E. N. Raykina

Pituitary stalk interruption syndrome is a rare congenital anomaly of the hypothalamic-pituitary region, often leading to multiple anterior pituitary hormone deficiency. Accumulating research postulates that hypothalamic-pituitary defects depend on variant changes in genes responsible for pituitary morphogenesis, particularly during early embryogenesis.We present a clinical case of a patient with an identified variant substitution in the GLI2 gene associated with impaired hypothalamic-pituitary development. The patient has been diagnosed with secondary hypothyroidism and growth hormone deficiency, along with signs of possible hypogonadotropic hypogonadism.Clinical features, current views on etiology, and the critical need for early diagnosis and long-term follow-up to detect new hormonal deficiencies and timely adjust replacement therapy are discussed.

BACKGROUND: Culler-Jones syndrome is a rare autosomal dominant disease caused by nucleotide sequence changes in the GLI2 gene. The prevalence of this pathology is unknown, as the number of observations is small, some carriers of variants in the GLI2 gene have no manifestations of the disease. The clinical phenotype of the disease is heterogeneous and includes hypopituitarism, malformations of internal organs, facial dysmorphisms, and polydactyly. Since the discovery of the GLI2 gene by Roessler E. et al. in 2003, the spectrum of clinical manifestations, as well as the understanding of the pathogenesis of the disease components, has expanded considerably. Incomplete penetrance has been described for the GLI2 gene, and the clinical phenotype of the disease differs even among members of the same family with the same nucleotide variant. AIM: Study clinical and molecular genetic polymorphism in patients with Culler-Jones syndrome. MATERIALS AND METHODS: A single-center, non-interventional, single-stage, non-comparative study was conducted. Children with Culler-Jones syndrome with a confirmed genetic cause of the disease were examined. All patients underwent a comprehensive examination, including laboratory and instrumental diagnostic methods and sequencing (by NGS (next-generation sequencing). RESULTS: 18 children (7 girls; 11 boys) with variants in the GLI2 gene were included in the study. The age at the time of examination was 8.95 years [4,6; 12.4]. Growth hormone deficiency was noted in all children at age of 2 years [1; 6,5]. Central hypothyroidism was diagnosed in 13 children at the age of 1.5 years [1; 3.5]. Free thyroxine level at the time of diagnosis was 8.9 pmol/L [7.5; 11.3]. Secondary hypoadrenocorticism was diagnosed in 10 children at the age of 2 years [1.5; 2.8], with a cortisol level of 84 nmol/L at the time of diagnosis [47; 152]. Extrahypophyseal manifestations characteristic of the syndrome were detected in half of the patients and included maxillofacial anomalies, malformations of the cardiovascular and urinary systems and eye malformations. Polydactyly was detected in two children. CONCLUSION: The present study demonstrates the clinical polymorphism of Culler-Jones syndrome and the lack of genotype-phenotype correlation for this disease.

Neonatal Hypoglycemia (NH) is one of the most frequent metabolic abnormalities, occurs in the neonatal period, affecting up to 15% of healthy neonates. The definition of NH remains controversial due to the lack of significant correlations between glucose levels blood glucose levels, clinical symptoms, and long-term outcomes. Some approaches define NH on the basis of clinical symptoms, others on the basis of plasma glucose levels. Because of this, there are currently no uniform recommendations on indications for glycemic fixation, reference values and critical glycemic thresholds. In recent years anumber of clinical recommendations for NH in different countries. Thus, the definition of clinically significant hypoglycemia remains one of the most confusing and controversial issues in modern neonatology. We analyzed the available clinical guidelines on neonatal hypoglycemia for the period from 2015 to the present, as well as the available dilemmas of clinical management of children with NH.

The recombinant technologies era, which began in the second half of the XX century, made it possible to produce recombinant growth hormone (rGH) necessary for the treatment of stunting of various genesis. The time of practically unlimited possibilities of rGH production has come, which served as a stimulus for studying the efficacy and safety of rGH application, searching for optimal ways of its use and dosing regimes. Many years of experience in the use of somatropin in clinical practice allowed us to obtain data on its effectiveness primarily in somatotropic insufficiency in children, to study its effect on the functional state of various organs and systems, and to expand the indications for the use of RGR.