Endocrine Abstracts

Introduction: In recent years, more attention is driven to the cause of hereditary forms of pituitary adenomas. Although for most cases causal genes are not discovered yet, AIP mutations are the most prevalent.

Materials and Methods: Case descriptions, high-parallel sequencing using a gene panel (MEN1, CDKN1B, PRKAR1A, GNAS, AIP, SDHA, SDHB, SDHS, SDHD, PRKCA, CDKN2C, CDKN2A, POU1F1, PTTG2).

Case description: Index case – a 59-year-old man with clinical features of acromegaly (the size of adenomas at baseline 3.9×3.2×3.9 cm, growth 165 cm), secondary diabetes mellitus, multinodular goiter, obesity I grade, arterial hypertension. First clinical symptoms were noted since the age of 30 years. At the age of 51 he underwent transcranial adenomectomy, then at the age of 58 years – transnasal adenomectomy. Because of persistent disease activity he was initiated medical therapy with sandostatin analogs (40 mg of octreotide depo) without hormonal control of acromegaly – IGF 497.5 ng/ml (15–250) and GH 80 ng/ml (0–1.2). MRI after surgery pituitary adenoma with supra-, infra- and parasellar extension. The patient’s 28-year-old son also has acromegaly (intrasellar pituitary macroadenoma at MRI (the size of adenomas 0.7×1.2×0.6 cm), first clinical symptoms were noted since the age of 27 years, growth 167 cm, without complication); he was operated transnasally at the age of 28 years without postoperative remission: GH at OGTT 2.67-2.52-1.95-2.05-2.37 ng/ml, IGF 567.2 ng/ml (60–280). Genetic investigation revealed a mutation in exon 6 of the AIP gene pR271W (not previously described, possible pathological).

Conclusion: AIP mutation in our family with hereditary pituitary adenoma is associated with high aggressiveness and resistance to medical therapy with somatostatin analogs.