Toxic Nodular Goiter

History and Epidemiology

Toxic nodular goiter, also known as Plummer disease, is a condition where one or more growths or nodules occur in the thyroid gland.1, 2 These nodules make excess thyroid hormone which is released into the bloodstream. This process results in a diagnosis of hyperthyroidism.

Toxic nodular goiter may mean that a single nodule (toxic nodule) is producing excess thyroid hormone. Another term for this is a toxic adenoma.1 Toxic nodular goiter may also mean that many nodules (toxic multinodular goiter) are present, with several producing excess thyroid hormone. With toxic multinodular goiter, some of the nodules may not be producing thyroid hormone.1 The extent of hyperthyroidism may range from subclinical to thyrotoxicosis.2

Toxic nodular goiter is the second most common cause of hyperthyroidism after Graves’ disease. It affects both men and women, particularly those who are aged 50 and older.

Toxic Nodular Goiter Presentation

Patients with toxic nodular goiter will typically present with symptoms of hyperthyroidism including intolerance to heat and excessive sweating, tachycardia and palpitations, tremors, unexplained weight loss, increased bowel frequency, irregular periods, and thinning of the skin and hair.2

Other toxic nodular goiter symptoms may include decreased libido, bedwetting (in children), muscle wasting and myopathy, atrial fibrillation, and upper eyelid dysfunction and staring.2 Symptoms caused by goiter may differ depending on the size of the mass and may include difficulty swallowing or breathing, hoarseness, and in severe cases, compression of the trachea.

Obtaining a complete history from the patient is helpful in making a diagnosis and should include age, gender, any iodine deficiency, medication use, exposure to radiation, where the patient spent most of their life. The last can help determine if they are from an area where goiter is endemic.2

Diagnostic Workup

Diagnosis of hyperthyroidism due to toxic nodular goiter is based on an evaluation of symptoms and a physical exam.1 Labs to check include thyroid function tests (TSH, T3, and T4), complete blood count, liver function tests, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid stimulating immunoglobulin.2 Patients with hyperthyroidism will typically have low TSH with high T3 and T4.

Other tests that aid in diagnosis include ultrasound, fine needle aspiration, thyroid scintigraphy, CT, MRI, and laryngoscopy.2 Upon physical examination, patients with an enlarged thyroid gland may have soft nodules that are movable when palpated.

Ultrasound results show the amount, size, and vascularity of nodules.2 Thyroid scintigraphy involves radioactive iodine or technetium, and helps determine if hyperthyroidism is due to toxic nodular goiter or another cause. Fine needle aspiration is done to determine if nodules are benign or malignant. CT and MRI may be helpful when the goiter is recurrent or lies partially or completely beneath the sternum. If surgery is planned to remove the goiter, laryngoscopy may be completed preoperatively to document the function of the vocal cords.

Differential Diagnosis

Other diagnoses to consider when evaluating hyperthyroidism include2:

  • Grave’s disease
  • Hashitoxicosis stage of Hashimoto’s thyroiditis
  • Thyroid nodules
  • Nodular nontoxic goiter
  • Papillary thyroid carcinoma
  • Subacute thyroiditis
  • Riedel thyroiditis
  • Struma ovarii

Toxic Nodular Goiter Management (Nonpharmacotherapy and Pharmacotherapy)

Toxic nodular goiter treatment depends on symptoms and lab values.1, 2 If the patient is not experiencing symptoms or the hyperthyroidism is subclinical, treatment may not be needed.2 Patients with subclinical hyperthyroidism should be advised to avoid imaging tests with iodinated contrast dye and avoid supplements containing iodine. Treatment for toxic nodular goiter should be started in patients with osteoporosis, osteopenia, and atrial fibrillation, or who are at risk for atrial fibrillation, even if they have subclinical hyperthyroidism.

Surgery is the standard treatment for toxic nodular goiter.2 This may include total or partial thyroidectomy, depending on the number of nodules. Selective removal of nodules helps preserve thyroid gland function but may lead to future recurrence of goiter.

Another treatment option for nonpregnant patients is radioactive iodine ablation (RAI) with sodium iodide-131.2 Typically, one dose of radiation is needed. Radiation shrinks the nodules but does not eliminate them. RAI may lead to an increased risk of secondary cancers from radiation. Other possible complications include tracheal compression, mild symptoms of thyrotoxicosis, hypothyroidism, worsening of atrial fibrillation and cardiac failure, and in rare cases, thyroid storm.

Ablation of toxic nodules with ethanol is an outpatient treatment that may be beneficial for patients that cannot undergo surgery.2 The process must be repeated once a week for several weeks and typically only helps in the short term.

While waiting for RAI and as a part of surgery preparation, propylthiouracil and methimazole may be given.2 Patients in the first trimester of pregnancy should be given propylthiouracil. Methimazole decreases the function of toxic nodules over time.2, 3 Methimazole is typically prescribed once every 8 hours.3 The daily dosage for adults is 15 to 60 mg depending on hyperthyroidism severity and is divided into 3 doses. The maintenance dosage is 5 to 15 mg daily. Pediatric dosing is based on body weight. The starting dosage is 0.4 mg/kg divided into 3 doses given every 8 hours. The maintenance dosage is typically 0.2 mg/kg given on the same schedule.

Monitoring Side Effects, Adverse Events, Drug-Drug Interactions

Prior to surgery, hypertension and tachycardia due to hyperthyroidism may be treated with beta blockers.2 Recurrence of toxic nodular goiter can occur, but is rare 10 years after surgery. Complications of surgery may include hypoparathyroidism, post-operative infection or bleeding, need for tracheostomy, and paralysis of vocal cords. Patients experiencing hypothyroidism after surgery should be treated with thyroid hormone.1 Because thyroidectomy disturbs the parathyroid glands, calcium level should be monitored after surgery.4

Side effects of methimazole include:

  • rash
  • nausea and vomiting
  • arthralgia, myalgia, and tingling
  • loss of taste
  • hair loss
  • headache and vertigo
  • drowsiness
  • neuritis
  • edema
  • changes in skin pigmentation
  • jaundice
  • inflammation of the salivary glands or lymph nodes

References

  1. American Thyroid Association. Toxic nodule and toxic multinodular goiter. Accessed September 9, 2022. https://www.thyroid.org/toxic-nodule-multinodular-goiter/
  2. Khalid N, Can AS. Plummer Disease. In: StatPearls. NCBI Bookshelf version. StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK565856/
  3. US Food and Drug Administration. Methimazole tablets. Revised January 2012. Accessed September 12, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/040350s016lbl.pdf
  4. Penn Medicine. What to expect before and after thyroid surgery. Accessed September 12, 2022. https://www.pennmedicine.org/for-patients-and-visitors/find-a-program-or-service/surgery/thyroid-surgery/what-to-expect-at-penn

Author Bio

Jen Seabright, PharmD, is a freelance medical writer based in Pittsburgh, PA.