Transcript Hypertension related to Endocrine Disorders

Hypertension associated with
Endocrine Disorders
Hypertension assoc with
Endocrine Disorders
Background
• Prevalence/Incidence- Unknown
– Requires the application of highly sensitive and specific
screening tests
• Expensive and not risk free
• Clues helpful in identifying patients
– Hypertension at a young age
• Essential hypertension onset typically 40s+
– Sudden onset or increased severity
– Drug resistant hypertension
Hypertension assoc with
Endocrine Disorders
Background
• Most common forms
– Primary aldosteronism
– Pheochromocytoma
– Cushings
Primary Aldosteronism
Prevalence and Pathophysiology
• Second only to renal
vascular hypertension
as a cause of curable
hypertension
• 2 large studies in
known hypertensives
revealed a prevalence
exceeding 9%
Primary Aldosteronism
Prevalence and Pathophysiology
Insert a picture of renal distal tubule and exchange of K
and H for Na
-hypervolemia/hypertension 2nd to increased Na
-alkalosis 2nd to decreased H+ and decreased K+
Primary Aldosteronism
Prevalence and Pathophysiology
• Associated findings
– Hypernatremia
• Usually in the range of 143-147
– Hypervolemia
• Usually without peripheral edema– due to aldosterone escape
(probably mediated by atrial naturitic peptide and a pressure
naturesis). Confirmed by decreased renin levels.
– Hypertension
• Due to the mild volume expansion (as above)
Primary Aldosteronism
Prevalence and Pathophysiology
Hypokalemia
• Esp intracellular depletion, leading to glucose intolerance,
EKG changes c/w LVH, muscle weakness, and polyuria
• Must have adequate sodium delivery for this to occur
– If sodium restricted, no hypertension/no hypokalemia
– If volume depleted (less distal sodium delivery), also no
hypokalemia
» That is why diuretics (HCTZ) paradoxically improves K
levels
– Hypomagnesemia
– Renal cysts- 2nd to hypokalemia
Primary Aldosteronism
Screening tests
• Serum potassium level
– Traditionally advocated as the most effective
single screening test
• One large study revealed normal plasma K levels in
ALL patients with primary aldosteronism (Fardella,
J Clin Endo Meta 2000)
• Another study (Loh, JCEM) only 6/16 with
biochemically confirmed hyperaldo had
hypokalemia
• 20% of surgically confirmed hyperaldo have normal
plasma K
– Some argue serum K artificially high due to increased
hemolysis which is increased in hyperaldosterone states
Primary Aldosteronism
Screening tests
• Serum potassium level
– Traditionally advocated as the most effective
single screening test
• GRH usually doesn’t have hypokalemia
– But the aldo in this disease is under ACTH stimulation
which peaks in the am. Therefore only exposed to
elevated levels for transient periods
• So recommended to w/u for hyperaldo, even with a
normal K, if:
– Severe or refractory hypertension
– Onset at a young age
– Sudden increase in BP
Primary Aldosteronism
Screening tests
• Serum potassium level
– If it is truly low, then measure a 24hr urine
potassium
– If >30meq/day in the face of hypokalemia, then renal
wasting (hyperaldo) is present
– If <30meq/day, the hypokalemia is due to an extrarenal
source
– Vomiting
– Diarrhea
• As K excretion is dependent upon adequate distal
sodium delivery
– Patient should be on a normal to high Na diet (so check a
concurrent urine Na)
– Can be used as a screening test as well– if increased Na
decreases K, this is a strong indication of non-suppressible
aldosteronism
Primary Aldosteronism
Screening tests
• Low renin
– Better screening test
– Almost all cases of uncomplicated primary
aldosteronism have low renin. Suppressed by:
• Elevated blood pressure
• Elevated sodium and expanded extracellular volume
Primary Aldosteronism
Screening tests
• Low renin
– Not diagnostic of hyperaldo
• 40% of patients with essential hypertension manifest
suppressed plasma renin levels
• Anti-hypertensive agents also known to lower renin
levels
– Antisympathetic drugs, central or peripheral can suppress
plasma renin levels (How?)
– Beta-blockers also suppress plasma renin levels
Primary Aldosteronism
Screening tests
• Aldo/PRA level—any provocative
measures?
– Most sensitive and specific screening test
– Performed only after agents known to suppress
renin (beta-blockers and alpha-blockers) have
been discontinued- no consensus on with or
without medications
– Draw out the feedback mechanism
– > 30 = primary aldosteronism, usually a
unilateral adenoma
– 15-30 = suggestive of aldosteronism, usually
due to bilateral adrenal hyperplasia
Primary Aldosteronism
Screening tests
• Aldo/PRA level—any provocative
measures?
– Best to try and suppress aldo and stimulate pra
• Suppress aldo– avoid K loading and maximize the
volume status (250meq Na qd x 3 days with liberal
water intake). Recumbent
• Stimulate PRA- standing or hypovolemic (diuretics)
– As can see, if you stimulate one, you suppress
the other
• If you suppress aldo, you suppress renin, so ratio
doesn’t change
• If you stimulate PRA, you stimulate aldo- so ratio
doesn’t change
Primary Aldosteronism
Screening tests
• Aldo/PRA level
– Theoretically can even be used with drugs
known to stimulate renin release
• Including: diuretics, ACE inhibitors, calcium
channel blockers, and other vasodilators
• Might decrease sensitivity slightly
– A positive test would still be valid
– A negative test might not be definitive, because the
increased renin level might artificially lower the ratio
• Best to try on the drugs first- it can allow you to
safely make the diagnosis without withdrawing the
drugs
Primary Aldosteronism
Diagnosis
• Traditionally
– Demonstration of excessive aldosterone
production plus suppression of the normal
stimulus (renin/angio II)
• Required suppressive maneuvers to demonstrate
hyperaldo
– Several days of high salt diet, intramuscular
mineralocorticoids to ensure sodium retention and volume
expansion, or bolus of NS
• Required a stimulative maneuvers to demonstrate
suppressed renin levels
– Low salt diet + diuretic
Primary Aldosteronism
Diagnosis
• Currently
– Application of the standard screening test–
unstimulated aldo/pra level in a patient not
taking any drugs known to impact the axis
(which leaves what?)
• Drug effect
• What about K level–
– If high– stimulates aldo
– If low– suppress aldo
» Must it be in the normal range for these tests?
» I would think low is ok, but high must be treated
Primary Aldosteronism
Differentiation of Subtypes
• Unilateral adrenal adenoma
– Most common form of primary
aldosteronism
• 60-65% of the cases
– Most amenable to surgical
intervention
– Usually small (1 cm or less)
• Therefore localization
techniques based on anatomy
alone may not be effective
– MRI- only 60% sensitive
– Adrenal venographydangerous
– Isotopoic scanningdisappointing
Primary Aldosteronism
Differentiation of Subtypes
• Unilateral adrenal adenoma
– Biochemical techniques the best
• Unilateral adenoma is modulated by ACTH, but not
angiotensin II
– Why?
» Adenoma is closer to malignancy, therefore more
autonomous and less likely to respond to normal feed
back. Versus hyperplasia which is still responsive to
normal feedback, just at an elevated level
Primary Aldosteronism
Differentiation of Subtypes
• Unilateral adenoma is modulated by ACTH, but not
angiotensin II
– Check aldo level when renin system quiescent (early
morning after sleeping recumbent) but ACTH maximally
stimulated by morning surge
– Check aldo again after activation of the renin system- in
the afternoon or after a diuretic dose, when the ACTH
system is quiescent
• Unilateral– high aldo in am (with ACTH surge) and
lower in the pm (refractory to renin surge)
• Bilateral- lower in the am due to quiescent renin
system, then peaking in the pm with the increased
renin
Primary Aldosteronism
Differentiation of Subtypes
• Unilateral adenoma is modulated by ACTH,
but not angiotensin II
– Check aldo level when renin system quiescent (early
morning after sleeping recumbent) but ACTH maximally
stimulated by morning surge
– Check aldo again after activation of the renin system- in
the afternoon or after a diuretic dose, when the ACTH
system is quiescent
• Unilateral– high aldo in am (with ACTH surge) and
lower in the pm (refractory to renin surge)
• Bilateral- lower in the am due to quiescent renin
system, then peaking in the pm with the increased
renin
Primary Aldosteronism
Differentiation of Subtypes
• Adrenal venous blood sampling
– Most sensitive and specific way of separating
unilateral and bilateral forms of the disorder
– Test often misleading due to errors
• Right adrenal vein difficult to locate
• Multiple adrenal venous drainage or adrenal effluent
diluted by blood from other sources such as the
phrenic vein or left renal vein
Primary Aldosteronism
Differentiation of Subtypes
• Attempts made to minimize these errors by
giving a continuous infusion of ACTH
(which stimulates cortisol) during the
sampling
– By expressing sampling as ratio of aldosterone
to cortisol
• Correct for dilution of the adrenal venous blood
• Even allows for identification in the absence of the
ability to sample on adrenal vein
– Check the ratio in the IVC, if higher, then the lesion is in
the unsampled gland
Primary Aldosteronism
Treatment
• Unilateral lesion
– Adrenalectomy almost always uniformly
effective in eliminating the hyperaldosteronism
– 70% of people can be withdrawn for antihypertensive agents completely
• May take months before the final nadir in blood
pressure is seen
Primary Aldosteronism
Treatment
• Bilateral disease
– Medical treatment is preferred
– Traditionally, spironolactone is the agent of
choice
• Required high dose– up to 800mg/day
• Painful gynecomastia, impotence, and decreased
libido often leads to discontinuation. Women also
affected- menstrual irregularities
– Amiloride is my drug of choice
• 5 mg po bid, increased to 15mg po bid
• Same effect as spironolactone with rare side effects
• Usually requires HCTZ as adjunct
Primary Aldosteronism
Treatment
• Bilateral disease
– ACE-I are still effective
• Would expect a poor response given the relatively
low renin/angio II state
• However patients with bilateral disease may simply
be due to increased sensitivity to even low levels of
angio II– therefore blocking it is very effective
Pheochromocytoma
Background
• Less frequent than primary
aldosteronism
• First manifestation can be a
catastrophic outcome
– Must r/o in a hypertensive
pregnant patient with labile bp
• Symptoms are protean
– Usually directly attributable to
catacholeamine excess and thus
must be differentiated from other
syndromes of catecholamine
excess (also known as
pseudopheochromocytoma)
– Only 1 in 300 work-ups positive
Pheochromocytoma
Background
• 85% result from adrenal
medullary tumors
– If extra adrenal, almost
always below the
diaphragm (usually in the
periaortic area)
– Can be associated with
MEN syndromes
• IIa- assoc with thyroid and
parathyroid tumors
• IIb- assoc
ganglioneuromas- Von
Hippel-Lindau syndrome
and other neuroectodermal
abnormalities
Pheochromocytoma
Symptoms
• Non-specific
– Headache, diaphoresis, pallor, tachycardia,
anxiety or tremulousness, nausea, weakness,
chest pain, dyspnea, fever, weight loss
– Sustained elevation of bp is the most frequent
finding
• But 1/3 patients have episodic or paroxysmal
hypertension
• 10-15% have normal blood pressure
• In a recent Italian review of 284 pts,
– 67% paroxysmal, 59% hypertensive crisis, and 21%
normal bp
Pheochromocytoma
• Non-specific
– Grade III or IV
hypertensive retinopathy
• In >50% of patients
– Presumably owing to
the intense
vasoconstriction
resulting from the
excessive catecholamine
production
– Dilated cardiomyopathydue to the toxic effects of
long term catechols
– Secondary erythrocytosis
due to overproduction of
erythropoietin
Symptoms
Pheochromocytoma
Symptoms
• Paroxysmal nature of
symptoms
– Understandable given
the variety of stimuli of
catecholamine release,
with an exaggerated
response occurring in
pheochromocytoma
cases
Pheochromocytoma
Background
• Normotensive or hypotensive variants
– Suggested that the intense vasoconstriction and
elevated bp induced by the release of
catecholamines
• Result in a contracted intravascular volume (like a
cold induced diuresis)
• Suppressed baroreceptor reflex
– Also could be the result of release of “renaldose dopamine” by the tumor
• Resulting in generalized vasodilitation
Pheochromocytoma
Background
• Paradoxical rise in BP with antihypertensive medications
– Beta-blockers can cause a paradoxical
hypertension
• Due to the resulting unopposed alpha induced
vasoconstriction
Pheochromocytoma
Background
• Metabolic abnormalities
– Hyperglycemia and glucose intolerance
• Associated with epinephrine induced insulin
resistance
– Lipid abnormalities
– Hypokalemia
• Due to cellular shifts associated with epi release
Pheochromocytoma
Pseudo-pheochromocytoma
• Pheo mimicked by a variety of
circumstances
– All usually feature excessive catecholamine
production or stimulation of adrenergic
receptors
• Use of sympathomimetic agents- nasal sprays, cold
remedies, diet aids, ephedrine, amphetamines,
• Administration of drugs with containing
sympathomimetic side effects- imipramine and
amitrypiptyline (esp if given MAO-Is*)
• Addictive Substance withdrawal
• Withdrawal from alpha or beta-blockers
Pheochromocytoma
Pseudo-pheochromocytoma
• MAO-Is
• 3 currently available in the United States
• All three are anti-depressant drugs
– Nardil (phenelzine)
– Parnate (tranylcypromine)
– Marplan (isocarboxazid)
Pheochromocytoma
Pseudo-pheochromocytoma
• Pheo mimicked by a variety of
circumstances
– All usually feature excessive catecholamine
production or stimulation of adrenergic
receptors
• Use of sympathomimetic agents- nasal sprays, cold
remedies, diet aids, ephedrine, amphetamines,
• Administration of drugs with containing
sympathomimetic side effects- imipramine and
amitrypiptyline (esp if given MAO-Is)
• Addictive Substance withdrawal
• Withdrawal from alpha or beta-blockers
Pheochromocytoma
Screening Tests
• Availability of sensitive and specific measures of catechols
and their metabolites in urine and plasma, provides for safer,
convenient, and reasonably accurate was to screen.
• Still fraught with inaccuracy
– Plasma values for catechols can be in the normal range if
the tumor releases catechols intermittently
– Urine studies can be incomplete collections. Spot samples
can be in error if episodic hormone release
– Choice of specific metabolite for measurement
• Often required to check total catechols, norepi, metanephrine,
normetanephrine, vanillylmandelic acid, and/or homovanillic acid
to ensure the patient does not have a pheo
Pheochromocytoma
Screening Tests
• Most antihypertensive agents elevate catechols
– Exceptions- centrally acting alpha-adrenergic
agonists (clonidine, guanabenz, guanfacine) and
reserpine)
– Much like with hyperaldo
• First do the screening tests while on their baseline
medications
• Then if elevated, you are forced to change their antihypertensive regimen to r/o a drug induced falsepositive
Pheochromocytoma
Screening Tests
• Measurement of plasma or urine catecholamines and metabolites is
diagnostic in 95% of patients with symptoms
– Uncertainty regarding the “best” test
– Urinary catecholamine
• Nearly all patients will have an elevated value for catechols and
metabolites
– Larger tumors have more metabolites (VMA and Metanephrines) due
to metabolism within the tumor itself
– Smaller tumors have a greater proportion of free catechols
• Urinary total metanephrines
–
–
–
–
May be the most useful test
Lest likely to be affected by drugs and foods *****
Above 1.2 mg/day is highly suggestive of pheo
False positive occurs with buspirone (metabolite measured as a
metanephrine)
Pheochromocytoma
Screening Tests
• Measurement of plasma or urine catecholamines and
metabolites is diagnostic in 95% of patients with symptoms
– Uncertainty regarding the “best” test
– Plasma catecholamines
• Total catechol level (Norepi + epi)
– >2000 pg/mL in a supine patient with an indwelling cath x 30
minutes is diagnostic
– >950 pg/mL is suggestive
– Because false positives are common, should also combine with
suppression testing
» Give 0.3mg of clonidine
» Measure total catechols before and 3 hours after
-No pheo, the level will drop to <500
Pheo
Diagnosis
• Localization
– Most pheos are > 2cm in
diameter
• CT sensitivity- 99% for
intraadrenal and 91% for
extra adrenal tumors
• MIBG isotopic scanslightly lower sensitivity at
88.5%
– Because hemorrhagic
necrosis and subsequent
calcification are frequent
• Often seen on plain films
Pheochromocytoma
Treatment
• Preferred treatment is surgical removal of the
tumor
– Surgeon must ligate the major blood supplies to
reduce the amount of catechols introduced into
circulation
– 7-10 days of pre-operative alpha-adrenergic
blockade prior to surgery
• Not for bp or arrhythmia control intra-op
• To permit the contracted intravascular volume to return
to normal
– Otherwise the vasodilitation associated with tumor removal
results in profound hypotension
Pheochromocytoma
Follow-up
• Multiple and malignant tumors occur in about
10% of patients
– Requires q 6-12 month follow-up
• Don’t forget to screen family members
– Need to r/o a familial (MEN-type) syndrome
• Esp if tumor is epi predominant
Pheochromocytoma
“Think of it, confirm it, find it, and remove it”
• Think of it
– Mayo review of over 40,000 autopsies found 54
pheos,
• 41 (76% ) not diagnosed until the time of death
• 23 (55%) had retrospectively been the cause of
death
– Swedish study (Svardsudd) found similar
results
• 40% had the diagnosis made at autopsy
Pheochromocytoma
“Think of it, confirm it, find it, and remove it”
• Think of it
– NE tumors
• Primarily present with stable hypertension
– Just like being on a chronic norepi drip
– Epi tumors
• Primarily associated with adrenaline-like symptoms
• Can have hypoK, hyperglycemia
Pheochromocytoma
“Think of it, confirm it, find it, and remove it”
• Think of it
– Differential diagnosis
Essential hypertension
Other forms of secondary HTN
MAO-I induced hypertensive crisis
Hypertensive encephalopathy
Anxiety
Hyperthyroidism- but never assoc c inc diastolic blood pressure
Migraine/Cluster Headaches
Intracranial Lesions
Pre-eclampsia
Carcinoid
Hypoglycemia, Mastocytosis, Adrenal Ca
Pheochromocytoma
“Think of it, confirm it, find it, and remove it”
• Confirm it
– Typically requires biochemical diagnosis
– Don’t go looking with a CT first
• Rate of incidentalomas = XXXX
• If you clinically suspect a pheo and get a scan first,
it will be nearly impossible to r/o an incidentalomas.
You have just committed the patient to surgery
Pheochromocytoma
Biochemical Diagnosis
• Diagnosis requires evidence of excessive
catecholamine production by the tumor
– Usually achieved by measurement of catechols and
metabolites in urine or plasma
• Unfortunately, norepi and epi are also produced by
sympathetic nerves and the adrenal medulla, and
therefore not specific for pheochromocytoma
– High levels of catechols and metabolites can be
produced disease states associated with increased
sympathetic nervous and adrenal medullary release
Pheochromocytoma
Biochemical Diagnosis
• Understanding catecholamine release and
metabolism under normal conditions as well
as disease states, can help understanding the
utility and limitations of biochemical tests
for the diagnosis of pheochromocytoma
1. Both norepi and epi are metabolized by a multiplicity
of pathways, resulting in a considerable number of
metabolites
2. MAO is a neuronal enzyme, COMT is a bloodstream
enzyme and in pheo/adrenal cells
Tyrosine
Dopa
3. Adrenal gland/pheo secrete directly into bloodstream.
Sympathetic nerves secrete into neurons
Homo-vanillic
acid
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheochromocytoma
Non-neuronal (bloodstream) metabolism
1. Pheos differ from sympathetic nerves, but are similar
to adrenal medullary cells, in that they secrete catechols
Tyrosine directly into the bloodstream. Acted upon by COMT
leading to the formation of metanephrines
Dopa
m-PST
Normetanephrine
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheochromocytoma
Neuronal Metabolism
1. Sympathetic nerves which have high concentrations of
MAO. As a result, all sympathetic nervous system norepi
Tyrosine is converted to DHPG. No metanephrine formation
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
1. Norepi from sympathetic nervous system appears
almost exclusively as DHPG. While non-sympathetic
norepi (adrenal and pheo) is metabolized to
normetanephrines
Tyrosine 2. High NE + high DHPG = sympathetic (No pheo)
High NE + normal DHPG = pheo
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
3. Can see why VMA is a lousy marker of a pheo. It is
primarily derived from the metabolism of neuronal
epi and norepi (i.e. non-pheo sources).
Tyrosine
1. For a pheo to raise VMA, it must take a nonfavored route of normetanephrine taken up by
sympathetic nerves, metabolized by MAO, to
VMA
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheochromocytoma
Pheo vs. Adrenal
Tyrosine
1. Adrenal gland primarily makes epi (adrenaline), while
most non-familial pheos make primarily norepi
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheochromocytoma
Pheo vs. Adrenal
1. Because COMT is IN pheo cells, the conversion of
norepi to metanephrines is always occurring. That is
Tyrosine why metanephrines are a better marker than elevated
norepi (which may be produced episodically).
Metanephrines are produced independent of norepi
Dopa
release.
m-PST
Normetanephrine
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheochromocytoma
Sensitivity
Tyrosine
Dopa
1. Problem with the use of plasma or urinary catechol
levels is some tumors are quiescent or may not
secrete large amounts of catechols.
2. In contrast, plasma metanephrines always elevated, so
a normal level rules out pheo
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheochromocytoma
Sensitivity
Tyrosine
1. Because m-PST is found throughout body tissues
(smooth muscle and liver), the metanephrine sulfates
(measured in the urine) are a less sensitive marker
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Specificity
1. Plasma and urinary catechols may be elevated in a
variety of physiological, pharmacological, and
pathologic conditions
Tyrosine
Dopa
Ex. Exercise, mental stress, low bp, low blood volume, hypoglycemia, CHF,
renovasc hypertension, shock, sepsis, panic disorder, etc
2. Can see that metanephrines less likely to be elevated
due to sympathetic nervous system over activity
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Specificity
1. Other problems
1. Metabolites cleared by the kidneys- so build up in
renal failure
Tyrosine
2. MAO-I obviously inhibit this pathway
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Specificity
1. Ruling out sympathetic over activity
1. Clonidine suppression test
Tyrosine
Dopa
Normetanephrine
m-PST
Normetanephrinesulfate
Dopamine
Norepi
MAO
DHPG
Epi
COMT
MHPG
ADH
VMA
MAO
m-PST
Metanephrine
Metanephrinesulfate
Pheo
confirm et
• Confirm it
– Interfering drugs
• Levadopa, MAO-Is, benzodiazepenes, buspirone,
methyldopa, chlorpromazine,
– Precipitate a crisis
• Reglan, TCAs, naxalone, and anti-dopaminergic
drugs
Pheo
“Think it, Confirm it, Find it, Remove it”
• Confirm it
– Catechol or metabolite secretion in 24hr urine is
checked at least twice, and/or
• In the case of definitely pathologic findings (at least 100% in
excess of the normal range), search for the tumor is begun
– Catechol plasma levels are determined under
standardized conditions (supine, 30 minutes after
cannulation), and/or
– Measurement of plasma metanephrines
– Clonidine testing is performed in patients with
moderately raised “basal” plasma catechols (NE + E
1000-2000). If insufficient suppression, search for
tumor is begun