Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Pediatr Diabetes. 2020 May;21(3):441-455. doi: 10.1111/pedi.12989. Epub 2020 Feb 11.
BACKGROUND/OBJECTIVE: Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with transient or persistent hypoglycemia. Histologically, focal, diffuse, and atypical forms of CHI exist, and at least 11 disease-causing genes have been identified.
We retrospectively evaluated the treatment and outcome of a cohort of 40 patients with non-focal, persistent CHI admitted to the International Hyperinsulinism Center, Denmark, from January 2000 to May 2017.
Twenty-two patients (55%) could not be managed with medical monotherapy (diazoxide or octreotide) and six (15%) patients developed severe potential side effects to medication. Surgery was performed in 17 (43%) patients with resection of 66% to 98% of the pancreas. Surgically treated patients had more frequently K -channel gene mutations (surgical treatment 12/17 vs conservative treatment 6/23, P = .013), highly severe disease (15/17 vs 13/23, P = .025) and clinical onset <30 days of age (15/17 vs 10/23, P = .004). At last follow-up at median 5.3 (range: 0.3-31.3) years of age, 31/40 (78%) patients still received medical treatment, including 12/17 (71%) after surgery. One patient developed diabetes after a 98% pancreatic resection. Problematic treatment status was seen in 7/40 (18%). Only 8 (20%) had clinical remission (three spontaneous, five after pancreatic surgery). Neurodevelopmental impairment (n = 12, 30%) was marginally associated with disease severity (P = .059).
Persistent, non-focal CHI remains difficult to manage. Neurological impairment in 30% suggests a frequent failure of prompt and adequate treatment. A high rate of problematic treatment status at follow-up demonstrates an urgent need for new medical treatment modalities.
背景/目的：先天性高胰岛素血症（CHI）是一种罕见的异质性疾病，表现为短暂或持续性低血糖。组织学上，CHI 存在局灶性、弥漫性和非典型性等多种形式，目前已经确定至少有 11 个致病基因。
我们回顾性评估了丹麦国际高胰岛素血症中心自 2000 年 1 月至 2017 年 5 月收治的 40 例非局灶性、持续性 CHI 患儿的治疗和结局。
22 例（55%）患儿无法通过药物（二氮嗪或奥曲肽）单药治疗控制，6 例（15%）患儿出现严重药物不良反应。17 例（43%）患儿接受了手术治疗，其中 66%98%的胰腺被切除。手术治疗的患儿更常发生 K 通道基因突变（手术治疗 12/17 例 vs 保守治疗 6/23 例，P =.013），疾病更严重（手术治疗 15/17 例 vs 保守治疗 13/23 例，P =.025），且发病年龄<30 天（手术治疗 15/17 例 vs 保守治疗 10/23 例，P =.004）。在中位随访 5.3 年（范围：0.331.3 年）时，40 例患儿中 31 例（78%）仍接受药物治疗，其中 12 例（71%）在手术后。1 例患儿在 98%胰腺切除术后发生糖尿病。40 例患儿中有 7 例（18%）治疗情况不理想。仅 8 例（20%）患儿达到临床缓解（3 例自发缓解，5 例经胰腺手术后缓解）。神经发育障碍（n = 12，30%）与疾病严重程度（P =.059）有一定相关性。
非局灶性、持续性 CHI 仍难以治疗。30%患儿存在神经发育障碍，表明及时、充分治疗的效果不佳。随访中存在高比例不理想的治疗情况，迫切需要新的治疗方法。
