Adherence to growth hormone therapy: results of a multicenter study.

OBJECTIVE: To evaluate the adherence to growth hormone (GH) therapy and identify the influencing factors and outcomes in children. METHODS: A total of 217 GH-naïve patients in 6 pediatric endocrinology clinics were enrolled in the study. Structured questionnaires were filled out and patients were evaluated at the initiation and 3rd, 6th, and 12th months of therapy. Patients were categorized into 4 adherence segments based on percentage of doses omitted at each evaluation period, classified as excellent if 0%, good if 5%, fair if 5 to 10%, and poor if > 10%. RESULTS: There was a decrement in adherence to GH therapy during the study period (P = .006). Patients who showed excellent and good adherence to therapy had better growth velocity and growth velocity standard deviation scores (SDSs) (P = .014 and P = .015, respectively). A negative correlation between growth velocity SDS and number of missed injections was also observed (r = -.412; P = .007). A positive correlation between delta insulin-like growth factor-1 (IGF-1) SDS and growth velocity was demonstrated (r = .239; P = .042). IGF-1 levels were significantly higher in patients who showed excellent and good adherence to therapy (P = .01). Adherence was better in boys than in girls (P = .035), but adherence rates were not associated with age, cause of GH treatment, socioeconomic status, person who administered the injections, type of injection device, or GH product. CONCLUSION: Poor adherence to GH therapy was common in our group of patients and was one of the factors underlying suboptimal growth during therapy. Before considering other problems that can affect growth, clinicians should confirm good adherence to therapy.

Increased Carotid Intima-media Thickness and Its Association with Carbohydrate Metabolism and Adipocytokines in Children Treated with Recombinant Growth Hormone

Objective: Reports on the association between growth hormone (GH) therapy and cardiovascular risk factors in children are limited. This study aimed to evaluate carotid intima-media thickness (cIMT) in children treated with recombinant human GH (rhGH) and assess the effects of rhGH therapy and changes in serum carbohydrate metabolism, lipid profile and adipocytokines on cIMT. Methods: Seventy-one isolated idiopathic GH deficiency (GHD) children and 44 age- and sex-matched healthy controls were enrolled in this study. The study group was divided into two subgroups according to insulin resistance (IR) on oral glucose tolerance tests. Insulin secretion [homeostatic model assessment (HOMA) B, total insulin] and sensitivity (HOMA-IR, QUICKI, Matsuda) indices were calculated. cIMT was measured and the standard deviation scores (SDS) were calculated. Associations between cIMT-SDS and insulin secretion and sensitivity indices, serum lipid levels, adipocytokines (leptin, resistin, ghrelin), and other rhGH treatment-related factors were evaluated. Results: cIMT-SDS was increased in GHD children treated with rhGH compared to the controls [0.02 (2.27) vs. -1.01 (1.63), p=0.003]. cIMT-SDS did not differ between those children on rhGH treatment with or without IR. High cIMT-SDS was significantly associated with higher serum ghrelin levels and lower serum high density lipoprotein (HDL) levels (ß=0.491, p=0.001 and ß=-0.027, p=0.017), but not with BMI-SDS, blood pressure, insulin secretion and sensitivity indices, or the dose and duration of rhGH therapy. Conclusion: Our findings showed that GHD children treated with rhGH have increased cIMT. Alterations in carbohydrate metabolism were not associated with cIMT in children treated with rhGH. GH therapy per se appears to be associated with this increased cIMT but causality should be elucidated in further studies. cIMT also appears to be associated with higher ghrelin and lower HDL levels.

The effect of growth hormone treatment on head circumference in growth hormone-deficient children.

The aim of this study was to analyze head circumference (HC) growth retrospectively in longitudinally followed growth hormone (GH)-deficient children on GH therapy. Data of 54 (25 F, 29 M) children with GH deficiency were analyzed by dividing the children into two groups: Group 1 with height age (HA) < or =5 years (yrs) (n:18) and Group 2 with HA >5 yrs (n:36). Anthropometric measurements were expressed as standard deviation score (SDS) for chronological age (CA), and HC was also expressed as SDS for CA and HA. Group 1, with CA 6.6 (2.9) yrs at onset of therapy, showed an increase in height SDS from -3.8 (1.4) to -2.4 (1.7) (p < 0.001) and in HC SDS for CA from -1.9 (1.5) to -1.3 (1.6) (p < 0.05) on 4.8 (3.5) yrs of therapy. Group 2, with CA 12.6(2.2) yrs, increased height SDS from -3.4 (1.3) to -2.5 (1.4) (p < 0.001) and HC SDS for CA from -1.2 (1.3) to -1.4(1.2) (NS). HC SDS for HA was -0.4(1.3) in Group 1 and -0.2 (1.1) in Group 2 and showed no significant change. When analyzed by quartiles for cumulative dose of GH, HC SDS for HA became 0.08(1.2) in the fourth dosage quartile (p = 0.043), not significantly different from the mean. HC is disproportionately small for age but normal for the height. GH treatment results in an increase in HC of the children towards normalization in younger children. An increase in cumulative GH dose is associated with an increase in HC, but this is not inappropriate.

Catch-up growth in appropriate- or small-for-gestational age preterm infants.

The aim was to evaluate postnatal growth of preterm infants in childhood and to determine factors that have an effect on catch-up growth (CUG). Ninety-six (42F, 54M) preterm born children with a gestational age of 32.6+/-2.9 weeks and birth weight of 1815+/-668 g were evaluated at age 4.7+/-1.1 years. Preterm children with birth weight and/or length below 10th percentile were accepted as small-for-gestational age (SGA) and those above as appropriate-for-gestational age (AGA). Height SDS was similar (-0.5+/-1.0) in preterm AGA and SGA children. Both groups had low body mass index (BMI) SDS (-0.6+/-1.4 and -1.0+/-1.5, respectively). Of the preterm SGA children, 65.8% showed a CUG in height and 3.8% catch- down growth. These rates were 24.6% and 33.5% in preterm AGA children. CUG in height was best explained by birth length and mother's height and CUG in weight by birth weight and mother's weight. In conclusion, although most of the preterm SGA children show CUG, they reach a compromised height in childhood. A number of preterm AGA children show a catch-down growth.

Ultrasonic evaluation of early atherosclerosis in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: To assess early atherosclerosis using B-mode imaging of the carotid artery in children and adolescents with type 1 diabetes mellitus (T1DM) and to evaluate the relationship between various risk factors and intimal plus medial thickness (IMT) in this population. METHODS: Fifty-two children and adolescents (aged 3-18 years) with uncomplicated T1DM and 43 age- and gender-matched healthy controls were examined. B-mode imaging was used to determine the intimal plus medial thickness (IMT) of the carotid artery in all subjects. Patients with T1DM and control subjects were divided into two groups according to age and gender. Furthermore, duration of DM was considered for comparison. RESULTS: Patients and control subjects showed no association between IMT and sex, systolic blood pressure (sBP), diastolic blood pressure (dBP), serum lipid levels or left ventricular ejection fraction (LVEF). However, statistical analysis indicated a good correlation between age and carotid arterial wall thickness in both diabetic and control groups. These findings were consistent with those in the literature. No correlation was found between IMT and the duration of DM. CONCLUSIONS: This study indicates that there is no association between T1DM and IMT in children and adolescents with T1DM.

Reevaluation of growth hormone deficiency during and after growth hormone (GH) treatment: diagnostic value of GH tests and IGF-I and IGFBP-3 measurements.

Retesting of patients with growth hormone (GH) deficiency (GHD), especially those with idiopathic GHD, has yielded normalization of the results in several studies. The aim of this study was to reevaluate patients diagnosed as GHD at completion or reconfirm the diagnosis before completion of GH treatment by retesting with provocative tests, and to evaluate the value of IGF-I and IGFBP-3 levels in the diagnosis of GHD. Fifty (33 M, 17 F) patients with GHD (peak GH level <0.46 pmol/l (10 ng/ml]) in two pharmacological tests were retested and IGF-I and IGFBP-3 levels measured. The age of the patients at retest was 15.2+/-5.0 yr. Thirteen of 50 patients (26%) normalized their GH secretion. According to the initial diagnosis, 69% of those with partial GHD (peak GH level 0.32-0.46 pmol/l [7-10 ng/ml]), 43% with isolated GHD, 33% idiopathic and 11% of those with complete GHD (peak GH level <0.32 pmol/l [7 ng/ml]) normalized their GH level at retesting. None of the patients with multiple hormone deficiency and none with small pituitary on MRI normalized GH levels at retest. The sensitivities of IGF-I and of IGFBP-3 were 70% and 67%, respectively, and the specificities were 100%, when peak GH cutoff is taken as 0.46 pmol/l (10 ng/ml) for the diagnosis of GHD. The sensitivities of IGF-I and IGFBP-3 increased to 76.5% and 73.5% when the cutoff level for GHD is taken as 0.32 pmol/l (7 ng/ml). Those patients who normalized their GH levels at retest showed a satisfactory height velocity when GH therapy was discontinued. In conclusion, reevaluation of GH status may also be undertaken while patients are still on treatment as well as at completion of treatment, especially in patients with idiopathic, partial and isolated GHD, by retesting and by IGF-I and IGFBP-3 measurements. Lowering the cutoff level of GH peak at pharmacological tests to 0.32 pmol/l (7 ng/ml) will lower the number of false positive results in the diagnosis of GHD.

Frequency and severity of ketoacidosis at onset of autoimmune type 1 diabetes over the past decade in children referred to a tertiary paediatric care centre: potential impact of a national programme highlighted.

AIMS: To assess the frequency and severity of diabetic ketoacidosis (DKA) at disease onset in children newly diagnosed with autoimmune type 1 diabetes (T1D) in Istanbul in the last decade. Also, to evaluate the potential contribution of the national diabetes awareness programme (NDAP) initiated in 2010. METHODS: Four hundred and one consecutive children (mean ± standard deviation, age 8.1 ± 4.1 years) with a diagnosis of autoimmune T1D were evaluated retrospectively with respect to demographic, clinical, and laboratory data in relation to DKA at disease onset. The possible impact of NDAP on the rate of DKA at disease onset in the last 2 years was also evaluated by comparing the data related to the time intervals before and after the onset of the programme. The results were evaluated at 95% confidence interval and significance was granted for p ≤ 0.05. RESULTS: The overall frequency of DKA at disease onset was 44.2%, with a significant trend for decline in rate of DKA at disease onset in the last decade (p=0.0001). There were no significant differences in proportions of newly diagnosed T1D patients with severe or moderate DKA over time. Mean body mass index standard deviation score tended to increase in the last decade, but not significantly (p=0.09). When the time intervals before and after the onset of NDAP were evaluated, there was a more than two-fold decrease in rate of DKA (from 49.3% to 23.9%) (p<0.0001). CONCLUSIONS: The frequency of a DKA event at onset of T1D is still high in Istanbul children despite a decreasing trend in the last decade. NDAP may significantly contribute to the reduction in rate of DKA.