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Primary hyperparathyroidism (PHPT) is a disorder characterized by the overproduction of parathyroid hormone (PTH) from one or more parathyroid glands, leading to hypercalcemia. It is most commonly caused by parathyroid adenomas, but it can also result from parathyroid gland hyperplasia, a condition where all four parathyroid glands are enlarged, typically in response to chronic stimulation by elevated levels of calcium or PTH. Parathyroid gland hyperplasia accounts for a smaller percentage of PHPT cases compared to adenomas but presents unique challenges in diagnosis and treatment. Radiological imaging plays a crucial role in the preoperative localization of abnormal parathyroid tissue, especially in cases of parathyroid gland hyperplasia. The imaging characteristics of this condition are essential for differentiating it from other causes of hyperparathyroidism and for guiding surgical management. This article examines the radiological features of primary hyperparathyroidism in the context of parathyroid gland hyperplasia [1].

Pathophysiology and Clinical Features of Parathyroid Gland Hyperplasia

Parathyroid gland hyperplasia is characterized by the uniform enlargement of all four parathyroid glands, as opposed to the more common parathyroid adenomas, which usually involve a single gland. In most cases, hyperplasia results from prolonged overproduction of PTH, often due to increased calcium levels. The condition is typically associated with other endocrine disorders, such as multiple endocrine neoplasia type 1 (MEN1) and type 2A (MEN2A). In MEN1, hyperplasia is a feature of the disease, alongside other tumors such as pituitary adenomas and pancreatic islet cell tumors [2]. Patients with parathyroid gland hyperplasia may present with the typical symptoms of hypercalcemia, including fatigue, weakness, bone pain, kidney stones, and gastrointestinal disturbances. However, some patients are asymptomatic, and the condition is discovered incidentally during routine laboratory tests revealing elevated calcium and PTH levels. Diagnosis is confirmed by imaging studies and, ultimately, histopathological examination of the parathyroid glands after surgical removal [3].

Role of Ultrasound in Parathyroid Gland Hyperplasia

Ultrasound is typically the first-line imaging modality for evaluating suspected parathyroid disorders, including hyperplasia. It is non-invasive, widely available, and offers real-time imaging, making it an essential tool for initial evaluation. However, ultrasound is less effective than other modalities in the detection of parathyroid gland hyperplasia, particularly when all four glands are involved. In cases of parathyroid gland hyperplasia, ultrasound may demonstrate multiple enlarged parathyroid glands, usually in the lower neck region. These glands tend to appear as hypoechoic or mildly hyperechoic masses, often with a homogeneous texture. Unlike parathyroid adenomas, which are typically more well-defined and localized, hyperplastic glands may be less distinct, and their borders may blend with surrounding structures. This lack of clear demarcation can make it difficult to distinguish hyperplasia from other pathological conditions, such as thyroid nodules or lymphadenopathy [4]. Despite these limitations, ultrasound can still provide valuable information in patients with suspected hyperplasia, especially when it helps identify enlarged glands that might otherwise be missed. When the hyperplasia is more focal or associated with a single enlarged gland, ultrasound can provide better resolution and allow for accurate localization for surgical planning [5].

Role of Sestamibi Scintigraphy

Sestamibi scintigraphy, a nuclear medicine technique that uses technetium-99m-labeled sestamibi to assess parathyroid function, is a valuable imaging tool in the evaluation of primary hyperparathyroidism, especially in cases of parathyroid gland hyperplasia. Sestamibi scanning provides functional imaging of parathyroid tissue by detecting areas of increased radiotracer uptake, which corresponds to active parathyroid tissue. In parathyroid gland hyperplasia, sestamibi scintigraphy often shows diffuse or symmetric uptake in all four glands, reflecting the hyperplastic nature of the condition. This uniform uptake is a distinguishing feature of hyperplasia, as opposed to parathyroid adenomas, which typically demonstrate focal uptake in a single gland. The ability to detect symmetric radiotracer uptake in all four glands is crucial in diagnosing parathyroid gland hyperplasia and helps differentiate it from adenomas or other causes of hyperparathyroidism [6]. However, sestamibi scintigraphy can still present challenges in the context of parathyroid gland hyperplasia. In some cases, the uptake may not be intense enough to be clearly distinguishable from the surrounding normal thyroid tissue. Additionally, the test’s sensitivity can be affected by the size and location of the hyperplastic glands, particularly if they are small or deeply located within the neck or thoracic cavity.

Role of CT and MRI in Parathyroid Gland Hyperplasia

Computed tomography (CT) and magnetic resonance imaging (MRI) are advanced imaging techniques that can be used to evaluate parathyroid gland hyperplasia, particularly when other imaging modalities, such as ultrasound and sestamibi scintigraphy, are inconclusive. These modalities are particularly useful in patients with large or ectopic parathyroid glands, where precise localization is critical for surgical planning. CT imaging provides detailed cross-sectional images of the neck and upper chest, allowing for the identification of enlarged parathyroid glands and their relationship to surrounding structures. In the case of parathyroid gland hyperplasia, CT may show bilateral enlargement of all four glands, typically with a uniform appearance. CT is also valuable in detecting ectopic parathyroid tissue, which can occasionally be located in the mediastinum or along the carotid sheath. While CT offers excellent anatomical detail, it is limited by its reliance on ionizing radiation, which makes it less suitable for repeated follow-up imaging in patients, particularly in younger individuals [7]. MRI offers similar advantages to CT in terms of anatomical detail but avoids the use of ionizing radiation. MRI is particularly useful in evaluating the soft tissues of the neck, where parathyroid glands are located, and provides high-resolution images that can clearly delineate the relationship between the parathyroid glands and adjacent structures such as the thyroid, trachea, and blood vessels. In cases of parathyroid gland hyperplasia, MRI may demonstrate symmetric enlargement of all four glands. Additionally, MRI is superior in assessing the retrosternal or mediastinal parathyroid glands, which are sometimes difficult to visualize with CT or ultrasound [8].

Advantages and Limitations of Imaging Modalities

The advantages of using ultrasound for the detection of parathyroid gland hyperplasia include its accessibility, lack of ionizing radiation, and ability to provide real-time images. However, ultrasound’s sensitivity is limited in detecting diffuse hyperplasia involving all four glands. It is particularly less effective in identifying deeply located or ectopic parathyroid glands. Sestamibi scintigraphy is effective in identifying diffuse uptake in all four glands in cases of hyperplasia, offering functional information that complements anatomic imaging. However, its sensitivity can be limited by the size and location of the hyperplastic glands, and it may not clearly distinguish between hyperplastic tissue and other structures in the neck. CT and MRI offer superior anatomic detail, especially in evaluating deeply located or ectopic parathyroid glands. MRI, in particular, is useful for assessing soft tissue structures and avoids the use of radiation. However, both CT and MRI are more expensive and less readily available than ultrasound and sestamibi scintigraphy. Additionally, CT involves ionizing radiation, which may be a concern for patients requiring multiple follow-up scans.

Conclusion

Parathyroid gland hyperplasia is a rare but important cause of primary hyperparathyroidism. The radiological evaluation of this condition is essential for accurate diagnosis, localization, and surgical planning. Ultrasound, sestamibi scintigraphy, CT, and MRI each play important roles in the assessment of parathyroid gland hyperplasia, with each modality offering unique strengths and limitations. While ultrasound and sestamibi scintigraphy are commonly used for initial evaluation, CT and MRI provide additional detailed anatomic and functional information, especially in complex cases involving ectopic glands or deep locations. A combination of imaging modalities is often necessary to ensure accurate diagnosis and successful surgical management of patients with primary hyperparathyroidism due to parathyroid gland hyperplasia.

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