Multiple Endocrine Neoplasia Type 5 – Definition
Multiple endocrine neoplasia type 5 (MEN5) is a genetic disorder caused by a pathogenic germline mutation in the MAX gene (MYC-associated factor X). It primarily predisposes individuals to adrenomedullary pheochromocytoma. Less commonly, extra-adrenal tumors or tumors originating from the neural crest are described.
Synonym:
MAX-associated MEN syndrome
Gene:
MAX gene (MYC-associated factor X)
Gene product:
MAX protein
Function:
MAX encodes a transcription factor involved in cell proliferation, differentiation, apoptosis, and angiogenesis.
Pattern of inheritance:
Autosomal dominant
Prevalence:
currently unknown
Genotype-phenotype correlation:
no clearly established correlation to date
Penetrance:
not yet definitively defined
Multiple Endocrine Neoplasia Type 5 – Diagnosis
MEN5 is diagnosed through genetic testing that detects a pathogenic germline mutation in the MAX gene.
If MEN5 is detected, further predictive testing may be performed due to its autosomal dominant inheritance pattern.
MEN2 is a common differential diagnosis.
Clinical Presentation
The clinical presentation of MEN5 most closely resembles that of MEN2, with the primary occurrence of pheochromocytomas. The following tumors have been described to date in MEN5:
- Adrenomedullary PCC, often bilateral and/or multicentric
- Less common: extraadrenal tumors and tumors arising from the neural crest
- Tumore
- Ganglioneuromas
- Ganglioneuroblastomas
- Neuroblastomas
- Combined tumours
- PitNETs (prolactin- or growth hormone-secreting tumours)
- PHPT
dpNEN has been observed in only one patient to date. No data are currently available for MTC.
Special Features of Treatment
The treatment of individual cases is similar to that of MEN1.
Diagnosis of Multiple Endocrine Neoplasia Type 5- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Multiple Endocrine Neoplasia Type 5 - What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Surveillance Recommendations
Recommendations According to AACR Guidelines (2025):
PCC/PGL
- Clinical Management: Annual screening for signs of catecholamine excess starting at age 10
- Diagnostics: RR monitoring (annually starting at age 10)
- Plasma/urine fractionated metanephrines (every 1 to 2 years, starting at age 10)
- MRI of the neck, chest, and abdomen (every 2 to 3 years, starting at age 15)If metanephrine levels are elevated, further evaluation may be considered in accordance with current guidelines for PCC/PGL in children
PitNET (prolactinoma, GH-producing tumor)
- Screening: starting at diagnosis, every 5 years
- Watch for clinical symptoms: excessive growth, delayed puberty, galactorrhea, amenorrhea
- Further diagnostic testing if symptoms occur: measurement of prolactin or IGF-1
PHPT
- Screening: ages 10 and up, annually
- Clinical presentation: signs of hypercalcemia
- Diagnostics: serum calcium measurement if symptoms are present
Multiple Endocrine Neoplasia Type 5 – Further Information
Open Clinical Trials/ Registers
Further Information
Unfortunately, we are not yet aware of any support groups for patients with multiple endocrine neoplasia type 4. As soon as we have new information, we will add it.
