The refractory secondary hyperparathyroidism presenting with retro-orbital brown tumor: a case report – BMC Nephrology

Chronic kidney disease-mineral and bone disorder (CKD-MBD) presents significant challenges in the management of dialysis patients, encompassing various clinical disturbances. In this case, we focused on refractory hyperparathyroidism, a condition that posed severe clinical manifestations. This patient showcases the challenges in clinic management through all treatment steps and wretched complications of SHPT. The bone fractures, muscle weakness, bone pain, exophthalmos, cranial-located BT, and recurrent parathyroid adenomas were among these complications. Moreover, the patient had an extra parathyroid adenoma atypically located in the mediastinum. Therefore, comprehensive surgical intervention was required in this case. Thanks to effective treatment options in recent medical practice, the incidence of such severe cases has decreased.

The pathophysiology of CKD-MBD is complicated, involving intricate feedback loops between the kidneys, parathyroid glands, bones, intestine, and vasculature [7]. The heterogeneity of bone disorders in CKD-MBD leads to the identification of two major clinical entities: high-turnover and low-turnover (adynamic) bone disease. SHPT is an essential component of CKD-MBD and signifies high-turnover osteodystrophy. The term tertiary hyperparathyroidism is defined as permanent hyperparathyroidism, representing severe parathyroid hyperplasia and autonomous secretion of PTH independently of plasma calcium concentration in CKD.

Bone pain, osteoporosis, fractures, and BT formation are among the primary skeletal complications of SHPT. However, complications extend beyond the skeletal system in SHPT. Persistent elevation of the calcium-phosphate product exacerbates extraskeletal calcifications, which can occur in various sites, including the lungs, myocardium, and periarticular areas. Pruritus, calciphylaxis, neuropsychiatric symptoms, calcific uremic arteriolopathy, vascular calcifications, and soft-tissue calcifications might occur. Furthermore, SHPT is associated with elevated cardiovascular risk which is attributed in part to excessive vascular calcification. Additionally, SHPT causes a poor response to erythropoiesis-stimulating agent therapy and growth retardation in pediatric patients [8].

The classical manifestation of hyperparathyroidism is OFC, however, BT represents a severe form of OFC in prolonged hyperparathyroidism. BT are benign, rapidly growing, fibrotic, cystic bone lesions [9]. Despite BT is benign bone lesions, occasionally presented on imaging as an aggressive bone tumor.Lesions of OFC and BT can affect any bone, but commonly are located in the ribs, clavicles, pelvis, spine, tibia, humerus, and skull [10].

Atypical locations and diverse clinical presentations of BT have been documented in the literature. The clinical significance of BT depends on its potential to compress various organs. For instance, spinal cord compression due to BT, though rare, has been observed on multiple occasions [11]. While there is no specific treatment protocol for BT, surgical resection becomes necessary in cases where complications arise. BT serves as an indicator of an aggressive SHPT course.Unusual locations for BT, including the forearm, foot, jaw, mandible, sphenoid sinus, and calcaneus, have been reported.Orbital bones are exceptionally rare reported as BT location [12, 13]. Exophthalmos and visual impairment are the most common complaints among patients with orbital BT. In reported cases, early surgical intervention was undertaken due to the abrupt onset of symptoms, leading to resolution of visual damage in almost all patients during the postoperative period.

It is noteworthy that the majority of reported cases involving orbital BT had pre-existing CKD diagnosis, and most of these patients had ongoing dialysis therapy. Gonzalez-Martínez et al. reported a 30-year-old woman with proptosis who had no chronic disease before, and orbital BT was detected on imaging. As distinct from, kidney dysfunction was defined during perioperative period. The determination of kidney disease through orbital BT was very interesting in this case [14].

SHPT significantly impacts the mortality rate in dialysis patients, underscoring the necessity for effective control. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining PTH levels within 2 to 9 times the upper normal limit for the assay as the target range [15].Managing SHP begins with addressing hyperphosphatemia, with the goal of lowering elevated phosphate levels towards the normal range. The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines advise maintaining serum phosphate levels between 3.5 and 5.5 mg/dL. Phosphate-lowering therapies encompass dietary phosphate restriction, oral phosphate binders, and efficient dialysis. Ensuring normocalcemia is another crucial step in SHPT management. Calcitriol and synthetic vitamin D analogs can be employed to reduce PTH levels [16].In this case, paricalcitol was utilized afterward phosphate control. Calcimimetic agents operate by increasing the sensitivity of the calcium-sensing receptor (CaSR) in the parathyroid glands, thereby reducing PTH levels. Cinacalcet and etelcalcetide are widely available calcimimetic agents. Studies have demonstrated that cinacalcet therapy reduces the necessity for parathyroidectomy in dialysis patients [17].

Parathyroid surgery is recommended for patients with severe hyperparathyroidism that cannot be effectively controlled through medical means. Parathyroidectomy proves to be an efficacious therapy for refractory hyperparathyroidism and also contributes to the improvement of renal osteodystrophy [18]. Several indications may necessitate parathyroidectomy, including hypercalcemia, bone pain, refractory pruritus, unexplained myopathy, and calciphylaxis. For dialysis patients with PTH levels persistently exceeding 1000 pg/mL, even in the absence of obvious associated clinical symptoms, and who do not respond to medical therapies, referral for parathyroid surgery is recommended [19].

Hypocalcemia is a common issue following parathyroidectomy. The severity of hypocalcemia after surgery is directly related to the duration and extent of parathyroid-mediated high-turnover bone disease. Prolonged and severe postoperative hypocalcemia is known as hungry bone syndrome, andrefers to the hyperdynamic reabsorption of calcium into bones following parathyroidectomy [20]. There is a high risk of recurrent SHPT after a successful parathyroidectomy, with rates as high as 80% in dialysis patients. Consequently, some ESKD patients require repeated parathyroid surgeries for refractory disease [21].

In conclusion, we attempted to summarize the approach of SHPT via this patient. Management of patients with ESKD could present challenging and astonishing clinical scenariosto physicians. These patients exhibit numerous complications related to dialysis procedures or uremia. This unusual case emphasizes the importance of vigilance among all physicians, not solely nephrologists, especially concerning dialysis patients.