Insulinoma differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Insulinoma}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Insulinoma]]
{{CMG}}; {{AE}} {{ADS}}
{{CMG}}; {{AE}} {{ADS}}


==Overview==
==Overview==
Insulinoma must be differentiated from other diseases that cause features of hypoglycemia like palpitations, profuse sweating, dizziness, such as [differential dx1], [differential dx2], and [differential dx3].
Insulinoma must be differentiated from other diseases that cause features of [[hypoglycemia]] like [[altered mental status]]/[[confusion]], profuse [[sweating]] and visual disturbances ([[Blurred vision|blurring]]/[[diplopia]]). These are classified on the basis of [[laboratory]] findings into exogenous [[insulin]], [[oral hypoglycemic agent]]<nowiki/>s (e.g. [[Sulphonylurea]]<nowiki/>s), [[Nesidioblastosis]], insulin autoimmune hypoglycemia.
 
OR
 
Insulinoma must be differentiated from the exogenous use of insulin, drugs causing hypoglycemia like sulfonylureas.


==Differentiating insulinoma from other Diseases==
==Differentiating insulinoma from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
Insulinoma must be differentiated from other diseases that cause features of [[hypoglycemia]]. These are classified on the basis of [[laboratory]] findings.
*[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
 
*As [disease name] manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. [Subtype name 1] must be differentiated from other diseases that cause [clinical feature 1], such as [differential dx1] and [differential dx2]. In contrast, [subtype name 2] must be differentiated from other diseases that cause [clinical feature 2], such as [differential dx3] and [differential dx4].


===Preferred Table for differentials for [[Hypoglycemia]]<ref name="pmid19088155">{{cite journal| author=Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER et al.| title=Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2009 | volume= 94 | issue= 3 | pages= 709-28 | pmid=19088155 | doi=10.1210/jc.2008-1410 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19088155  }} </ref>===
'''Differentials for [[Hypoglycemia]] on the basis of Laboratory findings:'''<ref name="pmid19088155">{{cite journal| author=Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER et al.| title=Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2009 | volume= 94 | issue= 3 | pages= 709-28 | pmid=19088155 | doi=10.1210/jc.2008-1410 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19088155  }} </ref>
{|
{| class="sortable"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="2" |Diseases
! rowspan="2" |Diagnoses
! colspan="7" |Laboratory Findings differentiating among causes of Hypoglycemia
! colspan="8" |Laboratory Findings differentiating among causes of Hypoglycemia
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!S.Glucose<br>(mg/dL)/(mmol/L)  
!S.Glucose<br>(mg/dL)  
!C Peptide (pmol/L)
!C Peptide (pmol/L)
!S.Insulin (μU/mL)/(pmol/L)
!S.Insulin (μU/mL)
!S.Proinsulin<br>(pmol/L)
!S.Proinsulin<br>(pmol/L)
!S. Beta hydroxybutyrate
!S. Beta hydroxybutyrate
!Glucose increase after glucagon(mg/dL)
!Glucose increase after glucagon(mg/dL)
!
!Oral Hypoglycemic agent
!Antibodies to Insulin
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Normal/Fasting
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<55
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<200
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<3
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<5
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>2.7
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<25
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Exogenous Insulin
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Exogenous Insulin
| style="background: #F5F5F5; padding: 5px;" |'''↓'''
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<55
| style="background: #F5F5F5; padding: 5px;" |↓
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<200
| style="background: #F5F5F5; padding: 5px;" |↑↑
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>>3
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<5
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≤2.7
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>25
|
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Insulinoma]]
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" |<55
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" |≥200
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" |≥3
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" |≥5
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" |≤2.7
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" |>25
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" | -
| rowspan="3" style="background: #F5F5F5; padding: 5px;text-align: center;" | -
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Nesidioblastosis]]
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Insulinoma
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Post gastric bypass hypoglycemia (PGPH)
| style="background: #F5F5F5; padding: 5px;" |'
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |↑
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Autoimmune Insulin  
| style="background: #DCDCDC; padding: 5px;text-align: center;" |Insulin autoimmune hypoglycemia
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<55
| style="background: #F5F5F5; padding: 5px;" |↓
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>>200<sup>‡</sup>
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>>3
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>>5<sup>‡</sup>
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≤2.7
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>25
|
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
| style="background: #F5F5F5; padding: 5px;text-align: center;" | +
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Differential Diagnosis 4
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Oral hypoglycemic agent]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<55
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≥200
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≥3
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≥5
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≤2.7
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>25
|
| style="background: #F5F5F5; padding: 5px;text-align: center;" | +
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Differential Diagnosis 5
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[IGF]]¤
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<55
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<200
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<3
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |<5
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |≤2.7
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;text-align: center;" |>25
|
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
| style="background: #F5F5F5; padding: 5px;text-align: center;" | -
|-
| colspan="9" style="background: #DCDCDC; padding: 5px; " |
‡ Free C-peptide and proinsulin concentrations are low<br>
¤ [[IGF]]= Insulin Growth Factor, Increased pro-IGF-2, free [[Insulin-like growth factor 2|IGF]]-2, IGF-2/[[IGF-1]] ratio
 
|}
|}


===Use if the above table can not be made===
'''Differentiating hypoglycemia from other diseases that cause autonomic hyperactivity symptoms :'''
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center"
{|
| valign="top" |
|+
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differential Diagnosis}}
! rowspan="3" style="background: #4479BA; color: #FFFFFF; " |Disease
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Similar Features}}
! colspan="5" style="background: #4479BA; color: #FFFFFF; " |Clinical Manifestation
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Differentiating Features}}
! rowspan="3" style="background: #4479BA; color: #FFFFFF; " |Investigations
|-
! colspan="4" style="background: #4479BA; color: #FFFFFF; " |Symptoms
! rowspan="2" style="background: #4479BA; color: #FFFFFF; " |Signs
|-
! style="background: #4479BA; color: #FFFFFF; " |Palpitations
! style="background: #4479BA; color: #FFFFFF; " |Fever
! style="background: #4479BA; color: #FFFFFF; " |Sweating
! style="background: #4479BA; color: #FFFFFF; " |Headache
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Differential 1
! style="background: #DCDCDC; text-align: center;" |[[Hypoglycemia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" | +
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].
| style="background: #F5F5F5; text-align: center;" | -
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" | +
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
| style="background: #F5F5F5; text-align: center;" | +
| style="background: #F5F5F5; " |
* [[Tachycardia]]
* Blurred vision
* [[Pallor]]
* [[Tremor|Tremors]]
* [[Seizures]]/ [[Coma]]
| style="background: #F5F5F5; " |
* Plasma [[glucose]] <70 mg/dL
* S. [[Insulin]]
* S. [[Proinsulin]]
* S. [[C-peptide|C-Peptide]]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Differential 2
! style="background: #DCDCDC; text-align: center;" |[[Anxiety disorders]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
| style="background: #F5F5F5;" |
*Patient looks irritable
*Rapid [[pulse]] and may be irregular
| style="background: #F5F5F5;" |
*Normal investigations
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Differential 3
! style="background: #DCDCDC; text-align: center;" |[[Pheochromocytoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
| style="background: #F5F5F5;" |
*[[Tachycardia]]
*Strong rapid [[pulse]]
*High [[pulse pressure]]
| style="background: #F5F5F5;" |
*Plasma fractionated [[Metanephrine|metanephrines]], 24-hour urinary fractionated [[Metanephrine|metanephrines]], [[catecholamines]].<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>
*[[Computed tomography]]: Radiological evaluation should follow lab tests to locate site of  the tumour.<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>
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Differential 4
! style="background: #DCDCDC; text-align: center;" |[[Arrhythmias|Arrhythmia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" | +
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" |<nowiki>-</nowiki>
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>-</nowiki>
| style="background: #F5F5F5;" |
*Irregular pulse
| style="background: #F5F5F5;" |
*ECG changes according to the cause
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Differential 5
! style="background: #DCDCDC; text-align: center;" |[[Hyperthyroidism]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" | +
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] also observed in [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
* On [physical exam; history; diagnostic test; imaging], [Differential 1] {has; demonstrates} [feature 1], [feature 2], [feature 3] that distinguish it from [disease name].
| style="background: #F5F5F5; text-align: center;" |<nowiki>+</nowiki>
| style="background: #F5F5F5;" |
*Hyperactive [[Deep tendon reflex|deep tendon reflexes]]
*[[Thyromegaly]]
*[[Exophthalmus]]
| style="background: #F5F5F5;" |
*Level of [[thyroid-stimulating hormone]] ([[TSH]])
*Levels of T4 and/or T3 in the blood
*[[Antibody|Antibodies]] such as anti-[[TSH receptor|TSH-receptor antibodies]] in [[Graves' disease]]
|}
|}


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[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Latest revision as of 21:26, 8 February 2019

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

Overview

Insulinoma must be differentiated from other diseases that cause features of hypoglycemia like altered mental status/confusion, profuse sweating and visual disturbances (blurring/diplopia). These are classified on the basis of laboratory findings into exogenous insulin, oral hypoglycemic agents (e.g. Sulphonylureas), Nesidioblastosis, insulin autoimmune hypoglycemia.

Differentiating insulinoma from other Diseases

Insulinoma must be differentiated from other diseases that cause features of hypoglycemia. These are classified on the basis of laboratory findings.

Differentials for Hypoglycemia on the basis of Laboratory findings:[1]

Diagnoses Laboratory Findings differentiating among causes of Hypoglycemia
S.Glucose
(mg/dL) 		C Peptide (pmol/L) S.Insulin (μU/mL) S.Proinsulin
(pmol/L) 		S. Beta hydroxybutyrate Glucose increase after glucagon(mg/dL) Oral Hypoglycemic agent Antibodies to Insulin
Normal/Fasting <55 <200 <3 <5 >2.7 <25 - -
Exogenous Insulin <55 <200 >>3 <5 ≤2.7 >25 - -
Insulinoma <55 ≥200 ≥3 ≥5 ≤2.7 >25 - -
Nesidioblastosis
Post gastric bypass hypoglycemia (PGPH)
Insulin autoimmune hypoglycemia <55 >>200‡ >>3 >>5‡ ≤2.7 >25 - +
Oral hypoglycemic agent <55 ≥200 ≥3 ≥5 ≤2.7 >25 + -
IGF¤ <55 <200 <3 <5 ≤2.7 >25 - -

‡ Free C-peptide and proinsulin concentrations are low
¤ IGF= Insulin Growth Factor, Increased pro-IGF-2, free IGF-2, IGF-2/IGF-1 ratio

Differentiating hypoglycemia from other diseases that cause autonomic hyperactivity symptoms :

Disease Clinical Manifestation Investigations
Symptoms Signs
Palpitations Fever Sweating Headache
Hypoglycemia + - + +
Anxiety disorders + - + +
  • Patient looks irritable
  • Rapid pulse and may be irregular
  • Normal investigations
Pheochromocytoma + + + +
Arrhythmia + - - -
  • Irregular pulse
  • ECG changes according to the cause
Hyperthyroidism + + + +

References

  1. ↑ Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER; et al. (2009). "Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 94 (3): 709–28. doi:10.1210/jc.2008-1410. PMID 19088155.
  2. ↑ 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.
  3. ↑ Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.

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