Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

Radioactive Iodine (RAI) for Thyroid Cancer – Who Really Needs It in 2026?

Radioactive iodine (RAI, I-131) is used after thyroid surgery in selected cases of differentiated thyroid cancer (papillary and follicular). Its goals are:

to destroy tiny remnants of thyroid tissue (“remnant ablation”), to reduce the risk of recurrence (“adjuvant therapy”), or to treat known persistent or metastatic disease. 

Over the last decade, we’ve learned that many low-risk patients do just as well without RAI, so we now use it much more selectively.

1. When is RAI usually recommended?

Most societies (ATA, ETA, NCCN, SNMMI/EANM) and recent data support using RAI mainly for intermediate- and high-risk disease. 

RAI is typically recommended when:

High-risk disease (ATA high risk) Gross extrathyroidal extension Large primary tumors Extensive nodal disease (multiple or large metastatic nodes) Distant metastases (lung, bone, etc.)  Selected intermediate-risk disease Microscopic extrathyroidal extension Multiple involved lymph nodes Aggressive histologic variants Here, RAI is considered and individualized based on age, tumor biology, thyroglobulin, and patient preferences.  Persistent or recurrent disease Elevated or rising thyroglobulin after surgery Iodine-avid metastatic disease on imaging 

2. When is RAI often not needed?

For many patients with true low-risk differentiated thyroid cancer, excellent outcomes can be achieved with surgery and careful follow-up without RAI.

The ESTIMABL2 randomized trial showed that in low-risk patients (small, node-negative tumors), follow-up without RAI was non-inferior to routine RAI at 5 years, with no loss of oncologic opportunity.  The 2015 ATA guidelines and subsequent analyses recommend that RAI is not routinely used in ATA low-risk patients, particularly for tumors ≤4 cm without worrisome features. 

For many patients, this means less treatment, fewer side effects, and the same excellent prognosis.

3. Common short-term side effects

Most side effects are mild and temporary:

Neck discomfort or swelling Nausea, metallic taste, or loss of taste Dry mouth or thick saliva Swollen, tender salivary glands (parotid/submandibular sialadenitis) Fatigue for days to weeks Temporary changes in blood counts (mild bone-marrow suppression) 

Some patients also report:

Dry eyes, tearing problems, or a “gritty” sensation Nasal dryness and crusting 

4. Less common or long-term risks

These are less frequent but important to discuss before treatment:

Chronic salivary gland dysfunction Persistent dry mouth (xerostomia) Difficulty with chewing/swallowing dry foods Increased dental caries and oral infections  Lacrimal (tear duct) problems Nasolacrimal duct obstruction → watery or irritated eyes Sometimes requires ophthalmology intervention  Fertility and pregnancy Transient effects on sperm parameters and ovarian reserve have been described at higher cumulative doses, so we usually recommend avoiding pregnancy for 6–12 months after RAI and consider sperm banking in selected young men likely to need repeated high-dose treatments.  Second primary malignancies (very rare) Large observational studies suggest a small increase in risk of secondary malignancies (e.g., leukemia, salivary gland tumors) at higher cumulative doses, which reinforces the move toward lower doses and more selective use. 

5. How we minimize and manage side effects

a) Use the lowest effective dose

Trials such as HiLo and related studies have shown that low-dose (≈30 mCi) RAI with recombinant TSH is as effective as higher doses for remnant ablation in low-risk patients, with fewer side effects. 

b) Protect salivary glands

Aggressive hydration for several days after therapy Frequent chewing (sugar-free gum) and sour candies starting after the first 24 hours, as guided by the treating team, to stimulate saliva flow Good oral and dental hygiene, with dental follow-up for patients receiving higher doses In selected patients with significant chronic symptoms, sialogogues (pilocarpine, cevimeline) and targeted ENT/salivary management may help 

c) Protect eyes and tear ducts

Artificial tears and ocular lubricants from the early post-treatment period Early evaluation by ophthalmology if tearing, pain, or recurrent eye infections develop In selected complex cases, interventional approaches to the nasolacrimal duct can be considered. 

d) Monitor blood counts and overall health

Baseline and follow-up blood counts in patients receiving moderate/high doses Correct nutritional deficiencies and manage anemia or other cytopenias if they occur 

e) Clear radiation-safety instructions

Temporary restrictions on close contact with children and pregnant women, sleeping in the same bed, and travel, adapted to the administered dose and national regulations. 

6. Take-home messages for patients

Not everyone with thyroid cancer needs RAI. Many low-risk patients do very well with surgery and surveillance alone. When indicated, RAI can reduce recurrence and treat iodine-avid metastatic disease, particularly in higher-risk patients.  Most side effects are short-term and manageable; long-term complications are less common and are more likely with higher cumulative doses. Careful risk stratification, dose selection, and prevention strategies (hydration, salivary and ocular care, blood count monitoring) are key to minimizing toxicity. Decisions about RAI should be personalized, ideally made in a multidisciplinary team with a thyroid surgeon, endocrinologist, and nuclear medicine specialist.

Suggested references (for the post footer)

Haugen BR, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016.  Pacini F, et al. What are the indications for post-surgical radioiodine therapy in differentiated thyroid cancer? Eur Thyroid J. 2022.  Leboulleux S, et al. Thyroidectomy without radioiodine in patients with low-risk thyroid cancer (ESTIMABL2, 5-year follow-up). Lancet Diabetes Endocrinol. 2025.  Mallick U, et al. Ablation with low-dose radioiodine and thyrotropin alfa. N Engl J Med. 2012. (HiLo trial)  Nguyen NC, et al. Radioactive Iodine Therapy in Differentiated Thyroid Cancer: An Update on Dose Recommendations and Risk of Secondary Primary Malignancies. Semin Nucl Med. 2024.  Orosco RK, et al. Radioactive iodine in differentiated thyroid cancer. Head Neck. 2019.  Jeong SY, et al. Salivary gland function 5 years after radioactive iodine ablation. J Nucl Med. 2013.  Solans R, et al. Salivary and lacrimal gland dysfunction after radioiodine therapy. J Nucl Med. 2001.  Baudin C, et al. Dysfunction of the salivary and lacrimal glands after radioiodine therapy: START study. Thyroid. 2023.  Rahmanipour E, et al. Eye-related adverse events after I-131 radioiodine therapy: systematic review. Endocr Pract. 2024.  Berta DM, et al. Effect of radioactive iodine therapy on hematological parameters: systematic review and meta-analysis. Front Endocrinol. 2025. 

Author:

Rodrigo Arrangoiz, MD

Surgical Oncologist & Thyroid Surgeon

Mount Sinai Medical Center – Miami, FL

• Mucinous breast cancer is a slow-growing neoplasm:

• • With an estimated growth rate of one third of invasive breast cancer no special type

• • This malignancy also shows:

    • Fewer axillary lymph node metastases

• Conventional, pure mucinous carcinomas:

  • Exhibit a rate of metastasis of less than 15%

• Current studies have shown that a subset of patients diagnosed with mucinous carcinoma:

  • Do not manifest such favorable outcomes:

• • • Some authors suggested that specific subtypes of pure mucinous carcinoma:

  • • • Those with a micropapillary pattern demonstrate significantly worse prognosis:

    • • • In one  study more than half of the patients with this particular type of pattern were found to have vascular invasion and synchronous axillary lymph nodes

Age plays an important role in how thyroid cancer behaves, how it is staged, and how it is treated.

👶 Thyroid cancer in younger patients

More common in women Often presents with lymph node involvement Tumors may look aggressive on imaging 👉 Despite this, prognosis is excellent

✔️ Patients under 55 years are staged differently

✔️ Even with lymph nodes, survival rates exceed 98–99%

✔️ Treatment focuses on curing disease while preserving quality of life

👴 Thyroid cancer in older patients

Less common, but tumors may be biologically more aggressive Higher likelihood of: Extrathyroidal extension Distant metastases Higher-stage disease Outcomes are still often very good, but treatment may need to be more comprehensive

⚖️ Why age matters

Age helps determine:

AJCC stage Expected prognosis Intensity of treatment and follow-up

🧠 Important clarification:

Age alone does not determine outcome.

➡️ Tumor biology, pathology, and response to treatment matter most.

🦋 What this means for patients

Thyroid cancer is not the same disease in every patient.

The goal is personalized, risk-adapted care—not one-size-fits-all treatment.

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Young patients do extremely well.

Older patients still have excellent outcomes with expert, individualized care.

📚 References

AJCC Cancer Staging Manual, 8th Edition Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Risk-adapted management of thyroid cancer. Lancet Diabetes Endocrinol

• Updated 2018 American Society for Radiation Oncology (ASTRO) guidelines:
  • State that patients 50 and younger, and 51 to 70 years of age with high-grade tumors or positive margins:
    • Should receive a tumor bed boost
  • A boost may be omitted for women:
    • Older than 70 with hormone receptor positive and low- or intermediate-grade disease with widely negative margins (> 2 mm)
  • If the patient does not meet either of those criteria, individualized decision making is recommended
  • For ductal carcinoma in situ (DCIS):
    • Tumor bed boost may be used for women:
      • 50 years of age and younger
      • Close (less than 2 mm) or positive margins
      • High-grade disease
    • It may be omitted for patients:
      • Older than 50 with screening detected
      • Total size less than 2.5 cm
      • Low to intermediate nuclear grade
      • Widely negative margins:
        • Greater than 3 mm
    • Long-term 20-year follow-up of a phase 3 trial of boost vs. no boost:
      • Reported a benefit in all groups with the largest absolute risk reduction in younger patients
• References
  • Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol. 2018;8(3):145-152.
  • Bartelink H, Maingon P, Poortmans P, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lanc Oncol. 2015;16(1):47-56.

Thyroid Cancer Staging (Simplified for Patients)

Staging describes how far a cancer has spread. In thyroid cancer, staging helps guide treatment intensity and follow-up, but it’s important to know that most patients do very well regardless of stage.

🧠 What factors are used to stage thyroid cancer?

The AJCC staging system considers:

Tumor size and whether it extends beyond the thyroid Lymph node involvement in the neck Distant spread (lungs or bones—uncommon) Age (patients under 55 are staged differently and typically have an excellent prognosis)

📊 What do the stages mean?

Stage I–II: ✔️ Most common ✔️ Often confined to the thyroid or nearby lymph nodes ✔️ Excellent long-term survival Stage III–IV: ✔️ Less common ✔️ More extensive local disease or distant spread ✔️ Still often highly treatable with modern, multidisciplinary care

⚖️ A key clarification for patients

Stage is not the same as risk of recurrence.

We also use ATA risk stratification to estimate the chance of the cancer returning and to tailor:

Extent of surgery Use of radioactive iodine Intensity of follow-up

🦋 Why this matters

Staging helps us:

Avoid overtreatment in low-risk patients Focus resources on patients who truly need more intensive therapy Provide accurate reassurance and individualized care

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

In thyroid cancer, stage helps guide care—but prognosis is excellent for the vast majority of patients.

📚 References

AJCC Cancer Staging Manual, 8th Edition Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Risk-adapted management of thyroid cancer. Lancet Diabetes Endocrinol

Most thyroid nodules are benign, and most people with thyroid nodules will never develop thyroid cancer.

Still, certain factors are associated with a higher risk and deserve closer evaluation.

☢️ Strongly Associated Risk Factors

Radiation exposure to the head and neck, especially during childhood or adolescence Prior therapeutic radiation for benign or malignant conditions Family history of thyroid cancer (especially first-degree relatives)

🧬 Genetic & Medical Factors

Certain inherited syndromes (rare, but important) Medullary thyroid cancer associated with RET mutations Autoimmune thyroid disease (e.g., Hashimoto’s thyroiditis) increases nodule prevalence; cancer risk remains low but evaluation is important

👥 Demographic Factors

Female sex (thyroid cancer is more common in women) Age (extremes of age can influence behavior and management)

🧠 Important clarification for patients

Having risk factors does NOT mean you have cancer.

➡️ Most patients with thyroid cancer have no identifiable risk factors.

➡️ Risk factors help guide how carefully we evaluate, not whether we panic.

🔍 What matters most?

High-quality ultrasound Appropriate biopsy when indicated Expert interpretation and risk-adapted management

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

Risk factors inform evaluation — ultrasound and pathology drive decisions.

📚 References

Haugen BR et al. ATA Guidelines for Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid Schneider AB et al. Radiation exposure and thyroid cancer. J Clin Endocrinol Metab SEER Cancer Statistics Review

Extended Endocrine Therapy in Very Young (≤40) Node-Positive HR+ Early Breast Cancer

Very young, node-positive, hormone receptor–positive (HR+) early breast cancer patients represent a uniquely high-risk subgroup, largely driven by persistent ovarian function and aggressive tumor biology. Emerging long-term data suggest that patients who remain premenopausal after completing 5 years of ovarian function suppression (LHRHa)–based endocrine therapy may derive clinically meaningful benefit from extended endocrine treatment.

In this population, extended endocrine therapy was associated with:

Improved invasive breast cancer–free survival (IBCFS) • 5-year IBCFS: 85% vs 78% • Hazard ratio (HR): 0.63, indicating a 37% relative risk reduction Improved distant recurrence–free survival (DRFS) • 5-year DRFS: 91% vs 83% • HR: 0.49, corresponding to a 51% relative reduction in distant relapse

Importantly, these efficacy gains were achieved without a major increase in long-term toxicity. Rates of fractures and cardiovascular events remained low (~1%), reinforcing the favorable therapeutic index of prolonged endocrine therapy in carefully selected young patients.

Clinical Implications

Chronologic age ≤40 years, node-positive disease, and persistent premenopausal status after 5 years identify a subgroup with sustained estrogen-driven recurrence risk. Extended endocrine therapy should be actively discussed in this setting, with shared decision-making that incorporates: Residual recurrence risk Tolerance of prior endocrine therapy Bone health and cardiovascular risk monitoring These data further support a risk-adapted, biologically driven approach to endocrine duration rather than a fixed 5-year strategy in very young patients.

Key References

Pagani O, et al. Long-term outcomes of adjuvant endocrine therapy in premenopausal women with hormone receptor–positive breast cancer. New England Journal of Medicine. 2014;371:107–118. Francis PA, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. New England Journal of Medicine. 2018;379:122–137. Regan MM, et al. Extended follow-up of the SOFT and TEXT trials: recurrence patterns and long-term toxicity. Journal of Clinical Oncology. 2022;40:3697–3708. Burstein HJ, et al. Endocrine therapy for hormone receptor–positive breast cancer: ASCO guideline update. Journal of Clinical Oncology. 2023.

Thyroid cancer is one of the most treatable cancers—and outcomes are excellent for the vast majority of patients.

📈 Survival in perspective

Overall 5-year survival >98% for most differentiated thyroid cancers Papillary thyroid cancer (the most common type) has >95% long-term survival Many patients live normal, full lives after treatment

🧠 What drives these excellent outcomes?

Several factors work in patients’ favor:

Slow tumor growth for most thyroid cancers Early detection with high-resolution ultrasound Accurate risk stratification (ATA / TI-RADS) Highly effective surgery when indicated Selective use of radioactive iodine and tailored follow-up

⚖️ Modern management matters

Today, thyroid cancer care focuses on:

✔️ Avoiding overtreatment for low-risk disease

✔️ Escalating treatment only when biology and risk justify it

✔️ Preserving quality of life without compromising cure

🦋 What this means for patients

A thyroid cancer diagnosis is serious—but not all thyroid cancers are the same.

The key is individualized, evidence-based care by an experienced team.

👨‍⚕️ Dr. Rodrigo Arrangoiz, MD

Surgical Oncologist – Thyroid, Head & Neck, Breast

Mount Sinai Medical Center

📌 Take-home message:

With proper evaluation and treatment, most patients with thyroid cancer do extremely well.

📚 References

SEER Cancer Statistics Review Haugen BR et al. ATA Guidelines for Differentiated Thyroid Cancer. Thyroid Tuttle RM et al. Risk-Adapted Management of Thyroid Cancer. Lancet Diabetes Endocrinol

• Warthin’s tumors most commonly present as an asymptomatic, slowly growing round or oval mass usually affecting men in the 5th and 6th decade:
  • The male to female ratio ranges from 2.6:1 to 10:1
  • They occur rarely in patients of  African American origin
  • The average size of Warthin’s tumor at diagnosis is about 2.5 centimeters
  • The great majority of these tumors are located in the lower pole of the parotid gland:
    • Tail of the parotid.
  • In about 10% to 12% of cases, there is bilateral tumor development:
    • Which is commonly synchronous
  • In about 6% of cases:
    • Multiple Warthin’s tumors may be observed in one parotid gland
  • They may occur simultaneously with pleomorphic adenomas, various types of carcinoma and malignant lymphomas
  • In large registries, Warthin’s tumors located outside of the parotid gland account for about 8% of the cases:
    • Case reports concern particularly cervical lymph nodes, the submandibular gland, and the larynx:
    • • The author assume that more attention is paid to these rather rare locations than to the numerous Warthin’s tumors located in the parotid gland which are extirpated worldwide

• These tumors are well encapsulated lesions with cystic and solid areas:
  • These tumors consist of an oncocytic epithelial cell component arranged in double layers:
    • Which develops cysts and papillary projections, and a variable amount of lymphoid tissue often with germinal centers:
      • The immunoprofile of the lymphocyte subsets is similar to that in normal or reactive lymph nodes.
  • A few Warthin’s tumors (about 8%) show areas of squamous cell metaplasia and regressive changes

• Several studies showed that a significant number of patients suffering from Warthin’s tumor are smokers, in contrast to patients with other salivary gland tumors:
  • The great majority of patients with Warthin’s tumor had a history of over 20 years of smoking:
    • The odds ratio for the incidence of Warthin’s tumor among current smokers compared with never smokers was 8.3
    • Compared with never smokers, clearly higher odds of Warthin’s tumor was observed in heavy smokers (more than 30 pack-years) (odds ratio=24.1) than patients who smoked less than 30 pack-years (odds ratio=4.9)

• Warthin’s tumor consists of oncocytic cells containing numerous mitochondria frequently showing structural abnormalities and reduced metabolic function:
  • Smoking can lead to damage to mitochondrial DNA due to the development of numerous reactive oxygen species
  • In this context, a high rate of deleted mitochondrial DNA has been detected in the oncocytic cells of Warthin’s tumor

• The role of hormones in the etiology of this disease has also been discussed:
  • In some malignant salivary gland diseases and even in Warthin’s tumor progesterone receptors have been found
  • A correlation with sex hormones could possibly play an important role in the development of those tumors and provide an explanation for the dominance of the male gender
  • However, it must be considered that more males than females used to smoke so that the role of the individual factors remains unclear and the intrinsic factor stimulating the development of Warthin’s tumor is still unknown

Rodrigo Arrangoiz MS, MD, FACS a head and neck surgeon / surgical oncologist and is a member of Mount Sinai Medical Center in Miami, Florida:

• He is an expert in the management of salivary gland neoplasms:

  • If you have any questions about salivary gland neoplasms  please fill free to ask Dr. Arrangoiz

Training:

• General surgery:

• Michigan State University:

• 2004 al 2010

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• Fox Chase Cancer Center (Filadelfia):

• 2010 al 2012

• Masters in Science (Clinical research for health professionals):

• Drexel University (Filadelfia):

• 2010 al 2012

• Surgical Oncology / Head and Neck Surgery / Endocrine Surgery:

• IFHNOS / Memorial Sloan Kettering Cancer Center:

• 2014 al 2016

#Arrangoiz

#HeadandNeckSurgeon

#SurgicalOncologist

#Surgeon

#CancerSurgeon

#CirujanodeCabezayCuello

#CirujanoOncologo

• Excisional biopsy:
  • Is recommended for most ADH lesions diagnosed on core needle breast biopsy (CNB)
• The chance of upgrade at excision to ductal carcinoma in situ (DCIS) or invasive carcinoma:
  • Is generally in the 12% to 22% range in the literature
• The need for routine excision of pure flat epithelial atypia (FEA) has been less clear:
  • Some authors have reported an upgrade rate of 9.6% following excision of lesions that show pure FEA without ADH when the vast majority of biopsies were done with a 14-gauge spring-loaded core biopsy device
  • It is not clear that biopsy with a vacuum-assisted device would yield the same results
  • In fact, in one study reporting biopsy of low-risk calcifications with a vacuum-assisted device, pure FEA never resulted in an upgrade to malignancy
  • An article from the Mayo Clinic showed that FEA does not seem to convey an independent risk of breast cancer beyond that of associated proliferative disease without atypia or associated ADH
• The risk of upgrade at surgical excision for ADH:
  • Has been reported to correlate with the number of ducts or terminal duct lobular units involved on vacuum-assisted core biopsy;
    • With 2 or fewer foci of involvement:
      • There was no upgrade on excision
    • With 4 or more foci of involvement:
      • There was a strong probability of upgrade to ductal carcinoma in situ or invasive carcinoma at excision
• Work continues to try to define a low-risk group who could potentially avoid excisional biopsy:
  • Particularly those with small areas of calcifications completely removed with core needle biopsy and only focal ADH on pathology
• Apocrine metaplasia, florid epithelial hyperplasia of the usual variety, and columnar cell change without atypia:
  • Do not confer a significant risk of upgrade and do not require excision
• References
  • Eby PR, Ochsner JE, DeMartini WB, Allison KH, Peacock S, Lehman CD. Is surgical excision necessary for focal atypical ductal hyperplasia found at stereotactic vacuum-assisted breast biopsy? Ann Surg Oncol. 2008;15(11):3232-3238.
  • Ely KA, Carter BA, Jensen RA, Simpson JF, Page DL. Core biopsy of the breast with atypical ductal hyperplasia: a probabilistic approach to reporting. Am J Surg Pathol. 2001;25(8):1017-1021.
  • Khoumais NA, Scaranelo AM, Moshonov H, Kulkarni SR, Miller N, McCready DR, et al. Incidence of breast cancer in patients with pure flat epithelial atypia diagnosed at core-needle biopsy of the breast. Ann Surg Oncol. 2013;20(1):133-138.
  • Said SM, Visscher DW, Nassar A, Frank RD, Vierkant RA, Frost MH, et al. Flat epithelial atypia and risk of breast cancer: a Mayo cohort study. Cancer. 2015;121(10):1548-1555.
  • McGhan LJ, Pockaj BA, Wasif N, Giurescu ME, McCullough AE, Gray RJ. Atypical ductal hyperplasia on core biopsy: an automatic trigger for excisional biopsy? Ann Surg Oncol. 2012;19(10):3264-3269.