EP1142 - ECE_1271 - Clinically diagnosed MEN 1: diagnostic challenges and delayed recognition

Abstract

Multiple endocrine neoplasia type 1 (MEN1) or Wermer syndrome) is a rare autosomal dominant disorder caused by germline mutations in the tumor suppressor gene MEN1. Gold standard for diagnosis is genetic testing, however the diagnosis is often clinically made by the combined occurrence of two or more of the following classical endocrinopathies: primary hyperparathyroidism (PHPT), anterior pituitary tumors, and duodenopancreatic neuroendocrine tumors (DP-NETs). Due to limited access to genetic testing, diagnosis can be established based on presence of two or more of the classical endocrinopathies. We present the case of a 58-year-old male who was referred to an endocrinologist following a new diagnosis of diabetes mellitus. During clinical evaluation, acromegalic features were noted, prompting inpatient endocrine assessment. Hormonal testing revealed elevated IGF-1 levels (992 ng/mL) and unsuppressed GH levels during oral glucose tolerance testing (OGTT), consistent with a somatotropinoma. Pituitary MRI confirmed the presence of a macroadenoma measuring 11 mm. Given the patient's history of recurrent kidney stones, parathyroid hormone (PTH) levels were assessed and found to be elevated (98 pg/mL), accompanied by mildly increased serum calcium levels, raising suspicion of primary hyperparathyroidism. MIBI scintigraphy was subsequently performed and confirmed the diagnosis, demonstrating an enlarged and hyperactive right lower parathyroid gland. On top of that, abdominal MRI revealed a cystic neoplasm in the pancreas and detailed gastroenterological evaluation was conducted. The patient underwent transsphenoidal pituitary surgery. The pathological examination showed a plurihormonal pituitary neuroendocrine tumor (PitNET). At the three-month reevaluation, disease remission had not been achieved, so somatoatatin analogue octreotid was introduced into the treatment. Parathyroidectomy is planned as the next step. Given the presence of multiple endocrine neoplasias, clinical diagnosis of MEN1 was established, and referral to a higher-level reference center for genetic testing is planned. This case highlights the importance of detailed clinical history and thorough physical examination in endocrinological outpatient clinic. Every patient with acromegaly should undergo comprehensive endocrine evaluation to rule out syndromic causes, given the implications for diagnosis, treatment, and family screening.