What are the diagnostic criteria for hypothyroidism (underactive thyroid)?

From the Guidelines

Hypothyroidism is diagnosed through a combination of clinical evaluation and blood tests, primarily measuring thyroid stimulating hormone (TSH) and free T4 levels, as recommended in the 2021 ASCO guideline update 1. The diagnosis of hypothyroidism involves a step-by-step approach, starting with the measurement of TSH levels, which can be checked every 4-6 weeks as part of routine clinical monitoring for asymptomatic patients on immune checkpoint inhibitor (ICPi) therapy.

• TSH levels are used for case detection in symptomatic patients, and low TSH with a low FT4 is consistent with central hypothyroidism, which requires evaluation as per hypophysitis.
• The grading of hypothyroidism is based on the severity of symptoms and TSH levels, with Grade 1 being asymptomatic patients with TSH levels between 4.5 and 10 mIU/L, Grade 2 being moderate symptoms with TSH levels persistently above 10 mIU/L, and Grade 3-4 being severe symptoms with medically significant or life-threatening consequences.
• For Grade 1 hypothyroidism, patients should continue ICPi with monitoring of TSH every 4-6 weeks, while for Grade 2, ICPi may be continued or held until symptoms resolve, and thyroid hormone supplementation may be prescribed.
• In severe cases (Grade 3-4), ICPi should be held until symptoms resolve, and hospital admission may be necessary for developing myxedema, with inpatient endocrinology consultation and IV levothyroxine dosing, steroids, and supportive care. The management of hypothyroidism involves thyroid hormone replacement, typically with levothyroxine (T4), with the goal of maintaining TSH within the reference range, as outlined in the 2021 ASCO guideline update 1.
• Regular monitoring of TSH levels is necessary, initially every 6-8 weeks until stable, then annually, with dose adjustments made based on TSH values.
• Proper diagnosis and treatment of hypothyroidism are crucial to prevent complications, including cardiovascular problems, infertility, and in severe cases, myxedema coma, as highlighted in the 2021 ASCO guideline update 1.

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. 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 In adult patients with primary hypothyroidism, 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 In patients with hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4.

Diagnosis of Hypothyroidism:

• The diagnosis of hypothyroidism is based on clinical and laboratory parameters, including serum TSH and free-T4 levels.
• The goal of therapy is to normalize the serum TSH level.
• Monitoring of serum TSH and free-T4 levels is necessary to assess the adequacy of replacement therapy.
• The frequency of monitoring depends on the patient's age, clinical status, and response to therapy.
• In adult patients, serum TSH levels should be monitored 6 to 8 weeks after any change in dosage, and clinical and biochemical response should be evaluated every 6 to 12 months.
• In pediatric patients, serum TSH and total or free-T4 should be monitored 2 and 4 weeks after initiation of treatment, 2 weeks after any change in dosage, and then every 3 to 12 months thereafter.
• Failure to achieve normalization of serum TSH and free-T4 levels may indicate inadequate therapy or other underlying conditions 2.

From the Research

Diagnosis of Hypothyroidism

• Hypothyroidism is diagnosed based on blood levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) 3.
• A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations 4.
• The signs and symptoms that suggest thyroid dysfunction are nonspecific and nondiagnostic, especially early in disease presentation 3.
• Symptoms of hypothyroidism can develop slowly and often mimic symptoms of other disorders, including menstrual cycle abnormalities 5.

Blood Tests for Diagnosis

• TSH levels are used to diagnose hypothyroidism, with elevated levels indicating hypothyroidism 3, 4.
• FT4 levels are also used to confirm the diagnosis of hypothyroidism 3.
• Thyroid peroxidase antibody (TPO) levels may be elevated in some patients with hypothyroidism, particularly those with autoimmune thyroiditis 3.

Treatment of Hypothyroidism

• Levothyroxine replacement therapy is the standard treatment for hypothyroidism, started at 1.5 to 1.8 mcg per kg per day 3.
• The dosage of levothyroxine should be increased gradually, and laboratory values should be monitored six to eight weeks after any dosage change 6.
• 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) 3.
• Women with hypothyroidism who become pregnant should increase their weekly dosage by 30% up to nine doses per week 3.