Idiopathic central diabetes insipidus in a large cohort of patients: the hypopituitarism ENEA rare observational (HEROS) study.

Central Diabetes Insipidus (CDI) is mainly associated with structural pathologies of the hypothalamic-pituitary area. Etiologies underlying CDI are identified in most patients, however idiopathic CDI is reported in 13-17% of cases after excluding other etiologies. The Hypopituitarism ENEA Rare Observational Study (HEROS study) retrospectively collected data of patients with idiopathic CDI from 14 pituitary centers in 9 countries. The cohort included 92 patients (59 females 64%), mean age at diagnosis was 35.4 ± 20.7 years, and a mean follow up of 19.1 ± 13.5 years following CDI diagnosis. In 6 women, diagnosis was related to pregnancy. Of 83 patients with available data on pituitary imaging, 40(48%) had normal sellar imaging, and 43(52%) had pathology of the posterior pituitary or the stalk, including loss of the bright spot, posterior pituitary atrophy or stalk enlargement. Anterior pituitary hormone deficiencies at presentation included hypogonadism in 6 (6.5%) patients (5 females), and hypocortisolism in one; during follow-up new anterior pituitary deficiencies developed in 6 patients. Replacement treatment with desmopressin was given to all patients except one, usually with an oral preparation. During follow up, no underlying disease causing CDI was identified in any patient. Patients with idiopathic CDI following investigation at baseline are stable with no specific etiology depicted during long-term follow-up.

Multiple bilateral hip fractures in a patient with dyskeratosis congenita caused by a novel mutation in the PARN gene.

We report a case of a young male patient with clinical signs of dyskeratosis congenita who presented with multiple bilateral low-traumatic hip fractures. Whole exome sequencing (WES) showed a previously unreported mutation in the poly(A)-specific ribonuclease (PARN) gene. Zoledronic acid 5 mg over 3 years was effective at preventing further fractures. A male patient was referred to our clinic at age 24 due to multiple bilateral hip fractures. At the time of admission, the patient's height was 160 cm and weight 40 kg; bone mineral density (BMD) at the lumbar spine was normal (L1-L4 0.0 Z-score). The patient was found to have abnormal skin pigmentation, hyperkeratosis of palms and soles, nail dystrophy, and signs of bone marrow failure (BMF). Bone fragility first presented at 5 years old with a wrist fracture, followed by multiple bilateral low-traumatic hip fractures without falls from 14 to 24 years. WES showed a previously unreported mutation (NM_002582.3: c.1652delA; p.His551fs) in the poly(A)-specific ribonuclease (PARN) gene. Flow fish telomere measurement result was 5.9 (reference range 8.0-12.6), which is consistent with the DC diagnosis. Permanent fixation with internal metal rods and zoledronic acid 5 mg over 3 years was effective at preventing further fractures over 4 years of follow-up. Additionally, BMF did not progress over 4 years of observation. DC associated with PARN gene mutations might predispose to low-traumatic multiple hip fractures in adolescents and young adults. Treatment with zoledronic acid in this case was effective and safe at preventing further fractures.

[Algorithm for morphological diagnosis of neoplasms in the chiasmal-sellar region]. / Algoritm morfologicheskoi diagnostiki novoobrazovanii khiazmal'no-sellyarnoi oblasti.

In the Turkish saddle area, there is a wide variety of pathological processes, the vast majority of which present as tumors of various origins (up to 90%). For a clear morphological verification of the diagnosis, it is proposed to use a diagnostic algorithm that includes the stages of differential diagnosis of normal adenohypophysis and neurohypophysis with tumors in the anterior and posterior lobes of the pituitary gland, non-pituitary origin neoplasms, as well as with non-tumor pathological processes (inflammation, cystic masses, and hyperplasia). For morphological diagnosis, histochemical and immunohistochemical methods are recommended using various staining techniques (silver impregnation, periodic acid Schiff reaction) of tissue specimens and antibody panels (pituitary hormones, low-molecular cytokeratins, pituitary transcription factors, neuroendocrine markers, etc.).

[The first Russian multicenter non-interventional registry study to study the incidence of vitamin D deficiency and insufficiency in Russian Federation].

AIM: To assess the incidence of vitamin D deficiency and insufficiency among the adult population living in the regions of the Russian Federation located at latitudes from 45 to 70. MATERIALS AND METHODS: Russian multicenter non-interventional registry study using the "cross-sectional" method. RESULTS: In this study, 72.1% of the examined have the status of vitamin D deficiency and insufficiency, while an adequate level was diagnosed in 27.8% of cases. When assessing the degree of vitamin D deficiency depending on the season, statistically significant differences (p0.00001) were found between the periods: vitamin D deficiency or insufficiency was observed in 84.2% of autumn and in 62.4% of spring. The highest incidence of vitamin D deficiency and insufficiency was recorded in males compared with females (p=0.013, 79 and 70.3% respectively). Vitamin D deficiency is observed in young people in the age subgroup of 1825 years (p0.001, 54% in the study as a whole) much more often than in older people Conclusion. The widespread high prevalence of vitamin D deficiency in the Russian Federation is not related to geographic region of residence, but to some extent depends on the season. The high-risk group for vitamin D deficiency and insufficiency is young men. The significant role of vitamin D in the human body justifies the need to supplement and clarify a single concept for the prevention, diagnosis and treatment of conditions associated with deficiency, so higher implementation of National Clinical Guidelines is needed.

Evaluation of monomeric prolactin level by TRACE method and precipitation with polyethylene glycol.

Prolactin exists in various forms including the monomeric biologically active form (23kDa) and a higher molecular weight form, bound most commonly to IgG, known as macroprolactin (>100kDa). Macroprolactin lacks biological activity and is one of the causes of false-positive results. In Russian Federation the most common method for macroprolactin determination is PEG precipitation test. We had conducted a retrospective analysis of 37 samples of patients with hyperprolactinemia (3 of them were males). The mean age was 30 [25;35] years. Prolactin level was measured by the immunoenzyme method with manual PEG precipitation and TRACE. The mean values found by the immunoenzyme method with manual PEG precipitation were 461,6 [375,0;821,2] mU/l, by TRACE - 449,9 [357,2;749,2] mU/l. The number of patients with normal prolactin levels was 30% (11) confirmed by two methods, high prolactin level at 46% (17). The prevalence of clinical symptoms of hyperprolactinemia was not differ depend the groups. The phenomenon of macroprolactinemia was registered in 32% (12) of patients. In 8 persons of this group normal prolactin level was revealed and in 4 patients hyperprolactinemia was found by TRACE. Measurements of prolactin levels by the TRACE method is useful for correct diagnosis in patients with equivocal results received by traditional method with PEG precipitation.

[The role of vitamin D in seasonal acute respiratory viral infections and COVID-19].

A link between vitamin D deficiency and susceptibility to infectious diseases was suggested over a hundred years ago. Epidemiological studies show a strong association between seasonal fluctuations in vitamin D levels and the incidence of various infectious diseases, including septic shock, acute respiratory infections, and influenza. Our understanding of vitamin D metabolism and its extra-skeletal functions has improved significantly over the past three decades, and the discovery that the vitamin D receptor and 1a-hydroxylase, an enzyme needed to convert vitamin D to its active form, is present in the cells of the immune system, revolutionized in this area. Recent studies have shown that vitamin D regulates the expression of specific endogenous antimicrobial peptides in immune cells, modulates the immune response and the course of autoimmune processes; these actions indicate the potential role of vitamin D in modulating the immune response to various infectious diseases. This publication reviews the literature on the effects of vitamin D on immunity, its potential in the prevention and treatment of viral diseases, with a particular focus on COVID-19.

[Morphofunctional features of non-functioning pituitary adenomas]. / Morfofunktsional'nye osobennosti gormonal'no-neaktivnykh adenom gipofiza.

Non-functioning pituitary adenomas (NFPAs) account for about 30% of all pituitary tumors. NFPAs are characterized by the lack of secretory potential or its weak expression insufficient for determination of the blood level of adenohypophyseal tropic hormones and for development of a specific clinical picture. Morphologically, NFPAs are a heterogeneous group of tumors, the classification of which was previously based only on immunoreactivity for pituitary tropic hormones. The WHO revised its Classification of Tumors of Endocrine Organs (4th edition) in 2017. The main changes relate to adenohypophysial-cell lineage for the designation of adenomas into subtypes. The introduction of transcription factor antibodies has become a fundamentally new approach to the classification of NFPAs, which is necessary to recognize less differentiated tumor types. This paper provides information on the new histopathological classification of pituitary adenomas, on the theories of silent adenomas, and on the proliferative and prognostic markers of NFPAs.

[Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics]. / Laktotrofnye adenomy gipofiza, rezistentnye k lecheniiu agonistami dofamina: gistologicheskaia i immunogistokhimicheskaia kharakteristika.

OBJECTIVE: To present the histological and immunohistochemical characteristics of pituitary lactotroph adenomas (PLAs) resistant to dopamine agonist treatment. SUBJECT AND METHODS: The investigators examined paraffin-embedded blocks and histological sections obtained from 19 patients (13 women, 6 men), whose median age was 29 (19, 38) years, after surgical treatment (adenomectomy) for PLAs resistant to dopamine agonist treatment. Immunohistological examination was performed using antibodies against prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), type 2 dopamine receptors (DR2), estrogen receptors-α (ERα), the proliferation marker Ki-67, and the endothelial cell marker CD34. RESULTS: The expression of PRL by adenoma cells was revealed in all the patients. The coexpression of PRL and GH without clinical and laboratory signs of acromegaly was established in 3 cases. No expression of TSH, ACTH, LH, or FSH was revealed in any cases. Positive immunoreaction using antibodies against DR2 and ERα was detected in 8 and 6 cases, respectively. No expression of any of the studied receptors was found in 6 patients. Ki-67 was more than 3% in 3 patients and higher in patients with supra- or retrosellar growth. There was a positive correlation between the serum level of Ki-67 and that of PRL at the onset of the disease. There were 37 (25, 85) adenoma vessels, as measured by CD34 immunoexpression. It was ascertained that the patients with parasellar adenoma had more tumor vessels than those without parasellar growth of adenoma and that with the latter invading the cavernous vessels, the number of vessels was statistically significantly more. CONCLUSION: PLAs resistant to dopamine agonists in addition to PRL (100%) can express GH in 16% of cases are characterized by the immunoexpression of DR2 (42%) and ERα (32%), a low proliferative activity, increased angiogenesis in the adenomas with parasellar growth and invasion into the cavernous sinus.

Vitamin D: effects on pregnancy, maternal, fetal and postnatal outcomes.

A high prevalence of vitamin D deficiency and its negative consequences for health is identified as area of primary concern for scientists and clinicians worldwide. Vitamin D deficiency affects not only bone health but many socially significant acute and chronic diseases. Observational studies support that pregnant and lactating women, children and teenagers represent the high risk groups for developing vitamin D deficiency. Current evidence highlights a crucial role of vitamin D in providing the fetal life-support system and fetus development, including implantation, placental formation, intra- and postpartum periods. Hypovitaminosis D during pregnancy is associated with a higher incidence of placental insufficiency, spontaneous abortions and preterm birth, preeclampsia, gestational diabetes, impaired fetal and childhood growth, increased risk of autoimmune diseases for offsprings. Potential mechanisms for the observed associations contain metabolic, immunomodulatory and antiinflammatory effects of vitamin D. Epigenetic modifications in vitamin D-associated genes and fetal programming are of particular interest. The concept of preventing vitamin D deficiency is actively discussed, including supplementation in different ethnic groups, required doses, time of initiation and therapy duration, influence on gestation and childbirth. An adequate supply of vitamin D during pregnancy improves the maternal and fetal outcomes, short and long term health of the offspring. Still current data on relationship between maternal vitamin D status and pregnancy outcomes remains controversial. The large observational and interventional randomized control trials are required to create evidence-based guidelines for the supplementation of vitamin D in pregnant and lactating women.

[Ectopic ACTH-syndrome caused by neuroendocrine tumor of lung]. / AKTG-éktopicheskii sindrom pri neiroéndokrinnoi opukholi legkogo.

Ectopic ACTH-syndrome is a relatively rare neuroendocrine disease. It is characterized by hypercortisolemia-associated severe complications that justifies need for timely diagnosis and radical therapy. Case report of young patient with ACTH-producing lung tumor is presented. There was 1-year diagnostic search on background of endogenous hypercorticism. Treatment resulted severe postoperative adrenal insufficiency that demonstrates current difficulties in management of these patients.

[CDC73 mutations in young patients with primary hyperparathyroidism: A description of two clinical cases]. / Mutatsii v gene CDC73 u molodykh patsientok s pervichnym giperparatireozom (opisanie dvukh klinicheskikh sluchaev).

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

[Multiple endocrine neoplasia type 1 syndrome with three classical components and chiasm glioma: specific features of target organ lesions and a clinical observation].

The article briefly reviews the specific features of target-organ lesions in multiple endocrine neoplasia type 1 (MEN1) syndrome and a clinical case of genetically confirmed MEN1 syndrome in a young female patient. Despite the relative rarity of this disease, timely diagnosis, treatment and screening for its main components are very important for the overall prognosis of patients with MEN1 and their first-degree relatives who are MEN1 gene mutation carriers. The described case is noteworthy for a number of specific features. The authors could find no account of optic chiasm glioma within the framework of MEN1 in the literature. Moreover, therapy-resistant somatoprolactinoma engages attention, which points to its aggressive nature with pituitary adenoma that is not been clearly visualized on magnetic resonance imaging. Of interest is the order of detection of neoplasms, in particular the manifestation of hypoglycemic episodes as a sign of organic hyperinsulinism. which have been initially regarded as epileptic seizures, after the use of sustained-release somatostatin analogues for the treatment of acromegaly.

[TYPE 1 MULTIPLE ENDOCRINE NEOPLASIA SYNDROME AND FAMILIAL ISOLATED HYPERPARATHYROIDISM].

Type 1 multiple endocrine neoplasia syndrome (MEN-1) is a rare autosomal dominant disorder caused by mutation in the MEN-1 gene and manifest as a combination of tumours of parathyroid glands, endocrine pancreas, and adenohypophysis. Familial isolated hyperparathyroidism (FIHP) is another rare autosomal dominant disorder characterized by the development ofparathyroid tumours as the sole endocrinopathy within a single family. The notion of FIHP encompasses different hereditary forms of primary hyperparathyroidism, such as a variant of MEN-1 syndrome. This paper is a brief literature review of the problems related to primary hyperparathyroidism, MEN-1, and FIHP. Also, It describes a family presenting with genetically confirmed MEN-1 syndrome, manifest as primary hyperparathyroidism.

[Multiple endocrine neoplasia type 1 variants and phenocopies].

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease due to a mutation in the MENI tumor suppressor gene. The risk of the disease in first-degree relatives of MEN1 mutation carriers is 50%. MENI gene mutations are not identified in 10-30% of familiar MEN1 patients and in 60-80% of sporadic MEN1 cases, which can be explained by mutations in the noncoding regions of the MEN1 gene, large gene deletions or mutations in other yet unknown genes. Molecular genetic testing can exclude the diagnosis of MEN1 in patients who do not harbor the MEN1 mutation, thus revealing a MEN1 phenocopy. This obviates the need for annual screening for the early detection of other remaining components of the disease and its risk in progeny.

[The history of the institute of higher and additional professional education of the Endocrinology Reserch Centre].

The Endocrinology Reserch Centre is proud not only of its achievements in the area of personalized approach to the examination and treatment of patients in accordance with the principles of evidence-based medicine, the use of modern diagnostic and treatment technologies, but also of its rich history of training scientific and medical personnel. For many years the Center has been attracting the best and most talented graduates of higher medical institutions, becoming the "alma mater" for young doctors - endocrinologists, pediatric endocrinologists and nutritionists. Specialists, graduates of NMRC, make a significant contribution to the development of medicine, conducting research, creating innovative methods of treatment and helping patients not only in our country, but also abroad. However, the State Research Center of the Russian Federation FGBU «NMRC Endocrinology¼ is famous not only for its high-quality and comprehensive training, but also for its experienced, dedicated teaching staff, giving students unique opportunities for professional growth. The purpose of this article is to reflect the most important milestones in the development of education at NMIC Endocrinology, which began its formation more than a century ago, during the most difficult period of transition for our country.

[Features of water-electrolyte balance in persons of the older age group].

Age-related changes have a great influence on the regulation of water and electrolyte homeostasis in the body, which is regulated by a complex interaction of environmental factors, drinking behavior, the secretion of a number of hormones and hormone-like substances, as well as the innervation and functional state of the kidneys. It is well known that the changes that are part of physiological aging underlie fluid and electrolyte imbalances, exacerbated by the presence of age-related diseases, medications, or a number of external factors such as malnutrition, fluid intake, and the presence of dementia. This review considers literature data on the effect of normal aging on the development of pathology of the water-sodium balance, including dehydration of senile patients, hyponatremia, hypernatremia, changes in the secretion of antidiuretic hormone and the activity of elements of the renin-angiotensin-aldosterone system.

[Differential diagnosis and tactics of managing a patient with primary hypophysitis on the example of a clinical case].

In recent years, there has been a significant increase in the prevalence of autoimmune endocrinopathies, which are known to affect various levels of the endocrine system, including the pituitary gland. Hypophysitis is a general term used to describe any form of sellar and suprasellar inflammation that leads to structural changes in the hypothalamic-pituitary region and manifests itself in varying degrees of hormonal deficiency of the anterior and posterior pituitary glands. To date, there is a primary form of hypophysitis, which occurs as a result of an autoimmune lesion directly to the pituitary gland, and a secondary form of hypophysitis, which occurs as a result of the presence of a systemic autoimmune disease. Regardless of the etiology, patients with hypophysitis show various signs and symptoms caused by an inflammatory process in the pituitary gland, which can lead to the development of hypopituitarism, compression of the sellar and parasellar structures. MRI is currently the best non-invasive diagnostic tool for diagnosing hypopituitarism, however, the diagnosis can be made with certainty only by histological examination of the pituitary tissue, which requires an invasive approach, which greatly reduces the feasibility of this procedure. In this article, we present a patient with MRI showing signs of hypophysitis in the absence of clear clinical symptoms.

[Overcoming therapy resistance in prolactinomas: from perspectives to real clinical practice].

The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.

[Resolution of the national interdisciplinary council of experts "High-dose vitamin D (Devilam) in the practice of an obstetrician-gynecologist"].

On March 28, 2024, the Council of Experts "High-dose vitamin D (Devilam) in the practice of obstetrician-gynecologist, gynecologist and endocrinologist" was held in Moscow with the participation of leading experts gynecologists, endocrinologists and obstetricians-gynecologists, during which new possibilities for the use of high-dose vitamin D in patients of various ages who need correction of existing vitamin D deficiency or insufficiency.

[Educational trajectories of the endocrinological service: the results of a survey].

Given the socio-economic, political and epidemiological changes in the regions of the Russian Federation, the issue of modernizing the training of medical personnel and planning to provide medical organizations with qualified specialists has remained extremely important for several years. The analysis of the survey showed that at present the highly topical issue of staffing the population with endocrinologists and pediatric endocrinologists does not have an unambiguous effective solution. The above measures to reorganize the educational environment require additional revision and correction for the most effective work in the field of medical education. Ultimately, these activities will have an impact on improving the level of training of specialists, improving the personnel situation in the constituent entities of the Russian Federation and improving the quality of medical care for the population of the country.