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Basic Information ⬇

Author: Brett Patrick, MD and Mark F. Brady, MD, MPH, MMSc, and Fred F. Ferri, MD

Definition

Pheochromocytomas are catecholamine-producing tumors that originate from the chromaffin cells of the adrenergic system. While they generally secrete both norepinephrine and epinephrine, norepinephrine is usually the predominant amine.

Synonym

Paraganglioma

ICD-10CM CODES
C74.9Malignant neoplasm of adrenal gland, unspecified
C75.9Malignant neoplasm of endocrine gland, unspecified
E27.5Adrenomedullary hyperfunction
Epidemiology & Demographics

  • Incidence: 0.05% of population; peak incidence in 30s and 40s.
  • Approximately 25% of patients with apparently sporadic pheochromocytoma may be carriers of mutations.
  • Approximately 25% of pheochromocytomas are familial and associated with genetic disorders (Table E1). Pheochromocytoma is a feature of two disorders with an autosomal dominant pattern of inheritance:
    1. Multiple endocrine neoplasia (MEN) type 2
    2. von Hippel-Lindau disease: Angioma of the retina, hemangioblastoma of the central nervous system, renal cell carcinoma, pancreatic cysts, and epididymal cystoadenoma
  • Pheochromocytomas occur in 5% of patients with neurofibromatosis type 1.

TABLE E1 Autosomal Dominant Syndromes Associated with Pheochromocytoma and Paraganglioma

SyndromeGeneGene LocusProtein ProductProtein FunctionGene MechanismTypical Tumor Location
SDHD (familial paraganglioma type 1)*SDHD11q23SDH D subunitATP productionTumor suppressorSkull base and neck; occasionally adrenal medulla, mediastinum, abdomen, pelvis
Familial paraganglioma type 2*SDHAF211q13.1Flavination cofactorATP productionTumor suppressorSkull base and neck; occasionally abdomen and pelvis
SDHC (familial paraganglioma type 3)SDHC1q21SDH C subunitATP productionTumor suppressorSkull base and neck
SDHB (familial paraganglioma type 4)SDHB1p36.1-35SDH B subunitATP productionTumor suppressorAbdomen, pelvis and mediastinum; rarely adrenal medulla, skull base, and neck
MEN-1MEN-111q13MeninTranscription regulationTumor suppressorAdrenal medulla
MEN-2A and MEN-2BRET10q11.2RETTyrosine kinase receptorProtooncogeneAdrenal medulla, bilaterally
Neurofibromatosis type 1NF117q11.2NeurofibrominGTP hydrolysisTumor suppressorAdrenal-periadrenal
von Hippel-Lindau diseaseVHL3p25-26VHLTranscription elongation suppressionTumor suppressorAdrenal medulla, bilaterally; occasionally paraganglioma
Familial pheochromocytomaFP/TMEM1272q11Transmembrane proteinRegulation of the mTORC1 signaling complexTumor suppressorAdrenal medulla

ATP,Adenosine triphosphate; GTP, guanosine triphosphate; MEN, multiple endocrine neoplasia; mTORC1, mammalian target of rapamycin complex 1; RET, "rearranged during transfection" proto-oncogene; SDH, succinate dehydrogenase; VHL, von Hippel-Lindau disease.

* Associated with maternal imprinting.

From Melmed S: Williams textbook of endocrinology, ed 12, Philadelphia, 2011, Saunders, Elsevier.

Physical Findings & Clinical Presentation

  • Hypertension: Can be sustained (55%) or paroxysmal (45%).
  • Headache (80%): Usually paroxysmal in nature and described as "pounding" and severe.
  • Palpitations (70%): Can be present with or without tachycardia.
  • Hyperhidrosis (60%): Most evident during paroxysmal attacks of hypertension.
  • Physical examination may be entirely normal if done in a symptom-free interval; during a paroxysm the patient may demonstrate marked increase in both systolic and diastolic pressure, profuse sweating, visual disturbances (caused by hypertensive retinopathy), dilated pupils (from catecholamine excess), paresthesias in the lower extremities (caused by severe vasoconstriction), tremor, and tachycardia.
  • Orthostatic hypotension is common among patients with pheochromocytoma due to reduction of blood volume and desensitization of adrenergic receptors by the chronic excess of catecholamines.
  • Table E2 summarizes signs and symptoms suggestive of pheochromocytoma.
  • A recent case study on diagnosis of pheochromocytoma1 revealed that two thirds of patients were identified because of adrenal incidentalomas rather than classic adrenergic symptoms.

TABLE E2 Signs and Symptoms of Pheochromocytoma

SymptomsSigns
Headaches++Hypertension++++
Palpitations+++#Tachycardia or reflex bradycardia+++=#
Sweating+++#Postural hypotension++
Anxiety/nervousness++Hypertension, paroxysmal++
Tremulousness++#
Nausea/emesis++#Weight loss++#
Pain in chest/abdomen++Pallor++#
Hypermetabolism++
Weakness/fatigue+++#Fasting hyperglycemia++
Dizziness+Tremor++#
Heat intolerance+Increased respiratory rate++
Paresthesias+Decreased gastrointestinal motility++
Constipation++#Psychosis (rare)very rare
Dyspnea+Flushing, paroxysmal (rare)+
Visual disturbances+
Seizures, grand malvery rare

Incidence: ++++, 76%-100%; +++, 51%-75%; ++, 26%-50%; +, 1%-25%.

Adapted from Lenders et al.1 and Geroula et al.16

# indicates a significant difference between patients with and without pheochromocytoma/paraganglioma.

From Robertson RP et al: DeGroot’s endocrinology, basic science and clinical practice, ed 8, Philadelphia, 2023, Elsevier.

Etiology

  • Catecholamine-producing tumors that are usually located in the adrenal medulla.
  • Specific mutations of the RET protooncogene cause familial predisposition to pheochromocytoma in MEN-2.
  • Mutations in the von Hippel-Lindau tumor suppressor gene (VHL gene) cause familial disposition to pheochromocytoma in von Hippel-Lindau disease.
  • Recently identified genes for succinate dehydrogenase subunit D (SDHD) and succinate dehydrogenase subunit B (SDHB) predispose carriers to pheochromocytoma and globus tumors.

Diagnosis ⬆ ⬇

Differential Diagnosis

  • Anxiety disorder
  • Thyrotoxicosis
  • Amphetamine or cocaine abuse
  • Carcinoid
  • Essential hypertension
  • The differential diagnosis of pheochromocytoma-type spells is summarized in Table E3.

TABLE E3 Differential Diagnosis for Pheochromocytoma Based on Clinical Presentations

Neuroblastoma, ganglioneuroblastoma, ganglioneuroma
Adrenal medullary hyperplasia
Hyperadrenergic essential hypertension
Baroreflex failure
Thyrotoxicosis
Anxiety, panic attacks
Migraine or cluster headaches
Autonomic epilepsy
Chronic use of amphetamines and steroids
Chronic use of cocaine, tricyclic antidepressants
Chronic use of monoamine oxidase inhibitors
Ingestion of tyramine-containing foods or over-the-counter cold and cough preparations
Hypoglycemia, insulin reaction
Paroxysmal tachycardias including postural tachycardia syndrome
Angina pectoris or myocardial infarction
Mitral valve prolapse
Abdominal catastrophic situations/aortic dissection
Renal parenchymal or renal artery diseases (e.g., stenosis)
Intracranial lesions, cerebral vasculitis, and hemorrhage
Menopausal syndrome
Lead poisoning
Toxemia of pregnancy
Pseudopheochromocytoma
Acute intermittent porphyria

From Robertson RP et al: DeGroot’s endocrinology, basic science and clinical practice, ed 8, Philadelphia, 2023, Elsevier.

Workup

Laboratory evaluation and imaging studies (Table E4) to locate the neoplasm (Fig. E1). Anatomic and functional imaging studies that can be used to localize pheochromocytomas are summarized in Table E5. Misdiagnosis of pheochromocytoma is common. Correct interpretation of biochemical tests and imaging is crucial to a correct diagnosis (Table E6).

TABLE E6 Causes of False-Positive and False-Negative Results for Plasma Free or Urinary Deconjugated Normetanephrine (NMN), Metanephrine (MN), and Methoxytyramine (MTY)

Plasma Free MetanephrinesUrinary Deconjugated Metanephrines*
NMNMNMTYNMNMNMTY**
Sympathoadrenal Activation
Exercise or stressful daily activityFP++FP+?FP++FP+?
Medical conditions (e.g., heart failure)FP++-?FP++-?
Medical emergenciesFP+++FP++?FP+++FP++?
Seated blood sampling/upright postureFP++--+--
Mental stress/anxiety (e.g., needle phobia)FP++FP+????
Cold ambient temperatureFP+--???
Pharmacophysiological Causes
NE uptake blockers (e.g., tricyclics)FP++--FP++--
Nonselective alpha blockersFP++--FP++--
MAO inhibitors (rare)FP+++FP+++FP+++FP+++FP+++FP+++
SympathomimeticsFP+--FP+--
Foods or Drugs Containing Catecholamine Precursors or Related Compounds
Certain fruits, nuts, cereals, and other foods†--FP++FP+-FP++
L-dopa--FP+++FP+-FP+++
MHBA in curry leaves§nananaFN+++FN+++FN+++
Miscellaneous Causes
Collection of urine beyond/less than 24 hNaNaNaFP+/FN+FP+/FN+FP+/FN+
Large/small body sizeNaNaNaFP+/FN+FP+/FN+FP+/FN+
Dopamine-producing tumor**NaNa-NaNaFN++
UC of reference intervals too high/lowFN+/FP+FN+/FP+FN+/FP+FN+/FP+FN+/FP+FN+/FP+
Small tumor size (<2 cm)FN++FN+FN+FN++FN+FN+
No tumoral catecholamine synthesisFN+++FN+++FN+++FN+++FN+++FN+++

+, Weak influence; ++, mild influence; +++, strong influence; -, no influence; ?, influence unknown; FN, false negative; FP, false positive; MAO, monoamine oxidase; MHBA, 3-methoxy-4-hydroxybenzylamine; na, not applicable; NE, norepinephrine; UC, upper cutoff.

* Interferences for urine are shown for deconjugated measurements after an acid-hydrolysis step, but except for MHBA are likely similar for urinary free measurements.

** Urine methoxytyramine is a poor marker of tumoral dopamine production.

† A wide array of foods (e.g., fruits, nuts, meats) can elevate methoxytyramine in plasma and deconjugated normetanephrine and methoxytyramine in urine.

§ MHBA is an internal standard used in assays involving liquid chromatography with electrochemical detection, so only causes false-negative results for those assays.

From Robertson RP et al: DeGroot’s endocrinology, basic science and clinical practice, ed 8, Philadelphia, 2023, Elsevier.

TABLE E5 Anatomic and Functional Imaging Studies That Can Be Used to Localize Pheochromocytomas and Paragangliomas

Imaging ModalityMRICT18F-FDG68Ga-DOTA Peptide18F-FDA18F-DOPAMIBG
AdvantagesAnatomic detailAnatomic detailWidely available, preferred functional imaging testMost sensitive functional imaging study for all sites of disease, potential for therapy with avid diseaseSensitive functional imaging for primary tumor (except skull base and neck)Most sensitive functional imaging study for skull base and neck paragangliomasPotential for therapy if disease avid tumor is not resectable
DisadvantagesLower specificityLower specificityLower sensitivity and higher false-positive rate as compared with other functional imaging studiesNot widely availableNot widely availableNot widely availableLower sensitivity than other functioning imaging studies
Best clinical setting to use imaging studiesInitial localization of tumorInitial localization of tumorRule out metastatic disease or multiple primaryRule out metastatic disease or multiple primary; SDHx mutation carriers; when planning treatment with peptide receptor radionuclide therapyRule out metastatic disease or multiple primaryPatients with primary skull base and neck paragangliomas; multiple and metastatic diseaseWhen planning treatment with 131I-MIBG

CT, Computed tomography; DOPA, dihydroxyphenylalanine; DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; FDA, fluorodopamine; FDG, fluorodeoxyglucose; MIBG, metaiodobenzylguanidine; MRI, magnetic resonance imaging; SDH, succinate dehydrogenase.

From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.

TABLE E4 Proposed Clinical Algorithm for Imaging Investigations in Pheochromocytoma

Anatomic ImagingFunctional Imaging
Pheochromocytoma (sporadic)Adrenal CT or MRI
  • In selected cases: inconclusive result on anatomic imaging, size >5 cm, borderline elevation of metanephrines or uncertainty regarding their accuracy
  • 18F-FDOPA or 123I-MIBG preferred as first choices
  • 68Ga-DOTA-SSAs as second choice
  • Hereditary pheochromocytoma (except SDHx):
  • NF1/RET/VHL/MAX
  • Thoracoabdominopelvic
  • CT or MRI
  • In selected cases: inconclusive results on anatomic imaging regarding bilaterality in NF-1/RET, in VHL (due to multifocality risk) and MAX (due to multifocality and malignancy risk)
  • 18F-FDOPA preferred
  • 123I-MIBG as second choice
Extraadrenal sympathetic and/or multifocal and/or metastatic and/or SDHx mutation
  • Thoracoabdominopelvic
  • CT, craniocervical MRI, and temporal bone CT (for TP and JP)
  • 68Ga-DOTA-SSA preferred
  • 18F-FDG as second choice in SDHx
  • 18F-FDOPA as second choice in VHL/HIF2A
Head and neck paraganglioma (sporadic or unknown genetic background)Craniocervical MRI (with DCE sequences), temporal bone CT (for TP and JP)
  • 68Ga-DOTA-SSA preferred
  • 18F-FDOPA as second choice

CT, Computed tomography; DCE, dynamic contrast enhanced; 18F-FDG, (18F)-fluorodeoxyglucose; 18F-FDOPA, (18F)-fluorodihydroxyphenylalanine; 68Ga-DOTA-SSA, 68Ga-DOTA-somatostatin analog; 123I-MIBG, 123I-metaiodobenzylguanidine; JP, jugular paraganglioma; MRI, magnetic resonance imaging; TP, tympanic paraganglioma.

From Robertson RP et al: DeGroot’s endocrinology, basic science and clinical practice, ed 8, Philadelphia, 2023, Elsevier.

Figure E1 Algorithm for the diagnosis, localization, and management of pheochromocytoma.

!!flowchart!!

Initial plasma-free metanephrine testing can effectively exclude the diagnosis if the result is negative. A 24-h urine collection for catecholamines and their metabolites is generally performed twice, with cutoffs approximately twice the upper limit of normal being criteria for positivity (see Table E7). Clonidine suppression testing can be used for the small fraction of patients in whom the diagnosis remains uncertain after urine testing. Localization with computed tomography (CT) or magnetic resonance imaging (MRI) follows biochemical confirmation of the diagnosis, with metaiodobenzylguanidine (MIBG) scanning performed for younger patients and those otherwise at risk for multifocal disease. Phenoxybenzamine is given in escalating doses for at least 2 wk before surgery.

(From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.)

Laboratory Tests

  • Although there is no consensus on the best test, plasma-free metanephrines have been suggested as the test of first choice for excluding the tumor. Elevated plasma concentrations of normetanephrine or metanephrine have a sensitivity of up to 100%, but the specificity is markedly lower (85%).
  • 24-h urine collection will also show increased metanephrines (90% sensitivity, 95% specificity); the accuracy of the 24-h urinary levels for metanephrines can be improved by indexing urinary metanephrine levels by urine creatinine levels.
  • Cutoff values for biochemical diagnosis of pheochromocytoma are summarized in Table E7.
  • Medications that may affect measured levels of fractionated catecholamines and metanephrines are summarized in Table E6.

TABLE E7 Cutoff Values for Biochemical Diagnosis of Pheochromocytoma

Cutoff Value
Test*molgDefinitionsSensitivity (%)Specificity (%)
Plasma-free metanephrine03 nmol/L59 μg/LPaired test, positive result if either or both values are elevated9985-89
Plasma-free normetanephrine06 nmol/L110 μg/L
Urinary total metanephrines66 μmol/day13 mg/day71996
Urinary epinephrine191 nmol/day35 μg/day29996
Urinary norepinephrine1005 nmol/day170 μg/day50996
Urinary dopamine4571 nmol/day700 μg/day8100
Urinary total metanephrines and catecholamines-Grouped test, positive result if any one of the following three urinary values is elevated: Total metanephrines, epinephrine, norepinephrine, dopamine8899
Urinary vanillylmandelic acid40 μmol/day79 mg/day6495
Clonidine suppression testPositive result = elevated level after clonidine and fall of <4096100
Plasma-free normetanephrine061 nmol/L112 μg/L

* When it is performed twice, 24-h urine testing of urinary total metanephrines and catecholamines (grouped test) is highly sensitive and highly specific.

From Townsend CM et al: Sabiston textbook of surgery, ed 21, St Louis, 2022, Elsevier.

Imaging Studies

  • Abdominal computed tomography (CT) scan (Fig. E2) with and without contrast (88% sensitivity) is useful in locating pheochromocytomas >0.5 inch in diameter (90% to 95% accurate).
  • MRI with contrast: Pheochromocytomas demonstrate a distinctive MRI appearance (up to 100% sensitivity); MRI may become the diagnostic imaging modality of choice.
  • Scintigraphy with 131 or 1-123 I-MIBG (up to 100% sensitivity) (see Fig. E2): This norepinephrine analog localizes in adrenergic tissue; it is particularly useful in locating extraadrenal pheochromocytomas.
  • 6-[18F]Fluorodopamine PET is reserved for cases in which clinical symptoms and signs suggest pheochromocytoma, and results of biochemical tests are positive but conventional imaging studies cannot locate the tumor. It is also used for identification of metastatic disease.

Figure E2 Computed Tomography (CT) and 123I-Metaiodobenzylguanidine (123I-MIBG) Imaging of a 44-Yr-Old Man

He presented with a 9-yr history of hypertension and recent onset of head throbbing, chest pressure, and abdominal pain. The 24-h urine studies were abnormal: norepinephrine, 900 μg (normal, <170); epinephrine, 28 μg (normal, <35); dopamine, 468 μg (normal, <700); and total metanephrines, 17,958 μg (normal, <1000). A, Axial CT image with contrast shows a large, partially vascular, and partially necrotic left adrenal tumor (arrow). B, 123I-MIBG whole-body scan shows a large focus of increased radiotracer uptake in the left upper abdomen (arrow) that corresponds to the mass seen on the CT image; no other abnormal uptake is seen. C, 123I-MIBG and single-photon emission computed tomography (SPECT) fusion images correlate the images seen on CT (anatomic) with those seen on 123I-MIBG (physiologic) in the axial, coronal, and sagittal planes. After α- and β-adrenergic blockade, a 13.5-cm × 12-cm × 9-cm, 680-g pheochromocytoma was removed.

(From Melmed S: Williams textbook of endocrinology, ed 12, Philadelphia, 2011, Saunders, Elsevier.)

Treatment ⬆ ⬇

General Rx

Laparoscopic adrenalectomy (surgical resection for both benign and malignant disease):

  • Preoperative stabilization (Table E8) with combination of alpha-adrenergic blocking agents (phenoxybenzamine, prazosin, doxazosin, or terazosin), β-blocker, and liberal fluid and salt intake starting 10 to 14 days before surgery. β-Blockers should be avoided until patients receive adequate alpha-adrenergic blockade for several days to avoid hypertensive crisis due to unopposed alpha stimulation. Amlodipine or verapamil can be added to β-blockers if blood pressure control is still inadequate. Table E9 describes orally administered drugs to treat pheochromocytoma. Contraindicated medications are summarized in Table E10.
  • Hypertensive crisis preoperatively and intraoperatively can be controlled with nitroprusside. Table E11 summarizes intravenously administered drugs used to treat pheochromocytoma.

TABLE E11 Intravenously Administered Drugs Used to Treat Pheochromocytoma

AgentDosage Range
For Hypertension
PhentolamineAdminister a 1-mg IV test dose, then 2- to 5-mg IV boluses as needed or continuous infusion.
NitroprussideIV infusion rates of 2 μg/kg of body weight per min are suggested as safe. Rates >4 μg/kg/min may lead to cyanide toxicity within 3 h. Doses >10 μg/kg/min are rarely required, and the maximal dose should not exceed 800 μg/min.
NicardipineInitiate therapy at 5 mg/h; the IV infusion rate may be increased by 2.5 mg/h q15min up to a maximum of 15 mg/h.
For Cardiac Arrhythmia
LidocaineInitiate therapy with an IV bolus of 1-1.5 mg/kg (75-100 mg); additional boluses of 0.5-0.75 mg/kg (25-50 mg) can be given q5-10min if needed up to a maximum of 3 mg/kg. Loading is followed by maintenance IV infusion of 2-4 mg/min (30-50 μg/kg/min) adjusted for effect and settings of altered metabolism (e.g., heart failure, liver congestion) and as guided by blood level monitoring.
EsmololAn initial IV loading dose of 0.5 mg/kg is infused over 1 min, followed by a maintenance infusion of 0.05 mg/kg/min for the next 4 min. Depending on the desired ventricular response, the maintenance infusion may then be continued at 0.05 mg/kg/min or increased stepwise (e.g., by 0.1 mg/kg/min increments to a maximum of 0.2 mg/kg/min), with each step being maintained for ≥4 min.

IV, Intravenous.

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Elsevier.

TABLE E8 Proposed Algorithm for the Preoperative Treatment of Patients with Pheochromocytoma

Start α-adrenoceptor blocker at least 7-14 days before surgery
Oral salt and fluid loading (e.g., keep regular salt diet, may use NaCl tablets/250 mmol = 15 g/one to three tablets a day)
Gradually increase α-adrenoceptor blocker until hemodynamic goals* are met (e.g., until maximum dose of phenoxybenzamine 30-40 mg three times daily or doxazosin 12-15 mg twice daily)
Add β-adrenoceptor blocker after at least 2-4 days of α-adrenoceptor blocker, when significant tachycardia or a catecholamine-induced arrhythmia occurs (e.g., atenolol 12.5-25 mg once or twice daily, metoprolol 25-50 mg once, twice, or three times daily)
Gradually increase β-adrenoceptor blocker until hemodynamic goals* are met
Add calcium-channel antagonist when hemodynamic goals* are not met despite maximum α-adrenoreceptor blockade (e.g., nifedipine or amlodipine)
Administer a saline infusion (e.g., 2 L NaCL 0.9% in 24 h) 12-24 h before surgery

* Hemodynamic goals: supine systolic/diastolic blood pressure <130/80 mm Hg, systolic blood pressure in the upright position between 90 and 110 mm Hg, heart rate <80 beats per minute in the supine position and <100 beats per minute while standing.

Adapted from Berends AMA et al: Approach to the patient: perioperative management of the patient with pheochromocytoma or sympathetic paraganglioma, J Clin Endocrinol Metab 105:3088-3102, 2020.

TABLE E9 Orally Administered Drugs Used to Treat Pheochromocytoma

DrugInitial Dosage, mg/day* (Maximum)Side Effects
α-Adrenergic Blocking Agents
Phenoxybenzamine10† (100)†Postural hypotension, tachycardia, meiosis, nasal congestion, diarrhea, inhibition of ejaculation, fatigue
Prazosin1 (20)‡First-dose effect, dizziness, drowsiness, headache, fatigue, palpitations, nausea
Terazosin1 (20)†First-dose effect, asthenia, blurred vision, dizziness, nasal congestion, nausea, peripheral edema, palpitations, somnolence
Doxazosin1 (20)First-dose effect, orthostasis, peripheral edema, fatigue, somnolence
Combined α- and β-Adrenergic Blocking Agent
Labetalol200† (1200)†Dizziness, fatigue, nausea, nasal congestion, impotence
Calcium Channel Blocker
Nicardipine sustained-release30† (120)†Edema, dizziness, headache, flushing, nausea, dyspepsia
Catecholamine Synthesis Inhibitor
α-Methyl-ρ-l tyrosine (metyrosine)1000‡ (4000)‡Sedation, diarrhea, anxiety, nightmares, crystalluria, galactorrhea, extrapyramidal symptoms

* Given once daily unless otherwise indicated.

† Given in two doses daily.

‡ Given in three or four doses daily.

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Elsevier.

TABLE E10 Medications That Are Contraindicated in Patients with Suspected or Proven Pheochromocytoma

Dopamine D2 receptor antagonists(e.g., metoclopramide, antiemetics)
Sympathomimetics(e.g., ephedrine)
Nonselective β-adrenoceptor blockers(e.g. propranolol)
Opioid analgesics
Noradrenaline reuptake inhibitors(including tricyclics)
Monoamine oxidase inhibitors
Corticosteroids(particularly in high doses)
Peptides(e.g., adrenocorticotropic hormone, glucagon)
Neuromuscular blocking agents(used for anesthesia)
Serotonin reuptake inhibitors(rare)

From Robertson RP et al: DeGroot’s endocrinology, basic science and clinical practice, ed 8, Philadelphia, 2023, Elsevier.

Pearls & Considerations ⬆ ⬇

Comments

  • Obtaining a detailed family history is important because 25% of pheochromocytomas are familial.
  • Screening for pheochromocytoma should be considered in patients with any of the following:
    1. Malignant hypertension
    2. Poor response to antihypertensive therapy
    3. Paradoxic hypertensive response
    4. Hypertension during induction of anesthesia, parturition, surgery, or thyrotropin-releasing hormone testing
    5. Hypertension associated with imipramine or desipramine
    6. Neurofibromatosis (increased incidence of pheochromocytoma)
  • All patients with pheochromocytoma should be screened for MEN-2 and von Hippel-Lindau disease with the pentagastrin test, serum parathyroid hormone, ophthalmoscopy, MRI of the brain, CT scan of the kidneys and pancreas, and ultrasonography of the testes.
  • In patients with pheochromocytoma, routine analysis for mutations of RET, VHL, SDHD, and SDHB is indicated to identify pheochromocytoma-associated syndromes.
Related Content

  • Pheochromocytoma (Patient Information)
  • Hypertension (Related Key Topic)

Related Content ⬆

  1. Aggarwal S : Pheochromocytomas most commonly present as adrenal incidentalomas: a large tertiary center experienceJ Clin Endocrinol Metab. 109(1):e389-e396, 2024.