Pheochromocytoma differential diagnosis: Difference between revisions

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, [[Panic disorder|panic disorder,]] [[Factitious hypertension]], [[carcinoid syndrome]], [[Migraine|Migraine headache]], [[Hyperthyroidism|Hyperthyroidism,]] [[Insulinoma|Insulinoma,]] [[Renovascular hypertension|Renovascular hypertension,]] [[Hypoglycemia]] and drugs.
, [[Panic disorder|panic disorder,]] [[Factitious hypertension]], [[carcinoid syndrome]], [[Migraine|Migraine headache]], [[Hyperthyroidism|Hyperthyroidism,]] [[Insulinoma|Insulinoma,]] [[Renovascular hypertension|Renovascular hypertension,]] [[Hypoglycemia]] and drugs.
{| class="wikitable"
!Disease
!Symptoms
!Signs
!Investigations
|-
|Pheochromocytoma
|
|
|
|-
|Pseudopheochromocytoma
|Paroxysmal activation of the sympathetic system causing hypertension and tachycardia <ref name="pmid10218745">{{cite journal| author=Mann SJ| title=Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment. | journal=Arch Intern Med | year= 1999 | volume= 159 | issue= 7 | pages= 670-4 | pmid=10218745 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10218745  }}</ref>that responds to alpha/beta blockade.<ref name="pmid102187452">{{cite journal| author=Mann SJ| title=Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment. | journal=Arch Intern Med | year= 1999 | volume= 159 | issue= 7 | pages= 670-4 | pmid=10218745 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10218745  }}</ref>Disorder is usually related to emotional distress.


DIFFERENTIAL DIAGNOSIS — In addition to pseudopheochromocytoma <ref name="pmid10218745">{{cite journal| author=Mann SJ| title=Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment. | journal=Arch Intern Med | year= 1999 | volume= 159 | issue= 7 | pages= 670-4 | pmid=10218745 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10218745 }}</ref>, the following diagnoses should be strongly considered among patients presenting with paroxysmal hypertension:
Acute onset of high blood pressure, headache, chest pain, nausea, palpitations, flushing. Duration of attacks ranges from minutes to hours.
 
|
Pseudopheochromocytoma most likely involves activation of the sympathetic system; this has been inferred from the following observations [5-11]:
|Increase in plasma catecholamines between and during attacks.<ref name="pmid8824124">{{cite journal| author=Mann SJ| title=Severe paroxysmal hypertension. An automatic syndrome and its relationship to repressed emotions. | journal=Psychosomatics | year= 1996 | volume= 37 | issue= 5 | pages= 444-50 | pmid=8824124 | doi=10.1016/S0033-3182(96)71532-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8824124 }}</ref><ref name="pmid17921824">{{cite journal| author=Sharabi Y, Goldstein DS, Bentho O, Saleem A, Pechnik S, Geraci MF et al.| title=Sympathoadrenal function in patients with paroxysmal hypertension: pseudopheochromocytoma. | journal=J Hypertens | year= 2007 | volume= 25 | issue= 11 | pages= 2286-95 | pmid=17921824 | doi=10.1097/HJH.0b013e3282ef5fac | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17921824 }}</ref>
 
|-
●Paroxysmal nature
|Panic attacks
 
|●Panic disorder Panic disorder can replicate many of the symptoms of pheochromocytoma because it is associated with increased sympathetic activity. Hypertension in these patients occurs primarily during treatment with a tricyclic antidepressant drug, which may increase the degree of sympathetic arousal.
●Association with tachycardia in some patients
 
●Increase in plasma catecholamines documented during attacks [5]
 
●Increase in baseline plasma epinephrine and metanephrines [9]
 
●Response to alpha/beta blockade [8]
 
The mechanism that underlies sympathetic activation is unclear but appears to involve emotional factors.
 
CLINICAL MANIFESTATIONS — In patients in whom the diagnosis of a pheochromocytoma has been excluded, who are considered to have pseudopheochromocytoma, hypertensive episodes are generally characterized by the following three features:
 
●An abrupt elevation of blood pressure (which can be greater than 200/110 mmHg in some patients) that is documented by a clinician or home blood pressure monitor
 
●Equally abrupt onset of distressful physical symptoms, such as headache, chest pain, dizziness, nausea, palpitations, flushing, and diaphoresis
 
●Attacks are not triggered by fear or panic, although fear does occur as a consequence of the frightening physical symptoms
 
The duration of episodes can range from 10 minutes to many hours, with frequency ranging from several per day to once every few months. Between episodes of paroxysmal hypertension, the blood pressure can be elevated (due to inadequately treated chronic hypertension), normal, or low (due to antihypertensive therapy initiated during an episode of paroxysmal hypertension).
 
Psychological characteristics — Patients with pseudopheochromocytoma usually insist that episodes are unrelated to emotional distress. This feature has tended to discourage consideration of a causal role for emotional factors. However, details of patients' psychosocial history and the success of psychologically based intervention in some cases (as described below) suggest that the disorder is usually related to emotions that have been kept from conscious awareness and therefore are not reported.
 
In the largest study to date, 14 of 21 patients (67 percent) acknowledged a past history of severe emotional trauma (such as the Holocaust or severe childhood trauma) or prolonged physical or emotional abuse [8]. They uniformly insisted that those events bore no lingering emotional impact. The remaining seven individuals did not report a history of overt emotional trauma or abuse, but careful interviewing indicated a pattern of minimizing awareness of distressful emotions and of not confiding in anyone.
 
Individuals with this disorder may feel some degree of emotional distress but seem immune to the more severe emotional distress experienced at times by most other people.
 
●Labile hypertension White coat hypertension, more commonly known as '''white coat syndrome''', is a phenomenon in which patients exhibit elevated [[blood pressure]] in a clinical setting but not in other settings.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid24107724-1|[1]]]</sup> The prevalence of white coat hypertension is approximately 13%.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid17921809-2|[2]]]</sup> Risk factors for white coat hypertension in observational studies include age, female sex, and being a non-smoker. The higher the blood pressure in the clinical setting, the lower the probability of white coat hypertension.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid24107724-1|[1]]]</sup>Ambulatory blood pressure monitoring and patient self-measurement using a home blood pressure monitoring device are being increasingly used to differentiate patients with white coat hypertension from patients with true hypertension. Ambulatory monitoring has been found to be a more practical and reliable method in detecting patients with white coat hypertension and for the prediction of target organ damage. The 2013 ESC/ESH recommendations recommend that white coat hypertension be confirmed within 3-6 months of initial diagnosis and that close follow-up and periodic out-of-office BP measurements be obtained.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid24107724-1|[1]]]</sup> The treatment of white coat hypertension remains controversial.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid16647616-3|[3]]]</sup> Finally, the risk of target organ damage and prognosis among patients with white coat hypertension is still unknown. Although white coat hypertension was initially considered intermediate in risk between normal blood pressure and hypertension, larger subsequent meta-analyses have not demonstrated a significant difference in outcomes between patients with white coat hypertension and those with normal blood pressure levels.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid17921809-2|[2]]][[Chronic hypertension differential diagnosis#cite note-pmid20847724-4|[4]]][[Chronic hypertension differential diagnosis#cite note-pmid22252396-5|[5]]]</sup><ref name="pmid28676236">{{cite journal| author=Wang XX, Shuai W, Peng Q, Li JX, Li P, Cheng XS et al.| title=White coat effect in hypertensive patients: the role of hospital environment or physician presence. | journal=J Am Soc Hypertens | year= 2017 | volume= | issue= | pages= | pmid=28676236 | doi=10.1016/j.jash.2017.06.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28676236 }}</ref>
 
●Panic disorder Panic disorder can replicate many of the symptoms of pheochromocytoma because it is associated with increased sympathetic activity. Hypertension in these patients occurs primarily during treatment with a tricyclic antidepressant drug, which may increase the degree of sympathetic arousal.
 
Pheochromocytoma — The diagnosis of pheochromocytoma must be excluded in all patients with unprovoked paroxysmal hypertension. Assays of plasma or urine catecholamines are diagnostic in 95 percent of patients with symptoms, and the high sensitivity of the plasma metanephrine assay is also documented  
Pheochromocytoma — The diagnosis of pheochromocytoma must be excluded in all patients with unprovoked paroxysmal hypertension. Assays of plasma or urine catecholamines are diagnostic in 95 percent of patients with symptoms, and the high sensitivity of the plasma metanephrine assay is also documented  


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The most critical clinical difference is that, in the absence of antecedent panic or emotional distress, pseudopheochromocytoma is viewed as an unexplained medical disorder. Therefore, clinicians and patients rarely consider an emotion-based cause or treatment because, by definition, patients fail to report any triggering emotional distress.
The most critical clinical difference is that, in the absence of antecedent panic or emotional distress, pseudopheochromocytoma is viewed as an unexplained medical disorder. Therefore, clinicians and patients rarely consider an emotion-based cause or treatment because, by definition, patients fail to report any triggering emotional distress.
 
|
Other causes of paroxysmal hypertension — Many additional disorders may present with paroxysmal hypertension, including the following:
|
 
|-
●Hyperthyroidism.<ref name="pmid15963064">{{cite journal| author=Iglesias P, Acosta M, Sánchez R, Fernández-Reyes MJ, Mon C, Díez JJ| title=Ambulatory blood pressure monitoring in patients with hyperthyroidism before and after control of thyroid function. | journal=Clin Endocrinol (Oxf) | year= 2005 | volume= 63 | issue= 1 | pages= 66-72 | pmid=15963064 | doi=10.1111/j.1365-2265.2005.02301.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15963064  }}</ref>: symptoms of hyperthyroidism include weight loss, heat intolerance, tremor, palpitations, anxiety, increased bowel disturbances , and shortness of breath. Goiter, skin flushing and eye proptosis are common clinical findings.
|Labile hypertension (White coat hypertension)
 
|Patients exhibit elevated [[blood pressure]] in a clinical setting but not in other settings.<sup>[[Chronic hypertension differential diagnosis#cite note-pmid24107724-1|[1]]]</sup> 
Increased sensitivity of beta receptors in heart to catecholamines <ref name="pmid20454652">{{cite journal| author=Mintz G, Pizzarello R, Klein I| title=Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment. | journal=J Clin Endocrinol Metab | year= 1991 | volume= 73 | issue= 1 | pages= 146-50 | pmid=2045465 | doi=10.1210/jcem-73-1-146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2045465  }}</ref> due to effect of thyroid hormones increase cardiac work and output and systolic hypertension.<ref name="pmid2045465">{{cite journal| author=Mintz G, Pizzarello R, Klein I| title=Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment. | journal=J Clin Endocrinol Metab | year= 1991 | volume= 73 | issue= 1 | pages= 146-50 | pmid=2045465 | doi=10.1210/jcem-73-1-146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2045465  }}</ref>  low thyroid-stimulating hormone (TSH) high free thyroxine (T4) and triiodothyronine (T3) concentrations.In patients with subclinical hyperthyroidism, TSH is below normal (but usually >0.05 mU/L)and serum free T4, T3, and free T3 are normal.
|Ambulatory blood pressure monitoring and patient self-measurement using a home blood pressure monitoring device are being increasingly used to differentiate patients with white coat hypertension from patients with true hypertension.
 
|Normal
●migraine headaches  (1) the [[prodrome]], which occurs hours or days before the headache, (2) the [[Aura (symptom)|aura]], which immediately precedes the headache, (3) the [[Pain and nociception|pain]] phase, also known as headache phase and (4) the postdrome phase.<ref name="pmid15447695">{{cite journal| author=Kelman L| title=The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. | journal=Headache | year= 2004 | volume= 44 | issue= 9 | pages= 865-72 | pmid=15447695 | doi=10.1111/j.1526-4610.2004.04168.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15447695  }}</ref>
|-
* [[Red eye|Conjunctival injection]] may be present
|Hyperthyroidism
 
|Symptoms of hyperthyroidism include: weight loss, heat intolerance, tremor, palpitations, anxiety, increased bowel disturbances , and shortness of breath. <ref name="pmid15963064">{{cite journal| author=Iglesias P, Acosta M, Sánchez R, Fernández-Reyes MJ, Mon C, Díez JJ| title=Ambulatory blood pressure monitoring in patients with hyperthyroidism before and after control of thyroid function. | journal=Clin Endocrinol (Oxf) | year= 2005 | volume= 63 | issue= 1 | pages= 66-72 | pmid=15963064 | doi=10.1111/j.1365-2265.2005.02301.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15963064  }}</ref>
* [[Horner's syndrome]] <sup>[[Migraine physical examination#cite note-1|[1]]]</sup> may be present
|Goiter, skin flushing and eye proptosis.
* [[Adie syndrome|Adie type pupil]] <sup>[[Migraine physical examination#cite note-2|[2]]]</sup> may be present
Increased sensitivity of beta receptors in heart to catecholamines <ref name="pmid20454652">{{cite journal| author=Mintz G, Pizzarello R, Klein I| title=Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment. | journal=J Clin Endocrinol Metab | year= 1991 | volume= 73 | issue= 1 | pages= 146-50 | pmid=2045465 | doi=10.1210/jcem-73-1-146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2045465  }}</ref> due to effect of thyroid hormones increase cardiac work and output and systolic hypertension.<ref name="pmid2045465">{{cite journal| author=Mintz G, Pizzarello R, Klein I| title=Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment. | journal=J Clin Endocrinol Metab | year= 1991 | volume= 73 | issue= 1 | pages= 146-50 | pmid=2045465 | doi=10.1210/jcem-73-1-146 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2045465  }}</ref>   
 
|Low thyroid-stimulating hormone (TSH) high free thyroxine (T4) and triiodothyronine (T3) concentrations.
* Cranial/ cervical muscle [[tenderness]] may be present
|-
* Listen for bruit at neck and head for clinical sights of [[Cerebral arteriovenous malformation|arteriovenous malformation]].
|Renovascular hypertension
[[CT]] is indicated in patients with: <sup>[[Migraine CT#cite note-1|[1]]]</sup> <sup>[[Migraine CT#cite note-pmid24400971-2|[2]]]</sup>
|
* Abnormal [[physical examination]]
** Increase of [[headache]]'s frequency
** Poor [[coordination]]
** [[Focal neurologic signs]]
** [[Headache]]'s awakening the patient at night<sup>[[Migraine CT#cite note-3|[3]]][[Migraine CT#cite note-4|[4]]]</sup>
* Atypical [[aura]]: sudden onset, lasting more than 1 hour, always at the same side and/or without [[visual]] symptoms
* Migraine attacks that begin after 50 years of age
[[CT]] is not indicated in:
* Patients with a diagnosis of migraine in accordance with the [[Migraine classification|criteria for migraine]].
* Differentiating a migraine from other primary [[headaches]]
 
●Renovascular hypertension
 
* Age of [[hypertension]] < 30 years and > 55 years
* Age of [[hypertension]] < 30 years and > 55 years
* Abrupt onset of [[hypertension]]
* Abrupt onset of [[hypertension]]
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* Refractory [[hypertension]] to 3 anti-hypertensive medications
* Refractory [[hypertension]] to 3 anti-hypertensive medications
* [[Malignant hypertension]]
* [[Malignant hypertension]]
 
|([[bruit]]) can be heard over the abdomen.
([[bruit]]) can be heard over the abdomen.
|Diagnosis by Duplex ultrasonography is considered class I recommendation. It may be used as an initial screening tool for diagnosis of atherosclerotic renal artery stenosis. [[Ultrasonography]] might not be very accurate in obese patients or those intestinal gas.<sup>[[Renal artery stenosis ultrasound#cite note-pmid23457117-1|[1]]]</sup>
 
|-
Diagnosis by Duplex ultrasonography is considered class I recommendation. It may be used as an initial screening tool for diagnosis of atherosclerotic renal artery stenosis. [[Ultrasonography]] might not be very accurate in obese patients or those intestinal gas.<sup>[[Renal artery stenosis ultrasound#cite note-pmid23457117-1|[1]]]</sup>
|Stroke and compression of lateral medulla
 
|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.<ref name="pmid10926969">{{cite journal| author=Phillips AM, Jardine DL, Parkin PJ, Hughes T, Ikram H| title=Brain stem stroke causing baroreflex failure and paroxysmal hypertension. | journal=Stroke | year= 2000 | volume= 31 | issue= 8 | pages= 1997-2001 | pmid=10926969 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10926969  }}</ref>
●Central nervous system lesions, such as stroke, tumor, hemorrhage, compression of lateral medulla, and trauma
|
 
|CT shows mass compressing lateral medulla or infarction in the same area.
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.<ref name="pmid10926969">{{cite journal| author=Phillips AM, Jardine DL, Parkin PJ, Hughes T, Ikram H| title=Brain stem stroke causing baroreflex failure and paroxysmal hypertension. | journal=Stroke | year= 2000 | volume= 31 | issue= 8 | pages= 1997-2001 | pmid=10926969 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10926969  }}</ref>
|-
 
|Seizures
Baroreflex failure, which is characterized by marked and frequent fluctuations in blood pressure, <ref name="pmid183225442">{{cite journal| author=Zar T, Peixoto AJ| title=Paroxysmal hypertension due to baroreflex failure. | journal=Kidney Int | year= 2008 | volume= 74 | issue= 1 | pages= 126-31 | pmid=18322544 | doi=10.1038/ki.2008.30 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322544  }}</ref>with both high and low readings . It is caused by hypofunctioning of the baroreflexes that normally buffer blood pressure fluctuations. The disorder is usually a result of injury to carotid baroreceptors, with most patients reporting a history of neck irradiation or surgery. <ref name="pmid18322544">{{cite journal| author=Zar T, Peixoto AJ| title=Paroxysmal hypertension due to baroreflex failure. | journal=Kidney Int | year= 2008 | volume= 74 | issue= 1 | pages= 126-31 | pmid=18322544 | doi=10.1038/ki.2008.30 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322544  }}</ref>
|Symptoms experienced by a person during a seizure depend on where in the brain the disturbance in electrical activity occurs. Recent studies show that seizures happen in sleep more often than was thought. A person having a tonic-clonic seizure may cry out, lose consciousness and fall to the ground, and convulse, often violently. A person having a [[complex partial seizure]] may appear confused or dazed and will not be able to respond to questions or direction. Some people have seizures that are not noticeable to others. Sometimes, the only clue that a person is having an [[absence seizure]] is rapid blinking or a few seconds of staring into space.
 
●Seizure disorder.
 
Symptoms experienced by a person during a seizure depend on where in the brain the disturbance in electrical activity occurs. Recent studies show that seizures happen in sleep more often than was thought. A person having a tonic-clonic seizure may cry out, lose consciousness and fall to the ground, and convulse, often violently. A person having a [[complex partial seizure]] may appear confused or dazed and will not be able to respond to questions or direction. Some people have seizures that are not noticeable to others. Sometimes, the only clue that a person is having an [[absence seizure]] is rapid blinking or a few seconds of staring into space.
* Change in alertness; the person cannot remember a period of time
* Change in alertness; the person cannot remember a period of time
* Mood changes, such as unexplainable fear, panic, joy, or laughter
* Mood changes, such as unexplainable fear, panic, joy, or laughter
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* Tasting a bitter or metallic flavor
* Tasting a bitter or metallic flavor
Many seizures, especially in children, are preceded by [[tachycardia]] that frequently persists throughout the seizure. This early increase in heart rate may supplement an aura as a physiological warning sign of an imminent seizure.
Many seizures, especially in children, are preceded by [[tachycardia]] that frequently persists throughout the seizure. This early increase in heart rate may supplement an aura as a physiological warning sign of an imminent seizure.
|
|An isolated abnormal electrical activity recorded by an [[electroencephalography]] examination without a clinical presentation is called subclinical seizure. They may identify background epileptogenic activity, as well as help identify particular causes of seizures.
|-
|[[Carcinoid syndrome]]
|Hypertensive crisis occurs with malignant carcinoid syndrome <ref name="pmid7969229">{{cite journal| author=Warner RR, Mani S, Profeta J, Grunstein E| title=Octreotide treatment of carcinoid hypertensive crisis. | journal=Mt Sinai J Med | year= 1994 | volume= 61 | issue= 4 | pages= 349-55 | pmid=7969229 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7969229  }}</ref> should be distinguished from pheochromocytoma. Patient 
|Cutaneous flushing Venous telangiectasia Diarrhea Bronchospasm Cardiac valvular lesions : tricusped incompitence.
|
* High urinary excretion of 5-HIAA <ref name="pmid3227292">{{cite journal| author=Sjöblom SM| title=Clinical presentation and prognosis of gastrointestinal carcinoid tumours. | journal=Scand J Gastroenterol | year= 1988 | volume= 23 | issue= 7 | pages= 779-87 | pmid=3227292 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3227292  }}</ref>
* High  urinary excretion of serotonin <ref name="pmid2421946">{{cite journal| author=Feldman JM| title=Urinary serotonin in the diagnosis of carcinoid tumors. | journal=Clin Chem | year= 1986 | volume= 32 | issue= 5 | pages= 840-4 | pmid=2421946 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2421946  }}</ref>
* High  chromogranin concentration Chromogranins (designated as A, B, and C) are proteins that are stored and released with peptides and amines in a variety of neuroendocrine tissues <ref name="pmid2316306">{{cite journal| author=Eriksson B, Arnberg H, Oberg K, Hellman U, Lundqvist G, Wernstedt C et al.| title=A polyclonal antiserum against chromogranin A and B--a new sensitive marker for neuroendocrine tumours. | journal=Acta Endocrinol (Copenh) | year= 1990 | volume= 122 | issue= 2 | pages= 145-55 | pmid=2316306 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2316306  }}</ref>
* High  blood serotonin concentration
* High  plasma 5-HIAA concentration


An isolated abnormal electrical activity recorded by an [[electroencephalography]] examination without a clinical presentation is called subclinical seizure. They may identify background epileptogenic activity, as well as help identify particular causes of seizures.
* CT is recommended for evaluation of all patients with carcinoid tumors <ref name="pmid19077417">{{cite journal| author=Sundin A, Vullierme MP, Kaltsas G, Plöckinger U, Mallorca Consensus Conference participants. European Neuroendocrine Tumor Society| title=ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. | journal=Neuroendocrinology | year= 2009 | volume= 90 | issue= 2 | pages= 167-83 | pmid=19077417 | doi=10.1159/000184855 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19077417  }}</ref>
|-
|[[Migraine headaches]] 
|[[prodrome|(1) '''Prodrome,''']] which occurs hours or days before the headache,


●Carcinoid syndrome: hypertensive crisis occurs with malignant carcinoid syndrome <ref name="pmid7969229">{{cite journal| author=Warner RR, Mani S, Profeta J, Grunstein E| title=Octreotide treatment of carcinoid hypertensive crisis. | journal=Mt Sinai J Med | year= 1994 | volume= 61 | issue= 4 | pages= 349-55 | pmid=7969229 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7969229  }}</ref> should be distinguished from pheochromocytoma. Patient
(2)  '''[[Aura (symptom)|Aura]],''' which immediately precedes the headache,  


CLINICAL FEATURES Cutaneous flushing Venous telangiectasia Diarrhea Bronchospasm Cardiac valvular lesions : tricusped incompitence. 
(3) [[Pain and nociception|'''the pain phase,''']] also known as headache phase and  
* Urinary excretion of 5-HIAA <ref name="pmid3227292">{{cite journal| author=Sjöblom SM| title=Clinical presentation and prognosis of gastrointestinal carcinoid tumours. | journal=Scand J Gastroenterol | year= 1988 | volume= 23 | issue= 7 | pages= 779-87 | pmid=3227292 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3227292  }}</ref>
* Urinary excretion of serotonin <ref name="pmid2421946">{{cite journal| author=Feldman JM| title=Urinary serotonin in the diagnosis of carcinoid tumors. | journal=Clin Chem | year= 1986 | volume= 32 | issue= 5 | pages= 840-4 | pmid=2421946 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2421946  }}</ref>
* Chromogranin concentration Chromogranins (designated as A, B, and C) are proteins that are stored and released with peptides and amines in a variety of neuroendocrine tissues <ref name="pmid2316306">{{cite journal| author=Eriksson B, Arnberg H, Oberg K, Hellman U, Lundqvist G, Wernstedt C et al.| title=A polyclonal antiserum against chromogranin A and B--a new sensitive marker for neuroendocrine tumours. | journal=Acta Endocrinol (Copenh) | year= 1990 | volume= 122 | issue= 2 | pages= 145-55 | pmid=2316306 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2316306  }}</ref>
* Blood serotonin concentration
* Plasma 5-HIAA concentration
CT is recommended for evaluation of all patients with carcinoid tumors <ref name="pmid19077417">{{cite journal| author=Sundin A, Vullierme MP, Kaltsas G, Plöckinger U, Mallorca Consensus Conference participants. European Neuroendocrine Tumor Society| title=ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. | journal=Neuroendocrinology | year= 2009 | volume= 90 | issue= 2 | pages= 167-83 | pmid=19077417 | doi=10.1159/000184855 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19077417  }}</ref>


●Drugs – cocaine, lysergic acid diethylamide, amphetamine, and clozapine <ref name="pmid11358774">{{cite journal| author=Krentz AJ, Mikhail S, Cantrell P, Hill GM| title=Drug Points: Pseudophaeochromocytoma syndrome associated with clozapine. | journal=BMJ | year= 2001 | volume= 322 | issue= 7296 | pages= 1213 | pmid=11358774 | doi= | pmc=31620 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11358774 }}</ref>. Sympathomimetic drugs that can induce symptoms simulating pheochromocytoma include high-dose phenylpropanolamine (a popular over-the-counter decongestant and appetite suppressant), cocaine, amphetamines, phencyclidine, epinephrine, phenylephrine, and terbutaline, and the combination of a monoamine oxidase (MAO) inhibitor and ingestion of tyramine-containing foods [7,26-29]. Mercury intoxication also can mimic pheochromocytoma, producing both hypertension and elevated urine and plasma catecholamines [30].
(4) '''[[Postdrome|The postdrome phase.]]<ref name="pmid15447695">{{cite journal| author=Kelman L| title=The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs. | journal=Headache | year= 2004 | volume= 44 | issue= 9 | pages= 865-72 | pmid=15447695 | doi=10.1111/j.1526-4610.2004.04168.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15447695 }}</ref>'''
|
* [[Red eye|Conjunctival injection]] may be present
 
* [[Horner's syndrome]] <sup>[[Migraine physical examination#cite note-1|[1]]]</sup> may be present
* [[Adie syndrome|Adie type pupil]] <sup>[[Migraine physical examination#cite note-2|[2]]]</sup> may be present


●Baroreflex failure, which is characterized by marked and frequent fluctuations in blood pressure, with both high and low readings [23]. It is caused by hypofunctioning of the baroreflexes that normally buffer blood pressure fluctuations. The disorder is usually a result of injury to carotid baroreceptors, with most patients reporting a history of neck irradiation or surgery.
* Cranial/ cervical muscle [[tenderness]] may be present
* Listen for bruit at neck and head for clinical sights of [[Cerebral arteriovenous malformation|arteriovenous malformation]].
|'''[[CT]] is indicated in patients with: <sup>[[Migraine CT#cite note-1|[1]]]</sup> <sup>[[Migraine CT#cite note-pmid24400971-2|[2]]]</sup>'''
* Abnormal [[physical examination]]
** Increase of [[headache]]'s frequency
** Poor [[coordination]]
** [[Focal neurologic signs]]
** [[Headache]]'s awakening the patient at night<sup>[[Migraine CT#cite note-3|[3]]][[Migraine CT#cite note-4|[4]]]</sup>
* Atypical [[aura]]: sudden onset, lasting more than 1 hour, always at the same side and/or without [[visual]] symptoms
* Migraine attacks that begin after 50 years of age
'''[[CT]] is not indicated in:'''
* Patients with a diagnosis of migraine in accordance with the [[Migraine classification|criteria for migraine]].
* Differentiating a migraine from other primary [[headaches]]
|-
|Drugs
|Sympathomimetic drugs that can induce symptoms simulating pheochromocytoma include high-dose phenylpropanolamin, cocaine, amphetamine, LSD, PCP. <ref name="pmid11358774">{{cite journal| author=Krentz AJ, Mikhail S, Cantrell P, Hill GM| title=Drug Points: Pseudophaeochromocytoma syndrome associated with clozapine. | journal=BMJ | year= 2001 | volume= 322 | issue= 7296 | pages= 1213 | pmid=11358774 | doi= | pmc=31620 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11358774  }}</ref> Combination of a monoamine oxidase (MAO) inhibitor and ingestion of tyramine-containing foods.<ref name="pmid3980057">{{cite journal| author=Kuchel O| title=Pseudopheochromocytoma. | journal=Hypertension | year= 1985 | volume= 7 | issue= 1 | pages= 151-8 | pmid=3980057 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3980057  }}</ref>
|
* Disturbed consciousness.
* nasal septum perforation in cocaine addiction.
* Needle marks in skin.
* History of antidepressants intake.
|Toxicology screening
|-
|Baroreflex failure
|
* Marked and frequent fluctuations in blood pressure, <ref name="pmid183225442">{{cite journal| author=Zar T, Peixoto AJ| title=Paroxysmal hypertension due to baroreflex failure. | journal=Kidney Int | year= 2008 | volume= 74 | issue= 1 | pages= 126-31 | pmid=18322544 | doi=10.1038/ki.2008.30 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322544  }}</ref>with both high and low readings .  
* It is caused by hypofunctioning of the baroreflexes that normally buffer blood pressure fluctuations.  
* The disorder is usually a result of injury to carotid baroreceptors, with most patients reporting a history of neck irradiation or surgery. <ref name="pmid18322544">{{cite journal| author=Zar T, Peixoto AJ| title=Paroxysmal hypertension due to baroreflex failure. | journal=Kidney Int | year= 2008 | volume= 74 | issue= 1 | pages= 126-31 | pmid=18322544 | doi=10.1038/ki.2008.30 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18322544  }}</ref>
|
|Neck CT
|} 


{{Reflist|2}}
{{Reflist|2}}

Revision as of 19:31, 6 July 2017

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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]

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, Insulinoma, Renovascular hypertension, Hypoglycemia and drugs.

Disease Symptoms Signs Investigations
Pheochromocytoma
Pseudopheochromocytoma Paroxysmal activation of the sympathetic system causing hypertension and tachycardia [1]that responds to alpha/beta blockade.[2]Disorder is usually related to emotional distress.

Acute onset of high blood pressure, headache, chest pain, nausea, palpitations, flushing. Duration of attacks ranges from minutes to hours.

Increase in plasma catecholamines between and during attacks.[3][4]
Panic attacks ●Panic disorder Panic disorder can replicate many of the symptoms of pheochromocytoma because it is associated with increased sympathetic activity. Hypertension in these patients occurs primarily during treatment with a tricyclic antidepressant drug, which may increase the degree of sympathetic arousal.

Pheochromocytoma — The diagnosis of pheochromocytoma must be excluded in all patients with unprovoked paroxysmal hypertension. Assays of plasma or urine catecholamines are diagnostic in 95 percent of patients with symptoms, and the high sensitivity of the plasma metanephrine assay is also documented

pseudopheochromocytoma insist that the disorder is unrelated to psychologic factors.

Panic disorder — Panic disorder is characterized by episodes of fear or panic, and is commonly associated with physical symptoms such as chest pain, headache, palpitations, flushing, and dizziness, along with some degree of blood pressure elevation [16-20]. Panic disorder and pseudopheochromocytoma share similar physical symptoms, and both respond to treatment with an antidepressant agent. As mentioned above, panic disorder is present in as many as 40 percent of patients evaluated for pseudopheochromocytoma,

However, the two disorders differ from each other in that the presentation of pseudopheochromocytoma is dominated by autonomic manifestations (ie, paroxysmal hypertension). In patients with pseudopheochromocytoma, fear occurs only in response to the physical symptoms. By contrast, panic disorder is dominated by emotional manifestations (ie, panic), and accompanying blood pressure changes are milder.

The most critical clinical difference is that, in the absence of antecedent panic or emotional distress, pseudopheochromocytoma is viewed as an unexplained medical disorder. Therefore, clinicians and patients rarely consider an emotion-based cause or treatment because, by definition, patients fail to report any triggering emotional distress.

Labile hypertension (White coat hypertension) Patients exhibit elevated blood pressure in a clinical setting but not in other settings.[1]  Ambulatory blood pressure monitoring and patient self-measurement using a home blood pressure monitoring device are being increasingly used to differentiate patients with white coat hypertension from patients with true hypertension. Normal
Hyperthyroidism Symptoms of hyperthyroidism include: weight loss, heat intolerance, tremor, palpitations, anxiety, increased bowel disturbances , and shortness of breath. [5] Goiter, skin flushing and eye proptosis.

Increased sensitivity of beta receptors in heart to catecholamines [6] due to effect of thyroid hormones increase cardiac work and output and systolic hypertension.[7]

Low thyroid-stimulating hormone (TSH) high free thyroxine (T4) and triiodothyronine (T3) concentrations.
Renovascular hypertension (bruit) can be heard over the abdomen. Diagnosis by Duplex ultrasonography is considered class I recommendation. It may be used as an initial screening tool for diagnosis of atherosclerotic renal artery stenosis. Ultrasonography might not be very accurate in obese patients or those intestinal gas.[1]
Stroke and compression of lateral medulla 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] CT shows mass compressing lateral medulla or infarction in the same area.
Seizures Symptoms experienced by a person during a seizure depend on where in the brain the disturbance in electrical activity occurs. Recent studies show that seizures happen in sleep more often than was thought. A person having a tonic-clonic seizure may cry out, lose consciousness and fall to the ground, and convulse, often violently. A person having a complex partial seizure may appear confused or dazed and will not be able to respond to questions or direction. Some people have seizures that are not noticeable to others. Sometimes, the only clue that a person is having an absence seizure is rapid blinking or a few seconds of staring into space.
  • Change in alertness; the person cannot remember a period of time
  • Mood changes, such as unexplainable fear, panic, joy, or laughter
  • Change in sensation of the skin, usually spreading over the arm, leg, or trunk
  • Vision changes, including seeing flashing lights
  • Rarely, hallucinations (seeing things that aren't there)
  • Falling, loss of muscle control, occurs very suddenly
  • Muscle twitching that may spread up or down an arm or leg
  • Muscle tension or tightening that causes twisting of the body, head, arms, or legs
  • Shaking of the entire body
  • Tasting a bitter or metallic flavor

Many seizures, especially in children, are preceded by tachycardia that frequently persists throughout the seizure. This early increase in heart rate may supplement an aura as a physiological warning sign of an imminent seizure.

An isolated abnormal electrical activity recorded by an electroencephalography examination without a clinical presentation is called subclinical seizure. They may identify background epileptogenic activity, as well as help identify particular causes of seizures.
Carcinoid syndrome Hypertensive crisis occurs with malignant carcinoid syndrome [9] should be distinguished from pheochromocytoma. Patient Cutaneous flushing Venous telangiectasia Diarrhea Bronchospasm Cardiac valvular lesions : tricusped incompitence.
  • High urinary excretion of 5-HIAA [10]
  • High urinary excretion of serotonin [11]
  • High chromogranin concentration Chromogranins (designated as A, B, and C) are proteins that are stored and released with peptides and amines in a variety of neuroendocrine tissues [12]
  • High blood serotonin concentration
  • High plasma 5-HIAA concentration
  • CT is recommended for evaluation of all patients with carcinoid tumors [13]
Migraine headaches (1) Prodrome, which occurs hours or days before the headache,

(2)  Aura, which immediately precedes the headache,

(3) the pain phase, also known as headache phase and

(4) The postdrome phase.[14]

CT is indicated in patients with: [1] [2]

CT is not indicated in:

Drugs Sympathomimetic drugs that can induce symptoms simulating pheochromocytoma include high-dose phenylpropanolamin, cocaine, amphetamine, LSD, PCP. [15] Combination of a monoamine oxidase (MAO) inhibitor and ingestion of tyramine-containing foods.[16]
  • Disturbed consciousness.
  • nasal septum perforation in cocaine addiction.
  • Needle marks in skin.
  • History of antidepressants intake.
 Toxicology screening
Baroreflex failure
  • Marked and frequent fluctuations in blood pressure, [17]with both high and low readings .
  • It is caused by hypofunctioning of the baroreflexes that normally buffer blood pressure fluctuations.
  • The disorder is usually a result of injury to carotid baroreceptors, with most patients reporting a history of neck irradiation or surgery. [18]
 Neck CT
  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.


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