What is the workup for hypothyroidism (underactive thyroid disease)?

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Dainyal Siddiqui, MD

Internal Medicine

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Manuel Jimenez, MD

Cardiology

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Franz Pierre-Louis, MD

Infectious Disease

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Last updated: April 13, 2025 • View editorial policy

From the Guidelines

The workup of hypothyroidism in patients on immune checkpoint inhibitor (ICPi) therapy should include measuring TSH, with the option of also including FT4, every 4-6 weeks as part of routine clinical monitoring for asymptomatic patients. This approach is based on the most recent guidelines from the Journal of Clinical Oncology, published in 2021 1. The guidelines recommend using TSH and FT4 for case detection in symptomatic patients, and evaluating low TSH with a low FT4 as consistent with central hypothyroidism.

Some key points to consider in the workup of hypothyroidism include:

  • TSH levels should be checked every 4-6 weeks in asymptomatic patients on ICPi therapy
  • FT4 should be included in the workup for symptomatic patients
  • Low TSH with a low FT4 is consistent with central hypothyroidism and should be evaluated as per hypophysitis
  • The development of hypothyroidism is commonly seen after the thyrotoxicosis phase of thyroiditis

In terms of management, the guidelines provide the following grading system:

  • G1: TSH < 4.5 and < 10 mIU/L and asymptomatic: continue ICPi with monitoring of TSH (option for FT4) every 4-6 weeks
  • G2: Moderate symptoms, able to perform ADL, TSH persistently > 10 mIU/L: may continue or hold ICPi until symptoms resolve to baseline, consider endocrine consultation, and prescribe thyroid hormone supplementation
  • G3-4: Severe symptoms, medically significant or life-threatening consequences, unable to perform ADL: hold ICPi until symptoms resolve to baseline with appropriate supplementation, and consider hospital admission for developing myxedema.

The management of hypothyroidism should be guided by the severity of symptoms and TSH levels, with a goal of normalizing TSH levels and alleviating symptoms. This approach is supported by the guidelines, which emphasize the importance of regular monitoring and adjustment of therapy as needed 1.

From the Research

Diagnosis of Hypothyroidism

  • Hypothyroidism is diagnosed based on blood levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) 2
  • The signs and symptoms of thyroid dysfunction are nonspecific and nondiagnostic, especially early in disease presentation 2
  • A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations 3

Treatment of Hypothyroidism

  • Symptom relief and normalized TSH levels are achieved with levothyroxine (LT4) replacement therapy, started at 1.5 to 1.8 mcg per kg per day 2
  • Patients older than 60 years or with known or suspected ischemic heart disease should start at a lower dosage of LT4 (12.5 to 50 mcg per day) 2
  • Women with hypothyroidism who become pregnant should increase their weekly dosage by 30% up to nine doses per week 2
  • The dose of LT4 used for treatment is based on the degree of preserved thyroid functionality and lean body mass, and usually ranges from 1.4 to 1.8 mcg/kg/day 4

Subclinical Hypothyroidism

  • 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 5
  • Generally, treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L 5
  • Treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L 5
  • The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient 3

Special Considerations

  • Hashimoto thyroiditis (HT) is a common autoimmune disorder that can lead to hypothyroidism, and its management is based on symptoms control, periodical TSH measurements, and thyroid hormone replacement therapy 4
  • Serum-negative-chronic-autoimmune-thyroiditis (SN-CAT) requires a lower substitution dose of LT4 to correct hypothyroidism compared to classic Hashimoto's thyroiditis (CHT) 6
  • 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 5

References

2
Research

Hypothyroidism: Diagnosis and Treatment.

American family physician, 2021

3
Research

Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2012

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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