Aromatase Inhibitors May Increase the Risk of Cardiometabolic Complications in Adolescent Boys.

INTRODUCTION: Aromatase inhibitors (AIs) are increasingly used in children and adolescents to augment adult height. The aim of this study was to investigate the effects AIs have on cardiac morphology, functions and their relation to several metabolic parameters in adolescent boys. METHODS: Three groups matched for sex (boys, n = 67), age (median age 13.5 years), weight, height, body mass index, and puberty stages were enrolled: (i) Group 1: 23 patients using AIs (only AI (n = 6) or in combination with growth hormone (GH) (n = 17)) for at least 6 months; (ii) Group 2: 22 patients using only GH, and (iii) Group 3: 22 healthy boys. Two-dimensional, M-mode conventional Doppler and tissue Doppler examinations of the left ventricle (LV) were performed. Bioelectrical bioimpedance analyses was conducted and follicle-stimulating hormone, luteinizing hormone, total testosterone, lipid, and hemogram parameters were obtained. RESULTS: Patients in Group 1 had significantly higher serum total testosterone (p < 0.001) and hemoglobin (p < 0.001) levels, fat free mass (p = 0.005), LV mass (LVM) (p = 0.002), as well as increased LV posterior wall diameter (LVPWD) (p = 0.002), interventricular septum diameter (IVSD) (p = 0.019), and myocardial systolic wave velocity (Sm) (p = 0.020) compared to the two other control groups. No significant differences were observed in terms of diastolic and systolic functions and lipid profiles (p > 0.05). There were positive correlations between total testosterone, hemoglobin levels, LVM, LVPWD and IVSD (p < 0.05). CONCLUSION: Increased LVM, LVPWD, IVSD and Sm of patients receiving AI therapy in comparison to the control groups, and the significant correlations of these parameters with total testosterone and hemoglobin levels were determined as potential side effects of AIs. These findings emphasize the need of routine cardiac follow-up in patients using AIs.

Anaemia-based screening for resistance to thyroid hormone alpha in children.

BACKGROUND: The hypothyroid phenotype associated with resistance to thyroid hormone alpha (RTH-α) is associated with a diverse clinical picture. On the other hand, thyroid-stimulating hormone (TSH) levels are normal. Free triiodothyronine (fT3) and free thyroxine (fT4) levels can also be normal; however, normo- or macrocytic anaemia is usually present in reported cases. Diagnosis is challenging and there is limited data regarding screening methods. OBJECTIVE: The study aimed to assess the efficiency of a screening strategy for RTH-α. SUBJECTS AND METHODS: Out of a total of 6540 children evaluated at the outpatient clinics of paediatric neurology over 2 years and who underwent complete blood count and thyroid function tests, 432 were found to have anaemia. Within this group, we identified 42 children without an underlying specific neurological aetiology who exhibited normo- or macrocytic anaemia, normal TSH levels, fT3 levels in the upper half of the normal range or high, and fT4 levels in the lower half of the normal range or low. We excluded one patient who had already been diagnosed with RTH-α and nine patients could not be reached. Subsequently, clinical evaluation, biochemical assessment, and THRA sequencing analysis were conducted on 32 children. The findings were compared with those of the known RTH-α patients in our unit. RESULTS: The median age of the patients was 5.7 (5.1-7.4) years, and 22 of them were males (69%). The main reasons for assessment in paediatric neurology clinics were autism spectrum disorder (n = 12, 38%), epilepsy (n = 11, 34%), and delay in developmental stages (n = 8, 25%). Constipation was present in five of the cases (16%), while the closure of the anterior fontanelle and tooth eruption were delayed in two cases (6%) and one case (3%), respectively. The median length/height and weight standard deviation (SD) scores were 0.3 [(-0.8)-(1.1)] and -0.1 [(-0.8)-(0.3)], respectively. The median fT3, fT4, and TSH levels were 4.6 (4.2-5.0) pg/mL, 0.9 (0.8-1.0) ng/dL, and 2.2 (1.8-3.1) uIU/mL, respectively. Thirteen of the patients (41%) had high fT3 levels, while none of them had low fT4 levels. The normo- or macrocytic anaemia rate was 47% (normocytic/macrocytic, n = 8/7) at the time of reassessment. Serum creatine kinase (CK) was elevated in five patients (16%; one had anaemia). None of the subjects had a pathological variant in THRA. Known RTH-α patients had significantly lower median height SD score, higher rates of delayed tooth eruption and closure of the anterior fontanelle, lower haemoglobin levels, and higher mean corpuscular volume (MCV) and CK levels as compared to those found without RTH-α. CONCLUSIONS: This approach found one known patient with RTH-α but did not reveal any new cases. Notably, normo- or macrocytic anaemia did not persist in nearly half of the screened patients. A screening strategy that takes clinical findings and prominent laboratory features suggestive of RTH-α into account could lower unnecessary genetic analysis of THRA in patients presenting with neurological problems.

Adverse Events Associated with COVID-19 Vaccination in Adolescents with Endocrinological Disorders: A Cross-Sectional Study

Objective: The aim was to evaluate the adverse events seen after Coronavirus disease-2019 (COVID-19) vaccination in pediatric patients with diagnosed endocrinological problems and to compare them with healthy controls. Methods: In this cross-sectional study, patients aged 12-18 years who attended a single department between January and May 2022 and were followed up for at least six months due to endocrine diseases, and healthy subjects in the same age group, all of whom had received a COVID-19 vaccine [BNT162b2 mRNA or inactivated vaccine] were included. Adverse events experienced after the vaccination were evaluated by questionnaire. Results: A total of 160 subjects (85 patients, 75 healthy controls) with a median (25-75p) age of 15.5 (14.1-16.9) years were included. The frequency of adverse events was higher in those vaccinated with the mRNA vaccine compared to the inactivated one after the first dose (p=0.015). The incidence of adverse events observed after the first and second doses of both COVID-19 vaccines was similar in the patient and control groups (p=0.879 and p=0.495, respectively), with local reactions being the most common. The frequency of adverse events was similar among the patients who did or did not receive any endocrinological treatment (p>0.05). The incidence and severity of systemic reactions were similar to those in healthy subjects for both vaccine doses, regardless of the underlying diagnosis, autoimmunity state, or treatment regimen used in patients with endocrine diseases. Conclusion: The incidence and severity of adverse events associated with COVID-19 vaccinations in adolescents with endocrinological disorders were similar to healthy subjects, in the early post-vaccination period.

Efficacy of aromatase inhibitor therapy in a case with large cell calcifying Sertoli cell tumour-associated prepubertal gynaecomastia.

OBJECTIVES: Large cell calcifying Sertoli cell tumours (LCCSCTs) are one of the infrequent causes of prepubertal gynaecomastia. Most of these tumours are in the content of Peutz-Jeghers syndrome (PJS) or other familial syndromes (Carney complex). CASE PRESENTATION: Here, we report a long-term follow-up of an 8.5-year-old prepubertal boy with a diagnosis of PJS, who presented with bilateral gynaecomastia, advanced bone age and accelerated growth velocity, and were found to have bilateral multifocal testicular microcalcifications. As the findings were compatible with LCCSCT, anastrozole was initiated. Gynaecomastia completely regressed and growth velocity and pubertal development were appropriate for age during follow-up. Testicular lesions slightly increased in size. After four years of medication, anastrozole was discontinued but was restarted due to the recurrence of gynaecomastia after six months. CONCLUSIONS: Testicular tumour should be investigated in a patient with PJS who presents with prepubertal gynaecomastia. When findings are consistent with LCCSCT, aromatase inhibitors may be preferred in the treatment.

Efficacy and safety of granulocyte transfusion in children: A single-center experience.

BACKGROUND: Granulocyte suspension transfusion (GTx) can be used in severely neutropenic patients with infections that cannot be controlled despite appropriate antibiotic therapy. OBJECTIVE: We aimed to evaluate the effectiveness and safety of GTx for the treatment of febrile neutropenia (FEN) in the pediatric age group. METHODS: Patients who underwent GTx in the Hematology Clinic of Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital between 2013 and 2017 were evaluated retrospectively. Hematologic and clinical response rates, effects on survival, and adverse effects were investigated. Clinical response was defined at two time points: clinical response I was evaluated after each transfusion, while clinical response II was evaluated after the final GTx in a FEN episode. RESULTS: During the study period, 343 GTx were given 107 FEN episodes of 74 patients. The mean number of granulocyte suspensions administered per patient and per FEN episode was 4.6 units and 3.2 units. The mean GTx volume administered was 237 ± 40 mL, and the mean granulocyte count was 2.8 ± 1.3 x 1010 /unit. Hematologic response was attained in 163 (47.6%) of 343 transfusions. Clinical response I was obtained in 88 (25.7%) of the GTx, and clinical response II was attained in 83 (78.5%) of 107 episodes. Life-threatening adverse event was not observed. The cumulative 1-month and 3-month survival rates were 87.8% and 76.5%, respectively. CONCLUSION: High hematologic response and clinical recovery rates were achieved with GTx, with no limiting adverse effects. Granulocyte transfusion appears to be a safe and effective treatment in pediatric patients with FEN.