What is the diagnosis and treatment for hypothyroidism (underactive thyroid)?

From the Guidelines

Hypothyroidism should be treated with oral T4 monotherapy (levothyroxine sodium) as the principal treatment, with the goal of improving morbidity, mortality, and quality of life. The diagnosis of hypothyroidism involves confirming or ruling out abnormal findings through multiple tests over a 3- to 6-month interval, and follow-up testing of serum T4 levels in persons with persistently abnormal TSH levels can differentiate between subclinical and overt thyroid dysfunction 1.

Key Considerations

• The optimal screening interval for thyroid dysfunction is unknown, and evidence that detection and treatment of abnormal TSH levels improves important health outcomes is lacking 1.
• Treatment is generally recommended for patients with a TSH level that is undetectable or less than 0.1 mIU/L, particularly those with overt Graves disease or nodular thyroid disease 1.
• For patients with subclinical hypothyroidism (TSH levels between 4.5 and 10 mIU/L), a trial of levothyroxine may be considered, but continuation of therapy should be predicated on clear symptomatic benefit 1.

Treatment Approach

• The standard approach to treating hypothyroidism involves starting with a lower dose of levothyroxine (especially in elderly or those with heart disease) and gradually increasing every 4-6 weeks based on TSH levels until reaching normal thyroid function.
• Most patients require lifelong therapy, taking medication on an empty stomach 30-60 minutes before breakfast or 3-4 hours after dinner for optimal absorption.
• Regular monitoring with TSH tests is essential, typically every 6-12 months once stable.

Important Outcomes

• Common symptoms that should improve with treatment include fatigue, cold intolerance, weight gain, dry skin, constipation, and mental sluggishness.
• Thyroid hormone replacement works by compensating for the body's inability to produce adequate hormones, which are crucial for regulating metabolism, energy production, and numerous bodily functions.
• Certain medications and foods (calcium, iron supplements, some antacids, soy products, high-fiber foods) can interfere with levothyroxine absorption, so timing of medication relative to these substances is important for effective treatment.

From the FDA Drug Label

The general aim of therapy is to normalize the serum TSH level TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Monitor serum TSH levels after an interval of 6 to 8 weeks after any change in dosage. In patients on a stable and appropriate replacement dosage, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient’s clinical status 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.

The diagnosis of hypothyroidism is based on serum TSH and free-T4 levels. The treatment for hypothyroidism involves levothyroxine sodium replacement therapy, with the goal of normalizing serum TSH levels. The recommended daily dosage of levothyroxine sodium varies depending on the patient population, including:

• Pre-existing primary hypothyroidism: pre-pregnancy dosage may increase during pregnancy
• New onset hypothyroidism: 1.6 mcg/kg/day for TSH ≥10 IU per liter and 1.0 mcg/kg/day for TSH < 10 IU per liter
• Pediatric patients: 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 Monitoring of serum TSH and free-T4 levels is essential to adjust the dosage and ensure adequate replacement therapy 2. In pregnant patients, serum TSH and free-T4 levels should be monitored as soon as pregnancy is confirmed and during each trimester of pregnancy 2.

From the Research

Diagnosis 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
• Symptoms of hypothyroidism include fatigue, bradycardia, constipation, and cold intolerance 3
• Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT4) and triiodothyronine (fT3) levels, while in manifest hypothyroidism serum fT4 and fT3 levels are reduced 3
• Common causes of primary hypothyroidism are autoimmune thyroiditis as well as therapeutic interventions, such as thyroid surgery or radioiodine therapy 3

Treatment of Hypothyroidism

• Levothyroxine (T4) therapy is the standard of care for treatment of hypothyroidism 3
• The biochemical treatment goal for T4 replacement in primary hypothyroidism is a TSH level within the reference range (0.4-4.0 mU/l) 3
• Initiation of levothyroxine (T4) therapy not only depends on the level of TSH elevation, but also on other factors, such as patient age, presence of pregnancy or comorbidities 3
• Treatment of patients with subclinical hypothyroidism is still a controversial topic, but in general, thyroid hormone replacement therapy in non-pregnant adults ≤ 70 years is clearly indicated if the TSH concentration is >10 mU/l 3
• Patients older than 60 years or with known or suspected ischemic heart disease should start at a lower dosage of levothyroxine (12.5 to 50 mcg per day) 4
• Women with hypothyroidism who become pregnant should increase their weekly dosage by 30% up to nine doses per week (i.e., take one extra dose twice per week), followed by monthly evaluation and management 4

Levothyroxine Dosage and Administration

• The starting dose of levothyroxine in primary hypothyroidism treatment can be a full starting dose of 1.6 mug/kg or a low starting dose of 25 mug (increased every 4 weeks) 5
• Levothyroxine can be administered in tablet or liquid form, with the liquid form permitting a quicker dissolution in the acid gastric pH and overcoming interactions with foods, drugs, or malabsorptive conditions that can impair tablet absorption 6
• The dosage of levothyroxine should be adjusted based on blood TSH assay, with dose adjustment considered after 6 to 12 weeks, given the long half-life of levothyroxine 7