Dyrka Kamil, Jamsheer Aleksander, Bartecki Michal, Bobkowski Waldemar, Pawelec-Wojtalik Malgorzata, Rajewska-Tabor Justyna, Tomaszewska Andzelika, Balcerzak Justyna, Aniol Zuzanna, Niedziela Marek, Obara-Moszynska Monika
Department of Pediatric Endocrinology and Rheumatology, Institute of Pediatrics, Doctoral School, Poznan University of Medical Sciences, Poznan, Poland.
Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.
Front Cardiovasc Med. 2025 Jan 3;11:1377510. doi: 10.3389/fcvm.2024.1377510. eCollection 2024.
Loeys-Dietz syndrome (LDS) is a clinically and genetically heterogeneous, autosomal dominant aortic aneurysm syndrome with widespread systemic involvement. We present the case of a 16.5-year-old girl with LDS type 2 (LDS2) caused by a heterozygous pathogenic variant, c.1582C>T (p.Arg528Cys), in the transforming growth factor-beta receptor type 2 (TGFBR2) gene who was treated with recombinant growth hormone (rGH) due to coexisting GH deficiency (GHD). This case report (observational study) presents the efficacy of rGH therapy and the safety aspects of this treatment, including aortal imaging follow-up (echocardiography, ECHO). To our knowledge, this is the first investigation of the effects of long-term rGH treatment on aortic dimensions in an LDS patient.
LDS was recognized in the patient in the 2nd year of life. After the 3rd year of life, growth deceleration was observed. At age 6, GHD was recognized [the maximum GH after stimulation 7.2 ng/ml; insulin-like growth factor-1 (IGF-1), 35 ng/ml; : 84-447]. At age 6.5 years, rGH was initiated (height standard deviation score, htSDS -2.4), which continued for up to 14.25 years (htSDS-1.4). Her height at 16.5 years was 155 cm. The dose of rGH was 0.025-0.028 mg/kg/day. After the age of 16 months, widening of the aortic root was observed via echocardiography. At nearly 16 years, due to dilated aortic root (Z score +5.95), the girl underwent a plastic operation on the aorta, which had a satisfactory outcome. The patient's current status is stable, but the management of patients with LDS requires multidisciplinary cooperation due to the many coexisting comorbidities.
Although aortic dilatation occurs in most LDS patients, the possible influence of GH therapy on aortic size must be considered. However, whether IGF-1, the main biochemical marker of GH activity, can be independently associated with increased aortic diameter has not been determined. In addition to its growth-promoting effect, the wide influence of GH on the human body, metabolic status, and muscle strength is also significant. The extremely low IGF-1 level before rGH therapy in the present patient and the strict monitoring of the IGF1/IGFBP3 ratio during rGH administration seem to be safe and beneficial for therapy.
洛伊斯-迪茨综合征（LDS）是一种临床和基因异质性的常染色体显性遗传性主动脉瘤综合征，可广泛累及全身。我们报告一例16.5岁患2型洛伊斯-迪茨综合征（LDS2）的女孩，其致病原因是转化生长因子-β受体2（TGFBR2）基因存在杂合致病性变异c.1582C>T（p.Arg528Cys），因同时存在生长激素缺乏（GHD）而接受重组生长激素（rGH）治疗。本病例报告（观察性研究）展示了rGH治疗的疗效以及该治疗的安全性方面，包括主动脉影像学随访（超声心动图，ECHO）。据我们所知，这是首次对长期rGH治疗对LDS患者主动脉尺寸影响的研究。
该患者在1岁时被诊断为LDS。3岁后观察到生长减速。6岁时确诊为GHD[刺激后最大生长激素7.2 ng/ml；胰岛素样生长因子-1（IGF-1），35 ng/ml；正常范围：84 - 447]。6.5岁时开始使用rGH（身高标准差评分，htSDS -2.4），持续使用达14.25年（htSDS -1.4）。她16.5岁时身高为155 cm。rGH剂量为0.025 - 0.028 mg/kg/天。16个月大后通过超声心动图观察到主动脉根部增宽。近16岁时，由于主动脉根部扩张（Z评分+5.95），该女孩接受了主动脉整形手术，手术效果满意。患者目前状况稳定，但由于存在多种合并症，LDS患者的管理需要多学科合作。
虽然大多数LDS患者会出现主动脉扩张，但必须考虑生长激素治疗对主动脉大小的可能影响。然而，生长激素活性的主要生化标志物IGF-是否能独立与主动脉直径增加相关尚未确定。除了其促生长作用外，生长激素对人体、代谢状态和肌肉力量的广泛影响也很显著。本患者在rGH治疗前IGF-1水平极低，且在rGH给药期间严格监测IGF1/IGFBP3比值，这似乎对治疗是安全且有益的。
