Ece Böber

Hypoparathyroidism (HP) is a rare endocrine disorder in childhood, characterized by hypocalcemia and hyperphosphatemia due to insufficient secretion of parathyroid hormone (PTH) or, less commonly, ...

Objective: In girls, a strong relationship exists between body fat percentage (BFP) and pubertal development, with a critical fat threshold considered essential for the initiation of puberty. In contrast, research addressing the impact of body composition on the timing of puberty in boys remains limited, and the available findings are inconsistent. To evaluate the association between body composition and delayed pubertal development in boys with constitutional delay of growth and puberty (CDGP) compared with healthy peers. Methods: Thirty-one boys with CDGP and 31 age-matched healthy males (Tanner stage 2-4) were included. Body composition was assessed using bioelectrical impedance analysis. Body fat percentage (BFP), fat mass (FM), fat-free mass (FFM), fat mass index (FMI), and fat-free mass index (FFMI) were evaluated. A BFP value of 17% was used as a descriptive reference rather than a validated biological cut-off. Results: The mean chronological age was 14.1 ± 0.5 years in the CDGP group and 13.9 ± 1.1 years in the control group (P = .4). Compared with controls, boys with CDGP had significantly lower body mass index (BMI) standard deviation (SD) scores (P = .01). FM and FM SD scores were also significantly lower (both P = .002), and BFP was reduced (P = .03). No significant difference in BFP SD score was observed between groups (P > .05). The FFM/FM ratio was higher in the CDGP group (P = .04). FMI, FMI SD score, FFMI, and FFMI SD score were all significantly lower in boys with CDGP (P = .02, P = .02, P = .009, and P = .009, respectively). A BFP below 17% was observed in 58.1% of CDGP patients compared with 9.7% of controls (P < .001). Conclusion: Lower BMI, FM, and FFMI were associated with delayed pubertal onset in boys with CDGP, suggesting a potential relationship between reduced adiposity, lean mass, and the timing of pubertal development.

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.

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: The hypothalamic-pituitary-gonadal axis is active during minipuberty, the timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been previously investigated. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female) while the remaining healthy infants constituted Group 2 (n=71, 47.9% female). Salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were measured by ELISA in duplicate. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar. However, in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs= 0.393, p=0.016 vs. Group 2, rs= 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs= 0.469, p=0.009 vs. Group 2, rs= -0.005, p=0.976). Conclusion: Random salivary sex steroid levels were similar in infants with and without infantile colic. However, in subjects with infantile colic, Esal levels in females were positively correlated with BMI and Tsal levels were higher later in the day among males. Thus, sex steroid production may be altered during minipuberty in subjects with infantile colic.

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.

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.