Roula BOU KHALIL Endocrinology Division SGHUMC Assistant
Professor, Balamand University Pheocromocytoma: An Update in
Genetic Profiling, Diagnosis, Treatment
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OUTLINE Overview Epidemiology Updates in Genetics Diagnosis
(biochemical and imaging) Treatment
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OVERVIEW
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Pheochromocytoma is a tumor arising from adrenomedullary
chromaffin cells that commonly produces one or more catecholamines:
epinephrine, norepinephrine, and dopamine Rarely, these tumors are
biochemically silent. Paraganglioma is a tumor derived from
extra-adrenal chromaffin cells sympathetic paravertebral ganglia of
thorax, abdomen, and pelvis parasympathetic ganglia located along
the glossopharyngeal and vagal nerves in the neck and at the base
of the skull, these do not produce catecholamines
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80 to 85% of chromaffin-cell tumors are pheochromocytomas, 15
to20%are paragangliomas During the last few years, a considerable
amount of new data concerning the genetics of PHEO/PGL or PPGL 25%
of cases develop secondary to germline mutations Tip of an iceberg
because beyond a single tumor there is potentially a broader
clinical picture
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EPIDEMIOLOGY
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Prevalence of PPGL is not precisely known Annual incidence of
pheochromocytoma is approximately 0.8 per 100,000 person years
Prevalence of PPGL in patients with hypertension in general
outpatient clinics varies between 0.2 and 0.6% Autopsy studies
demonstrate undiagnosed tumors in 0.050.1% In children with
hypertension, prevalence of PPGL is approximately 1.7% Nearly 5% of
patients with incidentally discovered adrenal masses on anatomical
imaging prove to have a pheochromocytoma
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Equally in men and women Mean age at diagnosis 4 th 5 th
decades large number of patients have non classic symptoms such as
abdominal pain, vomiting, dyspnea, heart failure, hypotension, or
sudden death, suggesting that the majority of PHEOs are not
diagnosed during life Most PHEOs are sporadic with prevalence of
malignancy 9% About 10% of patients with PHEOs present with
metastatic disease at the time of their initial work-up
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At least one-third of all patients with PPGLs have disease-
causing germline mutations (inherited mutations present in all
cells of the body) The prevalence of PPGL in individuals carrying a
germline mutation in PPGL susceptibility genes may be around 50%.
Patients with hereditary PPGLs typically present with multifocal
disease and at a younger age than those with sporadic
neoplasms
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CLINICAL IMPORTANCE OF DIAGNOSIS Cardiovascular morbidity and
mortality due to excess catecholamines if left untreated PPGL may
enlarge mass effect For familial disease, detection of a tumor in
the proband may result in earlier diagnosis and treatment in other
family members Some PPGLs have malignant potential, defined as the
presence of metastases in nonchromaffin tissue Mutations in the
gene encoding SDH subunit B (SDHB) can lead to metastatic disease
in 40% or more
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When to suspect pheochromocytoma? Hyperadrenergic spells
Resistant hypertension A familial syndrome that predisposes to
catecholamine-secreting tumors (eg, MEN2, NF1, VHL) A family
history of PPGL An incidentally discovered adrenal mass
Hypertension and new onset or atypical diabetes mellitus Pressor
response during anesthesia, surgery, or angiography Onset of
hypertension at a young age (eg,
Laparoscopic adrenalectomy Open adrenalectomy (large tumors
> 8 cm, malignant disease) Partial adrenalectomy with cortical
sparing in familial pheochromocytoma (High incidence of bilateral
disease) to prevent permanent glucocorticoid deficiency.
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Major potential postoperative complications are hypertension,
hypotension, and rebound hypoglycemia Blood pressure, heart rate
and plasma glucose levels should be closely monitored for 2448
hours Measure plasma or urine levels of metanephrines on follow- up
to diagnose persistent disease (2-4 weeks after surgery) Lifelong
annual biochemical testing to assess for recurrent or metastatic
disease