Addressing the Physiologic and Psychological Symptoms Associated with Carcinoid Tumors

Article Outline

• Abstract
• Case Exemplar
  • Introduction
  • Pathophysiology
  • Clinical Manifestations
  • Carcinoid Syndrome
  • Diagnosis
  • Acute Management
  • Mental Health Management
  • Patient Education
  • Conclusion
• References
• Copyright

Abstract 

Carcinoid tumors are atypical neoplasms that commonly originate in the gastrointestinal tract. Demographic characteristics such as age, sex, and race are relevant factors that contribute to the rising prevalence of the disease. A distinct feature of the tumor's progression is a condition referred to as carcinoid syndrome. Carcinoid syndrome is a rare but critical complication of the carcinoid tumor. A fluctuation in the neurotransmitter, serotonin, affects the mental health stability of clients with the disorder. Detection and management by nurse practitioners of carcinoid tumors requires astute knowledge of the carcinoid disease process and competency to address both the physiologic and psychological variations.

Keywords:  carcinoid syndrome , carcinoid tumor , mental health , neuroendocrine tumors , serotonin

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Case Exemplar 

Katie, a 35-year-old white female presented at an ambulatory clinic and was examined by a nurse practitioner (NP) for an onset of generalized abdominal discomfort. Her prior health history was unremarkable for physical, psychological, and sociologic concerns. Symptoms that accompanied the chief complaint of abdominal pain included nausea, vomiting, diarrhea, rectal bleeding, and anorexia during a 2-month interval. In addition to the physical symptoms, Katie now reported episodes of insomnia, irritability, labile mood that ranged from hypomania to depression, stress that intensified with the physical symptoms, and malaise. Katie denied any episodes of increased temperature, jaundice, respiratory complications, or cardiovascular distress. Physical assessment data indicated vital signs within normal limits and initial laboratory studies of a complete blood count, serum chemistries, and liver function tests that were within normal ranges. Despite the inconclusive laboratory findings at this time, Katie's symptoms failed to respond with rest, stress-reduction techniques, dietary modifications, or nutritional supplements. A gastroenterology consult was arranged by the NP for further evaluation and treatment. Under the gastroenterologist's care, a colonoscopy and esophogastroduodenoscopy was completed, and the pathologic impression described active gastritis with intestinal metaplasia of the stomach and benign lymphoid aggregates to the colonic mucosa. Katie's manifestation of symptoms did not subside after the procedure, and she began to experience intermittent facial flushing with increased episodes of diarrhea, and melena. Additional laboratory studies and radiographic imaging studies were ordered to ascertain a clinical diagnosis. A 24-hour urine collection for 5-hydroxyindoleacetic acid (5-HIAA) indicated a positive result at 10.7 mg/24 hours (reference range: 0.0-10.0 mg/24 hours) and serum serotonin was considerably elevated at 1350 ng/mL (carcinoid reference range: 500-3500 ng/mL). A chest X-ray was clear, and the computed tomography (CT) scan of the abdominal region was negative with no inflammatory changes involving the colon or small bowel. An octreotide imaging scan detected an increased uptake in the ileum which confirmed the diagnosis of a carcinoid tumor.

Introduction 

Carcinoid tumors are one of the most distinctive neuroendocrine tumors occurring at a rate of approximately 1 to 5 per 100,000 persons.¹ The true incidence may be even higher because carcinoids are rarely a symptomatic disease, progress gradually, and are detected incidentally during endoscopy or autopsy.² The distinctive characteristics of the carcinoid tumor were originally acknowledged by Lubarsch in the late 1800s, in which he identified multiple tumors in the distal ileum on performing an autopsy.³ In 1907, Obendorfer introduced the term karzinoide to designate that the development of carcinoid tumors are subtle in progression and a less-prominent neoplasm in relation to other malignancies.³ The cause of tumor development is still unknown because the clinical presentation of the symptoms is often associated with other differential diagnoses and hormonal production is absent or destroyed by the liver.⁴

The tumors were discovered to originate in various organs of the body wherever enterochromaffin cells exist. The enterochromaffin type I cells are the most predominant endocrine cells present in carcinoid tumors that secrete hormones.³ Primary tumor sites affect the gastrointestinal system, including the small intestine, appendix, and rectum. Bowel obstruction can occur from the carcinoid tumor invading adjacent tissues and organs which disrupts perfusion and leads to intestinal ischemia.⁴ The approximate occurrence of carcinoid tumors of clinical significance according to the location of origin is presented in Table 1.³, ⁵

Table 1. Organ Distribution of Carcinoid Tumors

Source: adapted from Schnirer II, Yao JC, Ajani JA. Carcinoid: a comprehensive review. Acta Oncol. 2003;42(7):672-692. Carcinoid Cancer Foundation. A review of carcinoid disease. Available at: www.carcinoid.org. Accessed July 5, 2005.

The client's age at time of diagnosis ranges from 10 years to 90 years; however, carcinoid tumors are most frequently reported between the ages of 50 and 70 years with a mean age of approximately 55 years. The diagnosis is more widespread in African Americans than in whites and women are at greater risk than are men; however, there is a vague relation between epidemiologic findings and demographic indicators.¹, ⁶ Survival rate is variable, depending on tumor location.

The purpose of this article is to heighten awareness of the NP to explore further assessment of gastrointestinal symptoms to delineate carcinoid tumors from differential diagnoses such as irritable bowel syndrome, ulcerative colitis, gastritis, and intestinal bleeding.

Pathophysiology 

The neuroendocrine cells are responsible for releasing such hormones as secretin, gastrin, insulin, and glucagons, and pancreatic hormones resembling somatostatin. It is recognized that cancer cells produce hormones, and carcinoid tumors create excessive secretion of hormonal products such as serotonin, bradykinin, and chromogranin-A, -B, and -C, which are common biochemical substances secreted.³, ⁷ Chromogranin levels are nonspecific markers; however, chromogranin-A is noted to be the most sensitive marker in the clinical diagnosis of carcinoid tumors.³ In addition to the typical hormonal profiles, other substances such as growth hormone, glucagon, histamine, prostaglandins, insulin, and grastrin can also be released depending on the carcinoid tumor site of origin.³ Serotonin (5-hydroxytryptamine [5-HT]) is synthesized by the carcinoid tumor from tryptophan and metabolized to 5-HIAA, which is presumed to be responsible for primary hypersecretion.⁷ Serotonin and the hormonal substances stimulate the progression of the disease that affects the cardiovascular, gastrointestinal, pulmonary, and other body systems that will eventually lead to malignant carcinoid syndrome.⁵ The pathologic features of carcinoid tumors are identified as benign or malignant. Benign carcinoids are well differentiated, and the nodules are typically grayish-white to yellow in color. The malignant carcinoids evolve from benign tumors that permeate the surrounding structures and invade the lymphatic system.⁸

Clinical Manifestations 

The clinical manifestations of carcinoid tumors derive from the local effects of tumor growth. Clinical signs and symptoms can be easily unrecognized by NPs because clients typically are asymptomatic with vague descriptors unless metastasis occurs to the liver. The ill-defined symptoms of carcinoid tumors are often misdiagnosed as irritable bowel syndrome or spastic colon because these tumors trigger intermittent abdominal pain, nausea, vomiting, abdominal distention, change in bowel habits, obscure intestinal bleeding, and the potential for bowel obstruction.⁸, ⁹ These advanced clinical findings typically do not surface until they generate painful enlargement of the liver and metastasis.¹⁰ However, some persons can maintain a high level of functioning with or without metastasis from malignant carcinoid tumors. In contrast to the typical slow-growing carcinoid tumor, a rare destructive type of tumor called adenocarcinoids can contribute to an abrupt exacerbation of symptoms with a poor prognosis.⁴

Carcinoid Syndrome 

One of the most critical complications of untreated carcinoid tumors is the carcinoid syndrome. Malignant carcinoid syndrome is the predominant clinical feature of carcinoid tumors, which occurs in approximately less than 10% of persons.¹ The progression of the carcinoid syndrome is associated with a higher incidence of mortality with a survival rate of 3.5 to 8.5 years.³ The consequences of the carcinoid syndrome produces clinical manifestations that are intermittent and consist of flushing, abdominal pain, diarrhea, wheezing, dyspnea, and right-sided heart failure in the late stages of the disease.³, ¹¹ The carcinoid syndrome is a late manifestation of the disease, resulting from the progression of the tumor. Cutaneous flushing, diarrhea, endocardial fibrosis, and bronchoconstriction are the most prevalent endocrine consequences of these tumors. Flushing is the hallmark clinical feature of the carcinoid syndrome that involves the upper half of the body and occurs spontaneously. This cardinal sign can unmask carcinoid syndrome. The differential diagnosis of flushing associated with carcinoid syndrome needs to be considered because not all clients display this clinical characteristic. Differential diagnoses for a NP's consideration may include menopause, alcohol withdrawal, adverse drug reactions, chronic myelogenous leukemia, and tumors.¹, ³, ⁴ The cause for the clinical manifestations associated with carcinoid syndrome depends on the causative hormone, summarized in Table 2.³

Table 2. Clinical Symptoms of Carcinoid Syndrome and Suspected Causative Agent

Source: adapted from Schnirer II, Yao JC, Ajani JA. Carcinoid: a comprehensive review. Acta Oncol. 2003;42(7):672-692.

Diagnosis 

Carcinoid tumors exhibit slow growth and may not be diagnosed for several years from the onset of clinical manifestations because of indistinct symptoms.⁴ In some cases, the diagnosis may not be detected for approximately 15 to 20 years.³ A carcinoid tumor is diagnosed by biopsy and clinical and histologic examinations. Standard radiographic imaging techniques are diagnostic modalities that assist in the identification of carcinoid tumors and metastasis. Routine chest X-ray, CT scan, magnetic resonance imaging (MRI), barium enema, and upper gastrointestinal and small bowel follow through with fluoroscopy can assist to establish the diagnosis. Endoscopic approaches are useful in the diagnosis of tumors located in the small bowel.³

The identification of carcinoid tumors strongly correlates with the production of serotonin. Serotonin is metabolized to a substance identified as 5-HIAA.³, ¹² With carcinoid tumors, 5-HIAA is overproduced, which is the quantitative measurement in the urine that a person excretes in a 24-hour period.¹² This is indicative of the amount of serotonin being produced by the body during that time frame. A 5-HIAA result greater than 9 mg/24 hours without malabsorption or greater than 30 mg/24 hours with malabsorption confirms the diagnosis of carcinoid tumor.⁸ Additional carcinoid markers can be measured such as chromogranin-A and serotonin in the blood platelets if the 5-HIAA is within normal limits.³, ¹³

The definitive diagnostic for carcinoid tumors is a sophisticated imaging study using diethylenetriamine pentaacetic acid (DTPA)-octreotide scintigraphy (OctreoScan).³, ¹⁴ OctreoScan technology possesses the capability to visualize and localize neuroendocrine tumors through the intravenous administration of a radioactive isotope.¹⁵ Following the injection, the ¹¹¹In-pentetreotide radioactive isotope binds to somatostatin receptors existing in body tissues.³ Nuclear imaging is typically obtained at 6, 24, and 48 hours after intravenous administration of the radiopharmaceutical. OctreoScan imaging is beneficial for patients with carcinoid tumors because testing can differentiate carcinoid tumors, expose metastasis, and localize carcinoid tumors. Overall, the OctreoScan is 90% accurate in identifying neuroendocrine tumors.³

The NP's role in the detection of carcinoid tumors is to complete a comprehensive clinical assessment and collaborate with the interdisciplinary health care team to ensure diagnostic procedures are integrated in the plan of care.

Acute Management 

The treatment for carcinoid tumors needs to be individualized for each patient based on the size, location, and tumor growth. Tumors that are producing gastrointestinal symptoms and greater than 1 cm in diameter are to be managed as malignant lesions that possess the capability to spread to other organs.³ The therapeutic approach for carcinoid tumors consists of conventional methods such as surgery, chemotherapy, and palliative relief with radiation therapy. A contemporary treatment option that has achieved favorable results in advanced disease with or without the carcinoid syndrome is somatostatin analogues.³, ¹⁵

Surgical resection of the primary tumor and involved lymph nodes is the principal therapy for the management of carcinoid tumors and may be a prospective curative intervention.³ Surgical management is also indicated to relieve intestinal obstruction and to control bleeding.

The administration of oral or intravenous chemotherapy is another treatment option for aggressive tumors, liver metastasis, signs of intestinal obstruction, and symptoms of the carcinoid syndrome.¹⁵ Patients undergoing chemotherapy may or may not necessarily respond to this form of treatment because of resistance of the carcinoid tumors to chemotherapy regimens.³ The therapeutic response for chemotherapy has been affective in approximately 30% of the cases.¹⁵ Single-agent chemotherapy treatment may include 5-fluorouracil, doxorubicin, actinomycin D, dacarbazine, and streptozotocin. However, a more favorable response is combination chemotherapy treatment.³ Radiation therapy is reserved solely for palliative relief of pain once tumors spread to the skeletal system.

A first-line therapy for advanced metastatic carcinoid tumors is a somatostatin analogue identified as octreotide. In some cases, octreotide has a therapeutic benefit of controlling and reducing tumor growth. Additionally, octreotide can be administered before surgical interventions to minimize carcinoid complications intraoperatively.¹⁵ Octreotide is administered three times daily subcutaneously and is effective in alleviating the clinical symptoms of carcinoid tumors such as flushing, diarrhea, abdominal discomfort, and respiratory complications. Long-acting forms of octreotide have recently been approved for therapeutic use in the United States at this time.¹⁵ Adverse effects from octreotide injections include nausea, vertigo, hyperglycemia, and abdominal pain.¹⁵ Differentiating the symptoms of advanced disease from the adverse effects of the octreotide may prove challenging for NPs.

Mental Health Management 

NPs need to assume responsibility for educating the patient about the potential mental health risk factors associated with carcinoid tumors or make a referral to a mental health provider. The connection between carcinoid tumors and the fluctuation of serotonin may contribute to a mental health imbalance that produces depressed mood, anxiety, or both.¹⁶, ¹⁷ Serotonin is a pivotal neurotransmitter that requires monitoring during clinical management. Providing mental health management should begin with a comprehensive psychiatric mental health assessment. Emotional status, appearance, behavior, speech, mood, affect, and thought process should be evaluated. Assessing for alterations in relationships, social interactions, interests and abilities, sexual concerns, usual daily living functioning patterns, and behavior are recommended.

Major depression is one of the critical mood disorders that can result from variable serotonin levels. According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), having 5 or more depressive symptoms, occurring nearly every day during a 2-week period, is the diagnostic criterion for the diagnosis major depression (Table 3).¹⁸

Table 3. Diagnostic Criteria for Major Depression

Source: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.

Noted depressive symptoms warrant further questioning about suicidal ideations and may indicate hospitalization, psychotherapy, or medication management with antidepressive agents.¹⁶

Symptoms of anxiety should also be assessed as a result of labile neurotransmitter variations. Depending on the level of the anxiety, symptoms could include narrowed perceptual fields, poor concentration, restlessness, irritability, and physical manifestations. The DSM-IV-TR identifies generalized anxiety disorder as excessive anxiety or worry more days than not during a 6-month period (Table 4). Managing anxiety could involve hospitalization, psychotherapy, or pharmacologic interventions.

Table 4. Diagnostic Criteria for Generalized Anxiety Disorder

Source: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000.

Assessing substance use is essential, as the patients may self-medicate to ameliorate their symptoms of depression or anxiety. Self-medicating behaviors complicate the illness and nursing interventions.

Patient Education 

Patient education is a critical component in the management of carcinoid tumors. Patient education is multidimensional and needs to address the physiologic and psychosocial symptoms. In addition, nutritional modifications and vitamin supplements are part of the educational intervention.

Patients need to be informed that specific foods can increase urinary and serum serotonin levels. Foods that need to be avoided for a 48-hour period before specimen collection would include avocados, bananas, kiwis, pineapples, plums, tomatoes, and walnuts.³ To prevent exacerbation of symptoms such as diarrhea and flushing associated with carcinoid tumors, recommendations consist of maintaining an ideal body weight, eliminating alcohol and spicy foods, and avoiding the ingestion of medications that contain ephedrine.¹⁵ Stress management is another approach to minimize the adverse symptoms which could include abdominal pain during the course of the illness. Supportive care interventions for stress and pain management encompass relaxation techniques, meditation, guided imagery, breathing exercises, physical exercise, massage or touch therapy, music, journaling, or a combination of techniques. Highlighted in Table 5 are websites for patients and significant others to access for educational support.

Table 5. Carcinoid Tumor Websites

Conclusion 

NPs play a pivotal role in the clinical management of patients with carcinoid tumors. A thorough assessment exploring the multidimensional clinical manifestations and implementation of therapeutic techniques can minimize the serious complications associated with carcinoid syndrome. In addition, assessing and monitoring mental health variations are an imperative component resulting from the fluctuations of serotonin. Possessing a heightened awareness of advances in health technology, such as OctreoScan imaging, can facilitate the diagnosis of carcinoid tumors and evaluation of symptoms during the course of the illness. Early detection, aggressive management, accurate patient education, and a supportive nursing approach are key elements of providing excellence in nursing care for patients with carcinoid tumors. The NP's role in the detection of carcinoid tumors is to complete a comprehensive clinical assessment and collaborate with the interdisciplinary health care team. Diagnostic imaging and biochemical studies are an essential component to correctly diagnose and direct the physical and psychological plan of care.

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