Nursel Muratoğlu Şahin

Objectives: Changes in thyroid volume (TV) during the course of treatment of primary congenital hypothyroidism (CH) have not been fully elucidated. This study aimed to evaluate changes in TV according to etiology and their impact on treatment withdrawal rates. Methods: Clinical features and thyroid ultrasonography (US) findings at diagnosis and at 3 years of age were evaluated in 178 patients with gland in situ CH. Results: At diagnosis, thyroid ultrasound showed normal volume (64.3 %, n=133), hyperplastic (16.9 %, n=35), and hypoplastic (4.8 %, n=10) glands. In hyperplastic cases, median TV decreased significantly from 4.08 SDS (2.00–22.63) to 0.55 SDS (−1.68–8.52) over 3 years (p<0.0001), while hypoplastic glands showed an increase from −2.25 SDS (−2.75–2.00) to −1.05 SDS (−2.50–0.70) (p=0.005). No significant change was observed in normal volume patients [−0.42 SDS (−1.93–1.87) vs. −0.23 SDS (−2.36–5.16), p=0.305]. Transient CH rates differed by morphology (60.9 , 48.6, and 20 %, respectively; p=0.025). At 3 years, 70 % (n=7) of initially hypoplastic glands reached normal volume, with a treatment withdrawal rate of 28.6 %. Conclusions: In this study, which is the first to evaluate TV changes during the course of CH treatment, a significant decrease in TV SDS was found in patients with hyperplasia, whereas a significant increase was observed in those with hypoplasia. Despite initial hyperplasia or hypoplasia, TV could normalize over time, and treatment withdrawal was possible even in these groups.

Objectives: The biosynthesis of 3′-phosphoadenosine 5′-phosphosulfate (PAPS), a universal sulfate donor, is catalyzed by two isoenzymes: PAPS synthetase 1 (PAPSS1) and PAPS synthetase 2 (PAPSS2). While PAPSS1 is ubiquitously expressed, PAPSS2 shows tissue-specific expression and plays a key role in cartilage development and adrenal steroid metabolism. PAPSS2 deficiency impairs dehydroepiandrosterone sulfation (DHEA-S), leading to increased bioactive androgens and hyperandrogenism. Biallelic PAPSS2 variants cause skeletal dysplasias from brachyolmia (BO) to severe spondyloepimetaphyseal dysplasia (SEMD). This study aimed to expand the PAPSS2 mutational spectrum and explore potential genotype–phenotype correlations, including the distribution of variants across functional domains. Case presentation: Two siblings with disproportionate short stature underwent clinical, radiological, and biochemical evaluation. Targeted next-generation sequencing of skeletal dysplasia-associated genes was performed. Serum DHEA-S levels were measured to assess steroid sulfation. A literature review of previously reported PAPSS2 variants was conducted to explore genotype–phenotype correlations. A novel homozygous missense variant, c.1466C>G (p.Pro489Arg), in the ATP sulfurylase domain of PAPSS2, was identified in both siblings. The male proband exhibited a severe SEMD phenotype, while his sister presented with milder BO features. Both had markedly reduced DHEA-S levels (4.04 μg/dL and 31.8 μg/dL), consistent with impaired adrenal androgen sulfation. Review of the literature indicates an enrichment of SEMD-associated variants within the ATP sulfurylase domain, although phenotypic overlap with BO is evident, as also observed in the present family. Conclusions: This study expands the known PAPSS2 mutational spectrum by identifying a novel pathogenic variant. The observed intrafamilial variability highlights the complexity of genotype–phenotype relationships, particularly in the context of limited case numbers, while low DHEA-S levels represent a robust biochemical marker of impaired steroid sulfation.

Objectives: Measuring the longitudinal axis of the thyroid in infants can be difficult because of their short necks. The tracheal index (TI) provides an estimate of thyroid size based only on transverse measurements. Three studies have examined TI in infants, all of which focused on establishing normative data. This study evaluated the usefulness of TI in infants with suspected congenital hypothyroidism. Methods: Eighty infants with elevated TSH levels, identified during newborn screening, were included in this study. The thyroid size of the infants was assessed using thyroid volume (TV), TV standard deviation score (SDS), and TI. Results: TI was positively correlated with both TV and TV SDS (r = 0.381, p = 0.0001 and r = 0.400, p = 0.0001, respectively). However, no correlation was found between TI and TV for infants born before 38 weeks of gestation, or for those with a BW of less than 2,700 g or a birth weight (BW) below −1 SDS (p > 0.05). The sensitivity and specificity of TI in identifying thyroid hyperplasia were 53.8 % and 65.7 %, respectively. Conclusions: TI showed a positive correlation with TV, highlighting its usefulness in both hypothyroid and normal infants. However, there was no correlation between TI and TV in infants born before 38 weeks of gestation or with a BW below 2,700 g. Additionally, the sensitivity and specificity of TI for assessing thyroid hyperplasia were found to be low. These results suggest that its use in infants—especially those who are preterm, have low BW, or present with thyroid hyperplasia—is limited.

What to Do for Atypia of Uncertain Significance in Pediatric Thyroid Nodules? - Journal of Clinical Research in Pediatric Endocrinology

To evaluate demographic characteristics, clinical, laboratory, imaging features, and treatment responses of boys who were diagnosed and treated for central precocious puberty (CPP). The data were collected from pediatric endocrinology clinics in Türkiye. Patients were classified into two groups based on magnetic resonance imaging (MRI) findings, idiopathic CPP (iCPP) and organic CPP (oCPP). The oCPP group was further cathegorized into three subgroups: oCPP-confirmed, oCPP-unrelated, and oCPP-uncertain lesions. Among 232 patients, 62.9% were diagnosed with iCPP. All patients aged <3 years had oCPP-confirmed lesions. Basal luteinizing hormone (LH) and total testosterone (T) levels were higher in oCPP group than in iCPP group (p = 0.004 and p = 0.02, respectively). Basal LH, basal follicle-stimulating hormone (FSH), T, and peak LH/FSH were lower in the iCPP-obese group (p < 0.05). T differed significantly among the oCPP-confirmed, oCPP-unrelated, and oCPP-uncertain subgroups (p = 0.032). Among patients that reached final height (FH), the difference between target height (TH) standard deviation score (SDS) and FH SDS was higher in oCPP group than in iCPP group (p < 0.05). A positive correlation was found between predicted adult height at the treatment initiation and FH (r = 0.463 p = 0.020). Factors affecting FH were height SDS at the beginning of treatment, paternal height SDS, and TH SDS. The prevelance of oCPP was found lower compared with previous literature data. Currently, there is no reliable marker to predict oCPP that would allow clinicians to safely omit MRI in iCPP cases. However, boys under 3 years of age should be carefully evaluated for potential organic causes of CPP.

Objectives: Silver–Russell syndrome (SRS) is a rare imprinting disorder characterized by intrauterine and postnatal growth retardation. Its genetic etiology shows a heterogeneous distribution. This study aimed to evaluate the clinical characteristics of children diagnosed with SRS, their response to growth hormone therapy, and compare the data of genetically confirmed and clinically diagnosed SRS cases. Methods: A total of 69 patients were included in the study. Genetically confirmed cases were considered Group 1, and cases with a clinical diagnosis according to the Netchine–Harbison scoring system were considered Group 2. The anthropometric data of the patients at birth, at the time of diagnosis, before and during the first year of growth hormone (GH) treatment, final height-SDS values of patients who reached final height, and accompanying comorbidities were recorded. Results: In Group 1, 75.8 % had hypomethylation in the ICR1 region, 13.7 % had maternal uniparental disomy 7, 6.8 % had an IGF-2 mutation, and 3 % had a duplication in the 11p15 region. Central precocious puberty, gastroenterological, and neurologic comorbidities were found to be more frequent than those from other systems. Final height-SDS was −2.32 ± 1.57 (n=5) in Group 1 and −2.41 ± 0.86 (n=5) in Group 2. Conclusions: 11p15 LOM was the most common genetic disorder in children with SRS in our case series. Gastroenterological problems and neurologic complications were observed frequently in these cases. Central precocious puberty was more commonly observed compared to the general population. The duration of treatment was the most critical factor in the success of GH therapy.

Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY. MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated. A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n=3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral antidiabetic treatment. This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.

A balanced and healthy diet is very important in type 1 diabetes mellitus in childhood. In addition to regulating blood glucose with diet, it should be aimed to support adequate growth. Low-carbohydrate diet aims to provide daily energy from fats and is originally used for childhood epilepsy. We will present a patient with type 1 diabetes mellitus who has the unfavorable effects of the low-carbohydrate diet.

Objective: Ischemia-modified albumin (IMA) formation is associated with increased reactive oxygen species (ROS) production, while increased cortisol leads to decreased ROS levels. We aimed to evaluate the effect of adrenocorticotropic hormone (ACTH) stimulation on IMA levels and whether the effect was dose -dependent or not. Methods: A total of 99 subjects with normal ACTH test results were included in the study. Of these, 80 had standard -dose ACTH test while 19 had low -dose ACTH test. Blood samples were collected to determine cortisol and IMA levels; at minutes 0, 30, and 60 following the standard -dose ACTH test and at minutes 0 and 30 following the low -dose ACTH test. Results: IMA levels decreased significantly within 30 minutes and the decrease continued up to the sixtieth minute (p=0.002) after standard -dose ACTH stimulation. After ACTH stimulation, a weak negative correlation was found between peak cortisol and IMA levels at the thirtieth minute (r=0.233, p=0.02). There was no significant difference in IMA levels after low -dose ACTH stimulation, despite an increase in cortisol (p=0.161). Conclusion: IMA levels decreased rapidly after standard -dose ACTH stimulation, while a decrease in IMA levels was not observed after low -dose ACTH stimulation. The lack of decrease in IMA levels after low -dose ACTH stimulation suggests a possible dose -dependent relationship between ACTH and IMA. The moderate increase in cortisol with no reduction in IMA levels after low -dose ACTH stimulation and the weak correlation between peak cortisol and 30 -minute IMA levels after standard -dose ACTH stimulation suggest that ACTH may have a direct effect on IMA.

Objective: The onset of puberty in children is occurring at an increasingly earlier ages. During the coronavirus 2019 pandemic, children experienced epidemic-related changes such as stress, sedentary lifestyle, and weight gain. Materials and Methods: Auxological, clinical, endocrinological, and radiological data in the files of 57 patients who were given gonadotropin-releasing hormone analog therapy with the diagnosis of central precocious puberty between April 1 and July 1, 2019 (group 1) and April 1 and July 1, 2020 (group 2) were analyzed retrospectively. Results: A total of 27 patients (26 girls, 1 boy) in group 1 and 30 patients (28 girls, 2 boys) in group 2 were diagnosed with central precocious puberty. Mean ages at diagnosis for groups 1 and 2 were 28.54 ± 0.94 and 7.92 ± 0.96 years, respectively (P = .018). Mean bone age at diagnosis for group 1 was 9.78 ± 1.48 (6.8-12), and for group 2 it was 8.78 ± 1.11 (6.5-12) years (P = .013). The mean age of starting treatment in groups 1 and 2 was 8.94 ± 0.17 (6.8-9.8) and 8.07 ± 0.02 (5.8-10) years, respectively (P = .002). Average birth weights for groups 1 and 2 were 950 ± 1100 (2300-3400) and 3180 ± 717 (870-3820) g, respectively (P = .012). Treatment was started when breast stage was T3 in 57.69% of group 1 and T2 in 75% of group 2, and a statistical difference was found between them (P = .006) and uterine length was higher in group 2 (P = .144). Conclusion: During the coronavirus 2019 pandemic, patients who start central precocious puberty therapy were of younger age. In our single-center experience, coronavirus 2019 was not seen to have a significant impact on central precocious puberty. Cite this article as: Orman B, Esen S, Keskin M, Şahin NM, Savaş-Erdeve Ş, Çetinkaya S. Status of central precocious puberty cases at the onset of coronavirus disease 2019 pandemic: A single-center experience. Turk Arch Pediatr. 2022;57(3):349-353.