Pituitary tumours in MEN1 syndrome : the new insight into the diagnosis and treatment

Pituitary tumours are a common pathology affecting 15-20% of the population. Only about 1‰ of adenomas are clinically manifested; among them, about two/thirds are hormonally active, most often secreting prolactin or growth hormone. Pituitary tumours are mainly an isolated pathology, without any genetic background. However, the latest studies pay special attention to the possibility of developing an adenoma as a result of genetic mutation. Among pituitary adenomas, the leading group of genetically determined lesions is related to a mutation in AIP or MEN1, followed by PRKAR1A, GRP101, DICER, and SDHx. The genetic basis of these pituitary tumours is related to positive family history, young age of the patient, aggressive clinical process, and resistance to treatment. Pituitary tumours occur in over 40% of patients with MEN1 syndrome - often in women, they are more than 1 cm in diameter, and secrete prolactin. They are usually diagnosed in the fourth decade of life and show a worse response to pharmacotherapy than sporadic ones. Confirmation of the genetic background of the pituitary tumour implies measurable implications; it might help to direct the diagnosis in patients’ family members, partially predict the development of the disease, and, above all, extend patients’ life expectancy

Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms

Neuroendocrine neoplasms constitute a diverse group of tumors that derive from the sensory and secretory neuroendocrine cells and predominantly arise within the pulmonary and gastrointestinal tracts. The majority of these neoplasms have a well-differentiated grade and are termed neuroendocrine tumors (NETs). This subgroup is characterized by limited proliferation and patients affected by these tumors carry a good to moderate prognosis. A substantial subset of patients presenting with a NET suffer from the consequences of endocrine syndromes as a result of the excessive secretion of amines or peptide hormones, which can impair their quality of life and prognosis. Over the past 15 years, critical developments in tumor grading, diagnostic biomarkers, radionuclide imaging, randomized controlled drug trials, evidence-based guidelines, and superior prognostic outcomes have substantially altered the field of NET care. Here, we review the relevant advances to clinical practice that have significantly upgraded our approach to NET patients, both in diagnostic and in therapeutic options

Nowotwory neuroendokrynne żołądka i dwunastnicy z uwzględnieniem gastrinoma — zasady postępowania (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

This paper presents the updated Polish Neuroendocrine Tumour Network expert panel recommendations on the management of neuroendocrine neoplasms (NENs) of the stomach and duodenum, including gastrinoma. The recommendations discuss the epidemiology, pathogenesis and clinical presentation of these tumours as well as their diagnosis, including biochemical, histopathological and localisation diagnosis. The principles of treatment are discussed, including endoscopic, surgical, pharmacological and radionuclide treatment. Finally, recommendations on patient monitoring are given. (Endokrynol Pol 2013; 64 (6): 444–458)W niniejszej pracy przedstawiono uaktualnione zalecenia grupy ekspertów Polskiej Sieci Guzów Neuroendokrynnych dotyczące zasad postępowania w nowotworach neuroendokrynnych żołądka i dwunastnicy z uwzględnieniem gastrinoma. Omówiono epidemiologię, patogenezę i obraz kliniczny tych nowotworów. Przedstawiono zalecenia dotyczące zasad postępowania diagnostycznego, z uwzględnieniem diagnostyki biochemicznej, histopatologicznej oraz lokalizacyjnej. Uwzględniono także zasady postępowania terapeutycznego, w tym leczenie endoskopowe i chirurgiczne, oraz omówiono możliwości leczenia farmakologicznego i radioizotopowego. Przedstawiono także zalecenia odnośnie monitorowania chorych z NEN żołądka, dwunastnicy z uwzględnieniem gastrinoma. (Endokrynol Pol 2013; 64 (6): 444–458

Current and emerging therapies for PNETs in patients with or without MEN1

Pancreatic neuroendocrine tumours (PNETs) might occur as a non-familial isolated endocrinopathy or as part of a complex hereditary syndrome, such as multiple endocrine neoplasia type 1 (MEN1). MEN1 is an autosomal dominant disorder characterized by the combined occurrence of PNETs with tumours of the parathyroids and anterior pituitary. Treatments for primary PNETs include surgery. Treatments for non-resectable PNETs and metastases include biotherapy (for example, somatostatin analogues, inhibitors of receptors and monoclonal antibodies), chemotherapy and radiological therapy. All these treatments are effective for PNETs in patients without MEN1; however, there is a scarcity of clinical trials reporting the efficacy of the same treatments of PNETs in patients with MEN1. Treatment of PNETs in patients with MEN1 is challenging owing to the concomitant development of other tumours, which might have metastasized. In recent years, preclinical studies have identified potential new therapeutic targets for treating MEN1-associated neuroendocrine tumours (including PNETs), and these include epigenetic modification, the β-catenin–wingless (WNT) pathway, Hedgehog signalling, somatostatin receptors and MEN1 gene replacement therapy. This Review discusses these advances

Aplicación de distintos sistemas de codificación en la búsqueda bibliográfica de enfermedades raras

A continuación, se analizan los resultados, obteniendo que se ofrecen prácticamente las mismas respuestas en las búsquedas por literal que en las búsquedas por MeSH. En 7 de las 21 enfermedades estudiadas, en las búsquedas por literal es mayor el número de artículos válidos que en las búsquedas por MeSH. En 8 de las 21 enfermedades estudiadas, el número de artículoses igual en las búsquedas por MeSH que en las búsquedas por literal. Por último, en el resto delos casos, el número de artículos es mayor en las búsquedas por MeSH que en las búsquedas por literal. En cuanto al tema de los documentos de la respuesta, en su mayor parte los artículos emanados de las búsquedas sí presentan la enfermedad. Son minoritarios los casos en los que solo se menciona la enfermedad, pero no tratan en realidad de la misma. Por último, en un caso de búsquedas por literal y otro por MeSH no se obtiene ningún resultado. Estos resultados nos hacen pensar que, al ser una diferencia tan mínima entre una y otra búsqueda, no importa qué método se utilice para la búsqueda.,

Sporadic multiple parathyroid gland disease-a consensus report of the European Society of Endocrine Surgeons (ESES)

BACKGROUND: Sporadic multiglandular disease (MGD) has been reported in literature in 8–33 % of patients with primary hyperparathyroidism (pHPT). This paper aimed to review controversies in the pathogenesis and management of sporadic MGD. METHODS: A literature search and review was made to evaluate the level of evidence concerning diagnosis and management of sporadic MGD according to criteria proposed by Sackett, with recommendation grading by Heinrich et al. and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results were discussed at the 6th Workshop of the European Society of Endocrine Surgeons entitled ‘Hyperparathyroidism due to multiple gland disease: An evidence-based perspective’. RESULTS: Literature reports no prospective randomised studies; thus, a relatively low level of evidence was achieved. Appropriate surgical therapy of sporadic MGD should consist of a bilateral approach in most patients. Unilateral neck exploration guided by preoperative imaging should be reserved for selected patients, performed by an experienced endocrine surgeon and monitored by intraoperative parathormone assay (levels of evidence III–V, grade C recommendation). There is conflicting or equally weighted levels IV–V evidence supporting that cure rates can be similar or worse for sporadic MGD than for single adenomas (no recommendation). Best outcomes can be expected if surgery is performed by an experienced parathyroid surgeon working in a high-volume centre (grade C recommendation). Levels IV–V evidence supports that recurrent/persistence pHPT occurs more frequently in patients with double adenomas hence in situations where a double adenoma has been identified, the surgeon should have a high index of suspicion during surgery and postoperatively for the possibility of a four-gland disease (grade C recommendation). CONCLUSIONS: Identifying preoperatively patients at risk for MGD remains challenging, intraoperative decisions are important for achieving acceptable cure rates and long-term follow-up is mandatory in such patients

The role of gastrin in the development of gastric preneoplastic and neoplastic changes

The hormone gastrin regulates gastric acid secretion and through its effects on cell proliferation, apoptosis and angiogenesis also regulates gastric epithelial and enterochromaffin-like (ECL) cell growth. The influence of various factors (host, bacterial and environmental) upon fasting serum gastrin concentrations and to what extent these factors interact to influence the progression of gastric preneoplastic pathology is not fully understood. Long standing hypergastrinaemia secondary to hypochlorhydria resulting from autoimmune gastritis can result in the development of ECL-cell hyperplasia. In some patients this progresses to type-1 gastric neuroendocrine tumour formation. The factors that influence this progression have not been fully characterised. The management of type-1 gastric neuroendocrine tumours is dependent on their size. However, there is still controversy regarding the optimal management of larger (> 1cm) tumours. Antrectomy is one option and the results of an octreotide suppression test (to determine gastrin dependency of type-1 gastric neuroendocrine tumours in order to predict response to antrectomy) have been reported in a single patient. This aims of this thesis were to assess: 1. The interaction between various factors (host, bacterial and environmental) that may influence fasting serum gastrin concentrations and the development of gastric preneoplastic pathology. 2. The roles of certain factors in the progression of ECL-cell hyperplasia to type-1 gastric neuroendocrine tumours. 3. The role of an octreotide suppression test in identifying patients with type-1 gastric neuroendocrine tumours who may benefit from antrectomy. In a large cohort of >1000 prospectively recruited patients, we demonstrated that in addition to H. pylori infection, the presence of a host factor (advancing age), a bacterial virulence factor (cagA) and elevated fasting serum gastrin concentrations (>100pM) were significantly associated with the presence of gastric preneoplastic pathology. Concurrent proton pump inhibitor therapy was however not associated with the presence of gastric preneoplastic pathology. The interactions between H. pylori infection, proton pump inhibitor use and the presence of gastric preneoplastic pathology in determining fasting serum gastrin concentrations were found to be complex. In addition, other host and environmental factors also influenced fasting serum gastrin concentrations. Although results from our study did not demonstrate any statistically significant associations, there did appear to be correlations between the presence of factors such as hypothyroidism, positive anti-gastric parietal and intrinsic factor antibodies and extent of gastric atrophy with the presence of more advanced degrees of gastric ECL-cell hyperplasia. Although a positive octreotide suppression test was associated with tumour regression following antrectomy in four patients with type-1 gastric neuroendocrine tumours, a fifth patient who had a positive test did not show tumour regression and needed additional surgery. In conclusion, gastrin appears to act as an important co-factor in the pathogenesis of epithelial and neuroendocrine neoplasia in the stomach, but interactions with other factors are complex