Transcript Pheochromocytoma

Anesthetic Implications of
Pheochromocytoma &
Cushing syndrome
&Addison’s disease
Moderator-Dr Jyoti Pathania
Presented by-Dr Kamal Prakash Sharma
Pheochromocytoma

0.01-0.1% of HTN population

Found in 0.5% of those screened

M=F
 3rd to 5th decades of life
 Rare, investigate only if clinically suspicion:
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Signs or Symptoms
Severe HTN, HTN crisis
Refractory HTN (> 3 drugs)
HTN present @ age < 20 or > 50 ?
Adrenal lesion found on imaging (ex. Incidentaloma)
Pheo: Signs & Symptoms
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The five P’s:
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Pressure (HTN)
Pain (Headache)
Perspiration
Palpitation
Pallor
90%
80%
71%
64%
42%
• Paroxysms (the sixth P!)
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The Classical Triad:
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Pain (Headache), Perspiration, Palpitations
Lack of all 3 virtually excluded diagnosis of pheo in a series of
> 21,0000 patients
Pheo: Paroxysms, ‘Spells’
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10-60 min duration
 Frequency: daily to monthly
 Spontaneous
 Precipitated:
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Diagnostic procedures, I.A. Contrast (I.V. is OK)
Drugs (opiods, unopposed -blockade, anesthesia induction,
histamine, ACTH, glucagon, metoclopramide)
Strenuous exercise, movement that increases intra-abdo
pressure (lifting, straining)
Pheo: Hypotension!
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Hypotension (orthostatic/paroxysmal)
occurs in many patients
 Mechanisms:
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ECFv contraction
Loss of postural reflexes due to prolonged
catecholamine stimulation
Tumor release of adrenomedullin (vasodilatory
neuropeptide)
Pheo: Signs & Symptoms

N/V, abdo pain, severe constipation (megacolon)
 Chest-pains
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Anxiety
Angina/MI with normal coronaries:
– Catecholamine induced:  myocardial oxygen consumption or
coronary vasospasm
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CHF
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HTN  hypertrophic cardiomyopathy  diastolic dysfn.
Catechols induce dilated cardiomyopathy  systolic dysfn.
Cardiac dysrhythmia & conduction defects
Pheo: Signs (metabolic)
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Hypercalcemia
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Associated MEN2 HPT
PTHrP secretion by pheo
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Mild glucose intolerance
 Lipolysis
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Weight-loss
Ketosis > VLDL synthesis (TG)
Pheo: ‘Rule of 10’
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10% extra-adrenal
 10% occur in children
 10% familial
 10% bilateral or multiple (more if familial)
 10% recur (more if extra-adrenal)
 10% malignant
 10% discovered incidentally
Catecholamines
Tyrosine
TH
L-Dopa
Metabolites
Dopamine
MAO, COMT
DBH
Homovanillic acid
(HVA)
NorepinephrineCOMT Normetanephrine
PNMT
Epinephrine
MAO
COMT
Metaneprine
MAO
Vanillymandelic Acid
(VMA)
Familial Pheo
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MEN 2a
 50% Pheo (usually bilateral), MTC, HPT
MEN 2b
 50% Pheo (usually bilatl), MTC, mucosal neuroma, marfanoid
habitus
Von Hippel-Landau
 50% Pheo (usually bilat), retinoblastoma, cerebellar
hemangioma, nephroma, renal/pancreas cysts
NF1 (Von Recklinghausen's)
 2% Pheo (50% if NF-1 and HTN)
 Café-au-lait spots, neurofibroma, optic glioma
Familial paraganglioma
Familial pheo & islet cell tumor
Other: Tuberous sclerosis, Sturge-Weber, ataxia-telangectgasia,
Carney’s Triad (Pheo, Gastric Leiomyoma, Pulm chondroma)
24h Urine Collection
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24h urine collection:
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Creatinine, catecholamines, metanephrines, vanillymandelic
acid (VMA), +/-dopamine
HPLC with electrochemical detection or mass spect
Positive results (> 2-3 fold elevation):
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24h Ucatechols > 2-fold elevation
• ULN for total catechols 591-890 nmol/d
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24h Utotal metanephrines > 1.2 ug/d (6.5 umol/d)
24h UVMA > 3-fold elevation
• ULN 35 umol/d for most assays
Sensitivity increased if 24h urine collection begun at onset of a
paroxysm
Plasma Catecholamines
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Drawn with patient fasting, supine, with an
indwelling catheter in place > 30 min
 Plasma total catechols > (2000 pg/mL)
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SEN 85% SPEC 80%
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False positives: same as for 24h urine testing, also
with diuretics, smoking
 CRF & ESRD:
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Oliguric to Anuric  24h Urines inaccurate
Plasma epinephrine best test for pheo in ESRD
Plasma norepi and metanephrines falsely elevated in ESRD
Plasma Metanephrines
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Not postural dependent: can draw normally
 Secreted continuously by pheo
 SEN 99% SPEC 89%
 False Positive: acetaminophen
 Assay not readily available in Canada
Suppression/Stimulation Testing
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Clonidine suppression
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May precipitate hypotensive shock!
Unlike normals, pheo patients won’t suppress their
plasma norepi with clonidine
Glucagon stimulation
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May precipitate hypertensive crisis!
Pheo patients, but not normals, will have a > 3x
increase in plasma norepi with glucagon
Localization: Imaging
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CT abdomen
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MRI
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Adrenal pheo SEN 93-100%
Extra-adrenal pheo SEN 90%
> SEN than CT for extra-adrenal pheo
MIBG Scan
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SEN 77-90% SPEC 95-100%
 111Indium-pentreotide
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Some pheo have somatostatin receptors
PET
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18F-fluorodeoxyglucose
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6-[18F]-fluorodopamine
(FDG)
Pheo Management
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Prior to 1951, reported mortality for excision of
pheochromoyctoma 24 - 50 %
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HTN crisis, arrhythmia, MI, stroke
Hypotensive shock
Currently, mortality: 0 - 2.7 %
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Preoperative preperation, -blockade?
New anesthetic techniques?
• Anesthetic agents
• Intraoperative monitoring: arterial line, EKG monitor, CVP
line, Swan-Ganz
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Experienced & Coordinated team:
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Endocrinologist, Anesthesiologist and Surgeon
Preoperative Workup
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CBC, Electroytes, creatinine, INR/PTT
 FBS
 Ca (if one of MEN syndrome is suspected)
 CXR
 EKG
 Echo (r/o dilated CMY 2º catechols)
Preop Preperation Regimens
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Combined  +  blockade
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Phenoxybenzamine
Selective 1-blocker (ex. Prazosin)
Propanolol
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Metyrosine
 Calcium Channel Blocker (CCB)
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Nicardipine
No Randomized Clinical Trials to compare
various regimens!
Preop:  +  blockade
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Start at least 10-14d preop
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Allow sufficient time for ECFv re-expansion
Phenoxybenzamine
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Drug of choice (noncompetitive & long acting)
Covalently binds -receptors (1 > 2)
Start 10 mg po bid  increase q2d by 10 mg/d
Maintenance 40-80 mg/d (some need > 200 mg/d)
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End points indicating adequate preop preparation are-
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1) Increase until BP control and no more paroxysms ,no in hospital BP
higher than 165/90 should be evident for 48 hours before surgery
2) FBS will return to normal
3) PCV will decline to around 40-43%
4) Orthostatic hypotension should be present, but BP on standing
mg/d)should not be lower than 80/45 mm of Hg
5) ECG must be free of ST-T changes that are not permanent
6) No > 1 premature ventricular contraction should occur every 5 minutes
Preop:  +  blockade
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Phenoxybenzamine (cont’d)
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Side-effect: orthostasis with dosage required to normalized
seated BP, reflex tachycardia
Drawback: periop hypotension/shock unlikely to respond to
pressor agent.
Selective 1-blockers
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Prazosin, Terazosin, Doxazosin
Some experience with Prazosin for Pheo preop prep
Not routinely used as incomplete -blockade
Less orthostasis & reflex tachycardia then phenoxybenzamine
Used more for long-term Rx (inoperable or malignant pheo)
Preop:  +  blockade
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-blockade
Used to control reflex tachycardia and
prophylaxis against arrhythmia during
surgery
 Start only after effective -blockade (may
ppt HTN)
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If suspect CHF/dilated CMY  start low dose
Propanolol most studied in pheo prep
• Start 10 mg po bid  increase to cntrl HR
Preop:  +  blockade
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If BP still not cntrl despite  +  blockade
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Add Prazosin to Phenoxybenzamine
Add CCB, ACE-I
Avoid diuretics as already ECFv contracted
Metyrosine
Preop:  +  blockade
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Medications given on Morning of surgery
 Periop HTN:
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1) IV phentolamine
– Short acting non-selective -blocker
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2) IV Nitroprusside (NTP)
Periop arrhythmia: IV esmolol
 Periop Hypothension: IV crystalloid +/- colloid
Pheo: Rx of HTN Crisis
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IV phentolamine
 IV NTP
 IV esmolol
 IV labetalol – combined  +  blocker
Preop: Metyrosine
Tyrosine
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TH
L-Dopa
Dopamine
Synthetic inhibitor of Tyrosine
DBH
Hydroxylase (TH)
Norepinephrine
Start 250 mg qid  max 1 gm qid
PNMT
S/E’s: sedation, extra pyramidal, diarrhea,, anxiety,
renal/cholelithiasis, galactorrhea N/V
Epinephrine
Alone may insufficiently control BP and reported HTN
crises during operation
Restrict use to inoperable/malignant phaeochromocytoma
or as adjunct to  +  blockade or other preoperative prep
Preop: CCB
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Nicardipine Block norepi mediated ca uptake into
vascular smooth muscles
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Started po 24h to few weeks preop to control BP and allow
ECFv restoration
After intubation  IV Nicardipine (start 2.5 ug/kg/min)
IV Nicardipine adjusted to SBP
Stopped prior to ligation of tumor venous drainage
Tachycardia Rx with concurrent IV esmolol
Advantage: periop hypotension may still respond
to presser agents as opposed to those patients who
are completely -blocked
Perioperative
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Admit night before for overnight IV saline
 2 large bore I/V lines should be secured
 Arterial line
 CVP line
 Routine Pulse oximetry,etCO2,EKG,Temperature
probe
 Known CHF: consider Swan-Ganz
 Regardless of preop medications:
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Have ready: IV phentolamine, IV NTP, IV esmolol
Rx hypotension with crystalloid +/- colloid 1st
Aim for CVP 12 or Wedge 15
Inotropes may not work!
Intraoperative considerations
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Three critical phases of tumor resection are
 1) Induction and intubation
 2) Surgical manipulation
 3) After ligation of the tumors venous
drainage
Induction & Intubation
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Etomidate, thiopental, and propofol can all be used
to initiate anesthesia.
 Increase anesthetic depth by bag mask ventilation
with volatile anesthetic
 Lidocaine 1-2mg/kg 1 min prior to induction
 Narcotics
 Fast acting antihypertensive readily available
 Anesthetic choice:
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En/Sevo/isoflurane: don’t sensitized myocardium to
catecholamines
Halothane: may sensitize heart  arrhythmia
Maintenance(During surgery)
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Anesthesia is maintained with gases and
narcotics. VA are easy to titrate, can help with
HTN (1.5-2 MAC)
 Pt should be kept normovolemic.
 Blood glucose monitoring
 Hypertensive episodes managed by
Deepening volatile anesthetic level
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Nitroprusside @ 0.5-10ugm/kg/m via infusion
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Phentolamine mixed at 10mg/100ml
D 5W(tachycardia can occur,small dose of
esmolol/propranolol can treat it)
Maintenance(During surgery)
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Propranolol/Short acting beta blocker Esmolol
may be required during this period if there is
persistent tachycardia/premature ventricular
contractions
Ligation of the tumors venous
drainage
↓ circulating catecholamine causing hypotension
 After ligation of all venous drainage arterial
pressure commonly declines r/t ↑CO, ↓ SVR
Treatment
 ↓ VA
 ↑ IVF
 Phenylephrine or nor epinephrine
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Postop
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1) Invasive lines should stay intact. Pt still at risk
for liable BP.
 2) Pt susceptible to hypotension that is refractory
to fluid volume expansion
 3) Still have high volumes of circulating
catecholamine despite tumor resection
 4) Catecholamine levels normalize after several
days. 75% of pts BP returns to normal after 10
days
 5) Prone to Hypoglycemia. Secondary to
suppression of β-cell function disappears after the
tumor is removed
Pheo & Pregnancy
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Diagnosis with 24h urine collections and MRI
 No stimulation tests, no MIBG if pregnant
 1st & 2nd trimester (< 24 weeks):
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Phenoxybenzamine + blocker prep
Resect tumor laprascopically
3rd trimester:
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Phenoxybenzamine + blocker prep
When fetus large enough: cesarian section followed by tumor
resection
Addison's disease

Addison's disease is characterized by decreased or absent glucocorticoid
secretion, usually combined with mineralocorticoid insufficiency. It can be
primary or secondary and may present as an acute, chronic, or acute-on-chronic
illness. The most common cause is autoimmune.
A) Clinical features
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Postural hypotension & dizziness
Hyperkalemia & Hyponatremia
Hypoglycemia
Nausea, vomiting, diarrhea, and weight loss.
Decreased body hair.
Pigmentation especially in areas exposed to the sun.
Can be associated with pernicious anemia, myasthenia gravis, and vitiligo
May not be clinically obvious until a significant stress occurs
B) Investigations1) Low serum glucose.
2) Low Na+, raised K+ and urea
3) Low Bicarbonates,Nomocytic anemia
4) Plasma ACTH-measure simultaneously with plasma cortisol at 08:00h. Even if
cortisol is normal the ACTH will be elevated.
5) Plasma renin activity and aldosterone—plasma renin activity is usually low with
a low aldosterone.
6) Short Synacthen(Cosyntropin) stimulation test—250 µg of Synacthen dissolved
in 1 ml of sterile water is given i/v or i/m. Serum cortisol is measured 30-60 min
later. A serum cortisol >495 nmol/litre excludes the diagnosis.
C) Management 1) Hydrocortisone 200 mg IV should be given immediately, then 100 mg 6hourly IM or 200 mg/24 h IV, until oral replacement is possible(Hydrocortisone
orally: 20 mg in the morning and 10 mg at night)
 2) Fludrocortisones to replace aldosterone:0.05- 0.1 mg daily orally.
 3) To maintain NaCl daily intake to 3-4gm/d
 4) Fluid resuscitation with CVP guidance. 0.9% saline is an appropriate fluid
with 50% dextrose infused if hypoglycaemia occurs.
 5) Inotropes if hypotension persists. The choice of inotrope will depend on the
clinical picture, i.e. noradrenaline if the patient has severe vasodilatation.
Perioperative management of
patients with Addison's disease
1)Give all medication up to the morning of surgery.
2)25 mg IV hydrocortisone should be given at induction.
3)Small or intermediate cases should be managed as per perioperative
steroids
4)In major cases, hydrocortisone 200 mg/24 h should be used until the
patient can be weaned back onto maintenance therapy.
5) Blood glucose and electrolytes.
POSTOPERATIVELY To continue Hydrocortisone I/v until oral maintenance dose is
started
 To start fludrocortisone 0.05-0.1 mg/d
 Monitor Blood glucose
 Monitor daily electrolytes
Cushing's syndrome
Cushing's syndrome is a collection of signs and symptoms due to an excessively
high plasma cortisol. The most common cause of Cushing's syndrome is
treatment with glucocorticoid drugs. Anesthetists will see this syndrome in:
1) Patients having pituitary or adrenal surgery to resects tumors causing a raised
cortisol.
2) Patients with malignant tumors. These occasionally secrete an ACTH-like
hormone that causes profound Cushinoid features. Oat cell carcinoma of the
lung is a common cause.
3) Patients on high-dose steroid therapy.
Clinical featuresMoon face and truncal obesity.
Proximal myopathy and osteoporosis.
Easy bruising and fragile skin.
Impaired glucose tolerance, diabetes.
Hypertension and left ventricular hypertrophy.
Hypernatremia and hypokalaemia.
Gastrointestinal reflux & Sleep apnea.
Diagnosis
1)Classical clinical features are often seen but will not differentiate the various causes
of a raised cortisol level. Urinary free cortisol or lack of diurnal variation will
confirm a pathological cause but will not define the etiology.
2)The ‘short dexamethasone suppression test’ (1 mg of dexamethasone is given at night
and a cortisol sample taken in the morning) is a sensitive test to confirm abnormally
raised serum cortisol. Serum cortisol will be suppressed in the morning if the HPA
axis is working normally.
3)Serum ACTH levels will help determine if adrenal or pituitary pathology is the cause.
4)Very high ACTH levels suggest ectopic production, e.g. carcinoma of the lung, and
very low levels suggest adrenal hyper secretion.
5)The ‘high dose dexamethasone suppression test’ (2 mg is given 6-hourly for 48 h and
serum cortisol measured) will cause a fall in early morning and urinary free cortisol
on the second day in pituitary-dependent Cushing's syndrome, but not in ectopic or
adrenal causes.
6)Inferior petrosal venous sinus sampling following CRH stimulation is the final
confirmatory test for pituitary Cushing's syndrome.
7)MRI scan of the pituitary fossa.
Treatment of cushing syndrome
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1) Selective Transsphenoidal resection is treatment of choice for Cushing
disease(Pituitary micro/macroadenoma)
2) Adrenalectomy uni/bilateral needed( for adrenal adenoma/carcinoma)
3) Pt will be medically treated prior to surgery with focus on decreasing synthesis
of steroids by -Aminoglutethimide,Ketoconazole
-Mitotane
-Metyrapone & Cyproheptadine
4) Spirinolactone to control BP & restore electrolyte balance may be needed
5) Insulin to control plasma glucose levels may be required
6) All above measures contd. to the day of surgery
Preoperative assessment
1) 85% of patients are hypertensive and are often poorly controlled.
2) ECG abnormalities (high-voltage QRS and inverted T waves) can make IHD
difficult to exclude but will revert to normal after curative surgery. These ECG
changes seem to be related to the Cushing's disease itself.
3) 60% of patients have diabetes or impaired glucose tolerance and a sliding scale
should be started before major surgery if glucose is >10 mmol.
4) Gastroesophageal reflux is common and preoperative acid suppression therapy
and rapid sequence induction should be considered.
5)Venous access can be very difficult.
6) Patients can be obese and appropriately sized blood pressure cuffs, operating
tables, and supports should be ordered.
INTRAOPERATIVELY
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1) Careful positioning of pt because of osteoporosis
2) Despite routine monitoring CVP is monitored as these pt tend to have higher
CVP
3) Adequate control of blood sugar
4) We normally begin administering glucocorticoids at the start of resectioning of
tumor @ 100 mg of Hydrocortisone hemi succinate/phosphate i/v
POSTOPERATIVELY 1) Hydrocortisone @ 100 mg/24 hr is contd. i/v on the day of surgery
& reduced over a period of 3-6 days until maintenance dose is
reached
 2 )Beginning on the day 3rd a mineralocorticoid fludrocortisone @
0.05-0.1mg/day orally started