How to evaluate a patient with suspected Graves' disease and a history of multidrug-resistant infections?

Evaluation of Graves' Disease

Begin with TSH and free T4 measurement, followed by TSH receptor antibody testing (TRAb or TSI) to confirm the autoimmune etiology of Graves' disease. 1

Initial Laboratory Workup

First-Line Tests

• Measure TSH and free T4 (FT4) simultaneously as the initial screening approach for any patient with suspected thyroid dysfunction 1
• The classic biochemical pattern shows suppressed TSH with elevated free T4 and/or T3 1
• If TSH is low but FT4 is also low, this suggests pituitary dysfunction rather than Graves' disease 1

Confirmatory Testing

• TSH receptor antibody testing (TRAb or TSI) is the most important confirmatory test and distinguishes Graves' disease from other causes of thyrotoxicosis such as thyroiditis, toxic adenoma, or toxic multinodular goiter 1
• Positive TSH receptor antibodies confirm the autoimmune etiology specific to Graves' disease 1

Additional Thyroid Hormone Assessment

• Measure T3 in highly symptomatic patients with minimal FT4 elevations or when T3 toxicosis is suspected 1
• Thyroid peroxidase (TPO) antibodies can be assessed but are less specific for Graves' disease than TSH receptor antibodies 1

Clinical Examination Findings

Pathognomonic Signs

• Ophthalmopathy (Graves' eye disease) is diagnostic when present and should prompt early endocrine referral 1
• Thyroid bruit on auscultation is diagnostic of Graves' disease 1
• If clinical presentation is unambiguous with clear extra-thyroid signs (ophthalmopathy or thyroid bruit), complementary etiological examinations may not be required after biochemical confirmation of thyrotoxicosis 1

Physical Examination Components

External examination can identify orbital manifestations of Graves' disease 2

• Ocular alignment and motility assessment may reveal neurological disorders associated with Graves' disease 2
• Thyroid palpation for diffuse enlargement (goiter) 3

Special Considerations in Patients with Multidrug-Resistant Infections

Monitoring for Agranulocytosis Risk

• Patients should be under close surveillance and cautioned to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise 4
• In such cases, obtain white blood cell and differential counts immediately to determine whether agranulocytosis has developed 4
• Exercise particular care with patients receiving additional drugs known to cause agranulocytosis 4

Laboratory Monitoring

• Monitor prothrombin time during therapy, especially before surgical procedures, as methimazole may cause hypoprothrombinemia and bleeding 4
• Monitor thyroid function tests periodically during therapy; a rising serum TSH indicates that a lower maintenance dose should be employed 4

Vasculitis Surveillance

• Inform patients to promptly report symptoms associated with vasculitis including new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 4

Common Pitfalls to Avoid

• Do not rely on TSH alone; always measure free T4 simultaneously to avoid missing the diagnosis 1
• Do not assume normal TSH rules out thyrotoxicosis in patients with suspected central hypothyroidism 1
• Do not skip TSH receptor antibody testing when the diagnosis is not clinically obvious, as this is the definitive confirmatory test 1
• In patients with history of multidrug-resistant infections, do not delay obtaining baseline white blood cell counts before initiating antithyroid therapy 4