mGlu Group III Receptors

Restaging CT scans after cycle 4 revealed an overall partial response, with the largest liver lesion shrinking by 32% in the long-axis (3

Restaging CT scans after cycle 4 revealed an overall partial response, with the largest liver lesion shrinking by 32% in the long-axis (3.6??3.9?cm from 4.4??5.7?cm), as seen in Fig.?1. calcitriol level (142?pg/mL), low parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) levels, and a normal 25-hydroxyvitamin D level. FDG-PET imaging showed hypermetabolic mediastinal, hilar, and intra-abdominal lymphadenopathy, however the subsequent lymph node biopsy only showed reactive lymphoid cells without malignancy or granuloma. The hypercalcemia was resistant to initial therapy with calcitonin, hydration, and zoledronic acid but quickly responded to high-dose prednisone (1?mg/kg), followed by normalization of calcitriol levels. The patient was rechallenged with nivolumab and ipilimumab which provided a partial response after 4 cycles. He was maintained on low dose prednisone (10?mg daily) leading to a sustained resolution of his hypercalcemia. Conclusion This case suggests calcitriol-mediated hypercalcemia as a novel immune-related adverse event. not FDG-avid but were stable in size, as were his prior lung nodules. He underwent a bronchoscopy with biopsy of four separate lymph Captopril disulfide nodes, none of which demonstrated malignancy nor granulomatous disease. He was initially treated with intravenous normal saline, calcitonin 4 units/kg every 12?h and 4?mg zoledronic acid. Despite seven days of aggressive treatment, his hypercalcemia persisted, as shown in Fig.?2. He was then started on 1?mg/kg of oral prednisone both for this calcitriol-mediated hypercalcemia as well as for his ongoing psoriatic arthritis flare. Within two days of starting systemic steroids, the patients calcitriol level normalized (56.6?pg/mL), as did his calcium level (8.9?mg/dL). He reported notable relief of arthritic symptoms immediately. He was then discharged home and slowly weaned down to prednisone 10?mg daily, which was continued for control of his arthritis. Open in a separate window Fig. 1 a FDG-PET/CT demonstrating hypermetabolic mediastinal lymph nodes. b FDG-PET/CT showing a hypermetabolic portacaval lymph node, though the known liver metastasis was not FDG-avid (red arrow). Below these PET images, two CT scans of the abdomen & pelvis are shown: Rabbit polyclonal to LIN28 one before treatment was initiated (c) and one 6?months after treatment was completed (d). The dominant right liver lesion decreased from 5.7??4.4?cm to 3.9??3.6?cm in size (red arrow) Open in a separate window Fig. 2 This graph demonstrates the changes in levels of Captopril disulfide calcium (shown in gray), 1, 25(OH) D (shown in blue), and 25(OH) D (shown in orange) throughout the patients hospitalization as various treatments were provided as labeled above. The X axis represents time measured in days. The left Y axis illustrates vitamin D levels in mg/dL. The right Y axis demonstrates the calcium levels in mg/dL. The green dashed lines indicate the start dates for the various treatments described above including steroids (prednisone), zoledronic acid, calcitonin, and immunotherapy (nivolumab and ipilimumab re-challenge) As an outpatient, he was re-challenged with nivolumab and ipilimumab 1?month later. Restaging CT scans after cycle 4 revealed an overall partial response, with the largest liver lesion shrinking by 32% in the long-axis (3.6??3.9?cm from 4.4??5.7?cm), as seen in Fig.?1. Prior to receiving cycle 6 nivolumab maintenance, routine lab work showed the development of immunotherapy-related hypothyroidism for which thyroid hormone replacement therapy was started. He remains on nivolumab maintenance therapy with ongoing partial response of his disease, no recurrent hypercalcemia, and no further immunotherapy-related adverse events (irAE) to date. Discussion and conclusions We report the first-known case of calcitriol-mediated hypercalcemia associated with immunotherapy. We come to this etiologic conclusion given the laboratory findings Captopril disulfide of a suppressed PTH, low PTHrP, and an elevated calcitriol level. In addition, multiple PET-avid mediastinal lymph nodes were biopsied and failed to demonstrate the presence of Captopril disulfide Captopril disulfide malignancy or granulomatous disease, though this does not definitively rule out either condition. Our suspicion that this may be an irAE is based on multiple factors, including onset soon after immunotherapy initiation, the concurrent worsening of his chronic autoimmune disorder (psoriatic arthritis), the rapid normalization of calcitriol levels with the introduction of high-dose glucocorticoid therapy, and partial responses noted on restaging scans. Given these findings, it seems likely that this episode of calcitriol-mediated hypercalcemia was in relation to immune checkpoint blockade. Despite this likely association, the mechanism of dysregulated calcitriol production in the setting of immunotherapy is unclear. It is well-known that certain inflammatory conditions with granuloma formation, such as sarcoidosis, can present with calcitriol-induced hypercalcemia [5]. This process.