From the Guidelines
Treatment with levothyroxine is recommended for patients with subclinical hypothyroidism, particularly those aged 40 to 70 years, as it may reduce the risk of cardiac morbidity and mortality, as well as all-cause mortality, as shown in a study by Razvi and colleagues 1. Subclinical hypothyroidism is a condition where thyroid-stimulating hormone (TSH) levels are elevated, but thyroid hormone levels (T4 and T3) remain within normal range. The decision to treat subclinical hypothyroidism depends on various factors, including age, symptoms, and cardiovascular risk factors. Some key points to consider when treating subclinical hypothyroidism include:
- The use of levothyroxine, a synthetic form of T4, as the standard treatment
- Starting doses of 25-50 mcg daily for older adults or those with heart disease, and 50-75 mcg daily for younger patients
- Adjusting the dosage every 6-8 weeks based on TSH levels, with the goal of achieving a TSH within the reference range (usually 0.4-4.5 mIU/L)
- Morning administration on an empty stomach, 30-60 minutes before food or other medications, to ensure optimal absorption
- Regular monitoring, with TSH checks 6-8 weeks after any dose change and annually once stable The study by Razvi and colleagues 1 found that levothyroxine use in patients aged 40 to 70 years was associated with lower risk for fatal or nonfatal ischemic heart disease events, death due to circulatory diseases, and all-cause mortality. However, it is essential to note that this study had some limitations, including the potential for residual confounding and the lack of adjustment for medications that reduce cardiovascular risk. Despite these limitations, the study's findings suggest that treatment with levothyroxine may have benefits for patients with subclinical hypothyroidism, particularly in terms of reducing cardiovascular risk. Therefore, treatment with levothyroxine should be considered for patients with subclinical hypothyroidism, especially those in the 40 to 70 age group, as it may improve outcomes and reduce morbidity and mortality, as supported by the study by Razvi and colleagues 1.
From the FDA Drug Label
Maternal hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, gestational hypertension, pre‑eclampsia, stillbirth, and premature delivery. Untreated maternal hypothyroidism may have an adverse effect on fetal neurocognitive development
The question of subclinical hypothyroidism is not directly addressed in the provided drug label. The label discusses the risks associated with maternal hypothyroidism during pregnancy, but does not provide information on subclinical hypothyroidism specifically. 2
From the Research
Definition and Prevalence of Subclinical Hypothyroidism
- Subclinical hypothyroidism is defined as an elevated serum thyrotropin (TSH) level with normal levels of free thyroxine (FT4) 3.
- It affects up to 10% of the adult population, with the prevalence increasing with age 3.
- The condition is most often caused by autoimmune (Hashimoto) thyroiditis, but serum TSH levels also rise with age in people without thyroid disease 3.
Diagnosis and Treatment
- The diagnosis of subclinical hypothyroidism should be confirmed by repeat thyroid function tests ideally obtained at least 2 months later, as 62% of elevated TSH levels may revert to normal spontaneously 4.
- Treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L, and treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L 4, 5.
- Levothyroxine is the preferred therapy, with the goal of maintaining serum TSH levels within the normal range 6, 5.
- TSH goals are age-dependent, with a 97.5 percentile (upper limit of normal) of 3.6 mIU/L for patients under age 40, and 7.5 mIU/L for patients over age 80 4.
Cardiovascular Risks and Treatment
- Subclinical hypothyroidism may be associated with an increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease 3, 7.
- Treatment with levothyroxine may only provide benefit in certain subgroups, such as patients who are younger or at higher risk of cardiovascular disease 5, 7.
- Caution is necessary when treating elderly subjects with levothyroxine, as it may be associated with iatrogenic thyrotoxicosis 4, 3.
Symptoms and Quality of Life
- Patients with subclinical hypothyroidism may have subtle hypothyroid symptoms, such as fatigue, and mild abnormalities of serum lipoproteins and cardiac function 6, 3.
- Treatment with levothyroxine may not improve symptoms related to vitality, weight, and quality of life in subclinical disease, and other causes should be explored 5.
- Combined treatment with levothyroxine and liothyronine may be preferred in some hypothyroid patients who are dissatisfied with treatment, especially those with a polymorphism in type 2 deiodinase 4.