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{{Thyroid nodule}}
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==Overview==
==Overview==
In case of active hot thyroid nodules that produce [[thyroid hormones]], [[Antithyroid agent|antithyroid drugs]] should be administered, that include [[beta-blockers]], antithyroid drugs ([[methimazole]],[[carbimazole]],[[propylthiouracil]]), [[Iodine-131|radioactive iodine]], and [[thyroidectomy]]. If the nodule excision treatment ([[lobectomy]], [[isthmectomy]], and total [[thyroidectomy]]) is not curative, then treatment with postoperative [[radioactive iodine]] ([[RAI1|RAI]]) remnant ablation and recombinant human TSH–mediated therapy is recommended.


==Medical Therapy==
==Medical Therapy ==
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{{familytree | | | | | | | | | | | | | A01 | | | | | | | | | A01=Thyroid nodule}}
{{familytree | | | | | | | | | | | | | |!| | | | | | | | | | | | }}
{{familytree | | | | | | |,|-|-|-|-|-|-|^|-|-|-|-|-|-|.| | | | | | }}
{{familytree | | | | | | C01 | | | | | | | | | | | | C03 | | | | | C01= Malignant |C03= Benign}}
{{familytree | | | | | | |!| | | | | | | | | | | | | |!| | | | | |}}
{{familytree | | | | | | C01 | | | | | | | | | | | | C02 | | | | | C01= Radioiodine therapy | C02 = Hyrperthyroidism evaluation}}
{{familytree | | | | | | | | | | | | | | | | | | |,|-|^|-|.| | | | |}}
{{familytree | | | | | | | | | | | | | | | | | | C02 | | C03 | | | | | | C02= Hyperthyroidism | C03 = Euthyroid }}
{{familytree | | | | | | | | | | | | | | | | | | |!| | | |!| | | | | | }}
{{familytree | | | | | | | | | | | | | | | | | | C02 | | C03 | | | | | C02= Antithyroid drugs | C03 = No medical treatment required <br> Monitor nodule }}
{{familytree/end}}


The goals of initial therapy of differentiated thyroid cancer (DTC) include:
In case of active hot thyroid nodule that produce [[thyroid hormones]], [[Antithyroid agent|antithyroid drugs]] should be administered. The table below summarizes the treatment options in case of hot thyroid nodules:
* To remove the primary tumor, disease that has extended beyond the thyroid capsule, and involved cervical lymph nodes. Completeness of surgical resection is an important determinant of outcome, while residual metastatic lymph nodes represent the most common site of disease persistence=recurrence<ref name="pmid14732779">{{cite journal |vauthors=Wang TS, Dubner S, Sznyter LA, Heller KS |title=Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes |journal=Arch. Otolaryngol. Head Neck Surg. |volume=130 |issue=1 |pages=110–3 |year=2004 |pmid=14732779 |doi=10.1001/archotol.130.1.110 |url=}}</ref> <ref name="pmid8256208">{{cite journal |vauthors=Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS |title=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 |journal=Surgery |volume=114 |issue=6 |pages=1050–7; discussion 1057–8 |year=1993 |pmid=8256208 |doi= |url=}}</ref><ref name="pmid21113383">{{cite journal |vauthors=Ito Y, Miyauchi A |title=Thyroidectomy and lymph node dissection in papillary thyroid carcinoma |journal=J Thyroid Res |volume=2011 |issue= |pages=634170 |year=2010 |pmid=21113383 |pmc=2989453 |doi=10.4061/2011/634170 |url=}}</ref>
* To minimize treatment-related morbidity. The extent of surgery and the experience of the surgeon both play important roles in determining the risk of surgical complications<ref name="pmid9742915">{{cite journal |vauthors=Sosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA, Udelsman R |title=The importance of surgeon experience for clinical and economic outcomes from thyroidectomy |journal=Ann. Surg. |volume=228 |issue=3 |pages=320–30 |year=1998 |pmid=9742915 |pmc=1191485 |doi= |url=}}</ref>
* To permit accurate staging of the disease. Because disease staging can assist with initial prognostication, disease management, and follow-up strategies, accurate postoperative staging is a crucial element in the management of patients with DTC <ref name="pmid26171797">{{cite journal |vauthors=Carhill AA, Litofsky DR, Ross DS, Jonklaas J, Cooper DS, Brierley JD, Ladenson PW, Ain KB, Fein HG, Haugen BR, Magner J, Skarulis MC, Steward DL, Xing M, Maxon HR, Sherman SI |title=Long-Term Outcomes Following Therapy in Differentiated Thyroid Carcinoma: NTCTCS Registry Analysis 1987-2012 |journal=J. Clin. Endocrinol. Metab. |volume=100 |issue=9 |pages=3270–9 |year=2015 |pmid=26171797 |pmc=5393522 |doi=10.1210/JC.2015-1346 |url=}}</ref><ref name="pmid12016468">{{cite journal |vauthors=Hay ID, Thompson GB, Grant CS, Bergstralh EJ, Dvorak CE, Gorman CA, Maurer MS, McIver B, Mullan BP, Oberg AL, Powell CC, van Heerden JA, Goellner JR |title=Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients |journal=World J Surg |volume=26 |issue=8 |pages=879–85 |year=2002 |pmid=12016468 |doi=10.1007/s00268-002-6612-1 |url=}}</ref>
* To facilitate postoperative treatment with radioactive iodine, where appropriate. For patients undergoing RAI remnant ablation, or RAI treatment of residual or metastatic disease, removal of all normal thyroid tissue is an important element of initial surgery . Near total or total thyroidectomy also may reduce the risk for recurrence within the contralateral lobe <ref name="pmid9499265">{{cite journal |vauthors=Lin JD, Chao TC, Huang MJ, Weng HF, Tzen KY |title=Use of radioactive iodine for thyroid remnant ablation in well-differentiated thyroid carcinoma to replace thyroid reoperation |journal=Am. J. Clin. Oncol. |volume=21 |issue=1 |pages=77–81 |year=1998 |pmid=9499265 |doi= |url=}}</ref><ref name="pmid11742318">{{cite journal |vauthors=Esnaola NF, Cantor SB, Sherman SI, Lee JE, Evans DB |title=Optimal treatment strategy in patients with papillary thyroid cancer: a decision analysis |journal=Surgery |volume=130 |issue=6 |pages=921–30 |year=2001 |pmid=11742318 |doi=10.1067/msy.2001.118370 |url=}}</ref>
* To permit accurate long-term surveillance for disease recurrence. Both RAI whole-body scanning (WBS) and measurement of serum Tg are affected by residual normal thyroid tissue. Where these approaches are utilized for long-term monitoring, near-total or totalthyroidectomy is required<ref name="pmid10365671">{{cite journal |vauthors=Mazzaferri EL |title=An overview of the management of papillary and follicular thyroid carcinoma |journal=Thyroid |volume=9 |issue=5 |pages=421–7 |year=1999 |pmid=10365671 |doi=10.1089/thy.1999.9.421 |url=}}</ref>
* To minimize the risk of disease recurrence and metastatic spread. 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<ref name="pmid12605980">{{cite journal |vauthors=Kim TH, Yang DS, Jung KY, Kim CY, Choi MS |title=Value of external irradiation for locally advanced papillary thyroid cancer |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=55 |issue=4 |pages=1006–12 |year=2003 |pmid=12605980 |doi= |url=}}</ref>
It is recommended to use thryoid hormone in iodine insufficient areas as a treatment for benign thyroid nodules. Thyroid hormone in doses that suppress the serum TSH to subnormal levels may result in a decrease in nodule size and may prevent the appearance of new nodules in regions of the world with borderline low iodine intake but in iodine sufficient areas, there are insufficient evidence of beneficial effect of thyroid hormone treatment for benign thyroid nodules
In pregnant women with FNA that is suspicious for or diagnostic of PTC, consideration could be given to administration of LT4 therapy to keep the TSH in the range of 0.1–1 mU=L<ref name="pmid19451480">{{cite journal |vauthors=Kuy S, Roman SA, Desai R, Sosa JA |title=Outcomes following thyroid and parathyroid surgery in pregnant women |journal=Arch Surg |volume=144 |issue=5 |pages=399–406; discussion 406 |year=2009 |pmid=19451480 |doi=10.1001/archsurg.2009.48 |url=}}</ref><ref name="pmid9103951">{{cite journal |vauthors=Rosen IB, Korman M, Walfish PG |title=Thyroid nodular disease in pregnancy: current diagnosis and management |journal=Clin Obstet Gynecol |volume=40 |issue=1 |pages=81–9 |year=1997 |pmid=9103951 |doi= |url=}}</ref>
==== postoperative RAI remnant ablation ====
Ablation of the remaining lobe with radioactive iodine has been used as an alternative to completion thyroidectomy<ref name="pmid12490076">{{cite journal |vauthors=Randolph GW, Daniels GH |title=Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid |journal=Thyroid |volume=12 |issue=11 |pages=989–96 |year=2002 |pmid=12490076 |doi=10.1089/105072502320908321 |url=}}</ref>
==== Recombinant human TSH–mediated therapy ====
Recombinant human TSH–mediated therapy may be indicated in selected patients with underlying comorbidities making iatrogenic hypothyroidism potentially risky, in patients with pituitary disease who are unable to raise their serum TSH, or in patients in whom a delay in therapy might be deleterious. Such patients should be given the same or higher activity that would have been given had they been prepared with hypothyroidism or a dosimetrically determined activity<ref name="pmid11701668">{{cite journal |vauthors=Braga M, Ringel MD, Cooper DS |title=Sudden enlargement of local recurrent thyroid tumor after recombinant human TSH administration |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue=11 |pages=5148–51 |year=2001 |pmid=11701668 |doi=10.1210/jcem.86.11.8055 |url=}}</ref>
=== Metastases treatment: ===
Treatment of endocrine metastases should be based on:
* Size of metastatic lesions (macronodular typically detected by chest radiography; micronodular typically detected by CT; lesions beneath the resolution of CT)
* Avidity for RAI and, if applicable, response to prior RAI therapy
* Stability absence of metastatic lesions
{| class="wikitable"
{| class="wikitable"
!Metastases
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Treatment
!
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mechanism
!Treatment
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Route of administration
!
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Advantages
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disadvantages
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Special considerations
|-
|-
|pulmonary metastases
![[Beta-blockers]]
|Micrometastases
|RAI therapy, and repeated every 6–12 months as long as disease continues to concentrate RAI and respond clinically, because the highest rates of complete remission are reported in these subgroups
|
|
* [[Beta adrenergic blockade|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 [[Beta-blockers|cardioselective beta-blockers]], especially in patients with [[COPD]]
* Use [[calcium-channel blockers]] as an alternative
|-
|-
! Antithyroid drugs ([[methimazole]],
[[carbimazole]],[[propylthiouracil]])
|
|
|macronodular metastases
* [[Methimazole]], [[carbimazole]], and [[propylthiouracil]] block [[thyroid peroxidase]] and [[Thyroid hormone|thyroid hormone synthesis]]
|RAI and treatment should be repeated when objective benefit is demonstrated (decrease in the size of the lesions, decreasing Tg), but complete remission is not common and survival remains poor. The selection of RAI activity to administer can be made empirically (100–200 mCi) or estimated by lesional dosimetry or dosimetry to limit wholebody retention to 80 mCi at 48 hours and 200 cGy to the red bone marrow.
 
* [[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]]
* [[Anti-neutrophil cytoplasmic antibody|Antineutrophil cytoplasmic antibody]]–associated [[vasculitis]] in ≤0.1% of patients
|-
![[Iodine-131|Radioactive iodine]]
(iodine-131)
|
* [[Irradiation]] causes [[thyroid]] [[Cell (biology)|cell]] damage and [[Cell (biology)|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 opthalmopathy|thyroid ophthalmopathy]]
* Contraindicated in women who are [[pregnant]] or [[breast-feeding]] and for 6 weeks after [[breast-feeding]] has stopped
|-
|-
|brain metastases
! [[Thyroidectomy]]
|
|
|Complete surgical resection of CNS metastases should be considered regardless of RAI avidity
* Most or all thyroid tissue is removed surgically
CNS lesions that are not amenable to surgery should be considered for external beam irradiation.
| -----
|
* 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|recurrent laryngeal-nerve]] damage)
|
* Should just be performed in patients with high suspicion towards [[malignancy]]
|}
 
Medical therapy goals in [[Thyroid malignancy|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]].<ref name="pmid14732779">{{cite journal |vauthors=Wang TS, Dubner S, Sznyter LA, Heller KS |title=Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes |journal=Arch. Otolaryngol. Head Neck Surg. |volume=130 |issue=1 |pages=110–3 |year=2004 |pmid=14732779 |doi=10.1001/archotol.130.1.110 |url=}}</ref><ref name="pmid8256208">{{cite journal |vauthors=Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS |title=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 |journal=Surgery |volume=114 |issue=6 |pages=1050–7; discussion 1057–8 |year=1993 |pmid=8256208 |doi= |url=}}</ref><ref name="pmid21113383">{{cite journal |vauthors=Ito Y, Miyauchi A |title=Thyroidectomy and lymph node dissection in papillary thyroid carcinoma |journal=J Thyroid Res |volume=2011 |issue= |pages=634170 |year=2010 |pmid=21113383 |pmc=2989453 |doi=10.4061/2011/634170 |url=}}</ref>
 
* Both [[Radioactive iodine uptake|RAI]] whole-body scanning (WBS) and measurement of serum [[thyroglobulin]] are affected by residual normal [[Thyroid|thyroid tissue]]. Where these approaches are utilized for long-term monitoring, near-total or total [[thyroidectomy]] is required.<ref name="pmid10365671">{{cite journal |vauthors=Mazzaferri EL |title=An overview of the management of papillary and follicular thyroid carcinoma |journal=Thyroid |volume=9 |issue=5 |pages=421–7 |year=1999 |pmid=10365671 |doi=10.1089/thy.1999.9.421 |url=}}</ref>
 
* Adequate surgery is the most important treatment variable influencing [[prognosis]], while [[radioactive iodine]] treatment, [[TSH]] suppression, and [[External beam radiotherapy|external beam irradiation]] each play adjunctive roles in at least some patients.<ref name="pmid12605980">{{cite journal |vauthors=Kim TH, Yang DS, Jung KY, Kim CY, Choi MS |title=Value of external irradiation for locally advanced papillary thyroid cancer |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=55 |issue=4 |pages=1006–12 |year=2003 |pmid=12605980 |doi= |url=}}</ref>
 
* There is a high risk of complication in thyroid nodule surgery. The most important factors determining surgical complications are:<ref name="pmid9742915">{{cite journal |vauthors=Sosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA, Udelsman R |title=The importance of surgeon experience for clinical and economic outcomes from thyroidectomy |journal=Ann. Surg. |volume=228 |issue=3 |pages=320–30 |year=1998 |pmid=9742915 |pmc=1191485 |doi= |url=}}</ref>
** The extent of [[surgery]]
** The experience of the surgeon


Whole brain and spine irradiation could be considered if multiple metastases are present.
* Removal of all [[Thyroid|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. <ref name="pmid9499265">{{cite journal |vauthors=Lin JD, Chao TC, Huang MJ, Weng HF, Tzen KY |title=Use of radioactive iodine for thyroid remnant ablation in well-differentiated thyroid carcinoma to replace thyroid reoperation |journal=Am. J. Clin. Oncol. |volume=21 |issue=1 |pages=77–81 |year=1998 |pmid=9499265 |doi= |url=}}</ref><ref name="pmid11742318">{{cite journal |vauthors=Esnaola NF, Cantor SB, Sherman SI, Lee JE, Evans DB |title=Optimal treatment strategy in patients with papillary thyroid cancer: a decision analysis |journal=Surgery |volume=130 |issue=6 |pages=921–30 |year=2001 |pmid=11742318 |doi=10.1067/msy.2001.118370 |url=}}</ref>
 
* 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 cancer|papillary thyroid carcinoma]] in a pregnant woman, [[Levothyroxine|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.<ref name="pmid19451480">{{cite journal |vauthors=Kuy S, Roman SA, Desai R, Sosa JA |title=Outcomes following thyroid and parathyroid surgery in pregnant women |journal=Arch Surg |volume=144 |issue=5 |pages=399–406; discussion 406 |year=2009 |pmid=19451480 |doi=10.1001/archsurg.2009.48 |url=}}</ref><ref name="pmid9103951">{{cite journal |vauthors=Rosen IB, Korman M, Walfish PG |title=Thyroid nodular disease in pregnancy: current diagnosis and management |journal=Clin Obstet Gynecol |volume=40 |issue=1 |pages=81–9 |year=1997 |pmid=9103951 |doi= |url=}}</ref>
 
==== postoperative RAI remnant ablation ====
If after complete [[thyroidectomy]], still [[Thyroid|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.<ref name="pmid12490076">{{cite journal |vauthors=Randolph GW, Daniels GH |title=Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid |journal=Thyroid |volume=12 |issue=11 |pages=989–96 |year=2002 |pmid=12490076 |doi=10.1089/105072502320908321 |url=}}</ref>
==== 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.<ref name="pmid11701668">{{cite journal |vauthors=Braga M, Ringel MD, Cooper DS |title=Sudden enlargement of local recurrent thyroid tumor after recombinant human TSH administration |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue=11 |pages=5148–51 |year=2001 |pmid=11701668 |doi=10.1210/jcem.86.11.8055 |url=}}</ref>
=== Metastases treatment: ===
Treatment of [[endocrine]] [[metastases]] should be based on:
* [[Metastasis|Metastatic]] lesions size
* Avidity for [[Radioactive iodine uptake|RAI]] therapy
* Response to prior [[Radioactive iodine uptake|RAI]] therapy
* Absence of [[metastatic]] lesions
{| class="wikitable"
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Metastases
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Treatment
|-
! rowspan="2" |[[Pulmonary]] [[metastases]]
!Micrometastases
|
* [[RAI1|RAI]] therapy
* As long as disease continues to concentrate [[Radioactive iodine uptake|RAI]] and respond clinically, repeat every 6–12 months
** Multiple repetitive [[RAIU|RAI]] therapy sessions are shown to be associated with a greater possibility of complete remission
|-
!Macronodular [[metastases]]
|
|
* Repetitive [[Radioactive iodine uptake|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]]
* [[Radioactive iodine uptake|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]]
|-
|-
|bone metastases
! colspan="2" |[[Brain]] [[metastases]]
|
|
|Complete surgical resection of isolated symptomatic metastases
* Total surgical resection of [[CNS]] [[metastases]]
RAI therapy of iodine-avid bone metastases
* [[External beam radiotherapy|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
|-
! colspan="2" |[[Bone]] [[metastases]]
|
|
* Complete surgical resection of isolated [[symptomatic]] [[metastases]]
* [[Radioactive iodine uptake|RAI]] therapy of iodine-avid [[bone metastases]]
|}
|}
Pulmonary pneumonitis and fibrosis are rare complications of high-dose radioactive iodine treatment
 
=== Complications ===
 
===== Radioactive iodine therapy: <ref name="pmid24751702">{{cite journal |vauthors=Fard-Esfahani A, Emami-Ardekani A, Fallahi B, Fard-Esfahani P, Beiki D, Hassanzadeh-Rad A, Eftekhari M |title=Adverse effects of radioactive iodine-131 treatment for differentiated thyroid carcinoma |journal=Nucl Med Commun |volume=35 |issue=8 |pages=808–17 |year=2014 |pmid=24751702 |doi=10.1097/MNM.0000000000000132 |url=}}</ref>=====
Early complications:
* [[Gastrointestinal]] symptoms
* Radiation thyroiditis
* [[Sialadenitis]]/[[xerostomia]]
* [[Bone marrow suppression]]
* [[Gonadal]] damage
* [[Dry eye]]
* [[Nasolacrimal duct]] obstruction
Late complications:
* Secondary [[cancers]]
* [[Pulmonary fibrosis]]
* [[Pneumonitis|Pulmonary pneumonitis]] (rare)
* Permanent [[bone marrow suppression]]
* [[Genetic]] effects
 
==References==
==References==
{{reflist|2}}
{{reflist|2}}

Latest revision as of 17:33, 2 November 2017


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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 Oral
  • Does not influence course of disease
Antithyroid drugs (methimazole,

carbimazole,propylthiouracil)

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

(iodine-131)

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
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
  • 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

Complications

Radioactive iodine therapy: [13]

Early complications:

Late complications:

References

  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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