Endocrine Abstracts

JOINT4044

Introduction: Familial isolated pituitary adenomas (FIPA) are one of the most important inherited settings for pituitary adenomas and the most frequent genetic cause is a germline mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene. AIP mutations lead to young-onset macroadenomas that are di cult to treat. Most are growth hormone secreting tumors.

Clinical case: A 14-year-old male patient complained for insulin resistance and physiognomic changes throughout the last 2 years. His mother was diagnosed with acromegaly at the age of 16, cured after 2 surgeries and a short period of somatostatin analogues. On physical examination his height was 180,5 cm (+2.51 SDS), weight of 78 kg (+2,18 SDS), and Tanner stage IV. Target height was 172,25 cm -0.08 SDS (Δ H/TH: +2,6 SDS). The shoe size 42, and had acanthosis nigricans on the neck. Hormonal assessment revealed a basal GH of 21.5 ng/ml, a nadir post-glucose GH of 18.5 ng/ml, and IGF-1 of 556 ng/ml (Range age/sex: 211-512) (+ 3.97 SDS). Prolactin and testosterone levels were within the normal range, as well as the evaluation of the adrenal and thyroid axes. MRI showed a macroadenoma with mild suprasellar extension, and sphenoid sinus invasion, with no extension to cavernous sinuses. The patient was operated on by transsphenoidal approach without complications; the histopathology reported a sparsely granulated somatotropinoma, with Ki 67 of 10%. The AIP gene analysis performed using the MLPA technique, resulted positive for both the patient and his mother (Heterozygous missense pathogenic variant c.136G>T (p.Glu46*) Three months after surgery, IGF1 decreased to +0.31 SDS, with a random GH of 0.8 ng/ml; insulin levels normalized and the MRI did not show images of tumor remnant. Two years after surgery, the patient remained in remission, with a post-glucose GH nadir of 1 ng/ml and IGF1 < 1 UNL, and normal gonadal axis (IGF1: 399 ng/ml (+ 1,42 SDS) (57-426), Testosterone: 5 ng/ml). During follow-up there was a significant slowdown in growth velocity.

Discussion: This is a 16-year-old patient with familial acro-gigantism, AIP positive, operated on for a macroadenoma with histopathological markers of poor prognosis with a high chance of recurrence and aggressiveness. Two years after surgery, he presents biochemical remission markers, without tumor remnant and asymptomatic. Strict clinical, biochemical and imaging monitoring is necessary given the poor prognostic tumor markers and positive genetics.