Barriers to Adolescents' Adherence to Medical Advice after Metabolic Bariatric Surgery: A Statistical Analysis.

Background: Adolescent obesity has markedly increased worldwide, and metabolic bariatric surgery is an effective treatment option. A major predictor of the outcomes of this procedure is adherence to post-surgery lifestyle changes and medical recommendations. While adolescents generally have more difficulty adhering to medical advice than adults, their failure to do so could adversely affect their physical and psychological health, the cost-effectiveness of medical care, and the results of clinical trials. To our knowledge, this is the first attempt to identify the characteristics associated with the adherence of adolescents and their families to medical advice after bariatric surgery. Methods: We investigated potential variables influencing adherence to medical advice in adolescents diagnosed with severe obesity enrolled in a nutritional and behavior-oriented bariatric program-a 3-month pre-surgical outpatient intervention and a 6-month post-surgical follow-up. The program monitored weight, program attendance, diet compliance, lifestyle changes, and daily activities. All participants and parents completed a standard battery of questionnaires, provided demographic information, and participated in a semi-structured interview about their lifestyle. Results: The study group consisted of 47 adolescents: 34 girls and 13 boys, aged 13-18 years. Over time, three groups emerged with different degrees of adherence-high, low, and delayed low adherence. The analyses showed that adolescents' depression, autonomy, and independence from their family had strong, significant effects on adherence across the groups. Conclusions: Using adherence typologies, practitioners may be able to identify, predict, and tailor interventions to improve adolescent adherence to post-surgery recommendations. Parents have an important role in ensuring that adolescents undergoing metabolic bariatric surgery follow medical advice after the procedure.

Endocrine-related adverse conditions in pediatric patients treated with immune checkpoint inhibition for malignancies.

BACKGROUND: In recent years, remarkable advances in cancer immunotherapy have been introduced in the field of oncology. Since the discovery of immune checkpoints inhibitors (ICIs), these groups of medications have become a crucial treatment for several types of adult cancer. SUMMARY: To date, pediatric experience with this group of medications is limited. Nevertheless, as clinicians we have to be aware of the possible immune-related adverse events including immune-related endocrinopathies (thyroid dysfunction, diabetes mellitus, adrenal insufficiency, and pituitary insufficiency) that have been reported regarding these medications. These adverse events probably result from uncontrolled activation of the immune system. KEY MESSAGE: Early diagnosis, monitoring, and treatment of immune-related endocrinopathies associated with ICIs treatment are also essential for the best supportive care and administration of ICIs in pediatric patients. This review presents the current data on the immune-related endocrinopathies associated with the ICIs treatment, with suggestions for management. .

Gonadotropin-releasing hormone analogs treatment in girls with central precocious puberty and early fast puberty.

BACKGROUND: Gonadotropin-releasing hormone analog (GnRHa) is the standard treatment for children with central precocious puberty (CPP). We assessed efficacy and safety of GnRHa treatment in girls with CPP and early fast puberty (EFP). METHODS: This retrospective observational study included anthropometric, clinical and laboratory data retrieved from medical files of girls with CPP or EFP, treated with GnRHa and followed at a tertiary endocrine clinic during 2007-2021. RESULTS: For both CPP (n = 144) and EFP (n = 231) groups, mean height-SDS at GnRHa initiation and termination and at the last follow-up visit was greater than mid-parental height-SDS (P < 0.001). Only among girls with EFP, mean BMI-SDS was higher at treatment termination than initiation (P = 0.025). Median ages at menarche of the CPP and EFP groups were 11.8 and 12.0 years. Menstrual irregularities were reported in 20.3% of girls with CPP and in 18.7% of those with EFP. Adverse effects to treatment were reported in 3.5% and 3.9% of girls with CPP and EFP, respectively. CONCLUSIONS: In this large cohort, GnRHa treatment in girls with EFP was effective without significant adverse effects as in those with CPP. A randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty. IMPACT STATEMENT: Gonadotropin-releasing hormone analog (GnRHa) is the standard treatment for central precocious puberty (CPP). We assessed efficacy and safety of GnRHa treatment in girls with early fast puberty (EFP), characterized by pubertal signs between ages 8-9 years with fast pubertal signs advancement and accelerated growth and bone maturation and in girls with CPP. We found in this large cohort that GnRHa treatment in girls with EFP was effective and safe as in those with CPP. A prospective randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty.

Optic pathway glioma and endocrine disorders in patients with and without NF1.

BACKGROUND: Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1. METHODS: We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated. RESULTS: Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence. CONCLUSIONS: Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments. IMPACT: The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG.

Clinical and Esophagogastroduodenoscopy Findings in Pediatric Patients With Severe Obesity Evaluated Before Bariatric Surgery.

OBJECTIVES: Severe obesity in the pediatric population has lifelong consequences. Bariatric surgery has been suggested for selected adolescents with severe obesity after careful evaluation. The indications for preoperative esophagogastroduodenoscopy (EGD) in this age group are not clear, despite its established usefulness in adults. We aimed to assess the usefulness of EGD before bariatric surgery in pediatric patients with severe obesity and metabolic comorbidities. METHODS: We conducted a retrospective chart review in a single tertiary pediatric medical center of adolescents treated during 2011 to 2018. Data collected from electronic medical records included patient demographics, endoscopic findings, and laboratory parameters. RESULTS: A total of 80 patients (40 boys) underwent evaluation. Macroscopic abnormalities were detected in 54% of the endoscopies, including gastritis, esophagitis, and duodenitis in 46%, 16%, and 13%, respectively. Forty-nine percentage of the biopsies showed histological abnormalities; in 35 (44%) patients, Helicobacter pylori was detected. Thirty-three patients (41%) received medical treatment and 2 (2.5%) required a second EGD. Metabolic comorbidities included hypertriglyceridemia (38% of the patients), low high-density lipoprotein (23%), and prediabetic (16%) or diabetic levels of HbA1C (4%). Fifty-five percentage of the cohort had elevated alanine aminotransferase (ALT), suggestive of nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: Endoscopies performed before bariatric surgeries suggest a higher prevalence of clinically significant findings, many of which required treatment. These findings support incorporating an EGD into the preoperative evaluation of this patient population.

The Beneficial Effect of Combined GH/GnRHa Therapy in Increasing Adult Height Outcome in Children With ISS.

CONTEXT: Management of GH-treated children with idiopathic short stature (ISS) with early puberty and adolescents in midpuberty at initiation of treatment is challenging. OBJECTIVE: To assess the effect of combined GH/GnRHa therapy during puberty on achieved adult height (AHt) in these children with ISS and to determine whether outcome depended on sex and pubertal status at initiation of GH therapy. DESIGN: Retrospective, single-center observational study from 2003-2018. SETTING: Tertiary endocrine center. PATIENTS: One hundred ninety-two GH-treated children with ISS; 58 of 192 were treated by GH/GnRHa during puberty; 31 of 58 were prepubertal (19 girls) and 27 of 58 pubertal (19 girls) at initiation of GH. MAIN OUTCOME MEASURES: AHt, gain-in-height standard deviation score (SDS), AHt vs predicted adult height (PAHt), AHt vs target height (THt). RESULTS: Most boys and girls attained AHt SDS within the normal range (-0.73 ± 0.60 and -0.85 ± 0.65, respectively). Treatment modality, pubertal status, and sex were tested for their joint effect on growth outcome measures. Combined GH/GnRHa therapy increased AHt vs PAHt (P < 0.001) and AHt vs THt (P = 0.035). Prepubertal status at onset of GH treatment increased AHt (P = 0.049), gain-in-height SDS (P < 0.001), AHt vs PAHt (P < 0.001), and AHt vs THt (P = 0.042). Female sex increased AHt vs PAHt (P < 0.001). CONCLUSIONS: Our study demonstrated a beneficial effect of combined GH/GnRHa therapy in increasing AHt outcome in children with ISS with early/normal puberty and in adolescents naïve to GH treatment who are in midpuberty at initiation of therapy. This effect was more pronounced in the prepubertal group and in girls. Prospective randomized controlled trials are needed to assess whether GnRHa can increase AHt in GH-treated children with ISS.

Endocrine and Metabolic Disturbances in Survivors of Hematopoietic Stem Cell Transplantation in Childhood and Adolescence.

BACKGROUND/AIMS: The objective was to evaluate endocrine complications in survivors of hematopoietic stem cell transplantation (HSCT) performed during childhood. METHODS: Endocrine dysfunction and metabolic syndrome parameters were assessed by chart review of 178 childhood HSCT survivors (median age at evaluation, 15.5 [range: 3.8-29.8] years; median follow-up, 8.5 [range: 2-23.4] years). RESULTS: The following statistically significant associations were identified (p < 0.05 for all): growth hormone deficiency (17.4%) was associated with cranial/craniospinal irradiation, total body irradiation (TBI), allogeneic HSCT, and longer follow-up. Short adult stature (23.3% of patients who had attained adult height) was associated with cranial/craniospinal irradiation and, in females, with younger age at HSCT. Primary gonadal failure was more prevalent in females (52.6 vs. 24.1%), and was associated with TBI in males and with a primary diagnosis of hematological malignancy in females. Hypothyroidism (25.2%) was associated with previous neck/mediastinal irradiation. Metabolic disturbances included obesity (3.9%), type 2 diabetes (2.2%), impaired glucose tolerance (2.8%), and dyslipidemia (18.5%). Dyslipidemia was associated with a primary diagnosis of hematological malignancy, TBI, and a positive family history of dyslipidemia. Endocrine dysfunction was less frequent in patients who had received fludarabine. CONCLUSIONS: Patients after HSCT require long-term surveillance for the detection of endocrine and metabolic disorders. Nonmyeloablative conditioning regimens may reduce the incidence of these complications.

Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Survivors of acute lymphoblastic leukemia (ALL) may experience endocrine dysfunction. This study evaluated growth and pubertal patterns in survivors of childhood ALL. METHODS: Longitudinal assessment of anthropometric measurements and pubertal status was performed in a retrospective cohort of survivors (n=183). Median age at last endocrine visit was 16.1 years (range 8.2-27.6); median follow-up time was 8.7 years (range 3-21.4). RESULTS: Treatment with chemotherapy+prophylactic cranial radiation (pCRT, n=29) was associated with lower mean height standard deviation score (SDS) than chemotherapy alone (n=154) (p=0.001) and higher prevalence of adult short stature (13% vs. 2.2%). Mean age at pubertal onset was normal (girls: 10.3±1.3 years; boys: 12.0±1.3 years). Precocious puberty, diagnosed in 8.7% of patients, was more prevalent in pCRT-treated girls. Rates of overweight and obesity were 22.9% and 9.3%, respectively. Predictors of endocrine disorders were pCRT (p=0.031) and female gender (p=0.041); of obesity, higher body mass index (BMI)-SDS at diagnosis (p=0.001); and of short stature, lower height-SDS at diagnosis (p=0.038). CONCLUSIONS: Most childhood ALL survivors given chemotherapy alone attain normal adult height and puberty. Childhood ALL survivors are at increased risk of overweight, especially those with increased BMI at diagnosis. Clinicians should screen for overweight early in survivorship and introduce early interventions.

Treated and untreated women with idiopathic precocious puberty: BMI evolution, metabolic outcome, and general health between third and fifth decades.

CONTEXT: Central precocious puberty (CPP) may have clinical implications in adulthood. OBJECTIVE: To assess the prevalence of obesity, metabolic outcome (hyperlipidemia, diabetes, and hypertension), and malignancy rate of former CPP women between the third and fifth decades of life. DESIGN: This was a case control study of a historical cohort using the computerized database of a health management organization. SETTING: The setting was the Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, and Clalit Health Services. PARTICIPANTS: The study group comprised of 142 CPP women aged 27-50 years [100 GnRH analog (GnRHa) treated; 42 untreated]. The control group comprised of 413 women randomly matched for age, year of birth, and community clinic (283 for the GnRHa treated; 130 for the untreated). METHODS: Extracted from the database were demographic data, medical history, medications dispensed, recorded anthropometric measurements, vital signs, and laboratory data. RESULTS: At young adulthood, body mass index (percentile and distribution) of treated and untreated former CPP women was comparable to that of their respective controls. Elevated body mass index at presentation was a risk factor for obesity in adulthood in the GnRHa-treated group (r = 0.257; P = .01). The prevalence of metabolic comorbidities (16 vs 13.4%; 21.4 vs 24.6%) and malignancy rate (1.0 vs 1.5%; 4.8 vs 1.5%) were similar in the former CPP women and their controls, with no significant difference between CPP groups. CONCLUSION: CPP (treated or untreated) is not associated with increased risk of obesity, metabolic derangements, or cancer morbidities in young adulthood. The finding that the health status of former CPP women is similar to that of the general population is reassuring.

Endocrine complications and components of the metabolic syndrome in survivors of childhood malignant non-brain solid tumors.

BACKGROUND/AIMS: The substantial improvement in survival of children with cancer has been achieved at the cost of late effects. We aimed to evaluate the endocrine outcome in survivors of childhood non-brain malignant solid tumors (NBMST). METHODS: We performed a retrospective medical record review for medical history, clinical and laboratory data of survivors (n = 139) followed at the endocrine clinic of a tertiary medical center. Outcome measures were frequency and types of endocrine dysfunction and components of the metabolic syndrome. RESULTS: Median follow-up time was 9.0 years (range 1.2-29.5 years). At least one endocrine abnormality was found in 44 patients (31.7%). Abnormalities included hypogonadism (11.5%), hypothyroidism (9.4%), short stature (9.4%), growth hormone deficiency (8.6%) and components of the metabolic syndrome (15.1%). Height SDS decreased significantly (p = 0.004) during follow-up, whereas body mass index SDS tended to increase. On logistic regression analysis, treatment with cranial irradiation (p = 0.003), local radiation (p = 0.042), or bone marrow transplantation (p = 0.0001), and older age at last visit (p < 0.001) were associated with a significantly higher hazard of an endocrinopathy. CONCLUSIONS: The high rate of late endocrine dysfunction among survivors of childhood NBMST highlights the need to optimize the follow-up at the late-effects clinics to identify endocrine problems and allow early and effective intervention.

Growth and metabolic control in patients with type 1 diabetes and celiac disease: a longitudinal observational case-control study.

BACKGROUND: The occurrence of celiac disease (CD) in patients with type 1 diabetes (T1D) is increasing. OBJECTIVE: To determine the effect of CD on growth and glycemic control in patients with T1D, and the effects of adherence to gluten-free diet (GFD) on these parameters. PATIENTS AND METHODS: A longitudinal retrospective case-control design was used. The medical files of 68 patients with T1D and duodenal-biopsy-confirmed CD were reviewed for data on weight, height, hemoglobin A1c (HbA1c), frequency of diabetic ketoacidosis (DKA), and severe hypoglycemic events before and after diagnosis and treatment of CD. Findings were compared with 131 patients with T1D only matched for age, gender, and duration of diabetes. RESULTS: CD was diagnosed in 5.5% of all patients with T1D attending our center during the study period; 26% of the patients with CD were symptomatic. There were no significant differences in glycemic control or frequency of severe hypoglycemia or DKA events between the study and control groups. Body mass index-standard deviation score (SDS), height-SDS, and HbA1c values were marginally but not significantly higher in the control than the study group and similar in subjects with CD with good or fair/poor adherence to a GFD throughout follow-up. CONCLUSIONS: Patients with T1D and CD treated with GFD have growth and measures of metabolic control similar to those with T1D without CD. The decision whether asymptomatic celiac patients should be put on a GFD or only symptomatic patients has to be weighed against possible short- and long-term consequences of no intervention, and should be based on more evidence from larger randomized studies.

Spontaneous normalization of anti-tissue transglutaminase antibody levels is common in children with type 1 diabetes mellitus.

BACKGROUND: The prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5-10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up. AIM: This study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors. MATERIALS AND METHODS: The files of all children diagnosed with type 1 diabetes mellitus from 2003-2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized. RESULTS: Forty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements. CONCLUSION: Physicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

Endocrine outcome in long-term survivors of childhood brain tumors.

AIM: To evaluate the rates of endocrine abnormalities in survivors of childhood brain tumors and identify risk factors. METHODS: The medical charts of patients were reviewed for background, disease-related and treatment-related data. Endocrine dysfunction was determined by clinical and laboratory evaluation. RESULTS: The study group included 114 patients with a mean age of 15.57 ± 5.93 years. Mean age at brain tumor diagnosis was 7.07 ± 5.42 years, and mean follow-up was 12.8 ± 6.25 years. Fifty-seven patients (50%) had an endocrine abnormality. The occurrence of several endocrine abnormalities was significantly associated with cranial irradiation and age <16 years at tumor diagnosis. The presence of growth hormone deficiency (n = 40) was associated with cranial or spinal irradiation, younger age and prepubertal stage at tumor diagnosis; the presence of hypogonadotropic hypogonadism (n = 9) was associated with prepubertal stage at diagnosis, and hypothyroidism (n = 23) was associated with cranial irradiation. Hypocortisolism was diagnosed in 9 patients, short stature in 20 patients and obesity in 8 male patients. Patients with early puberty (n = 19) and an abnormal lipid profile (n = 15) were significantly younger at tumor diagnosis than patients without these disorders. CONCLUSIONS: Childhood brain tumor survivors are at increased risk of late endocrine effects, particularly those treated with cranial radiation and diagnosed at a younger age. The frequency of hormonal deficits increases with time, warranting lifelong surveillance.

Natural history of idiopathic advanced bone age diagnosed in childhood: pattern of growth and puberty.

BACKGROUND: Significant idiopathic bone age (BA) advancement is defined as BA >2 SD above the mean chronological age (CA) with no underlying etiology. BA advancement due to endocrinopathies is associated with early puberty and compromised adult height (AHt), necessitating treatment. The natural history of idiopathic BA advancement is not well-established. AIM: to determine the pattern of growth and puberty, and validity of AHt prediction in idiopathic BA advancement. METHODS: fifty-five prepubertal patients (20 boys aged 6.7 ± 2.2 years, 35 girls aged 6.4 ± 2.0 years) evaluated between 1985 and 2008 were found to have idiopathic BA advancement. Assessed during follow-up were: BA, height (Ht), weight (Wt), pubertal course and predicted AHt (PAHt). Attained AHt was compared to PAHt and to midparental Ht (MPHt). RESULTS: throughout follow-up, BA-SDS (SD score) significantly declined (p < 0.001), Ht-SDS significantly decreased (p = 0.006) and Wt-SDS did not change. Pubertal onset, duration and growth were within the normal range. Attained AHts did not differ significantly from MPHts (boys: 172 ± 6.7 vs. 171 ± 6.1 cm; girls: 160.5 ± 6.5 vs. 159.0 ± 6.8 cm). PAHts using the 'accelerated' tables of Bayley and Pinneau were accurate. CONCLUSION: idiopathic BA advancement differs from BA advancement with underlying endocrinopathy in evolution of BA progression (decline in BA-SDS), growth pattern, validity of AHt prediction and uncompromised AHt. This indicates that it requires minimal clinical monitoring and usually does not mandate treatment.

Autoimmune thyroiditis in infants with Down's syndrome.

Children with Down's syndrome are at high risk of thyroid dysfunction, including autoimmune thyroiditis. We describe two infants with Down's syndrome in whom chronic autoimmune thyroiditis was diagnosed at ages 5 months and 8 months. We suggest that follow-up of thyroid function and thyroid autoantibodies should be started from infancy in Down's syndrome to prevent further deterioration of mental development and growth.