A case report on asymptomatic and biochemically silent pheochromocytoma in adrenal incidentaloma

Pheochromocytoma are rare tumours originating from the chromaffin tissue. The clinical manifestations are variable and are not specific as pheochromocytoma and often imitate other diseases. The diagnosis is established by measurement of catecholamines and their metabolites in urine or plasma and by radiographic studies for localisation. Surgical removal of the tumour is the preferred treatment. 45 years old female presented with adrenal incidentaloma of about 6.1×6.2×5.4 cm well defined heterogenous lesion with internal cystic areas seen in right adrenal region abutting upper pole of right kidney. Biochemical investigations for adrenal hormones including plasma aldosterones, cortisols, plasma metanephrines, 24 hrs urinary metanephrines and VMA were found to be normal. Proceeded with adrenelectomy and histopathology of the specimen revealed pheochromocytoma as diagnosis. Pheochromocytoma leads to high mortality and morbidity rates if untreated. Fractionised metanephrines and catecholamines in a 24 hrs urine analysis is the preferred biochemical test. In a biochemically silent pheochromocytoma imaging modalities are used to identify and locate the tumour. Adequete alpha and beta blockade should be ensured before tumour removal. Surgery is recommenced irrespective of size and normal biochemical study to prevent complications.

A UK national audit of the laboratory investigation of phaeochromocytoma and paraganglioma

Background Phaeochromocytomas and paragangliomas (PPGL) are catecholamine secreting tumours associated with significant morbidity and mortality. Timely diagnosis and management are essential. A range of laboratory tests can be utilised in the investigation of PPGL. There is scope for significant variation in practice between centres. We aimed to investigate how the laboratory investigation of PPGL is performed in laboratories across the United Kingdom. Methods A questionnaire consisting of 21 questions was circulated to Clinical Biochemistry laboratories in the United Kingdom via the Association for Clinical Biochemistry and Laboratory Medicine office. The survey was designed to allow audit against Endocrine Society Guidelines on the Investigation and Management of PPGL and to obtain information on other important aspects not included in these guidelines. Results Responses were received from 58 laboratories and the data were compiled. The majority of laboratories use either urine or plasma metanephrines in first-line testing for PPGL, although a number of different combinations of biochemistry tests are utilised in different centres. All laboratories measuring metanephrines or catecholamines in-house use LC or LC-MS/MS methods. There are some marked differences between laboratories in urine metanephrines reference ranges used and sample requirements. Conclusions There is evidence of good practice in UK laboratories (as assessed against Endocrine Society Guidelines) such as widespread use of urine/plasma metanephrines and appropriate analytical methodologies used. However, there is also evidence of variations in practice in some areas that should be addressed.

Extra-adrenal Non-functioning Paraganglioma – A Diagnostic and Surgical Challenge

Paragangliomas are rare neoplasms arising from the neuroendocrine cells. Extra-adrenal paragangliomas arise from the neuroendocrine cells spread in the retroperitoneum from the skull base to the retroperitoneum and sacrum. Non-functioning paragangliomas are a diagnostic challenge as they are clinically silent and attain large size. The clinical implication of these non-functioning paragangliomas is the greater metastatic potential of extra adrenal paraganglioma (20–42%) when compared to adrenal paraganglioma. We report a very rare case of a 60-year lady who presented with abdominal heaviness and retroperitoneal lump. Imaging was suggestive of a retroperitoneal tumor. Serum chromogranin A level was elevated with normal catecholamine levels. The tumor was resected along with metastasectomy of isolated liver metastasis. The patient has no recurrence or metastasis at one year of follow-up. To conclude paraganglioma should be considered as a differential diagnosis in all retroperitoneal tumors. Serum chromogranin A levels and plasma metanephrines should be routinely done for all retroperitoneal cases before planning for the biopsy of the lesion. Resection of the lesions should always be performed as per the oncological principles as pre-operative differentiation of benign and malignant lesions is difficult.

Plasma Metabolome Profiling for the Diagnosis of Catecholamine Producing Tumors

ContextPheochromocytomas and paragangliomas (PPGL) cause catecholamine excess leading to a characteristic clinical phenotype. Intra-individual changes at metabolome level have been described after surgical PPGL removal. The value of metabolomics for the diagnosis of PPGL has not been studied yet.ObjectiveEvaluation of quantitative metabolomics as a diagnostic tool for PPGL.DesignTargeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens and statistical modeling using ML-based feature selection approaches in a clinically well characterized cohort study.PatientsProspectively enrolled patients (n=36, 17 female) from the Prospective Monoamine-producing Tumor Study (PMT) with hormonally active PPGL and 36 matched controls in whom PPGL was rigorously excluded.ResultsAmong 188 measured metabolites, only without considering false discovery rate, 4 exhibited statistically significant differences between patients with PPGL and controls (histidine p=0.004, threonine p=0.008, lyso PC a C28:0 p=0.044, sum of hexoses p=0.018). Weak, but significant correlations for histidine, threonine and lyso PC a C28:0 with total urine catecholamine levels were identified. Only the sum of hexoses (reflecting glucose) showed significant correlations with plasma metanephrines.By using ML-based feature selection approaches, we identified diagnostic signatures which all exhibited low accuracy and sensitivity. The best predictive value (sensitivity 87.5%, accuracy 67.3%) was obtained by using Gradient Boosting Machine Modelling.ConclusionsThe diabetogenic effect of catecholamine excess dominates the plasma metabolome in PPGL patients. While curative surgery for PPGL led to normalization of catecholamine-induced alterations of metabolomics in individual patients, plasma metabolomics are not useful for diagnostic purposes, most likely due to inter-individual variability.

Optimized procedures for testing plasma metanephrines in patients on hemodialysis

Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

“Never Trust to General Impressions, My Boy, but Concentrate Yourself upon Details”: An Unusual and Challenging Presentation of Pheochromocytoma

We present the case of a 45-year-old woman admitted to our unit with acute heart failure and cardiogenic shock, requiring an intra-aortic balloon pump insertion and inotropes and vasopressors infusion. Despite such treatment, the patient developed multi organ failure and intravascular disseminated coagulation with haemolysis. The initial diagnosis of acute myocarditis was subsequently denied by the finding of bilateral adrenal masses by MRI scan, and urine and plasma metanephrines measurements confirmed a pheochromocytoma (PCC). Genetic analysis revealed a mutation in the neurofibromatosis type 1 (NF1) gene, and an accurate physical examination drew attention to small cafè-au-lait spots, usually associated with this syndrome. PCC diagnosis should be promptly considered in patients presenting with unexplained acute heart failure and cardiogenic shock of unknown origin, considering its life-threatening complications and the good prognosis after radical surgery.

Case of pheochromocytoma mimicking MINOCA

We present a 52-year-old woman who was admitted to the emergency department with a short history of palpitations, sweating and nausea. An electrocardiogram (ECG) that was performed suggested inferolateral ischaemia with a significant troponin rise. The patient underwent an invasive coronary angiogram that showed mild non-obstructive coronary disease. She was thus given a provisional diagnosis of myocardial infarction with non-obstructive arteries (MINOCA), treated as an acute coronary syndrome (ACS) and subsequently discharged home. The patient represented within 72 hours with a recurrence of symptoms and a further troponin rise. While on the ward severe recurrent orthostatic hypertensive episodes were noted. Further investigations revealed increased urinary and plasma metanephrines, increased plasma catecholamines and imaging revealed a left adrenal 5.7 cm mass, demonstrating probable pheochromocytoma. The patient was treated with curative surgery. This case highlights the importance of thorough history-taking in patients with atypical symptoms for acute coronary syndrome and diagnosed with MINOCA.

Adrenal Mass Hemorrhage Clinically Mimicking a Pheochromocytoma

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 &lt;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 &lt;0.5 nmol/L) and normetanephrine (1.2 nmol/L; reference ranges &lt;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.

Pheochromocytoma Masquerading as Weight Loss - a Diagnostic and Management Challenge

Introduction: Classic pheochromocytoma symptoms include headache, diaphoresis, palpitations and symptomatic pheochromocytomas are on average around 5cm. They respond to preoperative alpha blockade followed by surgery. We present a case of a giant 15.9cm pheochromocytoma with delayed presentation and diagnosis complicated by atypical symptoms of nausea, weight loss; preoperative preparation included a modified preparation of high-dose phenoxybenzamine but she underwent successful surgery. Case Description: A 62-year-old female with a history of hypertension and diabetes presented with nausea and 80 lbs weight loss over 18 months. CT scan revealed large centrally necrotic mass overlying the left kidney, measuring 15.9 x 12.7 x 14.7cm. Abdominal MRI showed claw sign; she was admitted to the urology service for tube feeding prior to resection of suspected renal cell carcinoma. Given the location of the mass and history of hypertension, plasma metanephrines, included in preoperative workup, were notable for: total metanephrines &gt;40000 pg/ml (reference range &lt;=205), normetanephrines &gt;20000 pg/ml (reference range &lt;=148), metanephrines 57 pg/ml (reference range &lt;=57). Endocrine was consulted and she was started on phenoxybenzamine; she underwent volume replacement with fluids and salt tablets. Due to nausea and vomiting she was unable to reliably tolerate oral medication; BP management was challenging. Oral pill dosing was minimized. Metoprolol was converted to metoprolol SA and a phenoxybenzamine suspension that could be delivered through the feeding tube with good absorption was made. On the day prior to surgery, BP was 117/76 mmHg, supine HR 92 bpm, on a total daily dose of phenoxybenzamine 240mg, metoprolol SA 200mg and amlodipine 10mg. She underwent a radical left nephrectomy and adrenalectomy. Plasma metanephrines six weeks later were normal: total metanephrines 84 pg/ml, normetanephrines 84 pg/ml, metanephrines &lt;25 pg/ml. Pathology showed benign pheochromocytoma. Conclusion: Giant pheochromocytomas present significant challenges for clinicians who must be aware of the potential for nonspecific symptoms which can delay diagnosis. Paroxysmal hypertension happens in only about 50% of pheochromocytoma patients; primary hypertension is often diagnosed, as had been the case with our patient. Additionally, initial imaging related to atypical presenting symptoms may not lead to the specific diagnosis, as in our patient; metanephrine screening revealed the correct diagnosis. Regarding management, preoperative alpha blockade dosage and delivery should be tailored to individual patient needs, with adjustment as needed and alternative preparations considered to optimally control BP and reduce risk of death and other perioperative complications. Our case highlights the diagnostic and management challenge of patients presenting with giant pheochromocytomas.