Nehama Zuckerman-Levin

Normal DXA bone mineral density but frail cortical bone in Turner's syndrome

Context  Patients with Turners syndrome have normal bone mineral density by dual energy X‐ray absorptiometry (DXA), but a predisposition for fractures. Quantitative ultrasonography (QUS) measures cortical bone strength.

Physiological and catecholamine response to sympathetic stimulation in turner syndrome.

Objective  Women with Turner syndrome have increased heart rate and high blood pressure (BP), and have been described as having high tolerance for emotional stress. We hypothesized that women with Turner syndrome have reduced catecholaminergic and physiological response to sympathetic stimulation, and that changes in BP and heart rate are related to their catecholamine response to sympathetic stimulation.

Bone health in eating disorders.

Eating disorders (EDs) put adolescents and young adults at risk for impaired bone health.

European Multicentre Study in Children Born Small for Gestational Age with Persistent Short Stature: Comparison of Continuous and Discontinuous Growth Hormone Treatment Regimens

Background: The most effective growth hormone (GH) treatment regimen for increasing height in short children born small for gestational age (SGA) has not been well defined. Methods: Short SGA children (n = 151, age 3–8 years, height less than –2.5 standard deviation scores) were randomised to receive low-dose GH for 2 years (0.033/0.033 mg/kg/day, n = 51), high-dose GH for 1 year and then no treatment for 1 year (0.100/0 mg/kg/day, n = 51) or were untreated for 1 year then received mid-dose GH for 1 year (0/0.067 mg/kg/day, n = 47). Height, bone age and adverse events were determined at check-ups every 3 months. Results: The mean ± SD additional height gain with GH after 1 year, relative to untreated controls, was higher with discontinuous high-dose than with continuous low-dose GH (6.5 ± 0.2 vs. 3.3 ± 0.2 cm). After 2 years, the additional height gain was similar between high- and low-dose GH groups (between-group treatment difference = 0.2, 95% CI = –0.8 to 1.2 cm, p = 0.702). Patients treated exclusively in the last year had a similar height gain to those in the other treatment groups (p = 0.604). Conclusions: In short SGA children, continuous low-dose and discontinuous high-dose GH regimens were associated with similar height gain. Treatment with mid-dose GH for 1 year also led to a similar improvement in growth.

Cortisol-Metabolizing Enzymes in Polycystic Ovary Syndrome.

Objective The aim of this study was to assess the activity of cortisol-metabolizing enzymes in women with polycystic ovary syndrome (PCOS), using a fully quantitative gas chromatography/mass spectrometry (GCMS) method. Design We investigated the glucocorticoid degradation pathways that include llβ-hydroxysteroid dehydrogenase (llβ-HSD) type 1, 5α-reductase (5α-R) and 5β-reductase (5β-R), 3α-hydroxysteroid dehydrogenase, and 20α- and 20β-hydroxysteroid dehydrogenase (20α-HSD and 20β-HSD, respectively) in young nonobese women with PCOS, using a fully quantitative GCMS method. Setting This study was conducted in a tertiary referral hospital in Israel. Patients This study group consisted of 13 young women, aged 20.1 ±2.8 years (mean ± SD), with the body mass index (BMI) of 22.6 ± 3.7 kg/m2, diagnosed with PCOS according to the Rotterdam criteria. The control group consisted of 14 healthy young women matched for weight, height, and BMI. Interventions Urine samples were analyzed using GCMS. We measured urinary steroid metabolites that represent the products and substrates of the study enzymes and calculated the product/substrate ratios to represent enzyme activity. Main Outcome Measures The calculation of enzymatic activity, based on glucocorticoid degradation metabolites, was done by GCMS in PCOS vs. controls. Results All glucocorticoid degradation metabolites were higher in the PCOS group than in controls. Of the adrenal enzymes, the activities of 21-hydroxylase and 17α-hydroxylase were reduced, whereas the activity of 17,20-lyase was enhanced in PCOS. Of the degradation enzymes, the activity of 11β-HSD type 1 was reduced in women with PCOS only when calculated from cortoles and cortolones ratios. The activities of 5α-R/5β-R were increased only when calculating the 11-hydroxy metabolites of androgens. The activity of 20α-HSD was elevated in the patients with PCOS and its relation with the substrate levels was lost. Conclusions We confirm PCOS association with low 21-hydroxylase activity. PCOS is associated with dysregulation in glucocorticoid degradation. The activity of 5α-R is enhanced only through the backdoor pathway. Marked increase in the activity of 20α-HSD suggests a hitherto unknown derangement in PCOS.

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.

11β–Hydroxysteroid Dehydrogenase Type 1 Activity in Short Small-For-GA Children and in Response to GH Therapy

Small for GA (SGA) children are at risk for developing the metabolic syndrome. Those who do not catch up, and remain short (SSGA), may benefit from GH therapy. 11β Hydroxysteroid dehydrogenase type 1 (11β-HSD-1) is expressed in visceral fat and is implicated in metabolic morbidity. We hypothesized that SSGA children will have increased basal and glucocorticoid (GC)-stimulated 11β-HSD-1 activity. Twenty SSGA children, aged 7.1 ± 1 y (mean ± SD), were studied before and while on GH therapy and compared with 12 normal age-matched controls. 11β-HSD-1 activity was evaluated by gas chromatography mass spectrometry (GCMS) of urinary steroid product/substrate ratios. GC-stimulated 11β-HSD-1 activity was assessed after overnight dexamethazone (DEX), by oral cortisone conversion to cortisol. In SSGA children, 11β-HSD-1 activity was lower (p < 0.05) and GC-stimulated activity enhanced. SSGA children had maximal cortisol generation of 883 ± 108 compared with 690 ± 63 nmol/L in controls (p < 0.04). GH treatment suppressed 11β-HSD-1 activity. GC-stimulated enzyme activity correlated negatively with GA (r = −0.53, p < 0.01) and birth weight (r = −0.55, p < 0.01). SSGA is associated with enhanced GC-stimulated 11β-HSD-1 activity. This may be programmed in utero, as it is not a function of body composition or secondary metabolic derangement. GH therapy normalizes GC-stimulated 11β-HSD-1 activity.

Subcutaneous regular insulin for the treatment of diabetic ketoacidosis in children

Diabetic ketoacidosis (DKA) treatment protocols vary, however low‐dose intravenous administration of regular insulin is the standard care for replacing insulin in most centers. Few studies, the majority in adults, demonstrated subcutaneous injection of rapid‐acting insulin every 1–2 hours to be a valid alternative.

Dietary patterns of patients with binge eating disorders with and without night eating

Objective This study aimed to compare dietary patterns (timing and frequency of binge episodes, caloric intake and macronutrient composition) of patients with binge eating disorders (BE) with and without night eating syndrome (NES). Design The study includes 59 women (18–60) who sought treatment for Eating Disorders (EDs) and were diagnosed with BED or BN (BE) with or without NES. They were divided into two groups: NES–BE and BE-only. The participants kept 7-day, 24-h food diaries and completed demographic and depression questionnaires. Results NES–BE reported significantly a higher frequency of binge days and binge episodes during the week, and more energy and fat consumption than BE-only. Conclusions Individuals with NES–BE exhibit higher levels of eating pathology than individuals with BE-only. Thus, NES–BE may not be simply a variant of BED or BN but rather a separate entity that may lead to a more severe disorder and require early assessment and more intensive and suitable treatment. Level of evidence Level V, cross-sectional descriptive study.

Skeletal Involvement in Eating Disorders

The effect of an eating disorder (ED) on bone health and the integrity of the skeletal structure, is an area of significant concern in terms of potential long-lasting, adverse consequences. Adolescence, in particular, represents a crucial developmental stage during which bone density accrues and peak bone mass is achieved. For this reason, EDs elevate the risk for bone loss among adolescents and young adults, and may jeopardize their ability to attain appropriate peak bone mass. Though some patients with EDs may not present with conspicuous symptomatology related to bone health, it is not uncommon for adolescents to develop stress fractures, kyphoscoliosis, or evidence height loss and for adults with EDs to suffer from bone pains and an increased incidence of fractures. In this chapter, we give an overview of the impact of eating disorder symptomatology on the skeletal system for both adults and adolescents with AN. A key characteristic of patients with AN is bone loss, which is evidenced by low bone turnover, greater osteoclastic (bone resorptive) activity as compared to osteoblasic (bone formation) activity, and deterioration in both trabecular and cortical bone, though particularly in the former. Factors that influence bone loss in AN include malnutrition and low weight, reduced fat mass, glucocorticoid excess, impairment of the GH-IGF1 axis, and insufficient levels of estrogen and androgen. On the other hand, in cases of bulimia nervosa (BN), bone loss occurs far less often and usually in patients with a history of low body weight or amenorrhea. From a treatment perspective, the most effective treatment for improving bone mineral density (BMD) is an increase in caloric intake, resulting in weight gain and resumption of menses. Other treatment modalities, such as those involving hormonal therapies, have not been found to have significant efficacy. Still, even in weight-restored patients with AN, long-lasting effects and permanent bone loss may result.