Endocrine Abstracts

Introduction: Multiple endocrine neoplasia syndrome type 1 (MEN-1) is an autosomal dominant disorder caused by germline mutations in the MEN1 gene encoding menin. MEN1 mutations are mainly represented by deletions/insertions, nonsense, splice site or missense mutations and can be detected by DNA sequencing. MEN-1 generally includes parathyroid, adenohypophysis, and pancreatoduodenal neuroendocrine tumors.

Clinical Case: Patient S., 26-years-old female, admitted with morbid obesity (BMI – 49, 5 kg/m²), weakness, vertigo, high blood pressure and irregular menstrual cycle. Primary hyperparathyroidism (PHPT) was diagnosed at 23 (2020): PTH – 481.6 pg/ml (15-65), Ca_adj. – 3.0 mmol/l (2.15-2.55). The patient underwent selective parathyroidectomy (histologic confirmation of adenoma) with postoperative PTH and blood Ca normalization. Three years later, laboratory tests revealed PHPT relapse: PTH – 158.0 pg/ml (15-65) with a high-normal Ca_adj. – 2.55 mmol/l (2.15-2.55), normophosphatemia – 0.8 mmol/l (0.74-1.52), normocalciuria – 5, 65 mmol/d (2.5-8.0). Screening for PHPT complications excluded nephrocalcinosis/nephrolithiasis, gastric and duodenal ulcer disease. DXA showed decreased bone mineral density in L_1-4 below age-expected values: -2.9 SD (Z-score). Imaging techniques (US;^99mTc-sestamibi scintigraphy with SPECT-CT) visualized left upper, right lower and upper abnormal parathyroid glands (PGs) (maximum size 1.6x0.85x0.5 cm) in typical locations. In 2023, S. had a surgical removal of three altered PGs with remission achievement. Histological analysis verified hyperplasia and adenoma. Therapy after discharge included alfacalcidol and Ca supplements. We diagnosed the patient with hyperprolactinemia – 1526 mEd/l (64-365). Brain MRI revealed an endosellar pituitary microadenoma (6x8 mm). Dopamine receptor agonist therapy was prescribed. Laboratory tests showed hypergastrinemia – 3283.0 pg/ml (13.0-115.0), chromogranin A elevation –34.6 nmol/l (<3.00). Сontrast-enhanced CT scan detected multiple pancreatoduodenal tumors (maximum size 2.0х2.0х2.0 cm) with focal SSTR2 overexpression at PET-CT with ⁶⁸Ga-DOTA-TATE, confirming its neuroendocrine origin. Considering clinical findings genetic analysis was performed identifying mutation in the MEN1 (an extended deletion in the heterozygous state of HG38:chr:11 chromosome with approximate boundaries 64804062-64810384 and p. 6322 bp, including 2-10 exons of the MEN1 gene (NM 130799.2). We used chromosomal microarray analysis as a reference method: microdeletion in chromosome 11 (67901 base pairs), imbalance region genes – MEN1, MAP4K2, CDC42BPG, EHD1.

Conclusions: There is currently no conclusive data on the genotype-phenotype correlation of MEN-1. Small or large deletions of the MEN1 gene are rare and have been described previously as pathogenic. Deletions of other genes are also of interest. Presumably they may affect the clinical manifestations of the disease.