Successful Use of Denosumab for Life-Threatening Hypercalcemia in a Pediatric Patient with Primary Hyperparathyroidism

Abstract

<b><i>Introduction:</i></b> Primary hyperparathyroidism (PHPT) is rare and usually symptomatic in children. There is no approved medication to lower serum calcium levels in this patient group. Denosumab is used in adult patients with osteoporosis and hyperparathyroidism. To our knowledge, only 1 case of denosumab treatment in a child with severe PHPT has been reported to date. <b><i>Case Presentation:</i></b> A 16-year-old female was referred to our clinic with symptoms including pathologic fractures, nausea, emesis, and progressive weight loss. At admission, her serum total calcium was 4.17 mmol/L (reference range 2.15–2.55), parathyroid hormone 2,151 pg/mL (15–65), and phosphate 1.07 mmol/L (1.45–1.78). Due to potentially life-threatening hypercalcemia, denosumab 60 mg subcutaneously was administered after obtaining informed consent. Serum calcium levels were reduced within 12 h of injection and the patient’s condition rapidly improved, which allowed genetic testing to be done prior to surgery. A heterozygous mutation in the <i>CDC73</i> gene was revealed, and a parathyroidectomy was performed on day 22 after denosumab administration. Morphological examination revealed solitary parathyroid adenoma. After surgery, hypocalcemia developed requiring high doses of alfacalcidol and calcium supplements. <b><i>Conclusion:</i></b> Our case supports the previous observations in adults that denosumab can be safely and effectively used as a preoperative treatment in patients with PHPT and severe hypercalcemia and shows that it may be used in pediatric patients.

Hypercalcemic crisis caused by primary hyperparathyroidism in a 11-year-old boy: a rare case report and review of the literature

“…Another patient (case 6) underwent surgery 22 days after admission. This case had family history of PHPT, and hence genetic testing was performed before surgery ( 8 ). Emergency surgeries after initial treatment might be imperative because a hypercalcemic crisis can result in fatal consequences in cases where prompt and proper treatment cannot be provided, and surgery is the only curative treatment for PHPT ( 6 ).…”

“…HPT-JT is another hereditary disease that can present with PHPT in pediatric patients. Among seven cases of hypercalcemic crisis in pediatric patients shown in Table 1 , one case (case 6) was diagnosed as HPT-JT, as evidenced by a pathogenic mutation in CDC73 ( 8 ). A single parathyroid tumor is usually responsible for the development of PHPT in patients with HPT-JT.…”

“…However, because PHPT is likely to be symptomatic in pediatric patients, even if the symptoms are vague, it is usually diagnosed before hypercalcemic crisis is developed. Indeed, there are only six reports of PHPT-induced hypercalcemic crisis in pediatric patients (7)(8)(9)(10)(11). Thus, an appropriate treatment approach for this condition has not been demonstrated.…”

“…Because it is necessary to lower serum calcium levels, the initial treatment consisting of normal saline infusion and/ or furosemide was immediately started for all six patients shown in Table 1. However, bisphosphonate (etidronate, pamidronate, or zoledronate) was used to decrease serum calcium levels in four out of six cases (7,(9)(10)(11), while in one case, denosumab, a human monoclonal antibody of the receptor activator of nuclear factor kappa-B ligand, was administered (8). In addition, calcitonin was used in one case (7).…”

Denosumab can be used successfully as a bridge to surgery in patients with severe hypercalcemia due to primary hyperparathyroidism

“…In cases where denosumab was used to manage hypercalcemia in PHPT, it was administered subcutaneously at a reduced dose of 60 mg. It has been reported that after a single dose, serum calcium levels begin lowering after 12 hours with normalization in three days (8)(9)(10)(11)(12). We also used a single dose of denosumab (60 mg), and calcium levels begun lowering after 12-24 hours.…”