Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Fort Worth, Texas, USA.
Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Fort Worth, Texas, USA,
Horm Res Paediatr. 2019;91(1):25-32. doi: 10.1159/000497458. Epub 2019 Mar 19.
Diazoxide is the first line and only Federal Drug Agency approved pharmacological agent for the treatment of hyperinsulinism. Its use has increased over the years to include patients with various genetic forms of hyperinsulinism, perinatal stress hyperinsulinism and infants of diabetic mothers with more babies than ever being exposed to this therapy.
We performed a retrospective analysis of 194 patients with hyperinsulinism in our clinic and looked for those who had experienced serious adverse events (SAE) including pulmonary hypertension and neutropenia. We compared the rates of SAE in the different types of hyperinsulinism.
Out of 194 patients with hyperinsulinism, 165 (85.1%) were treated with diazoxide. There were 17 SAEs in 16 patients including 8 cases of pulmonary hypertension and 8 of neutropenia. These data show that overall the frequency of SAE associated with diazoxide use is 9.7%, but that those with perinatal stress hyperinsulinism have a much higher rate than those with genetic forms of hyperinsulinism (16.7 vs. 3.6%; p = 0.01). We also found diazoxide is associated with pulmonary hypertension (4.8% of patients treated). Although more patients with perinatal stress hyperinsulinism (7.6%) were affected than genetic hyperinsulinism (1.2%), the difference was not significant (p = 0.088).
The rate of SAEs associated with (not necessarily caused by) diazoxide has been demonstrated. The rate of SAE in newborns with perinatal stress hyperinsulinism is significantly higher than that of otherwise healthy babies with genetic forms of hyperinsulinism, suggesting that caution should be used when prescribing diazoxide to this population. This information should help balance the risk benefit of treatment and provide guidance on screening for these complications in the population of treated patients.
二氮嗪是治疗胰岛素瘤的一线药物，也是唯一获得美国食品药品监督管理局批准的药理学药物。多年来，其应用范围不断扩大，包括各种遗传性胰岛素瘤、围产期应激性高胰岛素血症和糖尿病母亲所生婴儿，后两者的患儿接受该治疗的比例不断增加。
我们对我院 194 例胰岛素瘤患者进行了回顾性分析，寻找发生严重不良事件（SAE）的患者，包括肺动脉高压和中性粒细胞减少症。我们比较了不同类型胰岛素瘤患者中 SAE 的发生率。
在 194 例胰岛素瘤患者中，165 例（85.1%）接受了二氮嗪治疗。16 例患者发生 17 例 SAE，包括 8 例肺动脉高压和 8 例中性粒细胞减少症。这些数据表明，二氮嗪相关 SAE 的总体发生率为 9.7%，但围产期应激性高胰岛素血症患者的发生率明显高于遗传性胰岛素瘤患者（16.7%比 3.6%；P=0.01）。我们还发现二氮嗪与肺动脉高压有关（4.8%的患者接受治疗）。虽然围产期应激性高胰岛素血症患者（7.6%）受影响的比例高于遗传性高胰岛素血症患者（1.2%），但差异无统计学意义（P=0.088）。
证明了与（不一定由）二氮嗪相关的 SAE 发生率。围产期应激性高胰岛素血症新生儿 SAE 的发生率明显高于其他遗传性胰岛素瘤患者，这表明在给该人群开二氮嗪时应谨慎。这些信息有助于平衡治疗的风险效益，并为治疗患者人群的这些并发症提供筛查指导。
