Insulinoma diagnostic criteria: Difference between revisions

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Latest revision as of 16:39, 26 May 2020

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

Overview

The diagnosis of insulinoma is based on the Whipple's triad, which includes blood glucose < 55 mg/dL, symptoms of hypoglycemia that can be neuroglycopenic (visual disturbances, confusion, weakness, seizures, coma) or adrenergic symptoms (sweating, tremors, palpitations, and hyperphagia) and resolution of symptoms after ingestion/infusion of glucose. It is also diagnosed on the basis of radioimmunoassay (RIA) and Immunochemiluminescent assay (ICMA) in the absence of hypoglycemia causing agents e.g. insulin and oral hypoglycemic agents (e.g. sulfonylureas) by insulin level (>6 μU/mL (43 pmol/L by RIA and ≥ 3 μU/mL by ICMA, glucose level of < 2.5mmol/L (55mg/dL) and C-peptide level of ≥ 200 pmol/L and/or proinsulin level ≥ 25% or ≥ 22pmol/L. The gold standard for the diagnosis of insulinoma is 72-hour fasting test.

Diagnostic Criteria

The classical diagnosis of insulinoma is based on the Whipple's triad (1935), which includes:^[1]^[2]^[3]^[4]

Hypoglycemia (fasting blood glucose < 55 mg/dL)
Symptoms of hypoglycemia
- Neuroglycopenic symptoms including visual disturbances (blurring of vision, diplopia), confusion, weakness, behavioral changes, seizures and coma.
- Adrenergic symptoms including sweating, palpitations, tremors and hyperphagia/obesity.
Improvement of symptoms after glucose infusion

The diagnosis of insulinoma is based on the biochemical assay with radioimmunoassay (RIA) and immunochemiluminescent assay (ICMA) in the absence of plasma sulfonylureas (or drug causing hypoglycemia) as below: ^[5]^[6]
- Insulin level > 6 μU/mL (43 pmol/L by RIA and ≥3 μU/ml by ICMA
- Glucose level < 2.5mmol/L (55 mg/dL)
- C-peptide level ≥ 200 pmol/L
  - Proinsulin level ≥25% or ≥22pmol/L is also included in some criteria
The gold standard for diagnosis classically had been 72-hour fasting test.^[6]^[5]
- 33% patients develop symptoms in 12 hours, 80% at 24 hours, 90% after 48 hours and 100% after 72 hours of fasting.

Algorithm used commonly^[7]

Suspicion of Insulinoma

Whipple's triad confirmed

72 hour fast

Positive

Negative

MRI/CT

Prolonged OGTT or mixed meal

No visible lesion

Visible
lesion(s)

Unresectable
liver metastasis

No
hypoglycemia

Hypoglycemia

No follow up

Differential diagnosis of
postprandial hypoglycemia

EUS

Treat metastatic disease

No visible lesion(s)

Visible lesion(s)

GLP-1 Scan or ASVS

No lesion(s)

Identified lesion(s)

Medical control
and reevaluation

Surgical exploration
(intraoperative US)

Single lesion(s)

Multiple lesion(s)

Excision

ASVS

Excision based on ASVS

Abbreviations: EUS: Endoscopic ultrasound, ASVS: Arterial stimulation venous sampling, GLP-1: Glucagon-like-peptide 1, OGTT: Oral glucose tolerance test

References

↑ Whipple AO, Frantz VK (1935). "ADENOMA OF ISLET CELLS WITH HYPERINSULINISM: A REVIEW". Ann. Surg. 101 (6): 1299–335. PMC 1390871. PMID 17856569.
↑ 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.
↑ Metz DC, Jensen RT (2008). "Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors". Gastroenterology. 135 (5): 1469–92. doi:10.1053/j.gastro.2008.05.047. PMC 2612755. PMID 18703061.
↑ Boukhman MP, Karam JH, Shaver J, Siperstein AE, Duh QY, Clark OH (1998). "Insulinoma--experience from 1950 to 1995". West J Med. 169 (2): 98–104. PMC 1305178. PMID 9735690.
↑ ^5.0 ^5.1 Metz, David C.; Jensen, Robert T. (2008). "Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors". Gastroenterology. 135 (5): 1469–1492. doi:10.1053/j.gastro.2008.05.047. ISSN 0016-5085.
↑ ^6.0 ^6.1 Grant CS (2005). "Insulinoma". Best Pract Res Clin Gastroenterol. 19 (5): 783–98. doi:10.1016/j.bpg.2005.05.008. PMID 16253900.
↑ Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT (2016). "ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors". Neuroendocrinology. 103 (2): 153–71. doi:10.1159/000443171. PMC 4849884. PMID 26742109.

Template:WH Template:WS

[pmid17856569-1] Whipple AO, Frantz VK (1935). "ADENOMA OF ISLET CELLS WITH HYPERINSULINISM: A REVIEW". Ann. Surg. 101 (6): 1299–335. PMC 1390871. PMID 17856569.

[pmid19088155-2] 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.

[pmid18703061-3] Metz DC, Jensen RT (2008). "Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors". Gastroenterology. 135 (5): 1469–92. doi:10.1053/j.gastro.2008.05.047. PMC 2612755. PMID 18703061.

[pmid9735690-4] Boukhman MP, Karam JH, Shaver J, Siperstein AE, Duh QY, Clark OH (1998). "Insulinoma--experience from 1950 to 1995". West J Med. 169 (2): 98–104. PMC 1305178. PMID 9735690.

[MetzJensen2008-5] 5.0 ^5.1 Metz, David C.; Jensen, Robert T. (2008). "Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors". Gastroenterology. 135 (5): 1469–1492. doi:10.1053/j.gastro.2008.05.047. ISSN 0016-5085.

[pmid16253900-6] 6.0 ^6.1 Grant CS (2005). "Insulinoma". Best Pract Res Clin Gastroenterol. 19 (5): 783–98. doi:10.1016/j.bpg.2005.05.008. PMID 16253900.

[pmid26742109-7] Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT (2016). "ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors". Neuroendocrinology. 103 (2): 153–71. doi:10.1159/000443171. PMC 4849884. PMID 26742109.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

@@ Line 4: / Line 4: @@
 {{CMG}}; {{AE}}{{ADS}}
 ==Overview==
-The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
-OR
+The diagnosis of insulinoma is based on the [[Whipple's triad]], which includes blood [[glucose]] < 55 mg/dL, symptoms of [[hypoglycemia]] that can be [[Insulinoma history and symptoms|neuroglycopenic]] ([[Visual disturbance|visual disturbances]], [[confusion]], [[weakness]], [[seizures]], [[coma]]) or [[adrenergic]] symptoms ([[sweating]], [[tremors]], [[palpitations]], and [[hyperphagia]]) and resolution of symptoms after ingestion/infusion of [[glucose]]. It is also diagnosed on the basis of [[radioimmunoassay]] ([[Radioimmunoassay|RIA]]) and Immunochemiluminescent assay (ICMA) in the absence of [[hypoglycemia]] causing agents e.g. [[insulin]] and oral [[Hypoglycemia|hypoglycemic]] agents (e.g. [[sulfonylureas]]) by [[insulin]] level (>6 μU/mL (43 pmol/L by RIA and ≥ 3 μU/mL by ICMA, [[glucose]] level of < 2.5mmol/L (55mg/dL) and [[C-peptide]] level of ≥ 200 pmol/L and/or [[proinsulin]] level ≥ 25% or ≥ 22pmol/L. The gold standard for the [[diagnosis]] of insulinoma is 72-hour fasting test.
-The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
-OR
-The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
-OR
-There are no established criteria for the diagnosis of [disease name].
 ==Diagnostic Criteria==
-*The classical diagnosis of insulinoma is based on the Whipple's triad(1935)<ref name="pmid17856569">{{cite journal |vauthors=Whipple AO, Frantz VK |title=ADENOMA OF ISLET CELLS WITH HYPERINSULINISM: A REVIEW |journal=Ann. Surg. |volume=101 |issue=6 |pages=1299–335 |year=1935 |pmid=17856569 |pmc=1390871 |doi= |url=}}</ref>, which includes:
+*The classical diagnosis of insulinoma is based on the [[Whipple's triad]] (1935), which includes:<ref name="pmid17856569">{{cite journal |vauthors=Whipple AO, Frantz VK |title=ADENOMA OF ISLET CELLS WITH HYPERINSULINISM: A REVIEW |journal=Ann. Surg. |volume=101 |issue=6 |pages=1299–335 |year=1935 |pmid=17856569 |pmc=1390871 |doi= |url=}}</ref><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><ref name="pmid18703061">{{cite journal| author=Metz DC, Jensen RT| title=Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. | journal=Gastroenterology | year= 2008 | volume= 135 | issue= 5 | pages= 1469-92 | pmid=18703061 | doi=10.1053/j.gastro.2008.05.047 | pmc=2612755 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703061  }} </ref><ref name="pmid9735690">{{cite journal| author=Boukhman MP, Karam JH, Shaver J, Siperstein AE, Duh QY, Clark OH| title=Insulinoma--experience from 1950 to 1995. | journal=West J Med | year= 1998 | volume= 169 | issue= 2 | pages= 98-104 | pmid=9735690 | doi= | pmc=1305178 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9735690  }} </ref>
-#Hypoglycemia( fasting blood glucose <50 mg/dL)
+#[[Hypoglycemia]] (fasting [[blood glucose]] < 55 mg/dL)
-#Symptoms of hypoglycemia<ref name="pmid18703061">{{cite journal| author=Metz DC, Jensen RT| title=Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. | journal=Gastroenterology | year= 2008 | volume= 135 | issue= 5 | pages= 1469-92 | pmid=18703061 | doi=10.1053/j.gastro.2008.05.047 | pmc=2612755 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18703061  }} </ref><ref name="pmid9735690">{{cite journal| author=Boukhman MP, Karam JH, Shaver J, Siperstein AE, Duh QY, Clark OH| title=Insulinoma--experience from 1950 to 1995. | journal=West J Med | year= 1998 | volume= 169 | issue= 2 | pages= 98-104 | pmid=9735690 | doi= | pmc=1305178 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9735690  }} </ref>
+#Symptoms of [[hypoglycemia]]
-#*Neuroglycopenic- visual disturbances(blurring of vision, diplopia), confusion, weakness, behavioral changes, seizures and coma
+#*[[Insulinoma history and symptoms|Neuroglycopenic]] symptoms including [[Visual disturbance|visual disturbances]] ([[blurring of vision]], [[diplopia]]), [[confusion]], [[weakness]], behavioral changes, [[Seizure|seizures]] and [[coma]].
-#*Adrenergic-Sweating, palpitations, tremors and hyperphagia/obesity
+#*[[Adrenergic]] symptoms including  [[sweating]], [[palpitations]], [[tremors]] and [[hyperphagia]]/[[obesity]].
-#Improvement of symptoms after glucose infusion
+#Improvement of symptoms after [[glucose]] infusion
-*The diagnosis of insulinoma is based on the Biochemical assay with RadioImmunoAssay(RIA) and immunochemiluminescent assay(ICMA) in the abscence of plasma sulfonylureas (or drug causing hypoglycemia)<ref name="MetzJensen2008">{{cite journal|last1=Metz|first1=David C.|last2=Jensen|first2=Robert T.|title=Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors|journal=Gastroenterology|volume=135|issue=5|year=2008|pages=1469–1492|issn=00165085|doi=10.1053/j.gastro.2008.05.047}}</ref><ref name="pmid16253900">{{cite journal| author=Grant CS| title=Insulinoma. | journal=Best Pract Res Clin Gastroenterol | year= 2005 | volume= 19 | issue= 5 | pages= 783-98 | pmid=16253900 | doi=10.1016/j.bpg.2005.05.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16253900  }} </ref>
+*The diagnosis of insulinoma is based on the biochemical assay with [[radioimmunoassay]] (RIA) and immunochemiluminescent [[assay]] (ICMA) in the absence of plasma [[sulfonylureas]] (or drug causing [[hypoglycemia]]) as below: <ref name="MetzJensen2008">{{cite journal|last1=Metz|first1=David C.|last2=Jensen|first2=Robert T.|title=Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors|journal=Gastroenterology|volume=135|issue=5|year=2008|pages=1469–1492|issn=00165085|doi=10.1053/j.gastro.2008.05.047}}</ref><ref name="pmid16253900">{{cite journal| author=Grant CS| title=Insulinoma. | journal=Best Pract Res Clin Gastroenterol | year= 2005 | volume= 19 | issue= 5 | pages= 783-98 | pmid=16253900 | doi=10.1016/j.bpg.2005.05.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16253900  }} </ref>
-**Insulin level >6uU/mL(43p mol/L by RIA and ≥3uU/ml by ICMA
+**[[Insulin]] level > 6 μU/mL (43 pmol/L by RIA and ≥3 μU/ml by ICMA
-**Glucose level <2.5mmol/L(45 mg/dL)
+**[[Glucose]] level < 2.5mmol/L (55 mg/dL)
-**C-peptide level  ≥200 pmol/L
+**[[C-peptide]] level  ≥ 200 pmol/L
-***Pronsulin level ≥25% or ≥22pmol/L is included in some criteria also
+***[[Proinsulin]] level ≥25% or ≥22pmol/L is also included in some criteria
-*The gold standard for diagnosis classically had been 72 hour fasting test<ref name="pmid16253900">{{cite journal| author=Grant CS| title=Insulinoma. | journal=Best Pract Res Clin Gastroenterol | year= 2005 | volume= 19 | issue= 5 | pages= 783-98 | pmid=16253900 | doi=10.1016/j.bpg.2005.05.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16253900  }} </ref><ref name="MetzJensen2008">{{cite journal|last1=Metz|first1=David C.|last2=Jensen|first2=Robert T.|title=Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors|journal=Gastroenterology|volume=135|issue=5|year=2008|pages=1469–1492|issn=00165085|doi=10.1053/j.gastro.2008.05.047}}</ref>
+*The gold standard for diagnosis classically had been 72-hour fasting test.<ref name="pmid16253900">{{cite journal| author=Grant CS| title=Insulinoma. | journal=Best Pract Res Clin Gastroenterol | year= 2005 | volume= 19 | issue= 5 | pages= 783-98 | pmid=16253900 | doi=10.1016/j.bpg.2005.05.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16253900  }} </ref><ref name="MetzJensen2008">{{cite journal|last1=Metz|first1=David C.|last2=Jensen|first2=Robert T.|title=Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors|journal=Gastroenterology|volume=135|issue=5|year=2008|pages=1469–1492|issn=00165085|doi=10.1053/j.gastro.2008.05.047}}</ref>
 **33% patients develop symptoms in 12 hours, 80% at 24 hours, 90% after 48 hours and 100% after 72 hours of fasting.
+{{familytree/start}}'''Algorithm used commonly<ref name="pmid26742109">{{cite journal |vauthors=Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT |title=ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors |journal=Neuroendocrinology |volume=103 |issue=2 |pages=153–71 |year=2016 |pmid=26742109 |pmc=4849884 |doi=10.1159/000443171 |url=}}</ref>''' {{familytree | | | | | | | | | | | | A01 | | | | | |A01=Suspicion of Insulinoma}}
-{{familytree/start}}'''Algorithm used commonly''' {{familytree | | | | | | | | | | | | A01 | | | | | |A01=Suspicion of Insulinoma}}
 {{familytree | | | | | | | | | | | | |!| | | | | | | | }}
-{{familytree | | | | | | | | | | | | B01 | | | | | |B01=Whipple's triad confirmed}}
+{{familytree | | | | | | | | | | | | B01 | | | | | |B01=[[Whipple's triad]] confirmed}}
 {{familytree | | | | | | | | | | | | |!| | | | | | | | }}
 {{familytree | | | | | | | | | | | | C01 | | | | | | | |C01=72 hour fast}}
@@ Line 44: / Line 33: @@
 {{familytree | | | | | | | D01 | | | | | | | | | | |D02|D01= Positive|D02=Negative}}
 {{familytree | | | | | | | |!| | | | | | | | | | | | |!| }}
-{{familytree | | | | | | | E01 | | | | | | | | | | |E02 |E01=MRI/CT|E02= Prolonged OGTT or mixed meal}}
+{{familytree | | | | | | | E01 | | | | | | | | | | |E02 |E01=[[MRI]]/[[CT]]|E02= Prolonged [[OGTT]] or mixed meal}}
 {{familytree | | | |,|-|-|-|+|-|-|-|.| | | | | |,|-|-|^|-|-|.|}}
-{{familytree | | | F01 | |F02| |F03| | | |F04| | | |F05|F01=No visible lesion|F02=Visible<br>lesion(s)|F03=Unresectable<br>liver metastasis|F04=No<br>hypoglycemia|F05=Hypoglycemia}}
+{{familytree | | | F01 | |F02| |F03| | | |F04| | | |F05|F01=No visible lesion|F02=Visible<br>lesion(s)|F03=Unresectable<br>[[liver]] [[metastasis]]|F04=No<br>[[hypoglycemia]]|F05=[[Hypoglycemia]]}}
 {{familytree | | | | |!| | |!| | | |!| | | | | |!| | | | | |!| | | | |}}
-{{familytree | | | | |!| | |!| | | |!| | | | | |G01| | | |G02| |G01=No follow up|G02=Differential diagnosis of<br> postprandial hypoglycemia}}
+{{familytree | | | | |!| | |!| | | |!| | | | |G01| | | |G02| |G01=No follow up|G02=Differential diagnosis of<br> postprandial [[hypoglycemia]]}}
-{{familytree | | | |H01| |!| | |H03|H01=EUS|H03=Treat metastatic disease}}
+{{familytree | | | |H01| |!| | |H03|H01=EUS|H03=Treat [[metastatic]] disease}}
 {{familytree | | | | |!| | |!| | |}}
 {{familytree | | |,|-|^|.| |!| | ||}}
@@ Line 55: / Line 44: @@
 {{familytree | | |!| | | | |!|}}
 {{familytree | | |!| | | | |!|}}
-{{familytree | | |J1| | |!|J1=GLP-1 Scan or ASVS|}}
+{{familytree | | |J1| | |!|J1=[[GLP-1]] Scan or ASVS|}}
 {{familytree | | | |!| | | |!|}}
 {{familytree | |,|-|^|-|-|.|!|}}
@@ Line 70: / Line 59: @@
 {{familytree | | | | | | | | | | | |O01|O01=Excision based on ASVS|}}
 {{familytree/end}}
+Abbreviations: EUS: Endoscopic ultrasound, ASVS: Arterial stimulation venous sampling, GLP-1: Glucagon-like-peptide 1, OGTT: Oral glucose tolerance test
 ==References==
@@ Line 76: / Line 66: @@
 {{WH}}
 {{WS}}
+[[Category:Medicine]]
+[[Category:Endocrinology]]
+[[Category:Up-To-Date]]

Insulinoma diagnostic criteria: Difference between revisions

Latest revision as of 16:39, 26 May 2020

Overview

Diagnostic Criteria

References

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