A case of malignant pheochromocytoma of the adrenal gland in a young female

Background Pheochromocytoma is a tumour of the adrenal medulla, derived from catecholamine producing chromaffin cells. Malignant pheochromocytomas constitute 10–25% of all cases. These are difficult to diagnose microscopically. Therefore, malignant pheochromocytomas are diagnosed by the presence of local invasion or metastatic disease. Case presentation We present a case of malignant Pheochromocytoma in a 20-year-old woman from south India with classic symptoms whose urinary metanephrines levels were elevated. After controlling the blood pressure preoperatively and laparoscopic right-sided adrenalectomy was performed. The Postoperative period was uneventful. Histopathology proved to be malignant pheochromocytoma with a PASS score of 16/20 and immunohistochemical staining was positive. DOTATATE PET/CT showed no evidence of disease anywhere else in the body. Conclusion Malignant pheochromocytomas are rare tumor, so they pose a significant diagnostic and therapeutic challenge. Surgery is the mainstay of treatment. DOTATATE PET/CT helps in the localization of metastatic disease.

Young woman diagnosed with paraganglioma in primary care

A 15-year-old young woman was referred to the emergency room for admission by her general practitioner after receiving the results of urinary metanephrines and catecholamines requested to study the tachycardia, sweating and headaches that she had been presenting progressively last year. Imaging tests showed a large right supraumbilical para-aortic paraganglioma that was successfully removed with surgery after previous medical preparation with adrenergic blockers. Genetic testing showed a heterozygous mutation of the gene succinate dehydrogenase-B. The classic triad of symptoms in these disorders consists of headaches, sweating and tachycardia, usually accompanied by hypertension. We wanted to present this case, a challenging diagnosis of paraganglioma in primary care.

Concomitant Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review

Objective: The detection and management of concomitant pheochromocytoma (PHEO) and primary aldosteronism (PA) is not well understood. Our objectives were to investigate varying presentations and outcomes of cases with coexisting PHEO and PA to provide an approach to its diagnosis and management. Design: Retrospective case series from 2000–2020 at a single institution tertiary center; additional review of previously known cases before 2000 and from the medical literature. Patients and Measurements: Adult patients with concomitant PHEO and PA. Clinical, biochemical, radiologic, and histologic parameters were reviewed. Results: Fifteen patients (53% men, median age 53 years) were diagnosed with concomitant PHEO and PA. The majority presented with hypertension (13, 87%) and hypokalemia (13, 87%), but only 6 (40%) presented with symptoms suggestive of catecholamine excess. All patients with preoperative work-up for catecholamine excess (14, 93%) were found to have elevated plasma or urinary metanephrines/catecholamines above the upper limit of normal. Adrenal vein sampling (AVS) was performed in 9 (60%) patients, where 5 (56%) were diagnosed with bilateral PA, and 4 (44%) with unilateral PA. All patients underwent either unilateral (12, 80%) or bilateral (3, 20%) adrenalectomy to treat their PHEO and/or PA. Postoperative catecholamines and/or catecholamine breakdown products normalized or improved in 13 (87%) patients and were not measured in 2. Recurrence of PHEO was not observed. Six (40%) displayed persistent PA postoperatively, where 4 required long-term mineralocorticoid blockade. Conclusions: Concomitant PHEO and PA is a rare but likely under-reported condition. Hypertension with or without hypokalemia should prompt evaluation for PA, while any indeterminate adrenal mass should be worked up for PHEO. Coexisting disease warrants consideration of AVS to determine the laterality of PA to ensure appropriate management.

False elevations in urinary metanephrines: under-recognised pitfall with 24-hour urinary volume collection

One pitfall in 24-hour urine collection is the input of incorrect urinary volume by the reference laboratory. This may lead to an incorrect diagnosis of pheochromocytoma or paraganglioma. A 48-year-old African-American woman was seen in the clinic for an elevated 24-hour urine metanephrine screen during workup for secondary hypertension. Urine volume was found to be incorrectly inputted by the lab as 9750 mL rather than 975 mL. The urinary metanephrines were then recalculated and the 24-hour urinary metanephrines resulted within normal limits. This case highlights this unique and potentially under-recognised error in testing with 24-hour urine volume collection.

ELETRIPTAN (RELPAXA™) CAUSING FALSE POSITIVE ELEVATIONS IN URINARY METANEPHRINES

Objective: Pheochromocytoma is diagnosed biochemically by demonstrating an excessive production of catecholamines and their metabolites in the blood and urine. However, these tests are at times fraught with false-positive results due to drug effects. We report here a patient with markedly elevated urinary metanephrines associated with the use of eletriptan for migraine treatment. Methods: A literature search was conducted using the PubMed and Google Scholar databases for eletriptan and false positive metanephrine elevation. Urine and plasma metanephrine tests were performed via liquid chromatography/tandem mass-spectrometry. Results: A 29-year-old man with migraine recently started on eletriptan was evaluated for a worsening headache. Initially his blood pressure was 220/160 mm Hg with a creatinine of 1.9 mg/dL. He was treated with intravenous nicardipine. His lab tests showed normal aldosterone/plasma renin activity ratio, midnight salivary cortisol, thyroid function, and urinary drug screen. A 24-hour urine metanephrine level at 2,494 μg (normal, 45 to 290 μg) and normetanephrine level at 1,341 μg (normal, 82 to 500 μg) for secondary hypertension work-up were markedly elevated. In contrast, plasma metanephrines were at 27 pg/mL (normal, 0 to 62 pg/mL) and normetanephrines were at 255 pg/mL (normal, 0 to 145 pg/mL) were only mildly elevated. Adrenal CT and gallium-68 positron emission tomography/computed tomography showed no abnormalities. Within 1 week of eletriptan discontinuation, his urine and plasma metanephrine and normetanephrine levels completely normalized as well as a reduction of blood pressure (130’s/80’s mm Hg). Conclusion: The discrepancy between plasma and urine studies in our patient suggests the possibility of false positive tests. It is possible that eletriptan may affect the urine assays, but the exact mechanism causing elevated urine metanephrines/normetanephrines is not clear.

Random ‘spot’ urinary metanephrines compared with 24-h-urinary and plasma results in phaeochromocytomas and paragangliomas

Background In patients with phaeochromocytomas or paragangliomas (PPGLs), 24-h urine collections for metanephrines (uMNs) are cumbersome. Objective To evaluate the diagnostic utility of ratios to creatinine of ‘spot’ uMNs. Methods Concentrations of uMNs and plasma metanephrines (pMNs) were measured by HPLC-mass-spectrometry. We retrospectively compared correlations of 24-h-urine output and ratio to creatinine in historical specimens and prospectively assessed 24-h and contemporaneous spot urines and, where possible, pMNs. Using trimmed log-transformed values, we derived reference intervals based on age and sex for spot urines. We used multiples of upper limit of normal (ULNs) to compare areas under curves (AUCs) for receiver-operator characteristic curves of individual, and sum and product of, components. Results In 3143 24-h-urine specimens on 2416 patients, the correlation coefficients between the ratios and outputs of metanephrine, normetanephrine and 3-methoxytyramine in 24-h urines were 0.983, 0.905 and 0.875, respectively. In 96 patients, the correlations between plasma concentrations, urine output and ratios in spot specimens were similar to those for raw output or ratios in 24-h specimens. Of the 160 patients with PPGLs, the CIs for AUCs for individual metabolites overlapped for all four types of measurement, as did those for the sum of the multiple ULNs although these were slightly higher (AUC for spot urine: 0.838 (0.529–1), plasma: 0.929 (0.874–0.984) and output: 0.858 (0.764–0.952)). Conclusions Ratios of fractionated metanephrines to creatinine in spot urine samples appear to have a similar diagnostic power to other measurements. The ease of spot urine collection may facilitate diagnosis and follow-up of PPGLs through improved patient compliance.

Glucocorticoid Excess in Patients with Pheochromocytoma Compared with Paraganglioma and Other Forms of Hypertension

Context Catecholamines and adrenocortical steroids are important regulators of blood pressure. Bidirectional relationships between adrenal steroids and catecholamines have been established but whether this is relevant to patients with pheochromocytoma is unclear. Objective This study addresses the hypothesis that patients with pheochromocytoma and paraganglioma (PPGL) have altered steroid production compared with patients with primary hypertension. Design Multicenter cross-sectional study. Setting Twelve European referral centers. Patients Subjects included 182 patients with pheochromocytoma, 36 with paraganglioma and 270 patients with primary hypertension. Patients with primary aldosteronism (n = 461) and Cushing syndrome (n = 124) were included for additional comparisons. Intervention In patients with PPGLs, surgical resection of tumors. Outcome measures Differences in mass spectrometry–based profiles of 15 adrenal steroids between groups and after surgical resection of PPGLs. Relationships of steroids to plasma and urinary metanephrines and urinary catecholamines. Results Patients with pheochromocytoma had higher (P < .05) circulating concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone, and corticosterone than patients with primary hypertension. Concentrations of cortisol, 11-deoxycortisol, and corticosterone were also higher (P < .05) in patients with pheochromocytoma than with paraganglioma. These steroids correlated positively with plasma and urinary metanephrines and catecholamines in patients with pheochromocytoma, but not paraganglioma. After adrenalectomy, there were significant decreases in cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, aldosterone, and 18-oxocortisol. Conclusions This is the first large study in patients with PPGLs that supports in a clinical setting the concept of adrenal cortical–medullary interactions involving an influence of catecholamines on adrenal steroids. These findings could have implications for the cardiovascular complications of PPGLs and the clinical management of patients with the tumors.

A SERIES OF TWO PATIENTS WITH CARDIAC PARAGANGLIOMAS

Objective: The objective of this report is to present 2 cases of cardiac paragangliomas (PGLs), and to outline the presentation, management, and associated genetic mutations. Methods: Case 1, a 38-year-old female, presented with a 12-month history of paroxysmal palpitations, headaches, and weight loss. Her investigations included plasma free metanephrines and urinary metanephrines, 68-gallium DOTATATE positron emission tomography/computed tomography, and cardiac imaging. Case 2, a 28-year-old male, presented with a hypertensive crisis and abdominal pain on a background of hypertension. Given his abdominal pain, he was investigated with an abdominal computed tomography (CT) scan, followed by plasma free meta-nephrines and urinary metanephrines, echocardiogram, and 123-iodine meta-iodobenzylguanidine single-photon emission CT. Results: Case 1 had an elevated plasma normetadrenaline of 6,750 pmol/L (reference range is <900 pmol/L) and 3-methoxytyramine of 1,845 pmol/L (reference range is <110 pmol/L). 68-gallium DOTATATE positron emission tomography/computed tomography showed an avid cardiac lesion. The lesion was resected, and histopathology confirmed PGL. Genetic studies revealed an SDHC gene mutation. For case 2, abdominal CT revealed a para-spinal mass. Workup for this lesion revealed elevated normetadrenaline of 56,000 pmol/L (reference range is <900 pmol/L). An echocardiogram, arranged for investigation of hypertension, showed an additional cardiac mass. A 123-iodine meta-iodobenzylguanidine single-photon emission CT scan confirmed that both masses were functioning. The lesions were successfully excised. He was found to have an SDHB gene mutation. Conclusion: Both patients had long-standing symptoms secondary to catecholamine excess, thus it is important to promptly screen patients with unexplained hypertension or paroxysmal symptoms of palpitations, headaches, and diaphoresis with plasma free metanephrines or urinary metanephrines. All patients with PGLs should be offered genetic testing due to the high incidence of genetic mutations.