Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome mainly characterized by the occurrence of parathyroid (HPT), endocrine pancreas (PET), and pituitary tumors (PIT), although this condition may involve up to 20 endocrine and non-endocrine tumors.
PITs/MEN1 may occur early (first and second decade of life), are frequently aggressive and invasive, and are mostly represented by prolactin-secreting macroadenomas. The early diagnosis of PITs/MEN1 is essential for early treatment, aiming to start therapy before tumor invasiveness. Of note, PITs/MEN1 leading to gigantism are rare. Several recent advances have been made attempting to achieve optimal therapy for PIT/MEN1 cases, thus this topic should be stressed.
PETs/MEN1 – Insulinomas and mostly non-functional PETs (NF-PETs) have been verified to frequently occur at early ages, and NF-PETs is the major cause of death in MEN1. NF-PETs have been increasingly detected at young ages in MEN1, by using recent imaging approaches. Thus, a high prevalence of NF-PETs/MEN1 has been recently (2014) documented in the second decade of life, and some of these cases already harbored NF-PETs > 1-2cm, thus fullfiling criteria for surgery. There is an intense debate on when surgery should be performed in the later patients and this topic should be underlined.
HPT-MEN1 - Primary HPT is the most common clinical feature of MEN1 (73-100% of cases). It is usually (80%) the first clinical manifestation of MEN1 and differs from sporadic primary HPT in several aspects, as a) multiglandular parathyroid hyperplasia or adenoma; b) age-onset 2 decades earlier than sHPT (20 vs 40 y of age); c) sex ratio of 1:1 in contrast to the 1:3 for sHPT; and d) higher recurrence rates of HPT after parathyroidectomy. HPT-MEN1 usually occurs at ages < 30y and it was recently documented that bone mineral- and urolithiasis-related renal complications in HPT/MEN1 are early-onset, frequent, extensive, severe, and progressive.
In addition, the 2012 consensus on MEN1 recommended that, 1-MEN1 genetic testing should be performed as soon as possible in all cases with MEN1 and MEN1-like phenotypes and their at-risk relatives; 2-clinical screening for MEN1-associated tumors should be performed periodically in all cases harboring a MEN1 germline mutation. However, technical limitations in following the guidelines have been occurred. In this context, recent sequencing techniques as NGS assays may be of help in achieving this task, although few data are available on this specific topic.
Early genetic MEN1 testing and early clinical diagnosis are critical in MEN1, in the attempt to decrease morbitidy and also mortality in this condition. Another topic of interest is related with current therapy for advanced metastatic MEN1 tumors that has strongly expanded in recent years and needs to be revised.
To achieve the goal of this Research topic proposal, this special may contain original papers as well as review papers in order to expand our knowledge on the subject.
Furthermore, present challenges and controversies in MEN1 should be also stressed, and some of them are referred below.
Topics, challenges and controversies –
1 – Early clinical diagnosis of PITs/MEN1.
2 – Recent advances in therapy for PITs/MEN1.
3 - Optimal criteria to indicate surgery in NF-PETs/MEN1.
4 – Early diagnosis and management of non-functioning PETs/MEN1.
5 – Patients with NF-PETs should be operated based on tumors measuring either >1cm or >2cm.
6 - The optimal age for performing parathyroidectomy.
7 – Which is the best sequencing assay for MEN1 testing.
8 – Recent impact of early genetic diagnosis in MEN1.
9 – Update on impact of early clinical diagnosis in MEN1.
10 – Pituitary carcinoma in MEN1.
11 – PIT/MEN1 cases in the first decade of life.
12 - Rare or previously unreported tumors associated with MEN1.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome mainly characterized by the occurrence of parathyroid (HPT), endocrine pancreas (PET), and pituitary tumors (PIT), although this condition may involve up to 20 endocrine and non-endocrine tumors.
PITs/MEN1 may occur early (first and second decade of life), are frequently aggressive and invasive, and are mostly represented by prolactin-secreting macroadenomas. The early diagnosis of PITs/MEN1 is essential for early treatment, aiming to start therapy before tumor invasiveness. Of note, PITs/MEN1 leading to gigantism are rare. Several recent advances have been made attempting to achieve optimal therapy for PIT/MEN1 cases, thus this topic should be stressed.
PETs/MEN1 – Insulinomas and mostly non-functional PETs (NF-PETs) have been verified to frequently occur at early ages, and NF-PETs is the major cause of death in MEN1. NF-PETs have been increasingly detected at young ages in MEN1, by using recent imaging approaches. Thus, a high prevalence of NF-PETs/MEN1 has been recently (2014) documented in the second decade of life, and some of these cases already harbored NF-PETs > 1-2cm, thus fullfiling criteria for surgery. There is an intense debate on when surgery should be performed in the later patients and this topic should be underlined.
HPT-MEN1 - Primary HPT is the most common clinical feature of MEN1 (73-100% of cases). It is usually (80%) the first clinical manifestation of MEN1 and differs from sporadic primary HPT in several aspects, as a) multiglandular parathyroid hyperplasia or adenoma; b) age-onset 2 decades earlier than sHPT (20 vs 40 y of age); c) sex ratio of 1:1 in contrast to the 1:3 for sHPT; and d) higher recurrence rates of HPT after parathyroidectomy. HPT-MEN1 usually occurs at ages < 30y and it was recently documented that bone mineral- and urolithiasis-related renal complications in HPT/MEN1 are early-onset, frequent, extensive, severe, and progressive.
In addition, the 2012 consensus on MEN1 recommended that, 1-MEN1 genetic testing should be performed as soon as possible in all cases with MEN1 and MEN1-like phenotypes and their at-risk relatives; 2-clinical screening for MEN1-associated tumors should be performed periodically in all cases harboring a MEN1 germline mutation. However, technical limitations in following the guidelines have been occurred. In this context, recent sequencing techniques as NGS assays may be of help in achieving this task, although few data are available on this specific topic.
Early genetic MEN1 testing and early clinical diagnosis are critical in MEN1, in the attempt to decrease morbitidy and also mortality in this condition. Another topic of interest is related with current therapy for advanced metastatic MEN1 tumors that has strongly expanded in recent years and needs to be revised.
To achieve the goal of this Research topic proposal, this special may contain original papers as well as review papers in order to expand our knowledge on the subject.
Furthermore, present challenges and controversies in MEN1 should be also stressed, and some of them are referred below.
Topics, challenges and controversies –
1 – Early clinical diagnosis of PITs/MEN1.
2 – Recent advances in therapy for PITs/MEN1.
3 - Optimal criteria to indicate surgery in NF-PETs/MEN1.
4 – Early diagnosis and management of non-functioning PETs/MEN1.
5 – Patients with NF-PETs should be operated based on tumors measuring either >1cm or >2cm.
6 - The optimal age for performing parathyroidectomy.
7 – Which is the best sequencing assay for MEN1 testing.
8 – Recent impact of early genetic diagnosis in MEN1.
9 – Update on impact of early clinical diagnosis in MEN1.
10 – Pituitary carcinoma in MEN1.
11 – PIT/MEN1 cases in the first decade of life.
12 - Rare or previously unreported tumors associated with MEN1.