insulinoma

インスリノーマ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/08 21:51:52」(JST)

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Insulinoma
Classification and external resources
Histopathology of pancreatic endocrine tumor (insulinoma).
ICD-10	C25.4, D13.7
ICD-9	157.4, 211.7
ICD-O:	M8151/1
DiseasesDB	6830
MedlinePlus	000387
eMedicine	med/2677
MeSH	D007340

An insulinoma is a tumor of the pancreas that is derived from beta cells and secretes insulin.

Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose back to normal levels at which point further secretion of insulin is stopped. In contrast, the secretion of insulin by insulinomas is not properly regulated by glucose and the tumors will continue to secrete insulin causing glucose levels to fall further than normal.

As a result patients present symptoms of low blood glucose (hypoglycemia), which are improved by eating. The diagnosis of an insulinoma is usually made biochemically with low blood glucose, elevated insulin, proinsulin and C-peptide levels and confirmed by localizing the tumor with medical imaging or angiography. The definitive treatment is surgery.

Features

Insulinomas are rare neuroendocrine tumours with an incidence estimated at 1 to 4 new cases per million persons per year. Insulinoma is one of the most common types of tumor arising from the islets of Langerhans cells (pancreatic endocrine tumors). Estimates of malignancy (metastases) range from 5% to 30%. Over 99% of insulinomas originate in the pancreas, with rare cases from ectopic pancreatic tissue. About 5% of cases are associated with tumours of the parathyroid glands and the pituitary (Multiple endocrine neoplasia type 1) and are more likely to be multiple and malignant. Most insulinomas are small, less than 2 cm.

Signs and Symptoms

Patients with insulinomas usually develop neuroglycopenic symptoms. These include recurrent headache, lethargy, diplopia, and blurred vision, particularly with exercise or fasting. Severe hypoglycemia may result in seizures, coma, and permanent neurological damage. Symptoms resulting from the catecholaminergic response to hypoglycemia (i.e. tremulousness, palpitations, tachycardia, sweating, hunger, anxiety, nausea) are not as common. Sudden weight gain (the patient can become massively obese) is sometimes seen.

Diagnosis

The diagnosis of insulinoma is suspected in a patient with symptomatic fasting hypoglycemia. The conditions of Whipple’s triad need to be met for the diagnosis of "true hypoglycemia" to be made:

1. symptoms and signs of hypoglycemia,
2. concomitant plasma glucose level of 45 mg/dL (2.5 mmol/L) or less, and
3. reversibility of symptoms with administration of glucose.

Blood tests

The following blood tests are needed to diagnose insulinoma:

• glucose
• insulin
• C-peptide

If available, a proinsulin level might be useful as well. Other blood tests may help rule out other conditions which can cause hypoglycemia.

Suppression tests

Normally, endogenous insulin production is suppressed in the setting of hypoglycemia. A 72-hour fast, usually supervised in a hospital setting, can be done to see if insulin levels fail to suppress, which is a strong indicator of the presence of an insulin-secreting tumour.

During the test, the patient may have calorie-free and caffeine-free liquids. Capillary blood glucose is measured every 4 hours using a reflectance meter, until values < 60 mg/dL (3.3 mmol/L) are obtained. Then, the frequency of blood glucose measurement is increased to every hour until values are < 49 mg/dL (2.7 mmol/L). At that point, or when the patient has symptoms of hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and C-peptide levels. The fast is then stopped at that point, and the hypoglycemia treated with intravenous dextrose or calorie-containing food or drink.

Diagnostic imaging

The insulinoma might be localized by non-invasive means, using ultrasound, CT scan, or by MRI techniques. An Indium-111 pentetreotide scan is more sensitive than ultrasound, CT, or MRI for detection of somatostatin receptor positive tumors, but not a good diagnostic tool for insulinomas. An endoscopic ultrasound has a sensitivity of 40-93% (depending on the location of the tumor) for detecting insulinomas.

Sometimes, angiography with percutaneous transhepatic pancreatic vein catheterization to sample the blood for insulin levels is required. Calcium can be injected into selected arteries to stimulate insulin release from various parts of the pancreas, which can be measured by sampling blood from their respective veins. The use of calcium stimulation improves the specificity of this test.

During surgery to remove an insulinoma, an intra-operative ultrasound can sometimes localize the tumour, which helps guide the surgeon in the operation and has a higher sensitivity than noninvasive imaging tests.

Treatment

Gross appearance of insulinoma showing typical red-brown appearance of tumour.

The definitive management is surgical removal of the insulinoma. This may involve removing part of the pancreas as well (Whipple procedure and distal pancreatectomy).
Medications such as diazoxide and somatostatin can be used to block the release of insulin for patients who are not surgical candidates or who otherwise have inoperable tumours.
Streptozotocin is used in islet cell carcinomas which produce excessive insulin. Combination chemotherapy is used: either doxorubicin + streptozotocin, or fluorouracil + streptotozocin in patients where doxorubicin is contraindicated.[1]
In metastasizing tumours with intrahepatic growth, hepatic arterial occlusion or embolization can be used. [2]

Prognosis

Most patients with benign insulinomas can be cured with surgery. Persistent or recurrent hypoglycemia after surgery tends to occur in patients with multiple tumours. About two percent of patients develop diabetes mellitus after their surgery.

History

Hypoglycemia was first recognized in the 19th century. In the 1920s, after the discovery of insulin and its use in the treatment of diabetics, hyperinsulinism was suspected to be a cause of hypoglycemia in non-diabetics. A pioneering description of hyperinsulinism as a cause of hypoglycemia was published by Seale Harris in 1924. The first report of a surgical cure of hypoglycemia by removing an islet cell tumour was in 1929.

Notable Death

The Co-founder of Apple, Inc., Steve Jobs, died of Metastatic Insulinoma on October 5, 2011.

See also

• Hypoglycemia
• Causes of hypoglycemia
• Pancreas

External links

• www.endotext.org article
• The Johns Hopkins University Pancreatic Islet Cell Tumor / Pancreatic Endocrine Neoplasms webpage
• Insulinoma community website provides up to date, easily accessible information and support

Additional images

References

• Larsen PR, Williams RL (2003). Williams textbook of endocrinology (10th ed.). Philadelphia: WB Saunders. ISBN 0-7216-9184-6. 
• Doppman JL, Chang R, Fraker DL, et al. (Aug 1995). "Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium". Annals of Internal Medicine 123 (4): 269–73. PMID 7611592. 
• Service FJ. Insulinoma. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2005.

UpToDate Contents

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• 1. インスリノーマ insulinoma
• 2. 糖尿病でない成人における低血糖症：診断的アプローチ hypoglycemia in adults without diabetes mellitus diagnostic approach
• 3. 転移性の胃腸膵管系神経内分泌腫瘍：腫瘍増殖およびホルモン過剰分泌による症状を管理
  するための全身治療の選択肢 metastatic gastroenteropancreatic neuroendocrine tumors systemic therapy options to control tumor growth and symptoms of hormone hypersecretion
• 4. 多発性内分泌腫瘍1型：臨床症状および診断 multiple endocrine neoplasia type 1 clinical manifestations and diagnosis
• 5. 成人における低血糖：臨床症状、定義、および原因 hypoglycemia in adults clinical manifestations definition and causes

English Journal

• HDLs protect the MIN6 insulinoma cell line against tunicamycin-induced apoptosis without inhibiting ER stress and without restoring ER functionality.

• Puyal J, Pétremand J, Dubuis G, Rummel C, Widmann C.SourceDepartment of Fundamental Neurosciences, University of Lausanne, Switzerland.
• Molecular and cellular endocrinology.Mol Cell Endocrinol.2013 Dec 5;381(1-2):291-301. doi: 10.1016/j.mce.2013.08.016. Epub 2013 Aug 28.
• HDLs protect pancreatic beta cells against apoptosis induced by several endoplasmic reticulum (ER) stressors, including thapsigargin, cyclopiazonic acid, palmitate and insulin over-expression. This protection is mediated by the capacity of HDLs to maintain proper ER morphology and ER functions such
• PMID 23994023

• Mitochondrial phosphate transport during nutrient stimulation of INS-1E insulinoma cells.

• Quan X, Das R, Xu S, Cline GW, Wiederkehr A, Wollheim CB, Park KS.SourceDepartment of Physiology and Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
• Molecular and cellular endocrinology.Mol Cell Endocrinol.2013 Dec 5;381(1-2):198-209. doi: 10.1016/j.mce.2013.08.003. Epub 2013 Aug 9.
• Here, we have investigated the role of inorganic phosphate (Pi) transport in mitochondria of rat clonal β-cells. In α-toxin-permeabilized INS-1E cells, succinate and glycerol-3-phosphate increased mitochondrial ATP release which depends on exogenous ADP and Pi. In the presence of substrates, addit
• PMID 23939247

• Proteins differentially expressed in human beta-cells-enriched pancreatic islet cultures and human insulinomas.

• Terra LF, Teixeira PC, Wailemann RA, Zelanis A, Palmisano G, Cunha-Neto E, Kalil J, Larsen MR, Labriola L, Sogayar MC.SourceInstituto de Química, Departamento de Bioquímica, Universidade de São Paulo (USP), São Paulo, Brazil.
• Molecular and cellular endocrinology.Mol Cell Endocrinol.2013 Dec 5;381(1-2):16-25. doi: 10.1016/j.mce.2013.07.004. Epub 2013 Jul 24.
• In view of the great demand for human beta-cells for physiological and medical studies, we generated cell lines derived from human insulinomas which secrete insulin, C-peptide and express neuroendocrine and islet markers. In this study, we set out to characterize their proteomes, comparing them to t
• PMID 23891624

Japanese Journal

• Involvement of Phosphatidylinositol 3-Kinase/Akt Pathway in Gemcitabine-Induced Apoptosis-Like Cell Death in Insulinoma Cell Line INS-1

• Motoshige Hironori,Oyama Kyohei,Takahashi iyoshi [他]
• Biological & pharmaceutical bulletin 35(11), 1932-1940, 2012-11
• NAID 40019460398

• 症例報告 全身性強皮症に合併したGAD抗体およびIA-2抗体陽性劇症1型糖尿病の1例

• 佐々木 真弓,原田 範雄,佐藤 広規 [他]
• 糖尿病 55(10), 781-785, 2012-10
• NAID 40019480261

Related Links

• インスリノーマ - 京都大学医学部附属病院

京都大学・膵臓外科のページ．膵内分泌腫瘍であるインスリノーマ（インシュリノーマ）についての解説です． 大津赤十字病院・外科 Home 膵がんについて 一般向け 膵臓癌問答 膵がんについて --- 膵癌取扱い規約 膵がん関連出版物

• Insulinoma - Diseases & Conditions - Medscape Reference

Insulinoma. Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. ... Even when metastases are found, surgical excision is often feasible before any medical ...

Related Pictures

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★リンクテーブル★

リンク元	「膵内分泌腫瘍」「インスリノーマ」「beta-cell tumor」

「膵内分泌腫瘍」

　　[★]

英

pancreatic endocrine tumor, endocrine tumor of pancreas

同

膵内分泌性膿瘍、膵内分泌系腫瘍

• インスリノーマ(insulinoma)：インスリン分泌腫瘍：インスリン：膵内分泌腫瘍の中で最も多い
• グルカゴノーマ(glucagonoma)：グルカゴン分泌腫瘍：グルカゴン：膵内分泌腫瘍の15%
• ガストリノーマ(gastrinoma)：ガストリン分泌腫瘍：ガストリン：

「インスリノーマ」

　　[★]

英

insulinoma, insuloma

同

インスリン分泌性膵島細胞腫 insulin-secreting islet cell tumor

関

膵島細胞腫瘍

発生部位

• 膵体尾部(約70%)

検査

• 負荷試験

• 絶食試験
• グルカゴン負荷試験

「beta-cell tumor」

　　[★]

β細胞腫瘍

関

insulinoma