Carcinoid Heart Disease Associated with Primary Ovarian Carcinoid Tumor: A Rare Presentation

Abstract

Primary ovarian carcinoid tumors, an extremely rare subset of ovarian malignancies (<0.1% of cases), typically manifest with abdominal pain and bloating. The occurrence of carcinoid heart disease (CHD) without classic carcinoid syndrome features is exceptionally uncommon. We report a 54-year-old female presenting with dyspnea and edema over months, lacking typical carcinoid syndrome signs. Initial assessments diagnosed heart failure, supported by elevated NT-Pro BNP, echocardiographic right ventricular dilation, and pulmonary/tricuspid valve regurgitation (normal left ventricular function). Right heart catheterization showed normal pulmonary/right ventricular pressures. Subsequent investigations (computed tomography thorax abdomen pelvis, 5-hydroxyindole acetic acid levels) strongly suggested carcinoid disease, confirmed by an octreotide scan revealing an octreotide-secreting ovarian carcinoid tumor. Surgical intervention included tricuspid and pulmonary valve repair, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Primary ovarian carcinoid tumors, though rare, may lead to unexpected complications like CHD. Timely diagnosis and intervention are pivotal for optimizing patient outcomes in such cases.

INTRODUCTION

Neuroendocrine tumors, particularly carcinoids, often arise from gastrointestinal enterochromaffin cells. Ovarian carcinoids constitute merely 1% of all carcinoid tumors.[1] These tumors often remain asymptomatic or display nonspecific symptoms until they reach an advanced stage, making early diagnosis challenging. Carcinoid symptoms typically manifest in individuals aged 55–60, occurring between the fifth and seventh decades of life. The interval between symptom onset and diagnosis of carcinoid heart disease (CHD) typically spans 24–28 months but can extend up to 5 years.

Clinical presentation may involve non-specific symptoms such as abdominal discomfort, bloating, and bowel or bladder changes. While some individuals with carcinoid tumors may experience classic carcinoid syndrome symptoms, including diarrhea, abdominal pain, flushing, palpitations, dyspnea, and wheezing, the occurrence of CHD without these typical symptoms is exceptionally rare.

CHD stems from impaired hepatic metabolism due to widespread liver involvement by carcinoid tumors. This leads to excessive production of vasoactive chemicals like serotonin (5-HT),[2] which upregulates tissue growth factor-β and stimulates collagen synthesis by heart valve cells. This process may contribute to fibrosis of endocardial surfaces of the heart.

While primary diseases of the tricuspid or pulmonary valves are unusual, more common causes include congenital abnormalities, rheumatic heart disease, or infective endocarditis. CHD, although rare, is an important and intriguing contributor to intrinsic tricuspid and pulmonary valve diseases, resulting in significant morbidity and mortality due to right heart failure.[3]

Given the rarity of primary ovarian carcinoid tumors and their potential to cause unusual complications like CHD, this case serves as a valuable reminder for clinicians to consider such possibilities in the differential diagnosis of ovarian masses. Early recognition and prompt intervention are vital to achieving optimal patient outcomes. Therefore, this case report offers important insights into the diagnosis and management of an uncommon health issue and highlights the need for a high level of clinical suspicion when encountering atypical presentations in clinical practice.

CASE PRESENTATION

A 54-year-old woman with a history of rheumatoid arthritis, gout, hypertension, and benign paroxysmal positional vertigo presented with progressive dyspnea, leg swelling, and limited exercise capacity (500 yards). Cardiology evaluation revealed elevated jugular venous pressure (+7 cm), pedal edema, and a tricuspid region pansystolic murmur. Blood tests showed high NT-Pro BNP levels (1074 ng/L). Echocardiography indicated a severely dilated right ventricle (RV) with impaired function and tricuspid regurgitation. Right heart catheterization confirmed severe tricuspid regurgitation with normal pulmonary and RV pressures.

Further investigations, including 5-hydroxyindole acetic acid (5-HIAA) levels, computed tomography (CT) scans of the thorax, abdomen, and pelvis, and ovarian tumor histopathology, diagnosed CHD with a primary ovarian carcinoid. A multidisciplinary team, including neuroendocrine and gynecology specialists, recommended cardiac surgery before abdominal tumor resection. An octreotide scan confirmed an octreotide-secreting ovarian carcinoid. The patient started lanreotide, a somatostatin analog.

She underwent tricuspid and pulmonary valve replacement followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy to remove the ovarian carcinoid tumor. Biopsy results confirmed FIGO stage 1A with a low Ki67 proliferation index. The patient received comprehensive care from a multidisciplinary team involving neuroendocrine, cardiology, cardiac surgery, and gynecology experts for the best possible outcome.

Investigations

The diagnosis of CHD relied on two key investigations: the 24-h urinary excretion of 5-HIAA and transthoracic echocardiography.

Electrocardiogram

The patient’s electrocardiogram revealed a prolonged PR interval of 216 ms, partial right bundle branch block, and T wave inversion in the inferior and lateral leads.

Cardiac imaging

A transthoracic echocardiogram depicted a severely dilated RV with severely impaired function. Significant tricuspid stenosis appeared secondary to tethering due to RV dilatation with associated free-flow regurgitation [Figure 1].[4] Pulmonary (infundibular) stenosis stemmed from RV volume overload due to tricuspid regurgitation. The echocardiogram also identified severe pulmonary regurgitation, suggesting likely pulmonary hypertension.

Figure 1.

Echo showing free-flow tricuspid regurgitation

Right heart catheterization

Right heart catheterization results showed normal pulmonary and RV pressures and confirmed severe tricuspid regurgitation, suggesting that the tricuspid regurgitation might be primary in nature.

Biochemistry and NM octreotide scan whole body

Biochemical assessment revealed an elevated 24-h urinary excretion of 5-HIAA at 207 (reference range <45 umol/24 h). The NM Octreotide scan of the whole body demonstrated increased uptake within a large, heterogeneous pelvic soft-tissue mass (Krenning 3), most likely originating from the ovaries.

Computed tomography thorax abdomen pelvis with histopathology

CT imaging of the thorax, abdomen, and pelvis, coupled with histopathological analysis, were additional diagnostic tools employed in this case [Figure 2]. Postbiopsy histopathology report confirmed ovarian carcinoid tumor with FIGO stage 1A with low Ki67 proliferation index.

Figure 2.

Computed tomography showing a large heterogeneous mass in pelvis

Treatment

Caring for patients with CHD involves addressing right heart failure, pharmacotherapy to control tumor product secretion and surgical/interventional treatment of vulvar issues.

Medical management

General heart failure measures included salt and water restriction, along with careful fluid balance and weight monitoring. Bumetanide, a loop diuretic, was initiated to manage fluid retention. In addition, lanreotide, a somatostatin analog,[5] was prescribed to alleviate symptoms and enhance survival in CHD patients.

Surgical intervention

The patient underwent prosthetic tricuspid and pulmonary valve replacement. Subsequently, a total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed to remove the ovarian carcinoid tumor.

This comprehensive approach addressed the multifaceted management of CHD, encompassing medical and surgical strategies.

Outcome and follow-up

After the surgery, the patient underwent thorough evaluations by both the gynecology and cardiology departments. The histopathology report confirmed the presence of an ovarian carcinoid tumor at FIGO stage 1A, characterized by a low Ki67 proliferation index. The patient exhibited notable improvement, particularly in the alleviation of heart failure symptoms. Close monitoring in the heart failure clinic was instituted for effective symptomatic management. A follow-up plan has been established, encompassing the scheduling of a repeat CT scan and echocardiography at an appropriate interval. This comprehensive approach is designed to safeguard the patient’s ongoing well-being and meticulously track her recovery progress.

DISCUSSION

Primary ovarian carcinoid tumors are exceedingly rare,[6] constituting <1% of all ovarian neoplasms. These tumors originate from ovarian neuroendocrine cells, capable of secreting bioactive amines and peptides, resulting in various clinical symptoms and syndromes. Common presentations include abdominal pain, bloating, urinary frequency, and constipation. Some patients may experience carcinoid syndrome, characterized by flushing, diarrhea, and bronchospasm due to serotonin and vasoactive substance release.

CHD is a recognized complication of neuroendocrine tumors, affecting up to 20% of cases. Typically, it arises in the presence of significantly elevated serotonin and vasoactive hormones, often due to hypersecretory advanced tumors and impaired clearance, especially with liver metastases. The tricuspid valve is most commonly affected, exhibiting regurgitation and stenosis, followed by the pulmonary valve. Left-sided valves are less frequently involved. Diagnosis involves imaging studies (ultrasound, CT, or magnetic resonance imaging) and biopsy, with serum chromogranin A levels serving as a sensitive marker. Histologically, these tumors exhibit a trabecular pattern[7] with characteristic neuroendocrine markers such as chromogranin and synaptophysin.

Surgical resection is the primary treatment for primary ovarian carcinoid tumors. The extent of surgery depends on tumor size, stage, and metastases. Adjuvant chemotherapy and radiation therapy are reserved for advanced or metastatic cases. The overall prognosis is favorable, with a 5-year survival rate of 70%–80% for localized disease and <40% for advanced or metastatic disease.

Cardiac valve disease correction involves surgery, typically recommended when severe regurgitation results in heart failure, often with right-sided symptoms. Presurgical treatment with somatostatin analogs is crucial to ensure safer surgery and prevent carcinoid crisis, characterized by a sudden surge in vasoactive hormones causing severe hemodynamic instability. The prognosis depends on cardiac involvement, treatment response, and the underlying neuroendocrine tumor. Advanced or metastatic disease may have a median survival of approximately 2–3 years.

Published cases of primary ovarian carcinoid tumors with associated CHD are exceptionally rare. Most published literature focuses on carcinoid tumors originating from the gastrointestinal tract. The management approach outlined here aligns with established guidelines for neuroendocrine tumors, emphasizing the importance of a multidisciplinary team for comprehensive care.[8]

Learning points

• Primary ovarian carcinoid tumors are exceptionally rare, emphasizing the importance of considering unusual possibilities when faced with atypical patient presentations

• CHD is rare without classic carcinoid syndrome symptoms, highlighting the need for clinical vigilance even in the absence of typical signs

• Primary ovarian carcinoid tumors often lack specific symptoms until advanced stages, making early diagnosis challenging but critical for favorable outcomes. Multidisciplinary care, including presurgical preparation with somatostatin analogs, is crucial for managing this rare condition effectively.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.