Thyroid Workup in Symptomatic Patients
For patients presenting with symptoms suggestive of thyroid dysfunction, measure serum TSH as the initial test, which has 98% sensitivity and 92% specificity for detecting thyroid disease. 1, 2
Initial Diagnostic Approach
When to Test TSH
Test TSH immediately in any patient presenting with symptoms suggestive of thyroid dysfunction, including: 2, 3, 4
- Hypothyroidism symptoms: fatigue (68-83% of cases), weight gain (24-59%), cold intolerance, constipation, cognitive issues like memory loss and difficulty concentrating (45-48%), menstrual irregularities (23%), dry skin, voice changes 3, 4
- Hyperthyroidism symptoms: weight loss, palpitations, heat intolerance, anxiety, insomnia, diarrhea 2, 5
- Physical findings: diffusely enlarged thyroid gland, exophthalmos (in Graves disease), or palpable thyroid nodules 5
High-Risk Populations Requiring Testing
Even with minimal or nonspecific symptoms, test TSH in these high-risk groups: 1, 2
- Elderly patients (women >60 years, men >60 years) 1, 2
- Postpartum women 1, 2
- Patients with radiation exposure >20 mGy to the thyroid 1, 2
- Patients with Down syndrome 1, 2
- Type 1 diabetes mellitus (test at diagnosis and every 1-2 years) 1, 2
- Personal history of autoimmune disease 1
- Family history of thyroid disease 1
- Atrial fibrillation (especially elderly) 1, 2
- Patients on immune checkpoint inhibitor therapy (monitor every 4-6 weeks, as 6-20% develop thyroid dysfunction) 2
- Women of childbearing age before pregnancy or during first trimester 2
Interpretation Algorithm
Step 1: Evaluate TSH Level
- TSH <0.1 mU/L: Low, suggests hyperthyroidism 1
- TSH 0.1-4 or 5 mU/L: Normal range (rules out peripheral hypothyroidism) 6
- TSH >6.5 mU/L: Elevated, suggests hypothyroidism 1
Step 2: Measure Free T4 Based on TSH Result
If TSH is abnormal, measure free T4 to distinguish overt from subclinical disease: 2, 3, 5
- Low TSH + High free T4: Overt hyperthyroidism 2, 5
- Low TSH + Normal free T4: Subclinical hyperthyroidism 1, 5
- Low TSH + Low free T4: Central hypothyroidism (evaluate for hypophysitis) 2
- High TSH + Low free T4: Overt primary hypothyroidism 6, 3
- High TSH + Normal free T4: Subclinical hypothyroidism 1, 6
Step 3: Confirm Abnormal Results
Between 30-60% of elevated TSH levels are not confirmed on repeat testing, so recheck TSH in 6-12 weeks before committing to lifelong treatment, unless the patient has severe symptoms or TSH >10 mIU/L. 6
Critical Pitfalls to Avoid
False Positive TSH Results
Severe non-thyroid illness (euthyroid sick syndrome) can cause misleading TSH results, particularly in hospitalized or frail elderly patients where the positive predictive value drops dramatically (PPV 0.24 for hyperthyroidism, 0.06 for hypothyroidism in acute care settings). 1, 2 Defer testing in acutely ill patients unless thyroid dysfunction is strongly suspected.
Age-Related TSH Changes
TSH levels increase with age, so slightly elevated TSH in elderly patients may not represent true hypothyroidism. 6 Consider clinical context and symptoms before treating.
Transient Thyroid Dysfunction
Recognize transient hypothyroidism (from thyroiditis, postpartum thyroiditis, or medication effects) that may last weeks to months but does not require lifelong treatment. 6, 7 This is a major challenge in avoiding unnecessary lifelong levothyroxine therapy.
Additional Testing When Etiology Unclear
If the diagnosis remains uncertain after TSH and free T4 testing, consider: 7, 5
- Thyroid scintigraphy (radioactive iodine uptake): Distinguishes Graves disease (diffuse uptake) from toxic nodules (focal uptake) from thyroiditis (low uptake) 7, 5
- Thyrotropin-receptor antibodies: Confirms Graves disease 5
- Thyroid peroxidase antibodies: Identifies autoimmune thyroiditis 4
Population Screening Not Recommended
Do not screen asymptomatic adults for thyroid disease, as there is no evidence that routine screening improves clinical outcomes. 1, 3 The USPSTF found insufficient evidence to determine the balance of benefits and harms of screening. 1