Autoimmune Myasthenia, Primary Adrenal Insufficiency, and Progressive Hypothyroidism Due to Pembrolizumab and Axitinib Combination Regimen

Figueroa-Perez, Nikole; Kashyap, Rahul; Bal, Deepinder; Khan, Syed Anjum; Pattan, Vishwanath

doi:10.7759/cureus.16933

Cited by 6 publications

(8 citation statements)

References 19 publications

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“…Twenty-seven studies with detailed patients’ features have been published from 2013 to 2022 and are included in Table 1 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. These studies describe a total of 29 patients who experienced PAI following ICI therapy for various types of malignancy.…”

Section: Literature Review Resultsmentioning

confidence: 99%

“…Three patients (10.3%) were treated with anti-CTLA-4 monotherapy, 20 patients (69%) were treated with anti-PD-1/L1 monotherapy, and the remaining six patients (20.7%) were treated with anti-CTLA-4 and anti-PD-1 combination therapy. In at least eight cases [ 16 , 21 , 23 , 24 , 27 , 34 , 37 ], ICIs were chosen as the first-line systematic therapy for advanced disease, whereas, in four cases ICI, treatment was combined with a tyrosine kinase inhibitor [ 13 , 22 , 27 , 29 ], which has also been implicated for PAI development [ 40 ]. The ICI-induced PAI was diagnosed from 10 days to 1 year post ICI initiation.…”

Section: Literature Review Resultsmentioning

confidence: 99%

“…The assessment of antibodies was inconsistently reported throughout the studies. Six cases out of 10 [ 13 , 17 , 23 , 26 , 28 , 39 ] presented positive 21-hydroxylase antibodies (21-OHAbs), while antibodies were negative in four cases [ 20 , 29 , 35 ]. The 21-OHAbs and adrenal cortex antibodies (ACA) were both positive in two cases [ 13 , 23 ].…”

Section: Literature Review Resultsmentioning

confidence: 99%

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The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events

Mytareli

Ziogas

Karampela

et al. 2023

Cancers

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Immune checkpoint inhibitors (ICIs) have been approved for the treatment of many cancers, either in adjuvant or metastatic settings. Regarding safety, endocrine adverse events (AEs) are some of the most common AEs in ICI-treated patients, with thyroid dysfunction and hypophysitis being the most frequent disorders. However, there are also some rare and very rare immune-related (ir) endocrine complications (incidence between ≥1/10,000 to <1/1000 and <1/10,000, respectively, according to the established classification) that have been reported in isolated case reports, with limited data about their management. In this systematic review, we summarize all published cases with primary adrenal insufficiency, central diabetes insipidus, primary hypoparathyroidism, lipodystrophy, osteoporosis, hypergonadotrophic hypogonadism, or Cushing disease and discuss their diagnostic and therapeutic approaches as well as the current knowledge on their pathophysiology. In these ICI-treated cancer patients, the presentation of symptoms unrelated to their underlying malignancy has led to further diagnostic tests, including hormonal profile and functional assays which subsequently confirmed endocrinopathy, while the assessment of autoantibodies was rarely available. In most of these cases, the exact pathogenesis remained unknown, and the endocrine dysfunction was permanent, requiring lifelong supplementation. Although endrocine irAEs are rare, physicians must be aware of these irAEs to recognize them on time and treat them appropriately.

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Section: Literature Review Resultsmentioning

confidence: 99%

Section: Literature Review Resultsmentioning

confidence: 99%

Section: Literature Review Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Uncharted Landscape of Rare Endocrine Immune-Related Adverse Events

Mytareli

Ziogas

Karampela

et al. 2023

Cancers

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“…1 Pembrolizumab, a humanized IgG4 monoclonal antibody, inhibits the PD-1 receptor and is approved for various malignancies, including melanoma, non-small cell lung cancer (NSCLC), Hodgkin lymphoma, cervical cancer, and renal cell carcinoma. 2,3 Pembrolizumab's mechanism involves selectively silencing immunological cell surface proteins, thereby shielding both healthy and tumor cells from immune system-induced apoptosis. 4 Although ICIs have improved the survival rates in those suffering from malignancy, rare immune-related adverse effects such as endocrinopathies can occur.…”

Section: Introductionmentioning

confidence: 99%

“…4 Although ICIs have improved the survival rates in those suffering from malignancy, rare immune-related adverse effects such as endocrinopathies can occur. 3 One such endocrinopathy is adrenal insufficiency (AI), which has a reported incidence of 0.98%. 2 We describe a case of secondary AI and primary hypothyroidism in a 59-year-old man secondary to pembrolizumab use for lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Presentation of Secondary Adrenal Insufficiency and Primary Hypothyroidism due to Pembrolizumab: A Case Report

Khatri,

Alom,

Kashfi

et al. 2023

Journal of Investigative Medicine High Impact Case Reports

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Checkpoint inhibitors have gained increased traction in recent years as they have improved prognosis in various malignancies. Pembrolizumab, an anti-programmed cell death protein (PD-1) monoclonal antibody, has become a first-line chemotherapeutic agent for stage II non–small cell lung cancer since 2019. Although much more common with nivolumab, several immune-related adverse effects, particularly endocrinopathies, have been linked with pembrolizumab. We describe a case of a 59-year-old man with a history of unspecified lung cancer who presented with severe hyponatremia later attributed to secondary adrenal insufficiency and accompanying primary hypothyroidism secondary to pembrolizumab. Diagnosing adrenal insufficiency in patients on immune checkpoint inhibitors like pembrolizumab can be challenging due to nonspecific symptoms, making it crucial to rule out other causes of hyponatremia. Immunotherapy is known to cause thyroid immune-related adverse events, and anti-thyroid antibodies may not always be present in the diagnosis of hypothyroidism. Although there are some reported cases of pembrolizumab-induced adrenal insufficiency, the link between immunotherapy and endocrine disorders remains unclear. To our knowledge, no case reports exist that describe both primary hypothyroidism and secondary adrenal insufficiency after taking pembrolizumab, although such cases have been documented with axitinib. Timely diagnosis and treatment of adrenal insufficiency is crucial to prevent adverse effects, especially in patients with cancer receiving immunotherapy, as highlighted in this case.

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