When primary hyperparathyroidism (PHPT) is diagnosed in a young patient in the absence of other clinical manifestations differential diagnosis between a sporadic form of PHPT and PHPT as the first manifestation of one of hereditary syndromes may be challenging. Diagnosis of sporadic or hereditary PHPT determines the extent of surgical intervention, a strategy for further observation and treatment, and the need for examination and treatment of first-degree relatives. 

Aim of the study — to determine genetic characteristics of PHPT with manifestation at a young age (<40 years old) with clinically sporadic PHPT and familial isolated hyperparathyroidism (FIHP).

Material and methods. 40 patients with manifestation of PHPT at the age younger than 40 years, 4 of which with FIHP, were included in the study. In 11 patients Sanger sequencing of MEN1 gene was performed (ABI 3130 Genetic Analyser, «Applied Biosystems», USA). 37 patients underwent next-generation sequencing (NGS) (Ion Torrent PGM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). 

Results. In 3 (7,5%) patients (1 of which with FIHP) we revealed germline heterozygous mutations in MEN1 gene: in exon 9 p.D418N, exon 3 p.R176Q, intron 3 с.654+1G>A. In 4 (4/40, 10%) patients we revealed germline heterozygous mutations in CDC73 gene: 3 nonsense mutations in patients with parathyroid carcinoma — in exon 3 p.R91X, exon 6 p.Q166X, exon 7 p.R229X, and 1 missense mutation in a patient with parathyroid hyperplasia in exon 8 p.R263C. 

Conclusions. In the majority of cases (75%) PHPT in young patients without positive family history is sporadic. Search for germline mutations in the genes, leading to development of hereditary forms of PHPT (first of all in MEN1 and CDC73), is appropriate in young patients with positive family history, or when positive family history may be suspected, and in patients with parathyroid carcinoma. In the majority (75%) of FIHP cases search for other, probably yet unknown, genes is necessary.

Endocrine disorders are common in patients after treatment for brain tumors in childhood. Growth hormone (GH) deficiency is the most common consequence of cranial irradiation. 

Objective — to evaluate the prevalence of GH deficieny and metabolic disorders in patients after treatment for malignant tumors of the posterior cranial fossa (MT PCF) in childhood. 

Material and methods. In this study 40 patients (21 men, 19 women) who had undergone treatment for MT PCF were assessed. Patients underwent surgery, chemotherapy and craniospinal irradiation (CSI) in a dose of 34.9±1.6 Gy with a boost to the PCF 51.3±9.2 Gy. Age at the time of the survey — 19.8±3.05 years; age at the time of treatment — 10.9±3.4 years; follow-up — 7.2±4.2 years. Patient’s anthropometric and laboratory parameters were measured, GH failure was diagnosed by two tests – insulin tolerance test (ITT) and glucagon stimulation test (GST). 

Results. According to ITT GH deficiency was observed in 82.1% and according to GST in 60.0% of patients. When comparing two tests GST showed 100% specificity, but lower sensitivity (72.2%). Manifestation of GH deficiency depends on the age at the time of treatment (p=0.002). There is significant correlation between age at the time of treatment and SDS of final height (r=0.632; p<0.001). We found a significant correlation between age at the time of treatment and BMI (r=–0,327; p=0.04). Dyslipidemia occurred in 50% of cases. Insulin resistance was recorded in 16.7% of patients. We found significant correlation between the HOMA-IR and BMI (r=0.336; p=0.034). 

Hypoparathyroidism is one of major components of autoimmune polyglandular syndrome type 1 (APS type 1) with a prevalence 73—83%. The protein NALP5 has been described previously as an antigen of parathyroid glands. 

Aim — to investigate antibodies against NALP5 in patients with APS type 1. 

Material and methods. Seventy nine patients with APS type 1 were included in the study. Radio-immune assay was used for detecting antibodies against NALP5. 

Results. The correlation between hypoparathyroidism and high levels of antibodies against NALP5 was found (p<0.001). Sensitivity of the method was 69,4%, specificity — 83,3%, positive predictive value — 93,5%, negative predictive value — 44,1%. Correlations between other components of the disease and high levels of the antibodies were not found. 

Conclusions. We found a positive correlation between antibodies against NALP5 and hypoparathyroidism in APS type 1 patients. We did not find correlations between antibodies against NALP5 and other components of APS type 1.

Aim — the present research was aimed at identifying the genetic causes for hr in patients, as well as evaluating the clinical, hormonal and biochemical characteristics of the disease in this group of patients.

Material and methods. 75 patients (aged, of 3 months to 57 years; females, n=38; males, n=37) with clinical and radiological findings of rickets, low serum phosphate and low tubular reabsorption of phosphate were included. ‘rickets panel’ genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). The panel included primers for multiplex amplification of 22 genes associated with genetic calcium metabolism dysfunctions. Bioinformatic analysis was performed using torrent suite (Ion Torrent) and ANNOVAR software packages.

Results. Out of the 75 patients 36 were diagnosed with familial form of hr, and 39 probands had sporadic cases. Out clinical characteristics the most widespread symptoms of the disease included: lower limbs malformations since the patients started to walk (94.5%), hypotonia in the first 12 months of life (70.2%), multiple caries (58%). Mutations were identified in 100% of familial and 88,5% of sporadic cases. In 68 probands (90,5%) mutations were detected in PHEX, 40 of which were novel. For familial forms of the disease mutations were discovered in 100% cases, for sporadic — in 82% cases. One subject had both DMP1 and PHEX mutations. No mutations were detected in FGF23, SLC34A1, SLC34A3, SLC9A3R1, ENPP1, CLClCN5 and SLC2A2 genes.

Conclusion. The study confirmed predominance of PHEX mutations among the patients with HR. The identification of causative agent is very important for antenatal diagnostics for familial forms of disease and enables well-timed conservative treatment.

Aim — to investigate the methods of treatment, directed on increase in quantity of spermatozoa in an ejaculate.

Material and methods. In investigation was used: chorionic gonadotrophin, anti-estrogen, recombinant preparations FSH, and also their combinations.

Results. The worst efficiency (10%) was noted when using monotherapy by preparation HCG. Efficiency of monotherapy by a preparation of clomiphene was higher and made 20% concerning conception, and 63% concerning an oligoteratozoospermiya. Efficiency of the combined therapy of HCG in combination with recombinant FSH was 40% concerning conception, and 87% concerning an oligoteratozoospermiya.

Conclusion. At the same time the studied types of the stimulating therapy are effective, safe and don’t lead to development of side effects.

Syndrome Donahue (leprechaunism) is a rare form of neonatal diabetes mellitus associated with INSR gene mutations. 

There are three types of insulin resistance syndrome: Donohue syndrome, Rabson—Mendenhall syndrome and insulin resistance type A. These syndromes are distinguished from one another by severity of symptoms, age of onset and age of death. Donohue and Rabson—Mendenhall syndromes are associated with biallelic mutations in the α-subunit or/and β-subunit of INSR gene and are characterized by more severe phenotype and poor prognosis. Patients with Donohue syndrome usually die within the first two years of life. Life expectancy of patients with Rabson—Mendenhall syndrome is 5—15 years. 

Most patients with insulin resistance type A have heterozygous mutations in the β-subunit and demonstrate mild phenotype. 

Here, we describe the first genetically confirmed case of syndrome Donahue in the Russian Federation.

Thyroid hormones control growth, development and metabolism in animals. The iodothyronine deiodinases catalyze the removal of an iodine residue from outer or inner ring of the pro-hormone thyroxin (T4) molecule, thus producing either the active form triiodothyronine (T3; activation) or inactive metabolites (reverse T3; inactivation), respectively. Type 1 deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on thyroid metabolism in physiology and pathology. Type 2 deiodinase (D2) initiates thyroid hormone signaling by activating the T4 to the biologically active T3 molecule followed by gene expression on a cell-specific basis. Expression of D2 in such specific tissues as hypothalamus, pitutary, brain, brown adipose tissue, cochlea, retina, skeleton demonstrates the role of enzyme in physiology of these organs suggesting further therapeutic application. The current review intended to provide an updated picture of the recent advances concerning the molecular properties of D1 and D2 as well as their role in physiology.

Obesity is one of major threats to people health and life. It increases risk of many diseases, including type 2 diabetes, heart disease, arthritis, and several cancers. This is a serious problem for the Russian Federation. Half of adults in our country are considered to be overweight or obese. However, to assess objectively the prevalence of this pathology in children is very difficult. At present in Russia there is no single universally accepted system for child anthropometry. Several studies in Russian regions found that about 10% of children were overweight and obese. Main risk factors of obesity in intrauterine and perinatal periods: mother smoking during pregnancy, child accelerated weight gain during the first months of life, formula feeding and early complementary feeding. In older children main risk factors are high-calorie foods, lack of exercise and sedative behaviour. International expert community has defined preventive strategies that will support elimination of child obesity. These strategies include implementation of child development assessment system with body mass index measurement in accordance with the World Health Organization guidelines; training primary pediatricians on using this assessment system and effective obesity prevention counseling; and school-based obesity prevention programs. Physicians and teachers must understand how important obesity prevention for child health. Health and education stakeholders should actively support these preventive measures and ensure universal access to physical exercises and healthy diet in schools. Alfa-Endo Program will assist all these initiatives.

In the Russian Federation growth hormone therapy (GHT) for children with growth hormone deficient children is funded from the state budget. The clinical effectiveness of GHT with human recombinant growth hormone was proven repeatedly in both world wide and Russian practice. Nevertheless, the economic and financial aspects of this therapy are in need of a detailed analysis. Such an analysis could serve as a possible instrument for well-grounded weighed decisions in the health care sector. One such instrument is a cost-effectiveness analysis, which involves the calculation of cost-effectiveness ratios or incremental cost-effectiveness ratios for determining the economic viability of new medical technologies or programs. Moreover, social aspects of GHT are also of great importance. A physician or a health care manager need to be informed about the effect of any therapy, including GHT, on the patient’s quality of life. While there is an overall agreement about the necessity and positive effect of GHT in children, the question remains somewhat disputable in the case of adult patients with growth hormone deficiency. Both world wide and in Russia there is no uniform agreement as to weather treatment is necessary in all cases of adult growth hormone deficiency, or weather treatment should be subsidized and provided for by the state or other financial resources, or weather GHT has indeed such a profound effect on the patient’s quality of life. The present article reviews the state of discussion around these questions to date for both children and adult patients. Available data on the cost-effectiveness analyses of GHT from several countries is highlighted and the effects of GHT on the quality of life are reviewed.