Multiple endocrine neoplasia

From Ganfyd

Also referred to as MEN syndromes. Neurofibromatosis and von Hippel-Lindau disease can also manifest as MEN syndromes.

MEN I

(Wermer syndrome) (note there is a very different Werner syndrome)

• Primary hyperparathyroidism 95% -Parathyroid hyperplasia/adenomas
• Pituitary tumours
• Pancreatic tumours-adenomas, gastrinomas & islet cell tumors

also possible are

• Peptic ulcers due to Zollinger-Ellison syndrome (gastrinomas)
• Bronchial and thymic carcinoid
• Adrenal cortical adenoma
• Thyroid follicular adenoma

Aetiology

Chromosome 11q13 defect

MEN 2

Due to mutations in receptor tyrosine kinase (RET)

MEN 2a

(Sipple syndrome)

• Primary hyperparathyroidism- Parathyroid hyperplasia/adenoma
• Phaeochromocytoma
• Medullary carcinoma of the thyroid and thyroid C cell hyperplasia

also

• Adrenal medullary hyperplasia

Aetiology

Mutations in the RET protooncogene on chromosome 10 A codon 634 mutation is associated with presence of haeochromocytoma and hyperparathyroidism.

MEN 2b

• Adrenal medullary hyperplasia
• Medullary carcinoma of the thyroid and thyroid C cell hyperplasia
• Neuromas -Gastrointestinal and ocular-cutaneous ganglioneuromatosis
• Megacolon

Aetiology

Codon 918 mutation in the RET protooncogene on chromosome 10

familial MTC (FMTC)

• Medullary carcinoma of the thyroid (only)

Aetiology

Mutations at codons 768 and/or 804 in the RET protooncogene on chromosome 10

History

The first case description was by Erdheim in 1903. Wener characterised the autosominal inheritance of MEN 1 in 1954 which had been identified by Underdahl et al. Sipple described MEN 2a in 1961 and MEN 2b was described by Williams et al in 1966. Steiner et al coined the term "multiple endocrine neoplasia" in 1968.

Reference

Carney JA. Familial multiple endocrine neoplasia: the first 100 years. Am J Surg Pathol. 2005;29:254-74