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Tamara Spaic, R4. Testing in Cushing’s Syndrome and pheochromocytoma. Adrenal cortex and HPA axis Testing in Cushing’s syndrome Review of the Endocrine Society Clinical Practice Guidelines (JCEM, May 2008) Assessment of adrenal medullary function and disorders Which test is the best?.

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Tamara spaic r4

Tamara Spaic, R4

Testing in Cushing’s Syndrome and pheochromocytoma


  • Adrenal cortex and HPA axis

  • Testing in Cushing’s syndrome

  • Review of the Endocrine Society Clinical Practice Guidelines (JCEM, May 2008)

  • Assessment of adrenal medullary function and disorders

  • Which test is the best?


Adrenal gland

4 g weight

2x5x1 cm

Posteromedial surface of the kidney


Adrenal Gland

L adrenal metastasis
L adrenal metastasis

Unenhanced CT

PET scan

Figure 28.   Adrenal lymphoma in a 74-year-old woman with biopsy-proved non-Hodgkin lymphoma. Contrast-enhanced CT scan demonstrates bilateral adrenal masses (straight arrows). The patient also has a destructive lesion from the lymphoma in the right rib (curved arrow)

zona glomerulosa lacks

Only zona glomerulosa

  • Trophic hormone of zonae fasciculata and reticularis

  • Major regulator of adrenal androgen and cortisol production

  • Regulated by CRH (whose action is also potentiated by AVP -arginine vasopressin, and β adrenergic catecholamines)

  • Rapid synthesis and secretion of steroids (hormone levels rise within minutes)


Acth secretion

ACTH circadian rhythm generated in suprachiasmatic nc (signals CRH release)

Secreted with both circadian periodicity and ultradian pulsatility

Periodic secretory bursts at frequency of ~ 40 pulses/day

Entrained by visual cues, light –dark cycle

Continuous CRH administration desensitizes the ACTH response

Prolonged pulsatile CRH administration restores cortisol secretion

Corticosteroids directly suppress basal or stimulated ACTH pulse amplitude

ACTH secretion

Circadian rhythm
Circadian rhythm (signals CRH release)

Neuroendocrine control

Episodic secretion and circadian rhythm of ACTH (signals CRH release)

Stress responsivness of the HPA

Feedback inhibition by cortisol of ACTH secretion

Neuroendocrine Control

Rhythm changes

Rhythm changes

Stress responsivness

ACTH and cortisol secreted within minutes (Sx, hypoglycemia) starvation)

Abolish circadian periodicity (prolonged stress)

Stress →↑CHR → ↑ACTH

Stress response abolished by proior high dose glucocorticoids/Cushing’s syndrome

Enhanced following adrenalectomy

Stress responsivness

Feedback inhibition

FAST feedback inhibition – depends on the rate of increase of GC (not the dose)

Rapid (within minutes) and transient (up to 10 minutes)

DELAYED feedback inhibition is both time and dose dependent

Feedback Inhibition

Acth measurement

Ideally nonstressed resting subject should have venous sample drawn 6-9 am

Unstable on room temperature (must immediately go on ice, -20° C)

Siliconized glass tube containing EDTARandom ACTH values do not on their own provide an accurate assessment of HPA function

ACTH measurement

Cortisol secretion

Under basal (non stressed) conditions sample drawn 6-9 am

8-25 mg/day (22-69 μmol/day)

Mean 9.2 mg/day (25 μmol/day) – less than thought before (?20 mg/day)

Cortisol secretion

Cortisol circulation

Cortisol circulation

Produced by the liver inactive

Progesterone in late pregnancy

Synthetic steroids – do not significantly bind (except prednisolone)


High estrogen states (pregnancy, OCP) inactive



Hematologic d/s

Chronic active hepatitis


Familial CBG deficiency inactive

↓ T4

Protein deficiency states (nephrotic syndrome, liver failure)


Cortisol metabolism

Metabolism – liver (conjugation) inactive

Excretion – kidney (<1% in urine unchanged – “free”)

11β-hydroxysteriod dehydrogenase (inhibited by IGF-1)

Cortisol metabolism

Altered metabolism

↓ clearance in starvation/anorexia nervosa and pregnancy (↑CBG)

↓ metabolism and excretion – hypoT4

↑metabolism – OCP, liver disease

Also drugs : dilantin, barbiturates, mitotane, rifampin

Altered metabolism

Cushing s syndrome

ACTH Dependent (↑CBG)

ACTH Independent

Pseudo-Cushing’s Syndrome

Cushing’s Syndrome

Etiology (↑CBG)

Pseudo-Cushing’s Syndrome




Sign and symptoms

Sign/symptom Frequency (%) (↑CBG)

Truncal obesity 96

Facial fullness 82

Diabetes or glucose intolerance 80

Gonadal dysfunction 74

Hirsutism, acne 72

Hypertension 68

Muscle weakness 64

Skin atrophy and bruising 62

Mood disorders 58

Osteoporosis 38

Oedema 18

Polydipsia, polyuria 10

Fungal infections 6

The mean age of the 239 female and 63 male patients was 38·4 years (SD 13·5; range 8–75).

Sign and symptoms


  • Answer 2 questions: (↑CBG)

  • Does this patient have Cushing’s Syndrome?

  • Having confirmed Cushing’s syndrome clinically and biochemically – What is the cause?


Options for investigation
Options for investigation (↑CBG)

  • Diagnosis

  • UFC

  • Circadian Rhythm of plasma cortisol

  • Low dose dexamethasone

  • Salivary cortisol

  • Differential Diagnosis

  • Plasma ACTH

  • Plasma K, HCO3

  • High dose dexamathasone suppression

  • Metyrapone test

  • CRH

  • IPSS

  • CT/MRI pituitary, adrenals

  • Scintigraphy


Obesity epidemics (↑CBG)

Aging population

Suspicion - common

Rare diagnosis (5-10 cases/million population/year) – Cushing’s disease – (70% of all cases)

0.5% of lung cancer patients have ectopic ACTH syndrome

False positive tests



2-5% prevalence of unsuspected Cushing’s syndrome in pts with poorly controlled DM

0.5-1% in HTN

10.8% of pts with osteoporosis/vertebral #

3% in osteoporosis

Overlap with PCOS (5.8%)

9% pts with incidental adreanal nodules (>2 cm) have evidence of hypercortisolism


Who should be tested

  • To reduce FP rate (high with poorly controlled DMpretest probability)

  • Pts with unusual features for age (osteoporosis, HTN)

  • Pts with multiple and progressive features 9especially those predictive of Cushing’s

  • Children with decreasing height ‰ and increasing wt

  • Adrenal incidentaloma compatible with adenoma

Who should be tested?

<1% of secreted cortisol unchanged in urine with poorly controlled DM

Cushing’s – CBG binding capacity exceeded, so plasma free cortisol ↑ - ↑UFC

N range 50-250 nmol/24 h (80-120)

Not affected by conditions and meds that alter CBG

Use the upper limit of normal as cut-off point

Should do 2 or 3 complete consecutive collections (with 24 hr Cr)

Can not do in RF (falsely low)

False + if fluid intake >5 L /day


Issues ufc

  • Am with poorly controlled DMcortisol often not elevated in Cushing’s syndrome

    (late night usually increased)

  • Small increases in cortisol at circadian nadir may not be detected as ↑ UFC

  • Sn 45-71% (although most studies show excellent sn, sp is the problem)

  • Pseudo vs Cushing’s – ? Useful (also anxiety, starvation, AN)

  • To avoid overlap 4-fold increase

  • Levels elevated during stress

Issues UFC

Late night salivary cortisol

Abnormal circadian rhythm (absence of late night nadir) with poorly controlled DM

Same as in midnight serum cortisol (but impractical)

Sn 100%, Sp 77%

CBG absent in plasma (measures free, not dependent on CBG)

Not affected on saliva amount or composition

Stable on room temperature

Can be sampled at home by the pt

At least 2 measurements

Late-night salivary cortisol

Late night salivary cortisol1

  • N with poorly controlled DM(bedtime or 2300-2400) <4 nmol/L

  • Sn 92-100%

  • Sp 93-100% (highly accurate for differentiating from pseudocushing’s)

  • Circadian rhythm is blunted in depression, shift workers

  • May be absent in critically ill

  • Chewing tobacco or licorice may have falsely elevated result (inhibits which enzyme?)

  • ?Smokers

  • Different time zones

Late- night salivary cortisol


11 with poorly controlled DMβ hydroxysteriod dehydrogenase type 2

Cortisol → cortisone (inhibits)


1 mg dst

Assessing feedback inhibition of HPA axis with poorly controlled DM

Suppresses pituitary ACTH

↓plasma and urinary cortisol

Cushing’s – fails to suppress

Dexamethasone does not interfere with the measurment of cortisol

Measure simultaneously daxamethasone level (to assess compliance, etc)

1-mg DST

  • 1 mg po dexamethasone at 23 00 with poorly controlled DM

  • Am cortisol

  • If cortisol <50 nmol/L – excluded (Sn 95%)

  • FP 12.5%

    (dilantin, rifampin, chronically ill, etoh, uremia, estrogen, pseudocushing’s)

  • FN <2%

    (slow dex metabolizers)


48 hrs low dst

Plasma cortisol at day 0 and 48 hours (9 with poorly controlled DM:00 am)

Dexamethasone 0.5 mg q6h x 48 hours

FP <1%

TP 97-100% (increased specificity)

2 weeks absence from etoh and 6 weeks of OCP

?Pseudocushing’s r/o

48 hrs low DST


Cushing’s syndrome (CS) - may adequately suppress serum cortisol (sn 98% if 50 nmol/L used) (? Impaired clerance)

Pseudocushings (PC) - ↑CRH secretion, yet cortisol continues to exert negative feedback on HPA (allowing suppression by exogenous GC)

CS – HPA axis more responsive to CRH and less to dex

CRH test (CS vs PCS)


Lddst crh

O.5 mg dex q6h for 48 hrs cortisol (sn 98% if 50 nmol/L used) (? Impaired clerance)

In standard LDDST 6hrs post serum cortisol

CRH – 2 hrs after the last dose – serum cortisol, than iv 100 μg human rCRH (bw before and 15 min after)

LDDST – cut off 50 nmol/L

LDDST CRH - <38 nmol/L (excluded CS)


Addition of CRH to LDDST does not improve the diagnostic accuracy.

By adding CRH can not improve Sn beyond 100%, while sp went down to 67%

Special consideration

Pregnancy : UFC accuracy.

Epilepsy : UFC or late night salivary

RF: 1 mg DST

Cyclic Cushing’s syndrome : UFC

Adrenal incidentaloma : 1 mg DST

Special consideration

What is the cause

Plasma ACTH accuracy.

High dose dexamethasone suppression test



What is the cause ?

Acth 9 am

ACTH dependent vs independent accuracy.

Adrenal tumors < 1 pmol/L

CS : N (inappropriately) or elevated

Problem in differentiating CD and Ectopic ACTH syndrome (30% overlap)

Higer in EAS ( >20 pmol/L )

Normal range 2-11 pmol/L

ACTH (9 am)

Hddst high dose dexamethasone suppression test

  • Rational : resetting of the negative feedback control to ACTH at higher level in CD

  • DDx of Cushings Disease vs Ectopic ACTH syndrome

  • Originally described by Liddle in 1960

  • 2 mg q6h x 48 hours

  • Original to demonstrate >50% drop in urinary 17 OH CS

  • Liddle used only for adrenal dependent vs pituitary (at that time EAS not even described

HDDST (High Dose Dexamethasone Suppression Test)


Plasma and urinary free cortisol (0 and 48 hrs) ACTH at higher level in CD

>50% suppression

Problem : 20-30% EAS will suppress

~20 – 30 % of CD will not suppress

But 90% of pts will have CD

Diagnostic accuracy of test only 76%



You want very specific test (to identified rare/few cases of EAS)

Improve sp by changing cut off

100% sp with suppression of >90% of UFC



Sn 81% EAS)

Sp 66.7%

There was no cut off point that would yield 100% specificity

Diagnostic accuracy only



  • Gold standard EAS)

  • Function

  • Confirmation of pituitary ACTH secreting tumor

  • Localization


Anatomy EAS)

  • Simultaneous IPS and peripheral ACTH measuring EAS)

  • Before and after CRH

  • 5 time points (0,2,3,5,10 minutes)

  • Each petrosal sinus and peripheral vein

  • IPS/peripheral ACTH > 2 → CD

  • Absent gradient – EAS

  • Sn 97%, sp 100% (if ratio pf 3 used)



Technically demanding!!! EAS)

Proficient center

Complications : referred auricular pain, thrombosis, hemorrhage

Central location






Adrenal medulla1

Specialized part of autonomic nervous system EAS)

Sympathoadrenal system

System of “fight or flight”

Actions best characterized by the appearance of patient in shock

Adrenal Medulla



Catecholamine synthesis and metabolism

  • Catecholamines contain granules important in storage and secretion of catecholamines : dopamine, norepinephrine, and epinephrine

  • Chromogranin A (CgA) – peptide stored and released with catecholamines by exocytosis (higher in HTN patients)

  • Catestatin – fragment of prohormone that inhibits further catecholamine release (antagonist at neuronal cholinergic receptor), low level may increase the risk of EHTN

Catecholamine Synthesis and Metabolism

Synthesis contain granules important in storage and secretion of catecholamines

Abbreviations: TH, tyrosine hydroxylase; AAD, amino acid decarboxylase;

DβH, dopamine β-hydroxylase; PNMT, phenylethanolamine-N-methyltransferase.

Cont d

  • Tyrosine – derived from ingested food or synthesized from phenylalanine in the liver

  • First step – rate limiting

  • TH (expressed only in tissues that synthesize CCH) inhibited by dopa, dopamine, NE, ?alpha-methyltyrosine (Rx of pheo)

  • AADC – found in non-neuronal tissues (liver, kidney), methyldopa is competitive inhibitor

  • Dopamine taken up into chromaffin garnules

  • DHB – only in vesicles of cells synthesizing CCH

  • In the adrenal medulla NE returns to cytosol to be methylated by phenylethanolamine-N-methyl transferase (PNMT) to form epinephrine

  • PNMT – nonspecific (lung, kidney, pancreas, RBC), inducible by high dose corticosteroids, ?angiotensin II


Storage secretion transport

  • Stored in the phenylalanine in the liverchromaffin granules with several neuropeptides (neuropeptide Y, substance P, VIP, chromogranins, ACTH)

  • Released by exocytosis

  • Response to many stressful stimuli (pain, exercise, hemorrhage, anesthesia, hypoglycemia, anoxia..)

  • Secretion mediated by release of Acetylcholine from the terminals of preganglionicfibers

  • In circulation bound to albumin mostly

Storage, secretion, transport

Neuroadrenergic junction

  • Once NE released in the synapse : phenylalanine in the liver

    1. Reacts with α1 postsynaptic receptor

    2. Reacts with presynapticα2 receptor (down regulates its own synthesis and release)

    3. Taken up into the cell by “uptake 1” (blocked by TCA, cocaine) – main mode of removal

    4. Diffuse out and undergo degradation

    Note: NE can also be removed by extraneuronal uptake by “uptake 2” (inhibited by corticosteroids)

Neuroadrenergic junction

Metabolism and inactivation
Metabolism and Inactivation phenylalanine in the liver

Cont d1

MOA – regulates the CCH content of neurons, levels ↑progesteron, ↓estrogen

Peripheral circulating NE metabolized largely by COMT (catechol-O-methyltransferase)

COMT – found in most tissues (blood cells, liver, kidney, vascular smooth muscle)

Conjugation with sulfate or glucuronide


Receptor agonists and antagonists
Receptor Agonists and Antagonists ↑progesteron, ↓estrogen


Rare and often unrecognized adrenal medulla tumor ↑progesteron, ↓estrogen

Derived from chromaffin cells (paraganglioma if from extra-adrenal chromaffin cells: 10-15%)

Wide range of clinical presentation

Associated with different familial disorders (vHL, MEN2a, 2b, NF-1)


Common (>33% of patients) ↑progesteron, ↓estrogen

Less common (<33% of patients)

Hypertension (probably >90%)      Paroxysmal (50%)      Sustained (30%)      Paroxysms superimposed (about 50%)   Hypotension, orthostatic (10%-50%)   Headache (40%-80%)   Sweating (40%-70%)   Palpitations and tachycardia (45%-70%)   Pallor (40%-45%)   Anxiety and nervousness (20%-40%)   Nausea and vomiting (20%-40%)Funduscopic changes (50%-70%)   Weight loss (60%-80%)

   Tremor   Abdominal pain   Chest painPolydipsia, polyuria   ConstipationAcrocyanosis, cold extremities   FlushingDyspnea   Dizziness, syncope   ConvulsionsBradycardia   Fever

Clinical Presentation Werbel SS, Ober KP. Pheochromocytoma. Update on diagnosis, localization, and management. Med Clin NA 1995; 79:131–153


Paroxysm (or pheo crisis) is the consequence of CCH release ↑progesteron, ↓estrogen

CCH synthesis at increased rate likely due to lack of feedback inhibition of tyrosine hydroxylase

CCH produced in quantities that exceed the vesicular storage capacity – accumulate in cytoplasm – diffuse into the circulation

Most contain more NE than Epinephrine (unlike normal medulla)

May secrete other peptides


Secretion of cch in pheochromocytoma

  • Not innervated (unlike adrenal medulla) so catecholamine release is not initiated by neural impulses

  • Precipitated by any movement that displaces abdominal content, vigorous palpation of abdomen, spontaneous hemorrhage within tumor, surgical manipulation

  • Drugs – opioids (fentanyl), amphetamines, decongestants, histamine, TCA, dopamine antagonists (metoclopromide), glucagon, ACTH, intraarterial radiographic contrast

Secretion of CCH in pheochromocytoma

Biochemical diagnosis

24 hour urine catecholamines and metanephrines release is not initiated by neural impulses

Fractionated plasma free metanephrines

Other tests (clonidine suppression test, chromogranin A)

No role (plasma catecholamines, 24- hour urinary VMA, histamine, glucagon, tyramine stim tests)

Biochemical Diagnosis

Factors that affect test accuracy

  • Foods: coffee/decaffeinated drinks – inhibits adenosine – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)

  • Drugs – long list

  • Conditions: ALS, carcinoid, eclampsia, exercise, GBS, hypoglycemia, Pb poisoning, AMI, pain, porphyria, acute psychosis, RF (decreases excretion)

Factors that affect test accuracy

Medications that may increase measured levels of catecholamines and metanephrines

  • Tricyclic – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC) antidepressants

  • Levodopa

  • Drugs containing adrenergic receptor agonists (eg, decongestants)

  • Amphetamines

  • Buspirone and most psychoactive agents

  • Prochlorperazine

  • Reserpine

  • Withdrawal from clonidine and other drugs

  • Ethanol

  • Acetaminophen (may increase measured levels of fractionated plasma metanephrines in some assays)

  • Captopril (may cause confounding peak)

  • Codeine

Medications that may increase measured levels of catecholamines and metanephrines

24 hour urine cch and metanephrines

  • Fractionated – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)metanephrines (normetanephrine, metanephrine), total metanephrines, urinary vanillylmandelic acid (VMA)

  • Should include urinary Cr to verify adequate collection

  • Ability to follow instructions and cost

  • Should not be on TCA

  • Diagnostic cutoffs based on normotensive volunteers – may result in excessive FALSE POSITIVE testing

24-hour urine CCH and metanephrines

Fractionated plasma free metanephrines

  • Plasma free – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)normetanephrine and metanephrine

  • Requires overnight fast and intravenous cannula

  • Patient should be supine at least 20 minutes before collection

  • No tylenol for 5 days prior and avoid caffeinated beverages overnight

  • As CCH are metabolized within tumor cells, plasma levels of free metanephrines are very sensitive

Fractionated plasma free metanephrines

Clonidine suppression test

  • Centrally acting – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)α2 adrenergic agonist

  • Suppresses the release of CCH from neurons but it does not affect secretion for pheochromocytoma

  • Confirmatory test – distinguish between pheo and false positive increase in CCH (when ↑CCH but not diagnostic)

  • Administered orally (0.3 mg)

  • Plasma catecholamines or metanephrines measured before and 3 hrs post dose

  • In essential HTN – plasma CCH and normetanephrine concentrations decrease, while in pheo – remain increased

  • Patient should not take diuretics (euvolemic), β-blockers, TCA

Clonidine Suppression Test

Chromogranin a

  • Released from the – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)secretory granules

  • Increased in 80% of patients with pheo

  • Have circardian rhythm (lowest at 8:00 am, highest 11:00 pm)

  • Also secreted from extra-adrenal sympathetic nerves

  • Renal clearance

  • Sensitivity 98% and Specificity 97%

  • PPV 97% and NPV 98% (sporadic)

    Herbomez et al. An analysis of biochemical diagnosis of 66 Pheochromocytomas. European Journal of Endocrinology 2007, 156:569-75

Chromogranin A

Which test is the best

  • Ideal test has 100% sensitivity and specificity – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)

  • Sensitivity =TP/TP+FN (negative test r/o diagnosis)

  • Specificity =TN/TN+FP (positive test r/i diagnosis)

  • PPV = TP/ TP+FP

  • NPV = TN/TN+FN

    For any biochemical test - Sn low and Sp high for hereditary (high suspicion) vs sporadic case

    If the disease has low prevalence - ↑false positive

Which test is the best?

Lenders et al bichemical diagnosis of pheochromocytoma which test is best jama 2002 287 1427 34

  • Multicenter cohort study, over 5 years – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)

  • Objective – to determine the biochemical test or combination of tests that provide the best method of diagnosing pheochromocytoma

  • 1003 pt tested, 858 included (85%)

  • 443 sporadic, 415 hereditary

  • Conformation of pheodx required +path examination of surgical resection, biopsy, or inoperable malignant pheochromocytoma based on imaging.

  • Excluded if lack of tumor in CT/MRI, - path examination of Sx or bx, and lack of disease on 2 years patient follow up

Lenders et al. Bichemical Diagnosis of Pheochromocytoma. Which Test Is Best? JAMA. 2002, 287:1427-34

Results – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)


  • Since measurements of urinary fractionated – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)metanephrines and plasma free metanephrines offer similar high sensitivity, a negative result for either test is equally effective for excluding pheo.

  • However, because urinary fractionated metanephrines have low specificity, test of plasma free metanephrines exclude pheo in many more patients without tumor.

  • Plasma free MN provide the best test for excluding or confirming pheo and should be the test of choice for diagnosis.


Single center, retrospective study, over 1 year – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)

349 patients, 8(?) hereditary

Objective as above


Sawka, et al: A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. J ClinEndocrinolMetab 2003; 88:553.

Likelihood ratios

  • +LR 6.3 (plasma free MN) – inhibits release of CCH (false elevated results); bananas – tyrosine, peppers (may cause confounding peaks on HPLC)

  • + LR 58.9 (24 hrs urine total MN and CCH)

  • If prevalence of pheo is

    - 0.5% (screened HTN pt) –post test probability: 3% vs 23%

    - 5.1% (incidentaloma) : 25% vs 76%

  • 42 % (MEN2a) : 82% vs 98%

  • In addition specificity of plasma free MN falls to 77% in pt above age 60

Likelihood ratios


Suggested that measurement of fractionated plasma metanephrines may be the biochemical test of choice in high-risk patients (those with a familial syndrome or vascular adrenal mass).

However, in the more common clinical setting when sporadic pheochromocytoma is sought, particularly older hypertensive patients, measurement of 24-h urinary metanephrines and catecholamines may provide adequate sensitivity, with a lower rate of false positive tests.


Included 3 studies metanephrines may be the biochemical test of choice in high-risk patients (those with a familial syndrome or vascular adrenal mass).

56 pt with pheo and 445 without pheo

Sensitivity 97-100%

Specificities 82-100%

Pooled +LR 5.77, -LR 0.02 (sporadic cases)

Post-test probabilities : 2.8%, 23.7% and 0.01%, 0.11%

Conclusion : useful to r/o pheo, but a positive test only slightly increases suspicion when screening for sporadic pheochromocytoma.

Sawka et al: A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma. BMC Endocrine Disorders 2004; 4:2

Evaluation and treatment of catecholamine producing tumors
Evaluation and treatment of catecholamine-producing metanephrines may be the biochemical test of choice in high-risk patients (those with a familial syndrome or vascular adrenal mass).tumors