MEN1 Surveillance Guidelines: Time to (Re)Think?

Abstract

Clinical Practice Guidelines for patients with Multiple Endocrine Neoplasia type 1 (MEN1) recommend a variety of surveillance options. Given progress over the past decade in this area, it is timely to evaluate their ongoing utility. MEN1 is characterized by the development of synchronous or asynchronous tumors affecting a multitude of endocrine and non-endocrine tissues, resulting in premature morbidity and mortality, such that the rationale for undertaking surveillance screening in at-risk individuals appears robust. Current guidelines recommend an intensive regimen of clinical, biochemical and radiological surveillance commencing in early childhood for those with a clinical or genetic diagnosis of MEN1, with the aim of early tumor detection and treatment. Although it is tempting to assume that such screening results in patient benefits and improved outcomes, the lack of a strong evidence base for several aspects of MEN1 care, and the potential for iatrogenic harms related to screening tests or interventions of unproven benefit, make such assumptions potentially unsound. Furthermore, the psychological, as well as economic burdens of intensive screening remain largely unstudied. Although screening undoubtedly constitutes an important component of MEN1 patient care, this perspective aims to highlight some of the current uncertainties and challenges related to existing MEN1 guidelines with a particular focus on the role of screening for pre-symptomatic tumors. Looking forward, a screening approach that acknowledges these limitations and uncertainties and places the patient at the heart of the decision-making process, is advocated.

Genetic Basis of ACTH-Secreting Adenomas

“…MEN1 syndrome is characterized by the variable association of parathyroid hyperplasia, gastroenteropancreatic NETs, and pituitary adenomas, and less frequently by tumors of other tissues, without a clear genotype–phenotype correlation [ 77 ]. MEN1 syndrome is caused by germline mutations of MEN1 , encoding menin, which is a tumor suppressor gene involved in genome stability and cell cycle regulation.…”

Approach of Multiple Endocrine Neoplasia Type 1 (MEN1) Syndrome–Related Skin Tumors

“…A patient with MEN1 syndrome may associate malignant cutaneous tumors, with or without a clear genetic connection, and this scenario should not be overlooked, but we cannot routinely recommend a certain protocol of dermatologic assessment and re-assessment depending on what we know so far. Moreover, integrating the dermatological issues to a general panel of a MEN1 patient evaluation should take into consideration an already complicated panel of surveillance due to traditional endocrine and neuroendocrine components and it should not supplementarily impact the overall quality of life in such individuals [ 25 , 38 , 113 , 114 ].…”

“…The estimated penetrance by the age of 40 years reaches 90% for parathyroid tumors, 40% for gastrinoma, and 30–40% for pituitary NETs [ 3 , 23 ]. Although it is a highly penetrant syndrome, the types of tumors an affected individual might develop cannot be predicted due to a lack of genotype–phenotype correlation [ 24 , 25 , 26 , 27 ]. Based on guideline level, individuals can be diagnosed with MEN1 if they develop two of the three main MEN1-related tumors (pituitary, parathyroid, and pancreatic neuroendocrine tumors); if they present with one MEN1-associated tumor and are a first-degree relative of a patient diagnosed with MEN1; or if, despite being asymptomatic, a mutation of the MEN1 gene is confirmed [ 1 ].…”

“…Based on guideline level, individuals can be diagnosed with MEN1 if they develop two of the three main MEN1-related tumors (pituitary, parathyroid, and pancreatic neuroendocrine tumors); if they present with one MEN1-associated tumor and are a first-degree relative of a patient diagnosed with MEN1; or if, despite being asymptomatic, a mutation of the MEN1 gene is confirmed [ 1 ]. MEN1 patients present lactotroph tumors (the most frequent pituitary NETs associated with MEN1, followed by somatotroph tumors) in addition to primary hyperparathyroidism (which typically appears around the age of 20–25 years and is more frequently accompanied by nephrolithiasis than non-MEN hyperparathyroidism) [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Between 30 and 80% of patients develop pancreatic NETs.…”

Imaging surveillance in multiple endocrine neoplasia type 1: Ten years of experience with somatostatin receptor positron emission tomography

“…4 However, the optimal imaging surveillance program in MEN1 is debated. 11,12 The most recent clinical practice guidelines, published in 2012, recommend annual imaging of the pancreas with computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasound (EUS), thoracic imaging with CT or MRI every 1-2 years and imaging of adrenals with CT or MRI every 3 years. 1 On the one hand, metastatic disease or rapid growth tumors should not be missed.…”