Continuing Education Activity

Thyroid adenomas are benign lesions of the thyroid gland. These lesions may be inactive or active in producing thyroid hormones. In the case of being active, they may be referred to as toxic thyroid adenomas. There are two types of thyroid adenomas, follicular and papillary. Most thyroid adenomas do not cause any symptoms and are usually diagnosed incidentally by ultrasound of the thyroid gland. Thyroid adenoma usually presents as a solitary thyroid nodule. It is important to exclude malignancies from the differential diagnosis because thyroid carcinoma mimics adenoma. This activity reviews the evaluation and treatment of thyroid adenoma and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Identify the epidemiology of thyroid adenoma.
• Review the appropriate evaluation of thyroid adenoma.
• Outline the management options available for thyroid adenoma.
• Summarize interprofessional team strategies for improving care coordination and communication to improve the outcomes of patients with a thyroid adenoma.

Introduction

The thyroid gland, consisting of two connected lobes, is one of the largest endocrine glands in the human body, weighing 20 to 30 g in adults.[1] Thyroid lesions are often found in the gland, with a prevalence of 4% to 7%. Most of them are asymptomatic, and thyroid hormone secretion remains normal. The majority of thyroid lesions are non-cancerous. Benign lesions include simple or hemorrhagic cysts, colloid nodules, and thyroid adenomas.[2][3][4] 

Thyroid adenomas are benign lesions of the thyroid gland. These lesions may be inactive or active in producing thyroid hormones. In the case of being active, they may be referred to as toxic thyroid adenomas. Patients with thyroid adenomas are usually asymptomatic. However, biochemical and clinical hyperthyroidism can be caused by a toxic adenoma, defined as an autonomously functioning thyroid nodule (AFTN). Most thyroid adenomas do not cause any symptoms and are usually diagnosed incidentally by ultrasound of the thyroid gland. Less frequently, they might present as a palpable thyroid nodule or generally as an easily seen growth on a patient's neck.[5]

Etiology

Most thyroid adenomas are sporadic and not hereditary. However, some environmental and genetic factors are associated with the presence of a thyroid adenoma. For example, iodine deficiency is a well-known environmental risk factor accused of causing the development of a thyroid adenoma, and it is the most common reason for the development of thyroid nodules around the world, especially in underdeveloped countries. 

In addition, rare genetic mutations in BRAF, RET, KRAS, and genetic rearrangement of the PAX8-PPAR gene are strongly associated with the development of thyroid adenomas.[6][7] Newer techniques have become available and more widespread in studying the molecular basis of thyroid adenomas, and they have helped differentiate benign versus malignant tumors.[8][9][6]

Epidemiology

Thyroid adenomas usually present as solitary thyroid nodules and are more common in female patients. In two autopsy series, the incidence of thyroid adenomas was 3% and 4.3%, respectively. The incidence of thyroid adenomas used to be higher in the past, especially in iodine-deficient areas (endemic goiter). However, in recent years, their incidence has been reported at much lower levels due to the use of iodine-enriched salt.[10][11]

Pathophysiology

Genetic rearrangement of the PAX8-PPAR gene is strongly associated with developing a thyroid adenoma. PAX8 is a gene involved in follicular cell differentiation. The PAX8-PPAR gene rearrangement has been found in 4%-13% of follicular adenoma cases.[6] There are two major types of thyroid adenomas, functional and non-functional ones. Functional adenomas are more commonly the result of a monoclonal expansion of thyroid cells due to activating mutations in the TSH-receptor gene and less commonly due to a mutation in the adenylate cyclase stimulating G alpha protein gene. The K-RAS mutation is most commonly found in non-functional adenomas and is associated with developing thyroid carcinomas.[12][13]

Histopathology

Thyroid adenomas are homogeneous, solitary, and encapsulated tumors. They are usually classified as follicular or papillary based on pathology findings. The follicular type is the most commonly seen type, whereas the papillary adenomas are extremely rare. There are five subtypes of follicular adenomas:

• Fetal type
• Colloid type
• Embryonal type
• Hurthle cell type
• Hyalinizing trabecular type[14]

The classification of follicular adenomas into subtypes is based on histological findings such as cellular architecture and the amount of colloid content. It is highly recommended that thyroid adenomas be differentiated from thyroid carcinomas. This is usually done through histological evidence of capsular invasion and angioinvasion that strongly suggests when a thyroid lesion is of malignant nature.[15][16]

History and Physical

Most patients won't know they have a thyroid adenoma until they undergo a complete and thorough physical examination. In some cases, they might present with a complaint of visible and palpable neck growth. The patients rarely complain of dyspnea due to tracheal compression, hoarseness due to laryngeal nerve irritation or dysphagia due to esophagus compression. Most of the time, the patients are clinically euthyroid without any symptoms suggesting hyperactive or hypoactive thyroid function. However, about 1% of the patients with thyroid adenomas can be hyperthyroid, and in that case, they might have a constellation of symptoms including, but not limited to, weight loss, increased anxiety, heart palpitations, excessive sweating, changes in the bowel habits as well as changes in the hair or the skin and menstrual irregularities in women of reproductive age.[15]

Evaluation

The diagnostic evaluation of a patient with a palpable thyroid nodule first includes a thyroid-stimulating hormone (TSH) level measurement to assess the functional baseline status of the thyroid gland, and afterward, an ultrasound examination of the thyroid gland, and ultimately a fine needle aspiration biopsy. All patients with a palpable thyroid nodule should have their thyroid hormone levels (TSH and thyroxine) checked. A toxic adenoma is suspected in patients with low TSH levels. These patients should undergo an iodine-123 thyroid scan in order to differentiate a hyperfunctioning nodule (toxic adenoma) from a hypofunctioning nodule.[17]

A hyperfunctioning nodule is considered a benign lesion, as there is less than a 1% probability of malignancy. On the other hand, hypofunctioning nodules have a 20% probability of malignancy (through malignant transformation). However, most patients with a thyroid nodule are euthyroid, which means that TSH levels are within normal limits. All patients should undergo an ultrasound (US) examination of the thyroid gland to differentiate a thyroid adenoma, which is considered a benign lesion, from thyroid carcinoma. Sonographic features associated with a higher risk of malignancy are hypoechogenicity, microcalcifications, irregular margins, absent halo sign, and increased intramodular blood flow.[18][19][20] The American Thyroid Association (ATA) has published guidelines for the differentiation and management of thyroid nodules and thyroid cancers, and they propose a scoring system using the ultrasound characteristics of the thyroid nodules.[21] One of the newest radiology systems, called TIRADS, also uses a score sum based on points for the different features of the adenomas seen in the thyroid ultrasound. This score has been correlated with the risk of thyroid malignancy.[22][23][24][25]

Fine needle aspiration (FNA) has ultimately been used in evaluating a thyroid nodule with suspicious radiology features, especially in patients with a high risk of malignancy. It should be mentioned that fine-needle aspiration may not provide a definite diagnosis in all cases. In patients with thyroid adenoma, the cytological sample has organized follicular epithelial cells. On the other hand, aspiration can show follicular cells with abnormal architecture and atypia. These patients are characterized as having atypia of undetermined significance.[26] A benign thyroid adenoma is confirmed only after ruling out capsular and vessel invasion in the final histological examination done by pathologists after a partial or total thyroidectomy operation. Genetic testing has also helped a lot in predicting the risk of thyroid cancer, and it has frequently been used in the final decision-making of proceeding to surgical intervention of removing a thyroid nodule versus not.[27]

Treatment / Management

In some asymptomatic patients with small thyroid adenomas and no malignancy found by fine needle aspiration, regular monitoring with repeat ultrasonography is usually recommended. The FNA might need to be repeated if the nodule grows in size in future examinations or if other suspicious features are seen in a radiologic evaluation with an ultrasound.[2] The development of accurate molecular genetic testing of thyroid tissue obtained during thyroid biopsies has helped decrease unnecessary surgeries or at least limit the number of total thyroidectomies and favor less extensive thyroid gland operations.[28][29][30][31]

For patients with benign thyroid adenomas, thyroid lobectomy and isthmusectomy is a sufficient surgical treatment. This procedure is also adequate for patients with minimally invasive thyroid cancer. When histological examination shows no signs of malignancy, then no further intervention is required. These patients should only continue to have their thyroid hormone status regularly checked.[15][32]

Non-euthyroid patients with a solitary toxic nodule, which is a functioning thyroid adenoma, may be treated with anti-thyroid drugs to achieve a euthyroid state. Treatments with iodine-131 therapy or thyroidectomy are also recommended options. The advantages of surgical therapy are relief from compressive symptoms, immediate resolution of hyperthyroidism, and avoidance of radiation exposure to the normal part of the thyroid gland.[15][33] The use of local ethanol injections for ablation purposes of a toxic adenoma has been used in specialized centers, but it is not widely popular with questionable long-term effectiveness.[34]

Differential Diagnosis

Thyroid adenoma typically presents as a solitary nodule and should therefore be differentiated from:

• A cyst (parathyroid or thyroglossal)
• Multinodular goiter
• Parathyroid adenoma
• Thyroiditis
• Carcinoma (follicular, papillary, medullary, parathyroid, or any other carcinoma)[4]

Prognosis

Thyroid adenomas are the most common benign lesions and have an excellent prognosis.

However, there is a 20% probability of malignant transformation. In these cases, oncological management and an interprofessional team approach are necessary.[35][36]

Complications

Most patients with thyroid adenomas are asymptomatic. However, patients with functioning thyroid adenoma may have symptoms of hyperthyroidism, such as fatigue, sweating, tremor, palpitations, and anxiety.[37] Some patients may complain of dyspnea, hoarseness of voice, and dysphagia due to compression of the trachea or esophagus by a growing thyroid tumor.[15]

Consultations

The following consultations are required in cases of thyroid adenomas:

• Endocrinology
• Radiology
• Surgery (general or specialized endocrine)
• Pathology
• Nuclear medicine

Deterrence and Patient Education

As a result of the widespread use of ultrasound for evaluating different pathologies of the neck, many people have been found to have incidental thyroid nodules. Patients should be reassured that the majority of these nodules are benign lesions and they are too small to be palpated. Ultrasound-guided FNA should be done for the larger lesions, which can most of the time be palpated.[38][10]

Pearls and Other Issues

A close collaboration between an endocrinologist, a radiologist, and an experienced endocrine neck surgeon is warranted for the best approach to thyroid adenomas. The benign tumors do not need any aggressive management and can be followed conservatively, but the thyroid nodules showing suspicious radiographic features should be looked at more closely. A thyroid biopsy by fine needle aspiration is considered routine testing, and depending on its cytology results, the final treatment decision can be made. Different scoring systems have been developed to help differentiate benign versus malignant nodules, and further molecular genetic testing can assist medical providers in avoiding unnecessary interventions or more testing. The medical team should spend time explaining the process and the different steps to the patients in detail to increase the comfort level and patient collaboration.

Enhancing Healthcare Team Outcomes

Although thyroid adenomas are usually benign lesions, they should be monitored continuously for malignant potential; this requires the involvement of an interprofessional healthcare team consisting of clinicians (MDs, DOs, NPs, and PAs), specialists (particularly an endocrinologist), nursing staff, and depending on the therapeutic path chosen, possibly pharmacists. Clinicians may note the lesions on routine testing, and any ambiguity about how to proceed or the differential should involve an endocrinology consult. Nurses can assist in evaluation, counsel the patient, help monitor the condition, and coordinate activities between the various clinical personnel involved. In cases where thyroid tissue is surgically or otherwise removed or ablated, thyroid hormone therapy may be necessary, necessitating pharmacists performing medication reconciliation, verifying dosing, and patient medication counseling. The interprofessional team approach will help drive optimal patient outcomes with the fewest adverse events. [Level 5]

The probability of malignancy for palpable thyroid lesions is higher than for non-palpable nodules.[39] To date, there is no evidence supporting ultrasound screening for non-palpable thyroid nodules.[40] Thyroid adenomas remain a challenge for healthcare workers regarding their diagnosis and management. Collaboration and teamwork between different specialists can enhance the outcomes of these cases.