endocrine and metabolic disorders
Pheochromocytoma
Diagnosis of Pheochromocytoma
Plasma free metanephrines or urinary metanephrines Chest and abdomen imaging (CT or MRI) if catecholamine screen positive Possibly nuclear imaging with I-123 MIBG (metaiodobenzylguanidine) or Gallium-68 dotatate-PET scanning Pheochromocytoma is suspected in patients with typical symptoms or particularly sudden, severe, or intermittent unexplained hypertension. Diagnosis involves demonstrating high levels of catecholamine products in the serum or urine. Plasma free metanephrines are up to 99% sensitive with either metanephrine or more frequently normetanephrine being elevated. This test has superior sensitivity to measurement of circulatingepinephrineandnorepinephrinebecause plasma metanephrines are elevated continuously, unlikeepinephrineandnorepinephrine, which are secreted intermittently. Grossly elevated plasmanorepinephrinerenders the diagnosis highly probable. Plasma 3-methoxytyramine is a metabolite ofdopamineand is indicative of a more aggressive tumor. Urinary metanephrine and normetanephrine levels are slightly less specific for pheochromocytoma than plasma free metanephrine, but elevation of either metabolite has about 95% sensitivity . Two or 3 normal results while the patient is hypertensive render the diagnosis extremely unlikely. Measurement of urinarynorepinephrineandepinephrineis less accurate. The principal urinary metabolic products ofepinephrineandnorepinephrineare the metanephrines (metanephrine and normetanephrine), vanillylmandelic acid (VMA), and homovanillic acid (HVA). Healthy people excrete only very small amounts of these substances. Normal values for 24 hours are as follows: Freeepinephrineandnorepinephrine<100 mcg (<582 nmol) Total metanephrine<1.3 mg (<7.1 micromole), but fractionated metanephrine and normetanephrine are preferable VMA<10 mg (<50 micromoles), which is now rarely used HVA<15 mg (<82.4 micromoles), which is mainly used to detect neuroblastoma in children In pheochromocytoma, increased urinary excretion ofepinephrineandnorepinephrineand their metabolic products is intermittent. Elevated excretion of these compounds may also occur in Other disorders (eg, Neuroblastoma , coma, dehydration, sleep apnea) Extreme stress Patients being treated with rauwolfia alkaloids,methyldopa, monoamine oxidase inhibitors, or catecholamines Ingestion of foods containing large quantities of VMA Blood volume is constricted and may falsely elevate hemoglobin and hematocrit levels. Hyperglycemia, glycosuria, or overt Diabetes Mellitus (DM) may be present, with elevated fasting levels of plasma free fatty acid and glycerol. Plasma Provocative testswith histamine or tyramineare hazardous and should not be used.Glucagon0.5 to 1 mg injected rapidly IV provokes a rise in blood pressure of>35/25 mm Hg within 2 minutes in normotensive patients with pheochromocytoma but is now generally unnecessary.Phentolaminemesylate must be available to terminate any hypertensive crisis. Provocative tests with histamine,glucagon, or tyramine are hazardous and should not be done. Asuppression testusing oralclonidineor IV pentolinium can be used in patients with elevated plasma catecholamines, but is rarely necessary. Imaging tests to localize tumorsare usually done in patients with abnormal screening results. Tests should include CT and MRI of the chest and abdomen with and without contrast. With isotonic contrast media, no adrenoceptor blockade is necessary. Fluorodeoxyglucose (FDG)-PET has also been used successfully, especially in patients with succinate dehydrogenase mutations, but Gallium-68 dotatate-PET scanning is more useful. During catheterization of the vena cava, repeated sampling of plasma catecholamine concentrations at different locations, including the adrenal veins, can help localize the tumor: there will be an increase innorepinephrinelevel in a vein draining the tumor. Adrenal veinnorepinephrine:epinephrineratios may help in the hunt for a small adrenal source, but determining these ratios is now rarely necessary. Radiopharmaceuticals with nuclear imaging techniques can also help localize pheochromocytomas. Radionuclide imaging is rapidly advancing and increasingly I-123 MIBG is being replaced by Gallium-68 dotatate-PET scanning. Signs of an associated genetic disorder(eg, café-au-lait patches in neurofibromatosis) should be sought. Patients should be screened for MEN with a serumcalcitoninmeasurement and any other tests as directed by clinical findings. Most centers routinely do genetic testing, especially when the pheochromocytoma involves the sympathetic paraganglia and in younger patients, but probably all patients with pheochromocytoma should have genetic testing . 