Síndrome de Hedinger secundario a Tumor neuroendocrino bronquial. Presentación de un caso

El síndrome carcinoide es un síndrome paraneoplásico que se presenta en tumores neuroendocrinos. Aunque es una entidad infrecuente suele ser la primera manifestación de la enfermedad. La baja incidencia junto a la presentación inespecífica genera retrasos diagnósticos importantes. Se presenta el caso de una paciente con síntomas digestivos y tuforadas que posteriormente agrega insuficiencia cardíaca, logrando mediante un ecocardiograma típico y marcadores analíticos el diagnóstico de síndrome carcinoide. Posteriormente se evidencia que su origen en un tumor neuroendocrino bronquial. Conocer las características de este síndrome es fundamental para mantener una alta sospecha clínica en pacientes con síntomas sugestivos logrando un diagnóstico precoz y adecuado.

Carcinoid syndrome is a paraneoplastic syndrome that occurs in neuroendocrine tumors. Although It is an uncommon entity, it is usually the first manifestation of the disease. The low incidence besides the non-specific presentation generates important diagnostic delays. We present the case of a patient presenting digestive symptoms and flushing that subsequently adds heart failure, achieving though a typical echocardiogram and analytical markers the diagnosis of carcinoid syndrome. Later it is discovered its origin in a bronchial neuroendocrine tumor. Knowing the characteristics of this syndrome is essential to maintain a high clinical suspicion in patients with suggestive symptoms, in order to achieve an early and adequate diagnosis.

El síndrome carcinoide é um síndrome paraneoplásico que ocorre em tumores neuroendócrinos. Embora seja uma entidade rara, geralmente é a primeira manifestação da doença. A baixa incidência, juntamente com a apresentação inespecífica, resulta em atrasos importantes no diagnóstico. Apresentamos o caso de uma paciente com sintomas digestivos e ruborização cutânea, que posteriormente desenvolve insuficiência cardíaca. O diagnóstico de síndrome carcinoide foi estabelecido por meio de um ecocardiograma característico e marcadores analíticos. Posteriormente, foi evidenciada a origem em um tumor neuroendócrino brônquico. Conhecer as características deste síndrome é fundamental para manter uma alta suspeita clínica em pacientes com sintomas sugestivos, permitindo um diagnóstico precoce e adequado.

Efficacy of Racecadotril in a Patient Affected by a Therapy-Refractory VIPoma and Carcinoid Syndrome.

Neuroendocrine neoplasms (NENs) encompass a heterogeneous spectrum of tumors originating from the diffuse neuroendocrine cell system. Approximately 30% of NEN exhibit functional activity with clinical syndromes through hormone-mediated effects. Synchronous and metachronous functioning syndromes, resulting from the simultaneous release of distinct hormones, are exceptionally rare. Of note, hormonal excess syndromes can have a greater effect on patients' morbidity and mortality than the tumor mass itself. We present the case of a 49-year-old male patient affected by an oligo-metastatic ileal NEN, concurrently demonstrating vasointestinal peptide (VIP) and serotonin excretion, complicated by pulmonary tuberculosis. After the first cycle of Lutetium-177-DOTATATE peptide-radio-receptor therapy, the patient developed a severe watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome, despite receiving high-dose somatostatin analogues, everolimus, and telotristat ethyl, without any surgical options. The WDHA syndrome necessitated intensive-care-unit (ICU) admission with continual intravenous administration of electrolytes and fluids. With limited alternatives, an off-label intervention using the enkephalinase inhibitor racecadotril was initiated. After 5 days of treatment, the WDHA syndrome exhibited sufficient control, facilitating the patient's discharge from the ICU. This case report underscores racecadotril as an individualized, off-label treatment strategy for patients with severe VIPoma and serotonin-driven WDHA syndrome, where conventional therapeutic avenues have been exhausted.

Atypical morphoea, a herald of two malignancies: Lung adenocarcinoma and a neuroendocrine tumour.

Introduction: Morphoea is a disorder characterised by fibrosis and inflammation of the skin and on rare occasions can be precipitated by malignancy. Here, we describe a case of morphoea unmasking two malignancies. Case description: A 73-year-old woman presented with circumferential lower limb skin thickening, associated with violaceous, doughy oedema and significantly impaired mobility. Histology confirmed dermal sclerosis with no increased mucin and broader investigations excluded systemic sclerosis, scleromyxoedema and scleroedema. An atypical morphoea was diagnosed. In the context of atypical and subsequently treatment-resistant disease, further imaging uncovered a lung adenocarcinoma which was promptly treated. Despite this, the patient's atypical oedematous skin sclerosis continued to progress proximally, and she developed flatulence, bloating and atypical flushing. This prompted further investigation, which revealed a metastatic neuroendocrine tumour. The patient was commenced on octreotide, with rapid improvement in all her cutaneous and systemic symptoms. Conclusion: Atypical morphoea can be a herald for an underlying malignancy, representing a paraneoplastic presentation. Progressive treatment-resistant morphoea may be an indicator of metastatic disease, or in our case a second malignancy.

The challenging differential diagnosis of recurrent flushing episodes: systemic mastocytosis mimicking carcinoid syndrome.

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Management of carcinoid heart disease.

Carcinoid Heart Disease (CaHD) is defined as the constellation of all cardiac manifestations that occur in patients with carcinoid tumors. Cardiac manifestations are generally due to the paraneoplastic effects of vasoactive substances secreted by carcinoid tumors. These primarily cause cardiac valve dysfunction and resultant heart failure. Successful management of patients with CaHD requires a multidisciplinary team to address both the classical manifestations of carcinoid syndrome, as well as the additional manifestations of cardiac dysfunction. While the cornerstone of medical management for carcinoid syndrome are somatostatin analogs (SSAs), there is no evidence to suggest that the usage of SSAs influences the development or progression of CaHD. Additionally, while liver-directed therapies provide a survival benefit to symptomatic carcinoid syndrome patients with resectable disease, there are conflicting data on the survival benefit of hepatic resection among patients with CaHD. Cardiac surgery in patients with CaHD is a complex undertaking, and is the only definitive treatment for symptom management in CaHD with significant survival benefit for patients in advanced disease states. Two crucial surgical decisions to be made are determining which valve(s) should be replaced, and what prosthetic should be utilized. While challenging in this often medically frail population, cardiac surgery confers a survival benefit and should be pursued in cases of symptomatic CaHD or progressive right ventricular dysfunction.

Management of functional neuroendocrine tumors.

Functional neuroendocrine neoplasms (NENs) are those associated with specific symptoms related to the hormonal secretion of the NENs. Although less than 25 % of NENs are functional at diagnosis,1 the associated syndromes significantly increase the patient burden of disease. Management of hormonal NEN symptoms may involve tumor resection or other reduction strategies (e.g., chemotherapy, embolotherapy, etc), but also specific therapies directed at decreasing hormonal synthesis, secretion, or end-organ effects. In this review, we focus on specific symptomatic management of many of the NEN syndromes, which may be pursued in addition to management primarily directed at tumor bulk and growth. A continued focus on symptom management related to the hormonal secretions of NENs, in the context of other efforts to reduce tumor bulk and growth, could significantly improve patient wellbeing.

A case of carcinoid syndrome after CT guided lung biopsy of a neuroendocrine tumor.

Carcinoid tumors of the lung are an uncommon malignancy that can rarely lead to carcinoid syndrome. Carcinoid tumors represent less than 1% of all lung cancers. This case describes a rare presentation in which a previously asymptomatic woman began to experience tachycardia, shortness of breath, and anxiety after biopsy of a pulmonary carcinoid tumor. Chest CT, histology, and clinical course supported the diagnosis and the patient's symptoms quickly resolved with medication. Ultimately, surgical removal of the tumor led to complete resolution of symptoms.

Occult Pancreatic Neuroendocrine Tumor Presenting as Carcinoid Syndrome.

We present a case of a 50-year-old male who initially presented to the clinic with complaints of palpitations, shortness of breath, dizziness, night sweats, headaches with associated intermittent episodes of diarrhea, episodes of flushing, and rash on the upper body. Laboratory testing revealed elevated chromogranin A levels. Initial imaging with computed tomography (CT) of the abdomen and pelvis with contrast was negative for any lesions. However, due to his clinical presentation and high suspicion of a neuroendocrine tumor (NET), a positron emission tomography-CT (PET-CT) scan with Gallium 68-DOTATATE was obtained, confirming and localizing his NET in the neck of the pancreas and the liver. Following confirmation and localization of his tumor, he was referred for surgical evaluation and treatment. Pancreatic neuroendocrine tumors are rare and difficult to diagnose, highlighted by unsuccessful initial efforts to localize and confirm the tumor. This case underscores the importance of clinical suspicion and acumen in diagnosing neuroendocrine tumors. Upcoming imaging modalities of PET-CT scans provide promising avenues to uncover neuroendocrine tumors.

[Anaphylactic shock after mistletoe therapy]. / Anaphylaktischer Schock nach Misteltherapie.

Life-threatening side effects of mistletoe therapy are mostly negated by physicians working in complementary medicine. This article reports on a case of life-threatening anaphylactic shock after carrying out mistletoe therapy. In patients with a carcinoid syndrome (flushes, diarrhea, bronchoconstriction) the diagnosis of anaphylactic shock can be masked by the findings of a neuroendocrine neoplasm. Before a planned complementary medicine mistletoe therapy patients should also be well-informed on rare life-threatening side effects.

Carcinoid crisis: The challenge is still there.

Carcinoid crisis (CC) has classically been considered the extreme end of the spectrum of carcinoid syndrome (CS). However, this presumption and other aspects of CC remain poorly understood. Consequently, current clinical guidelines are based on a low quality of evidence. There is no standard definition of CC and its incidence is unknown. Patients with florid CS and elevated serotonin (or its derivatives) which develop CC have been reported during decades. Nevertheless, the hypothesis that CC is due to the sudden massive release of serotonin or other vasoactive substances is unproven. Many triggers of CC (surgery, anaesthesia, peptide receptor radionuclide therapy, tumour biopsy or liver-directed treatments) have been proposed. However, data from studies are heterogeneous and even contradictory. Finally, the role of octreotide in the prevention of CC has been questioned. Herein, we report a clinical case and perform a critical review of the evidence available today on this topic.

Anesthetic key points in a patient with a terminal ileum neuroendocrine tumor and a rare carcinoid left heart disease presented for non-cardiac surgery: case report.

BACKGROUND: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period. CASE PRESENTATION: We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc. CONCLUSION: Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients.

Primary Neuroendocrine Tumor of the Testis Associated With Cardiac Symptoms: A Case Report and Literature Review.

Well-differentiated neuroendocrine tumors of the testis are exceedingly rare. Here, we report the case of a 47-year-old male patient complaining of cardiac symptoms with a right testicular mass. A right radical orchiectomy was performed. The histopathological findings showed a well-differentiated neuroendocrine tumor with positive synaptophysin and chromogranin A immunostains.

Elevated sortilin expression discriminates functional from non-functional neuroendocrine tumors and enables therapeutic targeting.

A subset of neuroendocrine tumors (NETs) can cause an excessive secretion of hormones, neuropeptides, and biogenic amines into the bloodstream. These so-called functional NETs evoke a hormone-related disease and lead to several different syndromes, depending on the factors released. One of the most common functional syndromes, carcinoid syndrome, is characterized mainly by over-secretion of serotonin. However, what distinguishes functional from non-functional tumors on a molecular level remains unknown. Here, we demonstrate that the expression of sortilin, a widely expressed transmembrane receptor involved in intracellular protein sorting, is significantly increased in functional compared to non-functional NETs and thus can be used as a biomarker for functional NETs. Furthermore, using a cell line model of functional NETs, as well as organoids, we demonstrate that inhibition of sortilin reduces cellular serotonin concentrations and may therefore serve as a novel therapeutic target to treat patients with carcinoid syndrome.

Unique Presentation of Adult Ileocecal Intussusception Unveiling a Rare Culprit: A Carcinoid Tumor.

Intussusception is a prominent contributor to bowel obstruction, marked by the invagination of a proximal bowel section into a distal segment. Ileocecal intussusception occurs when a portion of the terminal ileum folds into the cecum. In adults, intussusception is infrequent compared to pediatric cases, and represents a minority of bowel obstructions. Structural lead points are more commonly observed in adult intussusception compared to pediatric cases where risk factors include infection, Meckel's diverticulum, and intestinal polyps. Obstructions in adults are usually a result of benign or malignant neoplasms. In this particular case, a carcinoid tumor originating in the ileum acted as the structural lead point for intussusception. The patient underwent exploratory laparotomy resulting in a right hemicolectomy. This patient did not present with the classic triad of symptoms associated with carcinoid syndrome. In response to this particular case, a laparoscopic right-sided hemicolectomy with lymph node dissection was performed.

Carcinoid syndrome with right-sided valve involvement - a case report and review of the literature.

BACKGROUND: The survival of patients with neuroendocrine tumors has substantially improved with modern treatment options. Although the associated carcinoid syndrome can be diagnosed early and controlled effectively, cardiologists still encounter patients with cardiac manifestations, particularly among individuals with persistently high levels of vasoactive mediators. Treatment options have been limited to surgical valve replacement in fully manifested disease. Since surgery is not always feasible, transcatheter valve implantation is becoming an interesting alternative. CASE: A case of a 50-year-old woman with carcinoid syndrome and right-sided valvular heart disease is presented. Moderate pulmonary valve stenosis and severe tricuspid valve regurgitation were diagnosed during the evaluation and treatment of neuroendocrine tumor. The possibility of rare valve involvement and the need for interdisciplinary cooperation in the diagnosis, monitoring and treatment of patients with neuroendocrine tumors producing vasoactive substances must be emphasized. CONCLUSION: The patient had a typically presenting carcinoid syndrome with a rare cardiac manifestation. Although monitoring and treatment were carried out in accordance with recommendations and appropriate to the clinical condition, rapid progression of the metastatic disease ultimately precluded invasive cardiac intervention.

Perioperative management of a double valve replacement and coronary artery bypass graft in a patient with carcinoid syndrome; a case report and literature review.

INTRODUCTION: Carcinoid tumors are rare neuroendocrine tumors; about 5% of patients develop the carcinoid syndrome. We present the case of a patient with carcinoid syndrome undergoing cardiac surgery. CASE REPORT: A 74-year-old patient with carcinoid heart disease and hepatic metastases underwent double valve replacement and CABG. The patient was on octreotide therapy and antihypertensive medication. An octreotide infusion was commenced perioperatively. Pharmaceutical agents that could potentially precipitate histamine release or exacerbate catecholamine secretion and carcinoid crises were avoided. Postoperatively, recovery was complicated by atrial fibrillation, chest infection, pleural effusions, acute kidney injury and delirium. DISCUSSION: Hepatic metastases cause systemic hormones' secretion, which cause a carcinoid crisis. Perioperative administration of octreotide is used, while vigilance is required to differentiate between hemodynamic effects related to the operation or disease specific factors. CONCLUSION: No carcinoid crisis was evident perioperatively. High vigilance with appropriate monitoring, aggressive management combined with meticulous choice of pharmaceutical agents led to this outcome.

A systematic review and meta-analysis of the diagnosis and surgical management of carcinoid heart disease.

Introduction: Carcinoid heart disease (CHD), a complication of carcinoid syndrome (CS), is a rare condition that can lead to right sided valvular heart disease and has been traditionally associated with a poor prognosis. We conducted a systematic review and meta-analysis to explore the accuracy of biomarkers and echocardiography in diagnosing CHD amongst patients who are already known to have neuroendocrine tumours and to assess whether surgical management of CHD leads to a reduction in mortality. Methods: A systematic literature search of MEDLINE, EMBASE, EBM Reviews, Google Scholar, ClinicalTrials.gov was conducted. All studies on patients with carcinoid heart disease (CHD) reporting on biomarkers, echocardiographic and surgical outcomes were included. The National Heart, Lung, and Blood Institute quality assessment tool was used to assess the methodological study quality. Data analysis was performed using Stata Statistical Software and R Studio, and individual meta-analyses were performed for biomarkers, echocardiographic findings, and surgical outcomes. Results: A total of 36 articles were included in the systematic review analysis. N terminal pro-brain natriuretic peptide (NTproBNP) and 5-hydroxyindole acetate (5-HIAA) levels were higher in patients with CHD compared with those without CHD. 32% of CS patients had echocardiographic evidence of cardiac involvement, of which 79% involved tricuspid valve abnormalities. Moderate-severe tricuspid regurgitation was the most common echocardiographic abnormality (70% of patients). However, these analyses had substantial heterogeneity due to the high variability of cardiac involvement across studies. Pooled surgical mortality for CHD was 11% at 1 month, 31% at 12 months and 56% at 24 months. When assessing surgical outcomes longitudinally, the one-month surgical results showed a trend towards more recent surgeries having lower mortality rates than those reported in earlier years, however this was not statistically significant. Discussion: There is not enough data in current literature to determine a clear cut-off value of NTproBNP and 5-HIAA to help diagnose or determine CHD severity. Surgical management of CHD is yet to show significant mortality benefit, and there are no consistent comparisons to medical treatment in current literature.

Managing end-stage carcinoid heart disease: A case report and literature review.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients' quality of life. Cardiovascular complications of GEP-NENs, primarily tricuspid and pulmonary valve disease, and right-sided heart failure, are the leading cause of death, even compared to metastatic disease. CASE SUMMARY: We present a case of a 35-year-old patient with progressive dyspnea, back pain, polyneuropathic leg pain, and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver metastases. During the initial presentation, serum biomarkers were not evaluated, and the patient received five cycles of doxorubicin, which he did not tolerate well, so he refused further therapy and was lost to follow-up. After 10 years, he presented to the emergency room with signs and symptoms of right-sided heart failure. Panneuroendocrine markers, serum chromogranin A, and urinary 5-hydroxyindoleacetic acid were extremely elevated (900 ng/mL and 2178 µmol/L), and transabdominal ultrasound confirmed hepatic metastases. Computed tomography (CT) showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and pelvis. Furthermore, an Octreoscan showed lesions in the heart, thoracic spine, duodenum, and ascendent colon. A standard transthoracic echocardiogram confirmed findings of carcinoid heart disease. The patient was not a candidate for valve replacement. He started octreotide acetate treatment, and the dose escalated to 80 mg IM monthly. Although biochemical response and symptomatic improvement were noted, the patient died. CONCLUSION: Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors, usually with liver metastases, which manifests as right-sided heart valve dysfunction leading to right-sided heart failure. Carcinoid heart disease and tumor burden are major prognostic factors of poor survival. Therefore, they must be actively sought by available biochemical markers and imaging techniques. Moreover, imaging techniques aiding tumor detection and staging, somatostatin receptor positron emission tomography/CT, and CT or magnetic resonance imaging, should be performed at the time of diagnosis and in 3- to 6-mo intervals to determine tumor growth rate and assess the possibility of locoregional therapy and/or palliative surgery. Valve replacement at the onset of symptoms or right ventricular dysfunction may be considered, while any delay can worsen right-sided ventricular failure.