Brown tumors (BTs) are benign osteolytic bone lesions resulting from excessive bone resorption in severe and prolonged hyperparathyroidism ¹²³⁴. Although uncommon, they are a potentially severe complication of hyperparathyroidism in patients undergoing dialysis, particularly in the refractory disease setting ¹³. BTs may involve multiple skeletal sites. They may be asymptomatic or present with localized bone pain, swelling, pathological fractures, or neurological symptoms related to nerve or spinal cord compression ²³. Their multifocal distribution and variable clinical presentation make their diagnosis challenging.

We report a case of multifocal BTs in a patient on hemodialysis with severe refractory secondary hyperparathyroidism, presenting with progressive neuropathic pain of the right lower limb. This unusual clinical presentation highlights the contribution of whole-body bone scintigraphy combined with single-photon emission computed tomography/computed tomography (SPECT/CT) for identifying and localizing multifocal skeletal lesions.

A 46-year-old man with end-stage kidney disease secondary to genetically confirmed nephronophthisis (NPHP1 complete deletion associated with c.1027G>A, p.Gly343Arg) had been treated with peritoneal dialysis (PD) for four years before transitioning to hemodialysis (HD) because of inadequate dialysis. He had previously undergone subtotal parathyroidectomy two years earlier but had persistent severe hyperparathyroidism, with poor adherence to cinacalcet. Three months before the onset of pain, he was switched from cinacalcet to intravenous etelcalcetide after transitioning from PD to HD. Laboratory investigations showed markedly elevated parathyroid hormone levels (1481 pg/mL, approximately 15 times the upper normal limit), elevated alkaline phosphatase (255 IU/L), hypercalcemia (2.70 mmol/L), and hyperphosphatemia (2.95 mmol/L). ¹¹C-methionine positron emission tomography suggested recurrent parathyroid adenoma at the inferior pole of the left thyroid lobe.

He presented with progressive neuropathic pain affecting the right lower limb, radiating from the ankle to the mid-thigh along a well-defined trajectory. Pain was reproducibly elicited by ankle mobilization and local pressure. No cutaneous abnormalities were observed.

Lumbar computed tomography excluded significant nerve root compression, and venous Doppler ultrasonography ruled out deep vein thrombosis. Because of persistent symptoms and severe refractory hyperparathyroidism, whole-body bone scintigraphy with SPECT/CT was performed. Planar imaging demonstrated multiple areas of markedly increased tracer uptake involving both tibias and distal femurs (Figure 1A). Fused SPECT/CT images localized the tracer uptake to elongated intramedullary lesions in both tibias associated with cortical thickening (Figure 1B–C), consistent with multifocal BTs ²³. The symptomatic right-sided lesion was identified, and revision parathyroidectomy was subsequently performed, resulting in marked symptomatic improvement one month later.

Brown tumors are an uncommon manifestation of uncontrolled hyperparathyroidism in patients with chronic kidney disease. They result from excessive osteoclastic bone resorption and replacement of bone by fibrovascular tissue containing macrophages and multinucleated giant cells, which may produce well-defined, sometimes expansile osteolytic lesions with a characteristic “blown-out” appearance ¹²³⁴. In this case, the clinical presentation was atypical, with progressive neuropathic pain initially suggesting a neurological or musculoskeletal disorder. The absence of significant lumbar nerve root compression or deep vein thrombosis, together with severe refractory hyperparathyroidism, raised the possibility of BTs.

Whole-body bone scintigraphy demonstrated multifocal skeletal involvement, revealing more extensive skeletal involvement than suggested by the focal symptoms. SPECT/CT further characterized the lesions by providing precise anatomical localization and demonstrating their intramedullary distribution and associated cortical thickening. The concordance between the symptomatic right lower limb and the corresponding tibial lesion provided a strong clinicoradiological correlation. This illustrates the complementary roles of whole-body scintigraphy and SPECT/CT: The former provides an overview of skeletal involvement, whereas the latter improves anatomical characterization and correlation with clinical findings ².

The differential diagnosis of focal hypermetabolic bone lesions in patients with chronic kidney disease includes other metabolic bone disorders, benign bone lesions, and malignant skeletal involvement. The combination of severe refractory hyperparathyroidism, multifocal skeletal abnormalities, and the compatible imaging findings supported the diagnosis of multifocal BTs ²³. Histological confirmation was therefore not deemed necessary given the clinical, biochemical, and imaging findings.

Management of BTs relies on controlling the underlying hyperparathyroidism. Medical treatment with calcimimetics and vitamin D analogs may be effective in selected patients, whereas parathyroidectomy should be considered in severe or refractory disease ¹³. In this case, persistent marked hyperparathyroidism despite previous subtotal parathyroidectomy and medical therapy led to revision parathyroidectomy. The subsequent marked improvement in symptoms supports a relationship between the skeletal lesion and the patient’s pain. Regression of the BTs and/or relief of local mechanical or neural effects may have contributed to the clinical improvement.

This case highlights that BTs should be considered in the differential diagnosis of dialysis patients with unexplained focal neuropathic pain and severe refractory hyperparathyroidism. Whole-body bone scintigraphy combined with SPECT/CT is particularly valuable by demonstrating the extent of skeletal involvement and providing precise anatomical localization with clinicoradiological correlation. Recognition of multifocal BTs may facilitate appropriate management of the underlying severe refractory hyperparathyroidism, in this case with revision parathyroidectomy resulting in marked symptomatic improvement.