WordNet

a pattern of symptoms indicative of some disease
a complex of concurrent things; "every word has a syndrome of meanings"
United States novelist who wrote about a young Black man and his struggles in American society (1914-1994) (同)Ralph Ellison, Ralph Waldo Ellison

PrepTutorEJDIC

(疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/22 13:45:46」(JST)

wiki en

Zollinger–Ellison Syndrome (ZES) is caused by a non–beta islet cell (islet of Langerhans), gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach (parietal cells) to maximal activity, with consequent gastrointestinal mucosal ulceration. ZES may occur sporadically or as part of an autosomal dominant familial syndrome called multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the pancreas, duodenum or abdominal lymph nodes, but ectopic locations have also been described (e.g., heart, ovary, gallbladder, liver, kidney).^[1]

Signs and symptoms

Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment.^{[citation needed]}

Chronic diarrhea, including steatorrhea (fatty stools)
Pain in the esophagus, especially between and after meals at night
Nausea
Wheezing
Vomiting blood (digested blood)
Malnourishment
Loss of weight due to loss of appetite

Gastrinomas may occur as single tumors or as multiple, small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type I (MEN I). MEN I patients have tumors in their pituitary gland and parathyroid glands, in addition to tumors of the pancreas.^{[citation needed]}

Pathophysiology

Gastrin works on the parietal cells of gastric glands causing them to secrete more hydrogen ions into the stomach lumen. In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Thus there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The increase in acidity contributes to the development of multiple peptic ulcers in the stomach and duodenum (first portion of the small bowel).^{[citation needed]}

Diagnosis

Clinical suspicion of Zollinger–Ellison syndrome may be aroused when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or endoscopy is suggestive. The diagnosis of Zollinger–Ellison syndrome is made by several laboratory tests and imaging studies.^{[citation needed]}

Secretin stimulation test, which measures evoked gastrin levels
Fasting gastrin levels, on at least three separate occasions^[2]
Gastric acid secretion and pH. Normal basal gastric acid secretion is less than 10 mEq/hour, while in Zollinger–Ellison syndrome it is usually more than 15 mEq/hour.^[3]
An increased level of chromogranin A is a common marker of neuroendocrine tumors

In addition, the source of the increased gastrin production must be discovered. This is either done using MRI or somatostatin receptor scintigraphy, the investigation of choice.^[4]

Treatment

Proton pump inhibitors (omeprazole, and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow down acid secretion. PPI and H2 antagonist are relatively ineffective for pharmacologic treatment^{[citation needed]}. Octreotide is the best drug for pharmacologic management.^{[citation needed]} Cure is only possible if the tumors are surgically removed, or treated with chemotherapy.^{[citation needed]}

History

Sporadic reports of unusual cases of peptic ulceration in the presence of pancreatic tumors occurred prior to 1955, but R.M. Zollinger and E. H. Ellison, surgeons at Ohio State University first postulated a causal relationship between these findings. The American Surgical Association meeting in Philadelphia in April 1955 heard the first public description of the syndrome; Zollinger and Ellison subsequently published their findings in the Annals of Surgery.^[5]

References

^ http://emedicine.medscape.com/article/183555-overview
^ http://www.patient.co.uk/showdoc/40001304/
^ Page 192 in: Elizabeth D Agabegi; Agabegi, Steven S. (2008). Step-Up to Medicine (Step-Up Series). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-7153-6.
^ Jensen RT (2004). "Gastrinomas: advances in diagnosis and management". Neuroendocrinology. 80 Suppl 1: 23–7. doi:10.1159/000080736. PMID 15477712.
^ Zollinger RM, Ellison EH (1955). "Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas". Ann. Surg. 142 (4): 709–23; discussion, 724–8. doi:10.1097/00000658-195510000-00015. PMC 1465210. PMID 13259432.

Footnotes

UpToDate Contents

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1. ゾリンジャー・エリソン症候群（ガストリノーマ）：臨床症状および診断 zollinger ellison syndrome gastrinoma clinical manifestations and diagnosis
2. ゾリンジャー - エリソン症候群（ガストリノーマ）のマネージメントおよび予後 management and prognosis of the zollinger ellison syndrome gastrinoma
3. 酸関連疾患治療のためのプロトンポンプ阻害剤の概要および比較 overview and comparison of the proton pump inhibitors for the treatment of acid related disorders
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. 多発性内分泌腫瘍1型：治療 multiple endocrine neoplasia type 1 treatment

English Journal

Zollinger-Ellison syndrome: Presentation, response to therapy, and outcome.

Wilcox CM, Seay T, Arcury JT, Mohnen J, Hirschowitz BI.SourceUniversity of Alabama at Birmingham, Division of Gastroenterology and Hepatology, Birmingham, AL, United States.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.2011 Jun;43(6):439-43. Epub 2010 Dec 30.
PMID 21193359

Zollinger-ellison syndrome: still a diagnostic challenge in the 21st century?

Pritchard DM.SourceDepartment of Gastroenterology, Institute of Translational Medicine, University of Liverpool, The Henry Wellcome Laboratory, Liverpool, United Kingdom.
Gastroenterology.2011 May;140(5):1380-3. Epub 2011 Mar 26.
PMID 21443889

Japanese Journal

十二指腸カルチノイドの病態と治療

丸山保彦,渡辺文利,花井洋行
日本消化器内視鏡学会雑誌 = Gastroenterological endoscopy 53(8), 1979-1990, 2011-08-20
… NETs）における分類でNET G1と定義された．十二指腸カルチノイドの多くは組織免疫染色でホルモン産生を認めるがホルモンによる症状を引き起こさないNon-functioning NETsで，gastrinoma（Zollinger-Ellison syndrome : ZES）等の症状を呈するものは一部である．緩徐に発育する一方，比較的初期からリンパ節転移を伴う症例もあり「癌もどき」とは言い切れない側面を持つ．明確な治療方針は確 …
NAID 10029562596

外科学の古典を読む(第5回)Zollinger-Ellison症候群の原典

國土典宏,山下俊
外科 73(5), 523-527, 2011-05
NAID 40018814604

Related Pictures

★リンクテーブル★

リンク元	「高カルシウム血症」「ガストリン」「ゾリンジャー・エリソン症候群」「ZES」
拡張検索	「Strom-Zollinger-Ellison syndrome」
関連記事	「syndrome」

「高カルシウム血症」

Zollinger–Ellison syndrome
	Endoscopy image of multiple small ulcers in the distal duodenum in a patient with Zollinger–Ellison syndrome
Classification and external resources
ICD-10	E16.4
ICD-9	251.5
MedlinePlus	000325
eMedicine	med/2437 ped/2472
Patient UK	Zollinger–Ellison syndrome
MeSH	D015043

　　[★]

英: hypercalcemia
同: 高Ca血症
関: カルシウム、低カルシウム血症; 研修医当直御法度症例帳 p.32

組織へのカルシウム蓄積を引き起こしうる (BPT.27)

病因

1. 原発性副甲状腺機能亢進症(甲状腺腺腫などによるPTHの分泌亢進)
2. 腫瘍に随伴

2-1. 肺の扁平上皮癌、成人性Ｔ細胞白血病→PTH関連蛋白(PTHrP)の分泌
2-2. 腫瘍の骨転移により、破骨細胞が骨破壊。

3. サルコイドーシス、肉芽細胞→異所性1,25(OH)2D3が発生する。

肉芽の構成成分であるマクロファージがビタミンD3を産生？

4. サイアザイド系利尿薬や骨粗しょう症の薬として1,25(OH)2D3製剤。

4-1. サイアザイド系利尿薬

チアジド系利尿薬の慢性使用により体液量が減少し、近位尿細管での再吸収が亢進するため (GOO.755)　？？
チアジド系利尿薬自体のDCTでの作用による；NCCTを阻害すると細胞内のNa濃度低下、これにより側底膜でのNa+-Ca2+交換系が亢進することでCa2+の再吸収↑ (GOO.755) 　→　ループ利尿薬と違ってチアジド系利尿薬ははCaを排泄しない！！ see.利尿薬

5. 家族性低Ca尿性高Ca血症
6. その他(リチウム？？？？ (ICU.558))

ECGP.223

USMLEより

Caused by calcium ingestion (milk-alkali syndrome), hyperparathyroid, hyperthyroid, iatrogenic (thiazides), multiple myeloma, Paget's disease, Addison's disease, Neoplasms, Zollinger-Ellison syndrome, Excess vitamin D, Excess vitamin A, sarcoidosis.

Calcium ingestion
Hyperparathyroid/Hyperthyroid
Iatrogenic
Multiplemyeloma
Paget's disease
Addison's disease
Neoplasms
Zollinger-Ellison syndrome: ZES単独ではなく、MEN Iによるparathyroid tumorに続発した病態
Excessive vitamin D
Excessive vitamin A
Sarcoidosis

定義

血清カルシウムが正常上限を超える場合。

疑い：常に≧10.3 mg/dl
確実：≧10.5 mg/dl

↑

基準値

血清総Ca 8.6-10.1 mg/dl(臨床検査法提要第32版)
血清Caイオン 1.15-1.30 mmmol/l(臨床検査法提要第32版), 4.6-5.1 mg/dl

症候

軽度(11-11.5 mg/dL)：通常は無症状。(HIM.285)

重度(>12-13 mg/dL)：傾眠、昏迷、昏睡、消化器症状が出現。(HIM.285)

精神・神経症状：錯乱、昏迷、昏睡。イライラ感、うつ傾向(QB.D-339)
消化器：食欲不振、悪心・嘔吐、便秘。膵炎、消化性潰瘍。腹部膨満(腸管運動抑制による(QB.D-339))

消化性潰瘍：高カルシウム血症は胃酸分泌を促進する
急性膵炎：高カルシウム血症は膵液の分泌を亢進する。(YN.B-78)　←　過剰に出ちゃうと炎症が起こってしまうらしい

泌尿器：多尿、腎結石(血清Ca 12mg/dLでできやすくなるらしい)　←　多尿は浸透圧利尿による(ICU.558)

急性腎不全

腎不全は一般的に低カルシウム血症となるが、高カルシウム血症に起因する腎不全は例外。

→高カルシウム血症性腎症 hypercalcemic nephropathy

腎の石灰化→髄質に蓄積→尿細管圧迫→尿濃縮力障害　←　続発性尿崩症の原因？？？

高カルシウム血症は腎の濃縮力を低下させる(HIM.286)　←　腎集合管におけるADHの作用を阻害(QB.D-339)

心血管：血管収縮による高血圧(出典不明！！)。徐脈、房室ブロック、QT短縮(HIM.284)。　←　YN.D-147には血圧上昇、ICU.558には低血圧とある。
筋　：筋力低下、筋痛
全身：易疲労感

異所性石灰化 red eye　強膜にカルシウムが沈着
多尿による脱水、高血圧、徐脈

心電図

EAB.114 SP.94,524

QT短縮、ST短縮　←　活動電位持続時間が短縮したことを示す。QRS幅については延長する場合もある(EAB.114)

↑細胞外カルシウム濃度→↑内向きカルシウム電流(↑流入速度)→さらに脱分極するように思えるが↑外向きカリウム電流により打ち消される→正味、カルシウムの移動が無くなるまでの時間が早まる→↓活動電位持続時間

PR間隔延長？？

高カルシウム血症→QT短縮：　←高カリウム血症

低カルシウム血症→QT延長：　←低カリウム血症　低マグネシウム血症

治療

症状が出たときか、症状無く血清Ca 14mg/dL以上の場合(ICU.558)

生理食塩水

1. 細胞外液の補充
2. ナトリウム利尿によるカルシウム排泄の促進

血液透析