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

Kuchay, Mohammad Shafi; Mathew, Anu; Kaur, Parjeet; Mishra, Sunil Kumar

doi:10.20945/2359-3997000000408

Cited by 6 publications

(10 citation statements)

References 11 publications

(17 reference statements)

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“…Data regarding denosumab to treat acute hypercalcemia are limited. Two small case series (total n = 14) reported that denosumab decreased serum calcium in patients presenting with severe hypercalcemia related to parathyroid crisis/severe hyperparathyroidism who could not undergo urgent parathyroidectomy . In 2015, the US Food and Drug Administration approved denosumab, 120 mg subcutaneously, for treating hypercalcemia of malignancy that is refractory to bisphosphonates.…”

Section: Observations and Discussionmentioning

confidence: 99%

“…Two small case series (total n = 14) reported that denosumab decreased serum calcium in patients presenting with severe hypercalcemia related to parathyroid crisis/severe hyperparathyroidism who could not undergo urgent parathyroidectomy. 73,74 In 2015, the US Food and Drug Administration approved denosumab, 120 mg subcutaneously, for treating hypercalcemia of malignancy that is refractory to bisphosphonates. In an open-label, single-group study of 33 patients with advanced cancer and persistent hypercalcemia after bisphosphonate treatment, 63.6% responded (serum calcium <11.5 mg/dL) within 10 days.…”

Section: How Should Severe Hypercalcemia Be Managed?mentioning

confidence: 99%

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Hypercalcemia

Walker

Shane

2022

JAMA

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ImportanceHypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (&lt;3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (&gt;3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma.ObservationsApproximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (&lt;20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival.Conclusions and RelevanceMild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

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Section: Observations and Discussionmentioning

confidence: 99%

Section: How Should Severe Hypercalcemia Be Managed?mentioning

confidence: 99%

Hypercalcemia

Walker

Shane

2022

JAMA

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“…The reported duration to lower serum calcium levels in various studies also averaged around 3vdays [6][7][8][9] or even earlier around 36 h after denosumab administration. 10 The patients should be meticulously observed for the occurrence of post-operative hypocalcaemia.…”

Section: Discussionmentioning

confidence: 99%

Utility of denosumab therapy in management of severe hypercalcaemia caused by primary hyperparathyroidism – Case report with review of literature

Jadhao

Mangaraj

2023

Journal of the Royal College of Physicians of Edinburgh

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Primary hyperparathyroidism (PHPT) is the leading cause of incidentally detected hypercalcaemia in asymptomatic individuals. Rarely, PHPT may present with severe hypercalcaemia or even hypercalcaemic crisis. We describe a case of a 53-year-old male who presented with acute severe hypercalcaemia as the index manifestation. Complete clinical, biochemical and radiological evaluation led to an eventual diagnosis of PHPT. He had a challenging clinical course as hypercalcaemia did not improve significantly despite undergoing multiple sessions of haemodialysis and other supportive measures. Furthermore, the presence of acute kidney injury precluded the use of bisphosphonates. In the end, he received subcutaneous denosumab injection and his serum calcium levels improved dramatically afterwards. Subsequently, he underwent successful parathyroidectomy. Denosumab therapy can play a critical role in managing such patients especially when other therapeutic modalities cannot adequately control hypercalcaemia.

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“…Thus, an increase in BMD was demonstrated after PTX with and without ZOL, but this effect was significantly greater with the use of ZOL postoperatively (35). In a small case series, denosumab was used to normalize serum calcium levels before PTX in four patients with severe hypercalcemia, demonstrating safety and efficacy (36).…”

Section: Perioperative Medical Treatmentmentioning

confidence: 97%

“…There were significant increases in BMD of LS (P = 0.039 and 0.017 for T and Z scores, respectively) and FN (P = 0.045 for Z score), as well as reductions in bone turnover markers in the ZOL group compared to placebo. Thus, an increase in BMD was demonstrated after PTX with and without ZOL, but this effect was significantly greater with the use of ZOL postoperatively ( 35 ).In a small case series, denosumab was used to normalize serum calcium levels before PTX in four patients with severe hypercalcemia, demonstrating safety and efficacy ( 36 ).…”

Section: Perioperative Medical Treatmentmentioning

confidence: 99%

Medical management of primary hyperparathyroidism

Bandeira¹,

Nóbrega²,

Oliveira³

et al. 2022

Archives of Endocrinology and Metabolism

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Primary hyperparathyroidism (PHPT) is an endocrine disorder resulting from the hyperfunction of one or more parathyroid glands, with hypersecretion of parathyroid hormone (PTH). It can be managed by parathyroidectomy (PTX) or non-surgically. Medical therapy with pharmacological agents is an alternative for those patients with asymptomatic PHPT who meet guidelines for surgery but are unable or unwilling to undergo PTX. In this review, we focus upon these non-surgical aspects of PHPT management. We emphasize the most studied and widely used pharmacological alternatives: bisphosphonates, denosumab, cinacalcet and hormone therapy, in addition to combined therapy. We also address the relevant aspects of perioperative management.

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

Cited by 6 publications

References 11 publications

Hypercalcemia

Hypercalcemia

Utility of denosumab therapy in management of severe hypercalcaemia caused by primary hyperparathyroidism – Case report with review of literature

Medical management of primary hyperparathyroidism

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