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Primary pigmented nodular adrenocortical disease (PPNAD) is a rare genetic disease mainly associated with Carney complex (CNC), which is caused by germline mutations of the regulatory subunit type 1A (RIα) of the cAMP-dependent protein kinase (PRKAR1A) gene. We report three cases suffering from CNC with unique features in diagnosis and follow-up. All cases had obesity and a cushingoid appearance and exhibited laboratory characteristics of hypercortisolism. However biochemical and radiological examinations initially suggested Cushing's disease in one case . All of the cases were treated surgically; two of them underwent bilateral adrenalectomy at once, one of them had unilateral adrenalectomy at first but required contralateral adrenalectomy after nine months. Contrary to what is usually known regarding PPNAD, the adrenal glands of two cases (case 2 and 3) had a macronodular morphology. Genetic analyses revealed pathogenic variants in PRKAR1A (case 1: c.440+5 G>A, not reported in the literature; cases 2 and 3: c.349G>T, p.V117F). One case developed Hodgkin lymphoma five year after adrenalectomy, this association was not previously reported with CNC. The findings of these families provide important information for a better understanding of the genetic pathogenesis, diagnosis, and clinical management of CNC. Hodgkin lymphoma may be a component of CNC.

Objectives: The aim of this research was to assess the psychological problems of pubertal girls who presented with early menarche. To the best of our knowledge, there is no similar prospective cross-sectional research in the medical literature. Methods: Group I included patients under 10 years old, who presented with menarche. Peripheral causes of puberty were excluded. Group II included 9–10-year-old prepubertal healthy girls. Four mental tests were employed to both groups. Children in Group I was recalled for re-evaluation after 6 months. Results: A total of 49 girls (Group I, n=28; Group II, n=21) were included. Median ages of the groups were similar (9.7 (0.4) years vs. 9.3 (0.6) years, p=0.06, respectively). Median bone age and the time between first signs of puberty and menarche in girls in Group I were 11.4 (1) years and 12 (0.1) months, respectively. Height age, height, weight, and BMI SD scores were significantly higher in Group 1 (p<0.01). Mental test scores and the frequency of mood disorders were similar among the groups (Group I, n=2, 7 % vs. Group II, n=2 (9 %), p=0.76)). Re-evaluation of 17 patients (60.7 %) in Group 1 revealed no significant differences in test scores and no new cases of psychiatric conditions. Conclusions: There was no significant difference in psychological and behavioral problem scores between the early menarche and control groups. Gonadotropin releasing hormone (GnRH) analogue therapy should not be based on the assumption that premature pubertal development will cause psychosocial effects and should only be considered after a thorough psychiatric evaluation.

Nailfold Capillaroscopy: A Non-invasive Tool for Early Detection of Microvascular Alterations in Children with Type 1 Diabetes Mellitus - Journal of Clinical Research in Pediatric Endocrinology

What is the Most Effective Method for Predicting Adult Height in Boys with Constitutional Delay of Growth and Puberty? - Journal of Clinical Research in Pediatric Endocrinology

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Methods: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 big/kg, the annual growth rate was 1.15 standard deviation score (minimum-2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

Introduction Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1 year in adolescent males with GHD. Subjects and methods Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II). Results Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9–13.7) and 12.8 (12.0–14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8–0.9) and 1.0 (0.9–1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4–10.1) cm/year [1.5 (0.8–5.0) SD score] and 8.7 (7.5–9.9) cm/year [1.1 (0.3–3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal. Conclusions When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1 year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients.

Objective: Both body weight (BW)-and body surface area (BSA)-based dosing regimens have been recommended for growth hormone (rhGH) replacement. The aim was to compare the two regimens to determine if either resulted in inadequate treatment depending on anthropometric factors.Methods: The retrospective study included children diagnosed with idiopathic isolated growth hormone deficiency. BW-based dosing in mcg/kg/day was converted to BSA in mg/m2/day to determine the equivalent amounts of the given rhGH. Those with a BW-to-BSA ratio of more than 1 were allocated to the "relatively over-dosed group", while the remaining patients with a ratio of less than 1 were assigned to the "relatively under-dosed" group. Patients with a height gain greater than 0.5 standard deviation score (SDS) at the end of one year were classified as the height gain at goal (HAG), whereas those with a height gain of less than 0.5 SDS were assigned as the height gain not at goal (NHAG).Results: The study included 60 patients (18 girls, 30%). Thirty-six (60%) patients were classified as HAG. The ratio of dosing based on BW-to-BSA was positively correlated both with the ages and body mass index (BMI) levels of the patients, leveling off at the age of 11 at a BMI of 18 kg/m2. The relative dose estimations (over-and under-dosed groups) differed significantly between the patients classified as HAG or NHAG. Fifty-six percent of NHAG compared to 44% of HAG patients received relatively higher doses, while 79% of HAG compared to 21% of NHAG received relatively lower doses (p=0.006). When the patients were subdivided according to their pubertal status, higher doses were administrated mostly to the pubertal patients in both the NHAG and HAG groups. In the pre-pubertal age group, 73% of NHAG compared to 27% of HAG received relatively higher doses, while 25% of NHAG compared to 75% of HAG received relatively lower doses (p=0.01). Conclusion: Dosing based on BW may be preferable in both prepubertal and pubertal children who do not show adequate growth responses. In prepubertal children, relatively lower doses calculated based on BW rather than BSA provide similar efficacy at lower costs.

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.

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.

Purpose The aim of the present study was to determine the efficiency of three different predictive models [Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner-Whitehouse 2 (TW2)] by comparing their predictions with near-adult height data of girls receiving gonadotropin-releasing hormone agonist (GnRHa) therapy. Methods Clinical findings were retrospectively analyzed. Bone ages obtained before treatment were evaluated from left hand and wrist radiographs by three researchers. Predicted adult height (PAH) was calculated using the BP, RWT, and TW2 methods for each patient at the beginning of therapy. Results The median age at diagnosis of the 48 patients included in the study was 8.8 (8.9-9.3) years. There was no significant difference between the mean bone ages evaluated separately with the Greulich-Pyle atlas and the TW3-RUS method (p=0.34). Among the PAH methods, only PAH measured by the BP method was very close to and no different from near adult height (NAH) [159.8±6.3 vs. 158.8±9.3 cm. p=0.3; (-0.5±1.1) vs. (-0.7±1.6) standard deviation score, p=0.1]. Accordingly, the BP method was found to be the most accurate prediction tool in girls with puberty treated with GnRHa. Conclusion The BP method is more effective at predicting adult height than the RWT and TW2 methods in female patients who will receive GnRHa treatment.