Brown Tumours of Hyperparathyroidism

Brown tumours (osteitis fibrosa cystica) are focal, lytic bone lesions caused by prolonged, severe hyperparathyroidism. They are collections of osteoclast type giant cells, fibrous tissue and haemosiderin, which gives the brown colour.

In modern practice with routine calcium testing they are now rare in primary hyperparathyroidism (under 2%), but remain seen where diagnosis is delayed, including regions with limited access to care and vitamin D deficiency. They also occur in secondary and tertiary hyperparathyroidism from kidney disease.

Common sites are the jaw (mandible, maxilla), pelvis, ribs, clavicle and femur. They may be multiple, and can mimic bone metastases or giant cell tumour.

Pathophysiology.

Persistent high parathyroid hormone stimulates osteoclast activity and bone turnover, which causes focal resorption with fibrous replacement and haemorrhage. Lesions are not neoplastic and regress after the hormone excess is corrected.

Vitamin D deficiency and kidney disease worsen secondary hyperparathyroidism.

• Bone pain, swelling (jaw, limbs), pathological fracture, loose teeth, and a mass.
• Features of hypercalcaemia (polyuria, thirst, constipation, kidney stones) and bone disease (deformity, height loss).

Red flags.

• Pathological fracture or spinal cord compression.
• Calcium over 3.5 mmol/L (hypercalcaemic crisis).
• Suspicion of malignancy in a patient with a lytic lesion.

• Albumin adjusted calcium raised, parathyroid hormone markedly raised (often several times the upper limit), phosphate low (primary) or high (kidney disease), alkaline phosphatase markedly raised, 25-hydroxyvitamin D often low, creatinine.
• Radiographs: well defined, expansile lytic lesions with thinned cortex, often with subperiosteal resorption of the phalanges, a "salt and pepper" skull and loss of the lamina dura. DXA shows severe loss at the distal radius.
• MRI or CT for complex lesions. Parathyroid localisation (ultrasound, technetium sestamibi, four dimensional CT).
• Biopsy only if the diagnosis is unclear, since histology resembles giant cell tumour.

Differential diagnosis.

• Giant cell tumour of bone, metastasis and myeloma.
• Fibrous dysplasia, simple or aneurysmal bone cyst, and Paget disease.
• Parathyroid carcinoma and secondary hyperparathyroidism from renal disease.

• Treat the hyperparathyroidism: parathyroidectomy for primary and tertiary disease, which leads to regression of lesions over months to years. Surgery on the bone is avoided unless there is fracture or instability.
• Correct vitamin D deficiency before surgery (target 25-hydroxyvitamin D over 50 nmol/L, 20 ng/mL) and monitor for hungry bone syndrome after surgery: calcium carbonate 1 to 2 g elemental calcium daily in divided doses with calcitriol 0.5 to 1 microgram daily, and intravenous calcium gluconate (10 mL of 10%, 2.25 mmol, over 10 minutes with monitoring) for tetany.
• Secondary hyperparathyroidism from kidney disease: phosphate control, vitamin D analogues and cinacalcet (30 mg daily, increased every 2 to 4 weeks up to 180 mg daily).
• Fracture or deformity: orthopaedic fixation. Avoid antiresorptives before surgery when hypocalcaemia is a risk.
• Hypercalcaemic crisis: intravenous 0.9% sodium chloride, zoledronic acid 4 mg intravenously over 15 minutes and urgent surgery.

Special groups. Pregnancy: surgery in the second trimester for severe disease. Children: look for familial syndromes (MEN1, CDC73).

Monitoring. Calcium, phosphate, parathyroid hormone and alkaline phosphatase after surgery at 24 hours, 1 week, and then every 3 months for the first year, with serial radiographs every 6 to 12 months and bone density yearly.

Referral and escalation. Endocrine surgery and endocrinology; orthopaedics for fracture; nephrology for kidney disease.