What is the workup and management of hyperthyroidism found on routine lab work?

Workup and Management of Hyperthyroidism Found on Routine Labwork

Initial Biochemical Confirmation

When hyperthyroidism is suspected on routine labs, confirm with TSH, free T4, and free T3 measurements—a suppressed TSH with elevated free T4 and/or T3 confirms the diagnosis. 1, 2

• TSH below the reference range (typically <0.4 mIU/L) has high sensitivity and specificity for diagnosing thyrotoxicosis 3
• Measure both free T4 and free T3, as some patients have isolated T3 toxicosis 1
• Distinguish overt hyperthyroidism (suppressed TSH with elevated thyroid hormones) from subclinical hyperthyroidism (suppressed TSH with normal thyroid hormones) 2

Establishing the Etiology

After confirming hyperthyroidism biochemically, determine the underlying cause using TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasound, and radioactive iodine uptake scan. 1

First-Line Diagnostic Tests:

• Measure TSH-receptor antibodies (TRAb): Positive results confirm Graves' disease, which accounts for 70% of hyperthyroidism cases 1, 3
• Check for thyroid eye disease on physical examination: Exophthalmos, lid lag, or stare is pathognomonic for Graves' disease 2, 3
• Perform thyroid ultrasound: Identifies nodules, diffuse enlargement, or increased vascularity 1

When to Order Radioactive Iodine Uptake Scan:

• Order scintigraphy if thyroid nodules are present or the etiology remains unclear after initial testing 2, 3
• Diffuse increased uptake indicates Graves' disease 3
• Focal areas of increased uptake indicate toxic adenoma or toxic multinodular goiter (16% of cases) 1, 3
• Low or absent uptake indicates thyroiditis (3% of cases) or exogenous thyroid hormone 1, 3

Drug-Induced Hyperthyroidism:

• Review medication history for amiodarone, tyrosine kinase inhibitors, or immune checkpoint inhibitors, which cause 9% of hyperthyroidism cases 1
• Thyroid dysfunction occurs in 5-10% of patients on anti-PD-1/PD-L1 therapy and 20% with combination immunotherapy 4

Immediate Cardiovascular Management

Start beta-blockers immediately for all symptomatic patients to control tachycardia, hypertension, and prevent cardiovascular complications. 4, 5

• Use atenolol 25-50 mg daily or metoprolol, titrating to heart rate <90 bpm if blood pressure allows 4
• Propranolol is an alternative beta-blocker option 4
• Beta-blockers prevent atrial fibrillation, heart failure, and other cardiovascular events that increase mortality in untreated hyperthyroidism 5, 2

Treatment Based on Etiology

Graves' Disease Treatment Algorithm:

For Graves' disease, initiate methimazole as first-line therapy for 12-18 months to induce remission, with radioactive iodine or surgery reserved for treatment failures or specific indications. 6, 1, 3

Antithyroid Drug Therapy:

• Start methimazole 10-40 mg daily (preferred over propylthiouracil except in first trimester pregnancy or thyroid storm) 7, 3
• Propylthiouracil carries significant hepatotoxicity risk and should be avoided except in specific circumstances 8, 1
• Continue treatment for 12-18 months, then attempt withdrawal 6, 1
• Recurrence occurs in approximately 50% of patients after 12-18 months of treatment 1
• Risk factors for recurrence include age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 1
• Long-term treatment (5-10 years) reduces recurrence to 15% compared to 50% with short-term treatment 1

Monitoring During Antithyroid Drug Therapy:

• Monitor thyroid function tests periodically during therapy 7, 8
• Check CBC with differential if patient develops sore throat, fever, or signs of infection to detect agranulocytosis 7, 8
• Monitor prothrombin time, especially before surgical procedures 7, 8
• A rising TSH indicates need for lower maintenance dose 7, 8

Radioactive Iodine (¹³¹I):

• Radioactive iodine resolves hyperthyroidism in >90% of patients with Graves' disease 3
• Use as first-line therapy or after antithyroid drug failure 6, 1
• Avoid in patients with active Graves' ophthalmopathy—may worsen eye disease 6, 5
• Consider corticosteroid cover to reduce risk of ophthalmopathy deterioration 6
• Hypothyroidism develops in most patients within 1 year after treatment 3
• Avoid pregnancy for 4 months following administration 6
• Contraindicated during pregnancy and lactation 6

Surgery (Thyroidectomy):

• Reserve surgery for patients with large goiters causing compressive symptoms (dysphagia, orthopnea, voice changes), concurrent thyroid cancer, pregnancy, or Graves' ophthalmopathy 5, 2, 3
• Perform subtotal or near-total thyroidectomy 6
• Render patient euthyroid with antithyroid drugs before surgery 6, 5
• Continue beta-blockers perioperatively for cardiovascular manifestations 5
• Surgery is cost-effective with high-volume surgeons 5

Toxic Nodular Goiter (Toxic Multinodular Goiter or Toxic Adenoma):

Treat toxic nodular goiter with radioactive iodine as first-line therapy or thyroidectomy; antithyroid drugs do not cure this condition. 6, 1

• Antithyroid drugs may be used temporarily to achieve euthyroid state before definitive therapy 6
• Radioactive iodine is the treatment of choice for toxic nodular goiter 6, 1
• Thyroid lobectomy for solitary toxic adenoma 5
• Total thyroidectomy for toxic multinodular goiter 5
• Radiofrequency ablation is rarely used 1

Thyroiditis (Destructive Thyrotoxicosis):

Thyroiditis is self-limiting and requires only supportive care with beta-blockers; steroids are reserved for severe cases. 4, 1

• Monitor with symptom evaluation and free T4 testing every 2 weeks during hyperthyroid phase 4
• Beta-blockers for symptomatic relief (atenolol 25-50 mg daily) 4
• High-dose corticosteroids (prednisone 1 mg/kg/day) only for severe cases 4, 1
• Introduce levothyroxine if patient becomes hypothyroid (low free T4/T3, even if TSH not elevated) 4
• Destructive thyrotoxicosis is usually mild and transient 1

Special Populations

Pregnancy:

• Use propylthiouracil in first trimester due to rare fetal abnormalities with methimazole 7, 8
• Switch to methimazole for second and third trimesters to avoid maternal hepatotoxicity from propylthiouracil 7, 8
• Avoid radioactive iodine during pregnancy and lactation 6
• Surgery is an option if medical management fails 5
• Untreated hyperthyroidism increases risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal/neonatal hyperthyroidism 7, 8

Subclinical Hyperthyroidism:

• Treat patients >65 years or with persistent TSH <0.1 mIU/L due to increased risk of osteoporosis and cardiovascular disease 2
• Subclinical hyperthyroidism affects 0.7-1.4% of people worldwide 2
• Treatment prevents progression to overt disease and reduces cardiovascular complications 2

Patients on Immune Checkpoint Inhibitors:

• Continue immunotherapy in most cases—thyroid dysfunction rarely requires treatment interruption 4
• Monitor TSH every 4-6 weeks for asymptomatic patients 4
• High-dose corticosteroids not routinely required for thyroid dysfunction 4

Critical Pitfalls to Avoid

• Never use radioactive iodine in patients with active Graves' ophthalmopathy—it worsens eye disease 6, 5
• Do not miss thyroid storm—a life-threatening complication requiring hospitalization, multidisciplinary care, and definitive treatment 5
• Avoid propylthiouracil except in first trimester pregnancy or thyroid storm due to hepatotoxicity risk 8, 1
• Do not delay beta-blocker therapy—untreated cardiovascular manifestations increase mortality 5, 2
• Monitor for agranulocytosis with antithyroid drugs—obtain CBC if patient develops fever, sore throat, or infection 7, 8
• Screen for vasculitis with antithyroid drugs—promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 7, 8