Efficacy and safety of treatment with Cinacalcet in patients with Primary Hyperparathyroidism due to a MEN-1 mutation

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcaemia
in the population. Less than 5% of the patients with PHPT has a hereditary
mutation, such as the MEN-I en MEN-IIa syndrome. More than 95% of the patients
with a MEN-I syndrome, however, develop PHPT, 50% develops a pituitary adenoma
and 33% develops a insulinoma, gastrinoma, or other pancreas tumor. Patients
with PHPT can only be definitively cured by surgical excision of all
pathological parathyroid glands. Recently it has been proven that
calcimimetics, such as cinacalcet (Primpara ®), can sensitize the
calcium-sensing receptor (CaSR) for extracellulair calcium, and decrease the
serum calcium and PTH concentrations. At the moment cinacalcet is the only
calcimimetic that is approved for the treatment of patients with PHPT. The CaSR
is located on the parathyroid cells, but also on the cells of the kidney,
bones, intestine, thyroid, brain, pancreas and gastrinoma cells of the stomach.
Therefore, it could be possible that cinacalcet does not only influence the
CaSR on the parathyroidcells, but also on the other organs, however this has
not yet been properly studied. Therefore, the aim of our study is to evaluate
the efficacy and safety of treatment with cinacalcet in patients with PHPT due
a MEN-I mutation.

1. What are the effects of cinacalcet on clinical and biochemical parameters,
including bone turnover markers, in patients with primary hyperparathyroidism
due to a MEN-I mutation?
2. What are the effects of cinacalcet on bone mineral density and
nefrolithiasis in patients with primary hyperparathyroidism due to a MEN-I
mutation?
3. What is the effect of cinacalcet on the development and/or growth of
pituitary adenomas, insulinomas, gastrinomas and/or other pancreatic tumors in
patients with primary hyperparathyroidism due to a MEN-I mutation?
4. Is there a loss or decrease of the CaR expression in pathological specimens
obtained at surgery in patients with primary hyperparathyroidism due to a MEN-I
mutation? And does this influence the response to treatment with cinacalcet?

One year single-centre, prospective intervention study

Treatment with cinacalcet (Mimpara) 30 mg twice daily for a duration of 1 year.

Patients will undergo the standard biochemical and radiological work-up
necessary for the evaluation of MEN-1 associated disorders and complications of
primary hyperparathyrodism.
They will also undergo a neuropsycological examination to evaluate the presence
of alteration in cognitive function during treatment with cinacalcet.