Denosumab for Management of Parathyroid Carcinoma-Mediated Hypercalcemia

Vellanki, Priyathama; Lange, Kirsten; Elaraj, Dina M.; Kopp, Peter; Muayed, Malek El

doi:10.1210/jc.2013-3031

Cited by 64 publications

(48 citation statements)

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“…It has been shown to have a profound effect in modulating malignant hypercalcaemia (6). Very recently, the use of denosumab in the treatment of hypercalcaemia related to parathyroid carcinoma has been reported in two case reports (7,8). We were contemporaneously using denosumab for a similar patient with hypercalcaemia and parathyroid carcinoma and report its high efficacy when all else had failed.…”

Section: Introductionmentioning

confidence: 99%

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab

Karuppiah

Thanabalasingham

Shine

et al. 2014

European Journal of Endocrinology

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Objective: Hypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective. Subject, methods and results: A 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l. Conclusions: Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear factor kB ligand (RANKL)', was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.

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Section: Introductionmentioning

confidence: 99%

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab

Karuppiah

Thanabalasingham

Shine

et al. 2014

European Journal of Endocrinology

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“…It also inhibits osteoclastic bone resorption [61][62][63][64]. It may lower calcium levels in some patients.…”

Section: Gallium Nitratementioning

confidence: 99%

“…Vellanki et al [64] described successful denosumab therapy in a patient with refractory hypercalcaemia in PC, who initially responded to surgery, bisphosphonates, calcium receptor agonist, and chemotherapy (dacarbazine).…”

Section: Denosumabmentioning

confidence: 99%

“…Azotan galu hamuje in vitro sekrecję PTH z komórek przytarczyc, jak również resorpcję kości przez osteoklasty [61][62][63][64]. Może powodować obniżenie stężenia wapnia u niektórych pacjentów.…”

Section: Polish Versionunclassified

“…[64] opisali skuteczną terapię denosumabem u pacjenta z oporną hiperkalcemią w przebiegu raka przytarczyc, która początkowo odpowiadała na leczenie chirurgiczne, bisfosfoniany, agonistę receptora wapniowego i chemioterapię (dakarbazynę).…”

Section: Polish Versionunclassified

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Pierwotna nadczynność przytarczyc w przebiegu raka przytarczyc — wyzwanie diagnostyczne i terapeutyczne

Dabrowska

Tarach

Zwolak

2015

Endokrynologia Polska

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Parathyroid carcinoma (PC) is a rare endocrine malignancy and the cause of primary hyperparathyroidism. It is usually associated with a high rate of local and distant recurrence. Laboratory findings and clinical symptoms may be similar to those in parathyroid adenoma. The histological features of PC may also be non-specific and the affected gland is often indistinguishable from a benign lesion. The proper diagnosis is commonly made months to years later when the disease recurs or metastases are present. Therefore, parathyroid carcinoma still remains a diagnostic and management challenge for many physicians. However, there are some features that, in combination, may help in diagnosis. Surgery still remains the only curative treatment, even in metastatic disease. In advanced, non-operable subjects, managing hypercalcaemia and controlling a tumour are the main goals. Morbidity is caused by hypercalcaemia rather than metastases. A multidisciplinary approach with experienced endocrinologists, pathologists, radiologists, nuclear medicine doctors, oncologists, and surgeons is needed to optimize patient outcome. StreszczenieRak przytarczyc (PC) jest rzadkim nowotworem złośliwym układu wewnątrzwydzielniczego, a także rzadką przyczyną pierwotnej nadczynności przytarczyc. Zazwyczaj wiąże się z wysokim odsetkiem miejscowych i odległych przerzutów. Wyniki badań laboratoryjnych i objawy kliniczne mogą przypominać te spotykane w przebiegu gruczolaków przytarczyc. Równie niespecyficzny jest obraz histopatologiczny raka przytarczyc, co powoduje trudności w diagnostyce różnicowej ze zmianami łagodnymi, będącymi gruczolakami. Właściwe rozpoznanie często jest stawiane z kilkumiesięcznym lub kilkuletnim opóźnieniem, w oparciu o nawrót choroby lub pojawiające się przerzuty. Mając na uwadze ten fakt, rak przytarczyc ciągle pozostaje wyzwaniem diagnostycznym i terapeutycznym dla wielu specjalistów. Jakkolwiek, wyróżnia się jednak pewne objawy, których obecność może pomóc w postawieniu właściwej diagnozy. Leczenie chirurgiczne pozostaje nadal jedyną skuteczną opcją terapeutyczną, nawet w sytuacji pojawienia się zmian przerzutowych. W zaawansowanych, nieoperacyjnych przypadkach głównym celem leczenia pozostaje obniżanie stężenia wapnia we krwi i kontrola wielkości guza. Śmiertelność związana z rakiem przytarczyc wynika raczej z hiperkalcemii, niż obecności przerzutów. W celu poprawy wyników leczenia, niezbędne jest podejście wielodyscyplinarne oraz współdziałanie wielu doświadczonych specjalistów: endokrynologów, patologów, radiologów, medyków nuklearnych, onkologów i chirurgów.

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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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Denosumab for Management of Parathyroid Carcinoma-Mediated Hypercalcemia

Cited by 64 publications

References 14 publications

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab

Pierwotna nadczynność przytarczyc w przebiegu raka przytarczyc — wyzwanie diagnostyczne i terapeutyczne

Hypercalcemia

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