Isolated Adrenocorticotropic Hormone Deficiency Associated with Severe Hyperkalemia During Pembrolizumab Therapy in a Patient with Ureteral Cancer and an Ileal Conduit: A Case Report and Literature Review

Hinata, Yudai; Ohara, Nobumasa; Sakurai, Yuhki; Koda, Ryo; Yoneoka, Yuichiro; Takada, Toshinori; Hara, Noboru; Nishiyama, Tsutomu

doi:10.12659/ajcr.931639

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…In our review, the ratio of male patients to female patients was 1.8. The predominance of male patients in ICI-induced IAD was consistent with the review reported by Iglesias ( 10 ) and Hinata ( 11 ). The average age at diagnosis of IAD was also similar, which was mainly affected by the time of onset of the tumor.…”

Section: Discussionsupporting

confidence: 91%

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review

Wang,

Shi,

et al. 2024

Front. Endocrinol.

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BackgroundImmune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease.MethodsWe comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded.ResultsWe identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD.ConclusionIAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.

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Section: Discussionsupporting

confidence: 91%

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review

Wang,

Shi,

et al. 2024

Front. Endocrinol.

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“…This could lead to delayed diagnosis [2]. However, concurrent hyponatremia could increase the clinical suspicion index of those symptoms as previously reported by others [9,[15][16][17][18][19]. In our case, headaches but not visual disturbances were one of the presenting symptoms.…”

Section: Clinical Presentationsupporting

confidence: 61%

“…Defects of the neurohypophysis are mainly reported in the context of pituitary metastasis [4]. Ascertainment of secondary adrenal failure used different testing strategies, including morning cortisol and ACTH [9,[11][12]15,[17][18][19][20][21][22][23][24][25][26][27], short Synacthen test [12,[16][17][18]21] and corticotropin-releasing hormone (CRH) stimulation test [12,16,24]. In our patient, three pituitary axes were affected: the adrenocorticotropic, thyroid and gonadotrophic axes.…”

Section: Hormonal Disturbancesmentioning

confidence: 99%

Exploring a New Entity of Single-Agent Pembrolizumab-Associated Hypophysitis

Balti¹,

Verhaeghe²,

Krüse³

et al. 2022

Cureus

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Hypophysitis is the inflammation of the pituitary gland primary or secondary to local or systemic disease. It tends to occur more with cytotoxic T-lymphocyte-associated protein 4 inhibitors (10-15% of cases), which is a different entity compared to that associated with anti-program death 1 (anti-PD1) inhibitors. We describe a case of pembrolizumab-associated hypophysitis and conduct a systematic review of the literature.A 55-year-old woman with stage pT3aN1a (TNM stadium IIIb) melanoma presented with headache, nausea and fatigue three and a half months after starting pembrolizumab. Blood analyses revealed secondary adrenal failure, thyrotropic insufficiency and defective gonadotrophin secretion. An imaging study showed an enlarged pituitary gland with a homogeneous enhancement of the gland and pituitary stalk. Interruption of anti-PD1 therapy and administration of hormonal supplementation lead to clinical, biological and radiologic improvement after eight months.We identified 17 studies (20 patients) on single-agent pembrolizumab-associated hypophysitis. Patients were treated for melanoma (n=7; 33.3%), urogenital (n=5 ; 23.8%), lung (n=4 ; 19.0%), larynx (n=1 ; 4.8%), pharynx (n=1, 4.8%), breast (n=1, 4.8%) and colon (n=1, 4.8%) neoplasia. The time to onset of pituitary insufficiency was most frequently six months (range 1.5-39.0 months) after treatment initiation. The most prevalent hormonal defect was isolated adrenocorticotropic hormone (ACTH) deficiency. Four cases were reported with multiple central hormonal defects. In those patients, an enlarged pituitary gland was also observed.Our case has distinct features, including early disease onset after single-agent pembrolizumab initiation, panhypopituitarism and increased pituitary mass. These findings are in contrast with the majority of other cases of pembrolizumab-induced hypophysitis, as most patients present an isolated ACTH deficiency. Whether or not this is a new clinical entity warrants further investigation.

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“…Although it was not our primary purpose for this study, we identified numerous factors associated with ACU for the population. Some factors associated with the development of irAEs requiring hospitalizations, such as type of ICI agents, 56 platelet count, 57 pre-existing lung, cardiovascular, 56 nutritional, 56 , 58 hyperchloremia, 59 , 60 and infection conditions, 61 are documented in the literature. Variation in red blood cell size and volume is, to our knowledge, not elucidated before and significantly contributes to the accuracy of our XGBT algorithm.…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Models Using Routinely Collected Clinical Data Offer Robust and Interpretable Predictions of 90-Day Unplanned Acute Care Use for Cancer Immunotherapy Patients

Knafl

Turin

et al. 2023

JCO Clinical Cancer Informatics

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PURPOSE Clinical management of patients receiving immune checkpoint inhibitors (ICIs) could be informed using accurate predictive tools to identify patients at risk of short-term acute care utilization (ACU). We used routinely collected data to develop and assess machine learning (ML) algorithms to predict unplanned ACU within 90 days of ICI treatment initiation. METHODS We used aggregated electronic health record data from 7,960 patients receiving ICI treatments to train and assess eight ML algorithms. We developed the models using pre–SARS-COV-19 COVID-19 data generated between January 2016 and February 2020. We validated our algorithms using data collected between March 2020 and June 2022 (peri–COVID-19 sample). We assessed performance using area under the receiver operating characteristic curves (AUROC), sensitivity, specificity, and calibration plots. We derived intuitive explanations of predictions using variable importance and Shapley additive explanation analyses. We assessed the marginal performance of ML models compared with that of univariate and multivariate logistic regression (LR) models. RESULTS Most algorithms significantly outperformed the univariate and multivariate LR models. The extreme gradient boosting trees (XGBT) algorithm demonstrated the best overall performance (AUROC, 0.70; sensitivity, 0.53; specificity, 0.74) on the peri–COVID-19 sample. The algorithm performance was stable across both pre– and peri–COVID-19 samples, as well as ICI regimen and cancer groups. Type of ICI agents, oxygen saturation, diastolic blood pressure, albumin level, platelet count, immature granulocytes, absolute monocyte, chloride level, red cell distribution width, and alcohol intake were the top 10 key predictors used by the XGBT algorithm. CONCLUSION Machine learning algorithms trained using routinely collected data outperformed traditional statistical models when predicting 90-day ACU. The XGBT algorithm has the potential to identify high–ACU risk patients and enable preventive interventions to avoid ACU.

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Isolated Adrenocorticotropic Hormone Deficiency Associated with Severe Hyperkalemia During Pembrolizumab Therapy in a Patient with Ureteral Cancer and an Ileal Conduit: A Case Report and Literature Review

Cited by 8 publications

References 19 publications

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review

Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review

Exploring a New Entity of Single-Agent Pembrolizumab-Associated Hypophysitis

Machine Learning Models Using Routinely Collected Clinical Data Offer Robust and Interpretable Predictions of 90-Day Unplanned Acute Care Use for Cancer Immunotherapy Patients

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