Sivan Bezalel, Lilos Pearl, Laron Zvi
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center, Petah Tikva, Israel.
J Pediatr Endocrinol Metab. 2003 Apr-May;16(4):509-20. doi: 10.1515/jpem.2003.16.4.509.
Primary insulin-like growth factor-I (IGF-I) deficiencies, such as in Laron syndrome (LS), are a unique model in man to study the consequences resulting from defects in growth hormone (GH) signal transmission.
To assess retrospectively the effect of IGF-I deficiency and its therapy on the various cells of the hematopoietic system as reflected by peripheral blood counts.
Two groups of patients were studied. The first group consisted of 11 untreated patients with LS, seven males and four females, who were followed from childhood into adult age. Average age at the time of data analysis was 45.4 +/- 9.6 years. The second group included ten children with LS, six males and four females, who received IGF-I replacement therapy for an average period of 6 years, ranging in age from 0.9-11 years. The mean age at initiation of therapy was 6.9 +/- 4.28 years. Only the seven children treated for 5 years or more were included in the analysis. Data on blood counts were collected from the patients' charts. Blood samples were drawn at baseline, weekly during the first month, once a month during the first year, and once every 3 months thereafter. Statistical analysis of the change over time was performed using repeated measures ANOVA.
Children with LS had red cell indices in the lower normal range and an elevated monocyte count. A statistically significant rise in red blood cell (RBC) indices was seen in children during IGF-I therapy: RBC rose from 4.66 x 10(6)/ml to 4.93 x 10(6)/ml (p = 0.011); hemoglobin from 11.55 g/dl to 13.01 g/dl (p < 0.001); hematocrit from 34.94% to 38.52% (p = 0.007), and mean corpuscular volume from 72.27 fl to 79.93 fl (p < 0.001). The platelet count diminished significantly during IGF-I therapy from 316 x 10(3)/ml to 219 x 10(3)/ml (p = 0.02), and the monocyte count from 0.74 x 10(3)/ml to 0.49 x 10(3)/ml (p < 0.001).
The present investigation, the first of its kind in this syndrome, confirms that IGF-I has a strong stimulatory effect on erythropoiesis. In addition, IGF-I therapy had a reducing effect on monocytes and platelets, an effect not previously described. The mechanism by which IGF-I mediates these effects needs further elucidation.
原发性胰岛素样生长因子-I（IGF-I）缺乏症，如拉伦综合征（LS），是研究生长激素（GH）信号传递缺陷所导致后果的独特人类模型。
通过外周血细胞计数回顾性评估IGF-I缺乏及其治疗对造血系统各种细胞的影响。
研究了两组患者。第一组由11例未经治疗的LS患者组成，其中7例男性，4例女性，从儿童期随访至成年期。数据分析时的平均年龄为45.4±9.6岁。第二组包括10例LS儿童，其中6例男性，4例女性，接受IGF-I替代治疗平均6年，年龄范围为0.9 - 11岁。治疗开始时的平均年龄为6.9±4.28岁。仅将接受治疗5年或更长时间的7例儿童纳入分析。从患者病历中收集血细胞计数数据。在基线、第一个月每周、第一年每月、此后每3个月采集血样。使用重复测量方差分析对随时间的变化进行统计分析。
LS儿童的红细胞指数处于正常范围下限，单核细胞计数升高。IGF-I治疗期间儿童的红细胞（RBC）指数有统计学意义的升高：RBC从4.66×10⁶/ml升至4.93×10⁶/ml（p = 0.011）；血红蛋白从11.55 g/dl升至13.01 g/dl（p < 0.001）；血细胞比容从34.94%升至38.52%（p = 0.007），平均红细胞体积从72.27 fl升至79.93 fl（p < 0.001）。IGF-I治疗期间血小板计数从316×10³/ml显著降至219×10³/ml（p = 0.02），单核细胞计数从0.74×10³/ml降至0.49×10³/ml（p < 0.001）。
本研究是该综合征的首例此类研究，证实IGF-I对红细胞生成有强烈刺激作用。此外，IGF-I治疗对单核细胞和血小板有降低作用，这一作用此前未被描述。IGF-I介导这些作用的机制需要进一步阐明。
