Multiple Endocrine Neoplasia

The goal of this observational study is to create a single macro registry system with data collection on common clinical features, grouping the different rare diseases (RD). Moreover, the specific goals are to generate an alert system for possible cases of RD with data from the electronic medical record, to describe the occurrence of RD in the evaluated population, to characterize the population, to describe patterns of diagnosis and treatment of RD present at the time, and to explore patient-reported outcomes.

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access. Visit sanfordresearch.org/CoRDS to enroll.

Objectives: The aim of the present study is to assess the significance of metabolomics and genetics in diagnosing and survival evaluation for pNET in the periodic follow-up of MEN1 patients. Aim 1: To evaluate the relationship of serum global metabolic profiles with subsequent development of aggressive PNET and evaluate patients survival in a nested case-control study of MEN1 patients who have developed aggressive PNETs (cases) and MEN1 patients who have developed non-aggressive PNETs (controls). Aim 2: Validate the top serum metabolites identified from Aim 1 in MEN1 patients who have developed aggressive PNETs and MEN1 patients who have developed non-aggressive PNETs, using a targeted metabolomics approach. Aim 3: Prospectively identify the potential miRNA biomarkers of serum with miRNA sequencing in MEN1 patients who have developed aggressive PNETs (cases) and MEN1 patients who have developed non-aggressive PNETs (controls). Aim 4: Validate the potential miRNA biomarkers identified from Aim 1 in MEN1 patients who have developed aggressive PNETs and in MEN1 patients who have developed non-aggressive PNETs, using a targeted qRT-PCR approach (in serums), as well as to see the relationship of potential miRNA biomarkers with patients survival.

Multiple Endocrine Neoplasia type I (MEN1) or Wermer syndrome is an autosomal dominant disease that predisposes patients to the development of endocrine tumours, principally parathyroid, pituitary or duodenal-pancreatic tumours. It is due to mutations that abolish the function of the MEN1 gene, which contributes to tumour regulation. It is a rare disease, with an estimated prevalence in the general population of 1/30,000. Penetrance of the disease is late but very high (almost 100% at 50 years of age). The first clinical manifestations usually appear after the age of 30 or 40 years. The three cardinal endocrine characteristics of MEN1 are secreting tumours of the parathyroid, the pituitary gland and the pancreas. Tumours of the adrenal glands, bronchial or thymic endocrine tumours, ependymoma and meningioma of the central nervous system, visceral leiomyomas, and certain cutaneous tumours can also be found as well as these cardinal tumours. The diagnosis of MEN1 is essential to ensure 1) appropriate therapeutic management of the proven endocrine manifestations 2) screening for other endocrine and non-endocrine tumours (lesions), 3) family screening of affected relatives whether they are symptomatic or not 4) the surveillance of thus diagnosed patients. Studies on mortality in MEN1 have shown that the causes of death are mainly due to the disease. The non-diagnosis of MEN1 is a cause of therapeutic failure in the management of the endocrine lesions. For the success of the surgical treatment of an isolated endocrine lesion it is important for patients to be oriented towards a diagnosis of MEN1 as the management is different from that in usual situations. Detection is thus of major importance, as early diagnosis can improve the management. Even though the syndrome was discovered in 1903 by Erdheim and correctly documented in 1954 by Wermer, it was only in the 1970s that we became aware of the variety of clinical forms and attempted to codify its treatment. Nonetheless, published studies are fragmented and concern selected populations of few patients. They only partially answer questions arising in clinical practice concerning the prognosis and optimal management of patients. The natural history of the disease in all of its clinical forms is still poorly understood. Although advances in genetics have helped in the diagnosis of MEN1, some clinical forms are still difficult to associate with the syndrome: atypical forms, forms with hardly any symptoms and no genetic diagnosis (10%). These clinical forms need to be clarified to ensure optimal care. Only a large cohort will make it possible to describe the different forms of this disease and to clarify its prognosis