DIAGNOSIS OF ENDOCRINE DISEASE: Biochemical diagnosis of phaeochromocytoma and paraganglioma

Abstract

Adrenal phaechromocytomas and extra-adrenal sympathetic paragangliomas (PPGLs) are rare neuroendocrine tumours, characterised by production of the catecholamines: noradrenaline, adrenaline and dopamine. Tumoural secretion of catecholamines determines their clinical presentation which is highly variable among patients. Up to 10-15% of patients present entirely asymptomatic and in 5% of all adrenal incidentalomas a PPGL is found. Therefore, prompt diagnosis of PPGL remains a challenge for every clinician. Early consideration of the presence of a PPGL is of utmost importance, because missing the diagnosis can be devastating due to potential lethal cardiovascular complications of disease. First step in diagnosis is proper biochemical analysis to confirm or refute the presence of excess production of catecholamines or their metabolites. Biochemical testing is not only indicated in symptomatic patients but also in asymptomatic patients with adrenal incidentalomas or identified genetic predispositions. Measurements of metanephrines in plasma or urine offer the best diagnostic performance and are the tests of first choice. Paying attention to sampling conditions, patient preparation and use of interfering medications is important, as these factors can largely influence test results. When initial test results are inconclusive, additional tests can be performed, such as the clonidine suppression test. Test results can also be used for estimation of tumour size or prediction of tumour location and underlying genotype. Furthermore, tumoural production of 3-methoxytyramine is associated with presence of an underlying SDHB mutation and may be a biomarker of malignancy.

Perioperative Management of Adrenalectomy and Inferior Vena Cava Reconstruction in a Patient With a Large, Malignant Pheochromocytoma With Vena Caval Extension

“…2,62,63 The prolific production of this pheochromocytoma resulted in ready detection of catecholamines, obviating the requirement for further diagnostic maneuvers such as a 24-hour urine metanephrine determination and/or the performance of a clonidine suppression test. 20,62,65 The failure of an adequate clonidine dose to reduce levels of epinephrine or norepinephrine by at least 50% is highly sensitive and specific for pheochromocytoma. 65 Although testing for metanephrines is a diagnostic technique of choice in suspected pheochromocytoma, it is important to remember that multiple factors still can interfere with this technique, such as age, sex, diet, medications, body position, cigarette smoking, and comorbidities.…”

“…20,62,65 The failure of an adequate clonidine dose to reduce levels of epinephrine or norepinephrine by at least 50% is highly sensitive and specific for pheochromocytoma. 65 Although testing for metanephrines is a diagnostic technique of choice in suspected pheochromocytoma, it is important to remember that multiple factors still can interfere with this technique, such as age, sex, diet, medications, body position, cigarette smoking, and comorbidities. 2,[62][63][64][65] In challenging diagnostic cases, replacement of disruptive medications may be warranted to optimize the precision of the biochemical testing.…”

“…65 Although testing for metanephrines is a diagnostic technique of choice in suspected pheochromocytoma, it is important to remember that multiple factors still can interfere with this technique, such as age, sex, diet, medications, body position, cigarette smoking, and comorbidities. 2,[62][63][64][65] In challenging diagnostic cases, replacement of disruptive medications may be warranted to optimize the precision of the biochemical testing. 3,[62][63][64][65] The biochemical diagnosis confirms the diagnosis of pheochromocytoma, rendering a tissue diagnosis from percutaneous adrenal biopsy unnecessary.…”

“…2,[62][63][64][65] In challenging diagnostic cases, replacement of disruptive medications may be warranted to optimize the precision of the biochemical testing. 3,[62][63][64][65] The biochemical diagnosis confirms the diagnosis of pheochromocytoma, rendering a tissue diagnosis from percutaneous adrenal biopsy unnecessary. 66 Given that many adrenal masses may not have diagnostic biochemical markers, adrenal biopsy in these settings often is required for definitive diagnosis.…”

“…2,62 Although the long-acting nonselective phenoxybenzamine has been the classic pharmacologic approach, its clinical niche recently has been challenged by the shorter-acting α-1 specific agents such as doxazosin, prazosin, and terazosin. 2,[62][63][64][65]69 Recent clinical trials have demonstrated that these selective agents are less protective against intraoperative hypertension than is phenoxybenzamine. 70 On the other hand, their shorter half-lives likely are protective against persistent hypotension after tumor removal.…”