Summary
We report the case of a 73-year old male with multiple Brown tumours of the left pelvis and low-trauma fractures due to secondary hyperparathyroidism in association with end-stage renal disease.
His past medical history included end-stage renal disease (ESRD) due to Type 2 diabetes requiring haemodialysis since 2011, ischaemic cardiomyopathy, gastro-oesophageal reflux disease, chronic obstructive pulmonary disease, obstructive sleep apnoea, polymyalgia rheumatica, multinodular goitre, previous vertebral compression fractures, a low-trauma left calcaneal fracture and bilateral trochanteric bursitis. He was diagnosed with secondary hyperparathyroidism (SHPT) in February 2008 and was managed with cinacalcet from July 2013 to January 2016 before it was removed from the Australian Pharmaceutical Benefit Scheme (PBS), subsequently he had been managed with calcitriol and sevelamer.
In August 2018, the man presented with atraumatic progressive right hip pain. Plain X-Ray did not demonstrate a fracture, however an MRI revealed a subcapsular anteroposterior insufficiency fracture of the right femoral neck. Three cancellous screws were inserted, and the post-operative course was complicated by hypotension and non-sustained ventricular tachycardia requiring Intensive Care Unit (ICU) stay. He was discharged home after completing rehabilitation.
He was readmitted in November 2018 with complete heart block requiring permanent pacemaker insertion and during the admission, he complained of atraumatic progressive left hip pain. CT pelvis demonstrated a 2.1 x 3.7 cm soft tissue mass involving the superomedial left acetabulum with bony destruction extending into the left hip joint. A bone scan showed a lytic left acetabular lesion with relatively reduced osteoblastic activity. Given his medical history of SHPT, the primary differential diagnosis was Brown tumour. His biochemistry at the time revealed PTH 212 pmol/L, corrected calcium 2.44 mmol/L, phosphate 1.29 mmol/L, 25-hydroxy-vitamin D (25-OHD) 43 nmol/L. Malignancy screen, including myeloma screen and CT chest, abdomen and pelvis was negative. His pain was managed with analgesia.
In March 2019, he represented with worsening bilateral hip pain. An MRI pelvis showed the lesion in the superomedial acetabulum had increased in size and two new lesions had developed in the iliac bone. All lesions demonstrated extremely low T2 signal and T1 signal with internal mottling, no adjacent bone reaction and no diffusion restriction. The largest lesion, measuring 3.2 x 2.2 x 1.5 cm, was located at superomedial acetabulum. The features of the three pelvic lesions were consistent with Brown tumours.
His anaesthetic risk was assessed as too high to proceed with surgical management, including a parathyroidectomy, and he was managed conservatively for his SHPT with calcitriol and sevelamer. Cinacalcet was recommenced at this stage after gaining compassionate access via the pharmaceutical company. He had persistent pain limiting his mobility, however repeat X-Rays of his pelvis and hip did not show any new fractures.
In May 2019, on a routine ward round his left hip was observed to be shortened and rotated with no history of trauma. An urgent CT pelvis revealed an acute left neck of femur fracture with external rotation of the distal fracture fragment, with no pathological fracture of the left acetabular Brown tumour. He underwent a left total hip replacement and debridement of left medial acetabulum with extensive cement bone grafting.
Histology of the left femoral neck and head showed bone and marrow with areas of granulation type tissue and no tumour identified; left acetabular tissue showed plump spindled cells, extravasated red blood cells, haemosiderin-laden macrophages, osteoclast-like multinucleated giant cells, trabeculae of woven bone rimmed by osteoblasts and osteoclasts, consistent with a Brown tumour.
His most recent biochemistry in June 2019 reveals PTH 200 pmol/L, 25-OHD 42 nmol/L, corrected calcium 2.19 mmol/L , phosphate 1.19 mmol/L and ALP 397 U/L. His dual-energy X-ray absorptiometry (DEXA) scan result is pending.
Brief outline of literature
Conventional therapeutic options for SHPT include calcitriol and phosphate binders, with a target of keeping phosphate levels below 1.78 mmol/L, maintaining normocalcaemia and keeping PTH levels below 2-9 times the upper limit for the assay.1 Parathyroidectomy should be considered in symptomatic patients (e.g. bone pain and/or fractures) when PTH levels are greater than 88 pmol/L, as it can improve reduce fracture risk, and improve bone density, quality of life and overall survival.2 Cinacalcet, a calcium sensing receptor agonist, has also been shown to be effective in treating SHPT by lowering the calcium set point and reducing PTH secretion,3 however it was removed from the PBS in 2015 after the EVOLVE trial failed to show a reduction in mortality or cardiovascular outcomes.4 Brown tumours are a rare complication of inadequately treated secondary hyperparathyroidism and may regress following parathyroidectomy for SHPT.5 In our case where the patient was deemed unsafe for surgery, compassionate access cinacalcet was used, however in an open-label study suggests that combination denosumab and high-dose calcitriol may also decrease parathyroid secretion and parathyroid hyperplasia in dialysis patients with SHPT.6 There is no evidence for the effectiveness of any antiresorptive treatment to reduce fracture risk in patients with ESRD and chronic kidney disease-mineral bone disorder.
Take home message