What is the initial workup for a patient with suspected hyperthyroidism?

Initial Workup for Suspected Hyperthyroidism

Measure serum TSH as the first-line test, and if suppressed (TSH <0.1-0.4 mIU/L), confirm with free T4 and free T3 to establish biochemical hyperthyroidism. 1, 2

Biochemical Confirmation

First-Line Laboratory Testing

• TSH measurement is the initial screening test with high sensitivity (98%) and specificity (92%) for detecting thyroid dysfunction 3, 1
• A suppressed TSH (<0.05-0.1 mIU/L) indicates possible hyperthyroidism and requires further evaluation 1, 4
• Measure free T4 and free T3 alongside TSH to confirm hyperthyroidism biochemically—elevated thyroid hormones with suppressed TSH establish the diagnosis 1, 2
• Free T3 may be elevated before free T4 in early hyperthyroidism, making both measurements valuable 1, 2

Critical Diagnostic Pitfall

• Do not diagnose hyperthyroidism based on a single suppressed TSH value alone—up to 37% of patients with suppressed TSH may have alternative explanations including nonthyroidal illness, medications, or transient suppression 4, 5
• Rule out nonthyroidal causes: acute illness, hospitalization, first trimester pregnancy, medications (glucocorticoids, dopamine), and central hypothyroidism (pituitary disease) 2, 5

Etiological Diagnosis After Biochemical Confirmation

Determine the Underlying Cause

Once hyperthyroidism is biochemically confirmed, identify the specific etiology using the following tests 1, 2:

• TSH-receptor antibodies (TRAb or TBII): Positive in Graves' disease (70% of hyperthyroidism cases) 1, 2
• Thyroid peroxidase antibodies (TPO): Supportive of autoimmune etiology when positive 1, 2
• Thyroid ultrasound: Identifies nodular disease, goiter size, vascularity patterns, and distinguishes diffuse from nodular pathology 1, 2
• Radioactive iodine uptake scan (RAIU) with scintigraphy: Differentiates high-uptake conditions (Graves' disease, toxic nodular goiter) from low-uptake conditions (thyroiditis, exogenous thyroid hormone) 1, 2

Specific Etiological Patterns

• Graves' disease (70% of cases): Positive TSH-receptor antibodies, diffuse uptake on scintigraphy, increased vascularity on ultrasound, possible ophthalmopathy 1, 2
• Toxic nodular goiter (16% of cases): Nodular uptake pattern on scintigraphy, nodules visible on ultrasound, negative TSH-receptor antibodies 1, 2
• Subacute thyroiditis (3% of cases): Low or absent radioiodine uptake, elevated inflammatory markers, tender thyroid on examination 1, 2
• Drug-induced (9% of cases): History of amiodarone, tyrosine kinase inhibitors, immune checkpoint inhibitors, or excessive levothyroxine intake 1, 2

Clinical Assessment Details

Specific History Elements to Obtain

• Symptoms of hyperthyroidism: Weight loss despite normal appetite, heat intolerance, palpitations, tremor, anxiety, increased bowel frequency, menstrual irregularities 1, 6
• Medication history: Levothyroxine, amiodarone, lithium, immune checkpoint inhibitors, tyrosine kinase inhibitors 1, 2
• Recent iodine exposure: CT contrast, amiodarone, kelp supplements 1, 2
• Family history: Autoimmune thyroid disease, Graves' disease 1
• Pregnancy status: First trimester can cause physiologic TSH suppression 2, 5

Targeted Physical Examination Findings

• Thyroid examination: Goiter size (WHO grading), nodules, tenderness, thyroid bruit (suggests Graves' disease) 3, 1
• Cardiovascular: Tachycardia, atrial fibrillation, widened pulse pressure, systolic hypertension 3, 1
• Ophthalmologic: Exophthalmos, lid lag, periorbital edema (diagnostic of Graves' disease when present) 3, 1
• Neurologic: Fine tremor, hyperreflexia, proximal muscle weakness 1, 6
• Dermatologic: Warm, moist skin, pretibial myxedema (Graves' disease) 1

Additional Baseline Testing

Assess for Complications

• Electrocardiogram: Screen for atrial fibrillation, especially in patients >60 years or with cardiac symptoms 3, 5
• Complete blood count: Baseline before antithyroid drug therapy (monitor for agranulocytosis) 7, 1
• Liver function tests: Baseline before antithyroid drug therapy 3, 1
• Serum calcium: Hyperthyroidism can cause hypercalcemia 3

Age-Specific Considerations

Elderly Patients (>65 years)

• Atypical presentations are common—may present with apathetic hyperthyroidism (minimal symptoms, weight loss, atrial fibrillation) rather than classic hypermetabolic symptoms 6, 5
• Prevalence of subclinical hyperthyroidism reaches 15% in elderly populations 5
• Higher risk for cardiovascular complications including atrial fibrillation and heart failure 3, 5

Younger Patients (<40 years)

• More likely to present with classic hypermetabolic symptoms 1, 6
• Higher recurrence rates after antithyroid drug therapy 1

Common Diagnostic Pitfalls to Avoid

• Failing to confirm suppressed TSH with repeat testing—transient TSH suppression occurs frequently and 37% of initially suppressed TSH cases remain undiagnosed due to inadequate follow-up 4, 5
• Missing hyperthyroidism in elderly patients who present with minimal or atypical symptoms (apathetic hyperthyroidism) 6, 5
• Treating euthyroid hyperthyroxinemia (elevated T4 with normal TSH)—this represents altered thyroid hormone binding, not true hyperthyroidism 6
• Overlooking drug-induced causes—always review medication history for amiodarone, immune checkpoint inhibitors, and excessive levothyroxine 1, 2
• Not distinguishing between high-uptake and low-uptake hyperthyroidism—treatment differs completely (antithyroid drugs/surgery/radioiodine for high-uptake vs. supportive care for thyroiditis) 1, 6

Severity Stratification

Subclinical Hyperthyroidism

• TSH <0.1-0.4 mIU/L with normal free T4 and T3 5
• Mild: TSH 0.1-0.4 mIU/L 5
• Severe: TSH <0.1 mIU/L 5
• Treatment mandatory in patients >65 years or with comorbidities (osteoporosis, atrial fibrillation) 5

Overt Hyperthyroidism

• TSH <0.1 mIU/L with elevated free T4 and/or T3 1, 2
• Requires prompt treatment to prevent complications 1