Calcitriol-mediated hypercalcemia as an immune-related adverse event in a patient receiving nivolumab and ipilimumab for metastatic renal cell carcinoma, case report

Johnson, Kai Conrad Cecil; Issa, Majd; Parikh, Anish B.; Monk, Paul; Yin, Ming; Mortazavi, Amir; Yang, Yuanquan

doi:10.1186/s12894-021-00825-4

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…Hypercalcemia in patients under ICI has also been reported, but seems to be non-PTH-mediated in the context of humoral hypercalcemia of malignancy or PTH-related peptide production. Recently, a case of calcitriol-mediated resistant hypercalcemia was reported in a patient treated by nivolumab (117). At present, there is no evidence for direct or indirect effect of ICI therapy on bone metabolism.…”

Section: Parathyroidsmentioning

confidence: 99%

Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline

Husebye

Castinetti

Criseno

et al. 2022

European Journal of Endocrinology

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Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, but are associated with significant autoimmune endocrinopathies that pose both diagnostic and treatment challenges. The aim of this guideline is to provide clinicians with the best possible evidence-based recommendations for treatment and follow-up of patients with ICI-induced endocrine side effects based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. As these drugs have been used a relatively short time, large systematic investigations are scarce. A systematic approach to diagnosis, treatment and follow-up is needed, including baseline tests of endocrine function before each treatment cycle. We conclude that there is no clear evidence for the benefit of high-dose glucocorticoids to treat endocrine toxicities with the possible exceptions of severe thyroid eye disease and hypophysitis affecting the visual apparatus. With the exception of thyroiditis, most endocrine dysfunctions appear to be permanent regardless of ICI discontinuation. Thus, the development of endocrinopathies does not dictate a need to stop ICI treatment.

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Section: Parathyroidsmentioning

confidence: 99%

Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline

Husebye

Castinetti

Criseno

et al. 2022

European Journal of Endocrinology

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“…The current hypothesis is that increased macrophage activation caused by immunotherapy may lead to increased production of a specific 25(OH)D-hydroxylase enzyme, which is nonresponsive to PTH [4]. Previous case reports have documented similar events with nivolumab and ipilimumab, with some cases requiring corticosteroid use for symptom resolution [5][6][7]. To our knowledge, this is the first documented case of immunotherapy-mediated hypercalcemia in the setting of metastatic melanoma.…”

Section: Discussionmentioning

confidence: 78%

Hypercalcemia Secondary to Calcitriol Production From Dual Combination Immunotherapy in Pulmonary Metastatic Melanoma

Strike,

Barker,

McGuire

et al. 2024

Cureus

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Nivolumab and ipilimumab are immunotherapy agents recommended for the treatment of metastatic melanoma. A rare adverse effect of these agents is hypercalcemia. The mechanism of immunotherapy-mediated hypercalcemia is thought to be due to ectopic calcitriol production from activated macrophages, similar to sarcoidosis. We present a case of a 76-year-old female with metastatic melanoma who developed severe hypercalcemia after completing a cycle of combined nivolumab and ipilimumab therapy. After other common causes of hypercalcemia in malignancy were ruled out, the decision was made to aggressively treat her hypercalcemia while inpatient and hold immunotherapy at discharge. Since holding immunotherapy, she has not had a repeat occurrence of hypercalcemia. This case stresses the importance of including immunotherapy adverse effects in the differential diagnosis for hypercalcemia in malignancy.

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“…Calcitriol-induced hypercalcaemia is managed by treating the cause in conjunction with steroids since a favourable response with the latter is often seen ( 3 , 6 ). Steroids inhibit both the activation of 25-hydroxy vitamin D and the resorption carried out by osteoclasts through suppression of cytokine production by the tumour ( 7 ). The optimal, most effective steroid dose remains unclear and various empirical regimens have been described in the literature.…”

Section: Discussionmentioning

confidence: 99%

An uncanny case of paraneoplastic calcitriol mediated hypercalcaemia

Shah

Saeed

Gonzalez

2023

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary A 77-year-old female patient with a history of treated breast cancer and a recently diagnosed laryngeal cancer presented with severe hypercalcaemia associated with suppressed parathyroid hormone (PTH) levels. Her initial investigations included 25-hydroxy vitamin D levels, short synacthen test, bone scan, myeloma screen and thyroid function tests which were within normality. A computerised tomography (CT) scan showed some right lung apical fibrotic changes. Her PTH-related peptide (PTHrP) was normal and sarcoidosis was also excluded. Her previous and current malignancies were thought to be unlikely behind her hypercalcaemia. Her 1,25-dihydroxy vitamin D (calcitriol) levels were found to be elevated. Her hypercalcaemia was initially managed with intravenous fluids and intermittent bisphosphonates infusions which would transiently reduce her calcium levels. Steroid treatment was initiated which improved her hypercalcaemia; however, the calcium levels rebounded on tapering the steroids down, a pre-requisite prior to a positron emission computerised tomography (PET-CT) scan to determine the source of the excess calcitriol production. This was cancelled following an emergency admission with marked hypercalcaemia and acute renal and liver injury. A contemporary CT scan showed a right apical lung mass with hepatic lesions suggestive of a disseminated lung primary. The histology obtained from a liver biopsy was compatible with metastatic small-cell lung carcinoma. Unfortunately, her clinical condition deteriorated further and she did not survive. To the best of our knowledge, this is the first report in the literature describing calcitriol-mediated hypercalcaemia due to a small-cell lung cancer. Learning points Paraneoplastic hypercalcaemia may manifest even without overt detection of the primary cancer. The workup for paraneoplastic hypercalcaemia should be meticulous. Both bisphosphonates and steroids are useful in the initial management of calcitriol-mediated hypercalcaemia, but the definitive management is the treatment of the cause.

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Calcitriol-mediated hypercalcemia as an immune-related adverse event in a patient receiving nivolumab and ipilimumab for metastatic renal cell carcinoma, case report

Cited by 8 publications

References 12 publications

Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline

Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline

Hypercalcemia Secondary to Calcitriol Production From Dual Combination Immunotherapy in Pulmonary Metastatic Melanoma

An uncanny case of paraneoplastic calcitriol mediated hypercalcaemia

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