Ori Eyal

Treatment with recombinant human growth hormone during childhood is associated with increased intraocular pressure.

OBJECTIVE To evaluate the association between recombinant human growth hormone (rhGH) treatment and intraocular pressure (IOP) in children. STUDY DESIGN This is an observational cohort study including comparison between children treated with rhGH for at least 12 months (treatment group), matched children prior to treatment (control group), and population age-adjusted normograms of IOP. All children underwent an ocular slit lamp assessment and Goldmann applanation tonometry. Charts were reviewed for cause of therapy, peak stimulated growth hormone level prior to therapy, treatment duration, insulin-like growth factor 1, and rhGH dosage. RESULTS The treatment group included 55 children and the control group included 24 children. Mean age at examination was comparable at 11.4 ± 3.3 years and 10.3 ± 2.6 years, respectively (P = .13). Mean treatment duration was 37.5 ± 22.8 months and mean rhGH dose was 0.04 ± 0.01 mg/kg/d. Mean IOP was significantly increased in the treatment group compared with the control group and compared with age-matched normograms (16.09 ± 2.2 mm Hg, 13.26 ± 1.83 mm Hg and 14.6 ± 1.97 mm Hg, respectively, P < .001). IOP was positively correlated with treatment duration (r = 0.559, P < .001) and rhGH dosage (r = 0.274, P = .043). CONCLUSION IOP in children treated with rhGH is increased compared with a similar population without treatment and compared with healthy population normograms. IOP is associated with longer treatment duration and higher dosages.

Homozygous p.V116* mutation in C12orf65 results in Leigh syndrome

Background Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder associated with mitochondrial dysfunction. LS is characterised by elevated lactate and pyruvate and bilateral symmetric hyperintense lesions in the basal ganglia, thalamus, brainstem, cerebral white matter or spinal cord on T2-weighted MRI. LS is a genetically heterogeneous disease, and to date mutations in approximately 40 genes related to mitochondrial function have been linked to the disorder. Methods We investigated a pair of female monozygotic twins diagnosed with LS from consanguineous healthy parents of Indian origin. Their common clinical features included optic atrophy, ophthalmoplegia, spastic paraparesis and mild intellectual disability. High-blood lactate and high-intensity signal in the brainstem on T2-weighted MRI were consistent with a clinical diagnosis of LS. To identify the genetic cause of their condition, we performed whole exome sequencing. Results We identified a homozygous nonsense mutation in C12orf65 (NM_001143905; c.346delG, p.V116*) in the affected twins. Interestingly, the identical mutation was previously reported in an Indian family with Charcot-Marie Tooth disease type 6, which displayed some overlapping clinical features with the twins. Conclusions We demonstrate that the identical nonsense mutation in C12orf65 can result in different clinical features, suggesting the involvement of unknown modifiers.

A Prototype of a New Noninvasive Device to Detect Nocturnal Hypoglycemia in Adolescents with Type 1 Diabetes—A Pilot Study

BACKGROUND Severe hypoglycemic events are a major consequence of tight diabetes control. Continuous glucose monitoring systems (CGMSs) were recently introduced in order to minimize the risk of hypoglycemia. However, the present CGMSs are invasive and costly and have been recently demonstrated to be intolerant for most children and adolescents. Hence there is a need for a simple, noninvasive, convenient, and inexpensive device to detect hypoglycemic events. The Gili Medical Hypoglycemia Non Invasive Monitoring System (GMHNIMS) (Gili Medical Ltd., Migdal HaEmek, Israel) has been currently developed for these purposes. SUBJECTS AND METHODS Ten patients 14-18 years old with type 1 diabetes for at least 1 year participated in a pilot study that was held at the Meyer Childrens Hospital, Rambam Medical Center, Haifa, Israel. All patients were either treated by insulin pump or by multiple daily injections. The GMHNIMS was connected to the study subjects during three consecutive nights in an inpatient setting while they received their usual insulin regimen. The system is composed of four sensors (heart rate, perspiration, skin temperature, and tremor) that detect physiologic changes during hypoglycemia. In addition, each patient was connected to a real-time CGMS for 3 nights. When a hypoglycemic event was suspected clinically by the patient, a bedside capillary glucose was checked by a glucometer. RESULTS The system was found to be convenient without any disturbances to sleep quality. The sensitivity of the GMHNIMS for detection of true hypoglycemic events was 100% with specificity of 85.7%. CONCLUSIONS The new device showed high detection rates of nocturnal hypoglycemic events with an acceptable degree of false-positive readings. Being inexpensive and noninvasive, this device has the potential for routine use in insulin-treated patients.

Establishing Normal Ranges of Basal and ACTH-Stimulated Serum Free Cortisol in Children.

Background: Normative data have been established for stimulated serum total cortisol in children but not for serum free cortisol. Methods: Children who were referred for ACTH testing to rule out adrenal insufficiency were enrolled. Only children with normal response and normal androgen levels were included. Total cortisol was determined by a chemiluminescence method, and free cortisol was measured by the same method following equilibrium dialysis. Results: The study group consisted of 85 subjects (28 male; 57 female) with a median age of 8.5 years (range 0.6-17.7). The mean basal and peak total cortisol levels were 11.5 ± 5.7 and 32.9 ± 6.2 μg/dl, respectively. The mean basal and peak free cortisol levels were 0.4 ± 0.3 and 1.8 ± 0.6 μg/dl, respectively. There was a negative correlation between peak total cortisol and age but not between peak free cortisol and age. The 3rd and 97th percentile values for peak free cortisol were 0.94 μg/dl (26 nmol/l) and 2.97 μg/dl (82 nmol/l), respectively. Conclusions: Measurement of free cortisol has the advantage of being independent of cortisol-binding globulin levels. This study provides reference ranges for stimulated free cortisol in children, with a cutoff value of 0.9 μg/dl (25 nmol/l) as a normal response to a standard ACTH test.

Prevalence of early and late prematurity is similar among pediatric type 1 diabetes patients and the general population

The incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades, as has the incidence of preterm births (<37 weeks). We aimed to evaluate and compare the prevalence of prematurity and early prematurity (<34 weeks) and birth season variability among T1DM and non‐T1DM children.

The effect of CAG repeats length on differences in hirsutism among healthy Israeli women of different ethnicities

[This corrects the article DOI: 10.1371/journal.pone.0195046.].

SERUM FREE CORTISOL DURING GLUCAGON STIMULATION TEST IN HEALTHY SHORT-STATURED CHILDREN AND ADOLESCENTS

OBJECTIVE The total cortisol (TC) response may be measured during the glucagon stimulation test (GST) for growth hormone (GH) reserve in order to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements of TC are unreliable in conditions of albumin and cortisol-binding globulin (CBG) alterations (e.g., hypoproteinemia or CBG deficiency). We aimed to measure the serum free cortisol (sFC) response to the GST in children and adolescents and determine whether it could predict the GH response to glucagon stimulation. METHODS Infants and children with either short stature or growth attenuation who were referred for evaluation of GH reserve underwent the GST. RESULTS The study population consisted of 103 subjects (62 females), median age 3.9 years (range, 0.5-14). The mean basal and peak TC levels were 13.3 ± 6.7 μg/dL and 29.6 ± 8.8 μg/dL, respectively. The mean basal and peak sFC levels were 0.7 ± 0.8 μg/dL and 1.7 ± 1.1 μg/dL, respectively. There was a negative correlation between peak TC and age ( r = -0.3, P = .007) but not between peak sFC and age ( r = -0.09, P = .36). Ninety-five percent of the patients had peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL. CONCLUSION Our results on a cohort of healthy short-statured children can serve as reference values for the sFC response during GST. Based on these results, we propose peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL for defining normalcy of the HPA axis during the GST in children and adolescents. ABBREVIATIONS ACTH = adrenocorticotrophic hormone BMI = body mass index CBG = cortisol-binding globulin GH = growth hormone GST = glucagon stimulation test HPA = hypothalamic-pituitary-adrenal SDS = standard deviation score sFC = serum free cortisol TC = total cortisol.

Front and Back Matter

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