[Hypophysitis and reversible hypopituitarism developed after COVID-19 infection - a clinical case report].

AIM: To present a clinical case of reversible hypopituitarism due to hypophysitis developed after COVID-19 infection. MATERIALS AND METHODS: A patient with residual clinical manifestations of hypopituitarism underwent clinical evaluation at the time of symptoms of hypopituitarism and in follow-up. Morning serum cortisol (171-536 nmol/l) was measured by electrochemiluminescence immunoassay. Morning ACTH (7.2-63.3 pg/ml), prolactin (66-436 mU/l), TSH (0.25-3.5 mIU/L), fT4 (9-19 pmol/l) and fT3 (2.6-5.7 pmol/l) were measured by chemiluminescence immunoassay. Data were analyzed throughout the course of the disease. RESULTS: A 35-year-old female developed clinical symptoms of hypopituitarism two months after recovery from a confirmed COVID-19 infection. Laboratory investigation confirmed hypocorticism, hypothyroidism, hypogonadism and the patient was prescribed appropriate hormonal therapy in January 2021. Four months later the symptoms were alleviated (April 2021) and there were signs of recovery shown by imaging and hormonal: morning serum cortisol 227 nmol/l, morning ACTH 33.96 pg/ml, prolactin 68.3 mU/l, TSH 2.626 mIU/L, fT4 10.75 pmol/l, fT3 3.96 pmol/l. Thyroid hormone was discontinued, but hypogonadism and hypocorticism persisted with estradiol - 51.48 pmol/l, 24h urine cortisol level - 41.8 nmol/day. MRI results showed that the signs of hypophysitis were alleviated in comparison with MRI from January 2021. Full recovery of pituitary axis was reported in October 2021, with recovery of normal menstrual cycle. Furthermore, hormonal profile was likewise normal. CONCLUSION: This report provides evidence of delayed damage to the pituitary gland after infection with the COVID-19, with recovery of its function and structure. To date, the mechanisms of such an impact are not entirely clear; further collection of data on such cases and analysis is required.

[Vitamin D deficiency in Russia: the first results of a registered, non-interventional study of the frequency of vitamin D deficiency and insufficiency in various geographic regions of the country].

BACKGROUND: In Russian Federation, there are no large-scale cross-sectional multicenter epidemiological studies assessing the prevalence of vitamin D deficiency and insufficiency in different geographical latitudes. Insufficient solar insolation and inadequate vitamin D content in food dictate the need to study the epidemiological structure of low vitamin D status in Russia. AIM: To assess the incidence of vitamin D deficiency and insufficiency among the population living in the regions of the Russian Federation located at latitudes from 45 ° to 70 °. MATERIALS AND METHODS: The first stage of the Russian multicenter non-interventional registry study using the «crosssectional¼ method was carried out from March 2020 to May 2020. RESULTS: In regions that represent a geographically representative sample of regions of the Russian Federation with a high risk of developing low levels of vitamin D, it's deficiency was noted in 55.96%, and the level of deficiency and insufficiency was recorded in 84.01%. CONCLUSION: Close attention to the wide scale of the problem of vitamin D deficiency and insufficiency in the Russian Federation will contribute to the progressive formation of various educational and preventive programs necessary to strengthen health and improve the quality of life of the population.

[Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization].

AIM: To study the clinical, biochemical characteristics, treatment results and follow-up of patients with ectopic ACTH syndrome EAS (ACTH adrenocorticotropic hormone ). MATERIALS AND METHODS: A retrospective, observational, single-center study of 130 patients with EAS. Demographic information of patients, medical history, results of laboratory and instrumental investigations at the pre- and postoperative stages and follow-up of EAS were analyzed. RESULTS: The mean age at the diagnosis ranged from 12 to 74 years (Me 40 years [28; 54]). The duration of the disease from the onset of symptoms to the verification of the diagnosis varied from 2 to 168 months (Me 17.5 months [7; 46]). Eighty-one (62,3%) patients had bronchopulmonary NET, 9 thymic carcinoid, 7 pancreatic NET, 5 pheochromocytoma, 1 cecum NET, 1 appendix carcinoid tumor, 1 medullary thyroid cancer and 25 (19.2%) had an occult source of ACTH. The median follow-up period of patients was 27 months [9.75; 61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.1%) patients, bilateral adrenalectomy was performed in 23 (18%) patients, in 16 of them there was an occult source of ACTH-producing NET and in 7 patients in order to control hypercortisolism after non-successful surgical treatment. Regional and distant metastases were revealed in 25 (19.2%) patients. At the time of the last observation 59 (72%) patients were exhibited a full recovery, 12 (14.6%) had relapse of the disease and 26 (20%) died from multiple organ failure (n=18), pulmonary embolism (n=4), surgical complications (n=2), disseminated intravascular coagulation syndrome (n=1) or COVID-19 (n=1). CONCLUSION: In our cohort of patients bronchopulmonary NET are the most frequent cause of EAS (62.3%). Surgical treatment leads to remission of hypercortisolism in 72% cases; the proportion of relapse (14.6%) and fatal outcome (20%) remains frequent in EAS.

[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.

[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.

[Hereditary Cushing's syndrome caused by primary bilateral macronodular adrenal hyperplasia due to ARMC5 mutation with concomitant primary hyperparathyroidism: the first known case in Russia].

Primary bilateral macronodular adrenal hyperplasia (PBMAH), a genetically heterogeneous disease, is a rare cause of Cushing's syndrome. Until recently, few cases were attributed to mutations in known genes. However, in 2013, ARMC5, a newly discovered tumor suppressor gene, was identified. Further studies have shown that mutations in the ARMC5 gene are found in 25-55% of all PBMAH cases. This article describes a clinical case of hereditary Cushing's syndrome caused by PBMAH in a 37-year old patient. The patient's family history is remarkable for the presence of Cushing's syndrome and PBMAH in the patient's mother. Bilateral adrenalectomy was performed as the treatment of choice. Genetic analysis using whole-exome sequencing confirmed the hereditary cause of the disease, revealing a germline heterozygous mutation in the ARMC5 gene. The patient also had concomitant mild primary hyperparathyroidism, which had not been observed before in genetic carriers with the ARMC5 mutation.

Effects of endogenous hypercortisolism on bone mRNA and microRNA expression in humans.

Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. INTRODUCTION: The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing's disease (CD). METHODS: Bone samples were obtained during transsphenoidal adenomectomy from the sphenoid bone (sella turcica) from 16 patients with clinically and biochemically evident CD and 10 patients with clinically non-functioning pituitary adenomas (NFPA) matched by sex, age, and body mass index. Quantitative polymerase chain reactions (qPCR) were used to examine the expression of genes (mRNA and miRs) known to be involved in bone remodeling regulation based on studies in animals and cell culture. RESULTS: Hypercortisolism was associated with the downregulation of genes involved in osteoblast function and maturation (ACP5, ALPL, BGLAP, COL1A1, COL1A2, BMP2, RUNX2, TWIST1). An excess of GC caused increased expression of Wnt-signaling antagonists (Dkk1, SOST) and changes in the levels of miRs that are known to suppress osteoblastogenesis (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) p < 0.05, q < 0.1. Interestingly, compensatory mechanisms were found in long-term hypercortisolism: upregulation of Wnt10b, LRP5, and LRP6; downregulation of SFRP4; changes in miRs involved in osteoblastogenesis (miR-210-5p, miR-135a-5p, miR-211, miR-23a-3p, miR-204-5p); and downregulation of genes associated with osteoclastogenesis. None of these changes prevented the suppression of bone formation. CONCLUSIONS: An excess of endogenous GC in humans suppresses bone formation through the upregulation of Wnt-signaling antagonists and dysregulation of miRs involved in mesenchymal stem-cell commitment. Both Wnt-signaling antagonists and miRs seem to be promising targets for further research in therapeutic intervention in glucocorticoid-induced osteoporosis.

Serum extracellular secreted antagonists of the canonical Wnt/ß-catenin signaling pathway in patients with Cushing's syndrome.

UNLABELLED: Patients with endogenous hypercortisolism have higher sclerostin, but do not differ in Dickkopf 1 (Dkk1) or secreted frizzled-related protein 1 (SFRP1) levels as compared to healthy control. INTRODUCTION: Endogenous Cushing's syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of the Wnt/ß-catenin signaling pathway (sclerostin, Dkk1, SFRP1) in patients with CS versus healthy individuals. METHODS: Forty patients with clinically and biochemically evident CS and 40 sex-, age-, and body mass index-matched healthy subjects provided fasting serum samples for sclerostin, SFRP1 and Dkk1, along with bone turnover markers. RESULTS: Patients with CS had higher sclerostin levels (34.5 (30.3-37.1) pmol/L) versus healthy individuals (29.9 (24.3-36.8) pmol/L) (p = 0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper limits of the healthy control. The odds of sclerostin levels being higher than 30 pmol/L were greater in patients with CS as compared with the odds in healthy subjects (odds ratio = 3.81 95 % confidence interval 1.45-10.02) (p = 0.01). It coexisted with suppressed bone formation and unchanged bone resorption markers. Dkk1, SFRP1 did not differ from the control group. CONCLUSIONS: Of all the tested proteins (sclerostin, Dkk1, SFRP1), only sclerostin showed a significant difference when contrasting CS with healthy subjects. Hypercortisolism might prevent the down-regulation of sclerostin. Targeting sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with CS.

[The cardiovascular system in patients with symptomatic and mild primary hyperparathyroidism].

The cardiovascular system was analyzed in patients with symptomatic (n = 31) and mild primary hyperparathyroidism (n = 34) whose mean age was 54.6 years; 95% females). In the patients with symptomatic primary hyperparathyroidism, the PQ interval was longer and the QT interval was significantly shorter than those in patients with mild hyperparathyroidism. Left ventricular hypertrophy was noted in 45.2% of patients with symptomatic and in 15.2% of those with mild hyperparathyroidism (p = 0.013). Left ventricular diastolic dysfunction was also more common in the group of symptomatic hyperparathyroidism. There was a statistically significant correlation between the levels of parathyroid hormone, total and ionized calcium and the duration of QT interval and the determinants of diastolic function and left ventricular hypertrophy. The revealed cardiovascular disorders in patients with primary hyperparathyroidism are presumed to depend on the increase rate of parathyroid hormone and total and ionized calcium.

[Pseudohypoparathyroidism: genetic aspects].

The review of literature details the issues of genetics, the specific features of inheritance, the clinical picture and treatment of pseudohypoparathyroidisms (PHPT). In practice, clinicians more frequently deal with type 1 PHPT and the diagnosis of this type creates no significant problems. However, despite the low prevalence of the other types of PHPT - 1b, 1c, and 2, the diseases may run with noticeably clinical symptoms and present a significant problem in the context of diagnosis and treatment. This review may be of concern to both clinicians and geneticists who are interested in this problem.

[The severe course of hyperparathyroidism in the elderly: Clinical cases].

Primary hyperparathyroidism (PHPT) is a disease of the endocrine system caused by excessive secretion of parathyroid hormone (PTH) and is characterized by a pronounced violation of calcium and phosphorus metabolism. More recently, in Russia, PHPT was detected extremely rarely and often hid under the mask of recurrent urolithiasis, generalized osteoporosis and other pathologies. As a result, patients did not receive adequate treatment, which in a certain percentage of cases led to the development of serious complications.The clinical cases of severe PHPT in postmenopausal women are presented in this article.

[The first experience with selective blood collection from the inferior petrosal sinuses in Russia (case reports)].

This paper reports two clinical cases of ACTH-dependent hypercorticism. Difficulties encountered in differential diagnosis of this condition were due to poor informative value of routine diagnostic methods. The use of selective blood collection from the inferior petrosal sinuses (for the first time in Russia) greatly facilitated the choice of the adequate treatment strategy. A detailed description of clinical features of ACTH-dependent hypercorticism in two young women is presented along with the results of laboratory and instrumental studies. Technical aspects of selective blood collection from the inferior petrosal sinuses in conjunction with the desmopressin stimulation protocol are considered. Indications for the use of this diagnostic method under real clinical conditions are proposed. Results of the study are discussed with reference to the treatment strategy chosen for the management of ACTH-dependent hypercorticism and the outcome of surgical intervention.

[Significance of the method of selective blood collection from the inferior petrosal sinuses for differential diagnosis of ACTH-dependent hypercorticism].

This review paper was designed to discuss the accumulated worldwide experience with selective collection of blood from the inferior petrose sinuses for the purpose of differential diagnostics of ACTH-dependent hypercorticism. The history of the development of the method is described, principal indications and contraindications to its clinical application are considered with reference to the informative value of this diagnostic tool. Possible causes of false positive and false negative results as well as complications ever reported as associated with the diagnostic procedure are discussed. Much attention is given to the comparative analysis of advantages and disadvantages of alternative techniques for blood collection and to the use of pharmaceutical agents that may increase efficiency of the method under consideration.

[Russian consensus on the diagnosis, treatment, and monitoring of acromegalia (draft)].

Acromegaly is a serious disease of the hypothalamic-pituitary system, caused by chronic overproduction of growth hormone (GH) in individuals with completed physiological growth, affecting mainly people of working age. The disease is characterized by significant disability of patients and a reduction in life expectancy, the main reasons for which are complications caused by prolonged hypersecretion of GH. These include primarily damage to the cardiovascular system, respiratory system, metabolic disorders, malignant neoplasms of the gastrointestinal tract. At the same time, timely diagnosis and adequate treatment can reduce mortality several times, significantly improve the quality of life of patients.Until now, the problem of optimizing the diagnosis of acromegaly, especially the so-called "soft" form, as well as the choice of the most effective and safe treatment method, is relevant all over the world and in our country in particular.At the V Russian Congress of Endocrinology, a draft consensus on the management of patients with acromegaly was discussed. Subject to the provisions of the international agreement and Russian experience, recommendations are offered for the diagnosis, treatment and monitoring of this disease for further discussion, followed by the adoption of a final consensus.

[Influence of clinical and subclinical thyrotoxicosis on the adult skeletal system].

This review analyzed information on the effect of manifest and subclinical thyrotoxicosis on the bone system of adults.

[Adrenal cortical steroidogenesis and adrenal androgen secretion in Cushing disease].

The daily time course of changes In the secretion of dehydroepiandrosterone, its sulfate, and Cortisol, as well as their precursors (17-α-hydroxypregnenolone, 17-α-hydroxyprogesterone, and 11-deoxycortisol) was studied in patients with Itsenko-Cushing syndrome and disease. The mean daily blood concentrations were calculated for each hormone. The activity of the enzymatic systems of steroidogenesis was estimated from the ratio of the mean daily concentrations of the precursor of an enzymatic reaction to those of its product. The findings suggest that production of elevated concentrations of corticosteroids (both Cortisol and androgens) through the Δ5-pathway with the enhanced activity of 11ß-hydroxylase and sulfatase is characteristic of patients with Itsenko-Cushing disease. In patients with Itsenko-Cushing syndrome, the generation of higher Cortisol levels is accomplished through the Δ4-pathway whereas the synthesis of androgens through the Δ5-pathway is minimal due to the decreased activity of 17,20-desmolase.

[Clinical and economic rationale for the use of bivalos (strontium ranelate) in women with postmenopausal osteoporosis].

The social significance of osteoporosis (OP) is determined by its consequences - fractures of the vertebral bodies and tubular bones. The most serious complication of OP is a fracture of the proximal femur, with which the highest rates of mortality, disability and medical and social costs are associated than with other osteoporetic fractures combined. In 2005, a new drug appeared on the Russia for the treatment of women with OP in the postmenopausal period and for the prevention of peripheral and vertebral fractures - strontium ranelate (bivalos), which simultaneously reduces bone resorption and stimulates bone formation.

[Current views of the effects of thyroid hormones and thyroid-stimulating hormone on bone tissue].

The relationship between thyroid pathology and bone tissue was first noticed as early as 1891, when Recklinghausen described multiple fractures in a patient with untreated thyrotoxicosis. Despite the fact that in the modern etiological and pathogenetic classification of osteoporosis, thyrotoxicosis is included in the group of secondary osteoporosis, various aspects of the action of thyroid hormones on bone tissue continue to be studied to this day. The purpose of this review is to discuss the mechanisms of the influence of thyroid hormones on bone and, to a greater extent, to analyze new information on the biological and clinical significance of TSH for bone tissue. The review also provides information on the physiology of bone remodeling and the mechanisms of activation of receptors for thyroid hormones and TSH, which is necessary for a more complete understanding of hypotheses that explain the possible ways TSH affects bone cells.

[New mutation in the CYP17 gene: description of a case].

Deficiency of 17α-hydroxylase is a rare variant of congenital adrenal cortical dysfunction. The defect was first described by E. Biglieri et al. in 1966 in patients with sexual infantilism, pronounced excess mineralocorticoids with salt retention and arterial hypertension. Currently, several variants of the nonclassical course of the disease are described (with an increased level of aldosterone and without the development of hypertension and hypokalemia), the pathophysiological mechanism of which could not be explained. Cases of isolated deficiency of 17,20-lyase activity associated with mutations of R347H and R358Q in the CYP17 gene are also described. Here is the observation of a patient with a new mutation in the CYP17 gene with 17α-hydroxylase/17,20-lyase deficiency.

[A case of olfactogenital dysplasia (Kallmann's syndrome) in females].

Kallman syndrome develops as a result of impaired migration of neuronal (gonadotropin-releasing hormone) -producing cells from the medial olfactory zone of the brain into the preoptic nuclei of the hypothalamus. Currently, the connection between the development of olfactogenital dysplasia and a mutation of a gene located in the region of the p. 22.3 of the X chromosome has been proved. Clinically, olfactogenital dysplasia in women is manifested by primary amenorrhea and, as a result, by primary infertility. On examination, a physique of the eunuchoid type can be detected, moderate development of the mammary glands is rarely observed. In men - hypoplastic testicles, eunuchoid appearance is formed by adolescence (high growth, prepubertal testicles, infantile penis, complete absence of secondary sexual characteristics). This article presents the own results of a patient with Kallman syndrome.