Could this be Graves' disease?

Diagnosing Graves' Disease

Graves' disease is primarily diagnosed through laboratory testing showing suppressed TSH with elevated thyroid hormones, and confirmed by positive TSH receptor antibodies (TRAb), making imaging unnecessary in most cases. 1, 2

Clinical Presentation That Suggests Graves' Disease

The diagnosis becomes almost unmistakable when specific extrathyroidal features are present 3:

• Ophthalmopathy (present in ~50% of patients) - including eyelid retraction, proptosis, and extraocular muscle enlargement 3, 4
• Thyroid bruit on auscultation - a highly specific finding 2
• Diffuse goiter with hypervascular appearance 5
• Pretibial myxoedema (dermopathy) - rare but pathognomonic 3, 4

Classic hyperthyroid symptoms include heat intolerance, tachycardia, anxiety, weight loss, and tremor 1. However, atypical presentations like "apathetic thyrotoxicosis" can delay diagnosis, particularly in elderly patients 6.

Laboratory Confirmation

The diagnostic algorithm follows this sequence 2, 5:

1. Initial screening: TSH (suppressed to <0.1 mU/L) with elevated free T4 and/or T3 6, 5
2. Confirmatory test: TSH receptor antibodies (TRAb) - positive in Graves' disease 1, 2, 3
3. If diagnosis unclear: Thyrotropin-releasing hormone (TRH) stimulation test 6

The presence of TRAb distinguishes Graves' disease from other causes of thyrotoxicosis such as toxic adenoma, toxic multinodular goiter, or subacute thyroiditis 1.

Role of Imaging

Imaging is NOT required for diagnosis in straightforward cases 1. However, specific imaging modalities have limited roles:

When Radioiodine Uptake and Scan Is Useful

• Ambiguous cases where toxic adenoma or multinodular goiter is suspected 1
• Shows diffusely increased uptake throughout the gland in Graves' disease 1
• Helps differentiate from destructive thyroiditis (which shows decreased uptake) 1
• Useful for planning radioactive iodine therapy 1

When Ultrasound May Be Helpful

• Adjunct to radioiodine scan to evaluate thyroid morphology and dimensions for RAI treatment planning 1
• Doppler ultrasound can show increased thyroid blood flow (sensitivity 95%, specificity 90%), though radionuclide uptake is still preferred 1
• Evaluates for suspicious nodules that may require biopsy 1
• Confirms diffusely enlarged, heterogeneous, hypervascular thyroid 5

When CT or MRI Is Indicated

• Thyroid eye disease - to evaluate extraocular muscle enlargement and orbital fat volume 2
• Not indicated for routine Graves' disease diagnosis 1

Differential Diagnosis to Exclude

The most common causes of thyrotoxicosis that must be differentiated include 1:

• Toxic adenoma - solitary hot nodule on scan
• Toxic multinodular goiter - multiple hot nodules
• Subacute thyroiditis - low uptake, painful thyroid, transient hyperthyroidism
• Lymphocytic thyroiditis - low uptake, may transition to hypothyroidism
• Factitious thyroid hormone ingestion - low uptake, no goiter

Critical Pitfalls to Avoid

• Failing to check TRAb when clinical features are ambiguous - this is the definitive confirmatory test 1, 2
• Ordering unnecessary imaging for straightforward cases with positive TRAb and typical presentation 1
• Missing ophthalmopathy on physical exam, which should prompt early endocrine referral 2
• Not recognizing atypical presentations in elderly patients who may present with apathetic thyrotoxicosis 6

When to Refer to Endocrinology

Immediate referral is warranted for 2:

• Presence of ophthalmopathy or thyroid bruit on examination
• Persistent hyperthyroidism >6 weeks despite initial treatment
• Severe symptoms affecting activities of daily living
• Pregnancy or planning pregnancy (requires medication adjustment)