Is Routine Screening of Young Asymptomatic MEN1 Patients Necessary?

Manoharan, Jerena; Raue, Friedhelm; Lopez, Caroline; Albers, Max B.; Bollmann, Carmen; Fendrich, Volker; Slater, Emily P.; Bartsch, Detlef K.

doi:10.1007/s00268-017-3992-9

Cited by 38 publications

(54 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Clinically evident disease appears uncommon prior to adolescence, with consensus guidelines currently recommending genetic testing and phenotype screening of confirmed MEN1 mutation carriers commencing by 10 years of age . Recommendations have suggested testing of children as young as age 5; however, the evidence supporting surveillance screening in early childhood is limited . Paediatric and adolescent case series for patients carrying an MEN1 mutation suggest the likelihood of developing phenotypic disease before 10 years of age is <15%, with asymptomatic primary hyperparathyroidism accounting for the majority of events and pituitary and enteropancreatic tumours occurring infrequently .…”

Section: Introductionmentioning

confidence: 99%

“…The guidance for therapeutic intervention in paediatric patients with mild and asymptomatic primary hyperparathyroidism (PHPT) and nonfunctioning pancreatic neuroendocrine tumours is also based on a limited number of case series and case reports . Consequently, there is uncertainty over the merits of early parathyroidectomy versus deferral of surgical intervention until completion of skeletal maturation .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1

Herath

Parameswaran

Thompson

et al. 2019

Clinical Endocrinology

View full text Add to dashboard Cite

Context Multiple endocrine neoplasia 1 (MEN 1) is an autosomal dominant disease presenting as hyperplasia and neoplasia of parathyroid, pituitary and enteropancreatic tissues. Over 90% of gene carriers develop phenotypic disease by age 30 years, potentially with onset of asymptomatic disease during childhood and adolescence. Objective To describe the paediatric and young adult manifestations of MEN 1. Design Descriptive retrospective study of 180 patients with a common MEN1 genotype. The paediatric and young adult (age <22 years) manifestations were determined using hospital records and disease surveillance data. Results Primary hyperparathyroidism (PHPT) was identified in 42 patients (mean age 17.2 ± 3.3 years). Parathyroidectomy was performed in 16 (38.1%; mean age 17.8 ± 3.2). Four patients experienced recurrent PHPT (25%), and six (37.5%) developed permanent hypoparathyroidism. Pituitary disease was identified in 13 patients. Prolactinoma was found in nine patients (mean age 16.6 ± 2.6 years) of whom four (44.4%) had macroprolactinoma. Two patients required surgical intervention; dopamine agonists showed efficacy in six patients. Two patients with Cushing's disease were successfully treated surgically. Three patients with nonfunctioning pituitary microadenoma managed conservatively. Pancreatic neuroendocrine neoplasms (pNENs) were diagnosed in 12 patients (mean age 17.0 ± 2.6 years): three patients with insulinoma successfully resected (two resected and one exhibiting perineural invasion) and nine patients with nonfunctioning adenomas (NFAs). Conclusion Pituitary adenomas, PHPT and pNENs are encountered in the paediatric and young adult MEN 1 population. Successful outcomes are typically achieved using standard medical and surgical paradigms; however, parathyroidectomy was associated with a substantial complication rate.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1

Herath

Parameswaran

Thompson

et al. 2019

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

“…, somatostatin analogs), possibly influencing growth rates. Two studies on age-related penetrance were derived from a population-based cohort [7, 54], whereas three other studies were multicenter studies [51, 55, 56]. …”

Section: Resultsmentioning

confidence: 99%

“…Another German study investigated the age-related penetrance in 166 MEN1 patients <19 years derived from two centers. Twenty patients had MEN1 manifestations, of whom three had NF-pNETs at the ages of 15, 17, and 18, respectively (penetrance 1.8%) [56]. Two patients underwent pancreatic surgery for NF-pNETs <15 mm.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Diagnosing Nonfunctional Pancreatic NETs in MEN1: The Evidence Base

Treijen

Beek

Leeuwaarde

et al. 2018

Journal of the Endocrine Society

View full text Add to dashboard Cite

In multiple endocrine neoplasia type 1 (MEN1), nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) are the most frequently diagnosed NETs and a leading cause of MEN1-related death. The high prevalence and malignant potential of NF-pNETs outline the need for an evidence-based screening program, as early diagnosis and timely intervention could reduce morbidity and mortality. Controversies exist regarding the value of several diagnostic tests. This systematic review aims to evaluate current literature and amplify an up-to-date evidence-based approach to NF-pNET diagnosis in MEN1. Three databases were systematically searched on the diagnostic value of biomarkers and imaging modalities. Twenty-seven studies were included and critically appraised (modified Quality Assessment of Diagnostic Accuracy Studies). Another 12 studies, providing data on age-related penetrance and tumor growth, were included to assess the optimal frequency and timing of screening. Based on current literature, biomarkers should no longer play a role in the diagnostic process for NF-pNETs, as accuracies are too low. Studies evaluating the diagnostic value of imaging modalities are heterogeneous with varying risks of bias. For the detection of NF-pNETs, endoscopic ultrasound (EUS) has the highest sensitivity. A combined strategy of EUS and MRI seems to be the most useful. Gallium 68 octreotate-DOTA positron emission tomography-CT could be added if NF-pNETs are diagnosed to identify metastasis. Reported growth rates were generally low, and two distinct phenotypes were observed. Surveillance programs should focus on and be adapted to the presence of substantial growth in NF-pNETs. The optimal age to start screening must yet be determined, as insufficient evidence for an evidence-based recommendation was available.

show abstract

Surgery for multiple endocrine neoplasia type 1-related insulinoma: long-term outcomes in a large international cohort

Beek¹,

Nell²,

Verkooijen

et al. 2020

British Journal of Surgery

View full text Add to dashboard Cite

Background Insulinomas are found in 10–15 per cent of patients with multiple endocrine neoplasia type 1 (MEN1) and lead to life‐threatening hypoglycaemia. Surgical outcome and the optimal surgical strategy for MEN1‐related insulinoma are unknown. Methods Patients with MEN1‐related insulinomas were identified in 46 centres in Europe and North America between 1990 and 2016. Insulinomas were considered localized if the lesion was in the pancreatic head or body/tail. Patients with pancreatic neuroendocrine tumours throughout the pancreas were suspected of having multifocal insulinoma. The primary outcome was postoperative hypoglycaemia, defined as persistent hypoglycaemia, or recurrent hypoglycaemia caused by a new insulinoma or insulin‐producing liver metastases. Hypoglycaemia‐free survival was estimated by the Kaplan–Meier method. Results Ninety‐six patients underwent resection for MEN1‐related insulinoma. Sixty‐three and 33 patients had localized and multifocal insulinomas respectively. After a median follow‐up of 8 (range 1–22) years, one patient (1 per cent) had persistent disease and six (6 per cent) had developed recurrent disease, of whom four had a new insulinoma. The 10‐year hypoglycaemia‐free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. Of those with localized disease, 46 patients underwent pancreatic resection and 17 enucleation. One of these patients had persistent disease and one developed recurrent insulinoma. Among patients with multifocal disease, three developed new insulinomas and two developed insulin‐producing liver metastases. Conclusion Surgery for MEN1‐related insulinoma is more successful than previously thought.

show abstract

Is Routine Screening of Young Asymptomatic MEN1 Patients Necessary?

Abstract: Symptomatic or severe manifestations in MEN1 patients rarely occur below the age of 16 years. With regard to psychological burden and cost-effectiveness, routine screening of asymptomatic MEN1 patients should be postponed at least until the age of 16 years.

Cited by 38 publications

References 62 publications

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1

Paediatric and young adult manifestations and outcomes of multiple endocrine neoplasia type 1

Diagnosing Nonfunctional Pancreatic NETs in MEN1: The Evidence Base

Surgery for multiple endocrine neoplasia type 1-related insulinoma: long-term outcomes in a large international cohort

Contact Info

Product

Resources

About