Clin J Gastroenterol DOI 10.1007/s12328-015-0565-z

CASE REPORT

Protein-losing enteropathy cured by resection of adenomatous goiter: report of a case Jun Takada1 • Hiroshi Araki1 • Masaya Kubota1 • Takashi Ibuka1 Makoto Shiraki1 • Masahito Shimizu1 • Hisataka Moriwaki1



Received: 17 February 2015 / Accepted: 24 March 2015 Ó Springer Japan 2015

Abstract A 51-year-old Japanese woman presented to our hospital with systemic edema and general fatigue. Her serum albumin level was very low (1.5 g/dL). Technetium99 m-human serum albumin (99mTc-HSA) scintigraphy showed albumin leakage from the upper small bowel. Magnetic resonance lymphangiography showed dilated lymphatic vessels in the chest, whereas double-balloon enteroscopy (DBE) showed white villi and chyle leakage in the deeper part of the duodenal mucosa. A duodenal mucosa biopsy specimen revealed lymphangiectasia. She was diagnosed with protein-losing enteropathy (PLE). Treatment with a fat-restricted diet and tranexamic acid—previously reported to be effective against PLE—was attempted, but was ineffective. A thyroid tumor was simultaneously detected in her left neck, and was found to extend to the mediastinum on computed tomography. The tumor (size, [5 cm) was resected, and a pathological diagnosis of adenomatous goiter was made. The patient’s serum albumin level increased to normal levels within 1 month postoperatively. After 6 months, 99mTc-HSA scintigraphy showed no albumin leakage from the gastrointestinal tract, and disappearance of white villi and chyle leakage on DBE. No lymphangiectasia was noted in the biopsy specimen. Adenomatous goiter was thus considered the cause of the PLE, possibly through lymph flow obstruction in the mediastinum.

& Jun Takada [email protected] Hiroshi Araki [email protected] 1

Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan

Keywords Protein-losing enteropathy  Adenomatous goiter  Double balloon enteroscopy

Introduction Protein-losing enteropathy (PLE) is a clinical condition caused by characteristic protein leakage in the digestive tract, resulting in hypoproteinemia. Such exudative protein loss can be caused by ulcerative or non-ulcerative enteropathies, lymphatic obstruction, or increased lymphatic hydrostatic pressure. Candidate diseases such as congenital intestinal lymphangiectasia, constrictive pericarditis, congestive heart failure, sarcoidosis, or a Fontan procedure can cause PLE by increasing intestinal lymph pressure or by inducing lymphatic obstruction. Similarly, mesenteric lymphatic obstruction also causes PLE, although there have been no reports of PLE caused by lymphatic obstruction due to a thyroid tumor. Here, we report the first case of PLE due to adenomatous goiter, and discuss the possible mechanisms of PLE.

Case report A 51-year-old Japanese woman presented to our department in January 2013 with a 6-month history of systemic edema and general fatigue. She had undergone surgical resection of mesenteric hemangioma in 2005, and continued to experience hypoproteinemia since the first visit to our hospital. Physical examination showed pitting edema on her legs and an elastic-hard tumor on her left neck. The laboratory findings were as follows: serum total protein, 2.9 g/dL (normal range, 6.5–8.2 g/dL); serum albumin, 1.5 g/dL (normal range 3.9–4.9 g/dL); immunoglobulin G (IgG),

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242 mg/dL (normal range, 890–1850 mg/dL); normal liver enzymes; normal kidney and thyroid functions; negative serology for rheumatoid factor; normal urinalysis findings without proteinuria; and normal stool analysis with no steatorrhea. Congestive heart failure or constrictive pericarditis was excluded by ultrasonic cardiogram. Technetium-99 m-human serum albumin (99mTc-HSA)

scintigraphy showed leakage of albumin from the upper small bowel (Fig. 1). No leakage was apparent from the stomach or colon. Magnetic resonance (MR) lymphangiography showed dilated lymphatic vessels and a lymphatic cyst in the chest (Fig. 2). Double-balloon enteroscopy (DBE) showed white villi and chyle leakage in the deeper part of the duodenal mucosa (Fig. 3). Moreover,

Fig. 1 Technetium-99m-human serum albumin (99mTc-HSA) scintigraphy on 10 January 2013 showed leakage of albumin from the upper small bowel (arrows)

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Fig. 2 Magnetic resonance lymphography on 14 February 2013 showed dilation of the lymphatic vessels (arrows) and lymphatic cyst (arrowhead)

multiple submucosal white plaques and submucosal cystic lesions were noted in the same area and in the upper part of the jejunum (Fig. 3). No mucosal erosions or ulcers were detected. In the endoscopically biopsied duodenal specimen, lymphangiectasia was apparent (Fig. 4), but mucosal erosion, or lymphocyte or eosinophil infiltration was not found. Computed tomography indicated a tumor of the left lobe of the thyroid gland, [5 cm in size, which extended into the mediastinum (Fig. 5). The patient was diagnosed with PLE, and treated with albumin transfusion, a fat-restricted diet, and oral administration of tranexamic acid, which has previously been reported to be effective against PLE. However, these therapies were not effective in the present case. The patient then underwent resection of the thyroid tumor. The tumor was [5 cm in size, and a pathological diagnosis of adenomatous goiter was made (Fig. 6). The patient’s serum albumin level increased to normal levels within a month after surgery. The IgG level also increased gradually to normal (Fig. 7). Six months after operation, DBE and 99mTc-HSA scintigraphy were performed again. DBE showed disappearance of white villi and chyle leakage. Examination of a biopsied duodenal specimen indicated improvement of lymphangiectasia (Fig. 8). 99mTc-HSA scintigraphy showed no leakage of albumin from the gastrointestinal tract. The MR lymphangiography at 1 year after operation showed improvement of lymphatic vessel dilation (Fig. 9).

Fig. 3 a Double-balloon enteroscopy on 15 January 2013 showed white villi and chyle leakage in the deeper part of the duodenal mucosa. b Multiple submucosal white plaques and submucosal cystic lesions were noted in the deeper part of duodenum and upper part of the jejunum (arrows)

Fig. 4 Microscopic examination of endoscopically biopsied duodenal specimen showed lymphangiectasia in the shallow layer of mucosa (arrows). D2-40 immunohistochemistry, 9100

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Fig. 6 Pathological diagnosis was adenomatous goiter (hematoxylin and eosin staining, 920) Fig. 5 Computed tomography (CT) scan on 24 January 2013 showed a tumor in the left lobe of the thyroid gland that extended into the mediastinum (arrow)

Discussion PLE is a condition characterized by excessive protein loss via the gastrointestinal tract, resulting in hypoproteinemia, edema, and, occasionally, cavity effusions. Although there are many causes of PLE, the primary causes can be classified into erosive gastrointestinal disorders (inflammatory bowel disease, pseudomembranous colitis, sarcoidosis, intestinal lymphoma, erosive gastropathy); non-erosive gastrointestinal disorders (celiac disease, microscopic colitis, rheumatic disorders, tropical sprue, Whipple’s disease, Fig. 7 Time course of changes in serum proteins. TP total protein, Alb albumin, IgG immunoglobulin G

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hypertrophic gastropathy); and disorders involving increased central venous pressure or mesenteric lymphatic obstruction (primary intestinal lymphangiectasia, congestive heart failure, portal hypertension, intestinal lymphatic fistula, retroperitoneal fibrosis, and mesenteric tuberculosis) [1]. In this case, 99mTc-HSA scintigraphy and DBE showed protein leakage from the deeper part of the duodenum. The MR lymphography showed dilated thoracic lymphatic vessels. The DBE also showed white villi and white submucosal plaques, where lymphangiectasia was seen in the biopsy specimen. No erosion of the mucosa or infiltration of lymphocytes or eosinophils was observed. These findings suggest congestion of lymph fluid and increased lymphatic hydrostatic pressure. At present, the

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Fig. 9 Magnetic resonance lymphography on 14 August 2014 showed improvement in dilation of lymphatic vessels (arrows)

Fig. 8 a, b Double-balloon enteroscopy on 2 February 2014 showed disappearance of white villi and chyle leakage. c Microscopic examination of an endoscopically biopsied duodenal specimen showed improvement of lymphangiectasia (arrows) (Immunohistochemistry of D2-40, 9100)

diagnosis of intestinal lymphangiectasia is based on characteristic DBE findings with further confirmation by histopathological examination of corresponding biopsy specimens. Endoscopy reveals scattered white spots, which

have been described as having a characteristic snowflake appearance, overlying the small intestinal mucosa and white submucosal plaques [2–5]. Both endoscopic and pathological findings in our case are in agreement with these descriptions. We treated with albumin transfusion, a fat-restricted diet, and oral administration of tranexamic acid [6, 7], which has previously been reported to be effective against PLE. However, these therapies were not effective in the present case. The resection of the adenomatous goiter successfully treated the PLE, and lymphangiectasia also improved both endoscopically and histologically. Improved lymphatic vessel dilation was also confirmed by MR lymphography. Such a clinical course suggests that the cause of the PLE in this case was a lymphatic obstruction by the adenomatous goiter. The lymphatic vessels drain lymph from the gastrointestinal tract and form a confluence at the intestinal trunk, and then ascend bilaterally along the spine. Thereafter, the lymph fluid flows into the thoracic duct and, finally, into the venous blood flow at the junction of the left subclavian vein and the left internal jugular vein. We speculate that, in the present case, this lymphatic flow was disturbed near the confluence point of the thoracic duct with the vein by the adenomatous goiter that extended to the mediastinum. This lymphatic obstruction increased the lymphatic hydrostatic pressure leading to the PLE of the duodenum. Unfortunately, we could not obtain direct evidence for lymphatic vessel obstruction by imaging diagnosis or surgical pathology. However, the post-surgical clinical course strongly suggests that this hypothesis is appropriate.

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A PLE due to lymphatic obstruction by a tumor is rare. Several case reports of PLE have described the disturbance of lymphatic flow by mesenteric or retroperitoneal malignant lymphoma [8–11]. Kinani et al. [12] reported a case of PLE caused by large left-sided thoracic cyst obstructing the thoracic duct, wherein the patient improved following surgical removal of the cyst. Our case is similar to the one described by Kinani in terms of pathogenetic mechanism; however, there have been no reports of PLE caused by thyroid tumors. We report here a case of PLE caused by adenomatous goiter, which is to our knowledge, the first case describing this complication. Disclosures Conflict of Interest: The authors declare they have no conflict of interest. Human/Animal Rights: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5). Informed Consent: Informed consent was obtained from all patients for being included in the study.

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3. Takenaka H, Ohmiya N, Hirooka Y, Nakamura M, Ohno E, Miyahara R, et al. Endoscopic and imaging findings in proteinlosing enteropathy. J Clin Gastroenterol. 2012;46(7):575–80 [Epub 2011/12/06]. 4. Lai Y, Yu T, Qiao XY, Zhao LN, Chen QK. Primary intestinal lymphangiectasia diagnosed by double-balloon enteroscopy and treated by medium-chain triglycerides: a case report. J Med Case Rep. 2013;7:19 [Epub 2013/01/16]. 5. Ingle SB, Hinge Ingle CR. Primary intestinal lymphangiectasia: minireview. World J Clin Cases. 2014;2(10):528–33 [Epub 2014/10/18]. 6. Mine K, Matsubayashi S, Nakai Y, Nakagawa T. Intestinal lymphangiectasia markedly improved with antiplasmin therapy. Gastroenterology. 1989;96(6):1596–9. 7. MacLean JE, Cohen E, Weinstein M. Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy. Pediatrics. 2002;109(6):1177–80 [Epub 2002/06/04]. 8. Kaneko H, Yamashita M, Ohshiro M, Ohkawara Y, Matsumoto Y, Nomura K, et al. Protein-losing enteropathy in a case of nodal follicular lymphoma without a gastrointestinal mucosal lesion. Intern Med. 2008;47(24):2171–3 [Epub 2008/12/17]. 9. Konar A, Brown CB, Hancock BW, Moss S. Protein losing enteropathy as a sole manifestation of non-Hodgkin’s lymphoma. Postgrad Med J. 1986;62(727):399–400 [Epub 1986/05/01]. 10. Laharie D, Degenne V, Laharie H, Cazorla S, Belleannee G, Couzigou P, et al. Remission of protein-losing enteropathy after nodal lymphoma treatment in a patient with primary intestinal lymphangiectasia. Eur J Gastroenterol Hepatol. 2005;17(12): 1417–9 [Epub 2005/11/18]. 11. Broder S, Callihan TR, Jaffe ES, DeVita VT, Strober W, Bartter FC, et al. Resolution of longstanding protein-losing enteropathy in a patient with intestinal lymphangiectasia after treatment for malignant lymphoma. Gastroenterology. 1981;80(1):166–8 [Epub 1981/01/01]. 12. Kinani A, Havelund T, Knudsen T. Protein-losing enteropathy caused by a thoracic cyst. Ugeskr Laeger. 2009;171(36):2573–4. (Epub 2009/09/08. Proteintabende enteropati forarsaget af torakal cyste).

Protein-losing enteropathy cured by resection of adenomatous goiter: report of a case.

A 51-year-old Japanese woman presented to our hospital with systemic edema and general fatigue. Her serum albumin level was very low (1.5 g/dL). Techn...
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