Copyright © 2007, The European Society of Cardiology
Echocardiographic diagnosis of carcinoid disease: Exceptional evolution after ovarian tumor resection without cardiac surgery
aService of Cardiology, Hospital Universitario de Getafe, Madrid, Spain
bDepartment of Pathology, Hospital Universitario de Getafe, Madrid, Spain
Received 8 April 2006; received in revised form 7 July 2006; accepted after revision 16 July 2006.
* Corresponding author. Tel.: +34 916839360. ogl1976{at}yahoo.es
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Abstract |
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There are very few cases described in literature with carcinoid heart disease caused by a pure ovarian tumor. Right heart failure remains the major cause of morbidity and mortality. Cardiac surgery is the only definitive treatment when cardiac symptoms become severe but with high perioperative mortality rates. We present a 68-year-old woman with a pure ovarian carcinoid tumor complicated with heart disease alive 7 years later after ovarian resection, without valve replacement and with regression of tricuspid and pulmonary injury. Echocardiography was the diagnostic clue.
Keywords: Ovarian tumor; Carcinoid disease; Tricuspid regurgitation
Carcinoid tumors release serotonin and other vasoactive substances in the circulation, causing the "carcinoid syndrome" that includes flushing, diarrhea, bronchospasm and cardiac valve involvement. Since most are located in the gastrointestinal tract and the liver metabolizes those substances, the carcinoid syndrome generally occurs in the presence of liver metastasis. On the other hand, the rare ovarian carcinoid tumors1 can produce the carcinoid syndrome in the absence of liver metastasis, because they do not drain into the portal circulation,2 and carcinoid tumors of this location can present with unexplained right-sided heart failure.
We report a patient with symptomatic carcinoid heart disease associated with a pure ovarian carcinoid tumor, in whom early diagnosis allowed cure by oophorectomy. After 7 years cardiac valve involvement has regressed and she maintains a good functional class under diuretic treatment.
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Case report |
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A 68-year-old woman was admitted to the hospital in July 1998 with a one month history of edema of the lower extremities, increase of abdominal perimeter and dyspnea on minor effort. Past medical history included bouts of bronchial hyperreactivity associated with respiratory infections for the previous years. From August 1997 until May 1998 the patient suffered from diarrhea and the diagnosis of irritable bowel syndrome was made after ruling out an infectious or other organic aetiology.
Neck vein engorgement was evident on inspection. On cardiac auscultation a soft systolic pulmonary ejection murmur and a pansystolic tricuspid murmur were audible. Ascites was present precluding the assessment of hepatomegaly and there was 3+ edema of both lower limbs. The ECG showed sinus rhythm with low voltages. The chest X-ray showed clear lung fields and moderate cardiomegaly with enlargement of right side of the heart, without pericardial calcification. Haematology and biochemistry were all within normal ranges. Transthoracic (TTE) and transesophageal (TEE) echocardiograms disclosed right atrial and right ventricular dilatation (Fig. 1). The tricuspid valve (TV) was markedly thickened, with very limited mobility, and the Doppler signal was "dagger-shaped", characteristic of severe tricuspid regurgitation. Peak regurgitation velocity was 3.6m/s. The pulmonary valve appeared normal. Right ventricular systolic function, left side valves and left ventricular systolic function were normal. There was moderate pericardial effusion without hemodynamic compromise. These findings were interpreted as suggestive of carcinoid heart disease and a tumor search was started.
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Abdominal computed tomography showed ascites and a right adnexal mass without hepatic metastases. Barium meal and barium enema were normal. Urinary 5-hydroxyindoleacetic acid (5HIAA) was 76mg/24h (reference value<2–8g/24h) in two different measurements. Somatostatin analogues were administered and surgery was scheduled. At laparotomy a right ovarian mass was excised while both fallopian tubes and the contralateral ovary were normal on inspection. The surgical specimen measured 14x10x8cm and weighed 650g. It consisted of a fibroid-like whitish to orange, mostly solid mass with focal areas of hemorrhage (Fig. 2). Histologically (Fig. 3) the tumor had the features of an insular variant of pure carcinoid tumor, without trace of associated teratoma or other tumor.
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The symptoms disappeared shortly after surgery and urinary 5HIAA levels returned to normal four weeks postoperatively. The patient was placed on diuretics to relieve symptoms of right heart failure with optimal results. Seven years after surgery, the patient is alive and receives only 40mg of furosemide, without recurrence of diarrhea or symptoms of right heart failure. Serial echocardiographic studies have shown progressive improvement of tricuspid leaflet movement and regurgitation which in the last exam was graded as mild. Pulmonary valve systolic velocity increased transiently to 3.1m/s, but by March 2006 it had decreased to 1.9m/s, in the face of moderate pulmonary regurgitation. Right chambers are normal in size (Fig. 4). The patient declined a new TEE exam.
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Discussion |
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The carcinoid syndrome, described by Thorson in 19543 is due to the release of large amounts of amines (serotonin, catecholamine...) causing gastrointestinal, bronchial, neuropsychological and cutaneous symptoms. Cardiac involvement is seen in up to 60% of patients, generally those with metastatic carcinoid and heart failure is the presenting symptom in 20%. Valvular changes that occur usually in the tricuspid and pulmonary valves4 are due to the development of fibrous plaques with secondary retraction and fixation of the valve leaflets. The formation of the fibrous plaques appears to be mediated by serotonin 1B receptor sub-type, which induces fibroblast proliferation on in vitro stimulation5 and can be detected in subendocardial cells.6,7 The fibrous reaction may also involve atrial and ventricular endocardium, vena cava, pulmonary artery, coronary sinus and subvalvular apparatus. Calcification of affected valves or pericardial involvement is rare.8 Left-sided cardiac involvement is seen in only 7% of patients with bronchial carcinoids or right-to-left intracardiac shunts.8 Valvular dysfunction can result in right heart failure, a major cause of morbidity and mortality, therefore the importance of early diagnosis.9,10 Mean life expectancy is 1.6 years for patients with carcinoid heart disease versus 4.6 years in those without cardiac involvement.11
Somatostatin analogues, which are potent inhibitors of serotonin release can produce symptomatic improvement and prolong survival, but there are no data to suggest that they can cause regression of the cardiac damage.8 Since most patients with valvular involvement die of progressive right heart failure within 1 year, cardiac surgery is the only treatment capable of producing marked symptomatic improvement, according to the experience of the last decades.12 However, perioperative mortality can be up to 35% from postoperative bleeding, mainly in patients with liver metastasis, and right ventricular failure.11
Primary ovarian carcinoid tumors are uncommon. In a review of the literature Soga et al.13 found that 57% were associated with an ovarian cystic teratoma. The remainder 43% "pure" carcinoid tumors were significantly larger, metastasised more frequently, featured the full carcinoid syndrome more often and showed a lower 5-year survival rate. Carcinoid syndrome was also more frequent in tumors with pure insular histopathological pattern (39%) than in those with a pure trabecular pattern (8%).
There are very few cases described in literature of carcinoid heart disease caused by an ovarian tumor. The largest series (17 patients, only two with heart disease) has been reported by Davis et al.9 In contrast to gastrointestinal tumors, carcinoid syndrome occurs in up to one-third of patients with ovarian tumors, due to the direct drainage into the vena cava, bypassing the liver. Most patients present with right-sided heart failure preceded by a long history of diarrhea1 or are found to have a pelvic mass. Abdominal computed tomography is essential for the differential diagnosis with small-bowel carcinoid.14
A history of bronchospasm and diarrhea was present in our patient, but it was the development of right-sided heart failure and the echocardiographic picture that led to the search for a carcinoid tumor. The relatively early detection and surgical cure resulted in an excellent outcome with regression of valvular involvement and disappearance of heart failure along 7 years of follow-up. This is in contrast with the majority of patients with carcinoid heart disease described in the literature, that needed tricuspid valve replacement11,15,16 and often also pulmonary valve surgery, with a complicated postoperative period. We have found only one case with a favorable course in the absence of cardiac surgery, similar to our patient, but with a follow-up of 1 year.17 Our long echocardiographic follow-up was interesting in that it showed continuous tricuspid valve improvement, while the degree of pulmonary valve involvement seemed to increase initially, although with later improvement.
In summary, isolated tricuspid and pulmonary valve disease detected by echocardiography can be the clue to the early diagnosis of a carcinoid tumor, leading to early treatment and potentially to the reversibility of the valvular damage. In the absence of liver metastasis a search for atypical tumor locations, such as the ovaries is mandatory, since cardiac involvement does not imply very advanced disease in these cases and stabilization or regression of right-sided cardiac valvular damage appears possible after tumor resection.
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