Endocrine Abstracts

Introduction: Most of pituitary adenomas are sporadic, with only 5% of them attributed to genetic mutations and syndromes such as Multiple Endocrine Neoplasia type 1 (MEN-1). However, how easy is it for a doctor to suspect it when there is no known family history?

Case Presentation: A 36-year-old patient with no personal or family history presented to our Endocrine Department reporting intermittent episodes of unconsciousness during the last 48 hours. The episodes lasted a few minutes without preceding aura or postictal phenomena. Biochemical analysis showed Glu=44 mg/dl, without accompanying symptoms. Brain imaging with CT revealed pathological tissue within the pituitary fossa with suprasellar and parasellar extension, without evidence of bleeding or optic chiasm compression. Further hormonal and imaging testing of the pituitary revealed a non-functioning adenoma measuring 2.3×3×2 cm on MRI, with concomitant thyrotroph and corticotroph axes deficiency. Despite hydrocortisone replacement therapy, the patient had consistently low fasting morning glucose levels (Glu<45 mg/dl) with inappropriately high insulin levels (Ins=9 IU/mmol), without neuroglycopenic symptoms. Prolonged fasting test confirmed endogenous insulin hypersecretion. Abdominal CT described an invasive lesion in the pancreas body. Endoscopic ultrasound identified a 2 cm mass in the uncinate process, a 3 cm mass between the body and the tail, and two smaller (<1 cm) satellite lesions. Cytology confirmed a pancreatic NET with characteristics of insulinoma. Additionally, biochemical analysis revealed elevated corrected calcium (11.9 mg/dl) and PTH=238 pg/ml levels, and 25OHD3 <8 mg/dl, indicating primary hyperparathyroidism. Neck ultrasound confirmed the presence of a parathyroid adenoma measuring 15.4×6.6×8 mm. Based on these findings, the diagnosis of MEN-1 syndrome was established and confirmed by genetic testing, detecting the rare nucleotide change c.467G>A heterozygosity in exon 3 of the MEN-1 gene. PET CT with Ga-68 showed no other lesions. The patient underwent initially transsphenoidal adenectomy and pathology report revealed “a well differentiated endocrine tumor consisting of a population of neoplastic cells expressing hormones (β-FSH, β-LH, PRL), with Ki-67=7% and absence of menin expression”. Then parathyroidectomy, thyroidectomy, total pancreatectomy, splenectomy, and cholecystectomy took place. Histology revealed parathyroid hyperplasia consistent with MEN-1 and a pancreatic NET G2 with Ki-67=5%, well-confined, without peripancreatic lymph node involvement.

Discussion: Many cases may seem to have an obvious diagnosis, but patience and persistence in clinical observation can reveal an underlying rare syndrome, while genetic testing serves as the confirmation. A multidisciplinary approach is crucial for the optimal management of patients with rare diseases.