Endocrine Hypertension:Endocrine Hypertension:Sorting through Complex CasesSorting through Complex Cases

Lawrence S. Kirschner, MD, PhDLawrence S. Kirschner, MD, PhD

Division of Endocrinology, Diabetes and Division of Endocrinology, Diabetes and MetabolismMetabolism

Human Cancer Genetics ProgramHuman Cancer Genetics ProgramThe Ohio State University Medical CenterThe Ohio State University Medical Center

Causes of HypertensionCauses of Hypertension

DiagnosisDiagnosis General popGeneral pop’’nn Specialty popSpecialty pop’’nn

EssentialEssential 9292--9494 6565--8585

Renal Renal (parenchymal, (parenchymal, renovascular)renovascular)

33--55 88--2020

EndocrineEndocrine 22--44 22--1414

OtherOther 11 11

From Harrison’s 11th ed.

Case history: EDCase history: ED

Mr D is a 56 year old man who presents to Mr D is a 56 year old man who presents to his new PCP with a history of hypertension his new PCP with a history of hypertension >10 years>10 years–– BP Meds: Hyzaar, NifedipineBP Meds: Hyzaar, NifedipineClinically without complaintsClinically without complaintsPMHxPMHx–– BPH, Renal cyst, hyperlipidemia, kidney stoneBPH, Renal cyst, hyperlipidemia, kidney stone–– Abd GSW requiring laparotomy, but no residual, Abd GSW requiring laparotomy, but no residual,

AppApp--x, GBx, GB--xxFamHx:FamHx:–– Mom: HTN, DM. Father: Kidney diseaseMom: HTN, DM. Father: Kidney disease

ED ED -- 22

Meds: Meds: –– Oxybutinin, Hyzaar, NifedipineOxybutinin, Hyzaar, Nifedipine

Exam:Exam:–– BP 160/100 (180/120), HR 72BP 160/100 (180/120), HR 72–– Exam otherwise WNLExam otherwise WNL

Labs:Labs:–– K 3.5, BUN 11, Creat 0.85K 3.5, BUN 11, Creat 0.85

Does this gentleman merit Does this gentleman merit evaluation for endocrine causes of evaluation for endocrine causes of

HTN?HTN?

1 2 3 4

20%

7%8%

65%1.1. Not necessaryNot necessary2.2. Yes, for hyperaldoYes, for hyperaldo3.3. Yes, for pheoYes, for pheo4.4. Yes, for Yes, for

something elsesomething else

When should patients be screened for When should patients be screened for Primary Hyperaldosteronism?Primary Hyperaldosteronism?

Stage 2 hypertensionStage 2 hypertension–– SBP 160SBP 160--179, DBP 100179, DBP 100--109109–– Incidence: ~8%Incidence: ~8%

Drug resistant hypertensionDrug resistant hypertension–– Requiring 3 or more drugsRequiring 3 or more drugs–– Incidence: ~20%Incidence: ~20%

Hypertensive patients with hypokalemiaHypertensive patients with hypokalemia–– Spontaneous hypokalemiaSpontaneous hypokalemia–– DiureticDiuretic--induced hypokalemia (?)induced hypokalemia (?)–– Incidence: unknownIncidence: unknown

Hypertension in patients with adrenal incidentalomaHypertension in patients with adrenal incidentaloma–– Incidence: ~2%Incidence: ~2%

Family history of earlyFamily history of early--onset HTN and/or CVA (<40 yo)onset HTN and/or CVA (<40 yo)–– Incidence: unknown, although these patients are rareIncidence: unknown, although these patients are rare

Endocrine Society Guidelines: 2008

ED ED -- 33

At followAt follow--up (2 weeks later), K=3.1up (2 weeks later), K=3.1PCP elects to perform endocrine W/UPCP elects to perform endocrine W/ULabs:Labs:–– Aldo: 19.1 ng/dl (nl 5Aldo: 19.1 ng/dl (nl 5--19.4)19.4)–– Renin: <0.1 ng/ml/hrRenin: <0.1 ng/ml/hr–– Urine metanephrines WNLUrine metanephrines WNL

What next?What next?

1 2 3 4

18%13%

32%

37%1.1. Order additional Order additional

static testingstatic testing2.2. Order additional Order additional

dynamic testingdynamic testing3.3. Order imagingOrder imaging4.4. Start therapyStart therapy

Static testing: Static testing: PheochromocytomasPheochromocytomas

Evaluation for pheochromocytoma takes 2 Evaluation for pheochromocytoma takes 2 forms:forms:–– Plasma metanephrinesPlasma metanephrines

Highly sensitive, less specific (many false positives)Highly sensitive, less specific (many false positives)

–– Urinary metanephrines + catecholsUrinary metanephrines + catecholsHighly sensitive, better specificity, more Highly sensitive, better specificity, more inconvenienceinconvenience

Tests for pheo Tests for pheo –– NIH dataNIH data

Lenders et al, Ann. NY Acad. Sci. 970:29-40 (2002)

Tests for pheo Tests for pheo –– Mayo dataMayo dataTestTest SensitivitySensitivity SpecificitySpecificity Likelihood Likelihood

ratio of a ratio of a positive test positive test

(95% CI)(95% CI)

Likelihood Likelihood ratio of a ratio of a

negative test negative test (95% CI)(95% CI)

Fractionated Fractionated plasma plasma metanephrinesmetanephrines

30/31 30/31 (97)(97)

221/261221/261(85)(85)

6.36.3(4.7(4.7--8.5)8.5)

0.040.04(0.006(0.006––0.26)0.26)

2424--h urinary h urinary total metatotal meta--nephrines or nephrines or catecholamines catecholamines (either test (either test positive)positive)

28/31 28/31 (90)(90)

257/261257/261(98)(98)

58.958.9(22.1(22.1--156.9)156.9)

0.100.10(0.03(0.03--0.29)0.29)

Sawka et al, JCEM 2003 88:553-558

Static testing?Static testing?

Evaluation for pheochromocytoma takes 2 Evaluation for pheochromocytoma takes 2 forms:forms:–– Plasma metanephrinesPlasma metanephrines–– Urinary metanephrines + catecholsUrinary metanephrines + catechols

However, elevated Aldo/renin ratio However, elevated Aldo/renin ratio probably means this is not necessaryprobably means this is not necessary

Caveat about Aldo/Renin ratioCaveat about Aldo/Renin ratio

As PRA drops, ARR increases dramatically

Montori et al, Mayo Clinic Proc. (2001) 76:877-883

Dynamic testingDynamic testing

Confirmatory tests for Confirmatory tests for hyperaldosteronism:hyperaldosteronism:–– Oral salt loading testOral salt loading test–– IV saline suppression testIV saline suppression test

What was actually done:What was actually done:

WhatWhat’’s the diagnosis?s the diagnosis?

1 2 3

31%

44%

25%

1.1. Unilateral hyperaldo Unilateral hyperaldo (tumor)(tumor)

2.2. Bilateral hyperaldo Bilateral hyperaldo (hyperplasia)(hyperplasia)

3.3. Not sureNot sure

Imaging:Imaging:In general, CT scan provides better spatial resolution In general, CT scan provides better spatial resolution than other modalitiesthan other modalitiesHowever, aldosteronomas may be quite small and However, aldosteronomas may be quite small and difficult to identifydifficult to identify–– Adrenal incidentalomas are also commonAdrenal incidentalomas are also common

In multiple studies, CT correctly identified a surgicallyIn multiple studies, CT correctly identified a surgically--proven adenoma in ~50% of casesproven adenoma in ~50% of casesFunctional imaging (e.g., metomidate PET) may be Functional imaging (e.g., metomidate PET) may be available available –– Although this can identify adrenocortical issue with high Although this can identify adrenocortical issue with high

specificity/sensitivity, functional differentiation between normspecificity/sensitivity, functional differentiation between normal al and abnormal adrenal is currently is not feasible.and abnormal adrenal is currently is not feasible.

Adrenal hyperplasia?Adrenal hyperplasia?

Remember that nodules can arise in the setting of hyperplasia

Is there value to additional Is there value to additional imaging?imaging?

Radiology report reads: Radiology report reads: ““Adrenal nodules Adrenal nodules detected by CT. Recommend MRI.detected by CT. Recommend MRI.””

Is this a reasonable recommendation?Is this a reasonable recommendation?–– Chemical shift MRI can identify lipid rich adrenal Chemical shift MRI can identify lipid rich adrenal

nodules, but this information available from nonnodules, but this information available from non--contrast CTcontrast CT

–– MRI may be valuable to detect pheo (T2 MRI may be valuable to detect pheo (T2 enhancement) but otherwise adds little to a good enhancement) but otherwise adds little to a good CT scan.CT scan.In general, NO!In general, NO!

What now?What now?

Confirmatory testing still would be valuable, Confirmatory testing still would be valuable, but likely to be (+)but likely to be (+)Cause of hyperaldosteronism Cause of hyperaldosteronism notnot yet yet establishedestablished–– unilateral (tumor) vs. bilateral (hyperplasia)unilateral (tumor) vs. bilateral (hyperplasia)

Radiology Radiology cannotcannot usually lateralize an usually lateralize an aldosteronomaaldosteronoma–– Adrenal incidentalomas may confoundAdrenal incidentalomas may confound–– Aldosteronomas may be quite smallAldosteronomas may be quite small

Differential diagnosis of primary Differential diagnosis of primary hyperaldosteronismhyperaldosteronism

Tumors: 50Tumors: 50--60% of PHA60% of PHA

Testing to identify a tumorTesting to identify a tumor–– 1818--OHOH--corticosterone: corticosterone:

Aldosterone precursorAldosterone precursorLevels higher in adenomas than hyperplasiaLevels higher in adenomas than hyperplasia

–– 22--hr Posture testhr Posture testAldo levels normally rise in response to standingAldo levels normally rise in response to standingIf levels fall If levels fall adenomaadenoma

–– However, ~2/3 of tumors will show a However, ~2/3 of tumors will show a ““normalnormal”” response in this response in this test. (specific, but not sensitive)test. (specific, but not sensitive)

–– Adrenal vein samplingAdrenal vein samplingNeeds experienced interventional radiologistNeeds experienced interventional radiologistGold standard testGold standard test

Does it matter?Does it matter?Establishing the presence of uniEstablishing the presence of uni-- vs. bivs. bi--lateral lateral disease only important disease only important ifif it would affect therapy it would affect therapy (e.g., surgery)(e.g., surgery)–– Bill Young: Bill Young: ““44thth and Long: Punt or Go For It?and Long: Punt or Go For It?””–– There is data to support that patients have improved There is data to support that patients have improved

QOL after resection of adenoma QOL after resection of adenoma Sukor et al, Sukor et al, JCEM.JCEM. 2010 95:13602010 95:1360--4. 4.

However, this patient was clear that he would not However, this patient was clear that he would not want surgerywant surgery

Empiric therapy startedEmpiric therapy startedPatient has done better, but we will await longPatient has done better, but we will await long--term term outcome as medications titratedoutcome as medications titrated

If a patient is found to have an adenoma If a patient is found to have an adenoma and undergoes surgery, what are the and undergoes surgery, what are the chances of chances of ““curecure”” of the HTN?of the HTN?–– Cohort of 54 patientsCohort of 54 patients–– ~40% cured, ~40% markedly improved~40% cured, ~40% markedly improved–– Can take up to 12 months for full effectsCan take up to 12 months for full effects–– Patients with HTN <6 years and requiring <3 Patients with HTN <6 years and requiring <3

meds more likely to be curedmeds more likely to be cured

Waldmann et al, World J Surg. 2011 35:2422-7.

Role for unilateral adrenalectomy in Role for unilateral adrenalectomy in patients with bilateral disease?patients with bilateral disease?

40 patients studied at a single institution, who were followed 40 patients studied at a single institution, who were followed for at least 12 months (median, 56.4 mo)for at least 12 months (median, 56.4 mo)ResultsResults–– Hypertension cured in 15%Hypertension cured in 15%–– Hypertension improved in 20% Hypertension improved in 20% –– PostPost--op HTN control was 65%, compared with 25% preop HTN control was 65%, compared with 25% pre--opop–– Improved cardiac parameters such as LV Mass IndexImproved cardiac parameters such as LV Mass Index

CONCLUSION: CONCLUSION: ““Although this retrospective analysis of Although this retrospective analysis of patients from a single center does not permit prediction of patients from a single center does not permit prediction of response rates among patients diagnosed elsewhere, it response rates among patients diagnosed elsewhere, it suggests that unilateral adrenalectomy can be beneficial in suggests that unilateral adrenalectomy can be beneficial in some patients with apparent bilateral PA and should not be some patients with apparent bilateral PA and should not be dismissed as a treatment optiondismissed as a treatment option””

Sukor et al JCEM. 2009 94:2437-45.

Take home pointsTake home points

Worthwhile to fully establish diagnosis before Worthwhile to fully establish diagnosis before treatment or further workuptreatment or further workupIn this case, imaging ruled out worry for a In this case, imaging ruled out worry for a cancer, but presence of bilateral nodules cancer, but presence of bilateral nodules makes it of limited valuemakes it of limited value–– Abd CT should be repeated in 1 year to document Abd CT should be repeated in 1 year to document

stability. If so, further imaging likely stability. If so, further imaging likely not not neededneededWorkup to distinguish adenoma vs. bilateral Workup to distinguish adenoma vs. bilateral hyperplasia only valuable in setting where hyperplasia only valuable in setting where surgery to be pursued.surgery to be pursued.

Case History: SWCase History: SW

56 year old lady presents in 2009 from 56 year old lady presents in 2009 from outside endocrinologist to an OSU surgeon outside endocrinologist to an OSU surgeon for removal of a pheochromocytomafor removal of a pheochromocytoma

PheochromocytomaPheochromocytoma

Rare tumor of adrenal medullaRare tumor of adrenal medulla–– Synthesizes and releases catecholaminesSynthesizes and releases catecholamines

NorephinephrineNorephinephrineEpinephrineEpinephrineDopamineDopamine

–– Releases catecholamines in responses to Releases catecholamines in responses to stress, exercise, insulin, hypotensionstress, exercise, insulin, hypotension

““Fight or flightFight or flight”” reflexreflex

Case History: SWCase History: SWPatient placed on prazosin prePatient placed on prazosin pre--op, but stops taking it op, but stops taking it (?instructions). Surgery is cancelled when she (?instructions). Surgery is cancelled when she presents with BP 180/100 on day of procedurepresents with BP 180/100 on day of procedureReturns two weeks later on meds with better control Returns two weeks later on meds with better control of BP. Is admitted 2 days preof BP. Is admitted 2 days pre--op for optimization of op for optimization of alphaalpha--blockade and fluid statusblockade and fluid statusHas uneventful laparascopic removal of tumor. Has uneventful laparascopic removal of tumor. Pathology confirms pheochromocytoma of 23.8 grams, Pathology confirms pheochromocytoma of 23.8 grams, measuring 7.5 x 2.4 x 2.3 cm. Margins clear measuring 7.5 x 2.4 x 2.3 cm. Margins clear No family history to suggest inherited syndromreNo family history to suggest inherited syndromre–– ~15% of pheos thought to be part of a syndrome~15% of pheos thought to be part of a syndrome–– w/u of all patients includes a family historyw/u of all patients includes a family history

Management of Management of PheochromocytomaPheochromocytoma

Medical therapy for acute symptoms: Alpha blockadeMedical therapy for acute symptoms: Alpha blockade–– Phentolamine (Regitine)Phentolamine (Regitine)

IV agent producing rapid responseIV agent producing rapid response–– Oral alpha blockersOral alpha blockers

Slower but more sustainable responseSlower but more sustainable responsePhenoxybenzamine (Dibenzyline), doxazosin, prazosinPhenoxybenzamine (Dibenzyline), doxazosin, prazosin

–– May also betaMay also beta--blockade, but only after adequateblockade, but only after adequatealpha blockadealpha blockade

Unopposed alpha Unopposed alpha -->severe vasoconstriction>severe vasoconstriction

Surgery as soon as possible (after alpha blockade)Surgery as soon as possible (after alpha blockade)–– Laparoscopic surgery effective and safeLaparoscopic surgery effective and safe–– Patients at risk for hemodynamic perturbations, so experienced Patients at risk for hemodynamic perturbations, so experienced

centers are bestcenters are best

SW SW -- 22Patient rePatient re--presents to an outside ER (Aug 2011) with presents to an outside ER (Aug 2011) with complaints of nausea, vomiting, diarrhea, complaints of nausea, vomiting, diarrhea, palpitations/tachycardia and headache, which were palpitations/tachycardia and headache, which were similar to her initial presentation. similar to her initial presentation. Meds: Toprol XL 50 mg BIDMeds: Toprol XL 50 mg BIDAt the outlying hospital, HR was reported to be rates At the outlying hospital, HR was reported to be rates of up to 200, although on review, these were felt to of up to 200, although on review, these were felt to be artifact. She was started on a labetolol drip and be artifact. She was started on a labetolol drip and transferred to OSU for further evaluationtransferred to OSU for further evaluationOn arrival to our ER, BP 125/75 range (on drip). She On arrival to our ER, BP 125/75 range (on drip). She was having runs of SVT in the 170s felt to be atrial or was having runs of SVT in the 170s felt to be atrial or reentrant tachycardia. reentrant tachycardia. Diagnosis: ?Recurrent pheochromocytomaDiagnosis: ?Recurrent pheochromocytoma

When to suspect a pheo?When to suspect a pheo?3 3 ““classicclassic”” symptomssymptoms–– PalpitationsPalpitations–– PerspirationPerspiration–– Pain (headaches)Pain (headaches)

Often associated with hypertensionOften associated with hypertension

However, symptoms of a pheo tend to be rather nonHowever, symptoms of a pheo tend to be rather non--specificspecific–– Postural hypotensionPostural hypotension–– Tremor Tremor -- anxietyanxiety–– Abdominal or chest pain (uncommon)Abdominal or chest pain (uncommon)–– Glucose intoleranceGlucose intolerance–– Heat intoleranceHeat intolerance

Symptoms may also vary depending on primary hormone released Symptoms may also vary depending on primary hormone released (Epi, NorEpi, Dopamine)(Epi, NorEpi, Dopamine)

What next?What next?Order lab testing plusOrder lab testing plus……

1 2 3 4

38%

20%16%

26%

1.1. CT scanCT scan2.2. MRI scanMRI scan3.3. MIBG scanMIBG scan4.4. PET scanPET scan

Imaging of PheochromocytomaImaging of Pheochromocytoma

Biochemical diagnosis should precede any Biochemical diagnosis should precede any imaging studyimaging studyIn general, dedicated adrenal CT provides best In general, dedicated adrenal CT provides best anatomic resolutionanatomic resolution–– Average diameter of symptomatic pheo is 4.5 cmAverage diameter of symptomatic pheo is 4.5 cm

MRI can be helpful with DdxMRI can be helpful with DdxMIBG specific but not very sensitiveMIBG specific but not very sensitiveMIBG and/or PET most helpful when tumor MIBG and/or PET most helpful when tumor biochemistry is clear but tumor not localized or biochemistry is clear but tumor not localized or suspicion of metastatic pheosuspicion of metastatic pheo

Pheo: CTPheo: CT

Pheo: MRIPheo: MRI

T2T1

Note the poorer spatial resolution!

MIBG scan MIBG scan -- idealideal

(False color)Ant Post

FDG PET showing metastatic FDG PET showing metastatic PheoPheo

Back to our patientBack to our patient……

She got set of CT images in the ERShe got set of CT images in the ER……

Surgical clips

LabsLabs8/26/20118/26/2011 8/25/20118/25/2011

NOREPINEPHRINE, PLASMA NOREPINEPHRINE, PLASMA pg/mlpg/ml 2186 (H) . . .(NL<1700)2186 (H) . . .(NL<1700)EPINEPHRINE, PLASMA EPINEPHRINE, PLASMA ““ 177 (H) . . . (NL <110)177 (H) . . . (NL <110)DOPAMINE, PLASMA DOPAMINE, PLASMA ““ 116 (H) . . . (NL <30)116 (H) . . . (NL <30)

NORMETANEPHRINE, FREE NORMETANEPHRINE, FREE nmol/Lnmol/L 3.4 (H) . . . (NL <0.45)3.4 (H) . . . (NL <0.45)METANEPHRINE, FREE, PLASMA METANEPHRINE, FREE, PLASMA ““ 0.76 (H) . . . (NL <0.9)0.76 (H) . . . (NL <0.9)

NOREPINEPHRINE, URINE NOREPINEPHRINE, URINE ug/dug/d 73 . . .73 . . . (NL <80)(NL <80)EPINEPHRINE, URINE EPINEPHRINE, URINE ““ 7.3 . . .7.3 . . . (NL <20)(NL <20)DOPAMINE, URINE DOPAMINE, URINE ““ 184 . . .184 . . . (NL <400)(NL <400)

METANEPHRINE, URINE METANEPHRINE, URINE ““ 229 . . .229 . . . (NL <400)(NL <400)NORMETANEPHRINE, URINE NORMETANEPHRINE, URINE ““ 876 . . .876 . . . (NL <900)(NL <900)METANEPHRINES, TOTAL, URINE METANEPHRINES, TOTAL, URINE ““ 1105 . . .1105 . . . (NL: <1300)(NL: <1300)

SW SW -- 33

She was given the diagnosis of metastatic She was given the diagnosis of metastatic pheochromocytomapheochromocytoma——location unknownlocation unknown–– Review of prior CT scan showed the liver Review of prior CT scan showed the liver

lesions were old and unchangedlesions were old and unchanged

Pt referred to Oncology and Endocrinology Pt referred to Oncology and Endocrinology (me) for further therapy(me) for further therapy

MIBG vs PET MIBG vs PET -- ??

RR

IMPRESSION: Status post left adrenalectomy. Focal increased activity within the right adrenal gland could represent normal physiologic activity versus pheochromocytoma with appropriate clinical setting.

Does the patient have pheo or Does the patient have pheo or not? If so, where is it?not? If so, where is it?

8/25/11 9/1/11 11/15/11 2/9/12Normetanephrine(<0.9)

nmol/L 3.4 0.77 1.1 0.72

Metanephrine(<0.45)

“ 0.76 0.33 0.37 0.30

Biochemistry unconvincing (probably Biochemistry unconvincing (probably negative)negative)Imaging fails to localize tumorImaging fails to localize tumor

No PheoNo Pheo

1) Acute myocardial ischemia or infarction

2) Acute cerebrovascular event

3) Severe congestive heart failure

4) Acute clonidine withdrawal

5) Acute alcohol withdrawal

6) Monotherapy with pure arterial vasodilators (as hydralazine or minoxidil)

7) Cocaine abuse

Disorders that may increase both plasma and urinary catecholamines metabolites to levels often seen in pheochromocytoma

Karagiannis et al., Pheochromocytoma: an update on genetics and management Endocr Relat Cancer, 2007 14: 935-956

As far as we know, none of these was applicable. However, labetoAs far as we know, none of these was applicable. However, labetolol itself lol itself may cause falsely elevated catecholamine/metanephrine measuremenmay cause falsely elevated catecholamine/metanephrine measurementt

“…“…Our studies indicate that labetalol produced a false elevation oOur studies indicate that labetalol produced a false elevation of urinary f urinary catecholamine levels. catecholamine levels. Although labetalol also interfered with the Although labetalol also interfered with the measurement of urinary excretion of metanephrine,measurement of urinary excretion of metanephrine, it did not interfere with it did not interfere with the measurement of urinary excretion of vanillylmandelic acid, hthe measurement of urinary excretion of vanillylmandelic acid, homovanillic omovanillic acid, 5acid, 5--hydroxyindoleacetic acid, and serotonin, and it probably did nothydroxyindoleacetic acid, and serotonin, and it probably did notinterfere with the measurement of plasma concentrations of dopaminterfere with the measurement of plasma concentrations of dopamine, ine, norepinephrine, and epinephrine. norepinephrine, and epinephrine. ““Feldman Feldman J Clin Pharmacol A, 1987 vol. 27 no. 4 288J Clin Pharmacol A, 1987 vol. 27 no. 4 288--292 292

Labetolol can cause both mild increases in levels (through blockLabetolol can cause both mild increases in levels (through blockade) and ade) and error in measurement.error in measurement.–– Likely exacerbated by IV infusionLikely exacerbated by IV infusion

Testing for pheosTesting for pheosThe single best test likely depends on the level of The single best test likely depends on the level of suspicionsuspicion–– Performing test correctly enhances accuracyPerforming test correctly enhances accuracy

Blood measurements made at rest, without stressBlood measurements made at rest, without stressAccurate 24 hr urine collection (if possible)Accurate 24 hr urine collection (if possible)

–– If suspicion is high, plasma free metanephrines are more If suspicion is high, plasma free metanephrines are more sensitive (fewer false negatives)sensitive (fewer false negatives)

–– If suspicion is low, urinary total metanephrines + If suspicion is low, urinary total metanephrines + catecholamines is more specific (fewer false positives) catecholamines is more specific (fewer false positives)

Be aware of possible drug effects on measurementsBe aware of possible drug effects on measurements–– Physiologic elevations (e.g. betaPhysiologic elevations (e.g. beta--blockers)blockers)–– Assay interferenceAssay interference

AcetominophenAcetominophenLabetalolLabetalolLL--DOPA/Carbidopa (Sinemet)DOPA/Carbidopa (Sinemet)

Confirmatory tests for pheoConfirmatory tests for pheo

Clonidine suppressionClonidine suppression–– 0.3 mg of clonidine given po0.3 mg of clonidine given po–– Measure plasma MN at 0, 3 hrsMeasure plasma MN at 0, 3 hrs

Normal patients will suppress >50% or to normal rangeNormal patients will suppress >50% or to normal range

Glucagon stimulationGlucagon stimulation–– 1 mg glucagon given IV1 mg glucagon given IV–– Measure catechols at 0, 2Measure catechols at 0, 2--3 min3 min

Stimulation indicates a pheoStimulation indicates a pheo–– Potentially dangerous ?Potentially dangerous ?

PhentolaminePhentolamine–– Give 1Give 1--5 mg phentolamine IV5 mg phentolamine IV–– >35/25 drop in BP within 2>35/25 drop in BP within 2--10 min is diagnostic10 min is diagnostic

Take home pointsTake home points

Biochemical diagnosis of pheo should Biochemical diagnosis of pheo should precede any imaging studiesprecede any imaging studies–– Be aware of effects of medications on test resultsBe aware of effects of medications on test results

Clinically significant pheos are almost always Clinically significant pheos are almost always radiologically evidentradiologically evidentFunctional imaging with MIBG has high Functional imaging with MIBG has high specificity but low sensitivity. FDG PET specificity but low sensitivity. FDG PET probably more sensitive for detecting occult probably more sensitive for detecting occult dieseasediesease