Multiple endocrine neoplasia type 1 (MEN1): its manifestations and effect of genetic screening on clinical outcome.

OBJECTIVE: Effect of genetic screening on outcome in multiple endocrine neoplasia type 1 (MEN1) remains unclear. Expression of MEN1 is described using currently available diagnostic techniques. Manifestations and outcome are compared in patients diagnosed because of clinical expression with those diagnosed by genetic screening.

DESIGN: Retrospective cohort study. Patients are divided into two groups: patients with a (i) clinical MEN1 diagnosis and (ii) MEN1 diagnosis by genetic screening.

PATIENTS AND MEASUREMENTS: Demographic and clinical data were collected on MEN1 patients treated in the UMCU up to 1 January 2008. Results of mutation analysis were obtained from the Department of Medical Genetics.

RESULTS: A total of 74 patients was included (median follow-up 5.5 year); 78% had hyperparathyroidism, 46% a pancreatic neuro-endocrine tumour (NET), 38% a pituitary abnormality, 8% a NET of other origin and 16% an adrenal adenoma at the end of follow-up. Of the patients 18% had no manifestation. All five MEN1-related tumours were seen as first manifestation. Compared with patients identified by genetic screening, patients with a clinical MEN1 diagnosis had significantly more manifestations at diagnosis (P < 0.001) and at end of follow-up (P = 0.002). Eleven of 30 patients with a genetic MEN1 diagnosis (mean age at diagnosis 30.0 years) already had manifestations at diagnosis. No malignancy or death was seen in genetically diagnosed patients.

CONCLUSIONS: MEN1 is a syndrome with high morbidity. Genetic diagnosis is associated with less morbidity at diagnosis and at follow-up. Early genetic diagnosis might therefore lead to improvement of long-term outcome.