Clinical Characteristics and Treatment Outcomes of Children with Primary Osteoporosis.

OBJECTIVE: Primary osteoporosis is a rare and essential problem in childhood that can cause severe skeletal deformities. We aimed to reveal the spectrum of primary osteoporosis and assess the effectiveness and safety of bisphosphonates in increasing bone mineral density and reducing fractures. MATERIALS AND METHODS: Patients with primary osteoporosis who received at least one course of pamidronate or zoledronic acid were included in the study. Patients were divided into 2 groups, osteogenesis imperfecta and non-osteogenesis imperfecta subjects. We evaluated bone densitometer parameters, activation scores, pain status, deformity status, and the number of fractures per year in all patients. RESULTS: Of the 31 patients, 21 with osteogenesis imperfect, 3 patients with spondyloocular syndromes, 2 with Bruck Syndrome, and 5 with idiopathic juvenile osteoporosis were included. A total of 21 patients had received pamidronate treatment, while only 4 received zoledronic acid, and 6 of them switched from pamidronate to zoledronic acid. At the end of the treatment, the mean bone mineral density height-adjusted Z-score increased from -3.39 ± 1.30 to -0.95 ± 1.34. The number of fractures per year decreased from 2.28 ± 2.67 to 0.29 ± 0.69. The activation score increased from 2.81 ± 1.47 to 3.16 ± 1.48. The pain decreased significantly. There was no difference in bone mineral density increase in patients treated with pamidronate or zoledronic acid. CONCLUSION: Those with osteogenesis imperfecta were diagnosed at an earlier age with severe deformity and fractures. Pamidronate and zoledronic acid increased bone mineral density in all types of primary osteoporosis.

Evaluation of Abnormal Uterine Bleeding in Adolescents: Single Center Experience

Objective: Abnormal uterine bleeding (AUB) is the most common gynecologic complaint in adolescent girls. The aim of this study was to identify the diagnostic and management differences between those with/without heavy menstrual bleeding. Methods: Retrospective data was collected from adolescents aged 10-19 years, diagnosed with AUB. Adolescents with known bleeding disorders at admission were excluded. All girls were classified according to the degree of anemia; group 1 had heavy bleeding [hemoglobin (Hb) <10 g/dL] and group 2 had moderate or mild bleeding (Hb >10 g/dL). Admission and follow-up characteristics were compared between the two groups. Results: The cohort consisted of 79 girls with a mean age of 14.3±1.8 years and mean age of menarche of 11.9±1.4 years, with 85% experiencing menstrual irregularity in the two years after menarche, rising to 95.3% in group 1 (p<0.01). Anovulation was evident in 80% of the cohort. Of these 79 girls, 13 (16.5%) had polycystic ovary syndrome and two (2.5%) had structural anomalies (uterus didelphys). Three girls (group 1, n=2) had previously undiagnosed clotting factor VII deficiency; no other clotting deficiencies were diagnosed. Nineteen of 34 (56%) with personal (n=2)/family history of thrombosis had MTHFR mutation. None had venous thromboembolism during follow-up of >6 months. Conclusion: The majority of AUB (85%) occurred in the first two years after menarche. A small proportion (3.8%) had undiagnosed clotting factor deficiency. The frequency of MTHFR mutation was 50% in girls with history of thrombosis; however this did not increase the risk of bleeding/thrombosis and so routine evaluation does not appear to be justified.

Clinical Profile of Parathyroid Adenoma in Children and Adolescents: A Single-Center Experience.

OBJECTIVE: Parathyroid adenoma is less common than in adulthood, but its morbidity is higher in children. We aimed to evaluate the clinical characteristics of parathyroid adenoma and our clinical experience since the early disease is often asymptomatic and late diagnosed. MATERIALS AND METHODS: From 2010 to 2020, all children diagnosed with parathyroid adenoma at our institution were reviewed. We evaluated clinical, biochemical, and radiological aspects and follow-up characteristics. RESULTS: Eight subjects (F/M = 6/2) ranged in age from 10 to 17 years. Three were symptomatic. The symptoms and findings were stomachache (n = 3), myalgia (n = 2), weakness (n = 2), pancreatitis (n = 1), constipation (n = 1), nausea (n = 1), bone ache (n = 1), and anorexia (n = 1). Laboratory findings on admission were as follows: the mean calcium was 12.59 ± 1.28 (11.2-15.3) mg/dL and the mean parathyroid hormone was 244.81 ± 173.61 (74.9-645.4) pg/mL. The most common localization was the lower part of the left parathyroid gland. Parathyroid adenoma could not be demonstrated by ultrasonography in 2 patients. Tc-99m-Sestamibi scintigraphy revealed the presence of parathyroid adenoma in only 7 of 8 patients. All underwent parathyroidectomy. In our follow-up, 2 subjects needed reoperation. A molecular analysis of 6 cases could be done. One was MEN1 positive. RET sequence analysis of 2, and Casr, GNA11, and AP2S1 sequence analysis of 3 were normal. CONCLUSION: Parathyroid adenoma should be considered in children older than the first decade with hypercalcemia. Suspected cases should undergo both ultrasonography and scintigraphy. Early diagnosis prevents the patients from serious complications of hypercalcemia such as nephrocalcinosis, diabetes insipid, and arrhythmia. It is significant to perform surgery in centers experienced in parathyroidectomy to minimize postoperative complications.

Steroid Hormone Profiles and Molecular Diagnostic Tools in Pediatric Patients With non-CAH Primary Adrenal Insufficiency.

CONTEXT: There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. OBJECTIVE: This work aimed to investigate the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. METHODS: Pediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targeted-gene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. This study comprised 18 pediatric endocrinology clinics with 41 patients (17 girls, median age: 3 mo, range: 0-8 y) with non-CAH PAI of unknown etiology. RESULTS: A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to a healthy control group, patients showed lower steroid concentrations, most statistically significantly in cortisone, cortisol, and corticosterone (P < .0001, area under the receiver operating characteristic curve: .96, .88, and .87, respectively). Plasma cortisol of less than 4 ng/mL, cortisone of less than 11 ng/mL, and corticosterone of less than 0.11 ng/mL had a greater than 95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. CONCLUSION: Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, but they are unlikely to point to a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, whereas little additional benefit is expected from WES.

Internipple Distance and Internipple Index in Prepubertal Turkish Girls

Objective: To determine internipple distance and internipple index in prepubertal Turkish girls. Methods: The internipple distance and chest circumference of 667 healthy prepubertal Turkish girls aged 6 to 11 years were measured in a school screening program in Düzce. Measurements were performed at the end of expiration with a standard non-stretch tape measure graduated in millimeters with the arms hanging in a relaxed position on the sides of the body. The internipple distance was measured between the centers of both nipples, and chest circumference was measured across the internipple line. The internipple index was calculated by dividing the internipple distance (cm) x100 by the chest circumference (cm). Age specific internipple index reference curves were constructed and smoothed with the Lambda-Mu-Sigma method. Mean and standard deviations of internipple distance and internipple index were calculated according to decimal ages. Results: Age was found to be positively correlated with internipple distance and chest circumference, while it was negatively correlated with internipple index. The reference values of internipple index, including 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles, and standard deviations were calculated for prepubertal girls. Conclusion: The reference ranges provided by this study might be helpful for the evaluation of syndromic cases by serving as normative data for internipple index in prepubertal girls aged 6-11 years in Turkey although ethnic differences may affect applicability to other countries.

Bone mineral density and vitamin D status in children with epilepsy, cerebral palsy, and cerebral palsy with epilepsy.

PURPOSE: We aimed to evaluate the relationship between bone mineral density (BMD) disorders and possible risk factors in patients with epilepsy only (EO), cerebral palsy only (CPO), and cerebral palsy-epilepsy (CP + E). METHODS: A total of 122 patients [EO (n = 54), CPO (n = 30), CP + E (n = 38)] and 30 healthy children were evaluated. BMD was only measured in patient groups, not in control subjects. BMD of lumbar vertebrae was determined by dual energy X-ray absorptiometry (DXA). An abnormal BMD was defined as low or low normal BMD. RESULTS: Low BMD rate in EO, CPO, and CP + E group was 3.7, 50, and 39.5 %, respectively. Abnormal BMD values were significantly related to inadequate dietary Ca intake (p = 0.017), severe intellectual disability (p < 0.001), and immobility (p = 0.018). In multivariate regression analysis, the risk of abnormal BMD was higher (3.9-fold) in patients not able to walk independently than the others (p = 0.029). However, serum Ca-Vitamin D levels, insufficient exposure to sunlight, low BMI, and use of AED were not correlated with abnormal BMD. CONCLUSION: Abnormal BMD is a common problem in patients with CP and CP + E. Abnormal BMD was related to the severity of CP, but not to vitamin D levels or AED treatment.