Multiple Endocrine Neoplasia Type 1 and Zollinger-Ellison Syndrome

Abstract

In patients with multiple endocrine neoplasia type 1 (MEN1), the most common functional pancreatic endocrine tumor (PET) syndrome is Zollinger-Ellison syndrome (ZES). ZES has been well studied in its sporadic form (that is, without MEN1); however, there are limited data on patients with MEN1 and ZES (MEN1/ZES), and the long-term natural history is largely unknown. To address this issue we report the results of a prospective long-term National Institutes of Health (NIH) study of 107 MEN1/ZES patients and compare our results with those of 1009 MEN1/ZES patients in 278 case reports and small series in the literature. Patients were clinically, radiologically, and biochemically evaluated yearly for all MEN1 manifestations (mean follow-up, 10 yr; range, 0.1-31 yr). Compared with patients from the literature, the NIH MEN1/ZES patients more frequently had pituitary (60%) and adrenal (45%) disease and carcinoid tumors (30%), but had equal frequency of hyperparathyroidism (94%), thyroid disease (6%), or lipomas (5%). Twenty-five percent of both the NIH and the literature patients lacked a family history of MEN1; ZES was the initial clinical manifestation of MEN1 in 40%. ZES onset preceded the diagnosis of hyperparathyroidism in 45%. However, ZES was rarely (8%) the only initial manifestation of MEN1 if careful testing was done. ZES occurred before age 40 years in 50%-60% of the current patients, in contrast to older studies. The diagnosis of ZES is delayed 3-5 years from its onset and is delayed as long as in sporadic ZES cases. Pituitary disease and carcinoid tumors (gastric > bronchial, thymic) are more frequent than generally reported, whereas a second functional PET is uncommon. In patients with MEN1/ZES without a family history of MEN1, the MEN1 manifestations are not as severe. This study shows that MEN1/ZES patients differ in many aspects from those commonly reported in older studies involving few MEN1/ZES patients. In this study we have identified a number of important clinical and laboratory features of MEN1/ZES that were not previously appreciated, which should contribute to earlier diagnosis and improve both short- and long-term management.

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'étude des Tumeurs Endocrines

“…However, pHPT is not the explanation for this gender difference because pHPT was found as frequently in males as in females. A previous pooled analysis of 16 worldwide studies, including 1009 MEN1 patients with ZES, also found that the proportion of males was 53.8%, thus very close to our value of 52% (16). This male predominance should be compared with the high percentages of men (ranging from 59.5 to 70.1%) reported in studies totally or mostly composed of patients with sporadic ZES, i.e.…”

“…Several cohort studies that did not focus on specific lesions suggested an overall female predominance of about 52-56% of MEN1 patients (11,12). In contrast, studies that focus on specific lesions provided discordant sex ratios with a proportion of females ranging, for example, from 36 to 58% in MEN1 patients with Zollinger-Ellison syndrome (ZES) (13)(14)(15)(16). Several years ago, the Groupe d'étude des Tumeurs Endocrines (GTE) already pointed out the higher prevalence of pituitary lesions in women than in men (17).…”

Nowotwory neuroendokrynne trzustki — zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynych)

“…Some studies confirm that in patients with MEN-1, insulin-secreting tumours are found more frequently than gastrin-secreting tumours and in 25% of patients insulinoma occurs before the age of 20 years [12,49,50]. Therefore, if an insulin-secreting tumour is found in a patient under 20 years old, or if multiple insulinsecreting tumours are found regardless of age, MEN-1 should be suspected, and suitable genetic tests performed [26,52,53].…”

The future: diagnostic and imaging advances in MEN1 therapeutic approaches and management strategies

“…The prevalence of adrenal lesions in MEN1 patients is up to 45% in cohorts that were investigated with new crosssectional imaging and EUS (Skogseid et al 1992, 1995, Langer et al 2002, Gibril et al 2004, Waldmann et al 2007. In most cases, the tumors are small and non-functioning lesions of the adrenal cortex.…”

“…Primary hyperaldosteronism and ACTH-independent Cushing's disease are the most common functioning lesions and occur in less than 10% of MEN1 patients (Gatta-Cherifi et al 2012). Only about 2% of MEN1 patients develop an adrenocortical carcinoma (ACC), but this is a life-threatening malignant tumor (Skogseid et al 1995, Gibril et al 2004, Waldmann et al 2007. Biochemical investigation, including plasma renin, aldosterone and cortisol concentrations and lowdose dexamethasone suppression test, is recommended in MEN1 patients with adrenal lesions with a size > 1 cm.…”