AUTHOR=Kubo Haremaru , Wada Ryota , Sekikawa Naohiro , Nomura Yasuhisa , Yamada Mutsuo , Inoue Minoru , Hattori Naoki , Yamazaki Yuto , Sugimoto Kazuhiro TITLE=Genotype-negative multiple endocrine neoplasia type 1 with prolactinoma, hyperparathyroidism, and subclinical Cushing’s syndrome accompanied by hyperglycemia: a case report JOURNAL=Frontiers in Endocrinology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1498991 DOI=10.3389/fendo.2024.1498991 ISSN=1664-2392 ABSTRACT=Background

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder, accompanied by multiple endocrine neoplasms of the parathyroid, pancreas, pituitary, and other neoplasms in the adrenal glands. However, in some cases, patients clinically diagnosed with MEN1 may be genotype-negative.

Case presentation

A 56-year-old female was diagnosed with MEN1 based on a macroprolactinoma (19 mm in diameter), primary hyperparathyroidism, and a cortisol-producing adrenal adenoma, without a family history. At first appearance, she had a hemoglobin A1c of 12.0% and a fasting plasma glucose level of 16.3 mmol/L (294 mg/dL). She complained of headaches and had a history of prolactinoma at 28 years of age, with concomitant elevated prolactin 1102.0 μg/L (ng/mL). Insulin therapy was initiated for glucose management following the administration of an oral hypoglycemic agent. Additionally, cabergoline was initiated for due to the prolactinoma, resulting in a normalized prolactin level. Thereafter, medication for diabetes could be withdrawn. Subsequently, surgery was performed for primary hyperparathyroidism and the cortisol-producing adrenal adenoma, which was consistent with the preoperative diagnosis. Additionally, a thyroid tumor resected with primary hyperparathyroidism revealed to be invasive papillary thyroid carcinoma (PTC). Target gene testing revealed a negative genotype for MEN1 gene, with only one common polymorphism that was non-pathogenic.

Conclusions

Genotype-negative MEN1 typically has a favorable clinical course without a third primary MEN1 manifestation. However, the present case had a symptomatic macroprolactinoma with an apparent elevated glucose level and three manifestations of tumors (pituitary, parathyroid, and adrenal) with invasive PTC, and a delayed diagnosis could have caused crucial deterioration. Clinicians should pay attention to the clinical features of MEN1 including glucose intolerance. In such cases, the treatment of endocrine disorders can lead to the normalization of the glucose level.