyrotoxicosis, especially in elderly patients, and there is no evidence that it is beneficial in persons aged 65 years or older.