Pheochromocytoma differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2] Mohammed Abdelwahed M.D[3]

Overview

Pheochromocytoma must be differentiated from other causes of paroxysmal hypertension including severe paroxysmal hypertension (pseudopheochromocytoma), panic disorder, factitious hypertension, carcinoid syndrome, migraine headache, hyperthyroidism, renovascular hypertension, hypoglycemia, labile hypertension (White coat hypertension), stroke, compression of the lateral medulla, seizures, baroreflex failure and drugs.

Differentiating pheochromocytoma from other diseases

Pheochromocytoma must be differentiated from other causes of paroxysmal hypertension. The differentials include:

Disease Symptoms Signs Investigations
Pheochromocytoma[1][4] Features of sympathetic nervous systemhyperactivity and include:
Pseudopheochromocytoma (idiopathic)[1][2][3][4] Paroxysmal activation of the sympathetic system may cause:
Panic attacks

Laboratory studies that can exclude medical disorders other than panic disorder include:

Labile hypertension (White coat hypertension) Elevated blood pressure, tachycardia, and may be anxiety in a clinical setting but not in other settings[1]
Hyperthyroidism
Renovascular hypertension
Stroke and compression of lateral medulla (Lateral medullary syndrome)
  • Difficulty sitting upright without support
  • Hypotonia of the ipsilateral arm
  • Ipsilateral decreased pain and temperature sensation in the face
  • The corneal reflex is usually reduced in the ipsilateral eye
  • Contralateral loss of pain and thermal sensation involving the body and limbs
Seizures According to type; it may be focal or generalized, clinical or subclinical:[7]
  • Tonic-clonic seizure:
    • Repetitive twitches of arm and legs
    • Tongue bitting
    • Loss of consciousness
    • Symptoms occur suddenly and may persist
    • Muscle tension or tightening that causes twisting of the body, head, arms, or legs
    • Amnesia
    • Mood changes (fear, panic, or laughter)
    • Change in sensation of the skin over the arm, leg, or trunk
    • Vision changes and light flashes
    • Hallucinations
    • Tasting a bitter or metallic flavor
  • Complex partial seizure:
    • Confused or dazed and
    • Not be able to respond to questions or direction
  • Absence seizure:
    • Rapid blinking
    • Few seconds of staring into space
Carcinoid syndrome Hypertensive crisis occurs with malignant carcinoid syndrome[10]. Symptoms include:
Migraine headaches
  • Prodrome:
  • Pain phase
  • Postdrome phase[15]
CT is indicated in patients with:[1][2]

CT is not indicated in:

Drugs Sympathomimetic drugs that can induce symptoms simulating pheochromocytoma include:
Baroreflex failure[18]
  • Baroreflex failure patients show a normal or even an increased pressor response to cold-pressor and handgrip testing. These responses are attenuated in patients with autonomic failure.
  • Neck CT scan

Pheochromocytoma must be differentiated from other adrenal tumors such as adrenocortical adenoma, adrenal metastasis, and Cushing's syndrome.

Differential Diagnosis Clinical picture Imagings Laboratory tests
Adrenocortical carcinoma
Adrenal adenoma
Cushing's syndrome
  • Imaging may show mass if presents
Pheochromocytoma
Adrenal metastasis


References

  1. Mann SJ (1999). "Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment.". Arch Intern Med. 159 (7): 670–4. PMID 10218745. 
  2. Mann SJ (1999). "Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment.". Arch Intern Med. 159 (7): 670–4. PMID 10218745. 
  3. Mann SJ (1996). "Severe paroxysmal hypertension. An automatic syndrome and its relationship to repressed emotions.". Psychosomatics. 37 (5): 444–50. PMID 8824124. doi:10.1016/S0033-3182(96)71532-3. 
  4. Sharabi Y, Goldstein DS, Bentho O, Saleem A, Pechnik S, Geraci MF; et al. (2007). "Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma.". J Hypertens. 25 (11): 2286–95. PMID 17921824. doi:10.1097/HJH.0b013e3282ef5fac. 
  5. Iglesias P, Acosta M, Sánchez R, Fernández-Reyes MJ, Mon C, Díez JJ (2005). "Ambulatory blood pressure monitoring in patients with hyperthyroidism before and after control of thyroid function.". Clin Endocrinol (Oxf). 63 (1): 66–72. PMID 15963064. doi:10.1111/j.1365-2265.2005.02301.x. 
  6. Mintz G, Pizzarello R, Klein I (1991). "Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment.". J Clin Endocrinol Metab. 73 (1): 146–50. PMID 2045465. doi:10.1210/jcem-73-1-146. 
  7. 7.0 7.1 Mintz G, Pizzarello R, Klein I (1991). "Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment.". J Clin Endocrinol Metab. 73 (1): 146–50. PMID 2045465. doi:10.1210/jcem-73-1-146. 
  8. Brigo F, Storti M, Lochner P, Tezzon F, Fiaschi A, Bongiovanni LG; et al. (2012). "Tongue biting in epileptic seizures and psychogenic events: an evidence-based perspective.". Epilepsy Behav. 25 (2): 251–5. PMID 23041172. doi:10.1016/j.yebeh.2012.06.020. 
  9. Fountain NB, Van Ness PC, Swain-Eng R, Tonn S, Bever CT, American Academy of Neurology Epilepsy Measure Development Panel and the American Medical Association-Convened Physician Consortium for Performance Improvement Independent Measure Development Process (2011). "Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology.". Neurology. 76 (1): 94–9. PMID 21205698. doi:10.1212/WNL.0b013e318203e9d1. 
  10. Warner RR, Mani S, Profeta J, Grunstein E (1994). "Octreotide treatment of carcinoid hypertensive crisis.". Mt Sinai J Med. 61 (4): 349–55. PMID 7969229. 
  11. Sjöblom SM (1988). "Clinical presentation and prognosis of gastrointestinal carcinoid tumours.". Scand J Gastroenterol. 23 (7): 779–87. PMID 3227292. 
  12. Feldman JM (1986). "Urinary serotonin in the diagnosis of carcinoid tumors.". Clin Chem. 32 (5): 840–4. PMID 2421946. 
  13. Eriksson B, Arnberg H, Oberg K, Hellman U, Lundqvist G, Wernstedt C; et al. (1990). "A polyclonal antiserum against chromogranin A and B--a new sensitive marker for neuroendocrine tumours.". Acta Endocrinol (Copenh). 122 (2): 145–55. PMID 2316306. 
  14. Sundin A, Vullierme MP, Kaltsas G, Plöckinger U, Mallorca Consensus Conference participants. European Neuroendocrine Tumor Society (2009). "ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations.". Neuroendocrinology. 90 (2): 167–83. PMID 19077417. doi:10.1159/000184855. 
  15. Kelman L (2004). "The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs.". Headache. 44 (9): 865–72. PMID 15447695. doi:10.1111/j.1526-4610.2004.04168.x. 
  16. Krentz AJ, Mikhail S, Cantrell P, Hill GM (2001). "Drug Points: Pseudophaeochromocytoma syndrome associated with clozapine.". BMJ. 322 (7296): 1213. PMC 31620Freely accessible. PMID 11358774. 
  17. Kuchel O (1985). "Pseudopheochromocytoma.". Hypertension. 7 (1): 151–8. PMID 3980057. 
  18. Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM (1993). "The diagnosis and treatment of baroreflex failure.". N Engl J Med. 329 (20): 1449–55. PMID 8413455. doi:10.1056/NEJM199311113292003. 
  19. 19.0 19.1 Zar T, Peixoto AJ (2008). "Paroxysmal hypertension due to baroreflex failure.". Kidney Int. 74 (1): 126–31. PMID 18322544. doi:10.1038/ki.2008.30. 
  20. Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R; et al. (2015). "Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays.". J Hypertens. 33 (12): 2500–11. PMID 26372319. doi:10.1097/HJH.0000000000000727. 

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