BackgroundInsulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).MethodsWe conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.ResultsA total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1–46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations.ConclusionsIn this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.

Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congenital hypopituitarism due to deletions in chromosome 18. All children had a characteristic dysmorphic features and delayed mental and speech development. Within first months of life, patients developed muscular hypotension, dysphagia, and respiratory disorders. The patients had various congenital malformations in combination with hypopituitarism (isolated growth hormone deficiency and multiple pituitaryhormone deficiencies). In the neonatal period, there were the presence of hypoglycemia in combination with cholestasis.Hormone replacement therapy led to rapid relief of symptoms.Сhromosomal microarray analysis in 2 patients allowed us to identify exact location of deleted area and deleted genes and optimize further management for them.

ПАПИЛЛЯРНЫЙ РАК ЩИТОВИДНОЙ ЖЕЛЕЗЫ У ПАЦИЕНТА С СЕМЕЙНЫМ АДЕНОМАТОЗНЫМ ПОЛИПОЗОМАвторы: А.В

КЛИНИЧЕСКИЙ СЛУЧАЙ СИНДРОМАЛЬНОЙ ЗАДЕРЖКИ РОСТА В СОСТАВЕ СИНДРОМА ШЕЙТХАУЭРА-МАРИ-СЕНТОНА (ЧЕРЕПНО-КЛЮЧИЧНАЯ ДИСПЛАЗИЯ)Еникеева С.Р., Болмасова А.В

Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and transient forms of hyperinsulinism are distinguished. Transient hyperinsulinism are the most common cause of severe hypoglycemia in newborns. The etiology of this disease is not known. There are risk factors for the development of transient hyperinsulinism: asphyxia at birth, prematurity, maternal diabetes, low or large weight by gestation. Hypoglycemia with hyperinsulinism is severe. Therefore, early diagnosis and therapy especially during the neonatal period, are necessary.The article describes 3 clinical cases of transient hyperinsulinism in children with different gestational age and concomitant pathology. All children recevied insulinostatic therapy with diazoxide with a positive effect: euglycemia without glucose requirement . In all children, therapy was completed subsequently. At the time of publication of the article, the physical and psychomotor development of children is normal.

The monosomy 18p-syndrome refers to an extremely rare disorder (1:50,000 live-born infants). Congenital hypopituitarism is one of the manifestations of this syndrome in 13% of cases. The rarity of this pathology causes difficulties in the early detection of congenital hypopituitarism due to lack of awareness among paediatricians and neonatologists. The article presents a clinical case of congenital hypopituitarism in a girl with monosomy 18p-syndrome, which manifested itself after birth in the form of cholestasis and hypoglycaemia.

Congenital hypothyroidism with goiter is a rare disease. In the early neonatal period, the pathology can manifest itself as both hypothyroidism symptoms and signs of tracheal compression with a large goiter. The most common cause of this disease is antithyroid maternal therapy, which accounts for 10-15% of congenital goiter cases. In the case of an unremarkable maternal history, the main cause of goiter is thyroid hormone dyshormonogenesis. Here, we present a case of congenital hypothyroidism with a giant goiter (55 cm3). The child was intubated soon after birth due to respiratory disorders and asphyxia caused by tracheal compression. In addition, the patient had tricuspid valve insufficiency and cardiomegaly. Levothyroxine substitution therapy initiated on the first day of life led to a rapid decrease in the thyroid volume and structural changes in the heart. The patient`s DNA was analyzed using a wide genetic panel «Congenital hypothyroidism»; no mutations were found. Despite the absence of mutations in genes involved in thyroid formation, we consider dyshormonogenesis as the most likely cause of goiter in our patient.

The idiopathic form of premature sexual development (PSD) is the commonest variety among the central forms of PSD (accounting for 30 to 70% of the total). It occurs primarily in the girls. The prevalence of hypothalamic hamartoma (HH) as a cause of premature sexual development is on the whole lower, but it is most frequently diagnosed in the children of either sex under the age of 3 years with the clinical manifestations of true PSD. Diagnostics and treatment of different forms of premature sexual development constitute an appreciable part of the practical work of a pediatric endocrinologist. The efficacy of PSD therapy with luliberin analogs has been definitively demonstrated in the context of increasing the final height of the children and suppressing the progression of their sexual development. Moreover, the reversibility of the effects of luliberin analogs on the gonadostatic activity has been confirmed. Nevertheless, peculiarities of the clinical course of various etiological variants of central PSD, principles of its treatment, and its efficacy remain a matter of debate. In the present paper, the special emphasis is laid on the consequences of PSD therapy using luliberin analogs including the recovery of the process of normal puberty, effects on the reproductive function, body weight, and the dependence of the treatment on the clinical form of central PSD. The data on the peculiarities of the clinical course of premature sexual development and the efficacy of its treatment in the children with the idiopathic form of gonadotropin-dependent PSD and hamartoma-associated PSD are presented

The idiopathic form of premature sexual development (PSD) is the commonest variety among the central forms of PSD (accounting for 30 to 70% of the total). It occurs primarily in the girls. The prevalence of hypothalamic hamartoma (HH) as a cause of premature sexual development is on the whole lower, but it is most frequently diagnosed in the children of either sex under the age of 3 years with the clinical manifestations of true PSD. Diagnostics and treatment of different forms of premature sexual development constitute an appreciable part of the practical work of a pediatric endocrinologist. The efficacy of PSD therapy with luliberin analogs has been definitively demonstrated in the context of increasing the final height of the children and suppressing the progression of their sexual development. Moreover, the reversibility of the effects of luliberin analogs on the gonadostatic activity has been confirmed. Nevertheless, peculiarities of the clinical course of various etiological variants of central PSD, principles of its treatment, and its efficacy remain a matter of debate. In the present paper, the special emphasis is laid on the consequences of PSD therapy using luliberin analogs including the recovery of the process of normal puberty, effects on the reproductive function, body weight, and the dependence of the treatment on the clinical form of central PSD. The data on the peculiarities of the clinical course of premature sexual development and the efficacy of its treatment in the children with the idiopathic form of gonadotropin-dependent PSD and hamartoma-associated PSD are presented