Follicular Adenoma

What is Follicular Adenoma?

The thyroid, a small gland in the middle of the neck, was first properly described by Andreas Vesalius (1514 -1564) in his anatomy book. Since then, our understanding of this gland has greatly improved. This gland comes from certain primitive cells in the neck region. As it develops, it divides to form two side parts and a connecting section. By the time a person is 2 years old, their thyroid gland is already half the adult size. Sometimes, unusual growths called ectopic thyroid tissue, cysts, and sinuses can form due to development issues.

Aside from those, the thyroid gland can also develop abnormal growths or tumors. These fall under the category of follicular lesions, ranging from benign (non-cancerous) follicular adenoma to harmful follicular carcinomas and various types of cancerous growths.

Follicular adenomas are a type of benign tumor that can grow in the thyroid gland or in ectopic thyroid tissue. They usually exist as a single lump in the thyroid or are associated with other conditions like nodular hyperplasia (overgrowth of normal cells) or thyroiditis (inflammation of the thyroid). While 4 to 7% of people can feel these thyroid nodules or lumps, more are found through ultrasound screenings, with 19 to 67% of individuals showing these nodules. Most people with thyroid nodules don’t have any symptoms. Similar to worldwide figures, about 60 to 70% of the US population are discovered to have thyroid nodules. The majority of these are benign, but 5% do show characteristics of cancer. Even though it can be a challenge to differentiate between the harmless adenoma and its cancerous equivalent, it’s generally considered a benign, or non-cancerous, lump.

What Causes Follicular Adenoma?

Follicular adenomas, a type of non-cancerous growth in the thyroid, can occur for various reasons. Often it happens by chance, but there are different factors that can increase the likelihood of it occurring.

One potential cause is a lack of iodine in the body, usually from regularly consuming non-iodized sea salt.

Sometimes, follicular adenomas can also be caused by changes in specific genes in your body. The PTEN hamartoma tumor syndrome (PHTS) – a group of genetic disorders that can cause tumors to grow in different parts of the body – includes several conditions like Cowden syndrome and BRRS. These conditions can sometimes cause multiple follicular adenomas to appear with other symptoms. Similarly, other gene changes in BRAF, NRAS, RET, and KRAS can also lead to unexplained follicular adenomas.

Follicular adenomas can also appear as part of other genetic conditions, one being Familial Adenomatous Polyposis, which causes polyps to develop in the gut and another being Carney Complex syndrome, where multiple tumors may occur in the body. One specific gene change is the rearrangement of the PAX8-PPAR gene which causes a loss of control in follicular cell growth, hence, leading to the creation of these growths or neoplasms.

Lastly, previous exposure to I-131 radiation, typically used in certain medical treatments, can increase the risk of malignant or potentially cancerous lesions in the thyroid.

Risk Factors and Frequency for Follicular Adenoma

Follicular adenomas, commonly appearing as solitary thyroid nodules, are benign tumors that affect about 2 to 4.3% of the population. In an autopsy study of 300 people, a 3% incidence of follicular adenomas was found, compared to a 2.7% incidence of follicular carcinoma. Small nodules, which are less than 15 mm in diameter, are found in 5 to 10% of populations based on autopsy studies. The incidence rates vary based on geography, with Finland having the highest reported rates of these hidden microcarcinomas. Thyroid adenomas are generally more common in females. These prevalence trends are consistent with data from the United States.

In the last three decades, the occurrence of thyroid cancer has grown from 4.3 cases per 100,000 people in 1980 to 12.9 cases per 100,000 people in 2008. This increase is debated among medical professionals, as some believe that it may just be due to improvements in detection methods, such as ultrasound imaging, more advanced medical equipment, public awareness and screening campaigns for people with a higher risk.

There has also been a rise in the discovery of thyroid nodules in children. Although improved detection is a part of the reason, it doesn’t explain it entirely. Other factors that might contribute include environmental exposure such as diagnostic radiography, cosmic radiation, and other unknown sources. Research on those exposed to I-131 radiation after the Chernobyl’s nuclear accident showed that the risk increased for people of both sexes with higher doses, and children under two had the highest risks. Some studies indicate that when radiation is involved, the incidence of these nodules changes compared to that in a normal population. The increase in incidence rates seen in the last 30 years cannot be fully explained by improved detection, suggesting a real increase. However, the exact cause of this increase is still unknown.

Signs and Symptoms of Follicular Adenoma

Follicular adenomas usually show up as a solitary thyroid nodule in an otherwise healthy thyroid gland. They may also happen with thyroiditis or nodular hyperplasia. Most solitary nodules don’t cause any symptoms, but there is less than 1% chance of experiencing hyperthyroidism. So, it’s important to check for signs of hyperthyroidism or hypothyroidism while examining a patient with neck swelling. The patient’s history of taking thyroid medication could provide useful insights into the cause of the nodule.

Family history should also be considered, especially if there are instances of autoimmune diseases like Hashimoto disease or Grave disease, thyroid carcinoma, or familial syndromes like Gardners. It’s common for patients to report a slowly growing mass in their neck or the feeling of pressure on their neck. Rarely, pain may occur, typically if there has been a hemorrhage or cystic degeneration in the nodule. Some might complain about the appearance of the mass. If the nodule is causing pressure, it could lead to breathing difficulties, a persistent cough, voice changes, and choking spells due to an irritated nerve and difficulty swallowing due to esophagus compression.

During the physical exam, doctors will examine the entire body to look for any signs indicating a non-euthyroid state, which means the thyroid gland isn’t working as it should. Follicular adenomas can be felt during the examination or might be identified on imaging studies. It is harder to identify nodules that are less than 1 cm unless it’s located in the front of the gland. Factors such as the size, location, shape, borders, and consistency of the nodule are all important. There might be more than one nodule, but it’s worth noting that nearly half of these nodules aren’t detected during the physical examination and are only identified through ultrasound.

Testing for Follicular Adenoma

The American Thyroid Association sets guidelines for evaluating thyroid nodules. This process usually involves four key steps: understanding your health history, conducting a physical examination, testing for thyroid-stimulating hormone (TSH) in your blood, and performing an ultrasound. The ultrasound can provide valuable insights into the size and characteristics of the nodule, which can guide further evaluation steps.

Follicular adenomas, generally benign thyroid nodules, could sometimes resemble follicular carcinoma, a type of thyroid cancer. It’s also important to distinguish it from the non-invasive follicular thyroid neoplasm with papillary-like nuclear features or NIFT. A tiny fraction (about 5%) of follicular adenomas, when examined microscopically, have been found to be follicular cancers.

Nodules that measure more than 1 cm need detailed evaluation, as they may be, or may turn into, cancer. Smaller ones may be checked if they show symptoms or linked to enlarged lymph nodes. Lab tests, including thyroid function tests, and aspirating a sample from the nodule with a fine needle (FNA), can help with the diagnosis.

Ultrasounds can help differentiate between follicular adenoma and carcinoma. Certain features, like large size, dark coloration, mixed or solid texture, absence of surrounding halo, tiny calcifications, may suggest a higher likeliness of cancer. If ultrasound shows any suspicious features like irregular edges, tiny calcifications, nodules appearing taller than wide, or nodules with rim calcifications, these should be evaluated with FNA if the size is at least 1 cm. On the other hand, nodules that are equal in all dimensions or taller than wide, solid, or partially fluid-filled without suspicious features should be evaluated with FNA only if they’re larger than 1.5 cm. Cystic (fluid-filled) nodules are typically not at risk and are not prioritized for evaluation with FNA.

If a thyroid nodule measures over 1 cm, it is advised to check the level of thyroid-stimulating hormone (TSH) in the blood. If TSH levels are low, a thyroid scan should be done. If TSH is normal or elevated, the radionuclide scan is usually not advised. In this case, the scan can be analyzed in conjunction with other findings like ultrasound results, FNA reports, and clinical information.

Protein levels in the blood, from a test for a protein called thyroglobulin, are not typically measured in the initial evaluation of a thyroid nodule. This is because it isn’t very specific, but it may be monitored in certain cases, like after thyroid removal. Tests for a hormone called calcitonin aren’t strictly recommended either but may be beneficial in some cases, for example, to detect certain conditions like C-cell hyperplasia or medullary thyroid cancer at an early stage, which can improve survival.

Imaging techniques like computerized tomography (CT) scanning or magnetic resonance imaging (MRI) are not commonly used in the first assessment of a solitary thyroid nodule but may be utilized if invaded or compressed airway is suspected, if there’s extension into the mediastinum (chest cavity), or in cases of recurrent disease.

The FNA procedure is typically performed to examine the nodule microscopically and is pivotal in assessing these lesions, although it might not provide a diagnosis in all cases. The success rate of FNA is improved when done under ultrasound guidance. The microscopic findings are classified using one of the three major international systems.

In case of follicular adenoma, the microscopic examination of the aspirated sample shows abundant follicular epithelial cells organized in sheets with crowding and overlapping of cells. Some patients have follicular cells with abnormal architecture that is more significant than usually seen with benign lesions but not sufficient to call it a tumor. According to the Bethesda classification system, these patients are characterized as having “atypia of undetermined significance” or “follicular lesion of undetermined significance”. Genetic testing of the indeterminate cytology can be helpful. A definitive diagnosis of follicular adenoma is only made after ruling out capsular and vessel invasion by surgical nodule removal or thyroid removal followed by microscopic examination.

Treatment Options for Follicular Adenoma

Usually, doctors prefer surgery when dealing with follicular lesions, which are irregularities or growths in your thyroid gland. However, there are options for medical management as well.

Medical treatment is used if the patient’s levels of thyroid hormones are not balanced. For example, if a patient has a low TSH level, a common thyroid hormone, it could indicate a condition called “toxic adenoma.” In cases like this, further hormone tests are done. Moreover, an ‘iodine-123’ thyroid scan may be used to see how the nodule in the thyroid is functioning. Doctors treat these cases with specific medicines. For some patients, observation or levothyroxine suppression treatment, a type of thyroid hormone replacement therapy, might be the first step. Levothyroxine is given for around six months to see if the nodule shrinks. If the nodule shrinks due to levothyroxine, the therapy is stopped and the nodule is rechecked in the next three to six months. If the nodule grows during treatment, that’s a strong indicator that surgery might be needed.

However, surgical intervention is often required for most cases.

In terms of surgery, if a diagnosis called ‘follicular neoplasm’ is made through fine-needle aspiration (FNA), which is a type of biopsy, there’s up to a 20% chance of cancer if the nodule isn’t functioning properly, but less than a 1% chance if it is. If such a diagnosis is made, a type of surgery called a thyroid lobectomy with isthmusectomy, which involves removing a portion of the thyroid, is commonly performed. Additional factors, like family medical history and previous radiation treatment, could influence the decision to perform a more complete surgery, a total thyroidectomy.

For patients with a single overactive nodule, they might be able to receive therapeutic iodine-131 treatment. However, partially removing the thyroid – unilateral thyroid lobectomy – is usually enough. After surgery, if the examination shows the follicular neoplasm to be an adenoma, a usually noncancerous tumor, no further treatment is required.

If the examination shows features of cancer, larger scale surgery might need to be performed. Treating any remaining thyroid tissue with radioactive iodine may be recommended about six weeks after surgery to reduce the risk of the disease returning. It’s important for patients to have regular check-ups after surgery to ensure there’s no recurrence or spread of the disease. Doctors often use periodic ultrasound and serum thyroglobulin level tests, a kind of blood test, to monitor the patient’s condition.

If the disease has spread, the doctor and a cancer specialist will work together to optimize patient outcomes.

The main benefits of surgical treatment include relief from symptoms like difficulty breathing, swallowing or changing voice pitch, reduction of patient anxiety, and a resolution of high thyroid hormone levels due to toxic adenomas. Using surgery also avoids unnecessary exposure of healthy thyroid tissue to radiation.

What else can Follicular Adenoma be?

Follicular adenomas often show up as a lone lump in the thyroid. Therefore, any other possible causes for a single thyroid lump should also be looked into. These could be:

• Follicular carcinoma (another type of thyroid cancer)
• Other benign tumors such as:
  • Hurtle cell adenoma
  • Non-invasive follicular tumor with papillary-like nuclear features (NIFTP)
• Other types of thyroid cancer:
  • Papillary thyroid carcinoma
  • Medullary carcinoma
• Thyroiditis, which can occasionally present as a thyroid lump

What to expect with Follicular Adenoma

Follicular adenomas are non-cancerous tumours that grow slowly. In some cases, they can become so large that they press onto other structures in the body, causing symptoms such as difficulty breathing, swallowing, and voice changes. When these symptoms occur, it’s important to evaluate them and help patients understand that they’re not caused by cancer; rather, it’s due to the bulge applying pressure on other organs.

Yet, it’s worth noting that 20% of follicular adenomas that are non-functioning can hold gene mutations which may end up transforming into a follicular carcinoma, a kind of cancer. This change has been linked to specific genes known as N-RAS and K-RAS. When confirmed that a follicular neoplasm, a type of tumour, is indeed cancerous, quick cancer-specific treatment is vital. However, patients with a confirmed benign follicular adenoma typically don’t need new treatments. It’s not suggested to provide them with additional thyroid hormone, unless they develop hypothyroidism (a condition where the thyroid doesn’t make enough hormones) after surgical removal of part of the thyroid gland. The risk of these tumors turning into cancer increases according to studies of people exposed to radiation after the Chernobyl nuclear accident.

Possible Complications When Diagnosed with Follicular Adenoma

Some issues aren’t necessarily complications, but they might occur when a growth becomes large enough to press against nearby structures. These problems include:

• Feeling a dull, dragging sensation because of the size and presence of the growth
• Difficulty breathing due to the growth pressing on the windpipe
• Trouble swallowing caused by compression on the oesophagus
• Hoarseness in voice, if the growth presses against the nerve that controls vocal cord movement
• Pain over the growth, which may worry the patient. This could indicate that spontaneous bleeding or cystic degeneration has occurred within the growth
• In the worst cases, a toxic nodule can cause thyroid storm, which requires additional care

The surgery to remove such a growth can also have some complications:

• Bleeding
• Infection
• Scarring, including hypertrophic or keloid (overgrown scar tissue) formation
• Thyroid crises, a severe and sudden worsening of symptoms
• Temporary or permanent low calcium levels, especially if the parathyroids, glands that control the calcium levels, are fully removed
• Cutting the recurrent laryngeal nerve, which could lead to a loss of voice and even, in serious situations, cause breathing problems that require the use of a mechanical ventilator

Recovery from Follicular Adenoma

After a surgery to relieve symptoms of pressure, there are key points to remember during recovery:

• Regularly clean and care for the wound
• Stay alert for any possible complications mentioned earlier
• Keep an eye out for signs of low parathyroid hormone levels and treat appropriately. The parathyroid glands control the amount of calcium in our bodies, so deficiency can lead to problems with muscles and nerves
• Regular check-ups should continue until biopsy results confirm a harmless follicular neoplasm (tumour formed from glandular tissue).

Preventing Follicular Adenoma

If you notice a growing lump in your neck, it is important to see a healthcare professional for a check-up. There are many types of growths that could form in your thyroid, and one of the most common types is called follicular neoplasms.

It can be difficult to determine if these growths are malignant (cancerous) or benign (non-cancerous) based solely on a procedure called Fine Needle Aspiration (FNA) cytology. This procedure, which involves using a thin needle to collect cells from the lump, can’t provide a definitive answer because it doesn’t allow doctors to examine the full structure of the tissue. Only a tissue biopsy, a procedure where a small piece of the lump is removed and examined, can provide this information.

Keep in mind that complications or changes happening within a follicular neoplasm don’t necessarily mean it is transforming into a malignant lump. In fact, if a follicular tumor is proven to be benign, it almost never turns into a cancerous lesion.