Isolated ACTH deficiency induced by cancer immunotherapy: a systematic review

Iglesias, Pedro; Sánchez, Juan Cristóbal; Díez, Juan J.

doi:10.1007/s11102-021-01141-8

Cited by 52 publications

(57 citation statements)

References 57 publications

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“…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 ]. Patients with anti-PD-1-related IAD present with cortisol deficiency symptoms, including anorexia, fatigue, and general weakness.…”

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

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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.

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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

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“…Fatigue and anorexia are the most common symptoms, while laboratory measurements reveal hyponatriemia, as in our case- and eosinophilia. Nevertheless, MRIs might be normal [ 25 ]. Detailed medical history and clinical investigation, can aid diagnosis, even before typical signs and symptoms occur.…”

Section: Discussionmentioning

confidence: 99%

Late-onset hypophysitis after discontinuation of nivolumab treatment for advanced skin melanoma: a case report

et al. 2021

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Background Nivolumab is an anti-programmed cell death protein 1 antibody, typically used as cancer immunotherapy agent. Despite multiple clinical benefits it might cause autoimmune-related side-effects, often involving the endocrine system. To our knowledge, this is the first case of nivolumab-induced hypophysitis manifesting several months after treatment discontinuation. Case presentation We, herein, report a 53-year-old patient with hypophysitis and isolated adrenocorticotropic hormone deficiency, who presented with recurring syncopal episodes and persistent mild hyponatremia. The performed challenged tests were consistent with secondary adrenal insufficiency, while responses of other anterior pituitary hormones were preserved. Magnetic resonance imaging revealed thickened pituitary stalk, consistent with hypophysitis. The patient’s condition gradually improved after administration of hydrocortisone, with normalization of sodium and glucose-levels. The related literature is discussed. Conclusions We conclude that even after discontinuation of nivolumab, isolated adrenal insufficiency can occur. Therefore, in case of administration of such agents, clinical assessment, and routine monitoring of blood pressure, sodium-, glucose-levels, pituitary hormones as well as magnetic resonance imaging are needed to identify such conditions and prevent an adrenal crisis.

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“…It is possible that the involvement of a single anterior pituitary cell type, in this case corticotroph, is insu cient to develop anatomical alterations that can be seen in imaging tests [21]. In addition, although AI is not associated with mineralocorticoid de ciency, hyponatremia often occurs in IAD as a result of reduced glomerular ltration rate, increased antidiuretic hormone secret and concomitant hypothyroidism [22]. Patients with IAD usually present with non-speci c manifestation, so it may be misinterpreted or underdiagnosed.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with IAD usually present with non-speci c manifestation, so it may be misinterpreted or underdiagnosed. Once cancer patients treated with ICIs develop non-speci c symptoms along with hyponatremia, the diagnosis of IAD should be considered [20,22,23]. In this case, the patient was treated with camrelizumab.…”

Section: Discussionmentioning

confidence: 99%

Isolated Adrenocorticotropic Hormone Deficiency Caused by Camrelizumab in a Patient with Lung Sarcoma: A Case Report and Literature Review

Huang

Feng

2021

Preprint

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Background Immune checkpoint inhibitors significantly increase survival in some malignant tumors, but they also lead to a variety of immune-related adverse events that affect multiple organs, including the liver, lung and endocrine system. Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare pituitary disorder characterized by secondary adrenal insufficiency with low or absent cortisol production but the normal secretion of pituitary hormones other than ACTH. IAD caused by atezolizumab, pembrolizumab and nivolumab therapy had been reported, but none is reported in camrelizumab, a new immune checkpoint inhibitor (ICI). Clinicians may not be aware of this unusual side effect. Case presentation: Here, we describe a 70-year-old male patient who had lung sarcoma and was treated with camrelizumab. After nine months of treatment, he developed immune-related pneumonia and hepatitis associated with camrelizumab. The patient discontinued the drug and recovered soon after administration of glucocorticoids. But he subsequently appeared severe hyponatremia, and was diagnosed with late-onset IAD induced by camrelizumab. His symptoms alleviated after glucocorticoid replacement therapy. Conclusion Regular monitoring serum sodium levels and testing endocrine function should be beneficial for cancer patients not only during the treatment of camrelizumab but also after discontinuation of the ICI. Clinicians should consider IAD induced by ICIs when hyponatremia occurs in the patients.

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Isolated ACTH deficiency induced by cancer immunotherapy: a systematic review

Cited by 52 publications

References 57 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 hypophysitis after discontinuation of nivolumab treatment for advanced skin melanoma: a case report

Isolated Adrenocorticotropic Hormone Deficiency Caused by Camrelizumab in a Patient with Lung Sarcoma: A Case Report and Literature Review

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