What is the diagnosis and recommended evaluation and management for a patient with low thyroid‑stimulating hormone and elevated free thyroxine and free triiodothyronine?

Diagnosis: Overt Hyperthyroidism (Thyrotoxicosis)

The combination of suppressed TSH with elevated free T4 and free T3 indicates overt hyperthyroidism, requiring immediate diagnostic workup to determine the underlying cause and guide treatment. 1

Biochemical Confirmation

• Low or suppressed TSH (<0.1 mIU/L) combined with elevated free T4 and/or free T3 definitively confirms thyrotoxicosis through negative feedback suppression of pituitary TSH production 1, 2
• When TSH is suppressed and free T4 is elevated, measuring free T3 helps assess severity and identify T3-predominant thyrotoxicosis 2, 3
• Approximately 70% of hyperthyroidism cases are caused by Graves' disease, 16% by toxic nodular goiter, 3% by subacute thyroiditis, and 9% by medications 2

Essential Diagnostic Workup

Measure TSH receptor antibodies (TRAb) immediately to distinguish Graves' disease from other causes—positive TRAb confirms Graves' disease as the etiology 1, 2

Check thyroid peroxidase (TPO) antibodies to evaluate for underlying autoimmune thyroid disease, which helps predict disease course and recurrence risk 1, 2

Obtain thyroid ultrasound to assess gland size, nodularity, and vascularity—diffuse enlargement with increased vascularity suggests Graves' disease, while nodules suggest toxic nodular goiter 2

Perform radioactive iodine uptake scan (RAIU) if the diagnosis remains unclear after antibody testing—high uptake indicates Graves' disease or toxic nodular goiter, while low/absent uptake indicates destructive thyroiditis 1, 2

Etiology-Specific Management

Graves' Disease (TRAb Positive, High RAIU)

• Initiate antithyroid drugs (methimazole preferred, propylthiouracil in first trimester pregnancy) as first-line therapy for 12-18 months 2
• Recognize that approximately 50% of patients experience recurrence after stopping antithyroid drugs 2
• Risk factors for recurrence include age <40 years, free T4 ≥40 pmol/L, TRAb >6 U/L, and goiter size ≥WHO grade 2 2
• Consider long-term antithyroid drug therapy (5-10 years) for patients at high recurrence risk, which reduces recurrence to approximately 15% 2
• Definitive therapy with radioactive iodine or thyroidectomy should be considered for patients who relapse after antithyroid drugs 2

Toxic Nodular Goiter (TRAb Negative, High RAIU with Nodules)

• Radioactive iodine (¹³¹I) or thyroidectomy are the primary treatment options 2
• Radiofrequency ablation may be considered in select cases 2

Destructive Thyroiditis (TRAb Negative, Low RAIU)

• Conservative management is sufficient during the thyrotoxic phase—antithyroid drugs are not indicated because the thyroid is not actively producing excess hormone 1, 2
• Beta-blockers (preferably non-selective with alpha-blocking capacity) control symptoms including tachycardia, tremor, and anxiety 1
• Corticosteroids are reserved only for severe cases 1, 2
• Monitor for progression to hypothyroidism, which typically occurs approximately 1 month after the thyrotoxic phase resolves 1

Drug-Induced Thyrotoxicosis

• Identify causative medications including amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors 2
• For immune checkpoint inhibitor-induced thyroiditis, continue immunotherapy in most cases—high-dose corticosteroids are rarely required 1
• Thyrotoxicosis from checkpoint inhibitors is typically self-limiting and leads to permanent hypothyroidism after approximately 1 month 1

Immediate Symptomatic Management

Start beta-blockers immediately for symptomatic patients to control heart rate, tremor, palpitations, and anxiety while awaiting definitive diagnosis 1

Screen for atrial fibrillation with ECG, especially in elderly patients or those with cardiac disease, as thyrotoxicosis significantly increases arrhythmia risk 1, 2

Assess for thyroid storm in severely symptomatic patients presenting with fever, altered mental status, severe tachycardia, or cardiovascular instability—this is a medical emergency requiring intensive care 2

Critical Pitfalls to Avoid

• Never delay diagnostic workup while waiting for symptoms to worsen—biochemical confirmation with suppressed TSH and elevated free thyroid hormones mandates immediate evaluation 2
• Do not assume all cases are Graves' disease without checking TRAb and considering RAIU—destructive thyroiditis requires completely different management (no antithyroid drugs) 1, 2
• Avoid missing drug-induced causes, particularly in patients on amiodarone, checkpoint inhibitors, or tyrosine kinase inhibitors 2
• Do not overlook cardiovascular complications including atrial fibrillation, heart failure, and increased mortality risk—these require urgent attention 1, 2
• Never start antithyroid drugs empirically before confirming the diagnosis with RAIU if antibodies are negative—treating destructive thyroiditis with antithyroid drugs is ineffective and delays appropriate management 1, 2