Today, I link to, embed, and excerpt from The Curbsiders‘ “#470 Thyroid Nodules and Thyroid Cancer for Primary Care“.*
*Burke ARM, Chindris AM, Desai KS, Williams PN, Watto MF. “#470 Thyroid Nodules and Thyroid Cancer for Primary Care”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast February 10, 2025.
All that follows is from the above resource.
Transcript available via YouTube
Management and Ongoing Monitoring of Thyroid Neoplasms
Join us as we dive deep into the approach for thyroid nodules with our two fantastic guests, Dr. Kaniksha Desai (Stanford Medicine) and Dr. Ana Chindris (Mayo Clinic)! Learn how to stratify these nodules for cancer risk and walk alongside our patients during treatment for thyroid cancer.
Claim CME for this episode at curbsiders.vcuhealth.org!
Show Segments
- Intro, guest bios
- Case From Kashlak
- Thyroid nodule evaluation and management
- Thyroid cancer diagnosis and treatment
- GLP-1s relationship to thyroid nodules and cancer
- Outro
Thyroid Nodules and Thyroid Cancer Pearls
- Thyroid nodules are common and the vast majority are benign.
- Thyroid ultrasound and TSH should be checked during the initial evaluation of all nodules. Radionuclide scan should be reserved for times when it changes management (expert opinion – see below).
- Ultrasound findings are typically reported as a TI-RADS level which guides the need for FNA and/or imaging surveillance (Kwak 2011)
- FNA cytology is interpreted as a Bethesda Category which stratifies the nodule’s risk of malignancy (Cibas 2009).
- For indeterminate nodules, molecular testing can help further delineate the cancer risk and guide next steps.
- There is no such thing as “good cancer”. Acknowledge that this can be an anxiety-inducing diagnosis and meet the patient where they are.
- The current paradigm in thyroid cancer treatment is shifting to less invasive modalities (lobectomy instead of total thyroidectomy, and less use of radioactive iodine and TSH suppression in those that are low risk).
- Personal and family history of medullary thyroid cancer or MEN2 are current contraindications to GLP-1 use, but benign nodules and differentiated thyroid cancers (e.g. follicular, papillary) do not preclude the use of these medications.
Thyroid Nodules
Initial Approach: History and Physical Exam
Thyroid nodules are common in the general population and incidence increases with age. The vast majority are benign, however once identified further investigation is needed to determine the likelihood of malignancy. It is important to inquire about personal history of radiation exposure, family history of thyroid cancer, and any symptoms that could be attributed to the nodule(s). Nodules can be hormonally active so we need to ask about symptoms of hyperthyroidism (palpitations, heat intolerance, etc). Dr. Chindris notes that other symptoms of hyperthyroidism can be subtle, including irritability/personality changes. Outside of symptoms related to hormonal fluctuations, patients can also experience compressive symptoms from nodules (e.g. neck tightness, dysphagia particularly with solids). The position of the nodule plays a role in how symptomatic a patient is; if nodules are lateral they are less likely to cause troublesome symptoms.
Relevant physical exam includes assessing whether the thyroid is mobile and whether there are any palpable masses in the neck (e.g. cervical lymphadenopathy). There are different styles for examining the thyroid (some perform the exam from the front, some from behind, but generally good to do one side at a time). Dr. Desai points out that we can’t generally palpate nodules that are under 1 cm unless they are very superficial, and if they are posterior we often cannot detect them by exam until they are closer to the 2cm mark.
Laboratory Testing and Imaging
Laboratory testing primarily includes checking a TSH, but it is important to know that TSH can fluctuate with toxic nodules so an isolated normal TSH does not rule out a functioning nodule (Chami, 2014). Free T4 and T3 can be checked if TSH is abnormal. There are some special circumstances where a calcitonin level can guide diagnosis of medullary thyroid cancer, however this is not generally recommended as part of the initial evaluation for all nodules (2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer).
For imaging, a thyroid ultrasound including cervical lymph nodes is recommended for all known or suspected thyroid nodules, regardless of TSH (ATA 2015). Dr. Chindris points out that nuclear imaging is only needed if it will change management. For example, if the patient is hyperthyroid and the plan is for antithyroid medication (e.g. methimazole), there is not a clear role for a radionuclide scan. However, if you suspect a unilateral toxic nodule in a patient with compressive symptoms and are considering surgery, it makes sense to check a nuclear study to confirm that it is an overactive nodule.
Thyroid nodules examined via ultrasound are typically given a risk level based on the Thyroid Imaging Reporting and Data System (Kwak 2011). TI-RADS incorporates thyroid nodule shape, composition, echogenicity, margins and presence of calcifications/echogenic foci. Points are assigned for each of these components and then added up to determine TI-RADS level.
- TR1 = benign
- TR2 = not suspicious
- TR3 = mildly suspicions
- TR4 = moderately suspicious
- TR5 = highly suspicious
The presence of abnormal lymph nodes is also a high-risk feature that should trigger biopsy. The TI-RADS score then guides next steps in regards to who gets fine needle aspiration versus imaging follow up. Spoiler alert: Dr. Chindris fills us in that the American Thyroid Association is going to be releasing new guidelines in 2025 that will hopefully address when we are able to space out and stop ultrasound monitoring. Her current expert opinion is that if a nodule is stable on multiple ultrasounds then can space out imaging gradually to every 3-5 years.
Fine-Needle Aspiration
If a nodule is determined to need fine-needle aspiration (FNA), the cytology is typically reported in terms of Bethesda System which dictates further management (Cibas 2009) :
- I: nondiagnostic
- II: benign
- III: atypia of unknown significance
- IV: follicular neoplasm
- V: suspicious for malignancy
- VI: malignant
Typically, for Bethesda I nodules, the recommendation is to repeat FNA. For Bethesda II, no surgical intervention is needed and nodules are monitored periodically with ultrasound (ATA 2015).
Category III and IV are considered indeterminate. Dr. Chindris mentions that in the past, lobectomy was the next step in these situations to obtain official diagnosis. In recent years, molecular testing has been used to look for genetic mutations that help assess the likelihood of these nodules being malignant. Mutational testing does provide a definitive diagnosis but can help risk stratify and guide next steps (ATA 2015).
Category V nodules should typically be referred for surgery. There may be a role for mutational testing to help with decision making for lobectomy vs total thyroidectomy (ATA 2015).
Treatment of Symptomatic Benign Nodules
In those suffering from symptoms of thyroid nodules that have been determined to be benign with two different cytology studies, there are some procedures outside of surgical removal that can be used as treatment. For benign fluid-filled cysts, aspiration and injection with alcohol can help produce scarring to reduce the likelihood of recurrence. For solid nodules, laser ablation and radiofrequency ablation are options often performed by surgeons, interventional radiologists and endocrinologists.
Thyroid Cancer
Classification and General Approach
Dr. Desai points out that there is a common misnomer of thyroid cancer as being referred to as a “good cancer.” She reminds us to avoid this language and emphasizes that prognosis varies based on the subtype of cancer. Thyroid cancer can be defined in the following categories:
- Differentiated
- Papillary thyroid carcinoma (80% of differentiated cancer)
- Follicular thyroid carcinoma (10-15%)
- Oncocytic carcinoma (previously known as Hürthle cell carcinoma – 2-3%)
- Medullary (C-cell)
- Anaplastic
General Overview of Thyroid Cancer Treatment
Differentiated thyroid cancer: In the past, patients with thyroid cancer would often receive total thyroidectomy, radioactive iodine and suppression with levothyroxine. In more recent years, lobectomy for papillary thyroid carcinoma (PTC) is becoming increasingly common. Total thyroidectomy, radioactive iodine and TSH suppression is used only in higher risk circumstances (ATA 2015). PTC can spread through the lymphatic system. PTC in general has a good prognosis, with a 5-year-survival of approximately 99% (ACA). Follicular thyroid carcinoma (FTC) is treated similarly to papillary, however an important difference is that FTC tends to metastasize more through the bloodstream so you can have more distant mets to bone. FTC has a slightly worse prognosis with a 5 year survival of approximately 96.6% (Xiaoyu 2024). Oncocytic carcinoma can have a worse prognosis particularly in the setting of certain mutations (TERT mutation).
Medullary thyroid cancer: Treatment is primarily surgical. Prognosis is based on stage with stages I-III having a 5-year survival around 93%, however stage IV drops to around 28% (Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology). Since medullary thyroid cancer originates from C cells, radioactive iodine and TSH suppression are not used in this group. Of note, this can occur in association with multiple endocrine neoplasia type 2 (MEN2). Genetic testing and referral to genetic counselors can help guide families if they need further screening.
Anaplastic thyroid cancer: This is the most aggressive type of thyroid cancer. Dr. Desai describes that a patient with anaplastic thyroid cancer can present with a rapidly expanding neck mass that can result in fatal airway compromise within 1-2 weeks in severe situations. Median survival is reported at around 5-6 months, with only approximately 20% surviving the first year (2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer). Depending on the presence of certain mutations, neoadjuvant chemotherapy can be used prior to resection. Radioactive iodine and levothyroxine suppression do not have a role in the treatment of anaplastic carcinoma.
Thyroid Cancer Survivorship
Ongoing monitoring for those with a history of thyroid cancer depends on the type of cancer they had. Higher risk patients will often maintain a relationship with endocrinology. If they are low risk and had an excellent response to treatment, Dr. Desai recommends annual thyroglobulin levels, TSH and periodic neck ultrasound. Current guidelines are vague on imaging intervals but Dr. Desai points out that there are newer guidelines in the works on this topic. In her practice, she gets thyroid ultrasound every 6-12 months initially and then spaces out from there. Of note, Dr. Chindris explains that following lobectomy, thyroglobulin is not helpful because it will be undetectable from the remaining lobe.
In terms of thyroid hormone replacement. Dr. Desai informs us that in the past, for those with lobectomy they used to aim for a TSH goal of 0.5 to 2.0 mIU/L (ATA 2015), though this may be relaxed in upcoming guidelines to keep TSH within normal range (0.5 to 5.0) unless the patient is higher risk or symptomatic. Data has not shown improved prognosis with this tighter control for those status post lobectomy for low-risk differentiated cancers (Won, 2022). With this approach, Dr. Desai notes about 80% of people with lobectomy would not need any hormone replacement.
GLP-1s and Thyroid Cancer
In 2023, there was a French retrospective study that found a slightly higher risk of thyroid cancer in those on GLP-1s with diabetes (Bezin 2023). However, since then Dr. Desai mentions multiple other studies have come out showing the risk was not as high as initially suspected (Espinosa De Ycaza, 2024). On the other hand, obesity and uncontrolled diabetes certainly have major risks that need to be considered.
GLP-1s should be avoided in those with personal or family history of medullary thyroid cancer or MEN2. Pro tip: If there is a history of thyroid cancer but the patient is uncertain of the specifics, Dr. Desai suggests asking what treatment was needed. If they received radioactive iodine or suppressive thyroid hormone, then we can feel confident it was not medullary as these treatments are not used for medullary carcinoma. With medullary thyroid cancer, oftentimes, it is in multiple family members as well. Medullary is also quite rare (3% of all thyroid cancers).
There is no recommendation for screening for thyroid nodules with imaging solely for the purpose of starting GLP-1. If you do a neck exam and feel a lump or if the patient otherwise has symptoms indicative of a nodule, then would get an ultrasound. Per Dr. Desai, it is okay to use GLP-1s in those with a history of non-medullary thyroid cancer.
