Primary Hyperparathyroidism due to Parathyroid Adenoma in Children and Adolescents.

OBJECTIVE: In contrast to adults, primary hyperparathyroidism (PHPT) in children and adolescents is a rare endocrine disorder. METHODS: A retrospective review of PHPT cases between 2005 and 2022 from a single tertiary university medical center, including clinical signs and symptoms, laboratory findings, radiological evaluation, treatment, and postoperative complications. RESULTS: Ten children (mean age at diagnosis 16.3 ± 1.3 years) were diagnosed with PHPT. All patients were in late pubertal stages without sex predominance and 8 were symptomatic. Mean calcium level was 13.6 ± 2.5 mg/dL, and mean parathyroid hormone levels were 204.8 ± 163.1 pg/mL. Parathyroid adenoma was confirmed by the postsurgical pathology results. CONCLUSIONS: PHPT in children and adolescents is often symptomatic and more severe than adults. The main cause is single parathyroid adenoma. Associated hypercalcemic syndromes were not found. Patients were cured after surgical removal of the adenoma without significant postoperative complications and no recurrence during 10.4 ± 5.9 years follow-up.

Reduced Growth Hormone Response to Anaerobic Exercise Among Children With Overweight and Obesity.

ABSTRACT: Hejla, D, Dror, N, Pantanowitz, M, Nemet, D, and Eliakim, A. Reduced growth hormone response to anaerobic exercise among children with overweight and obesity. J Strength Cond Res 36(8): 2194-2197, 2022-The aim of the present study was to examine the effect of an anaerobic exercise test on growth hormone (GH) secretion in children with overweight and obesity compared with children with normal weight. Fifteen children with overweight (body mass index percentile [BMI%ile] ≥85 < 95) and obesity (BMI%ile ≥95) and 10 children with normal weight (BMI%ile >5 < 85) participated in the study. Subjects performed a modification of the Wingate anaerobic test (WAnT), with 10 bouts of 15-second cycling separated by 1 minute of rest. Blood samples for GH and lactate were collected before and 15, 30, 45, and 60 minutes after the beginning of the exercise test. There was a significant increase in GH levels following the modified repeated WAnT in both groups, but the increase in GH levels was significantly greater among the normal weight children compared with those with overweight and obesity ( p < 0.003). Seven of the 10 subjects with normal weight had GH increase above the threshold for GH sufficiency compared with only 2 subjects with overweight and obesity. Growth hormone response to the modified repeated WAnT was significantly reduced among children with overweight and obesity compared with those with normal weight. Anaerobic interval-type training may not be a sufficient exercise alternative to stimulate appropriate GH levels among children with obesity.

The Effect of Growth Hormone Treatment on Physical Performance Indices in Children With Idiopathic Short Stature.

PURPOSE: To examine the effect of growth hormone (GH) treatment on physical performance in children with idiopathic short stature and normal GH secretion. MATERIALS AND METHODS: A total of 24 children participated in the study (13 GH-treated, 11 non-treated, aged 8-13 y, 11 males and 13 females, Tanner stage 1-2). Participants performed a battery of motor skill performance tests (Eurofit), as well as the Wingate anaerobic test. RESULTS: No statistically significant differences in any of the Eurofit physical fitness test results (eg, 20-m shuttle run 33.0 [15.1] vs 25.1 [21.0] laps in treated and nontreated participants, respectively, P = .25) or the Wingate anaerobic test were found between the groups (eg, peak power 5.0 [2.9] vs 3.9 [2.6] watts/kg in treated and nontreated participants, respectively, P = .2). CONCLUSIONS: Therapeutic usage of exogenous GH for pre and early pubertal children with idiopathic short stature and normal GH secretion was not associated with beneficial effects on physical performance indices. This suggests that the use of GH as a potential performance enhancing agent, in this age group, at least at commonly used doses, is not advantageous.

Body composition and neuromotor development in the year after NICU discharge in premature infants.

BACKGROUND: Hypothesis: neuromotor development correlates to body composition over the first year of life in prematurely born infants and can be influenced by enhancing motor activity. METHODS: Forty-six female and 53 male infants [27 ± 1.8 (sd) weeks] randomized to comparison or exercise group (caregiver provided 15-20 min daily of developmentally appropriate motor activities) completed the year-long study. Body composition [lean body and fat mass (LBM, FM)], growth/inflammation predictive biomarkers, and Alberta Infant Motor Scale (AIMS) were assessed. RESULTS: AIMS at 1 year correlated with LBM (r = 0.32, p < 0.001) in the whole cohort. However, there was no effect of the intervention. LBM increased by ~3685 g (p < 0.001)); insulin-like growth factor-1 (IGF-1) was correlated with LBM (r = 0.36, p = 0.002). IL-1RA (an inflammatory biomarker) decreased (-75%, p < 0.0125). LBM and bone mineral density were significantly lower and IGF-1 higher in the females at 1 year. CONCLUSIONS: We found an association between neuromotor development and LBM suggesting that motor activity may influence LBM. Our particular intervention was ineffective. Whether activities provided largely by caregivers to enhance motor activity in prematurely born infants can affect the interrelated (1) balance of growth and inflammation mediators, (2) neuromotor development, (3) sexual dimorphism, and/or (4) body composition early in life remains unknown.

Expert's Choice: 2018's Most Exciting Research in the Field of Pediatric Exercise Science.

This commentary highlights 23 noteworthy publications from 2018, selected by leading scientists in pediatric exercise science. These publications have been deemed as significant or exciting in the field as they (a) reveal a new mechanism, (b) highlight a new measurement tool, (c) discuss a new concept or interpretation/application of an existing concept, or (d) describe a new therapeutic approach or clinical tool in youth. In some cases, findings in adults are highlighted, as they may have important implications in youth. The selected publications span the field of pediatric exercise science, specifically focusing on: aerobic exercise and training; neuromuscular physiology, exercise, and training; endocrinology and exercise; resistance training; physical activity and bone strength; growth, maturation, and exercise; physical activity and cognition; childhood obesity, physical activity, and exercise; pulmonary physiology or diseases, exercise, and training; immunology and exercise; cardiovascular physiology and disease; and physical activity, inactivity, and health.

Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus.

BACKGROUND AND OBJECTIVES: Alpha-1 antitrypsin (AAT) has been shown to reduce pro-inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset type 1 diabetes mellitus (T1DM). METHODS: A 37-wk prospective, open-label, phase I/II interventional trial, comprised of 24 recently diagnosed subjects (12 males; age 12.9 ± 2.4 yr), who received 18 infusions of 40, 60, or 80 mg/kg/dose high-purity, liquid, ready to use AAT over 28 wk (Glassia(®) ; Kamada Ltd., Ness Ziona, Israel). PRIMARY OUTCOMES: safety and tolerability; secondary outcomes: glycemic control, C-peptide reserve, and autoantibody levels. Possible responders were defined as individuals with peak C-peptide that declined less than 7.5% below baseline. RESULTS: No serious adverse events, diabetic ketoacidosis (DKA), or severe hypoglycemic episodes were reported. Adverse events were dose-independent and transient. Glycemic control parameters improved during the study in all groups, independent of dosage. Hemoglobin A1c (HbA1c) decreased from 8.43 to 7.09% (mean, p < 0.001). At the end of the study, 18 subjects (75%) had a peak C-peptide ≥0.2 pmol/mL. Eight subjects (33.3%) were considered possible responders and were characterized by shorter duration of T1DM at screening (54.5 ± 34.3 vs. 95.9 ± 45.7 d, p = 0.036) and greater decrease in their HbA1c during the study period (-2.94 ± 1.55 vs.-0.95 ± 1.83%, p = 0.016). CONCLUSIONS: AAT treatment was safe and well tolerated in pediatric subjects with recently diagnosed autoimmune diabetes. Placebo-controlled studies with larger cohorts and dose range are warranted in order to assess efficacy in maintaining pancreatic beta cell reserve and glycemic control.

Polymorphism of the IGF-I System and Sports Performance.

The potential use genetic polymorphism, and in particularly polymorphism of hormone genes, as tool to predict athletic performance is currently very challenging. Recent studies suggest that single nucleotide polymorphisms in IGF-I and myostatin may be beneficial for endurance and short distance running, and may even be associated with elite performance. Polymorphism in IGF-I receptor may differentiate between the two edges of the endurance-power athletic performance running spectrum suggesting beneficial effects for endurance and prevent from success in power events. In contrast, and despite similar metabolic demands, the myostatin-IGF-I-IGF-IR system seems not to play an important role in swimming excellence. This suggests that combining different sport disciplines for sports genetic research purposes should be done with extreme caution. Finally, since any phenotype reflects a complex relationship between genes, environment, epigenetic factors, and the interactions between them, consulting the young athlete regarding future success cannot be based solely on genetic polymorphism.

Growth without growth hormone: can growth and differentiation factor 5 be the mediator?

Growth without growth hormone (GH) is often observed in the setup of obesity; however, the missing link between adipocytes and linear growth was until now not identified. 3T3L1 cells were induced to differentiate into adipocytes and their conditioned medium (CM) (adipocytes CM, CMA) was added to metatarsals bone culture and compared to CM derived from undifferentiated cells. CMA significantly increased metatarsals bone elongation. Adipogenic differentiation increased the expression of growth and differentiation factor (GDF)-5, also found to be secreted into the CMA. GDF-5 significantly increased metatarsal length in culture; treatment of the CMA with anti-GDF-5 antibody significantly reduced the stimulatory effect on bone length. The presence of GDF-5 receptor (bone morphogenetic protein receptor; BMPR1) in metatarsal bone was confirmed by immunohistochemistry. Animal studies in rodents subjected to food restriction followed by re-feeding showed an increase in GDF-5 serum levels concomitant with nutritional induced catch up growth. These results show that adipocytes may stimulate bone growth and suggest an additional explanation to the growth without GH phenomenon.

Rhabdomyolysis After Out-of-Water Exercise in an Elite Adolescent Water Polo Player Carrying the IL-6 174C Allele Single-Nucleotide Polymorphism.

We present an adolescent elite water polo player who despite a genetic predisposition to develop exercise-induced severe muscle damage due to carrying the IL-6 174C allele single-nucleotide polymorphism, developed acute rhabdomyolysis only after a vigorous out-of-water training, suggesting that water polo training may be more suitable for genetically predisposed athletes.

IGF-I and IGF-I receptor polymorphisms among elite swimmers.

In recent years several genetic polymorphisms related to the GH-IGF-I axis were suggested to promote athletic excellence in endurance and power sports. We studied the presence of the C-1245T SNP (rs35767), a nucleotide substitution in the promoter region of the IGF-I gene, and the presence of the 275124A > C SNP (rs1464430), a common nucleotide substitution in the intron region of the IGF-I receptor (IGF-IR) gene in elite long and short-distance swimmers compared with nonphysically active controls. The rare T/T IGF-I polymorphism was found only in 5.3% of the long-distance swimmers, and was not found at all in the short-distance swimmers or among the control group participants. The prevalence of the IGF-I receptor AA genotype was significantly lower in the swimming group as a whole (35%) compared with the control group (46%), in particularly due to reduced frequency of the AA genotype among short-distance swimmers (26%). In contrast to previous reports in elite endurance and power track and field athletes, single nucleotide polymorphisms of the IGF-I and the IGF-IR were not frequent among elite Israeli short- and long-distance swimmers emphasizing the importance of other factors for excellence in swimming. The results also suggest that despite seemingly similar metabolic characteristics different sports disciplines may have different genetic polymorphisms. Thus, combining different disciplines for sports genetic research purposes should be done with extreme caution.

High-intensity interval exercise test stimulates growth hormone secretion in children.

BACKGROUND: exercise stimulates growth hormone (GH) secretion and may serve as a promising physiological test for the diagnosis of GH deficiency. However, exercise standardization for a feasible GH test is still lacking. The aim of the present study was to examine the GH secretion to high intensity interval exercise. METHODS: Seventeen children (12.4 ± 2.6 years) with impaired growth rate performed high-intensity interval exercise test (HIIE) that included 10 intervals of 15 s all out pedaling against resistance determined by age, sex and weight on a cycle ergometer with 1-min active rest between each interval. Power output measurements were collected during the test. Blood samples were collected before, immediately after, 30, 45, and 60min after the beginning of the exercise test. GH response was compered to pharmacological provocation test (clonidine or glucagon). RESULTS: HIIE led to a significant increase in GH levels (p < 0.001), with high correlation to GH response following pharmacological stimulation (r = 0.82, r = 0.80 for clonidine and glucagon respectively, p < 0.001) A significant correlation was found between mean peak power to body weight and the GH response (r = 0.50, p = 0.04). 83% of the participants who reached peak power > 10 watts/kg had normal GH secretion. CONCLUSIONS: HIIE is a brief and individualized exercise protocol that may be used as a physiological provocation test for GH secretion. There might be a minimum of anaerobic power needed to induce adequate GH response during HIIE.

The "combined team" transition clinic model in endocrinology results in high adherence rates and patient satisfaction.

Background A structured transition process for young adults with chronic medical conditions from pediatric to adult clinics is strongly promoted. However, the most appropriate transition model has not yet been determined. This study evaluated the effect of a "combined team" Endocrinology Transition Clinic model, including a joint meeting with the patient and pediatric and adult endocrinologists, regarding medical treatment, adherence to follow-up and patient satisfaction with the process. Methods Clinical and demographic data of patients admitted to the Endocrinology Transition Clinic were collected. The clinical impact of the transition meeting was evaluated based on treatment modifications and patient adherence to follow-up. Patient satisfaction was evaluated using a questionnaire. Results From September 2014 through November 2018, 107 patients attended the Endocrinology Transition Clinic, 85.0% were females, mean age 19.7 ± 2.2 years (range 16-29), 97.2% were unmarried. The most common endocrine disorders were obesity (41.1%), Hashimoto's thyroiditis (41.1%) and ovarian hyperandrogenism (38.3%). The Transition Clinic visit modified treatment and/or evaluation for 48 (44.8%) patients. Adherence to follow-up in the adult clinic was 82.9% and was not associated with gender (p = 0.366), ethnicity (p = 0.725), age at transition (p = 0.479) or obesity (p = 0.375). Overall satisfaction reported by 65/85 patients was high (86.8%), although higher among patients who were adherent to follow-up (89.4% vs. 65.6%, p = 0.006). Conclusions The "combined team" transition model in endocrinology requires relatively few resources and has considerable clinical impact, high adherence to follow-up and high patient satisfaction rate. Implementing this model at the interface of pediatric and adult endocrinology units, and possibly in other medical fields, is feasible and efficient.

The Wingate anaerobic test cannot be used for the evaluation of growth hormone secretion in children with short stature.

PURPOSE: To assess the growth hormone (GH) response to the Wingate anaerobic test (WAnT) among children with short stature and suspected GH deficiency. We hypothesized that the GH response to the WAnT would be similar to the GH response to a commonly used pharmacologic provocation test. METHODS: Ten children (6 males and 4 females, age range 9.0-14.9 years) participated in the study. Each participant performed 2 tests: a standard all-out WAnT, cycling for 30 s against constant resistance, and a standardized pharmacologic test (clonidine or glucagon). Blood samples for GH were collected before and 10, 30, 45, and 60 min after the beginning of exercise. In addition, we collected pre- and post-exercise blood lactate levels. RESULTS: There was a significant increase in GH levels after the WAnT, yet in 9 of 10 participants, this increase was below the threshold for GH sufficiency. Peak GH after the WAnT was significantly lower compared to the pharmacologic GH provocation tests (with 9 of 10 demonstrating GH-sufficient response). CONCLUSION: The traditional WAnT cannot be used as a GH provocation test. Further research is needed to develop anaerobic exercise protocols sufficient to promote GH secretion.