Thyroid nodule medical therapy

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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
Radioiodine therapy
Hyrperthyroidism evaluation
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 Oral
  • Does not influence course of disease
Antithyroid drugs (methimazole,


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:
Radioactive iodine


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
  • 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
  • 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
  • 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.[4]
  • There is a high risk of complication in thyroid nodule surgery. The most important factors determining surgical complications are:[6]
    • The extent of surgery
    • The experience of the surgeon
  • 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.

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.[11]

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.[12]

Metastases treatment:

Treatment of endocrine metastases should be based on:

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
Bone metastases


Radioactive iodine therapy: [13]

Early complications:

Late complications:


  1. Wang TS, Dubner S, Sznyter LA, Heller KS (2004). "Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes". Arch. Otolaryngol. Head Neck Surg. 130 (1): 110–3. doi:10.1001/archotol.130.1.110. PMID 14732779.
  2. Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS (1993). "Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989". Surgery. 114 (6): 1050–7, discussion 1057–8. PMID 8256208.
  3. Ito Y, Miyauchi A (2010). "Thyroidectomy and lymph node dissection in papillary thyroid carcinoma". J Thyroid Res. 2011: 634170. doi:10.4061/2011/634170. PMC 2989453. PMID 21113383.
  4. Mazzaferri EL (1999). "An overview of the management of papillary and follicular thyroid carcinoma". Thyroid. 9 (5): 421–7. doi:10.1089/thy.1999.9.421. PMID 10365671.
  5. Kim TH, Yang DS, Jung KY, Kim CY, Choi MS (2003). "Value of external irradiation for locally advanced papillary thyroid cancer". Int. J. Radiat. Oncol. Biol. Phys. 55 (4): 1006–12. PMID 12605980.
  6. Sosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA, Udelsman R (1998). "The importance of surgeon experience for clinical and economic outcomes from thyroidectomy". Ann. Surg. 228 (3): 320–30. PMC 1191485. PMID 9742915.
  7. Lin JD, Chao TC, Huang MJ, Weng HF, Tzen KY (1998). "Use of radioactive iodine for thyroid remnant ablation in well-differentiated thyroid carcinoma to replace thyroid reoperation". Am. J. Clin. Oncol. 21 (1): 77–81. PMID 9499265.
  8. Esnaola NF, Cantor SB, Sherman SI, Lee JE, Evans DB (2001). "Optimal treatment strategy in patients with papillary thyroid cancer: a decision analysis". Surgery. 130 (6): 921–30. doi:10.1067/msy.2001.118370. PMID 11742318.
  9. Kuy S, Roman SA, Desai R, Sosa JA (2009). "Outcomes following thyroid and parathyroid surgery in pregnant women". Arch Surg. 144 (5): 399–406, discussion 406. doi:10.1001/archsurg.2009.48. PMID 19451480.
  10. Rosen IB, Korman M, Walfish PG (1997). "Thyroid nodular disease in pregnancy: current diagnosis and management". Clin Obstet Gynecol. 40 (1): 81–9. PMID 9103951.
  11. Randolph GW, Daniels GH (2002). "Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid". Thyroid. 12 (11): 989–96. doi:10.1089/105072502320908321. PMID 12490076.
  12. Braga M, Ringel MD, Cooper DS (2001). "Sudden enlargement of local recurrent thyroid tumor after recombinant human TSH administration". J. Clin. Endocrinol. Metab. 86 (11): 5148–51. doi:10.1210/jcem.86.11.8055. PMID 11701668.
  13. Fard-Esfahani A, Emami-Ardekani A, Fallahi B, Fard-Esfahani P, Beiki D, Hassanzadeh-Rad A, Eftekhari M (2014). "Adverse effects of radioactive iodine-131 treatment for differentiated thyroid carcinoma". Nucl Med Commun. 35 (8): 808–17. doi:10.1097/MNM.0000000000000132. PMID 24751702.

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