Insulinoma diagnostic criteria: Difference between revisions
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==Overview== | ==Overview== | ||
The diagnosis of insulinoma is based on the Whipple's triad, which includes blood glucose<50 mg/dL, symptoms of [[hypoglycemia]] that can be neuroglycopenic([[visual disturbances]],[[confusion]], [[weakness]] , [[seizures]], [[coma]]) or adrenergic ([[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( | The diagnosis of insulinoma is based on the Whipple's triad, which includes blood glucose<50 mg/dL, symptoms of [[hypoglycemia]] that can be neuroglycopenic([[visual disturbances]],[[confusion]], [[weakness]] , [[seizures]], [[coma]]) or adrenergic ([[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== | ==Diagnostic Criteria== | ||
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*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)<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)<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 >6 μU/mL(43 pmol/L by RIA and ≥3 μU/ml by ICMA | **Insulin level >6 μU/mL(43 pmol/L by RIA and ≥3 μU/ml by ICMA | ||
**Glucose level <2.5mmol/L( | **Glucose level <2.5mmol/L(55 mg/dL) | ||
**[[C-peptide]] level ≥200 pmol/L | **[[C-peptide]] level ≥200 pmol/L | ||
***[[Proinsulin]] level ≥25% or ≥22pmol/L is included in some criteria also | ***[[Proinsulin]] level ≥25% or ≥22pmol/L is included in some criteria also | ||
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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<50 mg/dL, symptoms of hypoglycemia that can be neuroglycopenic(visual disturbances,confusion, weakness , seizures, coma) or adrenergic (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)[1], which includes:
- Hypoglycemia( fasting blood glucose <50 mg/dL)
- Symptoms of hypoglycemia[2][3]
- Neuroglycopenic- visual disturbances(blurring of vision, diplopia), confusion, weakness, behavioral changes, seizures and coma
- Adrenergic-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)[4][5]
- 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 included in some criteria also
- The gold standard for diagnosis classically had been 72-hour fasting test[5][4]
- 33% patients develop symptoms in 12 hours, 80% at 24 hours, 90% after 48 hours and 100% after 72 hours of fasting.
| 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.
- ↑ 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.
- ↑ 4.0 4.1 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.
- ↑ 5.0 5.1 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.