DEFINITIONPheochromocytomas are catecholamine-producing tumors
that originate from chromaf n cells of the adrenergic system. They
generally secrete both norepinephrine and epinephrine, but
norepinephrine is usually the predominant amine.PHYSICAL FINDINGS
AND CLINICAL PRESENTATION Hypertension: can be sustained (55%) or
paroxysmal
(45%) Headache (80%): usually paroxysmal in nature;
described
as pounding and severe Palpitations (70%): can be present with
or without tachy-
cardia. Hyperhidrosis (60%): most evident during paroxysmal
at-
tacks of hypertension. Physical examination may be entirely
normal if done in a
symptom-free interval. During a paroxysm, the patient may
demonstrate marked increase in systolic and diastolic pressure,
profuse sweating, visual disturbances (caused by hypertensive
retinopathy), dilated pupils (secondary to catecholamine excess),
paresthesias in the lower extremi-ties (caused by severe
vasoconstriction), tremor, and tachycardia.
CAUSE Catecholamine-producing tumors that are usually
located
in the adrenal medulla (Fig. 2751) Speci c mutations of the RET
proto-oncogene cause familial
predisposition to pheochromocytoma in MEN-II.
Mutations in the von Hippel-Lindau tumor suppressor gene (VHL
gene) cause familial disposition to pheochromocy-toma in von
Hippel-Lindau disease.
Recently identi ed genes for succinate dehydrogenase sub-unit D
(SDHD) and succinate dehydrogenase subunit B (SDHB) predispose
carriers to pheochromocytoma and glo-bus tumors.
DIFFERENTIAL DIAGNOSIS Anxiety disorder Thyrotoxicosis
Amphetamine or cocaine abuse Carcinoid Essential hypertension
LABORATORY TESTS Plasma-free metanephrines are the best test for
excluding or
con rming pheochromocytoma and should be the test of rst choice
for diagnosis of the tumor. Plasma concentra-tions of
normetanephrines higher than 2.5 pmol/mL or metanephrine levels
higher than 1.4 pmol/mL indicate a pheochromocytoma with 100% speci
city.
24-hour urine collection for metanephrines (100% sensi-tive)
will also show increased metanephrines. The accuracy of the 24-hour
urinary levels for metanephrines can be im-proved by indexing
urinary metanephrine levels by urine creatinine levels.
The clonidine suppression test is useful for distinguishing
between high levels of plasma norepinephrine caused by release from
sympathetic nerves and those caused by release from a
pheochromocytoma. A decrease of less than 50% in plasma
norepinephrine levels after clonidine administra-tion is normal,
whereas persistent elevations are indicative of
pheochromocytoma.
IMAGING STUDIESSee Figure 2752. Abdominal CT scanning (88%
sensitivity) is useful in locat-
ing pheochromocytomas larger than 0.5 inch in diameter (90% to
95% accurate).
MRI: pheochromocytomas demonstrate a distinctive MRI appearance
(100% sensitivity). MRI may become the diag-nostic imaging modality
of choice.
Scintigraphy with 131I-MIBG (100% sensitivity): this
norepi-nephrine analogue localizes in adrenergic tissue. It is
particu-larly useful in locating extra-adrenal
pheochromocytomas.
6-18F- uorodopamine positron emission tomography is re-served
for cases in which clinical symptoms and signs sug-gest
pheochromocytoma and results of biochemical tests are positive but
conventional imaging studies cannot locate the tumor. An
alternative approach is to use vena caval sam-pling for plasma
catecholamines and metanephrines.
TREATMENT Laparoscopic removal of the tumor (surgical resection
for
both benign and malignant disease)
894894
275 Section 11: Endocrine and metabolic disorders
Chapter 275 Pheochromocytoma
Fig 2751Cross section of pheochromocytoma. The tumor is deep
brown and faintly nodular and had a positive chromatin
reaction.(From Silverberg SG, Frable WJ, Wick MR, et al [eds]:
Principles and Practice of Surgical Pathology and Cytopathology,
4th ed. Philadelphia, Elsevier, 2006.)
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