When to treat hypothyroidism (underactive thyroid gland)?

From the Guidelines

Hypothyroidism should be treated when a patient has elevated thyroid stimulating hormone (TSH) levels with low thyroid hormone (T4) levels, or when TSH is persistently above 10 mIU/L even with normal T4 levels, as indicated by the most recent guidelines 1.

Key Considerations

• The management of hypothyroidism is guided by the severity of symptoms and the level of TSH elevation.
• For patients with TSH levels between 4.5 and 10 mIU/L, treatment is not routinely recommended unless symptoms are present or there is a high risk of progression to overt hypothyroidism 1.
• Treatment typically involves levothyroxine (synthetic T4), with the goal of normalizing TSH levels and relieving symptoms.

Treatment Approach

• The initial dose of levothyroxine is typically 1.6 mcg/kg/day for most adults, though elderly patients or those with heart disease may start at lower doses (25-50 mcg/day) 1.
• Dosage adjustments are made based on TSH levels checked every 6-8 weeks until stabilized, then annually.
• The medication should be taken on an empty stomach, 30-60 minutes before breakfast or 3-4 hours after the last meal of the day, avoiding calcium, iron supplements, and certain foods that can interfere with absorption.

Special Considerations

• For patients with severe symptoms or life-threatening consequences, such as myxedema coma, hospital admission and urgent treatment with levothyroxine and supportive care are necessary 1.
• In patients with uncertainty about whether primary or central hypothyroidism is present, hydrocortisone should be given before thyroid hormone is initiated 1.

From the FDA Drug Label

Pediatric Patients at Risk for Hyperactivity To minimize the risk of hyperactivity, start at one-fourth the recommended full replacement dosage, and increase on a weekly basis by one-fourth the full recommended replacement dosage until the full recommended replacement dosage is reached Hypothyroidism in Pregnant Patients For pregnant patients with pre-existing hypothyroidism, measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In pregnant patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range The general aim of therapy is to normalize the serum TSH level Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of levothyroxine sodium therapy and/or of the serum TSH to decrease below 20 IU per litre within 4 weeks may indicate the patient is not receiving adequate therapy

Treatment of Hypothyroidism should be initiated when:

• Serum TSH levels are above the normal range in adults and pediatric patients
• Serum TSH levels are above the trimester-specific reference range in pregnant patients
• Clinical and laboratory evidence of hypothyroidism is present, such as low serum T4 levels
• Key considerations for treatment include:
  • Starting with a low dose and gradually increasing as needed
  • Monitoring serum TSH and free-T4 levels regularly to assess adequacy of therapy
  • Adjusting dosage based on laboratory results and clinical evaluation
  • Maintaining serum TSH levels within the normal range, or trimester-specific reference range in pregnant patients 2

From the Research

Treatment of Hypothyroidism

• The diagnosis of hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH) concentration 3.
• Treatment of patients with subclinical hypothyroidism is still a controversial topic, and initiation of levothyroxine (T4) therapy depends on the level of TSH elevation and other factors such as patient age, presence of pregnancy or comorbidities 3.
• The standard of care for treatment of hypothyroidism is T4 monotherapy, with the biochemical treatment goal being a TSH level within the reference range (0.4-4.0 mU/l) 3.

Levothyroxine Monotherapy vs. Combination Therapy

• Some studies suggest that combination therapy with levothyroxine (LT4) and liothyronine (LT3) may be considered for patients who remain symptomatic on LT4 therapy 4.
• However, other studies have found that LT4 monotherapy is sufficient for most patients, and that the addition of LT3 does not provide significant benefits 5.
• A double-blind, randomized, controlled trial found that patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy 6.

Treatment Outcomes

• A feasibility double-blind trial found that LT4/LT3 combination therapy appeared to prevent changes in weight and cholesterol associated with LT4 replacement alone in patients with post-surgical hypothyroidism 7.
• The trial also found non-significant improvements in quality of life measures in both the LT4/placebo and LT4/LT3 groups, as well as increases in energy expenditure and diastolic function in the LT4/LT3 group 7.
• The study suggests that LT4/LT3 combination therapy may be a viable treatment option for patients with hypothyroidism, particularly those who have undergone thyroidectomy 7.