Kubo Haremaru, Wada Ryota, Sekikawa Naohiro, Nomura Yasuhisa, Yamada Mutsuo, Inoue Minoru, Hattori Naoki, Yamazaki Yuto, Sugimoto Kazuhiro
Diabetes Center, Ohta Nishinouchi Hospital, Koriyama, Fukushima, Japan.
Department of Obstetrics and Gynecology, Ohta Nishinouchi Hospital, Koriyama, Fukushima, Japan.
Front Endocrinol (Lausanne). 2024 Dec 12;15:1498991. doi: 10.3389/fendo.2024.1498991. eCollection 2024.
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.
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 Thereafter, medication for diabetes could be withdrawn.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 gene, with only one common polymorphism that was non-pathogenic.
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.
1型多发性内分泌腺瘤病（MEN1）是一种罕见的常染色体显性疾病，伴有甲状旁腺、胰腺、垂体的多发性内分泌肿瘤以及肾上腺的其他肿瘤。然而，在某些情况下，临床诊断为MEN1的患者可能为基因阴性。
一名56岁女性，根据直径为19毫米的大泌乳素瘤、原发性甲状旁腺功能亢进和分泌皮质醇的肾上腺腺瘤，被诊断为MEN1，无家族病史。初诊时，她的糖化血红蛋白为12.0%，空腹血糖水平为16.3毫摩尔/升（294毫克/分升）。她主诉头痛，28岁时有泌乳素瘤病史，同时泌乳素升高至1102.0微克/升（纳克/毫升）。在给予口服降糖药后，开始胰岛素治疗以控制血糖。此外，因泌乳素瘤开始使用卡麦角林，使泌乳素水平恢复正常。此后，糖尿病用药可以停用。随后，对原发性甲状旁腺功能亢进和分泌皮质醇的肾上腺腺瘤进行了手术，与术前诊断一致。此外，在原发性甲状旁腺功能亢进手术中切除的甲状腺肿瘤被发现为侵袭性乳头状甲状腺癌（PTC）。靶基因检测显示该基因的基因型为阴性，只有一个常见的多态性是非致病性的。
基因阴性的MEN1通常临床病程良好，无第三种原发性MEN1表现。然而，本病例有一个有症状的大泌乳素瘤，血糖水平明显升高，有三种肿瘤表现（垂体、甲状旁腺和肾上腺），伴有侵袭性PTC，延迟诊断可能导致病情严重恶化。临床医生应注意MEN1的临床特征，包括葡萄糖不耐受。在这种情况下，内分泌疾病的治疗可导致血糖水平恢复正常。
