Pheochromocytoma Flashcards
Pheochromocytoma
-definition
- chromaffin cell tumor of the adrenal cortex secreting catecholamines: adrenaline, noradrenaline, dopamine
- tumors that develop from extra-adrenal chromaffin cells = paragangliomas, usually paravertebral
- excessive nervous system stimulation
Pheochromocytoma
-prevalence (3)
- mostly - sporadic
- 1/3 - familial disorders associated with gene mutations
- increases mortality from cardiovascular disease
Pheochromocytoma
-characteristic (3)
- location: 95% abdomen and pelvis, paraganglioma next to aorta 75%
- malignancy is detected only when the primary spread process is found or metastases occur –> no reliable markers
- long term follow up is needed
Pheochromocytoma
-with what genetic syndrome Pheo is associated?
-autosomal dominant inheritance
- MEN2 - Multiple endocrine neoplasia type 2
- VHL - von Hippel-Lindau
- NF1 - Neurofibromatosis type 1
Multiple endocrine neoplasia type 2 (MEN2)
- MEN2A (Sipple’s syndrome) - 100% prevalence of medullary thyroid carcinoma (MTC), pheochromocytoma, primary hyperparathyroidism,
- MEN2B - 100% prevalence of medullary thyroid carcinoma (MTC), pheochromocytoma, mucocutaneous neuromas, skeletal deformities
von Hipplel - Lindau (VHL) (6)
- pheochromocytoma
- paraganglioma
- hemangioblastoma
- retinal angioma
- clear cell renal cell carcinoma
- pancreatic neuroendocrine tumors
Neurofibromatosis type 1 (NF1) (7)
- neurofibromas
- multiple “cafe au lait” spots
- iris hamartomas
- bony abnormalities
- CNS gliomas
- pheochromocytoma and paraganglioma
- macrocephaly and cognitive deficits
SDH - succinate dehydrogenase mutations
Familial pheochromocytoma/ paraganglioma
Pheochromocytoma
-clinics (4)
- symptoms in about 50%
- classic triad: headache, increased sweating, palpitations
- some will have arterial hypertension
-other symptoms - less common: cardiomyopathy (takotsubo), orthostatic hypotension, visual disturbances, heart failure
Pheochromocytoma
-diagnostics - indications for Pheo testing (9)
- Classic symptoms
- Spontaneous episodes of palpitations, agitation, headaches, tremors, paleness
- Arterial hypertension at young age
- Familial syndromes
- Pheo in family history
- Adrenal incidentaloma
- Sudden rise in BP during anesthesia, surgery, diagnostic intervention
- Idiopathic dilated cardiomyopathy
- Former gastric stromal tumor or lung chondroma
Pheochromocytoma
-diagnostics - biochemical screening tests
- fractionated plasma metanephrines or fractionated methanephrines at 24 hours urine
- positive –> increase in methanephrine concentration exceeds the normal range by 2-3 times
Pheochromocytoma
-Chromogranin A (4)
- accumulated in secretory vesicles of chromaffin adrenal cells
- specific for neuroendocrine tumors, adrenocortical carcinoma, prostate cancer with neuroendocrine differentiation
- amount depends on the size and spread of the tumor
- increases –> drugs - proton pump inhibitors
Pheochromocytoma
-Dopamine
- rarely pheochromocytomas secrete dopamine alone
- test –> 3 methoxytiramine or plasma dopamine
Pheochromocytoma
-radiological testing (5)
- recommended only with biochemical confirmation of Pheo
- CT -first choice
- MRI - for suspected metastasis
- Scintigraphy with J123 MIBG - for patients with or with risk of metastasis, when the tumor is outside the adrenal gland (paraganglioma), in case of relapse
- PET - for patients with known metastasis, more sensitive than Scintigraphy
Pheochromocytoma
- Pheo at CT: (5)
- Pheo at MRI:
- large tumor (usually >3cm), hemorrhages, inhomogeneous, mostly >10 HU density, calcification is rare
- T1: hypo intense or isointense mass , T2: high-intensity mass
Pheochromocytoma
-genetic testing
- last step
- all patients who are diagnosed with Pheo or paraganglioma, should be referred for genetic counseling
Pheochromocytoma
-Associated genetic syndromes - after diagnosis of Pheo also investigate: (4)
- PTH and ionized calcium for primary hyperparathyroidism (MEN2A)
- Calcitonin for medullary thyroid carcinoma (MEN2A)
- Ophthalmologists consultation to evaluate retina for angiomas (VHL)
- Radiological examination to evaluate kidneys and pancreas for cysts (VHL)
Pheochromocytoma
-treatment (3)
- surgical
- imp. –> preoperative patient preparation
- medication for receptor blockade before surgery –> first-line: alpha-adrenoblockers (AAB)
Pheochromocytoma
-treatment - preparation scheme (6)
- alpha-adrenoblockers (AAB) are started 7-14 days prior to surgery
- if tachycardia –> add betablockers, not earlier than 3-4 days after AAB
- if high BP persists –> add calcium blockers
- if high BP persists –> add methyrosine
- ensure adequate salt >5 g/d and fluids intake
- 1-2 days before surgery –> administer crystalloid infusions
Pheochromocytoma
- preparation scheme:
1. Target BP
2. Target heart rate
- BP <130/80 mmHg sitting and diastolic >90 mmHg standing (range depends on patient age and comorbidities)
- HR - 60-80 t/min
Pheochromocytoma
-surgical treatment (4)
- Laparoscopy - first choice - solitary adrenal Pheo (tumor size <6cm)
- Laparotomy - locally invasive or malignant Pheo and paragangliomas - size >6cm
- Bilateral adrenalectomy - patients diagnosed with MEN2 syndrome
- Adrenal cortex sparing adrenalectomy - when Pheo is very small
Pheochromocytoma
-long-term follow up (3)
- 14-28d. after surgery –> measure fractionated metanephrines –> if increased –> look for metastasis
- long-term follow up –> once a year
- follow up duration –> 10 years for all –> high risk patients (young age, large mass, paraganglioma, genetic disease) –> whole life
Pheochromocytoma
-factors that may influence the results (4)
- the blood is drawn in the morning, on an empty stomach, patient must lie on the back
- food, coffee, alcohol or smoking 12 hours prior –> not allowed
- conditions causing sympathetic nervous system activation and promoting catecholamines secretion (aka stress conditions): stroke, MI, obstructive sleep apnea, congestive heart failure, hypoglycemia, increased intracranial pressure, hypoxia, acidosis, surgery, trauma –> up to 10 days after the event
- drugs –> if possible, discontinue at least 2 weeks before hormone testing
