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. This recommendation is based on the US Preventive Services Task Force (USPSTF) recommendation statement published in the Annals of Internal Medicine in 2015 1. The treatment approach typically involves daily oral levothyroxine, with starting doses usually between 25-100 mcg depending on age, weight, severity, and cardiac status.

Key Considerations

• Elderly patients or those with heart disease should start at lower doses (12.5-25 mcg) and gradually increase.
• 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.
• Regular monitoring with TSH blood tests is necessary, initially every 6-8 weeks until stable, then annually.
• Dose adjustments may be needed during pregnancy, with significant weight changes, or when starting certain medications.

Causes and Risks

• The most common cause of hypothyroidism in the United States is chronic autoimmune (Hashimoto) thyroiditis.
• Risk factors for an elevated TSH level include female sex, advancing age, white race, type 1 diabetes, Down syndrome, family history of thyroid disease, goiter, previous hyperthyroidism, and external-beam radiation in the head and neck area.
• Untreated hypothyroidism can lead to fatigue, weight gain, cold intolerance, constipation, dry skin, and in severe cases, myxedema coma.

Screening and Diagnosis

• The serum TSH test is the primary screening test for thyroid dysfunction.
• Multiple tests should be done over a 3- to 6-month interval to confirm or rule out abnormal findings.
• Follow-up testing of serum T4 levels in persons with persistently abnormal TSH levels can differentiate between subclinical (normal T4 levels) and “overt” (abnormal T4 levels) thyroid dysfunction.

From the FDA Drug Label

Thyroid hormone drugs are indicated: As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis 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

Hypothyroidism Treatment: Levothyroxine sodium and liothyronine sodium are indicated for replacement or supplemental therapy in patients with hypothyroidism of any etiology.

• Key Points:
  • Hypothyroidism should be treated promptly, especially during pregnancy.
  • Untreated maternal hypothyroidism may have adverse effects on fetal neurocognitive development.
  • Levothyroxine sodium dosage should be adjusted during pregnancy and returned to pre-pregnancy dose immediately after delivery 2.
  • Liothyronine sodium can be used as replacement or supplemental therapy in patients with hypothyroidism, including pediatric patients, adults, and the elderly 3.

From the Research

Hypothyroidism Treatment

• The treatment of hypothyroidism with levothyroxine is effective and simple, but recommendations for the starting dose vary considerably 4.
• A full starting dose of levothyroxine in cardiac asymptomatic patients with primary hypothyroidism is safe and may be more convenient and cost-effective than a low starting dose regimen 4.
• Levothyroxine doses should be optimized aiming for a TSH in the 0.3-2.0 mU/L range for 3 to 6 months before a therapeutic response can be assessed 5.

Liothyronine Use

• In some patients with confirmed overt hypothyroidism and persistent symptoms who have had adequate treatment with levothyroxine, a trial of liothyronine/levothyroxine combined therapy may be warranted 5.
• The use of liothyronine in primary hypothyroidism is suggested for patients who remain symptomatic despite achieving target TSH levels, especially if polymorphism of the deiodinase 2 (D2) genes is documented 6.
• The goals of combination therapy should be to achieve a physiological ratio of free triiodothyronine/free thyroxine (FT3/FT4) and non-suppression of TSH 6.

Subclinical Hypothyroidism

• Treatment of subclinical hypothyroidism is not necessary unless the TSH exceeds 7.0-10 mIU/L 7.
• In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L 7.
• 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 7.

Therapeutic Targets

• Recent evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at the tissue level in patients treated with levothyroxine 8.
• Mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range 8.
• Normalizing serum TSH in hypothyroid patients can reduce the risk of death, with an estimated reduction in risk for 28.3 million people in the USA and Europe alone 8.