Bourcigaux Nathalie, Arnault-Ouary Gwenaëlle, Christol Rémy, Périn Laurence, Charbonnel Bernard, Le Bouc Yves
Endocrinology and Metabolism Service, Center University Hospital, Nantes, France.
Clin Ther. 2005 Feb;27(2):246-51. doi: 10.1016/j.clinthera.2005.02.004.
Non-islet cell tumor hypoglycemia(NICTH) is a rare cause of recurrent hypoglycemia. It has been associated with the tumoral overproduction of high-molecular-weight insulin-like growth factor (IGF)-2 ("big IGF-2"). Big IGF-2 suppresses growth hormone (GH) biosynthesis and impairs the storage of IGFs by suppressing the formation of the GH-dependent ternary complexes containing IGF, IGF binding protein 3 (IGFBP-3), and acid-labile subunit (ALS). Thus, big IGF-2 exerts hypoglycemic activity. The only effective treatment of NICTH is surgery. However, in inoperable patients with NICTH, treatment of hypoglycemia may require high doses of glucocorticoid (30-60 mg/d [0.5-1.0 mg/kg x d]) or recombinant human GH (rhGH) (2.6-12.0 mg/d [0.043-0.20 mg/kg x d]).
We hypothesized that the association of low doses of glucocorticoid and rhGH could be an effective therapy for hypoglycemia in inoperable patients with NICTH.
A 3-phase treatment regimen was conducted in an inoperable 67-year-old woman with NICTH. Decreasing dosages of prednisone (from 30 to 10 mg/d [from 0.50 to 0.15 mg/kg x d]), followed by decreasing doses of rhGH (from 2.6 to 1.3 mg/d [from 0.043 to 0.016 mg/kg x d]), and then a combination of the lowest doses of each, were tested. Glucose, insulin, and IGF monitoring were performed at each of the 3 treatment phases.
Fasting plasma glucose (FPG) level was normalized and the IGF-1 concentration was increased with high-dose prednisone monotherapy (30 mg/d [0.50 mg/kg x d]) or rhGH (2.6 mg/d [0.043 mg/kg x d]). Prednisone monotherapy partially suppressed big IGF-2 secretion, and rhGH monotherapy acted on IGFBP-3 and ALS concentrations. FPG level was normalized with combined low-dose prednisone and rhGH, and this combination was more effective than high-dose monotherapy with either drug in reestablishing the IGF system. No adverse effects (AEs) were found.
In this patient with inoperable NICTH, the combination of low doses of prednisone and rhGH was a successful long-term therapy for hypoglycemia, with no AEs. This therapy could be proposed for use in patients with inoperable NICTH.
非胰岛细胞瘤性低血糖症（NICTH）是反复发生低血糖的罕见原因。它与高分子量胰岛素样生长因子（IGF）-2（“大IGF-2”）的肿瘤过度产生有关。大IGF-2抑制生长激素（GH）的生物合成，并通过抑制含有IGF、IGF结合蛋白3（IGFBP-3）和酸性不稳定亚基（ALS）的GH依赖性三元复合物的形成来损害IGF的储存。因此，大IGF-2具有降血糖活性。NICTH唯一有效的治疗方法是手术。然而，对于无法手术的NICTH患者，低血糖的治疗可能需要高剂量的糖皮质激素（30 - 60 mg/d [0.5 - 1.0 mg/kg×d]）或重组人生长激素（rhGH）（2.6 - 12.0 mg/d [0.043 - 0.20 mg/kg×d]）。
我们假设低剂量糖皮质激素和rhGH联合使用可能是无法手术的NICTH患者低血糖的有效治疗方法。
对一名67岁无法手术的NICTH女性患者进行了为期3个阶段的治疗方案。依次测试了泼尼松剂量递减（从30 mg/d [0.50 mg/kg×d]降至10 mg/d [0.15 mg/kg×d]）、rhGH剂量递减（从2.6 mg/d [0.043 mg/kg×d]降至1.3 mg/d [0.016 mg/kg×d]），然后是两者最低剂量联合使用的情况。在3个治疗阶段的每个阶段都进行了血糖、胰岛素和IGF监测。
高剂量泼尼松单药治疗（30 mg/d [0.50 mg/kg×d]）或rhGH单药治疗（2.6 mg/d [0.043 mg/kg×d]）时，空腹血糖（FPG）水平恢复正常，IGF-1浓度升高。泼尼松单药治疗部分抑制了大IGF-2的分泌，rhGH单药治疗影响了IGFBP-3和ALS的浓度。低剂量泼尼松和rhGH联合使用时FPG水平恢复正常，并且这种联合在重建IGF系统方面比任何一种药物的高剂量单药治疗更有效。未发现不良反应（AE）。
在这名无法手术的NICTH患者中，低剂量泼尼松和rhGH联合使用是低血糖的成功长期治疗方法，且无不良反应。这种治疗方法可推荐用于无法手术治疗的NICTH患者。
