Thyroid nodule medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

In case of active hot thyroid nodules that produce thyroid hormones, antithyroid drugs should be administered, that include beta-blockers, antithyroid drugs (methimazole,carbimazole,propylthiouracil), radioactive iodine, and thyroidectomy. If the nodule excision treatment (lobectomy, isthmectomy, and total thyroidectomy) is not curative, then treatment with postoperative radioactive iodine (RAI) remnant ablation and recombinant human TSH–mediated therapy is recommended.

Medical Therapy

Thyroid nodule

Malignant

Benign

Radioiodine therapy

Hyrperthyroidism evaluation

Hyperthyroidism

Euthyroid

Antithyroid drugs

No medical treatment required Monitor nodule

In case of active hot thyroid nodule that produce thyroid hormones, antithyroid drugs should be administered. The table below summarizes the treatment options in case of hot thyroid nodules:

Treatment	Mechanism	Route of administration	Advantages	Disadvantages	Special considerations
Beta-blockers	Block β-adrenergic receptors Propranolol may block conversion of T4 to T3	Oral	Ameliorates sweating, anxiety, tremulousness, palpitations, and tachycardia	Does not influence course of disease Administer just in case of hot thyroid nodule with thyrotoxicosis manifestations Use cautiously in patients with asthma, CHF , bradyarrhythmias or Raynaud’s phenomenon	Use cardioselective beta-blockers, especially in patients with COPD Use calcium-channel blockers as an alternative
Antithyroid drugs (methimazole, carbimazole,propylthiouracil)	Methimazole, carbimazole, and propylthiouracil block thyroid peroxidase and thyroid hormone synthesis Propylthiouracil also blocks conversion of thyroxine to triiodothyronine	Given as either a single, high fixed dose (e.g., 10–30 mg of methimazole or 200–600 mg of propylthiouracil daily) and adjusted as euthyroidism is achieved or combined with thyroxine to prevent hypothyroidism (“block–replace” regimen)	Outpatient therapy Low risk of hypothyroidism No radiation hazard or surgical risk	Frequent testing required unless block-replacement therapy is used Minor side effects in ≤5% of patients (rash, urticaria, arthralgia, fever, nausea, abnormalities of taste and smell)	Major side effects usually occur within first 3 months of therapy: Agranulocytosis in <0.2% of patients Hepatotoxicity in ≤0.1% Cholestasis for the thionamides and hepatocellular necrosis for propylthiouracil Antineutrophil cytoplasmic antibody–associated vasculitis in ≤0.1% of patients
Radioactive iodine (iodine-131)	Irradiation causes thyroid cell damage and cell death	Oral; activity either fixed (e.g., 15 mCi [555 MBq]) or calculated on the basis of goiter size and uptake and turnover investigations	Normally outpatient procedure Definitive therapy Low cost Few side effects Effectively reduces nodule size	Potential radiation hazards Adherence to a country’s particular radiation regulations Radiation thyroiditis Eventually destroys thyroid completely and leads to hypothyroidism in most patients	Should not be used in patients with active thyroid ophthalmopathy Contraindicated in women who are pregnant or breast-feeding and for 6 weeks after breast-feeding has stopped
Thyroidectomy	Most or all thyroid tissue is removed surgically	-----	Recurrence may happen in the case of metastasis and high stages of the cancer No radiation hazard Definitive histologic results Rapid relief of pressure symptoms	Most expensive therapy Hypothyroidism is the aim Risks associated with surgery and anesthesiology Minor complications in 1–2% of patients (bleeding, infection, scarring) Major complications in 1–4% (hypoparathyroidism, recurrent laryngeal-nerve damage)	Should just be performed in patients with high suspicion towards malignancy

Medical therapy goals in thyroid malignancies and differentiated thyroid cancers (DTC) include:

• To remove:
  • To remove primary tumor
  • To eliminate the disease that has extended beyond the thyroid capsule
  • To remove involved cervical lymph nodes
  • To minimize treatment-related morbidity
  • To permit accurate staging of the disease
  • To facilitate postoperative treatment with radioactive iodine where appropriate
  • To permit accurate long-term surveillance for disease recurrence
  • To minimize the risk of disease recurrence and metastatic spread

• A complete surgical resection of involved lymph nodes is one of the most important determinants of prognosis. Presence of lymph node involvement after the resection surgery represent a metastatic disease. The primary tumor in this case is mainly in the site of involved lymph node.

• Both RAI whole-body scanning (WBS) and measurement of serum thyroglobulin are affected by residual normal thyroid tissue. Where these approaches are utilized for long-term monitoring, near-total or total thyroidectomy is required.

• Adequate surgery is the most important treatment variable influencing prognosis, while radioactive iodine treatment, TSH suppression, and external beam irradiation each play adjunctive roles in at least some patients.

• There is a high risk of complication in thyroid nodule surgery. The most important factors determining surgical complications are:
  • The extent of surgery
  • The experience of the surgeon

• Removal of all thyroid tissue (both normal and nodular) in patients undergoing radioactive iodine remnant ablation or radioactive iodine treatment of residual or metastatic disease, is an important element of initial surgery. It has been recommended to perform a near total or total thyroidectomy, as evidences show it may reduce the risk for neoplasia recurrence within the contralateral lobe.

• Some experts recommend thyroid hormone administration in the case of benign thyroid nodule in iodine insufficient areas as a treatment. Thyroid hormone administration in larger than needed doses that decrease the serum TSH to subnormal levels, may lead to a decrease in nodule size and may be beneficial in regions of the world with borderline low iodine intake, as it may prevent new nodule formation. However, in iodine sufficient areas, there are insufficient evidences that administrating thyroid hormone may have a beneficial effect on benign thyroid nodules.

• If findings of FNA is suspicious for or diagnostic of papillary thyroid carcinoma in a pregnant woman, levothyroxin (T4) therapy should be considered as a primary therapy in order to keep the TSH in the normal range to avoid thyroid related problems in newborn.

postoperative RAI remnant ablation

If after complete thyroidectomy, still thyroid tissue is found, ablation of the remaining lobe with radioactive iodine can be considered as an alternative way to complete the resection of tissue.

Recombinant human TSH–mediated therapy

Indications of recombinant human TSH–mediated therapy:

• Patients with concurrent co-morbid illnesses that are more prone to adverse effects of iatrogenic hypothyroidism
• Patients with pituitary related disorders that can not produce TSH due to their underlying pituitary problem
• Patients in whom a delay in therapy might be associated with high morbidities

It is better to give a higher dosage of recombinant human TSH to these patients to avoid possible adverse effects.

Metastases treatment:

Treatment of endocrine metastases should be based on:

• Metastatic lesions size
• Avidity for RAI therapy
• Response to prior RAI therapy
• Absence of metastatic lesions

Metastases		Treatment
Pulmonary metastases	Micrometastases	RAI therapy As long as disease continues to concentrate RAI and respond clinically, repeat every 6–12 months Multiple repetitive RAI therapy sessions are shown to be associated with a greater possibility of complete remission
	Macronodular metastases	Repetitive RAI in the case of beneficial treatment is demonstrated: Decrease in the size of the lesions Decreasing thyroglobulin level Although repetitive treatments, survival rate is low and it is associated with poor prognosis RAI activity administration methods: Empirical therapy (100–200 mCi) Estimate calculation by lesional dosimetry To limit whole body retention to 80 mCi at 48 hours and 200 cGy to the red bone marrow
Brain metastases		Total surgical resection of CNS metastases External beam irradiation for CNS lesions that are not amenable to surgery In case of multiple metastases whole brain and spine irradiation should be considered
Bone metastases		Complete surgical resection of isolated symptomatic metastases RAI therapy of iodine-avid bone metastases

Complications

Radioactive iodine therapy:

Early complications:

• Gastrointestinal symptoms
• Radiation thyroiditis
• Sialadenitis/xerostomia
• Bone marrow suppression
• Gonadal damage
• Dry eye
• Nasolacrimal duct obstruction

Late complications:

• Secondary cancers
• Pulmonary fibrosis
• Pulmonary pneumonitis (rare)
• Permanent bone marrow suppression
• Genetic effects