Endocrine Abstracts

Neuroendocrine tumours (NETs) can be sporadic or can arise in complex hereditary endocrine disorders such as multiple endocrine neoplasias (MENs), familial paragangliomatosis (FPGLs), neurofibromatosis type 1 (NF1), von Hippel–Lindau disease (VHL), tuberous sclerosis (TSC). It has been estimated that hereditary NET occurrence varies with site of origin of the tumour, representing 5–30% of all cases of NET. These rates seems to be an underestimation and novel mutations of well known oncogenes or tumour suppressor genes as well as new genes and molecular pathways responsible for unknown syndromes are expected to be characterized.

Hereditary NETs generally occur at an earlier age and show higher secretive activity than sporadic ones. Diagnosis is made around sixth decade of life in sporadic NETs while it is anticipated of about three decades in hereditary tumours. The identification of hereditary NET syndromes is relevant to achieve a precocious diagnosis and this may be important to prevent severe complications and unfavourable outcome. For this reason, the genetic screening is nowadays a well established procedure in many tumour types allowing to reclassify as carrier of specific hereditary NET syndromes, a number of patients with an apparently sporadic tumours. Some studies, focusing in particular on MEN type 1, highlighted that the genetic screening impacts on the management and clinical outcome of NETs, because it allows to detect tumours at an early stage or even before their development.

In spite of these recent advances, at now, clinical pictures of most of the hereditary NET syndromes are incomplete or not updated. Furthermore, follow-ups of these patients are not standardized.

In summary, the genetic diagnosis has a strong impact on the clinical course and prognosis of hereditary NETs. However, natural history remains to be defined more in deep for most of the actually known hereditary NET syndromes.