Radiological Imaging of Hyperparathyroidism.

Dr/ ABD ALLAH NAZEER. MD.

Hyperparathyroidism is the effect of excess parathyroid hormone (PTH) in the body. It can be primary, secondary or tertiary. There are many characteristic imaging features predominantly involving the skeletal system.PathologyIncreased levels of the PTH lead to increased osteoclastic activity. The resultant bone resorption produces cortical thinning (subperiosteal resorption) and osteopenia.SubtypesPrimary hyperparathyroidism

parathyroid adenoma (~80%)multiple parathyroid adenomas (4%)

parathyroid hyperplasia (10-15%)parathyroid carcinoma (1-5%)

Secondary hyperparathyroidismCaused by chronic hypocalcaemia with renal osteodystrophy being the most common cause (others include malnutrition, vitamin D deficiency)results in parathyroid hyperplasia

Tertiary hyperparathyroidismAutonomous parathyroid adenoma caused by the chronic overstimulation of hyperplastic glands in renal insufficiency.

AssociationsHyperparathyroidism can occur in the context of the following conditions from parathyroid hyperplasia or less commonly multiple parathyroid adenomas:multiple endocrine neoplasia (MEN) type IMEN type IIafamilial hypocalciuric hypercalcaemiafamilial isolated primary hyperparathyroidism Radiographic featuressubperiosteal bone resorption

Classically affects the radial aspects of the proximal and middle phalanges of the 2nd and 3rd fingersmedial aspect of tibia, femur, humeruslamina dura: floating teeth (not specific)

Subchondral resorptionlateral end of the claviclessymphysis pubissacroiliac joints

subligamentous resorptionischial tuberositytrochantersinferior surface of calcaneus and clavicle

intracortical resorption: cigar/oval-shaped or tunnel-shaped radiolucency in the cortexterminal tuft erosion (acro-osteolysis)rugger jersey spineosteopaeniaBrown tumourssalt and pepper sign in the skull (pepper pot skull)chondrocalcinosisFindings in secondary (and tertiary) hyperparathyroidism are often associated with the osteosclerosis of renal osteodystrophy, and the osteomalacia of vitamin D deficiency:subperiosteal bone resorptionosteopaeniaosteosclerosis, e.g. rugger-jersey spinesoft tissue calcificationsuperscan: generalized increased uptake on Tc-99m pertechnetate bone scan (focal uptake with adenoma).Superior and inferior rib notching.

Primary hyperparathyroidism (PHP) is a disease in which one or more hyperactive parathyroid glands constantly make too much parathyroid hormone (PTH).In primary hyperparathyroidism, the "thermostat" controlling the calcium is always on high. This leads to calcium being taken out of the bones (leading to weakening of the bones or osteoporosis) and gastrointestinal tract and put into the blood stream.This increases the blood levels of calcium. Since the blood is cleaned (filtered) by the kidneys, this leads to the kidneys being exposed to high levels of calcium, which can lead to kidney stones, kidney damage, and other problems.In most patients with primary hyperparathyroidism (80%), only one of the four parathyroid glands is diseased - these people have what is called a "single adenoma." In about 10% of affected people, two or three glands are hyperactive- called "double or triple adenoma." Finally, in 10% of patients, all four glands are hyperactive- called "four gland hyperplasia." About 28 out of 100,000 people will have this disease and it is twice as common in women than men.The disease becomes more common as people get older and most commonly occurs after age 45 with an average age of 65.Primary hyperparathyroidism is the most common cause of abnormally high blood calcium levels in the general population.

Plain radiographic findings may include resorption and sclerosis of numerous sites in the skeletal system. X-Ray: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 DEXA, 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.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.

Anteroposterior radiographic view of the right hand in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism (same patient as in the previous image). This image shows subperiosteal bone resorption along the radial aspects of the middle phalanges (arrows).

This image demonstrates subperiosteal resorption that has resulted in severe tuftal resorption . Also, note the subperiosteal and intracortical resorption.

Radiograph of the phalanges in a patient with primary hyperparathyroidism. This image demonstrates subperiosteal resorption that has resulted in severe tuftal resorption (arrows).

In the skull, areas of decreased radio opacity are intermingled with sclerotic radio opaque areas, resulting in a classic appearance called the salt-and-pepper skull.

Salt and Pepper appearance of Skull. 

Radiograph of the shoulder in a patient with primary hyperparathyroidism. This image depicts subperiosteal distal clavicular resorption (arrows).

Radiograph of the distal femur in a patient with primary hyperparathyroidism. This image shows scalloped defects along the inner margin of the cortex, which denote endosteal

resorption.

Radiograph of the humerus in a patient with primary hyperparathyroidism. This image depicts a brown tumor. Note the osseous expansion and lucency of the proximal humerus. Brown tumors can have varied appearances.

Radiograph of the mid femoral diaphysis in a patient with primary hyperparathyroidism. This image depicts brown tumors. Note the eccentric (arrowheads) and central positions (arrow) of the lesions.

Rugger jersey spine - prominent vertebral sub endplate densities due to hyperparathyroidism and usually secondary to chronic renal failure.

Brown tumors.

Brown tumor.

(a) CT image shows a 7-mm-diameter calculus in the collecting system of the mid right kidney (black arrow). There is diffuse mottled osteosclerosis of the visualized bones. A healed fracture of the posterior right 12th rib (white arrow) and expansile lytic lesions of the anterior ribs (arrowheads) are seen. (b) CT image shows subchondral resorption on the iliac side of the sacroiliac joints; subsequent collapse due to weight bearing produced apparent joint widening (black arrows). There are lytic lesions of the right iliac crest (white arrow) and left hemisacrum (arrowhead) with violation of the left first sacral foramen.

(a) Computed tomography scan (axial section) showing well-defined soft tissue lesion within the left body of the mandible. (b) Axial section showing maxillary lesion. (c) Coronal section showing skull bone lesion on the left side. (d) 3D reconstruction showing bilateral lytic lesion within the body of the mandible and generalized reduction in the bone density (arrow indicating the lesion)

Medullary Nephrocalcinosis.

Ultrasonography: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.

Sonogram of the kidney in a patient with primary hyperparathyroidism. This image shows medullary nephrocalcinosis.

Ultrasound: parathyroid mass is marked by yellow arrows under the paler thyroid gland. Para-thyroid Adenoma, SPECT/CT image.

In recent years 4D-CT has emerged as a useful imaging technique in the work-up of patients with primary hyperparathyroidism to allow sensitive detection and localization of parathyroid adenomas and parathyroid hyperplasia. What is 4D-CT?4D-CT includes image sets in three planes (axial, coronal, sagittal) from the angle of mandible to the mediastinum (1). The “fourth” dimension of 4D-CT is the perfusion information derived from multiple contrast phases. It is most commonly performed with three phases: non-contrast, arterial, and delayed phase imaging (1, 2).

Findings of adenoma or hyperplasia: An oval shaped enhancing mass with low attenuation on non-contrast phase relative to thyroid, greatest attenuation in the arterial phase, and rapid washout of contrast in the delayed phase. There are variations in enhancement patterns and helpful morphological findings such as the polar vessel (1, 3, 4).

Axial noncontrast (A), axial early phase post contrast (B), and axial delayed phase post contrast (C) images show a hypo attenuated hypodense nodule contiguous with the left posterior thyroid gland, which demonstrates avid early contrast enhancement and washout. Pathology revealed a 600-mg parathyroid adenoma.

4D-CT scan of L upper parathyroid tumor, with 3D reconstruction (above) and cross-section.

A 49-year-old female with primary hyperparathyroidism and nephrolithiasis. 99mTc-Sestamibi SPECT/CT demonstrates a large parathyroid adenoma arising from the right lower neck, crossing the midline anterior to the trachea and extending towards the left side of the neck.

A 64-year-old man with chronic kidney disease and primary hyperparathyroidism. 99mTc-sestamibi SPECT/CT images confirm the focus of tracer retention correlating with a 1.4cm soft tissue nodule located immediately inferior to the left lobe of the thyroid, consistent with a parathyroid adenoma.

Modified 4D CT by using our suggested protocol demonstrates the enhancement characteristics of a hyperplastic parathyroid adenoma (region of interest 1) and an adjacent soft tissue structure (i.e., a normal-functioning thyroid gland) (region of interest 2). Contrast-enhancement analysis on the parathyroid adenoma shows an attenuation value of 36.1 HU on the virtual noncontrast scan (A), which rapidly enhanced to 175.5 HU in the arterial phase (B), and immediately decreased to 100.3 HU in the dual-energy venous phase (C) and 75.1 HU in the delayed (D) image. The parathyroid adenoma can be easily distinguished from the surrounding soft tissues on the basis of its characteristic “rapid contrast uptake and washout” feature.

CT examination of the patient by using our modified 4D CT protocol shows a 6 x 3 mm nodular parathyroid adenoma (arrows) lying in the superomedial aspect, posterior to the left thyroid lobe in both sagittal (A) and axial (B) sections. The iodine overlay image (acquired by using dual-energy CT in the venous phase), also obtained by using this protocol, allows the measurement of iodine concentration in the tissues, to differentiate between the parathyroid adenoma and surrounding thyroid tissues (C). Directed para-thyroidectomy and histopathologic examination, thereafter, confirmed the presence of a parathyroid adenoma.

Sestamibi scan.

Nuclear Imaging (Sestamibi scan): Sestamibi scans involve injecting a small amount of special radioactive material into a vein and taking an X-ray image of the chest, neck, and head. Sestamibi scans have an accuracy rate of about 80 to 95%. The accuracy of the test is very institution-specific and depends on the quality of the equipment used, the technique used to perform the test, and the skill of the interpreter. Centers that perform a lot of parathyroid surgery typically have more accurate sestamibi scans. The advantages of sestamibi scans are its wide availability and the ability to evaluate for diseased glands outside of the neck at the same time.

Hyperparathyroidism, Sestamibi scan; 32

Dual-tracer (subtraction) scintigraphy. Top left: Scintigram obtained after injection of 99mTc-sestamibi (which is taken up by both thyroid and parathyroid tissue) shows asymmetric increased activity at the lateral aspect of the lower right thyroid lobe (arrow). Bottom left: Scintigram obtained after injection of 99mTc-pertechnetate (which is preferentially taken up by the thyroid) shows a relatively photopenic focus in the same region (arrow). Right: Subtracted image shows differential 99mTc-sestamibi activity at the same location (arrowheads). This finding was shown to represent a parathyroid adenoma.

Scintigraphic manifestation of the "salt-and-pepper" sign of the skull in hyperparathyroidism.

Technetium-99m sestamibi (99mTc MIBI) images in a patient with primary hyperparathyroidism. The initial (A) and 3.5-hour delayed (B) images demonstrate a 6-cm parathyroid adenoma (arrows).

Technetium-99m sestamibi scan (99mTc MIBI) in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). This image demonstrates persistent abnormal activity of the inferior right parathyroid gland that is consistent with an adenoma.

Indium-111 (111In) octreotide scan in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) (same patient as in the previous 3 images). These nuclear images demonstrate abnormal activity in the pituitary macroadenoma (curved arrow), parathyroid adenoma (straight arrow), and gastrinoma metastases throughout the abdomen (arrowheads).

Superscan shows diffusely increased activity in the axial skeleton and perhaps in the calvaria and mandible. The ratio of bone to soft tissue is increased, and the kidneys and urinary bladder are absent.

Technetium-99m bone scan in a patient with chronic renal disease shows uptake in the lungs and calvaria. No renal or bladder activity was noted. (The kidneys are not shown.)

Scans performed on 64-y-old woman with primary hyperparathyroidism. Selected coronal (A–C) and transverse (D–F) tomograms of subtraction SPECT (A and D), CT (B and E), and fused SPECT/CT (C and F) demonstrate focus of residual activity associated with small soft-tissue nodule (arrow) located posterior to right thyroid lobe, found at surgery to represent 150-mg parathyroid adenoma. Larger, more intense site of residual activity associated with 3-cm nodule within left thyroid lobe (arrowhead) was found at surgery to represent 5-g well-encapsulated thyroid adenoma.

99mTc-Sestamibi scan of patient with osteitis fibrosa cystica (group III): early (A) and delayed (B) images of right inferior parathyroid adenoma (arrows) weighing 6.5 g before initial surgery.

MRI: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.

MRI scan with parathyroid adenoma identified low in the neck.

Sagittal (left image) and coronal (right image) T1-weighted magnetic resonance images of the brain in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) (same patient as in the previous image). These images show a pituitary macroadenoma (arrows).

Rugger-jersey spine.

ConclusionRadiographic findings of subperiosteal resorption are most specific for the disease and should prompt consideration of the primary hyperparathyroidism.Ultrasonography is approximately 75% sensitive in identifying adenomas, but this technique has low sensitivity in identifying ectopic lesions. The advantages of sestamibi scans are its wide availability and the ability to evaluate for diseased glands outside of the neck at the same time.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 MRI. MRI is one diagnostic modality that can be used to evaluate ectopic parathyroid adenomas

Thank You.