Parathyroid adenomas are benign tumors of the parathyroid glands and are the most common cause of primary hyperparathyroidism.

Epidemiology

Associations

There is an association with multiple endocrine neoplasia types I (MEN1) and IV (MEN4).

Clinical presentation

Patients typically present with primary hyperparathyroidism: elevated serum calcium levels and elevated serum parathyroid hormone levels. This results in multisystem effects including osteoporosis, renal calculi, constipation, peptic ulcers, mental changes, fatigue, and depression.

Rarely, parathyroid adenomas present with spontaneous hemorrhage, which can be large and potentially narrow the airway ²¹. 

Pathology

They are usually oval or bean-shaped, but larger adenomas can be multilobulated. The vast majority (up to 87% ²) of adenomas occur as solitary lesions.

Location

The majority of parathyroid adenomas are juxtathyroid and located immediately posterior or inferior to the thyroid gland. Superior gland parathyroid adenomas may lie posteriorly in the tracheo-esophageal groove, paraesophageal location, or even as inferior as the mediastinum ¹².

Up to 5% of parathyroid adenomas can occur in ectopic locations. Common ectopic locations include ^1,12:

• mediastinum

• retropharyngeal

• carotid sheath

• intrathyroidal

Variants

• parathyroid lipoadenoma ¹⁶

Markers

Parathyroid hormone levels are usually elevated (normal range 1.6-6.9 pmol/L or 10-55 pg/mL). Anticipated size of parathyroid adenoma is usually proportionate to the elevated parathyroid hormone level ^ref.

Radiographic features

Ultrasound

Ultrasound is one of the most commonly used initial imaging modalities.

Greyscale

• most nodules need to be >1 cm to be confidently seen on ultrasound ^ref

• parathyroid adenomas tend to be homogeneously hypoechoic compared to the overlying thyroid gland ^ref

• an echogenic thyroid capsule separating the thyroid from the parathyroid may be seen: some of the nodule may appear as fairly well-defined with no appreciable capsule ^ref

• atypical features include ²⁷

  • cystic degeneration: can range from minimal cystic change to mostly cystic (>50%) or cystic (~5%)

  • calcification (~1.5%)

Doppler

Color Doppler signal can be seen in ~90% (range 85-97%) ^29-31 of parathyroid adenomas in primary hyperparathyroidism, with a lower rate (~65%) in secondary hyperparathyroidism ²⁹. A variable pattern of color Doppler signal can be seen with combined patterns sometimes present ³³:

• variable central/internal color Doppler signal that can indicate small to abundant blood flow ^6,31-33

  • low resistive index, which decreases as serum PTH increase ^6,32

• polar/feeding vessel sign

  • extrathyroidal arterial feeder (usually a branch of the inferior thyroidal artery) at one of the parathyroid poles ^1,6

  • present in ~80% (range 70-97.6%) of parathyroid adenomas ^31,33 with smaller parathyroid adenomas less likely to have this sign ³¹

  • can help differentiate from lymph nodes (central/hilar vascularity) and thyroid nodules (vascularity not seen) ^32,33

• arc or rim of color Doppler signal ^29,30

• no color Doppler signal ³¹

Usually, parathyroid adenomas appear more vascularized than thyroid parenchyma ³³. The overlying ipsilateral thyroid gland commonly (~85%) shows asymmetric hypervascularity ³².

CT

CT can detect suspected ectopic glands (often mediastinal), such as in the case of failed parathyroidectomy ⁶. 4D parathyroid CT is a valuable modality in the era of minimally-invasive parathyroidectomy to precisely localize adenomas preoperatively. 4D CT has been shown to be more sensitive than sonography and scintigraphy for preoperative localization of parathyroid adenomas ^13,15. 

See the separate article on 4D parathyroid CT for an approach to interpretation and the imaging appearance of parathyroid lesions. The classic pattern of parathyroid adenomas, with intense enhancement on arterial phase, washout of contrast on delayed phase, and low attenuation on non-contrast imaging ¹², is present in only a minority of cases ¹⁹. 

Several morphologic features can support the diagnosis of an abnormal parathyroid gland ¹⁴:

• polar vessel sign

  • an enlarged feeding artery or draining vein leading to the end of a hypervascular parathyroid

  • most neuroendocrine tumors are hypervascular

• larger lesion: single adenomas tend to be larger than multiglandular disease and size increases diagnostic confidence

• on non-contrast imaging parathyroid adenomas are less dense than the thyroid as they are iodine-deplete

MRI

MRI is infrequently utilized in initial workup because of lower spatial resolution and artifacts. Adenomas can show variable signal intensity on MRI. Reported signal characteristics include:

• T1

  • typically intermediate to low signal

  • subacute hemorrhage can cause high signal intensity ⁶

  • fibrosis or old hemorrhage can cause low signal intensity ⁶

• T2

  • typically hyperintense

  • subacute hemorrhage can cause high signal intensity ⁶

  • fibrosis or old hemorrhage can cause low signal intensity ⁶

Since most lesions demonstrate high T2 signal intensity, the addition of contrast for MRI does not significantly increase detection.

Nuclear medicine

SPECT and planar scintigraphy using Tc-99m sestamibi (most common) or Tc-99m tetrofosmin can help localize parathyroid lesions, which show high radiotracer uptake and persistent activity on delayed (2 hour) images ⁶. Fusion SPECT-CT can further aid anatomic localization. 

18F-fluorocholine PET-CT is an emerging modality (c. 2021) with reported localization rates similar to sestamibi ^18,20.

Treatment and prognosis

Surgical treatment is reserved for symptomatic patients. Surgery is successful in treating primary hyperparathyroidism caused by parathyroid adenomas in 95-98% of cases ¹⁷. Ethanol ablation is an additional alternative treatment ²⁸.

Differential diagnosis

For a non-ectopic adenoma on ultrasound, consider:

• parathyroid hyperplasia

• eccentric thyroid nodule

• sequestered thyroid tissue

• lymph node

• blood vessel