Age / Sex : 29 / M

Age / Sex : M/29

1) What is your impression?

Two weeks later, you can see the final diagnosis with a brief discussion of this case.

* Send Application Answers to In Sook Lee, MD (lis@pusan.ac.kr)

Courtesy : Young Cheol Yoon,  Samsung Medical Center

Pathologic fracture of left proximal femur with underlying Brown tumor associated with Hyperparathyroidism

Discussion

Findings:

Multilocular cystic mass with heterogeneous enhancement in greater trochanter of left femur (X-ray and MRI)

Generalized increased attenuation of marrow space on X-ray and CT scan

Differential Diagnosis:

Brown Tumor

Giant cell tumor

Aneurysmal bone cyst

Chondroblastoma

Diagnosis:  

Brown Tumor associated with hyperparathyroidism

Discussion:

HYPERPARATHYROIDISM

The majority (80%) of patients with primary hyperparathyroidism have a single adenoma. Multiple parathyroid adenomas may occur in 4% of cases. Chief cell hyperplasia of all glands occurs in 15–20% of patients. Secondary hyperparathyroidism is induced by any condition, or circumstance, which causes the serum calcium to fall. This occurs in vitamin D deficiency, intestinal malabsorption of calcium, chronic renal failure (through lack of the active metabolite of vitamin D, 1,25(OH)₂D), and retention of phosphorus. If this secondary hyperparathyroidism is of sufficiently long standing, an autonomous adenoma may develop in the hyperplastic parathyroid glands, a condition referred to as tertiary hyperparathyroidism. This is usually associated with chronic renal disease but it has also been observed in patients with long-standing vitamin D deficiency and osteomalacia from other causes.

Clinical presentation

Most patients with primary hyperparathyroidism have mild disease and commonly have no symptoms, the diagnosis being made by the finding of asymptomatic hypercalcaemia. The most common clinical presentations, particularly in younger patients, are related to renal stones and nephrocalcinosis (25–35%), high blood pressure (40–60%), acute arthropathy (pseudogout) caused by calcium pyrophosphate dihydrate deposition (chondrocalcinosis), osteoporosis, peptic ulcer and acute pancreatitis, depression, confusional states, proximal muscle weakness and mild nonspecific symptoms such as lethargy, arthralgia and difficulties with mental concentration.

Treatment

Surgical removal of the overactive parathyroid tissue is generally recommended. In experienced hands surgical excision is successful in curing the condition in over 90% of patients. Conservative treatment may be judged to be the management of choice with monitoring of the serum calcium, renal function, blood pressure and bone density at regular intervals.

Radiological findings

With the increased number of patients with primary hyperparathyroidism being diagnosed with asymptomatic hypercalcaemia, the majority (95%) of patients will have no radiological abnormalities.

1.     Subperiosteal erosions

Subperiosteal erosion of cortical bone, particularly in the phalanges, is pathognomonic of hyperparathyroidism. The most sensitive site in which to identify this early subperiosteal erosion is along the radial aspects of the middle phalanges of the index and middle fingers. Other sites may be involved including the distal phalanges (acro-osteolysis), the outer ends of the clavicle, the symphysis pubis, the sacroiliac joints, the proximal medial cortex of the tibia, the proximal humeral shaft, ribs and femur. However, if no subperiosteal erosions are identified in the phalanges, they are unlikely to be identified radiographically elsewhere in the skeleton. Subperiosteal erosions in sites other than the phalanges indicate more severe and long-standing hyperparathyroidism, such as may be found secondary to chronic renal impairment.

2.     Intracortical bone resorption

This results from increased osteoclastic activity in Haversian canals. Radiographically it causes linear translucencies within the cortex (cortical ‘tunnelling’). This feature is not specific for hyperparathyroidism and may be found in other conditions in which bone turnover is increased (e.g. normal childhood, Paget's disease of bone).

3.     Chondrocalcinosis

The deposition of calcium pyrophosphate dihydrate (CPPD) causes articular cartilage and fibrocartilage to become visible on radiographs. This is most likely to be identified on radiographs of the hand (triangular ligament), the knees (articular cartilage and menisci) and symphysis pubis. Other joints less commonly involved are the shoulder and the hip. Clinically the patients may present with acute pain resembling gout, but on joint aspiration pyrophosphate crystals, rather than urate crystals, are found. Affected joints may however be asymptomatic, and chondrocalcinosis noted radiographically might bring the diagnosis of hyperparathyroidism to light in an asymptomatic patient. The combination of chondrocalcinosis in the symphysis pubis and nephrocalcinosis on an abdominal radiograph is diagnostic of hyperparathyroidism. Chondrocalcinosis is a feature of primary disease, rather than that secondary to chronic renal impairment.

4.     Brown tumours (osteitis fibrosa cystica)

Brown tumours are cystic lesions within bone in which there has been excessive osteoclastic resorption. Histologically the cavities are filled with fibrous tissue and osteoclasts, with necrosis and haemorrhagic liquefaction. Radiographically, brown tumours appear as low density, multiloculated cysts that can occur in any skeletal site and may cause expansion of bones. They are now rarely seen.

5.     Osteosclerosis

Osteosclerosis occurs uncommonly in primary hyperparathyroidism but is a common feature of disease secondary to chronic renal impairment. In primary disease with normal renal function it results from an exaggerated osteoblastic response following bone resorption. In secondary causes of hyperparathyroidism it results from excessive accumulation of poorly mineralized osteoid, which appears more dense radiographically than normal bone. The increase in bone density affects particularly the axial skeleton. In the vertebral bodies the end-plates are preferentially involved, giving bands of dense bones adjacent to the end-plates with a central band of lower normal bone density. These alternating bands of normal and sclerotic bone give a stripped pattern described as a ‘rugger jersey’ spine.

6.     Osteoporosis

With excessive bone resorption the bones may appear reduced in radio-density in some patients. This may particularly occur in postmenopausal women and the elderly, in whom bone resorption exceeds new bone formation, with a net reduction in bone mass. This can be confirmed by bone densitometry, which is an integral component in the evaluation of hyperparathyroidism. In primary hyperparathyroidism there is a pattern of skeletal involvement that preferentially affects the cortical, as opposed to the trabecular, bone. Bone mineral density measurements made in sites in which cortical bone predominates, e.g. in the distal forearm, may show the most marked reduction. Bone density increases after parathyroidectomy in primary hyperparathyroidism.

7.     Metastatic calcification

Soft tissue calcification, other than in articular cartilage and fibrocartilage, does not occur in primary hyperparathyroidism unless there is associated reduced glomerular function resulting in phosphate retention. The latter results in an increase in the calcium × phosphate product, and as a consequence amorphous calcium phosphate is precipitated in organs, blood vessels and soft tissues. If there are features of hyperparathyroidism, i.e. subperiosteal erosions and additionally extensive vascular or soft tissue calcifications, e.g. around joints and in tendons, this implies impaired renal function in association with hyperparathyroidism.

References:

Chapter 49 In Grainger & Allison’s diagnostic radiology, 5^th ed.