Evidence map›Paper›PMID 32581059›Full record

ArticleJournal for immunotherapy of cancer2020

Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up.

Ramona Dadu, Theresa E Rodgers, Van A Trinh, Elizabeth Helen Kemp, Trisha D Cubb, Sapna Patel, Julie M Simon, Elizabeth M Burton, Hussein Tawbi

Open access · goldAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Ramona DaduEndocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Theresa E RodgersMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Van A TrinhMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Elizabeth Helen KempOncology and Metabolism, The University of Sheffield, Sheffield, South Yorkshire, UK.
Trisha D CubbEndocrinology, Diabetes and Metabolism, Baylor College of Medicine, Houston, Texas, USA.
Sapna PatelMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0003-1339-1517
Julie M SimonSurgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Elizabeth M BurtonSurgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hussein TawbiMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA htawbi@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USUniversity of Sheffield · GB

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented. CASE AND

methodsA 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively.

resultsThe patient's symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient's hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient's clinical course of hypoparathyroidism. CaSR antibodies purified from the patient's serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1.

conclusionThe etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid.

Indexed as

AgedAntineoplastic Combined Chemotherapy ProtocolsAutoantibodiesFollow-Up StudiesHumansHypocalcemiaHypoparathyroidismIpilimumabMaleMelanomaNivolumabPrognosisReceptors, Calcium-SensingAutoantibodiesIpilimumabNivolumabReceptors, Calcium-Sensingantigensepitope mappingimmunity, humoralimmunotherapymelanoma

Identifiers

PMID32581059
PMCPMC7319718
OpenAlexW3037677291

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.