Nosakova Lenka, Banovcin Peter, Duricek Martin, Uhrik Peter, Bozikova Janka, Demeter Michal, Hyrdel Rudol
Clinic of internal medicine - gastroenterology, JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Slovakia.
Neuro Endocrinol Lett. 2021 Dec 21;42(8):522-527.
Insulinomas are rare neuroendocrine tumors of pancreas. Clinical manifestations include various symptoms of hypoglycemia, which is the result of insulin overproduction. Symptoms of hypoglycemia are heterogenous what most probably contributes to diagnostic delay. In this study we retrospectively evaluated clinical features of hypoglycemia. We discovered that a substantial number of patients suffered from hypoglycemia unawareness.
We performed retrospective analysis of prospectively collected patients with histologically confirmed insulinoma. We evaluated clinical features and signs of hypoglycemia and the duration of symptoms and performed thorough review of the patients' files in order to identify whether patients had been falsely diagnosed previously. Each patient underwent 72 hour fasting test during which levels of immunoreactive insulin (IRI), C-peptide and nadir blood glucose level were obtained. Based on the clinical findings and results of 72 hour fasting test we identified a subgroup of patients with hypoglycemia unawareness. These had an episode of clinically silent hypoglycemia. We compared IRI and C-peptide levels obtained at the time of the fasting test termination in the unawareness group and the group without hypoglycemia unawareness.
Twenty two patients with insulinoma that had been hospitalized in our tertiary center were included in the analysis. Mean age was 51±16.7 years. The most common symptom reported by 63.6% of patients was fatigue, followed by increased appetite with consequent weight gain and the loss of consciousness, both reported by 40.9% of patients. Based on the review of clinical features and the results of the fasting test we identified a group of patients with hypoglycemia unawareness. We labeled the patient accordingly in case of the loss of consciousness in personal history as well as asymptomatic hypoglycemia or severe neuroglycopenic symptoms during the fasting test without any accompanying or preceding clinical signs. There were 7 patients with hypoglycemia unawareness in our cohort (31.8%). Patients with this phenomenon had significantly lower levels of both IRI (2.35±1.25 vs. 5.88±3.92ng/ml, p=0.01) and C-peptide (9.14±7.36 vs. 50±42.8 µU/ml, p=0.01) than the rest of the patients. Nadir blood glucose level during the fasting test showed no significant difference (9.4±8.2 vs. 12.2±8.2 months, p=0.28) in the unawareness group and the rest of the patients, respectively.
We described the phenomenon of unawareness to hypoglycemia in the patients with insulinoma. This has not been recognized in insulinoma patients yet since available evidence mostly relates to type I diabetic patients. It might lead to higher morbidity and diagnostic delay. Further studies with prospective evaluation should be performed to further confirm relatively high prevalence in patients with insulinoma.
胰岛素瘤是胰腺罕见的神经内分泌肿瘤。临床表现包括各种低血糖症状，这是胰岛素分泌过多的结果。低血糖症状具有异质性，这很可能导致诊断延迟。在本研究中，我们回顾性评估了低血糖的临床特征。我们发现相当多的患者存在低血糖无知觉现象。
我们对前瞻性收集的经组织学确诊为胰岛素瘤的患者进行了回顾性分析。我们评估了低血糖的临床特征和体征、症状持续时间，并对患者病历进行了全面审查，以确定患者此前是否被误诊。每位患者均接受了72小时禁食试验，在此期间获取免疫反应性胰岛素（IRI）、C肽和最低血糖水平。根据临床发现和72小时禁食试验结果，我们确定了一组低血糖无知觉的患者。这些患者有临床无症状性低血糖发作。我们比较了无知觉组和无低血糖无知觉组在禁食试验结束时获得的IRI和C肽水平。
纳入分析的是在我们三级中心住院的22例胰岛素瘤患者。平均年龄为51±16.7岁。63.6%的患者报告的最常见症状是疲劳，其次是食欲增加伴体重增加以及意识丧失，两者均有40.9%的患者报告。根据临床特征回顾和禁食试验结果，我们确定了一组低血糖无知觉的患者。如果个人病史中有意识丧失，以及在禁食试验期间有无症状性低血糖或严重神经低血糖症状且无任何伴随或先前临床体征，我们会相应地对患者进行标记。我们的队列中有7例低血糖无知觉患者（31.8%）。有这种现象的患者的IRI（2.35±1.25 vs. 5.88±3.92ng/ml，p=0.01）和C肽（9.14±7.36 vs. 50±42.8µU/ml，p=0.01）水平均显著低于其他患者。禁食试验期间的最低血糖水平在无知觉组和其他患者中分别无显著差异（9.4±8.2 vs. 12.2±8.2个月，p=0.28）。
我们描述了胰岛素瘤患者中低血糖无知觉的现象。这在胰岛素瘤患者中尚未得到认识，因为现有证据大多与1型糖尿病患者有关。它可能导致更高的发病率和诊断延迟。应进行前瞻性评估的进一步研究，以进一步证实胰岛素瘤患者中相对较高的患病率。
