Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by an increased predisposition to the development of tumors of the endocrine tissues, such as parathyroid glands, anterior pituitary, and duodenopancreatic neuroendocrine tumors. It is an autosomal dominant disorder due to germline mutations in the MEN-1 tumor suppressor gene. This gene encodes the menin protein, which is involved in cell growth and differentiation, and in sensing or repairing DNA damage. We present the case of a patient whose diagnosis of MEN-1 syndrome was made incidentally during staging for breast cancer. The patient is a female, 43 years old, with no relevant personal history, and a family history of consanguinity – the patient’s parents are brother and sister. During the staging for breast cancer, the patient underwent breast mammography and biopsy after the detection of a 25 mm nodule in the right upper-external breast quadrant. The anatomopathological evaluation revealed invasive ductal carcinoma. Then, a genetic test was performed identifying a breast cancer pathogenic variant (CHEK2 c.1141 A>G VUS) and, incidentally, a MEN-1 pathogenic mutation (c.1117G>A). After the identification of the MEN-1 mutation, the patient was referred to an Endocrinology consultation. The initial laboratory evaluation accordingly to Clinical Practice Guidelines for MEN1 revealed no preliminary abnormalities: plasma calcium 9.3 mg/dl, albumin 4.2 g/dl, PTH 63.6 pg/ml, gastrin 23 pg/ml, glucagon 145 pg/ml, vasointestinal polypeptide 14 pmol/l, chromogranin A 7.3 nmol/l, insulin 16.0 μUI/ml, with an associated fasting glucose level of 90 mg/dl, prolactin 6.5 ng/ml, IGF-1 92 ng/ml, TSH 1.71 mUI/l, fT4 14.2 pmol/l, FSH 23.1 mUI/l, LH 7.6 mU/l, 17-Beta estradiol 80.6 pg/ml, ACTH 10.7 pg/ml, CA 125 11.7 U/ml. Imaging evaluation done during staging for breast cancer (including gynecological echography, thorax MRI and bone scintigraphy) showed no evidence of disease other than the referred nodule. There is growing evidence that MEN-1 increases the risk of development of breast tumors by at least two- to threefold (in frequency and in age of appearance) and several MEN-1 studies suggest the age of 40 years for the start of screening. However, Clinical Practice Guidelines for MEN-1 do not mention breast cancer and do not suggest changes in breast cancer screening compared to the general population. Since in Europe, the majority of countries conduct breast cancer screening programs starting at age 50, this case raises the question – Shouldn’t we start breast cancer screening earlier in the MEN-1 subpopulation?