The thyroid gland produces hormones (primarily T4/thyroxine and T3/triiodothyronine) that regulate metabolism, energy production, body temperature, cardiovascular and cognitive function, and many other processes across virtually every organ system.^1,2 When the thyroid underproduces these hormones, most commonly because of autoimmune thyroiditis (Hashimoto’s thyroiditis), the resulting metabolic slowdown can affect the entire body in ways that are subtle and gradual.^1,2,3 Because symptoms are often nonspecific, diagnosis requires confirmation with thyroid function testing.^1,2

Symptoms – Hypothyroidism is a great masquerader. Classic symptoms include fatigue, weight gain, cold intolerance, constipation, dry skin and hair, hair loss, brain fog, slow heart rate, depression, and heavy or irregular periods in women.^1,2 More subtle presentations can include elevated cholesterol, fluid retention, carpal tunnel syndrome, muscle aches, and progressive cognitive slowing that patients often attribute to aging or stress.² Because symptoms develop gradually over months to years, many patients adapt to feeling progressively worse without recognizing it as a medical condition.^1,2 Symptoms alone are not diagnostic, however, and a blood test is needed to confirm the diagnosis.^1,2

Testing – Diagnosis centers on TSH (thyroid stimulating hormone), the pituitary signal that tells the thyroid to produce more hormone. In primary hypothyroidism, an elevated TSH generally indicates the pituitary is working harder to compensate for insufficient thyroid output.^4,5 In adults when secondary thyroid dysfunction (pituitary disease) is not suspected, TSH is typically the initial test; if TSH is above the reference range, Free T4 is measured in the same sample.⁴ If pituitary disease is suspected, TSH may be unreliable and TSH and Free T4 are interpreted together.^4,5 Thyroid peroxidase antibodies (TPO-Ab) can identify autoimmune Hashimoto’s thyroiditis and help estimate the likelihood of progression, but repeat TPO-Ab testing is usually not necessary.⁴ Free T3 is not routinely needed for diagnosing hypothyroidism.⁵ We interpret these values in clinical context, and we also ask about biotin or biotin-containing supplements because they can interfere with thyroid test results.⁴

Subclinical Hypothyroidism – When TSH is mildly elevated but Free T4 remains normal, treatment decisions are nuanced. We consider symptom burden, antibody status, age, prior thyroid surgery or radioactive iodine treatment, and patient preferences.⁴ Treatment is more strongly considered when TSH is persistently 10 mIU/L or higher on repeat testing.⁴ In selected symptomatic adults under 65 with persistent milder elevations, a time-limited trial of levothyroxine may also be reasonable, and we make this decision collaboratively.⁴

Treatment – Levothyroxine (T4 Replacement) – Levothyroxine remains the guideline-recommended standard of care, and for most patients it is highly effective.⁴ It replaces T4, which the body then converts to active T3 as needed.³ We dose based on weight, age, TSH levels, comorbidities, and clinical response, starting low in older adults or those with cardiac conditions and titrating gradually.⁴ Most patients do well on either generic or brand-name levothyroxine, but if symptoms or unstable thyroid tests occur after a change in product or manufacturer, using a consistent formulation can help reduce fluctuations.⁶

Optimal TSH Targets – Standard reference ranges are population-derived, but in nonpregnant adults we generally aim to keep TSH within the laboratory reference range.^3,4 If symptoms persist, we may consider cautious dose adjustment while also evaluating for other causes of symptoms, but we avoid TSH suppression or overtreatment.⁴ We titrate based on both labs and symptom response, not symptoms in isolation.⁴

Monitoring and Follow-Up – After initiating or adjusting levothyroxine, we typically recheck TSH in about 6 to 8 weeks and continue periodic testing until the dose is stable.⁵ Once stable, annual TSH monitoring is appropriate for most patients.⁴ Important considerations: levothyroxine absorption is affected by food, calcium, iron supplements, and certain medications. It should be taken consistently, ideally on an empty stomach 30 to 60 minutes before eating.^3,5 Pregnancy significantly increases thyroid hormone requirements and requires prompt dose adjustment and more frequent monitoring.^5,7 Because autoimmune thyroid disease can coexist with other autoimmune conditions, we assess symptoms and risk factors and follow condition-specific screening recommendations, including celiac testing at diagnosis where appropriate.^2,4

Our approach to hypothyroidism goes beyond simply normalizing TSH. We evaluate symptoms comprehensively, confirm the diagnosis biochemically, address absorption issues, and look for other causes of persistent symptoms.^4,5 Levothyroxine remains first-line therapy.⁴ For a small minority of carefully selected adults with confirmed overt primary hypothyroidism who do not achieve adequate symptomatic recovery on optimized levothyroxine alone, specialist-supervised combination therapy may be considered, but routine liothyronine use is not recommended.^4,8 Natural thyroid extract is not recommended.^4,8

References

1. NHS. Underactive thyroid (hypothyroidism). Reviewed April 28, 2025. Accessed April 16, 2026.
2. American Thyroid Association. Hypothyroidism Web Brochure. 2019. Accessed April 16, 2026.
3. American Thyroid Association. Thyroid Hormone Treatment. Accessed April 16, 2026.
4. National Institute for Health and Care Excellence. Thyroid disease: assessment and management. NICE guideline NG145. Published November 20, 2019. Last reviewed October 3, 2025. Accessed April 16, 2026.
5. American Thyroid Association. Hypothyroidism. Accessed April 16, 2026.
6. Medicines and Healthcare products Regulatory Agency. Levothyroxine: new prescribing advice for patients who experience symptoms on switching between different levothyroxine products. Drug Safety Update. May 19, 2021. Accessed April 16, 2026.
7. American Thyroid Association. Hypothyroidism in Pregnancy. 2019. Accessed April 16, 2026.
8. Ahluwalia R, Baldeweg SE, Boelaert K, et al. Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for Endocrinology consensus statement. Clin Endocrinol (Oxf). 2023. doi:10.1111/cen.14935. Accessed April 16, 2026.