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]
Tertiary hyperparathyroidism with brown tumours
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1. Chest X-ray reveals expansile changes in the ribs, with locally increased radiodensity indicating bone hyperplasia or sclerosis. Some lucent areas are observed, suggesting possible lytic lesions (“brown tumors”).
2. Chest CT shows a well-defined, lytic lesion within the ribs, with partial localized expansion, consistent with the imaging characteristics of brown tumors.
3. Spinal X-ray demonstrates the “Rugger Jersey” sign (increased density of the superior and inferior endplates with relatively normal density in the middle), indicating sclerosis and metabolic abnormalities.
4. Pelvic and bilateral hip X-rays indicate locally increased bone density and thickened cortical bone.
5. X-ray of both hands shows subperiosteal bone resorption at the phalangeal tips, especially on the radial side of the middle phalanges of the second and third fingers, and at the distal phalanges, suggesting the typical signs of subperiosteal bone resorption.
6. Ultrasound reveals thickening or nodular changes of the parathyroid glands, suggesting hyperplasia or adenoma due to hyperparathyroidism.
Based on the above imaging findings and the patient’s history, the possible differential diagnoses include:
1. Secondary or Tertiary Hyperparathyroidism (HPT): The patient has longstanding chronic kidney disease, dialysis treatment, and post-transplant status with persistently elevated calcium and PTH levels. The imaging findings, including “brown tumors,” subperiosteal resorption, and the “Rugger Jersey” sign, strongly suggest hyperparathyroidism.
2. Fibrous Dysplasia (Fibrous Osteopathy): Can present with expansile bone changes and lytic lesions, but usually lacking persistent hypercalcemia and elevated PTH. Clinical correlation places it lower on the differential list.
3. Multiple Myeloma: May present with lytic skeletal lesions (“punched-out” lesions), but typically also involves abnormal protein electrophoresis, anemia, and renal impairment indicators, which can help differentiate it from this case.
4. Malignant Bone Metastases: Can also show lytic or mixed lesions, but the high PTH, hypercalcemia, and classic subperiosteal resorption point more towards hyperparathyroidism in this case.
5. Giant Cell Tumor: Often located at the epiphyseal end of long bones with lytic changes. However, it generally does not present with multiple lesions and lacks clinical and biochemical evidence of hyperparathyroidism.
Taking into account the following:
• Long-term chronic renal failure with 5 years on dialysis, followed by 1 year post kidney transplant.
• Laboratory results indicate persistently elevated serum calcium and PTH levels.
• Imaging showing typical features of hyperparathyroid bone changes, including “brown tumors,” subperiosteal bone resorption, and the “Rugger Jersey” sign.
The most likely diagnosis is: Tertiary Hyperparathyroidism (Tertiary HPT).
A definitive diagnosis can be confirmed by parathyroid scintigraphy (e.g., 99mTc-MIBI scan) or further pathological evaluation (surgical or biopsy) if needed.
1. Treatment Strategies:
- Pharmacological Management: Use medications that reduce PTH and calcium levels, such as calcimimetics (e.g., Cinacalcet), combined with phosphate binders and vitamin D analogs as necessary.
- Surgical Intervention: If medical therapy fails to adequately control hypercalcemia and bone damage, parathyroidectomy (total or subtotal) may be considered. In some cases, a portion of healthy parathyroid tissue can be autografted to maintain basic physiological function.
- Electrolyte and Mineral Balance: Monitor serum calcium, phosphate, and PTH levels closely before and after surgery, and correct abnormalities promptly.
2. Rehabilitation and Exercise Prescription:
- Initial Phase:
• Focus on low-intensity aerobic exercise, such as brisk walking or stationary cycling, for 15–20 minutes each session, 3–4 times per week, maintaining 50%–60% of maximum heart rate.
• Introduce simple resistance exercises (e.g., with elastic bands) using light loads and slow, controlled movements to avoid bone injury.
- Progressive Phase:
• Once serum calcium and PTH levels stabilize, moderate increases in aerobic exercise intensity can be considered: 20–30 minutes per session, 3–4 times per week, at 60%–70% of maximum heart rate.
• Gradually intensify resistance training with dumbbells or barbells, as approved by a physician or physical therapist after evaluating bone density and risk factors.
- Maintenance Phase:
• Continue aerobic exercise at about 30 minutes per session, 3–5 times per week.
• Emphasize core and lower-limb muscle strength and endurance in resistance training. Use multiple low-load sets, progressing gradually to reduce the risk of fracture and improve musculoskeletal health.
- Precautions:
- Prevent bone fractures: During phases of compromised bone structure, avoid high-impact and excessive weight-bearing activities.
- Monitor cardiovascular function: In cases of reduced cardiac function due to dialysis or transplantation, monitor heart rate, blood pressure, and symptoms during exercise to ensure safety.
- Adequate warm-up and cool-down are essential to prevent acute musculoskeletal injuries.
This report is based solely on the provided imaging and patient history for preliminary analysis and cannot replace in-person consultations or professional medical advice. Specific diagnosis and treatment plans must be determined by integrating clinical presentations, laboratory results, surgical or pathological findings, and comprehensive specialist evaluations and follow-ups.
Tertiary hyperparathyroidism with brown tumours
