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Kornreich L.,Tel Aviv University | Konen O.,Tel Aviv University | Lilos P.,Endocrinology and Diabetes Research Unit | Lilos P.,Tel Aviv University | And 2 more authors.
American Journal of Neuroradiology | Year: 2011

BACKGROUND AND PURPOSE: Patients with LS have an inborn growth hormone resistance, resulting in failure to generate IGF-1. The purpose of this study was to evaluate the size of the eye and orbit in LS. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging of the brain in 9 patients with LS for the following parameters: axial diameter of the globe, interzygomatic distance, perpendicular distance from the interzygomatic line to margins of the globe, medial-to-lateral diameter of the orbit at the anterior orbital rim, distance from the anterior orbital rim to the anterior globe, maximal distance between the medial walls of the orbits, lateral orbital wall angle, lateral orbital wall length, and mediolateral thickness of the intraorbital fat in the most cranial image of the orbit. All measurements were made bilaterally. Twenty patients referred for MR imaging for unrelated reasons served as control subjects. RESULTS: Compared with the control group, the patients with LS had a significantly smaller maximal globe diameter and shallower but wider orbits due to a shorter lateral wall, a smaller medial distance between the orbits, and a larger angle of the orbit. The ratio between the most anterior orbital diameter and the globe was greater than that in controls. The position of the globe was more anterior in relation to the interzygomatic line. CONCLUSIONS: Shallow and wide orbits and small globes relative to orbital size are seen in LS and may be secondary to IGF-1 deficiency.


Sella T.,Maccabi Healthcare Services | Sella T.,Tel Aviv University | Shoshan A.,Maccabi Healthcare Services | Goren I.,Maccabi Healthcare Services | And 7 more authors.
Diabetic Medicine | Year: 2011

Aims To determine the incidence and examine temporal trends of Type 1 diabetes among children aged < 18 years, in a large Israeli health organization.Methods All incident Type 1 diabetes cases diagnosed between 2000 and 2008 were ascertained from an automated diabetes registry based on members' electronic records and validated by comparison with the Israel Juvenile Diabetes Register.Results During the study period, a total of 648 incident cases of Type 1 diabetes were identified. The average annual age-and-sex-standardized incidence was 11.09 per 100 000 person-years. There was an annual 5.82% (95% CI 1.80-9.98%) rise in incidence, with a greater relative increase in toddlers under 5 years of age. Incidence increased with age and demonstrated seasonal variation. Mean age at onset of diabetes significantly (P = 0.07) decreased from 10.21 years (sd = 4.48) in 2000-2002 to 9.25 years (sd = 4.54) in 2006-2008. Among very young patients (< 5 years), average blood glucose values at diagnosis dropped from 32.4 mmol/l (sd = 9.5) to 19.5 mmol/l (sd = 11.0) over the study period, with little change in average glucose for older children.Conclusions Incidence of diagnosed Type 1 diabetes continues to increase in Israel at a rate that is high compared with similar American and European populations. At the same time, the clinical presentation of children is changing. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.


Attias J.,Haifa University | Attias J.,Institute of Audiology and Clinical Neurophysiology | Zarchi O.,Institute of Audiology and Clinical Neurophysiology | Zarchi O.,Tel Aviv University | And 4 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2012

The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age <2 years, and 1 adolescent who started replacement therapy at bone age 4.6 years. The auditory evaluation included pure tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic emissions, loudness dynamics, auditory brain stem responses and a hyperacusis questionnaire. All untreated patients and the patient who started treatment late had various degrees of sensorineural hearing loss and auditory hypersensitivity; acoustic middle ear reflexes were absent in most of them. All treated children had normal hearing and no auditory hypersensitivity; most had recordable middle ear acoustic reflexes. In conclusion, auditory defects seem to be associated with Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age. © 2011 Springer-Verlag.


PubMed | Endocrinology and diabetes Research Unit, Pediatric Endocrinology Unit, Israel Center for Disease Control and Israel Ministry of Health
Type: Journal Article | Journal: Clinical endocrinology | Year: 2016

The inconclusive evidence regarding long-term safety of recombinant human growth hormone (rhGH) therapy underlines the need for long-term large-scale cohorts.To assess long-term mortality and cancer incidence among patients treated with rhGH during childhood in Israel.A population-based cohort study.Data were retrieved from a national register established in 1988. Mortality data from the national population register were available through 31 December 2014. Data on cancer incidence from the national cancer registry were available through 31 December 2012.All patients 19 years approved for rhGH treatment during 1988-2009 were included. Patients were assigned to three risk categories, according to the underlying condition leading to growth disorder.All-cause mortality and cancer incidence rates were calculated, based on person-years at risk. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated, using the Israeli general population as a reference.Included were 1687 patients assigned to the low-risk category and 440 patients assigned to the intermediate-risk category. In the low-risk category, all-cause mortality and cancer incidence were not significantly different than expected (SMR 081, 95% CI 022-208 and SIR 076, 95% CI 009-273). In the intermediate-risk category, all-cause mortality and cancer incidence were significantly higher than expected (SMR 405, 95% CI 162-834 and SIR 452, 95% CI 122-1157).No increased risk of mortality or cancer incidence was found in low-risk patients treated with rhGH during childhood. Patients with prior risk factors were at higher risk of both mortality and cancer.


Farfel A.,Israel Defense Forces | Derazne E.,Israel Defense Forces | Tzur D.,Israel Defense Forces | Linder N.,Rabin Medical Center | And 3 more authors.
Israel Medical Association Journal | Year: 2012

Background: Measurements of adolescents who at birth were large (long and/or heavy) for gestational age are scant. Objectives: To determine the correlation between birth length and weight in female and male neonates born long and/or overweight for gestational age, with their height and weight at age 17. Methods: We reviewed the records of the Rabin Medical Center for birth data of 96 full-term neonates born long and overweight for gestational age (FT-lo,ow), 33 full-term neonates born long but with normal weight for gestational age (FT-lo,nw), 148 full-term neonates born overweight but with normal length for gestational age (FT-nl,ow), and 401 full-term neonates born with normal birth length and weight (FT-nl,nw). Results: Neonates of both genders born long and overweight at birth (FT-lo,ow) were taller and heavier at age 17 years than those born FT-nl,nw: females 167.8 ± 5.1 cm and 64.6 ± 10.3 kg vs. 162.6 ± 5.5 cm and 59.3 ± 11.1 kg (P < 0.001 for height and P = 0.026 for weight); and males 182.4 ± 8.1 cm and 80.6 ± 20.4 kg vs. 174.5 ± 6.2 cm and 67.4 ± 12.3 kg (P < 0.001). The correlations between birth length and height at age 17 for both genders were statistically significant (P < 0.001), as were those between birth weight and the weight and body mass index (BMI) at age 17 for both genders (P < 0.001). There was no correlation between birth length and weight or BMI at age 17. Conclusions: Full-term neonates of both genders born large for gestational age become tall adolescents and weigh more at age 17 than children with a normal birth length and weight.


Laron Z.,Endocrinology and Diabetes Research Unit | Laron Z.,Tel Aviv University
Pediatric Endocrinology Reviews | Year: 2012

Constitutional tall stature can be anticipated from neonatal length (1) and measurement at age 4 and 8 years (2). Mainly of genetic origin (3) it has been shown that tall children and parents have high normal or higher than normal serum hGH and/or IGF-I levels. (4-6). Also in a healthy adult population a significant (p<0.005) association between height and serum IGF-I has been reported (7). These within normal variations in "healthy" individuals should be distinguished from "gigantism" due to excessive GHR-H or hGH secretion (8, 9) and other pathological conditions leading to tall stature (3).


Steuerman R.,Endocrinology and Diabetes Research Unit | Shevah O.,Endocrinology and Diabetes Research Unit | Laron Z.,Endocrinology and Diabetes Research Unit | Laron Z.,Tel Aviv University
European Journal of Endocrinology | Year: 2011

Objective: To investigate whether congenital IGF1 deficiency confers protection against development of malignancies, by comparing the prevalence of malignancies in patients with congenital (secondary) deficiency of IGF1 with the prevalence of cancer in their family members. Method: Only patients with an ascertained diagnosis of either Laron syndrome (LS), congenital IGHD, congenital multiple pituitary hormone deficiency (cMPHD) including GH or GHRHR defect were included in this study. In addition to our own patients, we performed a worldwide survey and collected data on a total of 538 patients, 752 of their first-degree family members, of which 274 were siblings and 131 were further family members. Results: We found that none of the 230 LS patients developed cancer and that only 1 out of 116 patients with congenital IGHD, also suffering from xeroderma pigmentosum, had a malignancy. Out of 79 patients with GHRHR defects and out of 113 patients with congenital MPHD, we found three patients with cancer in each group. Among the first-degree family members (most heterozygotes) of LS, IGHD and MPHD, we found 30 cases of cancer and 1 suspected. In addition, 31 malignancies were reported among 131 further relatives. Conclusions: Our findings bear heavily on the relationship between GH/IGF1 and cancer. Homozygous patients with congenital IGF1 deficiency and insensitivity to GH such as LS seem protected from future cancer development, even if treated by IGF1. Patients with congenital IGHD also seem protected. © 2011 European Society of Endocrinology.


PubMed | Endocrinology and Diabetes Research Unit
Type: Comparative Study | Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society | Year: 2012

Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth.To determine the effects of long IGF-I deficiency and treatment on HC in patients with Laron syndrome (LS).20 untreated adult LS patients, aged 48.411.2 years and 13 LS patients treated between ages of 5.64 to 11.33 years were studied. 15 patients with congenital IGHD treated between age 6.14 and 134 by hGH served as controls.HC was expressed as standard deviation (SD) and Ht as SDS. HC was measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a Harpenden Stadiometer.The mean HC deficit of the adult untreated LS males was -2.90.6 SD compared to a Ht deficit of -7.01.7 SDS. The HC of the LS adult females was -3.61 SD compared to a Ht SDS of -6.91.5 (p<0.001). IGF-I treatment (150-200 g/kg once daily) increased the HC from -3.30.9 (mSD) to normal values (0.871.8 SD) (p<0.001) in 11/13 children. The Ht SDS deficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the HC from -2.01.8 to 0.31.2 SD and the Ht SDS from -4.81.6 to 1.61.0.


PubMed | Endocrinology and Diabetes Research Unit
Type: Historical Article | Journal: Revue medicale de Bruxelles | Year: 2011

Around 1960, it became clear that, with very few exceptions, the treatment of children with diabetes was not in the hands of paediatricians but in those of adult diabetologists. In 1972, Zvi Laron (Tel Aviv), Henri Lestradet (Paris) and Helmut Loeb (Bruxelles) decided that a separate paediatric association for the care and education of children and adolescents with diabetes was needed. The International Study Group on Diabetes in Children and Adolescents (ISGD) was born. In 1993, the name was changed to the International Society for Pediatric and Adolescent Diabetes (ISPAD). In 2009, a total of 891 members, from 89 countries, was counted. Pediatric Diabetes is the scientific membership journal with an impact factor of 2.424.


Around 1960, it became clear that, with very few exceptions, the treatment of children with diabetes was not in the hands of paediatricians but in those of adult diabetologists. In 1972, Zvi Laron (Tel Aviv), Henri Lestradet (Paris) and Helmut Loeb (Bruxelles) decided that a separate paediatric association for the care and education of children and adolescents with diabetes was needed. The "International Study Group on Diabetes in Children and Adolescents (ISGD)" was born. In 1993, the name was changed to the "International Society for Pediatric and Adolescent Diabetes (ISPAD)". In 2009, a total of 891 members, from 89 countries, was counted. "Pediatric Diabetes" is the scientific membership journal with an impact factor of 2.424.

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