A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency

Sonehara, Kei; Tateishi, Kazunari; Hirabayashi, Taro; Araki, Taisuke; Ikuyama, Yuichi; Machida, Ryosuke; Hanaoka, Masayuki

doi:10.1159/000508068

Cited by 7 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients do not usually present with headache or fever, and magnetic resonance imaging (MRI) of the sellar region usually does not reveal any abnormality, such as pituitary enlargement. Even in the absence of typical hypophysitis symptoms, however, PD-1 inhibitors often cause hypopituitarism with secondary AI [ 2 , 3 ]. In particular, many cases of isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) [ 4 , 5 ] have been reported [ 6 – 31 ].…”

Section: Introductionmentioning

confidence: 99%

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

Hinata¹,

Ohara²,

Sakurai³

et al. 2021

Am J Case Rep

View full text Add to dashboard Cite

Patient: Female, 78-year-old Final Diagnosis: Isolated adrenocorticotropic hormone deficiency Symptoms: Anorexia • general weakness • muscle pain Medication: Hydrocortisone Clinical Procedure: Endocrine test Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Immune checkpoint inhibitors (ICIs) are anticancer medications that enhance the antitumor immune response. The clinical benefit afforded by ICIs, however, can be accompanied by immune-related adverse events (IRAEs). One of the common endocrine IRAEs is hypophysitis, which often causes hypopituitarism with secondary adrenal insufficiency (AI). Secondary AI, including isolated adrenocorticotropic hormone (ACTH) deficiency (IAD), is often associated with hyponatremia. Here, we report an unusual case of ICI-related IAD associated with severe hyperkalemia. Case Report: A 78-year-old woman who had an ileal conduit, chronic kidney disease, type 2 diabetes mellitus, and hyper-tension and was taking an angiotensin II receptor blocker began treatment for advanced ureteral cancer with the anti-programmed cell death protein 1 inhibitor pembrolizumab. The therapy effectively controlled the cancer, but 4 1/2 months after starting it, the patient developed anorexia, general weakness, and muscle pain and was diagnosed with IAD associated with severe hyperkalemia and hyperchloremic metabolic acidosis. She recovered after prompt administration of corticosteroids and treatment with sodium bicarbonate, glucose/insulin, and cation exchange resins. Conclusions: Hyperkalemia is a common symptom of primary AI but is less common in patients with central AI because a lack of ACTH does not cause aldosterone deficiency and mineralocorticoid action is preserved. The present case demonstrates the need for physicians to be aware of severe hyperkalemia as a life-threatening complication of secondary AI induced by ICIs, particularly in patients with predisposing factors, such as kidney dysfunction, diabetes mellitus, an ileal conduit, and renin-angiotensin-aldosterone system inhibitor use.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Hinata¹,

Ohara²,

Sakurai³

et al. 2021

Am J Case Rep

View full text Add to dashboard Cite

show abstract

“… 9 , 10 , 11 , 12 However, severe irAEs occur in rare cases, 1 even after the discontinuation of ICIs. 2 , 3 , 4 , 5 , 6 , 7 , 8 The late‐onset toxicity of ICI therapy has been attracting increasing attention. 13 , 14 …”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] However, severe irAEs occur in rare cases, 1 even after the discontinuation of ICIs. [2][3][4][5][6][7][8] The lateonset toxicity of ICI therapy has been attracting increasing attention. 13,14 Type 1 DM is one of the most crucial irAEs caused by ICIs because it progresses rapidly and fatally.…”

Section: Discussionmentioning

confidence: 99%

“…Immune checkpoint inhibitors (ICIs) have markedly changed the treatment of lung cancer; however, severe immune‐related adverse events (irAEs) occur in rare cases, 1 even after the discontinuation of ICIs. 2 , 3 , 4 , 5 , 6 , 7 , 8 We encountered a lung cancer patient diagnosed with acute‐onset type 1 diabetes mellitus (DM) 7 months after the cessation of pembrolizumab. We herein present this case.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Late‐onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

et al. 2022

View full text Add to dashboard Cite

Immune‐related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute‐onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68‐year‐old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi‐CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first‐line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C‐peptide was 9.3 μg/day. The patient was diagnosed with acute‐onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI.

show abstract

“…However, in our case series, immunotherapy was effective in patients who developed AI and resulted in prolonged survival. In case 4, pembrolizumab was still discontinued after improvement of grade 4 AI, but had maintained CR for about 6 months [ 9 ]. In cases 1, 2, 3, and 4, immunotherapy was continued with corticosteroid replacement therapy, and the efficacy of pembrolizumab was good.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series

et al. 2021

Self Cite

View full text Add to dashboard Cite

Pembrolizumab-induced adrenal insufficiency (AI) is recognized as a rare immune-related adverse event (irAE) that can be fatal if diagnosis is delayed. Clinical features of AI in patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab as the first-line treatment were observed. Five out of 49 patients with untreated advanced NSCLC developed AI between April 2017 and February 2021. Of the 5 patients, 4 developed AI with a grade >3 and were hospitalized. The median time of the onset of AI from the start of first-line treatment was 4.63 months. All the patients improved after corticosteroid replacement therapy. The efficacy of treatment was complete response in 1 patient and partial response in 4 patients. Median progression-free survival was 37.7 months, and overall survival had not been reached. This case series revealed the efficacy of immunotherapy in AI as an irAE.

show abstract

A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency

Cited by 7 publications

References 15 publications

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

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

Late‐onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series

Contact Info

Product

Resources

About