What are the causes of T3 toxicosis?

Causes of T3 Toxicosis

T3 toxicosis is primarily caused by Graves' disease, toxic adenoma, toxic multinodular goiter, and subacute thyroiditis, with Graves' disease being most common in diffuse goiters and autonomous nodules most common overall (85% of cases). 1, 2

Definition and Pathophysiology

T3 toxicosis refers to a condition where there is elevated triiodothyronine (T3) with normal thyroxine (T4) levels, resulting in clinical thyrotoxicosis. Laboratory findings typically show:

• Elevated free T3 or total T3
• Normal free T4 or total T4
• Suppressed TSH

Major Causes of T3 Toxicosis

1. Autonomous Thyroid Function (Most Common - 85% of cases)

• Toxic adenoma (autonomous functioning nodule)
• Toxic multinodular goiter
  • These conditions preferentially produce T3 over T4, particularly in areas with iodine deficiency 2

2. Autoimmune Thyroid Disease

• Graves' disease - accounts for approximately 15% of T3 toxicosis cases but shows the highest rate of T3 elevation 2
• Hashimoto's thyroiditis (rare) - can occasionally present with transient T3 toxicosis 3

3. Inflammatory Conditions

• Subacute thyroiditis - characterized by inflammatory destruction of thyroid tissue with release of preformed hormone 1
• Lymphocytic thyroiditis - similar mechanism to subacute thyroiditis

4. Medication-Related Causes

• Amiodarone-induced thyroiditis
  • Type I: iodine-induced hyperthyroidism with excess production of T3
  • Type II: destructive thyroiditis with transient excess release of T3 4

5. Other Rare Causes

• Iodine deficiency - may contribute to preferential T3 secretion 3, 5
• TSH-secreting pituitary tumors (very rare) - one of the few causes with normal or elevated TSH 6
• Struma ovarii - ectopic thyroid tissue in ovarian teratoma 4
• Factitious ingestion of T3 - exogenous T3 intake 6

Diagnostic Approach

1. Laboratory testing:

   • TSH, free T3, free T4
   • Thyroid antibodies (TSH receptor antibodies, TPO antibodies)
   • Thyroglobulin (elevated in all causes except factitious ingestion) 6

2. Imaging:

   • Radioactive iodine uptake scan (RAIUS) - helps differentiate between causes:

     • Increased uptake: Graves' disease, toxic adenoma, toxic multinodular goiter
     • Decreased uptake: thyroiditis, factitious ingestion 4

   • Thyroid ultrasound with Doppler:

     • Increased blood flow: Graves' disease, toxic adenoma
     • Decreased blood flow: thyroiditis 4

Clinical Pearls and Pitfalls

• T3 toxicosis occurs in approximately 11% of untreated thyrotoxicosis cases 2
• When TSH is suppressed with normal free T4, T3 toxicosis should be suspected in about 40% of cases 2
• Iodine deficiency may be an important contributing factor to T3 toxicosis 3, 5
• Children can also develop T3 toxicosis, though it's less commonly reported 3, 5
• T3 toxicosis can occur during treatment of conventional thyrotoxicosis as T4 normalizes before T3 1
• In immune checkpoint inhibitor-induced thyroiditis, thyrotoxicosis is typically self-limited and resolves in weeks, often progressing to hypothyroidism 4

Management Considerations

Treatment should be directed at the underlying cause:

• For Graves' disease and toxic nodules: anti-thyroid medications (e.g., propylthiouracil), radioactive iodine, or surgery
• For thyroiditis: supportive care with beta-blockers for symptomatic relief
• For amiodarone-induced thyrotoxicosis: discontinuation of amiodarone if possible 4

Beta-blockers are recommended for symptomatic control in all forms of T3 toxicosis while the underlying cause is being addressed 4.