Effects of insulin-like growth factor-I deficiency and replacement therapy on the hematopoietic system in patients with Laron syndrome (primary growth hormone insensitivity).
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Sivan
Bezalel
B
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center, Petah Tikva, Israel.
Lilos
Pearl
P
Laron
Zvi
Z
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004906:Erythrocyte Count; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D006400:Hematocrit; D006410:Hematopoiesis / Q000187:drug effects*; D006454:Hemoglobins; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000172:deficiency* / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D010976:Platelet Count; D012189:Retrospective Studies
D006454:Hemoglobins; D007334:Insulin-Like Growth Factor I