Toxic Adenoma

  • Pathophysiology/Etiology
    • A toxic adenoma is a benign, solitary thyroid nodule that autonomously produces excessive thyroid hormone, independent of TSH regulation.
    • This leads to hyperthyroidism, which can be overt (low TSH, high T4/T3) or subclinical (low TSH, normal T4/T3).
    • The underlying cause is often a somatic activating mutation in the TSH receptor (TSHR) or Gs-alpha gene, leading to constitutive hormone production.
    • More common in women, older adults, and individuals in iodine-deficient regions.
  • Clinical Presentation
    • Symptoms of Hyperthyroidism: Weight loss despite increased appetite, heat intolerance, sweating, anxiety, palpitations, tremors, and fatigue.
    • Local Symptoms: A palpable, often painless, neck nodule. Large nodules may cause dysphagia or a feeling of fullness in the throat.
    • Unlike Graves’ disease, there are no autoimmune features like exophthalmos or pretibial myxedema.
  • Diagnosis
    • Thyroid Function Tests (TFTs): Show a low or undetectable TSH with an elevated free T4 and/or T3.
    • Radionuclide Thyroid Scan (Scintigraphy): This is the key diagnostic test. It reveals a focal area of intense radioiodine uptake (a “hot nodule”) with suppressed uptake in the surrounding thyroid tissue.
    • Thyroid Ultrasound: Used to assess the size and characteristics of the nodule.
    • Antibodies: TSH receptor antibodies (TRAb) are absent, which helps differentiate it from Graves’ disease.
  • DDx (Differential Diagnosis)
    • Graves’ Disease: Also causes hyperthyroidism but is an autoimmune disorder. Diagnosis is supported by positive TSH receptor antibodies (TRAb), diffuse uptake on thyroid scan, and clinical signs like exophthalmos.
    • Toxic Multinodular Goiter (TMNG): Presents with multiple “hot” nodules on thyroid scan, often in older patients from iodine-deficient areas.
    • Thyroiditis (Subacute/Painless): Causes transient hyperthyroidism due to hormone leakage from an inflamed gland, resulting in decreased radioiodine uptake.
  • Management/Treatment
    • Symptom Control: Beta-blockers (e.g., atenolol) are used initially to manage adrenergic symptoms like palpitations and tremors.
    • Definitive Treatment: The goal is to eliminate the hyperfunctioning nodule. Options include:
      • Radioactive Iodine (RAI) Therapy (I-131): The most common treatment in the U.S. The “hot” nodule preferentially takes up the I-131, leading to its destruction. This has a high success rate and a low risk of subsequent hypothyroidism compared to RAI for Graves’ disease.
      • Surgery (Thyroid Lobectomy): Recommended for patients with large nodules causing compressive symptoms, if malignancy is suspected, or when RAI is contraindicated (e.g., pregnancy).
      • Antithyroid Drugs (e.g., Methimazole): Used to achieve a euthyroid state before definitive therapy but are not a long-term solution as hyperthyroidism typically recurs after cessation.
  • Key Associations/Complications
    • Complications: Untreated hyperthyroidism can lead to cardiac complications (e.g., atrial fibrillation) and bone loss (osteoporosis).
    • Prognosis: Excellent with definitive treatment. Toxic adenomas are almost always benign.
    • Buzzwords: “Hot nodule” on thyroid scan, absent TRAb, focal/unilateral hyperthyroidism.