Update on the clinical management of multiple endocrine neoplasia type 1

Abstract

This review provides an overview of novel insights in the clinical management of patients with Multiple Endocrine Neoplasia Type 1, focusing on the last decade since the last update of the MEN1 guidelines. With regard to Diagnosis: Mutation-negative patients with 2/3 main manifestations have a different clinical course compared to mutation-positive patients. As for primary hyperparathyroidism: subtotal parathyroidectomy is the initial procedure of choice. Current debate centres around the timing of initial parathyroidectomy as well as the controversial topic of unilateral clearance in young patients. For duodenopancreatic neuroendocrine tumours (NETs), the main challenge is accurate and individualized risk stratification to enable personalized surveillance and treatment. Thymus NETs remain one of the most aggressive MEN1-related tumours. Lung NETs are more frequent than previously thought, generally indolent, but rare aggressive cases do occur. Pituitary adenomas are most often prolactinomas and nonfunctioning microadenomas with an excellent prognosis and good response to therapy. Breast cancer is recognized as part of the MEN1 syndrome in women and periodical screening is advised. Clinically relevant manifestations are already seen at the paediatric age and initiating screening in the second decade is advisable. MEN1 has a significant impact on quality of life and US data show a significant financial burden. In conclusion, patient outcomes have improved, but much is still to be achieved. For care tailored to the needs of the individual patient and improving outcomes on an individual basis, studies are now needed to define predictors of tumour behaviour and effects of more individualized interventions.

Keywords: disease management; genetic testing; multiple endocrine neoplasia type 1; neuroendocrine tumours; pituitary neoplasms; primary hyperparathyroidism; review.

Figure 1

Manifestations of the MEN1 syndrome. Figure created by JM de Laat. MEN1, multiple endocrine neoplasia type 1; NET, neuroendocrine tumour [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Previously published by Bioscientifica in ‘De Laat et al. Predicting the risk of multiple endocrine neoplasia type 1 for patients with commonly occurring endocrine tumours. Eur J Endocrinol. 2012; 167: 181‐7’. Nomogram. Example: a 54‐year‐old patient (score = 30 points) with the combination of a negative family history (score = 0 points), a nonrecurrent and nonmultiglandular pHPT (score = 63 points), and a pNET (n = 57 points) has a sum score of 150 points, corresponding with a linear predictor of −0.50 and a risk of 38% of having a MEN1 mutation. Example: a 41‐year‐old patient (score = 42 points) with a positive family history (score = 29 points) and recurrent pHPT (score = 100 points) has a sum score of 171 points, corresponding with a linear predictor of 0.50 and a risk of 63% of having a MEN1 mutation. Example: a 51‐year‐old patient (score = 33 points) with a negative family history (score = 0 points) of pituitary tumour (score = 31 points) and a pNET (score = 57 points) has a sum score of 121 points, corresponding with a linear predictor of −2.0 and a risk of 11% of having a MEN1 mutation. MEN1, multiple endocrine neoplasia type 1; NET, neuroendocrine tumour; pHPT, primary hyperparathyroidism