Incidentaloma differential diagnosis: Difference between revisions

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Revision as of 19:33, 16 October 2017

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

Overview

Adrenal incidentaloma must be differentiated from other diseases that cause adrenal masses such as adrenal adenoma, adrenocortical carcinoma, Cushing's syndrome, pheochromocytoma, and metastasis.

Differentiating different causese of Incidentaloma

The cause of adrenal incidentaloma commonly include adrenal adenoma, sub-clinical Cushing's syndrome, pheochromocytoma, and adrenocortical carcinoma. These causes can be differentiated from each other as follows:


Differential Diagnosis	Clinical picture	Imagings	Laboratory tests
Adrenal adenoma	Symptoms related to excess glucocorticoid Symptoms related to excess mineralocorticoid	Round and homogeneous density, smooth contour and sharp margination Diameter less than 4 cm, unilateral location Low unenhanced CT attenuation values (<10 HU) Rapid contrast medium washout (10 minutes after administration of contrast, an absolute contrast medium washout of more than 50 percent) Isointensity with liver on both T1 and T2 weighted MRI sequences Chemical shift: evidence of lipid on MRI	Cortisol level Fasting serum cortisol at 8 AM following a 1 mg dose of dexamethasone at bedtime Renin (PRA) or plasma renin concentration (PRC): very low in patients with primary aldosteronism, usually less than 1 ng/mL per hour for PRA and usually undetectable for PRCThe opening `<ref>` tag is malformed or has a bad name
Adrenocortical carcinoma	Mass effect symptoms Symptoms related to excess glucocorticoid Symptoms related to excess mineralocorticoid Symptoms related to excess androgen or estrogen secretion	Irregular shape Inhomogeneous density because of central areas of low attenuation due to tumor necrosis Tumor calcification Diameter usually >4 cm Unilateral location High unenhanced CT attenuation values (>20 HU) Inhomogeneous enhancement on CT with intravenous 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 MRI and high to intermediate signal intensity on T2 weighted MRI High standardized uptake value (SUV) on FDG-PET-CT study Evidence of local invasion or metastases	Adrenal androgens [[[DHEAS]]] Androstenedione Bioavailable testosterone should be measured in every patient. 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
Cushing's syndrome	Rapid 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.
Pheochromocytoma	Palpitations especially in epinephrine producing tumors.^[3] Anxiety often resembling that of a panic attack Sweating Headaches occurs in 90 % of patients. Paroxysmal attacks of hypertension but some patients have normal blood pressure. It may be asymptomatic and discovered incidentally after screening for MEN patients.	[null Insert paragraph] Increased attenuation on nonenhanced 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 MRI Cystic and hemorrhagic changes Variable size and may be bilateral	Plasma fractionated metanephrines 24-hour urinary fractionated metanephrines
Adrenal metastasis	Symptoms and signs of primary malignancy especially lung cancer General constitutional symptoms: Fever Fatigue Weight loss	Irregular shape and inhomogeneous nature Tendency to be bilateral High unenhanced CT attenuation values (>20 HU) and enhancement with intravenous contrast on 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 MRI and high to intermediate signal intensity on T2 weighted MRI (representing an increased water content) Elevated standardized uptake value on FDG-PET scan

Differential diagnosis of Cushing's disease from other diseases

The table below summarizes the findings that differentiate Cushing's disease from other conditions that may cause hypertension, hyperandrogenism, and obesity. Facial plethora, skin changes, osteoporosis, nephrolithiasis and neuropsychiatric conditions should raise the concern for Cushing's syndrome.^[1]^[2]^[3]^[4]

Conditions	Causes	Associated features	Diagnostic approach
Cushing's syndrome	Iatrogenic Pituitary adenoma Adrenal tumor Adrenal hyperplasia Ectopic ACTH secretion	Obesity Hypertension PCOS/hyperandrogenism Oligomenorrhea/hypogonadism Osteoporosis Myopathy/cutaneous wasting Neuropsychiatric problems Kidney stones	24-hour urine cortisol Midnight salivary cortisol Low dose dexamethasone challenge test CRH stimulation High dose dexamethasone test MRI brain CT/MRI adrenals
Pseudo-Cushing's syndrome	Obesity Alcoholism Depression HIV	Obesity Hypertension PCOS/hyperandrogenism Oligomenorrhea/hypogonadism	Urinary free cortisol Midnight salivary cortisol Low dose dexamethasone challenge test Glucose tolerance test Loperamide test
Metabolic syndrome X	Familial/genetic Obesity Insulin resistance	Obesity Hypertension PCOS/hyperandrogenism Oligomenorrhea/hypogonadism Dyslipidemia Diabetes/Glucose intolerance	Waist circumference Low-density lipoproteins High-density lipoproteins Glucose tolerance test Fasting blood sugar HbA1c

Differentiating pheochromocytoma from other diseases

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

Disease	Symptoms	Signs	Investigations
Pheochromocytoma	The symptoms of a pheochromocytoma are those of sympathetic nervous systemhyperactivity and include:^[1] Palpitations (especially in epinephrine producing tumors) Anxiety Sweating Headaches (90 % of patients) Paroxysmal attacks of hypertension May be asymptomatic (incidentally discovered in 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 metanephrines 24-hour urinary fractionated metanephrines, catecholamines Imaging studies (CT scan, MRI and iodine-123-meta-iodobenzylguanidine or MIBG scintiscan)^[1] Low-risk patients: 24-hour urinary fractionated catecholamines and metanephrines^[4]
Pseudopheochromocytoma (idiopathic)^[5]^[6]^[7]^[8]	Paroxysmal activation of the sympathetic system causing: Emotional distress Acute onset of high blood pressure Headache Chest pain Nausea 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 activity Episodes of fear or panic attacks Chest pain Headache Palpitations Flushing Response to antidepressants Fear precedes physical symptoms.	Patients look anxious with tired attitude Tachycardia Hypertension Sweating	Laboratory studies that can exclude medical disorders other than panic disorder include: Serum electrolytes Serum glucose Cardiac enzymes Urine toxicology 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^[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.
Hyperthyroidism	Weight loss Heat intolerance Tremors Palpitations Anxiety Increased bowel disturbances Shortness of breath^[9]	Goiter Skin flushing Proptosis Increased sensitivity of beta receptors in the heart to catecholamines^[10] due to an effect of thyroid hormones increase cardiac work and output Systolic hypertension^[11]	Low thyroid-stimulating hormone (TSH) High free thyroxine (T4) concentration High triiodothyronine (T3) concentration
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 medications Headache Nausea Subconjunctival hemorrhage	Bruit can be heard over the abdomen	Duplex ultrasonography 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 with intestinal gas)^[1]
Stroke and compression of lateral medulla (Lateral medullary syndrome)	Extensive unilateral infarction of the brain stem in the region of the nucleus tractus solitarius may result in partial baroreflex dysfunction, increased sympathetic activity, and neurogenic paroxysmal hypertension. Blurred vision or diplopia Weakness of bulbar muscles 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	CT shows mass compressing lateral medulla or infarction in the same area
Seizures	According to type; it may be focal or generalized, clinical or subclinical:^[11] 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	Physical examination is important when central nervous system infection or hemorrhage are diagnostic possibilities A tongue bite or laceration in generalized tonic-clonic seizure^[12]	Abnormal electroencephalography: a positive test without a clinical presentation is called a sub-clinical seizure.^[13] 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^[14]. 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 Cardiac valvular lesions (tricuspid incompetence)	High urinary excretion of 5-HIAA^[15] High urinary excretion of serotonin^[16] High chromogranin concentration(Chromogranin(A, B, and C) are proteins that are stored and released with peptides and amines in a variety of neuroendocrine tissues)^[17] CT is recommended for evaluation of all patients with carcinoid tumors.^[18]
Migraine headaches	Prodrome: Occurs hours or days before a headache Aura Immediately precedes the headache Pain phase Also known as headache phase Postdrome phase^[19]	Conjunctival injection Horner's syndrome^[1] Adie's pupil ^[2] Cranial/ cervical muscle tenderness Bruit at neck and head for clinical signs of an arteriovenous malformation Photosensitivity	CT is indicated in patients with:^[1]^[2] Abnormal physical examination: Increase of headache's frequency Poor coordination Focal neurologic signs Headaches awakening the patient at nigt^[3][4] 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 criteria for migraine Differentiating a migraine from other primary headaches
Drugs	Sympathomimetic drugs that can induce symptoms simulating pheochromocytoma include: High-dose phenylpropanolamine Cocaine Amphetamines Lysergic acid diethylamide (LSD) Phenylcyclidine (PCP)^[20] Combination of a monoamine oxidase (MAO) inhibitor and ingestion of tyramine-containing foods.^[21]	Disturbed consciousness Nasal septum perforation in cocaine addiction Needle marks on the skin History of antidepressantintake	Urine toxicology screening
Baroreflex failure^[22]	Marked and frequent fluctuations in blood pressure,^[23] with both high and low readings. It is caused by hypofunctioning of 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.^[23] 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. Determination of respiratory sinus arrhythmia, 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 CT scan

References

↑ Boscaro M, Barzon L, Fallo F, Sonino N (2001). "Cushing's syndrome". Lancet. 357 (9258): 783–91. doi:10.1016/S0140-6736(00)04172-6. PMID 11253984.
↑ Findling JW, Raff H (2001). "Diagnosis and differential diagnosis of Cushing's syndrome". Endocrinol. Metab. Clin. North Am. 30 (3): 729–47. PMID 11571938.
↑ Newell-Price J, Trainer P, Besser M, Grossman A (1998). "The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states". Endocr. Rev. 19 (5): 647–72. doi:10.1210/edrv.19.5.0346. PMID 9793762.
↑ "How Is Metabolic Syndrome Diagnosed? - NHLBI, NIH".
↑ Mann SJ (1999). "Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment". Arch Intern Med. 159 (7): 670–4. PMID 10218745.
↑ Mann SJ (1999). "Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment". Arch Intern Med. 159 (7): 670–4. PMID 10218745.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ ^11.0 ^11.1 Mintz G, Pizzarello R, Klein I (1991). "Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment". J Clin Endocrinol Metab. 73 (1): 146–50. doi:10.1210/jcem-73-1-146. PMID 2045465.
↑ Brigo F, Storti M, Lochner P, Tezzon F, Fiaschi A, Bongiovanni LG; et al. (2012). "Tongue biting in epileptic seizures and psychogenic events: an evidence-based perspective". Epilepsy Behav. 25 (2): 251–5. doi:10.1016/j.yebeh.2012.06.020. PMID 23041172.
↑ Fountain NB, Van Ness PC, Swain-Eng R, Tonn S, Bever CT, American Academy of Neurology Epilepsy Measure Development Panel and the American Medical Association-Convened Physician Consortium for Performance Improvement Independent Measure Development Process (2011). "Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology". Neurology. 76 (1): 94–9. doi:10.1212/WNL.0b013e318203e9d1. PMID 21205698.
↑ 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.
↑ Sjöblom SM (1988). "Clinical presentation and prognosis of gastrointestinal carcinoid tumours". Scand J Gastroenterol. 23 (7): 779–87. PMID 3227292.
↑ Feldman JM (1986). "Urinary serotonin in the diagnosis of carcinoid tumors". Clin Chem. 32 (5): 840–4. PMID 2421946.
↑ 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.
↑ 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.
↑ 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.
↑ Krentz AJ, Mikhail S, Cantrell P, Hill GM (2001). "Drug Points: Pseudophaeochromocytoma syndrome associated with clozapine". BMJ. 322 (7296): 1213. PMC 31620. PMID 11358774.
↑ Kuchel O (1985). "Pseudopheochromocytoma". Hypertension. 7 (1): 151–8. PMID 3980057.
↑ Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM (1993). "The diagnosis and treatment of baroreflex failure". N Engl J Med. 329 (20): 1449–55. doi:10.1056/NEJM199311113292003. PMID 8413455.
↑ ^23.0 ^23.1 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.

Template:WH Template:WS

[pmid11253984-1] Boscaro M, Barzon L, Fallo F, Sonino N (2001). "Cushing's syndrome". Lancet. 357 (9258): 783–91. doi:10.1016/S0140-6736(00)04172-6. PMID 11253984.

[pmid11571938-2] Findling JW, Raff H (2001). "Diagnosis and differential diagnosis of Cushing's syndrome". Endocrinol. Metab. Clin. North Am. 30 (3): 729–47. PMID 11571938.

[pmid9793762-3] Newell-Price J, Trainer P, Besser M, Grossman A (1998). "The diagnosis and differential diagnosis of Cushing's syndrome and pseudo-Cushing's states". Endocr. Rev. 19 (5): 647–72. doi:10.1210/edrv.19.5.0346. PMID 9793762.

[urlHow_Is_Metabolic_Syndrome_Diagnosed?_-_NHLBI,_NIH-4] "How Is Metabolic Syndrome Diagnosed? - NHLBI, NIH".

[pmid102187452-5] Mann SJ (1999). "Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment". Arch Intern Med. 159 (7): 670–4. PMID 10218745.

[pmid10218745-6] Mann SJ (1999). "Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment". Arch Intern Med. 159 (7): 670–4. PMID 10218745.

[pmid8824124-7] 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.

[pmid17921824-8] 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.

[pmid15963064-9] 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.

[pmid20454652-10] 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.

[pmid2045465-11] 11.0 ^11.1 Mintz G, Pizzarello R, Klein I (1991). "Enhanced left ventricular diastolic function in hyperthyroidism: noninvasive assessment and response to treatment". J Clin Endocrinol Metab. 73 (1): 146–50. doi:10.1210/jcem-73-1-146. PMID 2045465.

[pmid23041172-12] Brigo F, Storti M, Lochner P, Tezzon F, Fiaschi A, Bongiovanni LG; et al. (2012). "Tongue biting in epileptic seizures and psychogenic events: an evidence-based perspective". Epilepsy Behav. 25 (2): 251–5. doi:10.1016/j.yebeh.2012.06.020. PMID 23041172.

[pmid21205698-13] Fountain NB, Van Ness PC, Swain-Eng R, Tonn S, Bever CT, American Academy of Neurology Epilepsy Measure Development Panel and the American Medical Association-Convened Physician Consortium for Performance Improvement Independent Measure Development Process (2011). "Quality improvement in neurology: AAN epilepsy quality measures: Report of the Quality Measurement and Reporting Subcommittee of the American Academy of Neurology". Neurology. 76 (1): 94–9. doi:10.1212/WNL.0b013e318203e9d1. PMID 21205698.

[pmid7969229-14] 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.

[pmid3227292-15] Sjöblom SM (1988). "Clinical presentation and prognosis of gastrointestinal carcinoid tumours". Scand J Gastroenterol. 23 (7): 779–87. PMID 3227292.

[pmid2421946-16] Feldman JM (1986). "Urinary serotonin in the diagnosis of carcinoid tumors". Clin Chem. 32 (5): 840–4. PMID 2421946.

[pmid2316306-17] 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.

[pmid19077417-18] 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.

[pmid15447695-19] 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.

[pmid11358774-20] Krentz AJ, Mikhail S, Cantrell P, Hill GM (2001). "Drug Points: Pseudophaeochromocytoma syndrome associated with clozapine". BMJ. 322 (7296): 1213. PMC 31620. PMID 11358774.

[pmid3980057-21] Kuchel O (1985). "Pseudopheochromocytoma". Hypertension. 7 (1): 151–8. PMID 3980057.

[pmid8413455-22] Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM (1993). "The diagnosis and treatment of baroreflex failure". N Engl J Med. 329 (20): 1449–55. doi:10.1056/NEJM199311113292003. PMID 8413455.

[pmid183225442-23] 23.0 ^23.1 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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@@ Line 199: / Line 199: @@
 ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Investigations
 |-
-|[[Pheochromocytoma]]
+| style="background:#DCDCDC;" align="center" | [[Pheochromocytoma]]
 |The symptoms of a pheochromocytoma are those of [[sympathetic nervous system]]<nowiki/>hyperactivity and include:<sup>[[Renal artery stenosis ultrasound#cite note-pmid23457117-1|[1]]]</sup>
 * [[Palpitations]] (especially in [[epinephrine]] producing tumors)
@@ Line 220: / Line 220: @@
 ** 24-hour [[urinary]] fractionated [[catecholamines]] and [[Metanephrine|metanephrines]]<sup>[[Pheochromocytoma laboratory findings#cite note-pmid12574179-4|[4]]]</sup>
 |-
-|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>
+| style="background:#DCDCDC;" align="center" |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]] causing:
 * Emotional distress
@@ Line 238: / Line 238: @@
 * Increase in plasma [[catecholamines]] between and during attacks.
 |-
-|[[Panic attacks]]
+| style="background:#DCDCDC;" align="center" | [[Panic attacks]]
 |
 * Paroxysms of increased [[Sympathetic nervous system|sympathetic activity]]
@@ Line 260: / Line 260: @@
 * Urine [[toxicology]] [[Screening (medicine)|screening]]
 |-
-|Labile hypertension ([[White coat hypertension]])
+|style="background:#DCDCDC;" align="center" | Labile hypertension ([[White coat hypertension]])
 |
 * No history of [[hypertension]]
@@ Line 267: / Line 267: @@
 * 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]]
+| style="background:#DCDCDC;" align="center" | [[Hyperthyroidism]]
 |
 * [[Weight loss]]
@@ Line 287: / Line 287: @@
 * High [[triiodothyronine]] (T3) concentration
 |-
-|[[Renal artery stenosis|Renovascular hypertension]]
+| style="background:#DCDCDC;" align="center" | [[Renal artery stenosis|Renovascular hypertension]]
 |
 * Common in individuals < 30 years or > 55 years
@@ Line 302: / Line 302: @@
 * [[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]])
+|style="background:#DCDCDC;" align="center" | [[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]].
@@ Line 319: / Line 319: @@
 * [[Computed tomography|CT]] shows mass compressing [[Lateral medullary syndrome|lateral medulla]] or infarction in the same area
 |-
-|[[Seizures]]
+| style="background:#DCDCDC;" align="center" | [[Seizures]]
 |According to type; it may be focal or generalized, clinical or subclinical:<ref name="pmid2045465" />
 * [[Tonic-clonic seizure]]:
@@ Line 348: / Line 348: @@
 * 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]]
+|style="background:#DCDCDC;" align="center" |[[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
@@ Line 371: / Line 371: @@
 * [[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]]
+|style="background:#DCDCDC;" align="center" |[[Migraine headaches]]
 |
 * '''Prodrome:'''
@@ Line 408: / Line 408: @@
 * Differentiating a migraine from other primary [[headaches]]
 |-
-|Drugs
+|style="background:#DCDCDC;" align="center" |Drugs
 |[[Sympathomimetic drug|Sympathomimetic drugs]] that can induce symptoms simulating pheochromocytoma include:
 * High-dose [[phenylpropanolamine]]
@@ Line 424: / Line 424: @@
 * [[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>
+|style="background:#DCDCDC;" align="center" | [[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.