Familial syndromes associated with phaeochromocytomas

There are three syndromes associated with phaeochromocytomas. These are:

• von Recklinghausen disease
• von Hippel-Lindau disease
• multiple endocrine neoplasia type 2 (MEN 2)

Von Recklinghausen disease

This is also known as Neurofibromatosis type 1 (NF1). It is a genetic disease, and is autosomal dominantly inherited. It can occur in 5% of all patients with a phaeochromocytoma. Affected individuals will all eventually develop café-au-lait spots, iris Lisch nodules and multiple neurofibromas. Neurofibromas in patients may secrete noradrenaline with or without a phaeochromocytoma.

Von Hippel-Lindau disease

This is an autosomal dominant genetic disease that is characterised by haemangioblastomas in the retina and cerebellum. The incidence of phaeochromocytoma in von Hippel-Lindau (VHL) disease is 10-14%. Screening programmes for those with VHL should detect phaeochromocytomas before symptoms occur, although this is complicated by VHL patients being susceptible to a number of adrenal diseases, including cortical adenomas and haemangioblastomas. The accurate diagnostic methods used for phaeochromocytomas will address this difficulty.

Multiple endocrine neoplasia type 2 (MEN 2)

This consists of two types, 2a and 2b, and describes the occurrence of a number of tumours in some endocrine glands.

MEN 2a consists of:

• medullary thyroid carcinoma
• phaeochromocytoma
• tumours of the parathyroids

MEN 2b consists of:

• medullary thyroid carcinoma
• phaeochromocytoma
• ganglioneuromatosis
• Marfanoid habitus.

20-50% of those with MEN 2 develop phaeochromocytoma, and it is equally common in types 2a and 2b. The tumours are multicentric (diffusely spread in the medulla) and about half are bilateral. Malignancy is rare and is estimated to be between 0 and 8%. Phaeochromocytomas are usually detected in their early stages in MEN 2 as affected families undergo screening processes for disease.