Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking.To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population.Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of othe...

Thymic neuroendocrine tumor in a patient with multiple endocrine neoplasia type I : The limitations of surveillance

“…Overall, patients with MEN1 have a decreased life expectancy as surgical cure is unlikely given their predisposition to multiple and recurrent tumors. Historically, death occurred relatively early in life and was attributed to the complications of a gastrinoma, insulinoma, or severe hyperparathyroidism [2,3] . Advancements in medical treatment have enabled MEN1 patients to live longer with patients now rarely dying from said complications [3] .…”

“…Historically, death occurred relatively early in life and was attributed to the complications of a gastrinoma, insulinoma, or severe hyperparathyroidism [2,3] . Advancements in medical treatment have enabled MEN1 patients to live longer with patients now rarely dying from said complications [3] . Patients with MEN1, particularly those with non-functioning NETs, now require long-term monitoring for late disease manifestations.…”

“…Pancreatic NETs include functional gastrinomas, insulinomas, glucagonomas, and vasoactive intestinal polypeptidomas (VIPomas), as well as nonfunctioning tumors. In addition, patients with MEN1 are more likely to develop pituitary adenomas, benign adrenal tumors, skin tumors (angiofibromas, collangenomas and lipomas), and NETs of the thymus, stomach, and bronchus [2,3] . We present a patient whose thymic NET led to the diagnosis of MEN1.…”

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

“…The most common cause of death in MEN1 has shifted from functional pNET to nonfunctioning malignant pNET and thymic NETs [76,77]. Malignant pNET is responsible for 58-64% MEN1-related deaths in the NIH series and the pooled literature [76].…”

Radiological surveillance in multiple endocrine neoplasia type 1: A double edged sword?

“…Patients with MEN1 typically develop tumours or hyperplasia of multiple endocrine glands including the parathyroids, pancreas and pituitary (1,2,3).…”