Teaching Case

A 33-year-old woman presented with new radiopaque and expansile rib lesions at chest radiography with persistent high calcium and parathyroid hormone (PTH) levels, with no other associated symptoms.
She underwent haemodialysis for 5 years and received a kidney transplant 1 year prior to this time frame.
Poor therapeutic compliance was also reported.

Expansile, lobulated and radiopaque lesions, involving multiple costal arches, were evident at the Chest radiography (Fig.1).

Unenhanced chest CT revealed multiple lytic, expansile, well-corticated and “bubbly” lesions, involving several costal arches. The largest measured 60x30mm, and was located in the 6th left costal arch (Fig.2 a and b).

Given the patient’s history, the diagnosis of brown tumours (BT) was suggested.

This hypothesis was further supported by plain radiographs of the lumbar spine, pelvis and hands, which showed a “Rugger Jersey” spine (Fig.3), lytic and expansile lesions of the femur (Fig.4), and subperiosteal bone resorption in the radial aspect of the middle phalanges (Fig.5).

Neck ultrasonography also revealed an extra-thyroid, solid, hypoechoic nodule (approximately 23x12mm) with well-defined contours, adjacent to the left lower pole of the thyroid, suggestive of an enlarged parathyroid (Fig.6).

Lesion’s fine needle biopsy and 99mTc-sestamibi parathyroid scintigraphy were performed, with results supporting the diagnosis of parathyroid’s hyperplasia.

Tertiary hyperparathyroidism (3HPT) is a rare condition that occurs when patients with longstanding secondary hyperparathyroidism (2HPT) acquire a state of autonomous secretion of PTH.[1]

The most common cause of 3HPT is chronic kidney disease (CKD), which is related to 2HPT. Classically, it persists despite a successful kidney transplant.[1]

In 2HPT, there is increased parathyroid function caused by CKD that is characterised by high PTH and low/normal calcium levels. In this pathology, sustained parathyroid stimulation can induce diffuse polyclonal hyperplasia of parathyroid glands, which is followed by monoclonal nodular hyperplasia. [1, 2] Sometimes, hypertrophy can be limited to only one parathyroid gland. [1]
Persistence of this condition after kidney transplant leads to 3HPT, in which PTH is secreted despite hypercalcemia. [1, 2]

Hyperparathyroidism (HPT) can cause disturbances in numerous systems. Subperiosteal resorption, BT and osteosclerosis are some examples of HPT’s skeletal manifestations [3] and were observed in this case.

Subperiosteal resorption is pathognomonic and is the earliest bone feature of HPT. [3, 4, 5] It occurs due to accelerated osteoclastic activity and is more common at phalangeal tufts and along the radial aspects of the middle phalanges of the second and third fingers. [3, 4, 5] In advanced cases, bone resorption of the terminal phalanges may result in acro-osteolysis. [5]

Brown tumours are more common in women older than 50 years and usually appear late in the disease. [6, 7] They are benign, focal, lucent bone lesions resulting from osteoclastic resorption, fibrous tissue accumulation, necrosis and liquefaction. [3, 6] They usually appear as lytic, mono or polyostotic, well-defined, central or eccentric and expansile lesions at radiography and can be found most often in the pelvis, ribs, clavicles, facial bones and in extremities’ metaphysis. [3]

BT’s histology is nonspecific, so diagnosis is suggested by imaging, analytical and clinical findings. [7] Differential diagnosis include fibrous dysplasia, multiple myeloma, metastasis, giant cell tumour and infection.

Osteosclerosis is thought to be due to osteoblast’s stimulation by PTH and may affect different skeletal elements, predominantly in the axial skeleton. [5] Osseous deposition in the subchondral aspects of the vertebral bodies, with normal density of its middle section, is described as “Rugger Jersey” spine. [3, 4, 5]

Other skeletal features of HPT include: osteomalacia; osteoporosis; periosteal neostosis; cortical, endosteal, subligamentous, subchondral and trabecular resorption, including "salt and pepper" skull. [3, 5]

If medical therapy fails, 3HPT is usually treated surgically, involving parathyroidectomy. [1] Effective treatment may result in sclerosis, calcification or regression of BT. [5, 8] Contrary to subperiosteal resorption, osteosclerosis doesn’t resolve with HPT treatment. [8]