Testing For Pheochromocytoma Research Articles

Screening of primary aldosteronism and pheochromocytoma among patients with hypertension: an Italian nationwide survey.

The delayed or missed diagnosis of secondary hypertension contributes to the poor blood pressure control worldwide. This study aimed to assess the diagnostic approach to primary aldosteronism (PA) and pheochromocytoma (PHEO) among Italian centers associated to European and Italian Societies of Hypertension. Between July and December 2023, a 10-items questionnaire was administered to experts from 82 centers of 14 Italian regions and to cardiologists from the ARCA (Associazioni Regionali Cardiologi Ambulatoriali) Piemonte. Results were stratified for geographical area, specialty, and center category (excellence vs. non-excellence centers). Each center diagnosed an average of 2 cases of PA and 0.2 cases of PHEO annually, with higher figures in excellence centers. PA screening is performed mainly in patients with resistant hypertension (73.2%) or hypertension and spontaneous hypokalemia (84.1%), while only 17.1% and 35.4% of centers screen patients with grade 2-3 hypertension. Screening rate is lower for cardiologists compared to other specialists. The main barriers to wider testing were challenges in interpreting the aldosterone/renin ratio under interfering medications and switching to non-interfering drugs. Clinical scores to predict the likelihood of PA and the definition of Standard Operating Procedures were identified as potential tools to boost screening rates. Testing for PHEO was mostly conducted in patients with typical symptoms (75.6%) and/or hypertensive crisis (74.4%). Only 37.8% of centers screened all patients with adrenal incidentaloma. This study highlights significant gaps in the screening and diagnosis of PA and PHEO across Italian centers and underscores the need for widespread and standardized diagnostic protocols.

8059 An Interesting Case Of Hypogonadism Likely Caused By Cushing's Syndrome

Abstract Disclosure: R. Ripa: None. J. Su: None. R. Patel: None. Introduction: Cushing’s Syndrome is a rare endocrine disorder that comprises a multitude of symptoms caused by hypercortisolism. Given non-specific symptoms, the disease can often be overlooked for more common diseases, such as diabetes, obesity, and even hypogonadism. Hypogonadism is a clinical disorder defined by decreased functional activity of the gonads. The diagnosis can often be challenging in developed males, who present with hypogonadotropic hypogonadism without an obvious cause. Here we present a case of a male who presented with hypogonadism symptoms for at least 5 years before being diagnosed with Cushing’s syndrome. Case Presentation: 58-year-old Caucasian male with a medical history of hypertension, cardiomyopathy and a BMI of 23, presented with decreased libido and erectile dysfunction. He was started on testosterone therapy three years prior, however it was discontinued due to heart failure. Without testosterone replacement, lab work was notable for: low free and total testosterone, 21.4 and 50.6 ng/dL, respectively, inappropriately normal findings of LH, FSH (1.0 and 4.9 IU/L, respectively), as well as unremarkable findings of GH, Prolactin, TSH, pituitary MRI and testes ultrasound, leading to a suspicion of hypogonadism. Due to persistent symptoms of hypogonadism and low testosterone, clomiphene was started but later changed to testosterone therapy after cardiology consultation. Shortly after, he began reporting facial flushing, associated with facial roundedness and elevated blood pressure. Upon further work up, hyperaldosteronism and pheochromocytoma testing was negative and his baseline cortisol was 21.9 mcg/dL with a low adrenocorticotropic hormone (ACTH), <5 pg/mL. Further, dexamethasone suppression testing showed suboptimally suppressed cortisol (14.4 mcg/dL). An abdomen MRI with and without contrast revealed a 2.3 cm adrenal adenoma, confirming an adrenal source of Cushing’s syndrome, and he underwent an adrenalectomy. Post-procedure, his cortisol and ACTH levels normalized to 10.5 mcg/dL and 39 pg/mL, respectively, showing a revival of his hypothalamic - pituitary - adrenal axis. Unfortunately, however, his free and total testosterone levels continued to remain low (38.9 and 152 ng/dL, respectively) and he was continued on testosterone therapy. Discussion: Our patient initially presented with decreased libido, and low testosterone levels and was treated for hypogonadism, as he did not have typical Cushing’s symptoms. Due to eventual weight gain and facial edema, it was only then that work up was pursued showing hypercortisolism release, leading to a proper diagnosis of Cushing’s syndrome. Hypercortisolism can affect all parts of the body, including hormones, muscles, joints and bones. When presenting in the initial stages and with mild symptoms, the diagnosis of hypercortisolism is often challenging and can go undetected for many years. Presentation: 6/2/2024

THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism

Abstract Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None. Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (<1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size >4 cm, internal calcifications, and HU >10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was <0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events. Presentation: Thursday, June 15, 2023

Pheochromocytoma: Impact of genetic testing on clinical practice in Vietnam

Germline mutations in predisposing genes have been found in 30-40% of pheochromocytoma/paraganglioma patients. Screening for inherited genetic mutations provide clinicians with mutation-positive patient management strategies in addition to identifying family members at risk of disease. However, genetic testing for pheochromocytoma has not been performed widely in Vietnam. Seven patients diagnosed with pheochromocytoma in Vietnam underwent germline genetic testing in known pheochromocytoma-associated genes by direct sequencing. When a germline mutation was identified the first-degree relatives were counseled and offered genetic testing for the inherited mutation. Mutations were found in five of seven cases and all mutations were in RET proto-oncogene codon 634 indicating a high risk of developing aggressive medullary thyroid cancer and in some cases leading to prophylactic thyroidectomy as recommended. Genetic testing plays an essential role in the clinical management of pheochromocytoma patients. Genetic results have significantly changed the clinical approach in these patients and identified ‘at risk’ family members.

Clinical profile of pheochromocytoma and paraganglioma with normal plasma free metanephrines

Plasma free metanephrines (MNs) have been widely used as an initial test for pheochromocytoma and paraganglioma (PPGL). PPGL without MNs elevation has been reported on rare occasions. The objective of this study was to analyze the clinical profile of sporadic PPGL patients with normal MNs. In the study, 104 patients with sporadic PPGL diagnosed by histopathology in Peking University First Hospital from March 2015 to January 2020 were enrolled. All the patients had plasma MNs result, of whom, eight (7.69%) were with normal MNs. The reasons for their medical visits, clinical manifestations, the levels of plasma free MNs, 3-methoxytyramine (3-MT), catecholamines and chromogranin A (CgA), and the imaging findings were documented. Their preoperative diagnosis, perioperative medical management, and intraoperative blood pressure were analyzed. All the data mentioned above were compared with the MNs elevated group. The postoperative follow-up for MNs normal patients were applied. For the eight PPGL patients with normal plasma MNs, the most common clinical symptoms were sweating (3/8), abdominal and back pain (3/8), headache (2/8), palpitations (2/8), and fatigue (2/8). There were no significant differences in plasma free 3-MT and catecholamines' diagnostic positive rate between the MNs normal group and MNs elevated group, but the rate for plasma CgA was significantly decreased in the MNs normal group (2/5 vs. 41/43, P=0.005). No significant difference was found for the incidence of typical findings by enhanced CT between the two groups. In these eight MNs normal patients, six were diagnosed with PPGL by the previous history of PPGL, typical symptoms and CT findings, or elevation of 3-MT, CgA levels or positive results of PET-CT; two patients were misdiagnosed as nonfunctioning adenoma or primary aldosteronism. All these MNs normal patients underwent preoperative management with alpha adrenergic receptor blockers, of whom, one had an average intraoperative arterial pressure < 60 mmHg during surgery. The median follow-up time for the eight patients was 1.5 (0.5－4.5) years. No evidence of new tumors was found on the enhanced CT scans. Two MNs normal patients' plasma 3-MT and (or) CgA decreased to normal. For patients with adrenal or retroperitoneal tumors, typical symptoms or a previous history of PPGL, normal plasma MNs is not a sufficient exclusion for PPGL. Plasma 3-MT, catecholamine, CgA results and the imaging findings are helpful for the diagnosis of PPGL. We recommend patients with suspected MNs normal PPGL take alpha adrenergic receptor blockers as preoperative blockade, but should avoid overdose. Postoperative follow-up for patients with normal MNs should focus on the positive biochemical markers before surgery.

The role of plasma metanephrines and plasma catecholamines in the biochemical testing for Pheochromocytoma

The role of plasma metanephrines and plasma catecholamines in the biochemical testing for Pheochromocytoma

Comparison of plasma free metanephrines between healthy dogs and 3 dogs with pheochromocytoma

Adrenomegaly and hypertension are common clinical entities in canine medicine for which testing for pheochromocytoma is recommended. Yet, a validated biochemical test for the diagnosis of pheochromocytoma in dogs does not exist. In human medicine, plasma free metanephrine testing is the diagnostic standard for the biochemical diagnosis of pheochromocytoma. The purpose of this study was to investigate the utility of measurement of plasma free metanephrines in dogs for the diagnosis of pheochromocytoma. Plasma free metanephrines were measured in 11 healthy dogs and in 3 dogs confirmed to have a pheochromocytoma. The metanephrine assays were performed at a reference laboratory using high-performance liquid chromatography with electrochemical detection. The plasma free metanephrine and normetanephrine concentrations in 11 healthy dogs were normally distributed and were used to create tentative reference intervals. All 3 dogs with histologically confirmed pheochromocytoma clearly had higher concentrations of plasma free metanephrines. This pilot study demonstrates the potential utility of plasma free metanephrines levels for the biochemical diagnosis of pheochromocytoma in dogs.

Ordering pattern and performance of biochemical tests for diagnosing pheochromocytoma from 2000 to 2008

Objective To examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice. Methods In this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed. Results A total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%. Conclusions Ordering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation. (Endocr Pract. 2009;15:313-321)

Ordering Pattern and Performance of Biochemical Tests for Diagnosing Pheochromocytoma Between 2000 and 2008

To examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice. In this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed. A total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%. Ordering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation.

The Efficacy of MIBG Scan as a Diagnostic and Docalization Test for Pheochromocytoma

Background: Computed tomography (CT) is currently considered as the initial imaging procedure of choice for the localization of pheochromocytomas in most of the cases. 131I-or 123I-Metaiodobenzylguanidine scintigraphy (MIBG scan) was proven to be a highly specific tool for the detection of adrenal and extra-adrenal pheochromocytomas, but was less sensitive than CT. The present study is aimed to evaluate the usefulness of a MIBG scan in diagnosis and localization of pheochromocytoma when compared to CT. Methods: We retrospectively evaluated 27 patients who underwent a MIBG scan for a pheochromocytoma at the Seoul National University Hospital from the year 2000 and 2002. According to the pathological and clinical findings, in 16 the patients pheochromocytoma was confirmed to be positive and the rest 11 of the patients were excluded from the study. Results: Pheochromocytomas was identified in 16 patients. Eleven of them were localized in adrenal gland and 5 were extra-adrenal lesions. The sensitivity to MIBG scan in adrenal lesions and extra-adrenal lesions, was 72% (8/11) and 40% (2/5) respectively. In our study, the overall sensitivity to MIBG scan was 62% (10/16), and overall specificity was 90.9% (10/11). By CT four were identified to have equivocal biochemical abnormalities, but were definite and extraadrenal tumors by MIBG

False Positive Biochemical Testing for Pheochromocytoma Caused by Surreptitious Catecholamine Addition to Urine

False Positive Biochemical Testing for Pheochromocytoma Caused by Surreptitious Catecholamine Addition to Urine

REPCAT: Desktop expert system for interpreting and validating laboratory data for pheochromocytoma diagnosis with the database application Omnis 7™

To aid in the validation and interpretive reporting of results from multianalyte diagnostic testing for pheochromocytoma (PHEO), we have developed a desktop personal computer-based laboratory expert system (REPCAT). REPCAT utilizes a commercial database application to run procedures that assess analytical and clinical data relating to patient urine or plasma samples. REPCAT was used to evaluate the raw data from >4000 24-h urine samples submitted to our laboratory for testing for the presence of PHEO. REPCAT performed equivalently to an expert pathologist in assessing the presence and class of PHEO (epinephrine, norepinephrine, or mixed secretor). No false negatives were generated and it assigned a correct interpretation (on the basis of subsequent clinical and biochemical investigation) for each of the primary diagnostic samples from these patients.

Improved safety of glucagon testing for pheochromocytoma by prior alpha-receptor blockade. A controlled trial in a patient with a mixed ganglioneuroma/pheochromocytoma

Improved safety of glucagon testing for pheochromocytoma by prior alpha-receptor blockade. A controlled trial in a patient with a mixed ganglioneuroma/pheochromocytoma

Hypertension in renal transplant recipients

A 29-year-old black woman was evaluated at another hospital because of epistaxis and a blood pressure of 300/150mm Hg. At age 18 she was refused entrance to the military because of hypertension. Between the ages of 20 and 24 years, she had 3 pregnancies, each complicated by toxemia. Although hypertension was noted on occasion over the subsequent years, she did not take any antihypertensive medications. Her mother and 3 of her 7 siblings had hypertension. On physical examination, the optic fundi showed grade II hypertensive changes. Urinalysis revealed: specific gravity, 1.016; 1 + protein; negative glucose; 10 red blood cells/high-power field; and no casts. The serum creatinine was 2.0 mg/dl; endogenous creatinine clearance, 55 mI/mm; and 24-hour protein excretion, 1.2 g. Hemoglobin electrophoresis was within normal limits. Chest x-ray and electrocardiogram disclosed evidence of left ventricular hypertrophy. Tests for pheochromocytoma were negative. An excretory urogram revealed no evidence of refiux nephropathy; renal arteriogram showed bilateral intrarenal small-vessel disease, which was thought to be consistent with nephrosclerosis. The patient returned for only some of her scheduled followup visits and took the prescribed antihypertensive medications only intermittently. Renal function gradually deteriorated. At age 36, the serum creatinine was 9.5 mgldl and BUN 90 mg/dl, and she was referred for renal transplantation. At that time, she was taking hydralazine, 50 mg; propranolol, 80 mg; and furosernide, 40 mg, all twice daily; blood pressure ranged between 130—140/90—100 mm Hg. After completing a donor-specific blood transfusion protocol [11, but prior to hemodialysis, the patient received a renal allograft (one

Evaluation of screening tests for pheochromocytoma.

Autonomous and excessive synthesis of catecholamines is the predominant feature of pheochromocytoma tissue. An increased amount of catecholamines in the sympathetic neuron is the precondition for positive pharmacological tests. High rates of false-negative results are seen because of a down-regulation of adrenoceptors in pheochromocytoma patients. The separate measurement of the catecholamines adrenaline and noradrenaline and their metabolites metanephrine and normetanephrine in urine or serum are the most sensitive screening tests.

Lactic Dehydrogenase Activity in Human Pheochromocytoma

Lactic dehydrogenase (LDH), a cytosolic enzyme found in neural and endocrine tissue, was measured in serum and tumor tissue of 15 patients with pheochromocytoma, a neuroendocrine neoplasm. Mean serum total LDH activity was higher in patients with pheochromocytoma than in patients with essential hypertension, normotensive control subjects, or those with various other categories of secondary hypertension. The prominent isoenzyme was LDH type 3. Their pheochromocytoma tissue, as well as normal human adrenal tissue, also contained LDH, maximally type 3; the amount of LDH in tumors far exceeded that in normal adrenal glands, suggesting that the tumor tissue is the source of the excessive serum LDH in these patients. While a large percentage of false-negative results (40%) does not render serum LDH activity a reasonable screening test for pheochromocytoma, and even though the true-positive rate is high (100%), we cannot yet recommend that hypertensive patients with high serum LDH activity undergo investigation for this tumor.

A Bit of Heresy?

Hypertension remains undetected and/or untreated in a large number of individuals, and the limited medical facilities, manpower, and resources that are available to evaluate these cases demand a critical reassessment of how much is really necessary in the pretreatment examination of the hypertensive patient. These limitations have led to the discard of the intravenous pyelogram and tests for pheochromocytoma as routine examinations. Now, in this issue ofArchives(p 1211), Bartha and Nugent present data from a retrospective review of the records of 116 hypertensive patients to indicate that routine roentgenograms of the chest and ECGs did not materially influence decisions on the management of hypertension in any case. Their conclusion was, ... the value of routine chest roentgenograms and ECGs cannot be defended on the basis of their contribution to the workup of hypertension. It is important to distinguish those examinations that are pertinent to the diagnosis and/or management of

A Modified Phentolamine Test for the Diagnosis of Pheochromocytoma

The usefulness of phentolamine mesylate in testing for pheochromocytoma is limited by false-positive blood pressure responses in other hypertensive states not characterized by elevated catecholamine levels. Since phentolamine can release the suppression of insulin secretion caused by catecholamines, changes in plasma insulin and glucose levels were measured following phentolamine administration in an attempt to enhance this test's specificity. Three patients with proven pheochromocytoma and positive reactions had a mean fall in glucose value of 52 mg/100 ml and a mean rise in insulin level of 39 microunits/ml. Six patients with false-positive reactions had a mean fall in glucose content of 3 mg/100 ml and a mean rise in insulin value of 7 microunits/ml. Ten patients with negative reactions had similar changes. Thus, these measurements during a modified phentolamine test may identify the falsepositive reactions and strengthen this procedure.

Histamine and Glucagon Tests in Diagnosis of Pheochromocytoma

The glucagon hydrochloride test of Lawrence was compared with the standard cold pressor-histamine test in 12 patients with pheochromocytoma and in 35 control patients without tumor. Urinary and blood catecholamine levels and the values for urinary vanilmandelic acid and total metanephrine were also determined. One patient without a tumor had a pressor response after receiving histamine; none had a pressor response after receiving glucagon. Eleven patients with tumor were given 1 mg of glucagon; six had a positive pressor response, and four of these six had a positive response after receiving histamine as well. One patient with tumor responded positively to histamine but not to 0.5 mg of glucagon. Although determination of the level of urinary metanephrine remains the preferred screening test for pheochromocytoma, when adjunctive studies are desired we recommend the cold pressor-glucagon test (1 mg) instead of histamine as the standard provocative pharmacologic test for pheochromocytoma.

Evaluation of the Tyramine Test In Hypertensive Patients and Controls

Tyramine hydrochloride has been proposed for use as a provocative test for pheochromocytoma. It has been evaluated in 46 hypertensive patients and 58 normotensive controls by members of the US Public Health Service Cooperative Study. Positive tests were obtained preoperatively in two patients with elevated catecholamine and vanilmandelic acid (VMA) levels with proved pheochromocytomas. Seven patients with labile blood pressure responses also had a positive tyramine test. In the latter group, results of catecholamine and VMA determinations were all normal. The tyramine test is a useful and safe addition to the screening procedures in the evaluation of hypertensive patients for remediable causes of elevated blood pressure. Twenty-four-hour urine collections for catecholamine or VMA determinations still are required to confirm the diagnosis of pheochromocytoma.