scholarly journals Multiple endocrinopathies, hypercalcaemia and pancreatitis following combined immune checkpoint inhibitor use- case report and review of literature

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christine Newman ◽  
Oratile Kgosidalwa ◽  
Osamah A. Hakami ◽  
Carmel Kennedy ◽  
Liam Grogan ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Incidental Finding ◽  
Oral Prednisolone ◽  
Thyroid Stimulating Hormone ◽  
Free T4 ◽  
Cross Sectional ◽  
Remarkable Case ◽  
Acth Deficiency

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy. Case presentation A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38–5.33) mIU/L, free T4 of 66.9 (7–16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2–2.5) mmol/l and parathyroid hormone (PTH) of 9 (10–65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis – both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient’s thyrotoxicosis had resolved without anti-thyroid mediations – consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone. Conclusion This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.

scholarly journals History of Radiation to the Neck Increases the Risk of Denovo Thyroid Dysfunction after Receiving Immune Checkpoint Inhibitors

Endocrines ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 82-89
Author(s):  
Koosha Paydary ◽  
Muhammad Zain Farooq ◽  
Ankit Mangla
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Previous History ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Disorder ◽  
Free T4 ◽  
History Of

Thyroid dysfunction is a common endocrine side effect of immune checkpoint inhibitors (ICI). We designed a retrospective study, including patients who received ICI for any cancer at our institution. Thyroid-stimulating hormone (TSH), free T4 levels, and time to development of thyroid dysfunction were measured, and medication used to treat thyroid dysfunction were identified. We reviewed the charts of 104 patients with complete records obtained from our tumor registry. A total of 91 patients were included in the analysis, after excluding 13 patients with a pre-existing thyroid disorder. Twenty-eight (30.77%) patients developed thyroid dysfunction after starting ICI. Race (p-0.048), age (p-0.014), history of radiation therapy (RT) to the neck (p-0.004), history of RT to the chest (p-0.012), and history of venous thrombosis (p-0.004) were significantly associated with thyroid dysfunction on univariate analysis. For multivariate analysis, the history of RT to the neck, adjusted for age, race, and sex, was significantly associated with thyroid dysfunction (adjusted OR-9.64, 95%CI: 1.88, 49.36, p-0.007). In patients receiving ICI for any type of cancer, the previous history of RT to the neck was significantly associated with the development of thyroid dysfunction after starting ICI.

scholarly journals Immune checkpoint inhibitor combination therapies very frequently induce secondary adrenal insufficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsunori Manaka ◽  
Junichiro Sato ◽  
Maki Takeuchi ◽  
Kousuke Watanabe ◽  
Hidenori Kage ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adrenal Insufficiency ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Delayed Diagnosis ◽  
Secondary Adrenal Insufficiency ◽  
Acth Deficiency ◽  
Life Threatening ◽  
Inhibitor Combination

AbstractImmune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.

scholarly journals Diffuse Cystic Metastases in the Lung after Nivolumab Treatment in a Patient with Non-Small Cell Lung Cancer: A Case Report

2021 ◽  
pp. 34-38
Author(s):  
Satoshi Muto ◽  
Yuki Ozaki ◽  
Takuya Inoue ◽  
Naoyuki Okabe ◽  
Yuki Matsumura ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Sialyl Lewis X ◽  
Ground Glass ◽  
Cystic Lesions ◽  
Positron Emission ◽  
Ground Glass Nodules

Although diffuse cysts in the lung can be found in many diseases, they are uncommon in metastatic lung adenocarcinoma. They are even more unusual after the administration of immune checkpoint inhibitors. A case of lung adenocarcinoma that developed diffuse cysts in the lungs during treatment with nivolumab is reported. The patient was a 60-year-old woman with postoperative recurrent lung adenocarcinoma in mediastinal lymph nodes and pleural dissemination. After first-line treatment with cisplatin, pemetrexed, and bevacizumab, computed tomography (CT) showed disease progression. Treatment was then switched to nivolumab. After 5 courses of nivolumab, CT showed multiple ground-glass nodules in her lungs. After 4 more courses of nivolumab, the ground-glass nodules increased in size, and cystic air spaces appeared in their centers. The patient did not have any symptoms. Laboratory tests showed no evidence of infection or nivolumab-induced pneumonitis. Sialyl Lewis X-i antigen increased, and positron emission tomography showed abnormal uptake of 18F-fluorodeoxyglucose in these lesions. Considering this evidence, the cystic lesions were diagnosed as multiple lung metastases. Various differential diagnoses should be considered when diffuse cystic lesions are found in the lungs after the administration of immune checkpoint inhibitors.

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 (&lt;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 &lt;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 Thyroid dysfunction in patients of metabolic syndrome: A study from a tertiary care center in India

2021 ◽  
Vol 12 (10) ◽  
pp. 47-50
Author(s):  
Ritu Gupta ◽  
Akhil K Vijayan ◽  
Sushma Choudhary
Keyword(s):  
Metabolic Syndrome ◽  
Thyroid Dysfunction ◽  
Care Center ◽  
Tertiary Care ◽  
Cross Sectional Study ◽  
Thyroid Stimulating Hormone ◽  
P Value ◽  
Overt Hypothyroidism ◽  
Free T4 ◽  
Cross Sectional

Background: Metabolic syndrome is characterized by hypertension, dyslipidemia, central obesity, glucose intolerance, insulin resistance. Thyroid hormone acts as general pacemaker, accelerating metabolic process and may be associated with metabolic syndrome. There is no information available in literature regarding the prevalence and association of thyroid dysfunction in metabolic syndrome in this central region of the country. Aims and Objective: To estimate the prevalence of thyroid dysfunction in patients of metabolic syndrome. Materials and Methods: It is a duration based prospective cross sectional study including 200 patients of metabolic syndrome. A detailed history, clinical examination and relevant investigations including serum Free T4 (FT4), Free T3 (FT3), Thyroid Stimulating Hormone (TSH) were done. Range, frequencies, percentage, mean, standard deviation and P value were calculated. P value of < 0.05 was taken as significant. Results: Prevalence of thyroid dysfunction in metabolic syndrome patients was 28.5%. Prevalence of subclinical and overt hypothyroidism was 18.5% and 8.5% respectively. In patients with both metabolic syndrome and thyroid dysfunction, most common components associated are diabetes mellitus and hypertriglyceridemia. Conclusion: Thyroid dysfunction is significantly common in metabolic syndrome patients. It should be aggressively detected and treated in these patients for better outcome.

Reduction of Lung Metastases in a Mouse Osteosarcoma Model Treated With Carbon Ions and Immune Checkpoint Inhibitors

2021 ◽  
Vol 109 (2) ◽  
pp. 594-602 ◽  
Author(s):  
Alexander Helm ◽  
Walter Tinganelli ◽  
Palma Simoniello ◽  
Fuki Kurosawa ◽  
Claudia Fournier ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Carbon Ions

scholarly journals Prevalence of thyroid dysfunction in patients with polycystic ovarian syndrome: a cross sectional study

2018 ◽  
Vol 7 (8) ◽  
pp. 3055 ◽  
Author(s):  
Deepa Shanmugham ◽  
Sindhu Natarajan ◽  
Arun Karthik
Keyword(s):  
Thyroid Dysfunction ◽  
Polycystic Ovarian Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Thyroid Stimulating Hormone ◽  
Endocrine Disorders ◽  
Free T4 ◽  
Cross Sectional ◽  
The Mean ◽  
Ovarian Syndrome

Background: Polycystic ovary syndrome (PCOS) and thyroid disorders are two of the most common endocrine disorders in the general population. Both of these endocrine disorders share common predisposing factors, gynaecological features and have profound effect on reproductive function in women. The aim of this study is to study the prevalence of thyroid dysfunction in patients with polycystic ovarian syndrome and to evaluate the relationship between polycystic ovarian syndrome and thyroid dysfunction.Methods: This is a cross sectional observational study done on 100 patients with Poly Cystic Ovarian Syndrome based on Rotterdam’s criteria. The exclusion criteria was hyperprolactinemia, congenital adrenal hyperplasia and virilising tumour. Thyroid function was evaluated by measurement of fasting serum thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4).Results: The mean age of the study patients was 26±4.2 years. Among the study patients, 11% of them had goitre. 18% of the patients with presented with subclinical hypothyroidism. The mean TSH levels in the study patients was 4.62±2.12 mIU/ml. The overall prevalence of thyroid dysfunction was 33% in the study patients with PCOS.Conclusions: This study concludes that the prevalence of hypothyroidism is increased in women with PCOS patients.

Pembrolizumab-induced thrombotic thrombocytopenic purpura

2019 ◽  
Vol 26 (5) ◽  
pp. 1237-1240 ◽  
Author(s):  
Marcus SR Dickey ◽  
Anant J Raina ◽  
Peter J Gilbar ◽  
Brendan L Wisniowski ◽  
Joel T Collins ◽  
...  
Keyword(s):  
Adverse Events ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Oral Prednisolone ◽  
Autoimmune Disorder ◽  
Community Acquired Pneumonia ◽  
Thrombocytopenic Purpura ◽  
Life Threatening

Introduction Pembrolizumab is a humanised monoclonal antibody targeting the receptor programmed cell death protein-1 (PD-1), with anti-tumour activity demonstrated for many malignancies. Such immune checkpoint inhibitors are associated with many immune-related adverse events including rash, colitis, hepatitis, pneumonitis, endocrinopathy and, rarely, haematological adverse events, including immune-related thrombocytopenia. Case report We report a 60-year-old female with metastatic non-small cell lung cancer treated with pembrolizumab every three weeks. Following her fifth cycle, she presented to our hospital with community-acquired pneumonia. Thrombocytopenia developed the next day and, after detailed investigations, thrombotic thrombocytopenic purpura was diagnosed. Management and outcome Pembrolizumab was immediately ceased and plasma exchange commenced along with IV methylprednisolone 250 mg daily for three days followed by oral prednisolone. After five days of plasma exchange, platelet counts normalised and haemolytic anaemia resolved. Discussion Acquired thrombotic thrombocytopenic purpura is an autoimmune disorder caused by an inhibitory autoantibody against ADAMTS-13. While most cases of acquired thrombotic thrombocytopenic purpura are idiopathic, certain conditions (e.g. bacterial infection, autoimmune disorders, malignancies) and medications are associated with thrombotic thrombocytopenic purpura. Other potential causes were eliminated in our patient. As acquired thrombotic thrombocytopenic purpura is an autoimmune disorder, pembrolizumab, given its unique mechanism of action and association with immune-related adverse events, is believed to be implicated in the development of thrombotic thrombocytopenic purpura. This case is one of only two linking anti-PD-1 therapy to thrombotic thrombocytopenic purpura development (the other occurring in a patient on nivolumab plus ipilimumab). Thrombotic thrombocytopenic purpura is life-threatening and clinicians are advised to be aware of its possible occurrence in immune checkpoint inhibitor-treated patients.

PD-L1 expression of high grade glial tumors at diagnosis and change of expression status at recurrence.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2035-2035 ◽  
Author(s):  
Basak Oyan ◽  
Seyma Eren ◽  
Ozlem Sonmez ◽  
Ferda Ozkan ◽  
Kaan Yaltırak ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
High Grade ◽  
Cross Sectional ◽  
Glial Tumors ◽  
The Impact ◽  
Expression Status ◽  
Over Time

2035 Background: PD-L1 expression status is the main predictive factor for response to immune checkpoint inhibitors. PD-L1 status may change over time with the impact of therapies. The aim of this study is to determine if PD-L1 expression status changes in recurrent gliomas after chemoradiotherapy. Methods: Thirty eight patients with recurrent high grade gliomas who had surgical excision at least two times were included in this retrospective cross-sectional study. Nine patients were excluded because of the lack of appropriate pathology slides for pathologic evaluation. PD-L1 expression of 29 patients was evaluated by an expert pathologist with immunohistochemical methods. PD-L1 positivity was defined as expression in ≥1% of tumor cells. Change in PD-L1 expression status was defined as an absolute 5% difference between two resections. Results: Of the 29 patients, 15 patients (51.7%) had PD-L1 expression in ≥1% of tumor cells and 7 patients (24.1%) had PD-L1 expression in ≥10% of tumor cells. Tumor PD-L1 expression (defined as expression in ≥1% of tumor cells) was positive in 15 (51.7%) of 29 patients at diagnosis and at the time of recurrence. The PD-L1 status did not change in 17 patients (58.6%). 8 patients had PD-L1 negative tumors both at diagnosis and at recurrence, while 9 patients had PD-L1 positive tumors both at diagnosis and at recurrence. In 6 patients (20.7%) a negative-to-positive switch and in 6 patients (20.7%) a positive to negative switch were seen. Tumor PD-L1 expression increased in 7 of 29 patients (24.1%) and decreased in 9 of 29 patients (31.1%). PD-L1 expression remained stable in 13 of 29 patients (34.4%). The change in PD-L1 status over time was not statistically significant. Conclusions: More than 50% of high grade glial tumors express PD-L1 at diagnosis, so these tumors are good candidates for immune checkpoint inhibitors. The expression status changes in more than 40% of high grade glial tumors at recurrence, so immune responsiveness of glial tumors can be modified by treatments like chemotherapy and radiotherapy.

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