IMPE Abstracts

Background: Pituitary adenomas are rarely encountered in children. If present, they are associated with a heavy clinical burden due to local compressive symptoms, the systemic effects of hormonal hypersecretion, and the need for neurosurgery, chronic medical therapy, or radiotherapy. The genetic analysis can provide essential information on the course of the disease and the best choice of treatment. Cases: Here, we describe 3 patients with acromegaly due to genetically determined pituitary adenomas The first patient is a 15-year-old boy with von Willebrand disease who was admitted to the endocrinology department after endoscopic pituitary transsphenoidal surgery complicated by combined pituitary hormone deficiency. Unfortunately, the initial surgery failed and therefore he was reoperated twice by the transcranial method. Three months later the treatment with a somatostatin analogue was introduced and six months later he received 6 cycles of radiotherapy. Genetic analysis revealed a heterozygotic deletion of c.229del1G in the AIP gene. Currently, the boy is treated with a somatostatin analogue in a maximum dose of 40 mg and receives hormonal substitution with a satisfactory effect (the tumor mass is stable on MRI). The second patient is an 8-year-old boy that was referred to the endocrinology department because of tall stature and foci of fibrous dysplasia in several bones (mandibular shaft, tibia, femoral shaft) y. High levels of IGF-1 and no GH inhibition during oral glucose tolerance test were observed. MRI examination revealed a pituitary tumor (16 x 23 x 27 mm) and additional foci of fibrous dysplasia in the skull. The treatment with a somatostatin analogue was initiated. McCune Albright syndrome is highly suspected, but despite improved diagnostic methods (including digital PCR for low levels of activating GNAS mutations) we could not confirm the diagnosis. The last one patient is a 13-year-old-girl with heterotaxis syndrome. Similarly, high levels of IGF-1 and no GH inhibition during oral glucose tolerance test were observed. MRI examination revealed a pituitary tumor (33 x 41 x 31 mm). The treatment with a somatostatin analogue was initiated. The patient died couple months later because of heart failure. The genetic analysis was inconclusive. Conclusions: Until now, only few genes are known in which mutations lead to inherited pituitary tumors. Germline AIP mutations are associated with large pituitary adenomas (>50% macroadenomas) that occur at an early age, mainly in children/adolescents and young adults. Further studies should be performed to elucidate the genetic background of these tumors.