Pheochromocytoma differential diagnosis: Difference between revisions

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{{Pheochromocytoma}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Pheochromocytoma]]
{{CMG}}; {{AE}} {{AAM}}
{{CMG}}; {{AE}} {{AAM}} {{MAD}}
 
==Overview==
Pheochromocytoma must be differentiated from other causes of [[paroxysmal hypertension]] including severe [[paroxysmal hypertension]] (pseudopheochromocytoma), [[Panic disorder|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:
{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Investigations
|-
|Pheochromocytoma<sup>[[Renal artery stenosis ultrasound#cite note-pmid23457117-1|[1]]][[Pheochromocytoma laboratory findings#cite note-pmid12574179-4|[4]]]</sup>
|Features of [[sympathetic nervous system]]<nowiki/>hyperactivity and include:
* [[Palpitations]] (especially in [[epinephrine]] producing tumors)
* [[Anxiety]] 
* [[Sweating]]
* [[Headaches]] (90 % of patients)
* Paroxysmal attacks of [[hypertension]]
* May be asymptomatic (incidentally discovered in [[Multiple endocrine neoplasia|MEN]] syndrome patients)
|
* [[Tachycardia]]
* [[Hypertension]], including paroxysmal (sporadic, episodic) high [[blood pressure]], which sometimes can be more difficult to detect.
* [[Orthostatic hypotension]]
|
* '''High-risk patients''':
** [[Plasma]] fractionated [[Metanephrine|metanephrines]]
** 24-hour [[urinary]] fractionated [[Metanephrine|metanephrines]], catecholamines
** Imaging studies ([[CT scan]], [[Magnetic resonance imaging|MRI]] and  iodine-123-meta-iodobenzylguanidine or MIBG scintiscan)
 
* '''Low-risk patients''':
** 24-hour [[urinary]] fractionated [[catecholamines]] and [[Metanephrine|metanephrines]]
|-
|Pseudopheochromocytoma (idiopathic)<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><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><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 activation of the [[Sympathetic nervous system|sympathetic system]] may cause:
* Emotional distress
* Acute onset of high [[blood pressure]]
* [[Headache]]
* [[Chest pain]]
* [[Nausea]]
* [[Palpitation|Palpitations]]
* [[Flushing]]
* Duration of attacks ranges from minutes to hours
* Physical symptoms occur before feeling fear
 
|
* [[Hypertension]]
* [[Tachycardia]]
|
* Increase in plasma [[catecholamines]] between and during attacks
|-
|[[Panic attacks]]
|
* Paroxysms of increased [[Sympathetic nervous system|sympathetic activity]]
* Episodes of fear or [[panic attacks]]
* [[Chest pain]]
* [[Headache]]
* [[Palpitations]]
* [[Flushing]]
* Response to [[antidepressants]]
* Fear precedes physical symptoms.
|
* Patients look anxious
* [[Tachycardia]]
* [[Hypertension]]
* [[Sweating]]
|
Laboratory studies that can exclude medical disorders other than [[panic disorder]] include:
* [[Electrolyte|Serum electrolytes]]
* [[Serum glucose]]
* [[Cardiac enzymes]]
* Urine [[toxicology]] [[Screening (medicine)|screening]]
|-
|Labile hypertension ([[White coat hypertension]])
|
* No history of [[hypertension]]
|Elevated [[blood pressure]], [[tachycardia]], and may be [[anxiety]] in a clinical setting but not in other settings<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]].
|-
|[[Hyperthyroidism]]
|
* [[Weight loss]]
* Heat intolerance
* [[Tremors]]
* [[Palpitations]]
* [[Anxiety]]
* Increased [[bowel]] disturbances
* [[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>
|
* [[Goiter|Goiter]]
* Skin [[flushing]]
* [[Proptosis]]
* Increased sensitivity of [[beta receptors]] in the 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 an effect of [[Thyroid hormone|thyroid hormones]] increase [[cardiac]] work and [[Cardiac Output|output]]
* [[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 [[Thyroxine|free thyroxine]] (T4) concentration
* High [[triiodothyronine]] (T3) concentration
|-
|[[Renal artery stenosis|Renovascular hypertension]]
|
* Common in individuals < 30 years or > 55 years
* Abrupt onset of [[hypertension]]
* Accelerated [[hypertension]] that was previously well-controlled
* Refractory [[hypertension]] to 3 [[Anti-hypertensive|anti-hypertensive medications]]
* [[Headache]]
* [[Nausea]]
* [[Subconjunctival hemorrhage]]
|
* [[Bruit]] can be heard over the [[abdomen]]
|
* [[Duplex ultrasound|Duplex ultrasonography]] may be used as an initial [[Screening (medicine)|screening]] tool for diagnosis of [[Atherosclerotic disease|atherosclerotic]] [[renal artery stenosis]]
* [[Ultrasonography]] (might not be very accurate in [[obese]] patients or those with [[intestinal]] gas)<sup>[[Renal artery stenosis ultrasound#cite note-pmid23457117-1|[1]]]</sup>
|-
|[[Stroke]] and [[Lateral medullary syndrome|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|baroreflex dysfunction]], increased sympathetic activity, and neurogenic [[paroxysmal hypertension]].
* [[Blurred vision]] or [[diplopia]]
* Weakness of [[Bulbar palsy|bulbar muscles]]
* [[Respiratory failure|Respiratory dysfunction]]
* [[Nystagmus]]
* [[Dizziness]]
|
* 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
|
* [[Computed tomography|CT]] shows mass compressing [[Lateral medullary syndrome|lateral medulla]] or infarction in the same area
|-
|[[Seizures]]
|According to type; it may be focal or generalized, clinical or subclinical:<ref name="pmid2045465" />
* [[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
** [[Hallucination|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
|
* Physical examination is important when [[central nervous system infection]] or hemorrhage are diagnostic possibilities
 
* A tongue bite or laceration in [[Tonic-clonic seizure|generalized tonic-clonic seizure]]<ref name="pmid23041172">{{cite journal|author=Brigo F, Storti M, Lochner P, Tezzon F, Fiaschi A, Bongiovanni LG et al.|title=Tongue biting in epileptic seizures and psychogenic events: an evidence-based perspective.|journal=Epilepsy Behav|year=2012|volume=25|issue=2|pages=251-5|pmid=23041172|doi=10.1016/j.yebeh.2012.06.020|pmc=|url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23041172}}</ref>
|
* Abnormal [[electroencephalography]]: a positive test without a clinical presentation is called a [[Subclinical seizure|sub-clinical seizure]].<ref name="pmid21205698">{{cite journal|author=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|title=Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology.|journal=Neurology|year=2011|volume=76|issue=1|pages=94-9|pmid=21205698|doi=10.1212/WNL.0b013e318203e9d1|pmc=|url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21205698}}</ref>
* [[Lumbar puncture]] is useful to exclude acute [[central nervous system infections]].
* A neuroimaging study should be performed in all adults with a first seizure to evaluate structural brain abnormalities. [[Magnetic resonance imaging]] is preferred over [[computed tomography]].
|-
|[[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>. Symptoms include:
* Severe [[chest]] pain
* Severe [[headache]]
* [[Confusion]] and [[blurred vision]]
* [[Nausea and vomiting]]
* Severe [[anxiety]]
* [[Shortness of breath]]
* [[Seizures]]
* Unresponsiveness
|
* [[Cutaneous]] [[flushing]]
* [[Venous]] [[telangiectasia]]
* [[Diarrhea]]
* [[Bronchospasm]]
* [[Valvular heart disease|Cardiac valvular lesions]] ([[Tricuspid regurgitation|tricuspid incompetence]])
|
* 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[[Chromogranin|(Chromogranin]](A, B, and C) are proteins that are stored and released with [[peptides]] and [[amines]] in a variety of [[Neuroendocrine cells|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>
 
* [[Computed tomography|CT]] is recommended for evaluation of all patients with [[Carcinoid syndrome|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:'''
** Occurs hours or days before a [[headache]]
 
* '''[[Aura (symptom)|Aura]]'''
** Immediately precedes the [[headache]]
 
* Pain phase
** Also known as [[headache]] phase
 
* 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]]
 
* [[Horner's syndrome]]<sup>[[Migraine physical examination#cite note-1|[1]]]</sup> 
* [[Adie's pupil]] <sup>[[Migraine physical examination#cite note-2|[2]]]</sup> 
 
* [[Cranial]]/ [[Cervical spine|cervical]] [[muscle]] [[tenderness]] 
* [[Bruit]] at [[neck]] and [[head]] for clinical signs of [[Cerebral arteriovenous malformation|an arteriovenous malformation]]
* [[Photosensitivity]]
|'''[[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]]<nowiki/>s awakening the patient at nigt<sup>[[Migraine CT#cite note-3|[3]]][[Migraine CT#cite note-4|[4]]]</sup>
* Atypical [[aura]]
* Sudden onset
* Lasting more than 1 hour
* Always on the same side
* With or without [[visual]] symptoms
* [[Migraine]] attacks that begin after 50 years of age
'''[[CT]] is not indicated in:'''
* Patients with a diagnosis of a migraine in accordance with the [[Migraine classification|criteria for migraine]]
* Differentiating a migraine from other primary [[headaches]]
|-
|Drugs
|[[Sympathomimetic drug|Sympathomimetic drugs]] that can induce symptoms simulating pheochromocytoma include:
* High-dose [[phenylpropanolamine]]
* [[Cocaine]]
* [[Amphetamine|Amphetamines]]
* Lysergic acid diethylamide ([[Lysergic Acid Diethylamide|LSD]])
* Phenylcyclidine (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 inhibitor|monoamine oxidase (MAO) inhibitor]] and ingestion of [[Tyramine|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 on the [[skin]]
* History of [[antidepressants|antidepressant]]<nowiki/>intake
|
* [[Urine]] [[Toxicology screen|toxicology screening]]
|-
|[[Baroreflex|Baroreflex failure]]<ref name="pmid8413455">{{cite journal| author=Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM| title=The diagnosis and treatment of baroreflex failure. | journal=N Engl J Med | year= 1993 | volume= 329 | issue= 20 | pages= 1449-55 | pmid=8413455 | doi=10.1056/NEJM199311113292003 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8413455  }}</ref>
|
* 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 [[Baroreflex|baroreflexes]] that normally buffer [[blood pressure]] fluctuations.
* The disorder is usually a result of injury to [[Baroreceptors|carotid baroreceptors]], with most patients reporting a history of neck [[irradiation]] or [[surgery]].<ref name="pmid183225442" />
* History of changes of heart rate during normal daily activities
|
* Increase in blood pressure with standing.
* Profound [[orthostatic hypotension]] in the absence of an adequate heart rate increase. The [[hypotension]] is immediately reversible in the [[Supine position|supine position.]]
 
* Determination of [[respiratory sinus arrhythmia]], [[Valsalva maneuver|a Valsalva maneuver,]] and cold-pressor and handgrip testing, can be helpful to diagnose it.
 
* 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.
 
* Twenty-four–hour [[blood pressure]] monitor can be useful to demonstrate the large [[blood pressure]] fluctuations and the tracking of [[blood pressure]] and [[heart rate]].
|
* Neck [[Computed tomography|CT]] scan
|} 
Pheochromocytoma must be differentiated from other adrenal tumors such as [[adrenocortical adenoma]], adrenal [[metastasis]], and [[Cushing's syndrome]].
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center"
 
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differential Diagnosis}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Clinical picture}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Imagings}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Laboratory tests}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''Adrenocortica'''l carcinoma
| style="padding: 5px 5px; background: #F5F5F5;" |
* Mass effect symptoms
* Symptoms related to  excess [[glucocorticoid]]
* Symptoms related to  excess [[mineralocorticoid]]
* Symptoms related to  excess [[androgen]] or [[estrogen]] secretion
|
* Irregular shape
* Non-[[homogeneous]] density because of central areas of low attenuation due to [[tumor]] [[necrosis]]
* [[Tumor]] [[calcification]]
* Diameter usually >4 cm
* Unilateral location
* High unenhanced [[Computed tomography|CT]] attenuation values (>20 HU)
* Non-[[homogeneous]] enhancement on [[Computed tomography|CT]] with [[intravenous]] [[Contrast medium|contrast]]
* Delay in [[contrast medium]] washout (10 minutes after administration of [[contrast]], an absolute [[contrast medium]] washout of less than 50 percent)
* Hypointensity compared with [[liver]] on T1 weighted [[Magnetic resonance imaging|MRI]] and high to intermediate signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]]
* High standardized uptake value (SUV) on [[FDG-PET|FDG]]-[[PET scan|PET-CT]] study
* Evidence of local [[invasion]] or [[Metastasis|metastases]]
|
* [[Androgen|Adrenal androgens]] ([[DHEAS|DHEAS)]]
* [[Androstenedione]]
* Bioavailable [[testosterone]] should be measured in every patient.
* [[17-Hydroxyprogesterone|17-hydroxyprogesterone]]
* Serum [[estradiol]] in men and postmenopausal women
* [[Cortisol level]]
* Fasting serum [[cortisol]] at 8 AM following a 1 mg dose of [[dexamethasone]] at bedtime
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Adrenal adenoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Symptoms related to  excess [[glucocorticoid]]
* Symptoms related to  excess [[mineralocorticoid]]
|
* Round, [[homogeneous]] with sharp margination
* Unilateral with diameter less than 4 cm
* Low unenhanced [[Computed tomography|CT]] attenuation values (<10 HU)
* Rapid [[contrast medium]] washout after administration of contrast
* An absolute [[contrast medium]] washout of more than 50 percent
* [[Chemical shift]]: evidence of [[lipid]] on [[Magnetic resonance imaging|MRI]]
* Isointensity with [[liver]] on both T1 and T2 weighted [[Magnetic resonance imaging|MRI]] sequences
|
* [[Cortisol level]]
* Fasting [[serum]] [[cortisol]] at 8 AM following a 1 mg dose of [[dexamethasone]] at bedtime
* [[Renin]] ([[Plasma renin activity|PRA]]) or plasma renin concentration (PRC): very low in patients with [[primary aldosteronism]], usually less than 1 ng/mL per hour for [[Plasma renin activity|PRA]] and usually undetectable for PRC<ref name="pmid26372319">{{cite journal| author=Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R et al.| title=Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. | journal=J Hypertens | year= 2015 | volume= 33 | issue= 12 | pages= 2500-11 | pmid=26372319 | doi=10.1097/HJH.0000000000000727 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26372319  }}</ref>
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Cushing's syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Rapid [[Obesity|weight gain]], particularly of the [[trunk]] and [[face]] with [[limbs]] sparing ([[central obesity]])
* Proximal [[muscle weakness]]
* A [[round face]] often referred to as a "[[moon face]]"
* Excess [[sweating]]
* [[Headache]]
|
* Imaging may show [[mass]] if presents
|
* 24-hour [[urine]] [[cortisol]]
* Midnight salivary [[cortisol]]
* Low-dose [[dexamethasone]] suppression test; high [[cortisol]] level after the [[dexamethasone]] test is suggestive of [[hypercortisolism]].
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Pheochromocytoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Palpitations]] especially in [[Epinephrine|epinephrine-]]<nowiki/>producing [[Tumor|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 incidentally after [[Screening (medicine)|screening]] for [[MEN, type 2|MEN]] patients.
|
* Increased [[attenuation]] on non-enhanced [[Computed tomography|CT]] (>20 HU)
* Increased [[mass]] [[vascularity]]
* Delay in [[contrast medium]] washout (10 minutes after administration of [[contrast]], an absolute [[contrast medium]] washout of less than 50 percent)
* High signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]]
* [[Cystic]] and [[hemorrhagic]] changes
* Variable size and may be [[bilateral]]
|
* [[Plasma]] fractionated [[Metanephrine|metanephrines]] 
* 24-hour [[urinary]] fractionated [[Metanephrine|metanephrines]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Adrenal metastasis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Symptoms]] and [[signs]] of primary [[malignancy]] especially [[lung cancer]]
* General constitutional symptoms:
**[[Fever]]
**[[Fatigue]]
**[[Weight loss]]
|
* Irregular shape and non-[[homogeneous]] nature
* Tendency to be [[bilateral]]
* High un-enhanced [[Computed tomography|CT]] [[attenuation]] values (>20 HU) and enhancement with [[Contrast medium|intravenous contrast]] on [[Computed tomography|CT]]
* Delay in [[contrast medium]] washout (10 minutes after administration of contrast, an absolute [[contrast medium]] washout of less than 50 percent)
* Isointensity or slightly less intense than the [[liver]] on T1 weighted [[Magnetic resonance imaging|MRI]] and high to intermediate signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]] (representing an increased water content)
* Elevated standardized uptake value on [[FDG-PET|FDG]]-[[PET scan]]
|
|}


{{PleaseHelp}}


==Overview==
{| class="wikitable"
Pheochromocytoma must be differentiated from [[anxiety]], [[carcinoid]], and [[hypoglycemia]].
! rowspan="2" |S.No.
! rowspan="2" |Disease
! colspan="3" |Symptoms
! colspan="2" |Signs
! colspan="3" |Diagnosis
! rowspan="2" |Comments
|-
!Abdominal Pain
!Hematuria
!Headache
!Abdominal mass
!Abdominal tenderness
!Ultrasonography
!CT scan
!Histology
|-
|1.
|[[Wilms' tumor|Wilms tumor]]
|<nowiki>+</nowiki>
|<nowiki>+ </nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|
*It is the best initial diagnostic study used in cases suspected with [[Wilms tumor]].
*[[Ultrasonography]] can help identify the mass as a kidney mass.
*It can distinguish [[tumor]] mass from other causes of renal swelling like [[hydronephrosis]].<ref name="pmid61529362">{{cite journal |vauthors=Hartman DS, Sanders RC |title=Wilms' tumor versus neuroblastoma: usefulness of ultrasound in differentiation |journal=J Ultrasound Med |volume=1 |issue=3 |pages=117–22 |date=April 1982 |pmid=6152936 |doi= |url=}}</ref>
*[[Doppler ultrasonography]] can help to detect invasion of [[renal vein]] and [[Inferior vena cava|IVC]] by the tumor.<ref name="pmid30036602">{{cite journal |vauthors=De Campo JF |title=Ultrasound of Wilms' tumor |journal=Pediatr Radiol |volume=16 |issue=1 |pages=21–4 |date=1986 |pmid=3003660 |doi= |url=}}</ref>
|
*Findings on [[CT scan]] which can be suggestive of  [[Wilms tumor]] include:<ref name="pmid4080660">{{cite journal |vauthors=Cahan LD |title=Failure of encephalo-duro-arterio-synangiosis procedure in moyamoya disease |journal=Pediatr Neurosci |volume=12 |issue=1 |pages=58–62 |date=1985 |pmid=4080660 |doi= |url=}}</ref>
**Heterogeneous soft-tissue density masses
**These masses have frequent areas of [[calcification]] (~10%) and fat-density regions
**[[Lymph node]] metastasis
*[[CT scan]] of the renal mass can further reveal:
**Invasion of surrounding organs
**[[Thrombus]] in or occlusion of the [[renal vein]] and/or the [[inferior vena cava]]
**Abdominal lymph nodes and contralateral involvement
|
*Wilms tumor has a triphasic appearance.
*It is comprised of 3 types of cells:
**[[Stromal]]
**[[Epithelium|Epithelial]]
**[[Blastema|Blastemal]]
*All the 3 types are not required for the diagnosis of Wilms tumor.
*Primitive tubules and [[Glomerulus|glomeruli]] are often seen comprised of [[Cancer|neoplastic]] cells.
*Beckwith and Palmer reported in NWTS the different histopathologic types of Wilms tumor to categorize them based on prognosis.<ref name="pmid1978">{{cite journal |vauthors=Jolly RD, Stellwagen E, Babul J, Vodkaĭlo LV, Titov VL, Moldomusaev DM, Maianskiĭ AN |title=Mannosidosis of Angus Cattle: a prototype control program for some genetic diseases |journal=Adv Vet Sci Comp Med |volume=19 |issue=23 |pages=1–21 |date=November 1975 |pmid=1978 |doi= |url=}}</ref>
 
*Spindled cell [[stroma]] surrounding abortive tubules and [[Glomerulus|glomeruli]] is characteristic.
*The stroma may include:
**Striated [[muscle]] [[cartilage]]
**[[bone]]
**[[Adipose tissue|Fat tissue]]
**[[Fibrous connective tissue|Fibrous tissue.]]
|
|-
|2.
|[[Renal cell carcinoma]]
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+/-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
* [[Ultrasound]] (US) may be helpful when CT scan results are equivocal. It is noteworthy to mention that not all renal cell [[carcinomas]] are detectable on [[ultrasound]].
|Both [[CT]] and [[MRI]] may be used to detect [[neoplastic]] masses that may define renal cell carcinoma or metastasis of the primary cancer. [[CT]] scan and use of intravenous (IV) contrast is generally used for work-up and follow-up of patients with [[Renal cell carcinoma|renal cell carcinom]]<nowiki/>a.
|The histological pattern of renal cell [[carcinoma]] depends whether it is [[Papillary|papillary,]] [[chromophobe]] or [[collecting duct]] renal cell carcinoma.
|
|-
|3.
|[[Malignant rhabdoid tumor|Rhabdoid kidney disease]]
| +
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
* [[Ultrasound]] shows a complex cystic mass.
|
* [[CT]] scan may be diagnostic of malignant rhabdoid tumor. Findings on [[CT]] scan suggestive of malignant rhabdoid tumor include a large, heterogenous, centrally located mass, which is lobulated with individual lobules separated by intervening areas of decreased attenuation, relating to either previous [[hemorrhage]] or [[necrosis]]. Enhancement is similarly heterogeneous. [[Calcification]] is relatively common, observed in 20-50% of cases and is typically linear and tends to outline tumor [[lobules]].
|
* [[Malignant]] rhabdoid tumor is characterized by the round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of [[eosinophilic]] cytoplasm with frequent mitotic figures.
|
|-
|4.
|[[Polycystic kidney disease]]
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+ (from hypertension)</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
Ultrasound may be helpful in the diagnosis of polycystic kidney disease. Findings on an ultrasound diagnostic of polycystic kidney disease include:<ref name="pmid25786098">{{cite journal |vauthors=Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, Kasiske BL, Odland D, Pei Y, Perrone RD, Pirson Y, Schrier RW, Torra R, Torres VE, Watnick T, Wheeler DC |title=Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference |journal=Kidney Int. |volume=88 |issue=1 |pages=17–27 |date=July 2015 |pmid=25786098 |pmc=4913350 |doi=10.1038/ki.2015.59 |url=}}</ref><ref name="pmid18945943">{{cite journal |vauthors=Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, Parfrey P, Cramer B, Coto E, Torra R, San Millan JL, Gibson R, Breuning M, Peters D, Ravine D |title=Unified criteria for ultrasonographic diagnosis of ADPKD |journal=J. Am. Soc. Nephrol. |volume=20 |issue=1 |pages=205–12 |date=January 2009 |pmid=18945943 |pmc=2615723 |doi=10.1681/ASN.2008050507 |url=}}</ref>
*At least three unilateral or bilateral [[cysts]] in patients 15 - 39 years old
*Atleast two [[cysts]] in each [[kidney]] in patients 40 - 59 years old
*Atleast four [[cysts]] in each [[kidney]] in patients 60 years of age or older
|
[[Renal]] CT scan may be helpful in the diagnosis of polycystic kidney disease. Findings on CT scan diagnostic of ADPKD include:
* Numerous [[renal]] [[cysts]] of varying size and shape with little intervening [[parenchyma]] with water [[attenuation]] and very thin wall.
* Reduction in [[sinus]] [[fat]] due to expansion of the [[cortex]]
* Occasional complex [[cysts]] with hyperdense appearance, with possible septations or calcifications
* Multiple [[homogeneous]] and hypoattenuating [[cystic]] lesions in the [[liver]] in patients with [[liver]] involvement
|
*On microscopic histopathological analysis, interstitial fibrosis, tubular atrophy, thickening and lamellation of tubular basement membranes, microcysts and negative immunofluorescence for complement and immunoglobulin are characteristic findings of ADPKD.<ref name="pmid12234310">{{cite journal |vauthors=Stavrou C, Koptides M, Tombazos C, Psara E, Patsias C, Zouvani I, Kyriacou K, Hildebrandt F, Christofides T, Pierides A, Deltas CC |title=Autosomal-dominant medullary cystic kidney disease type 1: clinical and molecular findings in six large Cypriot families |journal=Kidney Int. |volume=62 |issue=4 |pages=1385–94 |date=October 2002 |pmid=12234310 |doi=10.1111/j.1523-1755.2002.kid581.x |url=}}</ref><ref name="pmid24509297">{{cite journal |vauthors=Bleyer AJ, Kmoch S, Antignac C, Robins V, Kidd K, Kelsoe JR, Hladik G, Klemmer P, Knohl SJ, Scheinman SJ, Vo N, Santi A, Harris A, Canaday O, Weller N, Hulick PJ, Vogel K, Rahbari-Oskoui FF, Tuazon J, Deltas C, Somers D, Megarbane A, Kimmel PL, Sperati CJ, Orr-Urtreger A, Ben-Shachar S, Waugh DA, McGinn S, Bleyer AJ, Hodanová K, Vylet'al P, Živná M, Hart TC, Hart PS |title=Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1 |journal=Clin J Am Soc Nephrol |volume=9 |issue=3 |pages=527–35 |date=March 2014 |pmid=24509297 |pmc=3944763 |doi=10.2215/CJN.06380613 |url=}}</ref><ref name="pmid21775974">{{cite journal |vauthors=Faguer S, Decramer S, Chassaing N, Bellanné-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengelé JP, Dahan K, Ronco P, Devuyst O, Chauveau D |title=Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood |journal=Kidney Int. |volume=80 |issue=7 |pages=768–76 |date=October 2011 |pmid=21775974 |doi=10.1038/ki.2011.225 |url=}}</ref><ref name="pmid20378641">{{cite journal |vauthors=Heidet L, Decramer S, Pawtowski A, Morinière V, Bandin F, Knebelmann B, Lebre AS, Faguer S, Guigonis V, Antignac C, Salomon R |title=Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases |journal=Clin J Am Soc Nephrol |volume=5 |issue=6 |pages=1079–90 |date=June 2010 |pmid=20378641 |pmc=2879303 |doi=10.2215/CJN.06810909 |url=}}</ref>
 
|
|-
|5.
|[[Pheochromocytoma]]
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+ (as a part of the hypertension paroxysm)</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|
* CT is the preferred imaging modality for the diagnosis of pheochromocytoma.
|The following findings may be observed on [[CT scan]]:<ref name="pmid1787652">{{cite journal| author=Bravo EL| title=Pheochromocytoma: new concepts and future trends. | journal=Kidney Int | year= 1991 | volume= 40 | issue= 3 | pages= 544-56 | pmid=1787652 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1787652  }}</ref>
*Most common extra-[[Adrenal gland|adrenal]] locations are superior and inferior [[abdominal]] [[Paraaortic lymph node|paraaortic]] areas, the [[urinary bladder]], [[thorax]], [[head]], [[neck]] and [[pelvis]].<ref name="pmid1729490">{{cite journal| author=Whalen RK, Althausen AF, Daniels GH| title=Extra-adrenal pheochromocytoma. | journal=J Urol | year= 1992 | volume= 147 | issue= 1 | pages= 1-10 | pmid=1729490 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1729490  }}</ref>


==Differentiating Pheochromocytoma from other Diseases==
*In sporadic pheochromocytoma, [[CT]] and [[MRI]] are good choices. The choice depends on availability and cost.<ref name="pmid191248172">{{cite journal| author=Baid SK, Lai EW, Wesley RA, Ling A, Timmers HJ, Adams KT et al.| title=Brief communication: radiographic contrast infusion and catecholamine release in patients with pheochromocytoma. | journal=Ann Intern Med | year= 2009 | volume= 150 | issue= 1 | pages= 27-32 | pmid=19124817 | doi= | pmc=3490128 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19124817  }}</ref>
The [[differential diagnosis]] of pheochromocytoma includes:
*In patients with the [[multiple endocrine neoplasia]] type 2 ([[Multiple endocrine neoplasia type 2|MEN2]]) syndrome, [[CT]] may miss the [[tumors]].<ref name="pmid17876522">{{cite journal| author=Bravo EL| title=Pheochromocytoma: new concepts and future trends. | journal=Kidney Int | year= 1991 | volume= 40 | issue= 3 | pages= 544-56 | pmid=1787652 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1787652  }}</ref>
*[[Anxiety disorder]]s
|
*[[Carcinoid tumor]]
* On microscopic pathology, [[Pheochromocytoma]] typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing [[eosinophilic]] cytoplasm separated by fibrovascular [[stroma]].
*[[Paraganglioma]]s
|
*[[Essential hypertension]]
|-
*[[Hyperthyroidism]]
|6.
*[[Insulinoma]]
|[[Burkitt's lymphoma|Burkitt lymphoma]]
*[[Paroxysmal supraventricular tachycardia]]
|<nowiki>+/- (in non-endemic or sporadic form of the disease)</nowiki>
*[[Renovascular hypertension]]
|<nowiki>-</nowiki>
*[[Hypoglycemia]]
|<nowiki>-</nowiki>
*[[Stress]]
|<nowiki>-</nowiki>
*[[Exercise]]
|<nowiki>-</nowiki>
*[[Medication]]s such as [[stimulant]]s, [[methyldopa]], and [[dopamine agonist]]s
|
* Abdominal [[ultrasonography]] may show [[splenomegaly]] and [[ascites]].
|
* Chest, abdomen, and pelvis [[CT]] scan may be helpful in the diagnosis of [[Burkitt's lymphoma]] but it is not done routinely.<ref name="medlineplus">Burkitt lymphoma. MedlinePlus. https://www.nlm.nih.gov/medlineplus/ency/article/001308.htm Accessed on September 30, 2015</ref>
|
*On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:<ref name="pmid12610094">{{cite journal |author=Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L |title=Burkitt's lymphoma: new insights into molecular pathogenesis |journal=J. Clin. Pathol. |volume=56 |issue=3 |pages=188–92 |year=2003 |month=March |pmid=12610094 |pmc=1769902 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=12610094}}</ref>
:*Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- '''key feature''' (i.e. tumor nuclei size similar to that of [[histiocytes]] or [[endothelial cells]])
:*Round nucleus
:*Small nucleoli
:*Relatively abundant cytoplasm ([[basophilic]])
:*Brisk mitotic rate and [[apoptotic]] activity
:*Cellular outline usually appears squared off
:*"Starry-sky pattern":
::*The ''stars'' in the pattern are tingible-body macrophages (macrophages containing [[apoptotic]] tumor cells.
::*The tumour cells are the ''sky''
|
|-
|7.
|[[Intussusception]]
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+/- </nowiki>
|<nowiki>+</nowiki>
|
* [[Ultrasound]] is the [[Gold standard (test)|gold standard]] imaging modality used to diagnose intussusception<ref name="pmid17308922">{{cite journal |vauthors=Ko HS, Schenk JP, Tröger J, Rohrschneider WK |title=Current radiological management of intussusception in children |journal=Eur Radiol |volume=17 |issue=9 |pages=2411–21 |year=2007 |pmid=17308922 |doi=10.1007/s00330-007-0589-y |url=}}</ref>
**Target or doughnut sign<ref name="pmid8470658">{{cite journal |vauthors=Boyle MJ, Arkell LJ, Williams JT |title=Ultrasonic diagnosis of adult intussusception |journal=Am. J. Gastroenterol. |volume=88 |issue=4 |pages=617–8 |year=1993 |pmid=8470658 |doi= |url=}}</ref>
***Edematous intussuscipien forms an external ring around the centrally located intussusceptum
***Target sign is usually seen in right lower quadrant
**Layers of intussusception forms pseudo-kidney appearance on the transverse view
|
* [[Computed tomography|CT scan]] may be helpful in the [[diagnosis]] of intussusception. [[Computed tomography|CT scan]] maybe used when other image modalities like [[x-ray]] and [[ultrasound]] have not given positive results but suspicion of intussusception is high.
|
* Intussusception occurs if there is an imbalance between the longitudinal and radial [[smooth muscle]] forces of [[intestine]] that maintain its normal structure. This imbalance leads to a segment of [[intestine]] to invaginate into another segment and cause entero-enteral intussusception. [[Etiology]] of intussusception is either idiopathic or [[Pathology|pathologic]] (lead point). 
|
|-
|8.
|[[Hydronephrosis]]
|<nowiki>+</nowiki>
|<nowiki>+/-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+ (CVA tenderness in case of pyelonephritis)</nowiki>
|
* [[Ultrasound]] allows for visualization of the [[ureters]] and [[kidneys]] and can be used to assess the presence of [[hydronephrosis]] and/or [[hydroureter]]. 
|
* In the case of [[renal colic]] (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually an intravenous urogram. This has the advantage of showing whether there is any obstruction of flow of urine causing [[hydronephrosis]] as well as demonstrating the function of the other kidney. Many [[Stones- kidney|stones]] are not visible on [[X ray|plain x ray]] or IVU but 99% of [[Stones- kidney|stones]] are visible on [[CT]] and therefore CT is becoming a common choice of initial investigation.
|
* The kidney undergoes extensive dilation with atrophy and thinning of the renal cortex.
|
|-
|9.
|[[Dysplasia|Dysplastic kidney]]
|N/A
|N/A
|N/A
|N/A
|N/A
|
MCDK is usually diagnosed by [[ultrasound]] examination before birth.
* Mass of non-communicating cysts of variable size.
* Unlike severe [[hydronephrosis]], in which the largest cystic structure (the renal pelvis) lies in a central location and is surrounded by dilated calices, in multicystic dysplastic kidney the cyst distribution shows no recognizable pattern.
* [[Dysplasia|Dysplastic]], echogenic [[parenchyma]] may be visible between the cysts, but no normal renal parenchyma is seen.
|
* MCKD can be discovered accidentally on [[CT]] scan.
* [[CT scan]] shows myltiple cysts with absence of renal parenchyma.
|
* MCKD is the result of abnormal differentiation of the renal parenchyma.
|
|-
|10.
|[[Neuroblastoma|Pediatric Neuroblastoma]]
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+/-</nowiki>
|<nowiki>+/-</nowiki>
|
* On ultrasound, neuroblastoma is characterized by a heterogeneous [[echogenicity]] due to the [[vascular]], [[necrotic]], and calcified content of the mass.<ref name="radio">Neuroblastoma. Radiopaedia (2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 8 2015</ref>
|
*CT scan is the investigation of choice for the diagnosis of neuroblastoma.<ref name="pmid21736987">{{cite journal| author=Colon NC, Chung DH| title=Neuroblastoma. | journal=Adv Pediatr | year= 2011 | volume= 58 | issue= 1 | pages= 297-311 | pmid=21736987 | doi=10.1016/j.yapd.2011.03.011 | pmc=PMC3668791 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21736987  }}</ref>
*On CT scan, neuroblastoma is characterized by:<ref name="radio2">Neuroblastoma. Radiopaedia (2015) http://radiopaedia.org/articles/neuroblastoma Accessed on October, 8 2015</ref>
:*Heterogeneous mass
:*[[Calcification]]
:*[[Necrosis]]
:*Compression of the surrounding vessels
:*Invasion of the [[psoas]] [[muscle]] or [[kidney]]s
:*Swollen [[lymph node]]s
|
*On microscopic histopathological analysis the presence of round blue cells separated by thin [[fibrous]] septa are characteristic findings of neuroblastoma.
*Other findings of neuroblastoma on [[light microscopy]] may include:<ref name="patho">Neuroblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Adrenal_gland#Neuroblastoma Accessed on October, 5 2015</ref>
:*Homer-Wright rosettes (rosettes with a small  meshwork of fibers at the center)
:*Neuropil-like [[stroma]] (paucicellular stroma with a cotton candy-like appearance)
*On [[electron microscopy]] neuroblastoma is characterized by:
:*Dendritic processes with longitudinally oriented [[microtubule]]s
:*Membrane bound electron-dense [[granule]]s that contain [[catecholamine]]s
:*Presence of [[desmosomes]]
:*Absence of [[glycogen]]
|
|-
|11.
|[[Rhabdomyosarcoma|Pediatric Rhabdomyosarcoma]]
|<nowiki>+</nowiki>
|<nowiki>+/-</nowiki>
|<nowiki>+/-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+/-</nowiki>
|
|On [[CT scan]], rhabdomyosarocma is characterized by:
* Soft tissue density
* Some enhancement with [[contrast]]
* Adjacent bony destruction (over 20% of cases)
|
* Rhadbomyosarcoma has an appearance similar to the other round blue cell tumors such as [[Ewing sarcoma]] and [[Osteoblastoma|small cell osteoblastoma]].
|
|-
|12.
|[[Mesoblastic nephroma]]
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|
*[[Ultrasound]] may be helpful in the diagnosis of mesoblastic nephroma.
*Mesoblastic nephroma may presents as a well-defined [[mass]] with low-level homogeneous echoes.<ref name="radio3">Mesoblastic nephroma.Dr Ayush Goel and Dr Yuranga Weerakkody et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/mesoblastic-nephroma</ref>
*The presence of concentric echogenic and hypoechoic rings can be a helpful diagnostic feature of [[mesoblastic nephroma]].
|
* [[CT scan]] may be helpful in the diagnosis of mesoblastic nephroma.
* Findings on CT scan suggestive of mesoblastic nephroma include:
:* Solid hypoattenuating renal lesion
:* Variable contrast enhancement
:* No [[calcification]]
|
Classic mesoblastic nephroma
* [[Spindle cells]] in [[fascicles]]
* Infiltrative border
Cellular mesoblastic nephroma
* Plump cells with vesicular nuclei
* Well-defined border
* Mitotically active
Mixed mesoblastic nephroma
* Both classic pattern and cellular pattern areas are present
|Most common renal tumor that occurs in 1st month of life
|}


==References==
==References==
Line 27: Line 643:


[[Category:Endocrinology]]
[[Category:Endocrinology]]
 
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Latest revision as of 19:31, 25 February 2019

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
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


S.No. Disease Symptoms Signs Diagnosis Comments
Abdominal Pain Hematuria Headache Abdominal mass Abdominal tenderness Ultrasonography CT scan Histology
1. Wilms tumor + + - + +
  • Wilms tumor has a triphasic appearance.
  • It is comprised of 3 types of cells:
  • All the 3 types are not required for the diagnosis of Wilms tumor.
  • Primitive tubules and glomeruli are often seen comprised of neoplastic cells.
  • Beckwith and Palmer reported in NWTS the different histopathologic types of Wilms tumor to categorize them based on prognosis.[24]
2. Renal cell carcinoma + + +/- + -
  • Ultrasound (US) may be helpful when CT scan results are equivocal. It is noteworthy to mention that not all renal cell carcinomas are detectable on ultrasound.
Both CT and MRI may be used to detect neoplastic masses that may define renal cell carcinoma or metastasis of the primary cancer. CT scan and use of intravenous (IV) contrast is generally used for work-up and follow-up of patients with renal cell carcinoma. The histological pattern of renal cell carcinoma depends whether it is papillary, chromophobe or collecting duct renal cell carcinoma.
3. Rhabdoid kidney disease + + - + -
  • CT scan may be diagnostic of malignant rhabdoid tumor. Findings on CT scan suggestive of malignant rhabdoid tumor include a large, heterogenous, centrally located mass, which is lobulated with individual lobules separated by intervening areas of decreased attenuation, relating to either previous hemorrhage or necrosis. Enhancement is similarly heterogeneous. Calcification is relatively common, observed in 20-50% of cases and is typically linear and tends to outline tumor lobules.
  • Malignant rhabdoid tumor is characterized by the round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures.
4. Polycystic kidney disease + + + (from hypertension) + -

Ultrasound may be helpful in the diagnosis of polycystic kidney disease. Findings on an ultrasound diagnostic of polycystic kidney disease include:[25][26]

  • At least three unilateral or bilateral cysts in patients 15 - 39 years old
  • Atleast two cysts in each kidney in patients 40 - 59 years old
  • Atleast four cysts in each kidney in patients 60 years of age or older

Renal CT scan may be helpful in the diagnosis of polycystic kidney disease. Findings on CT scan diagnostic of ADPKD include:

  • Numerous renal cysts of varying size and shape with little intervening parenchyma with water attenuation and very thin wall.
  • Reduction in sinus fat due to expansion of the cortex
  • Occasional complex cysts with hyperdense appearance, with possible septations or calcifications
  • Multiple homogeneous and hypoattenuating cystic lesions in the liver in patients with liver involvement
  • On microscopic histopathological analysis, interstitial fibrosis, tubular atrophy, thickening and lamellation of tubular basement membranes, microcysts and negative immunofluorescence for complement and immunoglobulin are characteristic findings of ADPKD.[27][28][29][30]
5. Pheochromocytoma - - + (as a part of the hypertension paroxysm) - -
  • CT is the preferred imaging modality for the diagnosis of pheochromocytoma.
The following findings may be observed on CT scan:[31]
  • On microscopic pathology, Pheochromocytoma typically demonstrates a nesting (Zellballen) pattern on microscopy. This pattern is composed of well-defined clusters of tumor cells containing eosinophilic cytoplasm separated by fibrovascular stroma.
6. Burkitt lymphoma +/- (in non-endemic or sporadic form of the disease) - - - -
  • Chest, abdomen, and pelvis CT scan may be helpful in the diagnosis of Burkitt's lymphoma but it is not done routinely.[35]
  • On microscopic histopathological analysis, characteristic findings of Burkitt's lymphoma include:[36]
  • Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells)
  • Round nucleus
  • Small nucleoli
  • Relatively abundant cytoplasm (basophilic)
  • Brisk mitotic rate and apoptotic activity
  • Cellular outline usually appears squared off
  • "Starry-sky pattern":
  • The stars in the pattern are tingible-body macrophages (macrophages containing apoptotic tumor cells.
  • The tumour cells are the sky
7. Intussusception + - - +/- +
  • Ultrasound is the gold standard imaging modality used to diagnose intussusception[37]
    • Target or doughnut sign[38]
      • Edematous intussuscipien forms an external ring around the centrally located intussusceptum
      • Target sign is usually seen in right lower quadrant
    • Layers of intussusception forms pseudo-kidney appearance on the transverse view
  • CT scan may be helpful in the diagnosis of intussusception. CT scan maybe used when other image modalities like x-ray and ultrasound have not given positive results but suspicion of intussusception is high.
  • Intussusception occurs if there is an imbalance between the longitudinal and radial smooth muscle forces of intestine that maintain its normal structure. This imbalance leads to a segment of intestine to invaginate into another segment and cause entero-enteral intussusception. Etiology of intussusception is either idiopathic or pathologic (lead point). 
8. Hydronephrosis + +/- - - + (CVA tenderness in case of pyelonephritis)
  • In the case of renal colic (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually an intravenous urogram. This has the advantage of showing whether there is any obstruction of flow of urine causing hydronephrosis as well as demonstrating the function of the other kidney. Many stones are not visible on plain x ray or IVU but 99% of stones are visible on CT and therefore CT is becoming a common choice of initial investigation.
  • The kidney undergoes extensive dilation with atrophy and thinning of the renal cortex.
9. Dysplastic kidney N/A N/A N/A N/A N/A

MCDK is usually diagnosed by ultrasound examination before birth.

  • Mass of non-communicating cysts of variable size.
  • Unlike severe hydronephrosis, in which the largest cystic structure (the renal pelvis) lies in a central location and is surrounded by dilated calices, in multicystic dysplastic kidney the cyst distribution shows no recognizable pattern.
  • Dysplastic, echogenic parenchyma may be visible between the cysts, but no normal renal parenchyma is seen.
  • MCKD can be discovered accidentally on CT scan.
  • CT scan shows myltiple cysts with absence of renal parenchyma.
  • MCKD is the result of abnormal differentiation of the renal parenchyma.
10. Pediatric Neuroblastoma + - - +/- +/-
  • CT scan is the investigation of choice for the diagnosis of neuroblastoma.[40]
  • On CT scan, neuroblastoma is characterized by:[41]
  • On microscopic histopathological analysis the presence of round blue cells separated by thin fibrous septa are characteristic findings of neuroblastoma.
  • Other findings of neuroblastoma on light microscopy may include:[42]
  • Homer-Wright rosettes (rosettes with a small meshwork of fibers at the center)
  • Neuropil-like stroma (paucicellular stroma with a cotton candy-like appearance)
11. Pediatric Rhabdomyosarcoma + +/- +/- - +/- On CT scan, rhabdomyosarocma is characterized by:
  • Soft tissue density
  • Some enhancement with contrast
  • Adjacent bony destruction (over 20% of cases)
12. Mesoblastic nephroma + + - + -
  • Ultrasound may be helpful in the diagnosis of mesoblastic nephroma.
  • Mesoblastic nephroma may presents as a well-defined mass with low-level homogeneous echoes.[43]
  • The presence of concentric echogenic and hypoechoic rings can be a helpful diagnostic feature of mesoblastic nephroma.
  • CT scan may be helpful in the diagnosis of mesoblastic nephroma.
  • Findings on CT scan suggestive of mesoblastic nephroma include:
  • Solid hypoattenuating renal lesion
  • Variable contrast enhancement
  • No calcification

Classic mesoblastic nephroma

Cellular mesoblastic nephroma

  • Plump cells with vesicular nuclei
  • Well-defined border
  • Mitotically active

Mixed mesoblastic nephroma

  • Both classic pattern and cellular pattern areas are present
Most common renal tumor that occurs in 1st month of life

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