Imaging in Primary Hyperparathyroidism 

Hyperparathyroidism is a disease of increased bone resorption and bone formation. Subsequently, plain radiographic findings may include resorption and sclerosis of numerous sites in the skeletal system.

Historically, osteitis fibrosa cystica was used to describe the advanced skeletal disease in primary hyperparathyroidism. Bone findings were characterized by the osteoclastic resorption of bone, osteoblastic bone formation, and fibrous replacement of marrow, with radiographic findings of subperiosteal resorption, brown tumors, bone cysts, and sclerosis.

These days, the most common radiologic finding in primary hyperparathyroidism is osteopenia, which may be generalized or asymmetric. Fine trabeculations are initially lost, with resultant coarse and thickened trabeculae. The disease may progress with further destruction that results in a ground-glass appearance in the trabeculae. About 30-50% of the bone density must be lost to show changes on radiographs. Other methods for the quantification of bone density, such as QCT scanning and DXA, are more sensitive in the evaluation of osteopenia.

Additional findings include bone resorption, which may occur at many different anatomic sites. Bone resorption may be classified as subperiosteal, intracortical, trabecular, endosteal, subchondral, subligamentous, or subtendinous. Subperiosteal bone resorption is an early and virtually pathognomonic sign of hyperparathyroidism, and this finding is marked by marginal erosions with adjacent resorption of bone and sclerosis. An unusual lacelike appearance may be seen beneath the periosteum with an occasional spiculated external cortex. The underlying resorptive process may progress to complete cortical disappearance.

Although subperiosteal bone resorption can affect many sites, the most common site in hyperparathyroidism is the middle phalanges of the index and middle fingers, primarily on the radial aspect (see the images below).

Other sites of subperiosteal resorption include the phalangeal tufts (acro-osteolysis), the lamina dura around the teeth, the medial aspect of the tibia, the humerus, the femur, and the distal clavicle. For depictions of these sites, see the images below. When the resorption extends to the margins of joints, particularly in the hands, wrists, and feet, findings may appear articular.

Other areas of resorption, such as cortical or endosteal regions, are usually accompanied by subperiosteal findings. Intracortical bone resorption is an indicator of rapid bone turnover and is described as linearly oriented striations in the cortex. The linear lucencies are produced by resorption of bone in the haversian canals and are best seen on the cortical surface of the second metacarpal.

Trabecular bone resorption may occur throughout the skeleton and usually accompanies advanced disease. In the skull, areas of decreased radiopacity are intermingled with sclerotic radiopaque areas, resulting in a classic appearance called the salt-and-pepper skull (see the image below).

In endosteal resorption, the medullary cavity widens, with thinning of the inner cortex (see the images below). Changes are usually best seen in the hands and appear as scalloped lucencies on the inner aspect of the bony cortex. Endosteal changes are usually accompanied by subperiosteal or cortical resorption.

Subchondral bone resorption is most common in the joints of the axial skeleton, such as the sacroiliac, acromioclavicular (see the image below) discovertebral, sternoclavicular, and symphysis pubis, but it may also occur in the joints of the appendicular skeleton. Subchondral bone is resorbed; collapse with subsequent new bone formation and fibrous replacement may result.

On radiographs, areas of subchondral lucency are noted with surrounding sclerosis. In the sacroiliac joint, bilateral findings affect the ilium more than the sacrum and may produce an irregular articular margin with the appearance of a widened joint. At the acromioclavicular joint, bilateral erosions affect the clavicle side more than the acromion, whereas the sternum and clavicle are equally affected at the sternoclavicular joint.

Subligamentous and subtendinous resorption occurs at insertion sites on bones. Common sites are the plantar aspect of the calcaneus, dorsal aspect of the patella, inferior margin of the distal clavicle, trochanters, and ischial and humeral tuberosities.

Brown tumors are well-circumscribed lytic lesions of bone that represent the osteoclastic resorption of a confluent area of bone with subsequent fibrous replacement (see the images below). The lesions may be single or multiple, with expansion of overlying bone, and they may be present in any site, although the lesions usually occur in cortical bone. Common sites include the mandible, clavicle, ribs, pelvis, and femur.

After resection of an adenoma, lesions may become sclerotic on radiographs. Once considered a finding that was characteristic of primary hyperparathyroidism, brown tumors are more common in secondary hyperparathyroidism because of the increasing population and life expectancy of patients undergoing dialysis.

Calcium pyrophosphate dihydrate crystal deposition disease (CPPD) is more common in association with primary hyperparathyroidism than with secondary hyperparathyroidism. Chondrocalcinosis may affect the menisci of the knee, the triangular cartilage of the wrist, and the symphysis pubis. CPPD arthropathy is less common in these patients than in patients with idiopathic disease.

Other radiographic findings in primary hyperparathyroidism include varying degrees of sclerosis, although generalized sclerosis is more common in secondary hyperparathyroidism. Soft-tissue and vascular calcification is more common in secondary disease, as is superior and inferior band sclerosis of the spine, which is called rugger-jersey spine. The laxity of ligaments and tendons primarily affects the sacroiliac and acromioclavicular joints, whereas rupture may be seen at several sites, including the quadriceps, triceps, and patellar tendons.

Degree of confidence

In the setting of elevated serum calcium levels and elevated PTH levels, the diagnosis of primary hyperparathyroidism is certain. However, radiographic findings of subperiosteal resorption are most specific for the disease and should prompt consideration of the primary hyperparathyroidism.

MRI is one diagnostic modality that can be used to evaluate ectopic parathyroid adenomas. On T1-weighted images, adenomas appear as low-signal-intensity masses, whereas intermediate or high signal intensity is seen on T2-weighted images. Gadolinium enhancement with fat suppression results in diffuse enhancement of the adenoma. (See the images below.)

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

MRI findings of brown tumors are nonspecific. Bony expansion can be visualized, and the extent of the lesion can be determined. The imaging characteristics depend on the amount of fibrous tissue, hemorrhage, and cystic changes that are present in the lesion. Lack of an associated soft-tissue mass is a pertinent negative finding that can be demonstrated on MRIs.

Ultrasonography is one of the primary modalities used to localize parathyroid tumors. The size of the adenoma is usually correlated with the degree of parathyroid elevation. Adenomas appear as well-defined hypoechoic lesions with potential cystic or necrotic areas. Ultrasonography offers the advantage of depicting potential concomitant thyroid disease, which is present in approximately 40% of patients with parathyroid disease.

In renal imaging, ultrasonography can demonstrate bilateral hyperechoic medullary pyramids that are consistent with medullary nephrocalcinosis; this is a nonspecific finding (see the image below).

Degree of confidence

Ultrasonography is approximately 75% sensitive in identifying adenomas, but this technique has low sensitivity in identifying ectopic lesions.

In parathyroid imaging, localization of the parathyroid glands may be accomplished with ^99m Tc MIBI scanning (see the image below). Both thyroid and parathyroid tissues demonstrate radionuclide uptake, but sestamibi washes out of thyroid tissue early after its injection, leaving only parathyroid tissue that demonstrates activity at 2-4 hours.

In musculoskeletal imaging, bone densitometry is extremely valuable in assessing primary hyperparathyroidism because it can be used to quantify bone loss, and it may help making predictions regarding the fracture risk. DXA helps in evaluating the mineral content of all bone in the path of the beam. Bone mineral density is expressed as either a T score, which is based on the standard deviations from a young-adult mean, or as a Z score, which is compared with an age-matched mean. The T score is used to clinically diagnose osteopenia or osteoporosis and to predict the fracture risk. DXA may also be used after an intervention to document improvements in bone density.

The diagnosis of primary hyperparathyroidism is based on biochemical determinations, and bone scanning has a limited role in making the diagnosis. In addition, a few patients with hyperparathyroidism have insufficient disease for its demonstration on bone scans. However, bone scanning may assist in differentiating hyperparathyroidism from metastatic disease in the setting of elevated calcium levels. Because bone turns over significantly in hyperparathyroidism, findings on bone scans include generalized increased radionuclide uptake throughout the skeleton in contrast to soft tissues; this observation is called a superscan. Because the contrast of the skeletal system is increased, renal activity may not be apparent.

With parathyroid imaging, ectopic adenomas can be assessed by using contrast-enhanced CT scan studies. However, sestamibi and MRI are more sensitive, and these are the imaging studies of choice in most patients (see the images below).

In musculoskeletal imaging, QCT scanning is another method of bone densitometry. This modality offers the advantage of selective evaluation of the mineral content in trabecular bone, which makes QCT scanning more sensitive in detecting small changes in bone density.

With parathyroid imaging, ectopic adenomas can be assessed by using contrast-enhanced CT scan studies. However, sestamibi and MRI are more sensitive, and these are the imaging studies of choice in most patients (see the images below).

In musculoskeletal imaging, QCT scanning is another method of bone densitometry. This modality offers the advantage of selective evaluation of the mineral content in trabecular bone, which makes QCT scanning more sensitive in detecting small changes in bone density.