A case of cancer-associated hyponatraemia: primary adrenal insufficiency secondary to nivolumab

2021 ◽  
Vol 21 ◽  
Author(s):  
Silvia Galliazzo ◽  
Filippo Morando ◽  
Paola Sartorato ◽  
Michela Bortolin ◽  
Ernesto De Menis
Keyword(s):  
Adverse Events ◽  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Serum Cortisol ◽  
Sodium Concentration ◽  
Primary Hypothyroidism ◽  
Biochemical Tests ◽  
Primary Adrenal Insufficiency ◽  
Replacement Treatment

Background: Immunotherapy with immune checkpoint inhibitors is a new frontier for cancer treatment. On the safety profile, this drug class is associated with a new spectrum of side effects, the so-called immune-related adverse events that can potentially affect any organs, mainly endocrine glands. Scant data are available to inform the appropriate strategy of their management and treatment. Case Presentation: A 74-years man with squamous non-small cell lung cancer on nivolumab was hospitalized for fatigue, nausea, vomiting and severe hyponatremia. Biochemical tests were significant for hypotonic hyponatremia with a high urine sodium concentration. Endocrine tests showed overt primary hypothyroidism and low serum cortisol and aldosterone levels associated with an elevated circulating level of adrenocorticotrophic hormone. Adrenal antibody screening and the search of adrenal lesion on CT abdomen were negative. Thus, a nivolumab-induced primary adrenal insufficiency was diagnosed. Nivolumab withdrawal and replacement treatment with glucocorticoid and mineralocorticoid allowed clinical and biochemical recovery. Conclusion: Physicians need to be aware of potential immune-related adverse events in all patients treated with an immune checkpoint inhibitor. Their timely recognition is essential to carry out the proper treatment.

scholarly journals A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors

2019 ◽  
Vol 51 (03) ◽  
pp. 145-156 ◽  
Author(s):  
Jeroen de Filette ◽  
Corina Andreescu ◽  
Filip Cools ◽  
Bert Bravenboer ◽  
Brigitte Velkeniers
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Adverse Events ◽  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Primary Adrenal Insufficiency ◽  
High Incidence

AbstractMonoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9–8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2–1.2) and pembrolizumab (1.1%; 95% CI, 0.5–2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction – particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4–9.8; pembrolizumab, 8.5%; 95% CI, 7.5–9.7; PD-L1, 5.5%; 95% CI, 4.4–6.8; ipilimumab, 3.8%; 95% CI, 2.6–5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2–16.4%), hyperthyroidism (9.4–10.4%), hypophysitis (8.8–10.5%), and primary adrenal insufficiency (5.2–7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.

scholarly journals Adrenal Insufficiency Masquerading as Primary Hypothyroidism Following Immune Checkpoint Inhibitors Treatment

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A110-A111
Author(s):  
Michael Salim ◽  
Wafa Dawahir ◽  
Janice L Gilden ◽  
Andriy Havrylyan
Keyword(s):  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Primary Hypothyroidism ◽  
Adrenal Crisis ◽  
Thyroid Peroxidase ◽  
Endocrine Disorders ◽  
Free T4

Abstract Background: Immune checkpoint inhibitors (ICIs) are novel immunotherapy agents that have been used to treat multiple advanced cancer. Even though they confer potential clinical advantages by regulating immune reactions, they have been linked with serious immune-mediated adverse events. Here we present a case of a patient who was treated with ICIs, Nivolumab (programmed death-1 inhibitor) and Ipilimumab (cytotoxic T lymphocyte antigen-4 inhibitor), and subsequently developed two concurrent immune-related endocrine disorders. Clinical Case: An 83-year-old man with advanced renal cell carcinoma presented with generalized weakness. He had finished four cycles of immunotherapy with Nivolumab and Ipilimumab, and Ipilimumab was discontinued afterward. Two days after the fifth cycle of immunotherapy with Nivolumab, he developed worsening fatigue, nausea, and anorexia. He appeared mildly volume depleted with borderline hypotensive (104/63 mmHg). The rest of the physical exam was unremarkable. Initial tests showed elevated levels of TSH (13.15 uIU/mL, ref 0.45–5.33 uIU/L), reduced levels of free T4 (<0.25 ng/dL, ref 0.58–1.64 ng/dL), free T3 (1.72 pg/mL, ref 2.5–3.9 pg/mL), negative thyroglobulin antibody, and elevated levels of thyroid peroxidase antibody (429 IU/mL, ref <9 IU/mL), thus suggesting primary hypothyroidism. Serum levels of sodium and potassium were unremarkable (136 meQ/L, ref 136–145 mEq/L; 3.6 meQ/L, ref 3.5–5.1 meQ/L respectively). His baseline TSH was normal three months prior to arrival (1.31 uIU/mL) and suppressed one month prior to arrival (0.01 uIU/mL). Immune-related thyroiditis with immune checkpoint inhibitors was suspected. He was given levothyroxine and observed in the hospital. After two days of hospitalization, weakness had slightly improved. However, he still had persistent nausea. He also developed low blood pressure (90/47 mmHg) and mild hyponatremia (133 mEq/L) with a normal potassium level. Further investigation showed low cortisol (1.0 ug/dL, ref 5.0–21.0), low ACTH (13 pg/mL, ref 6–50 pg/mL), cortisol level at 30 and 60 minutes post-cosyntropin stimulation test of 10.8 ug/dL (ref 13.0–30.0 ug/dL) and 14.8 ug/dL (ref 14.0–36.0 ug/dL) respectively, and negative adrenal antibodies, suggesting of secondary adrenal insufficiency due to hypophysitis. The patient was started on hydrocortisone, and his symptoms improved afterward. Conclusion: This case report highlights the common pitfall of managing immune-related endocrine disorders of ICIs. Adrenal insufficiency may present with a broad range of nonspecific symptoms, which could be attributed to hypothyroidism, underlying illness, or medications. Although a rare adverse effect, it is prudent to recognize adrenal insufficiency superimposed on primary hypothyroidism. Introducing thyroxine before replacing glucocorticoids can lead to an adrenal crisis.

scholarly journals Incidence and Phenotypes of Endocrinopathies in Association With Immune Checkpoint Inhibitors: The Experience of Integrated Health Network

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1022-A1022
Author(s):  
Hassan Mehmood ◽  
Farhad Hasan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Hypothyroidism ◽  
Small Cell ◽  
Small Cell Lung ◽  
Health Network

Abstract Introduction: Since 2011 FDA has approved several immune checkpoint inhibitors (ICI) as antineoplastic agents with very promising results. The side effects profile of ICI is different from that of conventional cancer therapies and predominated by immune-related adverse effects (IRAEs). Autoimmune endocrinopathies (AEs), such as disorders of the thyroid, pituitary, and adrenal glands are increasingly recognized IRAEs of ICI. If not diagnosed and treated early, AEs may cause serious harm in an already compromised patient by advanced malignancy. Therefore, it is necessary to recognize the incidence, phenotypes, and time to onset of various AEs in association with ICI. This retrospective study of a large cancer population treated at an integrated health network aims to do so. Methods: We conducted a retrospective chart review of adult patients treated with ICI as cancer therapy at Allegheny Health Network—a major healthcare provider in Western Pennsylvania—between 1/1/2016 and 6/30/2019. Inclusion criteria were ages 18-90 years who received one or more ICI within the study period, laboratory data available for a minimum of 6 months from date of the first ICI dose, and no pre-existing outcome of interest at the time of, or prior to, receiving the first ICI dose. Exclusion criteria were pre-existing thyroid, pituitary, or adrenal diseases. Results: We screened the records of 1200 patients who were treated for 47 different cancers for AEs. Of this sample, 57% were males 92.5% were White. Follow up period ranged between 6-57 months, during which 56% of patient died at a mean age of 67.1 years. The most common cancer diagnoses were non-small cell lung cancer (45.4%), malignant melanoma (11.7%), renal cell carcinoma (6.3%), and small cell lung cancer (6.2%). These patients received one or more agents from the three classes of ICI, including PD-1 (75.86%), PDL-1 (12.57%), and CTLA-4 (11.57%). The overall incidence of AEs was 18%. The distribution of AEs was as follows: primary hypothyroidism 15.3%, secondary hypothyroidism 0.5%, primary hyperthyroidism 3.5%, primary adrenal insufficiency 0.2%, secondary adrenal insufficiency 2.7%, and type 1 diabetes mellitus 0.2%. Of the 42 patients diagnosed with hyperthyroidism, 28 (66.7%) later developed primary hypothyroidism within a mean time of 9 weeks. There was no statistically significant association between the incidence of AEs and gender (P=0.748) or age (P=0.998). Conclusion: AEs are common sequelae of ICI and primary hypothyroidism is the most prevalent AEs among our study sample. This study should help increase awareness about the importance of routine screening of the AEs in cancer patients receiving ICI.

scholarly journals Primary Adrenal Insufficiency during Immune Checkpoint Inhibitor Treatment: Case Reports and Review of the Literature

2020 ◽  
Vol 13 (2) ◽  
pp. 621-626
Author(s):  
Carlos Salinas ◽  
Alex Renner ◽  
Carlos Rojas ◽  
Suraj Samtani ◽  
Mauricio Burotto
Keyword(s):  
Adrenal Insufficiency ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Review Of The Literature ◽  
Primary Adrenal Insufficiency ◽  
High Degree ◽  
Inhibitor Treatment

As the indications and clinical use of immune checkpoint inhibitors increase, it is expected that we will face some of their less frequently reported complications. Primary adrenal insufficiency is one of them, and given its unspecific symptoms and potentially serious consequences, it is important to have a high degree of clinical suspicion. We present 3 cases and a review of the literature concerning its main clinical characteristics, diagnostics, and management.

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