Knowledge of the Natural History of Paediatric MEN1 is Required to Inform Decision Making for Predictive Testing in Childhood

Julie Park; Catherine Collingwood; Astrid Weber; Joanne Blair

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is a dominantly inherited syndrome characterised by parathyroid hyperplasia, pancreatic neuroendocrine tumours (PNET) and pituitary adenomas, although >20 tumours are described. Clinical guidelines¹ recommend annual biochemical surveillance and abdominal imaging from <10yrs and pituitary imaging every 3yrs. Age at start of surveillance is derived from the youngest reported patient with an MEN1 manifestation. The commonest paediatric manifestation is hyperparathyroidism, affecting approximately 50% of patients by age 20yrs.

Methods: Retrospective, observational study of paediatric patients screening according to international guidelines¹.

Results: Data from 13 patients diagnosed on predictive testing aged 5-13yrs are presented in Table 1. No patient has required an intervention to date.

**Table 1**
Patient	Age at diagnosis (years)	Number of hospital visits	No of blood tests (prolactin, IGF1, calcium and PTH)	No of MRIs (pituitary and abdominal)	Manifestations of MEN1
1	13	5	4	2	none
2	8	9	6	2	Asymptomatic eucalcaemic hyperparathyroidism
3	5	7	5	2	none
4	11	3	2	3	none
5	13	3	2	3	none
6	10	3	2	3	none
7	12	3	2	3	Asymptomatic eucalcaemic hyperparathyroidism
8	12	2	1	2	none
9	9	11	8	2	Asymptomatic eucalcaemic hyperparathyroidism
10	5	2	1	2	none
11	5	2	1	2	none
12	7	2	1	2	none
13	8	2	1	2	none

Discussion: In our small population, a large number of appointments, MRI scans and biochemical tests were performed and days at school and work were lost. Whether tumour surveillance heightens or reduces anxiety is likely to be highly individual.

Tumour prevalence of MEN1 in childhood is largely unknown. There is likely to be a publication bias, favouring description of patients with tumours. Predictive testing is often undertaken in children too young to give consent. Some adults, diagnosed in childhood, may have elected not to be tested.

Surveillance imaging risks identification of incidental findings of uncertain significance. The natural history and optimal timing of surgery for small, non-functioning PNETs and adrenal tumours is unknown, while the timing of parathyroid surgery is debated.

To enable families to make informed decisions about predictive testing and surveillance, international collaboration is required to generate data describing the prevalence and natural history of MEN1 related tumours in childhood.

References: 1. Thakker R et al. Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1), JCEM (2012) 97: 9 (1); 2990–3011

ESPE Abstracts

P1-246