scholarly journals SUN-183 Adrenalitis Induced by Nivolumab

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Muhammad Atique Alam Khan ◽  
Iqra Iqbal ◽  
Puneet Dhillon ◽  
Waqas Ullah
Keyword(s):  
Adrenal Insufficiency ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Stimulation Test ◽  
Adrenal Crisis ◽  
High Dose ◽  
Acth Stimulation ◽  
Activated T Cells ◽  
Programmed Death ◽  
Cortisol Levels

Abstract Introduction: Tumor cells often express a programmed death-ligand 1 (PD-L1), which binds to the programmed death receptor-1 (PD-1) on activated T-cells to induce immune tolerance. Among the class of immune checkpoint inhibitors (ICI), Nivolumab is an anti-PD-1 antibody which blocks these tumor cell interactions. Although some endocrinopathies have been reported for other PD-1 inhibitors, the adverse event of adrenalitis with nivolumab has not been reported before. Clinical Case: A 65-year-old female presented to the hospital with complaints of nausea, vomiting, fatigue, and headache for five days. She was recently diagnosed with metastatic lung adenocarcinoma, complicated by cerebellar metastases, and the left cerebellar mass was resected. She was also started on Nivolumab. Her blood pressure was 98/65 mmHg on the presentation. Serum sodium was 122mEq/L (normal 135–145) and potassium was 5mEq/L (3.5–5). TSH, LH, and prolactin were all normal. Aldosterone was low: 23pmol/L (27.7–582.5) and renin was high: 11 ng/ml/h (0.167- 1.38). Morning cortisol levels were low: 2.2 ug/dl (5- 25) and concomitant ACTH was high: 78 pg/ml (7.2- 63.3). Upon standard high dose cosyntropin stimulation test, basal cortisol was 2.0 ug/dl (5- 25). Cortisol level 30 minutes post cosyntropin was 7.1 ug/dl, while Cortisol 60 minutes post cosyntropin was 12.2 ug/dl (normal >18 -20 ug/dl). Considering the low cortisol levels with high ACTH, and an inadequate rise in cortisol after the ACTH stimulation test, adrenal insufficiency was suspected as a result of adrenalitis due to Nivolumab. Hyponatremia along with low aldosterone and high renin levels also reinforced this clinical diagnosis. A computerized tomographic scan of the chest abdomen and pelvis only showed calcified uterine fibroids. She was initially resuscitated with intravenous fluids. Hydrocortisone 100 mg every 8 hours was started and then gradually tapered down to 60mg every 12 hours. Fludrocortisone was also initiated at 0.2mg daily. Symptoms began to improve, and sodium levels normalized to136 mEq/dl. She was discharged on 30mg of hydrocortisone and 0.1 mg of fludrocortisone daily and is stable since then. Conclusion: This is a rare case of Nivolumab-induced adrenalitis. It highlights the importance of checking for adrenal insufficiency in a patient who presents with symptoms of hypotension and hyponatremia while being on ICI drugs, as unidentified adrenal insufficiency and adrenal crisis can be fatal.

scholarly journals Occult Adrenal Insufficiency in Renal Amyloidosis Patients

2021 ◽  
Author(s):  
Didem Turgut ◽  
Serhan Vahit Pişkinpaşa ◽  
Havva Keskin ◽  
Kemal Agbaht ◽  
Ezgi Coşkun Yenigün
Keyword(s):  
Adrenal Insufficiency ◽  
Renal Involvement ◽  
Stimulation Test ◽  
Renal Amyloidosis ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Cross Sectional ◽  
Control Subjects ◽  
Free Cortisol ◽  
Cortisol Levels

Objective: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. Methods: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 μg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. Results: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients’ stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). Conclusion: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.

scholarly journals Careful Evaluation of Cosyntropin Dose in the Diagnosis of Adrenal Insufficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A122-A123
Author(s):  
Clio Musurakis ◽  
Solab Chitrakar ◽  
Randa Eldin Sharag ◽  
Ekta Shrestha ◽  
Gauri Pethe ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Gold Standard ◽  
Low Dose ◽  
Treatment Plan ◽  
Stimulation Test ◽  
Diagnostic Process ◽  
High Dose ◽  
Secondary Adrenal Insufficiency ◽  
Acth Stimulation ◽  
Primary Adrenal Insufficiency

Abstract Introduction: The use of the 250μg cosyntropin dose or otherwise called high-dose ACTH test is the gold standard test for diagnosis of primary adrenal insufficiency. The 1μg dose test or the low-dose test is mostly reserved for diagnosis of secondary adrenal insufficiency. Careful consideration of the results produced during the diagnostic process is imperative to avoid mislabeling of patients with a disease that requires lifelong treatment. Case Report: This is the case of a 45-year-old female with a history of asthma and psoriasis who presented with emesis. Home medications included monthly TNF-alpha inhibitor injections for psoriasis, triamcinolone acetonide topical spray and budesonide-formoterol inhaler. On admission, she also had nausea, chills and diaphoresis, as well as palpitations, lightheadedness, and shortness of breath. When she arrived at the ER, vitals were remarkable for low blood pressure. Labs were unremarkable except for CMP concerning for anion gap metabolic acidosis, hyponatremia, and hypokalemia. A random serum cortisol was 6.4 mcg/dL, which was relatively low. ACTH was within normal range. Due to concern for adrenal insufficiency, a 1μg cosyntropin test was performed which showed a peak cortisol concentration of less than 18 mcg/dL. As the response was assessed as suboptimal, endocrinology was consulted to offer a treatment plan for steroids. However, the test was repeated using the gold standard 250μg cosyntropin dose and the patient then showed an adequate response and she was not started on steroids. Conclusions: This is a case that demonstrates how the 250 μg ACTH or high-dose stimulation test should be used for diagnosis of primary adrenal insufficiency (AI), as it is the gold standard. The 1 μg ACTH or low-dose stimulation test can be used for diagnosis of primary AI but only when the high dose test is not available. On the other hand, the 1 μg ACTH stimulation test has been shown to be more sensitive than the 250 μg test in diagnosing secondary adrenal insufficiency. When using the most appropriate test correctly, the clinician can only then offer the patient the best treatment strategies. Our patient did not require chronic replacement therapy. The steroids in this case could have harmed the patient as chronic administration could cause adrenal gland suppression.

scholarly journals Endocrinopathies Associated With High Dose Methadone

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A130-A130
Author(s):  
Charles C Farmer ◽  
Monica Agarwal
Keyword(s):  
Adrenal Insufficiency ◽  
Chronic Back Pain ◽  
Antibody Test ◽  
Insulin Level ◽  
Inhibitory Effect ◽  
Adrenal Crisis ◽  
High Dose ◽  
Micronutrient Deficiencies ◽  
Acth Stimulation ◽  
Health Crisis

Abstract Introduction: The opioid epidemic is a public health crisis and clinicians should be aware of the many under-recognized endocrinopathies associated with opioids. Herein, we present a case that exemplifies the endocrine-related adverse effects of methadone therapy. Clinical Case: A 43-year-old Caucasian female with chronic back pain with opioid dependence, high dose methadone use (195 mg daily), and diabetes presented with refractory hypoglycemia. She was diagnosed with ketone prone diabetes eight months prior. She had since been weaned off insulin and her most recent HbA1c was 4.2%. During this time, she had an intentional weight loss of 60 pounds. On examination, she had bilateral lower extremity pitting edema with scaly plaques on the extremities. Laboratory tests showed C-peptide of 0.8 (0.9–7.1 ng/mL), insulin level of &lt; 2 (3–25 mcIntUnits/mL), proinsulin of 4.6 (&lt;18.8 pMol/L) with concurrent glucose of 48 mg/dl. She failed the ACTH stimulation test with 60 minute cortisol of 16.8 mcg/dL and was started on prednisone for adrenal insufficiency (AI). The pituitary and adrenal were normal on imaging. Her albumin was 1.5 (3.7–5.5 gm/dL) and she had vitamin and micronutrient deficiencies including copper, zinc, thiamine, selenium, and vitamin A. The insulin antibody test, paraneoplastic panel, celiac panel, A1 antitrypsin test, EGD, and colonoscopy were all non-revealing. A liver biopsy showed glycogenic hepatopathy. She improved clinically after prednisone initiation and treatment of malnutrition. The hypoglycemia improved but did not resolve as she refused to reduce methadone dose. Discussion: The proposed mechanism of opioid-induced AI is the inhibitory effect on the hypothalamic-pituitary-adrenal axis, similar to the effect on the gonadal axis which causes hypogonadism. The risk for hypoglycemia is increased in patients taking more than 40 mg of oral methadone per day, and although the mechanism remains unclear, it is independent of adrenal function. Our patient had adrenal insufficiency and hypoglycemia related to methadone, which was further complicated by malnutrition. The glycogenic hepatopathy is a benign reversible condition that is believed to be a consequence of fluctuation in glucose levels. Conclusion: Given the life-threatening nature of adrenal crisis and the overlap in symptomatology with opiate overdose, clinicians should be prompt in evaluating for endocrinopathies in patients on chronic high dose opiates, and patients should be appropriately counseled on the potential consequences of methadone use. References: 1.Flory, J. H., et al. (2016). Methadone use and the risk of hypoglycemia for inpatients with cancer pain. JPSM, 51(1), 79–87.2.Li, T. et al. (2020). Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids. JCEM, 105(10), dgaa499.

scholarly journals Adrenal Insufficiency After Unilateral Adrenalectomy in Primary Aldosteronism: Long-Term Outcome and Clinical Impact

2019 ◽  
Vol 104 (11) ◽  
pp. 5658-5664 ◽  
Author(s):  
Daniel A Heinrich ◽  
Christian Adolf ◽  
Finn Holler ◽  
Benjamin Lechner ◽  
Holger Schneider ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Primary Aldosteronism ◽  
Serum Cortisol ◽  
Adrenal Crisis ◽  
Acth Stimulation ◽  
Term Outcome ◽  
Unilateral Adrenalectomy ◽  
Long Term Outcome ◽  
Cortisol Levels

Abstract Context Primary aldosteronism (PA) represents a secondary form of arterial hypertension that can be cured by surgery. Evidence of adrenal insufficiency (AI) was recently found in patients with PA who had undergone unilateral adrenalectomy (uADX). Objective To study the incidence and long-term outcome of postoperative AI after uADX for PA. Design Prospective registry study (August 2014 until the end of 2018). Setting Tertiary referral center. Patients One hundred consecutive patients undergoing uADX for PA were included. All patients underwent postoperative ACTH stimulation testing. Intervention Postoperative ACTH stimulation testing to identify patients with AI. Main Outcome Measures Incidence of patients with postoperative AI and definition of long-term outcome. Results Twenty-seven percent of patients developed postoperative AI. Of these, 48% had postoperative ACTH stimulation serum cortisol levels ≤13.5 µg/dL (severe AI); 52% were classified into the group with moderate AI (stimulated serum cortisol levels: 13.5 to 17 µg/dL). Patients with severe AI required significantly longer hydrocortisone replacement therapy than the moderate group (median [25th, 75th percentiles]: 353 [294, 476] days; 95% CI: 284 to 322 days; vs 74 [32, 293] days; 95% CI: 11 to 137 days; P = 0.016). One patient with severe AI was hospitalized for an acute adrenal crisis. With a cumulative follow-up of 14.5 years, this produced an incidence rate of 6.9 adrenal crises per 100 patient-years. Conclusion We suggest performing postoperative ACTH stimulation tests in all patients who undergo uADX for PA.

Employing a results-based algorithm to reduce laboratory utilization in ACTH stimulation testing

2018 ◽  
Vol 31 (4) ◽  
pp. 429-433 ◽  
Author(s):  
Ryan J. McDonough ◽  
Patria Alba ◽  
Kavitha Dileepan ◽  
Joseph T. Cernich
Keyword(s):  
Adrenal Insufficiency ◽  
Cortisol Level ◽  
High Dose ◽  
Dynamic Tests ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Endocrine Society ◽  
A Value ◽  
Laboratory Utilization ◽  
Cortisol Levels

AbstractBackground:The High Dose Adrenocorticotropic Hormone (ACTH) Stimulation Test is the gold standard to diagnose adrenal insufficiency. Normal adrenal function is defined as a peak cortisol response to pharmacologic stimulation with cosyntropin of ≥18 μg/dL. Our practice was to obtain cortisol levels at 0, 30 and 60 min after cosyntropin administration. Once a value of ≥18 μg/dL has been obtained, adrenal insufficiency is ruled out and there is little diagnostic utility in subsequent stimulated levels.Methods:We aimed to decrease laboratory utilization by developing a results-based algorithm in the electronic medical record (EMR). Cortisol levels were analyzed on the 0 and 60 min samples; then an EMR discern rule automatically generated an order to analyze the 30-min sample if the 60-min cortisol level was subnormal.Results:Exclusion of adrenal insufficiency was excluded using one stimulated cortisol level in 8% prior to algorithm development. After several plan-do-study-act cycles, 99% of normal tests were performed using only one stimulated cortisol level.Conclusions:This laboratory-based algorithm resulted in reduced laboratory utilization, and aligned our practice to recommendations of the Pediatric Endocrine Society. Similar algorithms could be created for other dynamic tests to reduce unnecessary laboratory utilization.

scholarly journals Immune-Related Pancytopenia Induced by Anti-PD-1 Therapy – Interrupt or Continue Treatment – The Role of Immunohistochemical Examination

2019 ◽  
Vol 12 (3) ◽  
pp. 820-828 ◽  
Author(s):  
Bożena Cybulska-Stopa ◽  
Andrzej Gruchała ◽  
Maciej Niemiec
Keyword(s):  
Bone Marrow ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Positive Outcomes ◽  
Hematological Disorders ◽  
Therapeutic Outcomes ◽  
Appropriate Treatment ◽  
Programmed Death

Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed death receptor-1/ligand-1 (anti-PD-1/anti-PD-L1) caused a breakthrough in oncology and significantly improved therapeutic outcomes in cancer patients. ICIs generate a specific reaction in T cells, directed against antigens on cancer cells, leading to their damage and death. Through similar or the same antigens, activated lymphocytes may also have a cytotoxic effect on healthy cells, causing development of specific adverse effects – so-called immune-related adverse events (irAEs). We present the case report of a 56 year old patient with disseminated melanoma. During treatment with immunotherapy (anti PD-1), neutropenic fever and pancytopenia occurred. Trepanobiopsy of the bone marrow was performed to determine the cause of pancytopenia. Histopathological assessment of bone marrow combined with immunophenotype investigations may explain the cause of hematological disorders occurring in the course of treatment with ICIs, and support the choice of an appropriate treatment, directly translated into positive outcomes.

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