Multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1

Epidemiology and genetics MEN /uni00A0 1 is an autosomal dominant inherited disorder. It was originally called Wermer’s syndrome. It is rare (1 in 30 /uni00A0 000) in the general population but accounts for 10% of primary hyperparathyroidism (PHPT) in patients under 30 years and 30–40% of all cases of gastrinoma. The tumour-suppressor gene MEN1 encodes for menin, a protein that regulates tran - - scription, cell division and proliferation. The pathophysiology followed by a second-hit somatic mutation in the specific tissues. There are many hundreds of germline mutations of MEN1 on chromosome 11, but there is no genotype/pheno type association. Clinical presentation The manifestations of MEN /uni00A0 1 are listed in Table 57.7 Virtually all patients develop PHPT (see Chapter 56 screening programmes, non-functioning P-NETs are seen in up to 70% of patients. The most common functioning P-NET is gastrinoma, followed by insulinoma. The remainder are extremely rare. Most pituitary tumours are microadenomas and are either non-functioning or secrete prolactin. The latter can be treated medically . /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF /uni25CF Surgery MEN /uni00A0 1 PHPT treatment di ff ers from sporadic disease because it is secondary to four-gland hyperplasia and so the surgical approach is always bilateral neck exploration. Whether to perform subtotal or total parathyroidectomy with autotrans plantation is debatable. All patients should receive counselling about the inevitability of recurrent hyperparathyroidism. At the time of cervical surgery , a prophylactic thymectom y is also performed (see also Chapter 56 ). Gastrinoma is typically managed medically for tumours <2 /uni00A0 cm in diameter. Functioning P-NETs are excised as previ ously described, but the treatment of NF-P-NET is challenging owing to the widespread distribution of multiple tumours in John H Sipple , b. 1930, physician, The State University of New Y ork, Syracuse, NY , USA. and the preservation of endocrine function. Functional adre - nal tumours in MEN /uni00A0 1 are rare and have to be operated on. Non-functioning tumours should be resected if they r each a - size of 4 /uni00A0 cm.

TABLE 57.7 Clinical manifestations of multiple endocrine neoplasia type 1 (MEN /uni00A0 1). Tumour site Frequency (%) PHPT (four-gland disease) 95 Pancreatic islet cell tumours 30–80 Gastrinoma NF-P-NET Insulinoma Glucagonoma VIPoma Somatostatinoma Pituitary tumours 15–50 Prolactin (60%) Growth hormone (25%) ACTH (5%) Non-functioning Adrenocortical tumours – mainly non

40–50 functioning NET lung, thymus, stomach 3–10 Lipomas 5–10 MEN /uni00A0 1 is also associated with meningiomas and facial angio /f_i bromas ACTH, adrenocorticotropic hormone; NET, neuroendocrine tumour; NF-P-NET, non-functioning pancreatic neuroendocrine tumour; PHPT, primary hyperparathyroidism; VIP , vasoactive intestinal polypeptide.