ABSTRACT: To compare foot length deficits between patients with Laron syndrome (LS) (primary growth hormone [GH] insensitivity) and congenital isolated GH deficiency (IGHD) and their response to replacement therapy with insulin-like growth factor-I (IGF-I) and hGH, respectively.
Data for the study were collected from the records of nine children with LS (3 M, 6 F) 7.8 +/- 4.8 years old (mean +/- SD), and nine children with IGHD (3 M, 6 F), 3.8 +/- 3.3 years old. Fifteen non-treated adult patients with LS were also included in the study.
Measurements of foot length were recorded without treatment and monitored during 9 years of treatment in the children and in the untreated adult patients. For statistical analysis the non-parametric Mann-Whitney U test was used.
With almost similar basal values in growth deficit and pre-treatment growth velocities, the achievements towards norms after 9 years of treatment were greater in the patients with IGHD than in the patients with LS: foot length reached -1.4 +/- 0.8 vs. -3.3 +/- 1.0 SDS (mean +/- SD), and body height -2.2 +/- 1.0 vs. -3.9 +/- 0.5 SDS. The difference between the two groups could be due to the initiation of replacement therapy in the patients with IGHD at a younger age. Adult foot size of untreated patients with LS is small but less retarded than the height deficit.
Both IGF-I and hGH are potent growth stimulating hormones of linear growth and acrae as exemplified by foot growth.
Journal of pediatric endocrinology & metabolism: JPEM 01/2008; 20(12):1325-8. · 0.88 Impact Factor
ABSTRACT: To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia.
Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls.
Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females.
Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition.
Lifelong congenital IGF-I deficiency leads to extreme adiposity.
Clinical Endocrinology 08/2006; 65(1):114-7. · 3.17 Impact Factor
ABSTRACT: To evaluate the ocular dimensions in patients with primary growth hormone receptor insensitivity (Laron syndrome [LS]) and to study the effect of supplemental insulinlike growth factor I (IGF-I) on ocular growth.
Retrospective case series.
Twelve patients with LS, 8 untreated (LS group) and 4 treated (LS-T group) with supplemental IGF-I, and 30 healthy controls.
Ocular dimensions and refraction were measured, and a full ophthalmologic examination was performed.
Differences in the average ocular dimension data among IGF-I-treated patients, untreated ones, and controls.
The average axial length of eyes in the LS group was 21.94 mm (standard deviation [SD], 0.81). Corresponding values for the LS-T and control group eyes were 22.53 mm (SD, 1.74) and 23.20 mm (SD, 1.35) respectively. The average anterior chamber depth of eyes in the LS group was 2.55 mm (SD, 0.26). Corresponding values for eyes in the LS-T and control groups were 3.48 mm (SD, 0.09) and 3.84 mm (SD, 0.16) respectively. The average lens thickness of eyes in the LS group was 4.56 mm (SD, 0.36). Corresponding values for the LS-T and control groups were 3.77 mm (SD, 0.23) and 3.51 mm (SD, 0.25), respectively. The average corneal curvature of eyes in the LS group was 46.9 diopters (D) (SD, 2.32). Corresponding values for the LS-T and control groups were 47.6 D (SD, 2.83) and 44.4 D (SD, 1.5), respectively.
Insulinlike growth factor I seems to be an important regulator of ocular growth as documented in patients with primary growth hormone insensitivity. The mechanism of this observation should be investigated further.
Ophthalmology 08/2006; 113(7):1197.e1-5. · 5.45 Impact Factor
ABSTRACT: To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS).
Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII).
Tertiary care, university-affiliated medical center. Patients Twenty-three children and adolescents with type 1 diabetes mellitus.
The CGMS was applied for 72 hours after 1 month and at the end of each study arm.
Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm.
The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04).
Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia.
Archives of Pediatrics and Adolescent Medicine 08/2004; 158(7):677-84. · 4.14 Impact Factor
ABSTRACT: To compare the efficacy and feasibility of continuous subcutaneous insulin infusion (CSII) with multiple daily insulin injections (MDI) in children with type 1 diabetes.
The study sample included 23 children (10 males) aged 9.4 to 13.9 years with type 1 diabetes. An open randomized crossover design was used to compare 3.5 months of CSII to 3.5 months of MDI therapy for the following variables: diabetic control, incidence of adverse events, daily insulin requirement, body mass index standard deviation scores, treatment satisfaction, and quality of life.
The changes in HbA(1c) and fructoseamine values were similar in the 2 arms over time. At the end of the study, mean HbA(1c) level measured 8.05 +/- 0.78%. There were no differences between the treatment modes in frequency of symptomatic hypoglycemic or hyperglycemic events. There was 1 event of severe hypoglycemia during pump therapy and 3 during MDI, yielding a rate of 0.26 events per patient-year. There were no episodes of diabetic ketoacidosis. Body mass index standard deviation scores decreased during CSII and increased during MDI, as did mean insulin dose. Patients expressed a higher treatment satisfaction from CSII than MDI, although there was no difference in quality of life between the 2 modes.
Intensive insulin therapy by either insulin pump or MDI is safe in children and young adolescents with type 1 diabetes, with similar diabetes control and a very low rate of adverse events. We suggest that both modes be available to the diabetic team to better tailor therapy.
PEDIATRICS 10/2003; 112(3 Pt 1):559-64. · 4.47 Impact Factor
ABSTRACT: While regular yearly screening for diabetic retinopathy and nephropathy is well established in patients with diabetes mellitus, there are no standardized diagnostic tests for diabetic peripheral neuropathy (DPN). In the present study, we compared the bedside neuropathy disability score (NDS) with quantitative sensory testing (QST) for screening for DPN in youth with type 1 diabetes mellitus.
One hundred sixty-six patients aged 10 to 34 years (median 21 years) were evaluated for DPN by the NDS and QST. Quantitative sensory testing was also done in 43 healthy, age-matched controls. Diabetic peripheral neuropathy grade by both methods was correlated with disease-related variables.
On QST, the diabetic group had significantly higher mean scores for vibration (P<.001) and warm sensation (P<.01) than controls, and lower scores for cold sensation (P<.05); however, there was a great degree of overlap. The NDS significantly correlated with the vibration threshold, but not with the warm and cold thresholds. The NDS significantly correlated with age at testing, diabetes duration, and long-term and current HbA1c levels (P<.001), and with the presence of microalbuminuria and diabetic retinopathy (P<.001). Analysis of the QST variables yielded significant correlations of vibration and warm sensation with age at testing (P<.001, P<.05, respectively) and of vibration with diabetes duration (P<.001) and retinopathy (P=.05); none of the quantitative tests correlated with glycemic control.
The stronger association of the NDS with glycemic control and other microvascular complications compared to the perception thresholds, and its shorter time of performance and lack of costly equipment, may make the NDS the preferred method for measuring DPN in this population.
Journal of Diabetes and its Complications 21(1):13-9. · 2.03 Impact Factor
ABSTRACT: The cortisol response in patients with nonclassical 21-hydroxylase deficiency (NC21OHD) was assessed before and during hydrocortisone therapy and the findings were related to genotype.
The study sample comprised 41 patients (10 males) with NC21OHD, divided into two groups according to the genetic analysis of the CYP21 gene: Group A carried two mild mutations (n = 29), and Group B were compound heterozygotes for one mild and one severe mutation (n = 12). The 250 microg short ACTH test was performed at diagnosis. To evaluate the degree of treatment-induced suppression of adrenal function, 31 patients also underwent the 1 microg/1.73 m2 ACTH test during hydrocortisone therapy. Basal and stimulated cortisol levels and the increment in cortisol response were compared between Groups A and B and between the whole patient sample and healthy controls (32 subjects for the 250 microg test and 29 for the 1 microg/1.73 m2 test).
The basal, stimulated, and incremental cortisol levels were similar in Groups A and B; therefore, all the patients were considered together. At diagnosis, the basal cortisol levels were similar in the patients and controls, but the stimulated and incremental cortisol levels were significantly lower in the patients (p <0.001 for both). During hydrocortisone therapy, the patients had slightly higher basal cortisol levels than the controls (p = 0.04), but significantly lower stimulated and incremental cortisol levels (p <0.001 for both).
Cortisol levels in NC21OHD are similar in patients carrying two mild mutations and in compound heterozygotes for one mild and one severe mutation. Stimulated and incremental cortisol levels in response to the short ACTH test might be decreased not only during but also before hydrocortisone therapy. Therefore, coverage with a stress dose of hydrocortisone during serious intercurrent illness or surgery is recommended in patients with NC21OHD, especially those previously treated with corticosteroids.
Journal of pediatric endocrinology & metabolism: JPEM 15(7):985-91. · 0.88 Impact Factor
ABSTRACT: 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.
Journal of pediatric endocrinology & metabolism: JPEM 16(4):509-20. · 0.88 Impact Factor