Objective: Acid-labile subunit (ALS) deficiency (ACLSD), caused by homozygous or compound heterozygous IGFALS mutations, is associated with moderate short stature, delayed puberty, low serum IGF-I and ALS and extremely low serum IGFBP-3. Its effect on birth weight, head circumference, bone mineral density (BMD), serum IGF-II and IGFBP-2 is uncertain, as well as the phenotype of heterozygous carriers of IGFALS mutations (partial ACLSD). Design: From all available members of five Turkish families, carrying three mutations in exon 2 of IGFALS (c.1462G > A, p.Asp488Asn (families A, B, E); c.251A > G, p.Asn84Ser (families C and E) and c.1477del, p.Arg493fs (family D)), clinical, laboratory and BMD data were collected. Methods: Auxological and biochemical findings were expressed as SDS for age and gender. Ternary complex formation in serum was investigated by size-exclusion chromatography. BMD using DXA bone densitometry was adjusted for height and age (Ha-BMD z-score). Results: In ACLSD (n = 24), mean ± s.d. height SDS (−2.7 ± 1.2), head circumference SDS (−2.3 ± 0.5) and body mass index (BMI) (−0.6 ± 1.0 SDS) were lower than those in partial ACLSD (n = 26, P ≤ 0.01) and birth weight SDS (n = 7) tended to be lower (−2.2 ± 1.1 vs −0.6 ± 0.3 in partial ACLSD (P = 0.07)). Serum IGF-I was −3.7 ± 1.4 vs −1.0 ± 1.0, IGF-II: −5.6 ± 0.7 vs −1.3 ± 0.7, ALS: <−4.4 ± 1.2 vs −2.1 ± 0.9 and IGFBP-3: −9.0 ± 1.9 vs −1.6 ± 0.8 SDS respectively (P < 0.001). Ha-BMD z-score was similar and normal in both groups. Conclusions: To the known phenotype of ACLSD (i.e. short stature, reduced serum levels of IGF-I and ALS, extremely low serum IGFBP-3 and disturbed ternary complex formation), we add reduced birth weight, head circumference and serum IGF-II.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. Recessive inactivating mutations in the ABCC8 and KCNJ11 genes account for approximately 50% of all CHI cases. Hyperinsulinaemic hypoglycaemia in infancy and diabetes in later life have been reported in patients with HNF1A, HNF4A and ABCC8 mutations. Herein, we present a child who was diagnosed with CHI at birth, then developed diabetes mellitus at the age of nine years due to a novel homozygous missense, p.L171F (c.511C>T) mutation in exon 4 of ABCC8. The parents and one sibling were heterozygous carriers, whilst a younger sibling who had transient neonatal hypoglycemia was homozygous for the mutation. The mother and (maternal) uncle, who was also heterozygous for the mutation, developed diabetes within their third decade of life. The preliminary results of sulphonylurea (SU) treatment was suggestive of SU responsiveness. Patients with homozygous ABCC8 mutations can present with CHI in the newborn period, the hyperinsulinism can show variability in terms of clinical severity and age at presentation and can cause diabetes later in life. Patients with homozygous ABCC8 mutations who are managed medically should be followed long-term as they may be at increased risk of developing diabetes after many years.

Thyroid hormone resistance (THR) is a dominantly inherited syndrome characterized by reduced sensitivity to thyroid hormones. It is usually caused by mutations in the thyroid hormone receptor beta (THRB) gene. In the present report, we describe the clinical and laboratory characteristics and genetic analysis of patients with a novel THRB gene mutation. The index patient had been misdiagnosed as hyperthyroidism and treated with antithyroid drugs since eight days of age. Thyroid hormone results showed that thyrotropin (thyroid-stimulating hormone, TSH) was never suppressed despite elevated thyroid hormone levels, and there was no symptom suggesting hyperthyroidism. A heterozygous mutation at codon 350 located in exon 9 of the THRB gene was detected in all the affected members of the family. It is important to consider thyroid hormone levels in association with TSH levels to prevent inappropriate treatment and the potential complications, such as clinical hypothyroidism or an increase in goiter size.

Fibroblast growth factor 21 (FGF21) is mainly secreted by the liver. It is a factor that is not fully understood in relation to growth. Sirtuin 1 (SIRT1) is a deacetylase protein. It is thought that may have an effect on the release and function of GH and IGF-1. Visfatin is synthesized from adipose tissue as primary. It may be prognostic marker associated with growth factors. As a result of our work, FGF21 is not associated with short stature but levels of SIRT1 and visfatin are associated with short stature. The decrease in visfatin value in the short-stature group is thought to be due to an insufficient amount of adipose tissue, which is important for growth and development. SIRT1 might decrease GH effect by increasing STAT5 deacetylation in the liver and we think that the result of this reduction of SIRT1 would negatively impact IGF-1 and IGFBP-3 production.

Insulin-like growth factor-1 (IGF-1) is the main driver of growth during prenatal life and acts through IGF-1 receptor (IGF1R). Patients with IGF1R defects exhibit variable phenotypic features. A 10.9-year-old boy presented with severe short stature, microcephaly, minor dysmorphic features and mental retardation. Genetic analysis for IGF1R revealed heterozygous deletion of the complete IGF1R. At the age of 12.3 years, daily subcutaneous recombinant human growth hormone (rhGH) was started and continued for a total of 5.7 years in two courses with improvement of height velocity as well as final height. Puberty was delayed and eventually he did not achieve full puberty, suggesting partial hypogonadotropic hypogonadism. Hypothyroidism initially developed during rhGH therapy. However, low T4 levels persisted after cessation of rhGH therapy and thus central hypothyroidism is a likely diagnosis. rhGH has partial effect for induction of growth in cases with IGF1R defects. However, long-term treatment with an early initiation may have more beneficial effects. In addition, patients with IGF1R defects should be followed for delayed puberty-hypogonadism, and hypothyroidism.

Objective: Publications have shown increased rate of precocious puberty and rapidly progressing puberty during the pandemic period. During the pandemic period, obesity has become widespread in children due to sedentary life, an increase in the time spent at home, and prolonged use of mobile devices. Obesity is a significant contributor to early puberty in females.We aimed to investigate whether obesity is a factor in the increase of puberty precocious cases during the pandemic. Material and Methods: In the study, female patients diagnosed with Puberty precocious /Rapidly Progressive Puberty in our clinic were divided into three groups August 2019-February 2020 before the pandemic (Group1-G1), August 2020-February 2021 during the pandemic (online education - Group2-G2), August 2021-February 2022 during the pandemic (face-to-face education -Group3-G3). The groups were retrospectively compared in terms of clinical, laboratory, and imaging findings. Results: A total of 495 female patients were included in the study. There was no difference between the groups in terms of age at the presentation. The most common complaint at presentation in the three groups was thelarche. Also, presentation with combination of thelarche and pubarche was more common in G3, and presentation due to menarche was more common in G2 (p=0.011). No difference was found between the groups regarding body weight SDS, and height SDS. The BMI SDS was 0.69±1 SD for all patients, 0.78±0.94 SD for G1, 0.67±1 SD for G2, and 0.67±1 for G3, and the BMI SDS of the groups were comparable (p=0.630). The majority of patients at the presentation were Breast Tanner stage 3. G2 (9%) and G3 (9%) were presented with Breast Tanner stage 4 at a higher frequency compared to G1 (2%). There was no difference between the groups’ FSH, LH, estradiol, LHRH test peak FSH, peak LH, and LH/FSH values. There was no difference between the bone ages of the groups at the presentation. The uterus size, right and left ovary volumes of G2 and G3 were significantly bigger than those of G1 (p=0.001). No difference was found between the groups in the rates of precocious puberty and rapidly progressing puberty cases. Conclusion: In our study, the age at presentation and BMI were similar pre-pandemic group G1 and during the pandemic, online education (G2) and pandemic face-to-face education (G3). We determined that obesity may not be one of the factors triggering precocious puberty cases during the pandemic period.