What is the approach to diagnose thyroid toxicosis?

How to Diagnose Thyroid Toxicosis

Diagnose thyrotoxicosis by measuring TSH, free T4, and total T3—elevated free T4 or total T3 with suppressed or low-normal TSH confirms the diagnosis. 1

Initial Laboratory Assessment

The diagnostic workup begins with thyroid function testing:

• Measure TSH, free T4, and total T3 as the initial laboratory panel 1, 2
• Biochemical confirmation requires: elevated free T4 or total T3 combined with suppressed TSH (typically <0.1 mU/L) 3, 4
• Most patients are asymptomatic at diagnosis, with thyrotoxicosis detected through routine laboratory monitoring 3, 1

Clinical symptoms when present include: weight loss, palpitations, heat intolerance, tremors, anxiety, and diarrhea, though these may be masked in patients taking beta-blockers 3

Determining the Etiology

Once biochemical thyrotoxicosis is confirmed, distinguish between causes:

Radioiodine Uptake Scanning (Preferred Method)

• Low or absent uptake indicates destructive thyroiditis (transient, self-limiting) 1
• High uptake indicates: Graves' disease, toxic multinodular goiter, or toxic adenoma 5
• Use iodine-123 rather than iodine-131 for superior imaging quality 1
• Perform uptake scan only when TSH is suppressed—it has no value in euthyroid patients 6

Alternative: Doppler Ultrasound

• Measures thyroid blood flow to differentiate overactive thyroid (increased flow) from destructive thyroiditis (decreased flow) 1, 5
• Sensitivity 95%, specificity 90% for this distinction 6
• Use when radioiodine uptake is contraindicated (recent iodinated contrast, pregnancy) 3, 1

Antibody Testing

• Measure TRAb or TSI to exclude Graves' disease in suspected transient thyrotoxicosis 3, 1
• Measure TPO antibody to support autoimmune thyroiditis 3, 1

Confirming Transient vs. Persistent Thyrotoxicosis

For suspected thyroiditis (most common with immune checkpoint inhibitors):

• The thyrotoxic phase occurs an average of 1 month after drug initiation 3
• Spontaneous resolution occurs within 2-14 weeks in most cases 1
• Repeat thyroid function tests every 2-3 weeks to document resolution and detect subsequent hypothyroidism 3, 1
• Permanent hypothyroidism develops an average of 1 month after the thyrotoxic phase (2 months from immunotherapy initiation) 3

Structural Evaluation with Ultrasound

Thyroid ultrasound should be performed:

• As first-line imaging after TSH measurement to evaluate thyroid morphology 6
• To identify coexisting nodules that may require biopsy, even in hyperthyroid patients 6
• To detect substernal extension or compressive features that alter treatment decisions 6
• To measure thyroid size for calculating radioactive iodine treatment doses 6

Critical Pitfalls to Avoid

• Never initiate thionamides or radioactive iodine for transient thyrotoxicosis—it is self-limiting and requires only conservative management 1
• Always obtain imaging or uptake studies before definitive treatment in ambiguous cases 1
• Do not skip ultrasound and proceed directly to uptake scan—you may miss coexisting nodules requiring malignancy evaluation 6
• In patients with both adrenal insufficiency and hypothyroidism, always start steroids before thyroid hormone to avoid adrenal crisis 3
• Do not use radionuclide scanning in euthyroid patients—it has low diagnostic value and wastes resources 6

Management During Diagnostic Workup

While confirming the diagnosis:

• Use non-selective beta-blockers (preferably with alpha-receptor blocking capacity) for symptomatic patients during the thyrotoxic phase 3
• Conservative management is sufficient for thyroiditis—no antithyroid drugs needed 3
• Initiate thyroid hormone replacement when hypothyroidism develops after the thyrotoxic phase resolves 3