Subclinical hypothyroidism: When to treat

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Adverse effects of subclinical hypothyroidism and the role for levothyroxine
Subclinical hypothyroidism has been associated with adverse metabolic, cardiovascular, neuromuscular, and cognitive effects and has been shown to have a detrimental impact on quality of life. However, studies of levothyroxine therapy in subclinical hypothyroidism have yielded mixed results.16 Subclinical hypothyroidism affects many biologic systems, and levothyroxine may have a role (Table 2).32–117


The management of subclinical hypothyroidism should be individualized on the basis of extent of thyroid dysfunction, comorbid conditions, risk factors, and patient preference.118 Shared decision-making is key, weighing the risks and benefits of levothyroxine treatment and the patient’s goals.

Factors favoring levothyroxine therapy in subclinical hypothyroidism
There is some evidence to support levothyroxine treatment in nonpregnant patients with overt hypothyroidism (TSH > 10 mIU/L) or in patients with TSH 5 to 10 mIU/L with symptoms or hyperlipidemia and in younger patients at risk of cardiovascular disease.118 Table 3 describes various patient factors that should be considered during clinical evaluation and decisions about levothyroxine treatment in subclinical hypothyroidism.

The risks of treatment should be kept in mind and explained to the patient. Levothyroxine has a narrow therapeutic range, causing a possibility of overreplacement, and a half-life of 7 days that can cause dosing errors to have longer effect.118,119

Adherence can be a challenge. The drug needs to be taken on an empty stomach because foods and supplements interfere with its absorption.118,120 In addition, the cost of medication, frequent biochemical monitoring, and possible need for titration can add to financial burden.

When choosing the dose, one should consider the degree of hypothyroidism or TSH elevation and the patient’s weight, and adjust the dose gently.

If the TSH is high-normal

It is proposed that a TSH range of 3 to 5 mIU/L overlaps with normal thyroid function in a great segment of the population, and at this level it is probably not associated with clinically significant consequences. For these reasons, levothyroxine therapy is not thought to be beneficial for those with TSH in this range.

Pollock et al121 found that, in patients with symptoms suggesting hypothyroidism and TSH values in the upper end of the normal range, there was no improvement in cognitive function or psychological well-being after 12 weeks of levothyroxine therapy.

However, due to the concern for possible adverse maternal and fetal outcomes and low IQ in children of pregnant patients with subclinical hypothyroidism, levothyroxine therapy is advised in those who are pregnant or planning pregnancy who have TSH levels higher than 2.5 mIU/L, especially if they have thyroid peroxidase antibody. Levothyroxine therapy is not recommended for pregnant patients with negative thyroid peroxidase antibody and TSH within the pregnancy-specific range or less than 4 mIU/L if the reference ranges are unavailable.

Keep in mind that, even at these TSH values, there is risk of progression to overt hypothyroidism, especially in the presence of thyroid peroxidase antibody, so patients in this group should be monitored closely.

If TSH is mildly elevated

The evidence to support levothyroxine therapy in patients with subclinical hypothyroidism with TSH levels less than 10 mIU/L remains inconclusive, and the decision to treat should be based on clinical judgment.2 The studies that have looked at the benefit of treating subclinical hypothyroidism in terms of cardiac, neuromuscular, cognitive, and neuropsychiatric outcomes have included patients with a wide range of TSH levels, and some of these studies were not stratified on the basis of degree of TSH elevation.

The risk that subclinical hypothyroidism will progress to overt hypothyroidism in patients with TSH higher than 8 mIU/L is high, and in 70% of these patients, the TSH level rises to more than 10 mIU/L within 4 years. Early treatment should be considered if the TSH is higher than 7 or 8 mIU/L.

If TSH is higher than 10 mIU/L

Treatment algorithm for subclinical hypothyroidism in nonpregnant patients.

Figure 2. Treatment algorithm for subclinical hypothyroidism in nonpregnant patients.

The strongest evidence in favor of treating subclinical hypothyroidism is in patients with TSH levels higher than 10 mIU/L.2 Thyroid dysfunction with this degree of TSH elevation has been associated with adverse cardiometabolic, neuromuscular, cognitive, and psychiatric effects as described above, and has been shown to improve with levothyroxine therapy.

Figure 2 outlines an algorithmic approach to subclinical hypothyroidism in nonpregnant patients as suggested by Peeters.122

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There is more to the TSH than a number

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