Pheochromocytoma laboratory findings: Difference between revisions

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==Overview==
==Overview==
Laboratory findings consistent with the diagnosis of pheochromocytoma include elevated 24-hour urinary fractionated catecholamines and metanephrines for low risk patients and plasma fractionated metanephrines for high risk ones.
Laboratory findings consistent with the diagnosis of pheochromocytoma include elevated 24-hour urinary fractionated [[catecholamines]] and [[metanephrine]]<nowiki/>s for low-risk patients and [[plasma]] fractionated [[Metanephrine|metanephrines]] for high-risk patients.


==Laboratory Findings==
==Laboratory Findings==
Diagnostic lab findings associated with pheochromocytoma include:
An elevated concentration of the following is diagnostic of [[pheochromocytoma]].
* Elevated plasma and urinary [[catecholamine]]s and [[metanephrine]]s
* Elevated 24-hour urine fractionated metanephrines and catecholamines. The cutoff values are: <ref name="pmid12574179">{{cite journal| author=Sawka AM, Jaeschke R, Singh RJ, Young WF| title=A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. | journal=J Clin Endocrinol Metab | year= 2003 | volume= 88 | issue= 2 | pages= 553-8 | pmid=12574179 | doi=10.1210/jc.2002-021251 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12574179 }}</ref>
* Elevated urinary [[vanillyl mandelic acid]]
** [[Normetanephrine]] >900 mcg/24 hours
'''Indications of pheochromocytoma testing''':<ref name="pmid17121518">{{cite journal| author=Gimenez-Roqueplo AP, Lehnert H, Mannelli M, Neumann H, Opocher G, Maher ER et al.| title=Phaeochromocytoma, new genes and screening strategies. | journal=Clin Endocrinol (Oxf) | year= 2006 | volume= 65 | issue= 6 | pages= 699-705 | pmid=17121518 | doi=10.1111/j.1365-2265.2006.02714.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17121518 }}</ref>
** [[Metanephrine]] >400 mcg/24 hours
* Triad of tachycardia, headache, and sweating.
** [[Norepinephrine]] >170 mcg/24 hours
* Episodes of palpitation, headache and tremors for unknown reasons.
** [[Epinephrine]] >35 mcg/24 hours
* Hypertension at age <20 years), resistant hypertension.
** [[Dopamine]] >700 mcg/24 hours
* A family history of pheochromocytoma, , multiple endocrine neoplasia type 2, neurofibromatosis type 1, or von Hippel-Lindau.
* Elevated plasma fractionated metanephrines. The cutoff values are:
* Presence of bilateral, extra-adrenal or multiple tumours or a malignant tumour, should be seen as indications for genetic testing.
** Metanephrine > 0.3-0.5 nmol/L
* An incidentally discovered adrenal mass that does not have imaging characteristics consistent with pheochromocytoma.
** Normetanephrine > 0.66- 0.9 nmol/L <ref name="pmid7778821">{{cite journal| author=Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC | display-authors=etal| title=Plasma metanephrines in the diagnosis of pheochromocytoma. | journal=Ann Intern Med | year= 1995 | volume= 123 | issue= 2 | pages= 101-9 | pmid=7778821 | doi=10.7326/0003-4819-123-2-199507150-00004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7778821 }} </ref> <ref name="pmid8849581">{{cite journal| author=Pattarino F, Bouloux PM| title=The diagnosis of malignancy in phaeochromocytoma. | journal=Clin Endocrinol (Oxf) | year= 1996 | volume= 44 | issue= 2 | pages= 239-41 | pmid=8849581 | doi=10.1046/j.1365-2265.1996.657475.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8849581 }} </ref>
'''High risk patients''': plasma fractionated metanephrines is the first test, if elevated; 24-hour urinary fractionated metanephrines, catecholamines, and imaging shuld be the second test for diagnosis. <ref name="pmid11903030">{{cite journal| author=Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P et al.| title=Biochemical diagnosis of pheochromocytoma: which test is best? | journal=JAMA | year= 2002 | volume= 287 | issue= 11 | pages= 1427-34 | pmid=11903030 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11903030 }}</ref>
 
High risk patients include: family history of  MEN2 and VHL syndrome or past history of pheochromocytoma.
 
DIagnostic cutoffs to exclude pheochromocytoma are metanephrine <0.3 nmol/L and normetanephrine <0.66 nmol/L.<ref name="pmid7778821">{{cite journal| author=Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC et al.| title=Plasma metanephrines in the diagnosis of pheochromocytoma. | journal=Ann Intern Med | year= 1995 | volume= 123 | issue= 2 | pages= 101-9 | pmid=7778821 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7778821 }}</ref>


'''Low risk patients''': 24-hour urinary fractionated catecholamines and metanephrines.<ref name="pmid12574179">{{cite journal| author=Sawka AM, Jaeschke R, Singh RJ, Young WF| title=A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. | journal=J Clin Endocrinol Metab | year= 2003 | volume= 88 | issue= 2 | pages= 553-8 | pmid=12574179 | doi=10.1210/jc.2002-021251 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12574179 }}</ref>
* Elevated urinary [[vanillyl mandelic acid]] <ref name="pmid11903030">{{cite journal| author=Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P et al.| title=Biochemical diagnosis of pheochromocytoma: which test is best? | journal=JAMA | year= 2002 | volume= 287 | issue= 11 | pages= 1427-34 | pmid=11903030 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11903030  }}</ref> <ref name="pmid7778821">{{cite journal| author=Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC et al.| title=Plasma metanephrines in the diagnosis of pheochromocytoma. | journal=Ann Intern Med | year= 1995 | volume= 123 | issue= 2 | pages= 101-9 | pmid=7778821 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7778821 }}</ref>


24-hour urine fractionated metanephrines and catecholamines, results cut offs are:  
The following drugs interfere with [[urinary]] [[catecholamines]] metabolism and shoudl be discontinued two weeks before any [[hormonal]] assessments: <ref name="pmid171215182">{{cite journal| author=Gimenez-Roqueplo AP, Lehnert H, Mannelli M, Neumann H, Opocher G, Maher ER et al.| title=Phaeochromocytoma, new genes and screening strategies. | journal=Clin Endocrinol (Oxf) | year= 2006 | volume= 65 | issue= 6 | pages= 699-705 | pmid=17121518 | doi=10.1111/j.1365-2265.2006.02714.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17121518  }}</ref>
* Normetanephrine >900 mcg/24 hours.
* Tricyclic antidepressants (TCAs)
* metanephrine >400 mcg/24 hours.
* Levodopa
* Norepinephrine >170 mcg/24 hours.
* Antipsychotics
* Epinephrine >35 mcg/24 hours.
* Ethanol
* Dopamine >700 mcg/24 hours.
* Acetaminophen
No further evaluation is necessary if results are negative.
* Phenoxybenzamine <ref name="pmid14557417">{{cite journal| author=Kudva YC, Sawka AM, Young WF| title=Clinical review 164: The laboratory diagnosis of adrenal pheochromocytoma: the Mayo Clinic experience. | journal=J Clin Endocrinol Metab | year= 2003 | volume= 88 | issue= 10 | pages= 4533-9 | pmid=14557417 | doi=10.1210/jc.2003-030720 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14557417  }} </ref>


'''NB''': Discontinue TCAs two weeks before any hormonal assessments because they interrupt  24-hour urinary catecholamines metabolism.<ref name="pmid171215182">{{cite journal| author=Gimenez-Roqueplo AP, Lehnert H, Mannelli M, Neumann H, Opocher G, Maher ER et al.| title=Phaeochromocytoma, new genes and screening strategies. | journal=Clin Endocrinol (Oxf) | year= 2006 | volume= 65 | issue= 6 | pages= 699-705 | pmid=17121518 | doi=10.1111/j.1365-2265.2006.02714.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17121518  }}</ref>
Patients with spells of elevated [[blood pressure]] (sudden onset of a [[symptom]] or [[symptoms]]) can be negative in-between spells and should be tested directly after the attacks.<ref name="pmid7630214">{{cite journal| author=Young WF, Maddox DE| title=Spells: in search of a cause. | journal=Mayo Clin Proc | year= 1995 | volume= 70 | issue= 8 | pages= 757-65 | pmid=7630214 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7630214  }}</ref>
 
Patients with spells of eleveated blood pressure (sudden onset of a symptom or symptoms) can be negative during inbetween spells and should be ltested directly after the attacks.<ref name="pmid7630214">{{cite journal| author=Young WF, Maddox DE| title=Spells: in search of a cause. | journal=Mayo Clin Proc | year= 1995 | volume= 70 | issue= 8 | pages= 757-65 | pmid=7630214 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7630214  }}</ref>
 
'''Genetic testing :'''
 
It is suggested for:
* Bilateral adrenal pheochromocytoma.
* Family history of  Von Hippel-Lindau syndrome, MEN2 and  neurofibromatosis type 1.
* Paraganglioma.
* Unilateral pheochromocytoma at a young age.
It is autosomal dominant inheritance and has two pathways of tumor pathogenesis. Cluster 1 tumors are noradrenergic and extra adrenal except VHL. Cluster 2 tumors are adrenergic.<sup>[[Pheochromocytoma pathophysiology#cite note-pmid23933153-3|[3]]]</sup>
{| class="wikitable"
!Cluster 1
!Cluster 2
|-
!
* Succinate dehydrogenase (SDH) subunit genes
* Von Hippel-Lindau (VHL) disease
* Fumarate hydratase gene mutations
|
* '''Multiple endocrine neoplasia type 2A'''
* '''Multiple endocrine neoplasia type 2B'''
* '''Neurofibromatosis type 1 (NF1)'''
|}


==References==
==References==
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Latest revision as of 21:44, 28 July 2020

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

Overview

Laboratory findings consistent with the diagnosis of pheochromocytoma include elevated 24-hour urinary fractionated catecholamines and metanephrines for low-risk patients and plasma fractionated metanephrines for high-risk patients.

Laboratory Findings

An elevated concentration of the following is diagnostic of pheochromocytoma.

  • Elevated 24-hour urine fractionated metanephrines and catecholamines. The cutoff values are: [1]
  • Elevated plasma fractionated metanephrines. The cutoff values are:
    • Metanephrine > 0.3-0.5 nmol/L
    • Normetanephrine > 0.66- 0.9 nmol/L [2] [3]

The following drugs interfere with urinary catecholamines metabolism and shoudl be discontinued two weeks before any hormonal assessments: [5]

  • Tricyclic antidepressants (TCAs)
  • Levodopa
  • Antipsychotics
  • Ethanol
  • Acetaminophen
  • Phenoxybenzamine [6]

Patients with spells of elevated blood pressure (sudden onset of a symptom or symptoms) can be negative in-between spells and should be tested directly after the attacks.[7]

References

  1. ↑ Sawka AM, Jaeschke R, Singh RJ, Young WF (2003). "A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines". J Clin Endocrinol Metab. 88 (2): 553–8. doi:10.1210/jc.2002-021251. PMID 12574179.
  2. ↑ 2.0 2.1 Lenders JW, Keiser HR, Goldstein DS, Willemsen JJ, Friberg P, Jacobs MC; et al. (1995). "Plasma metanephrines in the diagnosis of pheochromocytoma". Ann Intern Med. 123 (2): 101–9. doi:10.7326/0003-4819-123-2-199507150-00004. PMID 7778821.
  3. ↑ Pattarino F, Bouloux PM (1996). "The diagnosis of malignancy in phaeochromocytoma". Clin Endocrinol (Oxf). 44 (2): 239–41. doi:10.1046/j.1365-2265.1996.657475.x. PMID 8849581.
  4. ↑ Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P; et al. (2002). "Biochemical diagnosis of pheochromocytoma: which test is best?". JAMA. 287 (11): 1427–34. PMID 11903030.
  5. ↑ Gimenez-Roqueplo AP, Lehnert H, Mannelli M, Neumann H, Opocher G, Maher ER; et al. (2006). "Phaeochromocytoma, new genes and screening strategies". Clin Endocrinol (Oxf). 65 (6): 699–705. doi:10.1111/j.1365-2265.2006.02714.x. PMID 17121518.
  6. ↑ Kudva YC, Sawka AM, Young WF (2003). "Clinical review 164: The laboratory diagnosis of adrenal pheochromocytoma: the Mayo Clinic experience". J Clin Endocrinol Metab. 88 (10): 4533–9. doi:10.1210/jc.2003-030720. PMID 14557417.
  7. ↑ Young WF, Maddox DE (1995). "Spells: in search of a cause". Mayo Clin Proc. 70 (8): 757–65. PMID 7630214.
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