OBJECTIVE Previous studies have found that neurofibromatosis 1 (NF1) is associated with an increased risk for endocrine disorders, but no comprehensive overview of the risk for specific endocrine disorders has been published. We assessed endocrine morbidity in individuals with NF1 from information on hospital admissions, surgery for endocrine disorders, and relevant medication. DESIGN A nationwide population registry-based cohort study. METHODS We identified 2467 individuals with NF1 diagnosed between 1977 and 2013 from the Danish National Patient Register and the RAREDIS database and 20 132 randomly sampled age- and sex-matched population comparisons. Information on endocrine diseases was identified using registrations of discharge diagnoses, surgery, and medication prescriptions. The rates of endocrine disorders in individuals with NF1 were compared with those in the comparison cohort in Cox proportional hazard models. RESULTS Individuals with NF1 had a higher rate than the comparison group of any endocrine discharge diagnosis (hazard ratio [HR] 1.72, 95% confidence interval [CI]: 1.58-1.87), endocrine-related surgery (2.03, 1.39-2.96), and prescribed medications (1.32, 1.23-1.42). Increased HRs were observed for diseases and surgical operations of several glands, including pheochromocytoma, and for osteoporosis, and osteoporotic fractures. Decreased rates were observed with drugs for type 2 diabetes. Women with NF1 had higher HRs for surgery of the ovaries, uterus, and sterilization, but lower rates of surgeries of cervix and prescriptions for birth control pills. CONCLUSIONS Neurofibromatosis 1 is associated with a variety of endocrine disorders, surgery, and medication related to endocrine disease. Awareness of endocrine morbidity is important in the clinical follow-up of individuals with NF1.

中文翻译：

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神经纤维瘤病的内分泌发病率 1：一项全国性的、基于登记的队列研究。

目的 先前的研究发现神经纤维瘤病 1 (NF1) 与内分泌疾病风险增加相关，但尚未发表对特定内分泌疾病风险的全面概述。我们根据入院、内分泌疾病手术和相关药物的信息评估了 1 型 NF 个体的内分泌发病率。设计一项基于全国人口登记的队列研究。方法 我们从丹麦国家患者登记册和 RAREDIS 数据库中确定了 1977 年至 2013 年间诊断出的 2467 名 NF1 患者，并对 20132 名随机抽样的年龄和性别匹配的人群进行了比较。通过出院诊断、手术和药物处方的登记来确定内分泌疾病的信息。在 Cox 比例风险模型中，将 NF1 个体的内分泌紊乱发生率与对照组进行比较。结果 NF1 个体的任何内分泌分泌物诊断（风险比 [HR] 1.72，95% 置信区间 [CI]：1.58-1.87）、内分泌相关手术（2.03、1.39-2.96）、和处方药（1.32、1.23-1.42）。观察到多种腺体疾病和外科手术（包括嗜铬细胞瘤）以及骨质疏松症和骨质疏松性骨折的 HR 增加。使用治疗 2 型糖尿病的药物观察到发生率降低。患有 NF1 的女性进行卵巢、子宫手术和绝育手术的 HR 较高，但宫颈手术和服用避孕药的比例较低。结论 神经纤维瘤病 1 与多种内分泌疾病、与内分泌疾病相关的手术和药物治疗有关。对内分泌发病率的认识对于 NF1 患者的临床随访非常重要。