The thyroid gland, consisting of two connected lobes, is one of the largest endocrine glands in the human body, weighing 20 - 30 g in adults. Thyroid lesions are often found on the gland, with a prevalence of 4%–7%. Most of them are asymptomatic, and thyroid hormone secretion is normal. The majority of thyroid lesions are non-cancerous. Benign lesions include simple or hemorrhagic cysts, colloid nodules, and thyroid adenomas.
Thyroid adenomas are benign lesions of the thyroid gland. These lesions may be inactive or active, producing thyroid hormones. In this case, 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, which is defined as an autonomously functioning thyroid nodule (AFTN). The majority of the thyroid adenomas are asymptomatic, and they are diagnosed incidentally by ultrasound of the thyroid gland. Less often, they occur as a palpable thyroid nodule.
Most thyroid adenomas are sporadic. However, there are also environmental and genetic factors that are associated with the presence of a thyroid adenoma. Iodine deficiency is a well-known environmental risk factor for the development of a thyroid adenoma. In addition, genetic mutations in BRAF, RET, KRAS, and genetic rearrangement of the PAX8-PPAR gene are strongly associated with the development of a thyroid adenoma.
Thyroid adenomas usually present as a solitary thyroid nodule. They are more common in females. 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 the past few decades, with the use of iodine-salt, their incidence is much lower.
Genetic rearrangement of the PAX8-PPAR gene is strongly associated with the development of a thyroid adenoma. PAX8 is a gene involved in follicular cell differentiation. In fact, the PAX8-PPAR gene rearrangement has been found in 4%-13% of follicular adenomas. There are two major types of thyroid adenomas, functional and non-functional adenomas. Functional adenomas are most commonly the result of a monoclonal expansion of thyroid cells, due to activating mutations in the TSH-receptor gene and less commonly in adenylate cyclase stimulating G alpha protein gene. K-RAS mutation is most commonly found in non-functioning adenomas and is associated with the development of thyroid carcinomas.
Thyroid adenomas are homogenous, solitary, encapsulated tumors. They are usually classified as follicular or papillary. Follicular is the most common type, whereas papillary adenomas are considered extremely rare. There are 5 subtypes of follicular adenomas:
The classification of follicular adenomas into subtypes is based on histological findings such as cellular architecture and the amount of colloid. It is worth mentioning that thyroid adenomas should be differentiated from thyroid carcinomas. Histological evidence of capsular invasion and angioinvasion suggests a malignant lesion of the thyroid gland.
Most patients with thyroid adenomas present with a palpable thyroid nodule. Rarely, they complain of dyspnea due to tracheal compression, hoarseness due to laryngeal nerve irritation, or dysphagia due to esophagus compression. Most of the time, they are euthyroid. However, about 1% of patients with thyroid adenomas are hyperthyroid.
The diagnostic evaluation of a patient with a palpable thyroid nodule includes a TSH level measurement to evaluate the functional baseline status of the thyroid gland, an ultrasound examination of the thyroid gland, and a fine needle aspiration biopsy. All patients with a palpable thyroid nodule should have their thyroid hormone levels (thyroid-stimulating hormone and thyroxine) checked. A toxic adenoma is suspected in patients with low thyroid-stimulating hormone (TSH) levels. These patients should undergo an iodine-123 thyroid scan in order to differentiate a hyperfunctioning nodule (toxic adenoma) from a hypofunctioning nodule.
A hyperfunctioning nodule is considered a benign lesion, as there is less than a 1% possibility of malignancy. On the other hand, hypofunctioning nodules have a 20% possibility of malignancy (malignant transformation). However, most of the 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 in order to differentiate a thyroid adenoma, which is considered a benign lesion from thyroid carcinoma. Sonographic features that are associated with a higher risk of malignancy are hypoechogenicity, microcalcifications, irregular margins, absent halo sign, and increased intramodular blood flow.
Fine needle aspiration (FNA) is necessary, 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, the aspiration can show follicular cells with abnormal architecture with atypia. These patients are characterized as having atypia of undetermined significance. It should be mentioned that the definite diagnosis of a thyroid adenoma is made only after ruling out capsular and vessel invasion in the histological examination after partial or total thyroidectomy.
In some asymptomatic patients with small thyroid adenomas and no malignancy found by FNA, regular monitoring with repeat ultrasonography can be an option. The FNA may be repeated if the nodule grows.
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 continue to have their thyroid hormone status regularly checked.
Non-euthyroid patients that have a solitary toxic nodule, which is a functioning thyroid adenoma, may be treated with anti-thyroid drugs in order to achieve a euthyroid state. Treatments with iodine-131 therapy or thyroidectomy are also good 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.
Thyroid adenoma typically presents as a solitary nodule and should therefore be differentiated from:
Thyroid adenomas are benign lesions and have an excellent prognosis. However, there is a 20% possibility of malignant transformation. In these cases, oncological management and an interprofessional team approach are necessary.
Most of the patients with thyroid adenomas are asymptomatic. However, patients with functioning thyroid adenoma may have hyperthyroidism symptoms, such as fatigue, sweating, tremor, palpitations, and anxiety. Some patients may complain about dyspnea, hoarseness of voice, and dysphagia due to compression of the trachea or esophagus.
The following consultations are required in cases of thyroid adenomas:
As a result of the widespread use of ultrasound for the evaluation of different pathologies of the neck, many people have been diagnosed with 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 larger lesions that can be palpated.
Although thyroid adenomas are usually benign lesions, they should be monitored continuously for malignant potential. The probability of malignancy for palpable thyroid lesions is higher than in non-palpable nodules. To date, there is no evidence supporting US screening for non-palpable thyroid nodules. Thyroid adenomas remain a challenge for healthcare workers when it comes to diagnosis and management. Cooperation and teamwork amongst them can enhance the outcomes of these cases.
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