TP53 mutations in functional corticotroph tumors are linked to invasion and worse clinical outcome.

Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing's disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors.

Health-Related Quality of Life in Patients with Multiple Endocrine Neoplasia Type 1.

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine tumor syndrome characterized by the triad of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumors (pNETs), and pituitary tumors. Patients are confronted with substantial morbidity and are consequently at risk for an impaired quality of life (QOL). Meticulous assessment of QOL and associated factors in a representative population is needed to understand the full spectrum of the burden of the disease.

Driver mutations in USP8 wild-type Cushing's disease.

Background: Medical treatment in Cushing's disease (CD) is limited due to poor understanding of its pathogenesis. Pathogenic variants of ubiquitin specific peptidase 8 (USP8) have been confirmed as causative in around half of corticotroph tumors. We aimed to further characterize the molecular landscape of those CD tumors lacking USP8 mutations in a large cohort of patients.

High Fear of Disease Occurrence Is Associated With Low Quality of Life in Patients With Multiple Endocrine Neoplasia Type 1: Results From the Dutch MEN1 Study Group.

Objective: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary disease characterized by a high risk of developing primary hyperparathyroidism, duodenopancreatic neuroendocrine tumors, and pituitary tumors (PITs). It is unclear if having MEN1 leads to psychological distress because of fear of disease occurrence (FDO), thereby potentially affecting quality of life.

Design: A cross-sectional study was performed using the Dutch MEN1 cohort.

Somatic mutations are frequent events in corticotroph tumor progression causing Nelson's tumor.

Objective: Somatic mutations in the ubiquitin-specific protease 8 () gene are frequent in corticotroph tumors causing Cushing's disease (CD). Corticotroph tumor progression, the so-called Nelson's syndrome (NS), is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory CD that is caused by the development of an ACTH-secreting tumor of the pituitary gland. Whether alterations are also present in progressive Nelson's tumors has not been studied in detail so far.

Enhanced self-efficacy after a self-management programme in pituitary disease: a randomized controlled trial.

Context: Patients with pituitary disease report impairments in Quality of Life (QoL) despite optimal biomedical care. Until now, the effects of a self-management intervention (SMI) addressing psychological and social issues for these patients and their partners have not been studied.

Objective: To examine the effects of a SMI i.

Management of MEN1 Related Nonfunctioning Pancreatic NETs: A Shifting Paradigm: Results From the DutchMEN1 Study Group.

Objective: To assess if surgery for Multiple Endocrine Neoplasia type 1 (MEN1) related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) is effective for improving overall survival and preventing liver metastasis.

Background: MEN1 leads to multiple early-onset NF-pNETs. The evidence base for guiding the difficult decision who and when to operate is meager.

PROGNOSTIC FACTORS FOR SURVIVAL OF MEN1 PATIENTS WITH DUODENOPANCREATIC TUMORS METASTATIC TO THE LIVER: RESULTS FROM THE DMSG.

Objective: Duodenopancreatic neuroendocrine tumors (DP-NETs) develop in a majority of patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Overall survival (OS) and prognostic factors for patients with liver metastases from DP-NETs are not known.

Methods: This was a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population treated between 1990 and 2014.

Conditioning Immune and Endocrine Parameters in Humans: A Systematic Review.

Background: Conditioned pharmacological effects may provide relevant clinical opportunities to improve treatment for patients with a variety of conditions. The aim of this systematic review was to create an overview of studies in this field of research and to investigate whether specific characteristics of the study design make for successful conditioning.

Methods: The protocol of this review was registered in Prospero (PROSPERO 2015: CRD42015024148).

Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

Context: Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare.

Patient: We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement.

MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is diagnosed when two out of the three primary MEN1-associated endocrine tumors occur in a patient. Up to 10-30 % of those patients have no mutation in the MEN1 gene. It is unclear if the phenotype and course of the disease of mutation-negative patients is comparable with mutation-positive patients and if these patients have true MEN1.

Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines.

Purpose: The benefits of aerobic exercise training on insulin sensitivity in subjects with metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g.

Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

Background: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity.

Objective: The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active.

Impact of Delay in Diagnosis in Outcomes in MEN1: Results From the Dutch MEN1 Study Group.

Objective: Identifying a germline mutation in the multiple endocrine neoplasia type 1 (MEN1) gene in an index case has consequences for a whole family. Eligible family members should be offered genetic counseling and MEN1 mutation testing. Subsequently, clinical screening of mutation carriers according to the guidelines should be initiated.

Genotype-Dependent Brown Adipose Tissue Activation in Patients With Pheochromocytoma and Paraganglioma.

Context: Patients with pheochromocytomas and paragangliomas (PGLs) may have brown adipose tissue (BAT) activation induced by catecholamine excess. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) can be used for the localization of both PGLs and BAT. It is unknown whether BAT is specifically affected by altered cellular energy metabolism in patients with SDHx- and VHL-related PGLs.

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1.

Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood type O was proposed as an additional factor to personalize screening criteria for neuroendocrine tumors in MEN1 patients.

Incidence of adrenal crisis in patients with adrenal insufficiency.

Background: An adrenal crisis (AC) is a potential life-threatening event in patients with adrenal insufficiency (AI). This study aims to determine the incidence, causes, and risk factors of AC in AI.

Methods: Patients with AI diagnosed and treated at the University Medical Center Utrecht for the past 30 years were identified, and all medical records were assessed by two independent investigators.

Long-Term Natural Course of Pituitary Tumors in Patients With MEN1: Results From the DutchMEN1 Study Group (DMSG).

Context: Guidelines advise lifelong radiological followup for asymptomatic pituitary adenomas (PITs) because of the risk for growth and subsequent visual field defects. In the context of multiple endocrine neoplasia type 1 (MEN1) an even more comprehensive screening is advised because PITs are presumed to manifest more aggressive behavior. We studied the long-term course of MEN1-related PITs, which may be used as a model for sporadically occurring PITs.

Semiquantitative 123I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters.

Unlabelled: (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). (123)I-MIBG targets cell membrane and vesicular catecholamine transporters of chromaffin cells and facilitates localization of the primary tumor and metastatic lesions. Its specificity for the diagnosis of adrenomedullary chromaffin cell tumors can be jeopardized by physiologic uptake by the normal adrenal medulla.

Thyrotropin versus age relation as an indicator of historical iodine intake.

Background: In populations with mild iodine deficiency, the serum level of thyrotropin (TSH) is negatively and the serum free thyroxine (FT4) is positively associated with age. An ongoing decrease of TSH and increase of FT4 can be found after iodine supplementation. The aim of this study was to investigate whether there are current differences in the relation between thyroid function and age in relation to differences in iodine intake in the past.

Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1.

Objective: Currently, little is known about the prevalence of thyroid tumors in multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was to assess the prevalence of thyroid incidentalomas in MEN1 patients compared with nonMEN1 patients and to verify whether thyroid tumorigenesis is MEN1-related.

Design: A cross-sectional study.

Molecular characterization of testicular adrenal rest tumors in congenital adrenal hyperplasia: lesions with both adrenocortical and Leydig cell features.

Context: Testicular adrenal rest tumors (TART) are one of the major long term complications in patients with congenital adrenal hyperplasia. Although several adrenal-like properties have been assigned to these benign lesions, the etiology has not been confirmed yet.

Objective: The aim of this study was to describe TART in more detail by analyzing several (steroidogenic) characteristics that may be classified as adrenal cortex or Leydig cell specific.