scholarly journals MON-220 Real World Performance of Urinary and Plasma Metanephrine Assays in Diagnosing Phaeochromocytoma/Paraganglioma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Eithar Deyab ◽  
Dina Saleh ◽  
Ravi Kumar Menon
Keyword(s):  
Real World ◽  
Financial Burden ◽  
Adrenal Adenoma ◽  
Hospital Setting ◽  
Patient Anxiety ◽  
Positive Urine ◽  
Plasma Metanephrines ◽  
Positive Results ◽  
Urine Metanephrines ◽  
Urinary Metanephrines

Abstract Introduction: Diagnosis of pheochromocytoma/paraganglioma (PPGL) can be challenging. Plasma metanephrines have highest sensitivity (96-99%) yet lowest specificity (85%)1 whereas 24-hour urinary metanephrines have 87.5% sensitivity and 99.7% specificity. Diagnostic accuracy depends on factors such as patient positioning and medications, questioning its potential value in a hospital setting. Methods: The audit was performed in a hospital which caters to a population of 400,000. Data was collected retrospectively on patients who had a request for plasma or urine metanephrines from March 2018 – September 2018. Results: A total of 85 patient order requests (58% male, 42% female) were reviewed; only 2 patients were ultimately diagnosed with a pheochromocytoma. The mean age of patients was 48 years. The most common indication for requests was hypertension (64 patients). Locations of order requests included 42% from outpatient clinics, 32% inpatient requests, 18% from Ambulatory Care, 6% by A&E and 2% by GP. Of the 27 (32%) inpatient requests, 10 had positive results: 1 diagnosed with primary aldosteronism, 1 with hypercortisolism and the others had no definite diagnosis. 8/10 patients with positive results did not have a repeat test. Focusing on plasma metanephrines, 52% plasma metanephrines samples were negative, 22% were positive and 26% were not processed due to laboratory error. From the 19 positive plasma metanephrines, adrenal adenoma was present in 7 patients (from this group, 1 was referred for surgery with confirmed diagnosis of pheochromocytoma), 1 patient’s MIBG scan was negative and 1 diagnosis of stress-related raised metanephrines was made. The remaining 10 patients did not undergo an adrenal scan. 9 out of 18 cases with positive urine metanephrines had an adrenal adenoma. In 7/9, plasma metanephrines were positive, the remaining 2 had negative plasma metanephrines. 34 cases with initial negative test still had another urine/plasma metanephrines performed with similar negative result. Furthermore <50% of the positive urine or plasma metanephrines were referred to and reviewed by the Endocrine team. Discussion: This audit highlights the potential pitfalls of investigating PPGL with plasma and urinary metanephrines, and in fact raises the question of its accuracy as an inpatient diagnostic tool as none of the positive inpatient tests resulted in a diagnosis of PPGL. Inappropriate urine and plasma metanephrines requests cause financial burden and patient anxiety. Even with outpatient requests, few positive results led to a PPGL diagnosis. Patient selection and conditions of testing must be more rigorously scrutinised and threshold for positive result must be raised for specificity of the test to be improved in ‘real world’ conditions. References: 1. Lenders JW al. Biochemical diagnosis of pheochromocytoma: which test is best? JAMA. 2002.

Properly collected plasma metanephrines excludes PPGL after false positive screening tests

2021 ◽  
Author(s):  
Gregory A Kline ◽  
Jessica Boyd ◽  
Brenda Polzin ◽  
Adrian Harvey ◽  
Janice L Pasieka ◽  
...  
Keyword(s):  
False Positive ◽  
Adrenal Mass ◽  
Chart Review ◽  
False Positive Rate ◽  
Total Positivity ◽  
Screening Tests ◽  
Positive Rate ◽  
Plasma Metanephrines ◽  
Positive Results ◽  
Urine Metanephrines

Abstract Context False positive results are common for pheochromocytoma/paraganglioma(PPGL) real-world screening. Objective Determine the correlation between screening urine and seated plasma metanephrines in outpatients where PPGL was absent, compared to meticulously prepared and supine-collected plasma metanephrines with age-adjusted references. Design Retrospective cohort study Setting Databases from a single-provider provincial laboratory(2012-2018), a validated PPGL registry and a manual chart review from a specialized endocrine testing unit. Patients PPGL registry data excluded known PPGL cases from the laboratory database. Outpatients having both urine and plasma metanephrines <90 days apart. Methods The correlation between urine and seated plasma measures along with the total positivity rate. All cases of plasma metanephrines drawn in the endocrine unit were reviewed for test indication and test positivity rate. Results There were 810 non-PPGL pairs of urine and plasma metanephrines in the laboratory database; 46.1% of urine metanephrines were reported high. Of seated outpatient plasma metanephrines drawn a median of 5.9 days later, 19.2% were also high (r=0.33 and 0.50 for normetanephrine and metanephrine, respectively). In contrast, the meticulously prepared and supine collected patients(n=139, 51% prior high urine metanephrines) had <3% rate of abnormal high results in patients without known PPGL/adrenal mass. Conclusions There was a poor-to-moderate correlation between urine and seated plasma metanephrines. Up to 20% of those with high urine measures also had high seated plasma metanephrines in the absence of PPGL. Properly prepared and collected supine plasma metanephrines had a false positive rate of <3% in the absence of known PPGL/adrenal mass.

scholarly journals Adrenal Mass Hemorrhage Clinically Mimicking a Pheochromocytoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A112-A112
Author(s):  
Panadeekarn Panjawatanan ◽  
Muhammad Daniyal ◽  
Juan Jose Delgado Hurtado
Keyword(s):  
Adrenal Mass ◽  
Reference Range ◽  
Case Reports ◽  
Adrenal Adenoma ◽  
Vital Signs ◽  
Healthy Woman ◽  
Reference Ranges ◽  
Mri Findings ◽  
Plasma Metanephrines ◽  
Urine Metanephrines

Abstract Background: A pheochromocytoma is diagnosed clinically using correlation of clinical, imaging, and laboratory studies. We report the case of an adrenal mass hemorrhage that presented with significantly elevated urine metanephrines mimicking a pheochromocytoma. Clinical Case: A 59-year-old healthy woman presented to the ED with chest pain, left flank and upper quadrant pain associated with diaphoresis and palpitations. Vital signs were significant for a pulse of 92 bpm, and a BP of 213/88 mm Hg. Physical exam revealed tenderness to palpation on the left upper quadrant and left costovertebral angle. Laboratory tests were significant for an elevated D-dimer (2,449 ng/mL, reference range 215–499 ng/mL). CT abdomen with IV contrast showed a 3.5 x 2.9 cm round mass abutting the lateral limb of the left adrenal gland with surrounding fat stranding with suspicion of inflammation or hemorrhage. 24-hour urine metanephrines showed elevated metanephrine (7,227 mcg/24hr; reference range <400 mcg/24 hr) and normetanephrine (1,209 mcg/24hr; reference range 900 mcg/24 hr). In the setting of up trending cardiac enzymes and inferior-lateral ST segment depression, a cardiac catheterization was performed which was unrevealing. She was discharged from the hospital and referred to endocrinology. On that visit, ~ 1 month after the patient was admitted to the hospital, plasma metanephrines were ordered which showed mildly elevated plasma metanephrine (0.83 nmol/L; reference range <0.5 nmol/L) and normetanephrine (1.2 nmol/L; reference ranges <0.9 nmol/L). An MRI abdomen with and without contrast revealed a 2.7 x 2.2 x 1.8 cm nodule arising from the lateral limb, with loss of signal on in-phase images suggestive of blood products. Plasma metanephrines and MRI findings ruled out the diagnosis of a pheochromocytoma. Conclusion: To our knowledge, few cases of an adrenal mass hemorrhage clinically mimicking a pheochromocytoma have been reported. Although the inpatient clinical presentation of our patient was consistent with this, the outpatient plasma metanephrines and MRI were not. An adrenal adenoma hemorrhage should be considered as a potential differential diagnosis for elevated metanephrines, which can clinically mimick a pheochromocytoma. References: (1)Sekos K, Short T, Ing SW. Adrenal hemorrhage due to hypercoagulable state mimicking pheochromocytoma. Journal of Clinical and Translational Endocrinology: Case Report. 8. 9–12. 2018.(2)Wordsworth S, Thomas B, Agarwal N, Hoddell K, Davies S. Elevated urinary cathecholamines and adrenal haemorrhage mimicking phaechromocytoma. BMJ Case Reports. 2010.

384-P: Impact of Concurrent Use of Oral Antidiabetes Agents with Insulin in the Real-World Hospital Setting

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 384-P
Author(s):  
BHARGAVI PATHAM ◽  
SOUMYA CHIKERMANE ◽  
AISHA VADHARIYA ◽  
MICHAEL L. JOHNSON ◽  
ARCHANA R. SADHU
Keyword(s):  
Real World ◽  
Hospital Setting ◽  
The Real ◽  
Concurrent Use

Unresectable hepatocellular carcinoma: prospects for drug therapy with lenvatinib

2022 ◽  
Vol 11 (3) ◽  
pp. 45-52
Author(s):  
V.  V. Breder ◽  
D.  T. Abdurakhmanov ◽  
V.  V. Petkau ◽  
P.  V. Balakhnin ◽  
M.  V. Volkonsky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Therapy ◽  
Liver Function ◽  
Real World ◽  
Systemic Therapy ◽  
Efficacy And Safety ◽  
Study Results ◽  
Class B ◽  
Pugh Class ◽  
Positive Results

There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.

Characteristics of Education and the Current State of Teacher Effectiveness in Japan

2021 ◽  
pp. 148-171
Author(s):  
Takeshi Miyazaki ◽  
Hideki Watanabe ◽  
Emiko Furukawa ◽  
Masako Nezu ◽  
Shigeki Ohono ◽  
...  
Keyword(s):  
Elementary Schools ◽  
Teacher Effectiveness ◽  
Real World ◽  
Educational Policies ◽  
Postwar Period ◽  
Positive Role ◽  
Current State ◽  
The Difference ◽  
Positive Results ◽  
The Way

This chapter analyzed how Japanese teachers' qualifications and abilities, as well as educational policies, have been promoted since the postwar period to the present day and summarized these results. There are discrepancies between the needs of students' families and the real world and the ideas and contents required by the Course of Study. Teachers have tried to play a positive role in bridging the gap and in merging the reality and the ideals. In order to bridge the “difference” faced by school sites, it is necessary to start by examining the contents of the reforms required from the bottom and reforms required from the top. As an initiative from below, in most elementary schools in Japan, groups of teachers have voluntarily gathered, and “Jugyo-Kenkyu” have been conducted for many years to analyze the challenges of their own school's students as a team. Although Jugyo-Kenkyu has achieved some positive results, the way to measure the effectiveness of the research is still an issue.

scholarly journals Prognosis and Therapeutic Response Transfer Learning Model for Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1883-1883
Author(s):  
Jerome Voegeli ◽  
Dana Moreno ◽  
Maxim Kryukov ◽  
Gregory Mathez ◽  
Remy Petremand ◽  
...  
Keyword(s):  
Neural Networks ◽  
Multiple Myeloma ◽  
Transfer Learning ◽  
Real World ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Full Range ◽  
Hospital Setting ◽  
Bone Lesions ◽  
Therapeutic Effects

Abstract The combination of clinical knowledge (applicable for a majority of patients, published in the form of review articles), real world evidence (describing more nuanced outcomes for small cohorts) and innovative artificial intelligence algorithms opens potent avenues to re-examine clinical findings and uncover new biomarkers for the prognosis / prediction of therapeutic responses--in a manner that can directly be incorporated in clinical decision support tools. In this work, neural networks are first developed to reproduce clinical guidelines with >95% accuracy. After mastering the complex knowledge that is generally expected from human doctors, a transfer learning technique was used to sift through de-identified longitudinal data of 9267 patients with multiple myeloma-related conditions at the Vanderbilt University Medical Center using progression free survival (PFS) to quantify therapeutic outcomes. The "precision medicine neural networks" obtained as a result can be compared with conventional and less portable survival model algorithms, using Shapley values to explain prediction differences. Testing a first hypothesis that "lytic bone lesions are a prognostic factor for poor PFS", a study involving 1530 patients confirmed that the median PFS of 54 ± 6 months (684 censored patients showing progression) in the presence of bone lesions is significantly lower than the 107 ± 40 months (90 censored patients) in the absence of lesions. Keeping only 179 patients for which a full range of cytogenetic factors are available and using a Cox regression & Random Survival Forests that provide the best fit of the data, we confirmed previous findings for high-risk trisomies 1 and 7, monosomy 13, deletion 12p and translocation t(11;14)(q13;q32). We furthermore uncovered new additional adverse factors del6q, 2+, 21-, 16- to formulate a model that achieves a statistically significant concordance of 0.72 ± 0.07. Comparing therapeutic effects for patients in a real-world hospital setting with clinical trials, we found that lenalidomide + bortezomib + dexamethasone used in a first-line therapy resulted in lower median PFS of 17-47 months than the 39-52 months published in the SWOG S0777 trial, most likely because comorbidities contributed to shortening the PFS in real-world settings. We conclude with an analysis of concrete examples where therapeutic recommendations differ from guidelines, explaining the reason with statistically significant cohorts observed in the data. Disclosures No relevant conflicts of interest to declare.

scholarly journals SAT-192 Eletriptan (RelpaxaTm) Causing False Positive Elevations in Urinary Metanephrine

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Zachary Bloomer ◽  
Nath Priti ◽  
Thanh Duc Hoang ◽  
Mohamed K M Shakir
Keyword(s):  
Blood Pressure ◽  
False Positive ◽  
Arterial Blood Flow ◽  
Positive Test ◽  
Uncontrolled Hypertension ◽  
False Positive Test ◽  
Arterial Blood ◽  
History Of ◽  
Plasma Metanephrines ◽  
Urine Metanephrines

Abstract Background: The diagnosis of pheochromocytoma depends crucially on the demonstration of excessive production of catecholamines. This step, however, is fraught with several difficulties, in particular with false-positive test results. Drugs such as phenoxybenzamine and tricyclic antidepressants are the most frequently associated causes for false-positive results. Other medications are also known to cause a false positive elevation of urinary metanephrines. We are reporting a patient with markedly elevated urine metanephrines associated with the use of Eletriptan hydrobromide (RelpaxaTM), a drug commonly used for treating migraine. Clinical Case: A 29-year-old man with a history of migraine managed on ibuprofen and recently started Eletriptan presented to the emergency room complaining of a 24-hour history of progressively worsening headaches. At the time of initial evaluation his blood pressure was in the 220s/160s with a creatinine of 1.9 mg/dL with unknown baseline. He was managed on an IV nicardipine drip. Due to his young age he underwent an evaluation for secondary causes of his hypertension. Laboratory: normal aldosterone/renin level (ratio was 0.4), normal midnight salivary cortisol and normal thyroid function studies. Urine screening for drug abuse was also negative. A 24-hour urine metanephrine level, while the patient was taking Eletriptan, was markedly elevated (normetanephrine 1341mcg (ref 82–500) and metanephrine level of 2494 mcg (ref 45–290). In contrast, the plasma metanephrines were only mildly elevated (metanephrines level 27 pg/ml (ref 0–62) and normetanephrine level of 255 pg/ml (ref 0–145)). Adrenal CT did not reveal any evidence of adrenal nodules. Additionally a Gallium-68 PET/CT scan did not reveal any evidence of pheochromocytoma or paraganglioma. Eletriptan was discontinued and his blood pressure was controlled on oral medications. Within one week of stopping Eletriptan his urine metanephrines (metanephrine 76 mcg/ 24 hrs, normetanephrine 277 mcg/dL) and plasma metanephrines (metanephrine 39 pg/mL, normetanephrine 148 pg/mL) normalized. Conclusion: The discrepancy between plasma and urine metanephrines in our patient suggests the possibility of a false positive test. Eletriptan, a second generation triptan drug, is a selective 5-hydroxytryptamine 1B/1D receptor agonist and has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. However, Eletriptan has no significant affinity or pharmacological activity at adrenergic α1, α2, or β; dopaminergic D1 or D2; muscarinic; or opioid receptors. It is also interesting to note that Eletriptan use is contraindicated in uncontrolled hypertension. It is possible Eletriptan may affect the assay of urine metanephrines. However, the exact mechanism of Eletriptan causing elevated urine metanephrines in our patient is not clear.

scholarly journals Case report of a phantom pheochromocytoma

2020 ◽  
Vol 30 (2) ◽  
pp. 325-330
Author(s):  
Caroline M Joyce ◽  
Audrey Melvin ◽  
Paula M O’Shea ◽  
Seán J Costelloe ◽  
Domhnall J O’Halloran
Keyword(s):  
Reference Intervals ◽  
Patient Anxiety ◽  
Biochemical Tests ◽  
Drug Interference ◽  
High Clinical Suspicion ◽  
Liquid Chromatography Tandem Mass ◽  
History Of ◽  
Plasma Metanephrines ◽  
Plasma Free Metanephrines ◽  
Test Probability

Plasma free metanephrines or urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma as they have greater sensitivity and specificity than catecholamines for pheochromocytoma detection. This case highlights the preanalytical factors which can influence metanephrine measurement and cause a false positive result. It describes a patient with a high pre-test probability of pheochromocytoma due to hypertension and a past medical history of adrenalectomy for a purported pheochromocytoma in her home country. When biochemical screening revealed grossly elevated urine normetanephrine in the presence of a previously identified right adrenal lesion, there was high clinical suspicion of a pheochromocytoma. However, functional imaging did not support this view which prompted additional testing with plasma metanephrines. Results for plasma and urine metanephrines were discordant and preanalytical drug interference was suspected. Patient medications were reviewed and sulfasalazine, an anti-inflammatory drug was identified as the most likely analytical interferent. Urinary fractionated metanephrines were re-analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS) and all metanephrines were within their reference intervals. This case illustrates how method-specific analytical drug interference prompted unnecessary expensive imaging, heightened patient anxiety and resulted in lengthy investigations for what turned out to be a phantom pheochromocytoma.

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