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 The symptoms of a pheochromocytoma are those of sympathetic nervous systemhyperactivity and include:
Pseudopheochromocytoma[1][2][3][4] Paroxysmal activation of the sympathetic system causing:
Panic attacks

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

Labile hypertension (White coat hypertension)
Hyperthyroidism
Renovascular hypertension
Stroke and compression of lateral medulla (Lateral medullary syndrome) Extensive unilateral infarction of the brain stem in the region of the nucleus tractus solitarius may result in partial baroreflex dysfunction, increased sympathetic activity, and neurogenic paroxysmal hypertension[8]
Seizures According to type; it may be focal or generalized, clinical or subclinical:
  • 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[9]. Symptoms include:
Migraine headaches
  • Prodrome:
  • Pain phase
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
  • Neck CT scan
Disease Prominent clinical features Investigations
Hyperthyroidism The main symptoms include:
Essential hypertension Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below: JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension:
Generalized anxiety disorder According to DSM V, the following criteria should be present to fit the diagnosis of generalized anxiety disorder:
  1. The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months
  2. Difficulty to control the apprehension
  3. Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations)
  4. The anxiety or the physical manifestations must affect the social and the daily life of the patient
  5. Exclusion of another medical condition or the effect of another administered substance
  6. Exclusion of another mental disorder causing the symptoms
-
Menopause The perimenopausal symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of estrogens, progestin, and testosterone. Some of these symptoms such as formication etc may be associated with the hormone withdrawal process.
  • B-HCG should always be done first to rule out pregnancy especially in women under the age of 45 years
  • FSH can be measured but it can be falsely normal or low
  • TSH, T3 and T4 to rule out thyroid abnormalities
  • Prolactin can be measured to rule out prolactinoma as a cause of menopause
Opioid withdrawal disorder According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal:
  1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an opioid antagonist after a period of opioid use.
  2. Development of three or more of the following criteria minutes to days after cessation of drug use: dysphoric mood, nausea or vomiting, muscle aches, Lacrimation or rhinorrhea, pupillary dilation, piloerection, or sweating, diarrhea, yawning, fever, and insomnia.
  3. The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient.
  4. The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.
  • Urine drug screen to rule out any other associated drug abuse
  • Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
Pheochromocytoma The hallmark symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include:
  • Palpitations especially in epinephrine producing tumors.
  • Anxiety often resembling that of a panic attack
  • Sweating
  • Headaches occur in 90 % of patients.
  • Paroxysmal attacks of hypertension but some patients have normal blood pressure.
  • It may be asymptomatic and discovered by incidence screening especially MEN patients.

Please note that not all patients with pheochromocytoma experience all classical symptoms.

Diagnostic lab findings associated with pheochromocytoma include:
  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. doi:10.1016/S0033-3182(96)71532-3. PMID 8824124.
  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. doi:10.1097/HJH.0b013e3282ef5fac. PMID 17921824.
  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. doi:10.1111/j.1365-2265.2005.02301.x. PMID 15963064.
  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. doi:10.1210/jcem-73-1-146. PMID 2045465.
  7. 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. doi:10.1210/jcem-73-1-146. PMID 2045465.
  8. Phillips AM, Jardine DL, Parkin PJ, Hughes T, Ikram H (2000). "Brain stem stroke causing baroreflex failure and paroxysmal hypertension". Stroke. 31 (8): 1997–2001. PMID 10926969.
  9. 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.
  10. Sjöblom SM (1988). "Clinical presentation and prognosis of gastrointestinal carcinoid tumours". Scand J Gastroenterol. 23 (7): 779–87. PMID 3227292.
  11. Feldman JM (1986). "Urinary serotonin in the diagnosis of carcinoid tumors". Clin Chem. 32 (5): 840–4. PMID 2421946.
  12. 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.
  13. 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. doi:10.1159/000184855. PMID 19077417.
  14. Kelman L (2004). "The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs". Headache. 44 (9): 865–72. doi:10.1111/j.1526-4610.2004.04168.x. PMID 15447695.
  15. Krentz AJ, Mikhail S, Cantrell P, Hill GM (2001). "Drug Points: Pseudophaeochromocytoma syndrome associated with clozapine". BMJ. 322 (7296): 1213. PMC 31620. PMID 11358774.
  16. Kuchel O (1985). "Pseudopheochromocytoma". Hypertension. 7 (1): 151–8. PMID 3980057.
  17. Zar T, Peixoto AJ (2008). "Paroxysmal hypertension due to baroreflex failure". Kidney Int. 74 (1): 126–31. doi:10.1038/ki.2008.30. PMID 18322544.
  18. Zar T, Peixoto AJ (2008). "Paroxysmal hypertension due to baroreflex failure". Kidney Int. 74 (1): 126–31. doi:10.1038/ki.2008.30. PMID 18322544.