[Primary Generalized Glucocorticoid Resistance: a case report].

Primary glucocorticoid resistance (OMIM 615962) is a rare endocrinologic condition caused by resistance of the human glucocorticoid receptor (hGR) to glucocorticoids (GR) and characterised by general or partial insensitivity of target organs to GK. Compensatory activation of hypothalamic-pituitary-andrenal axis results in development of a various pathological conditions caused by overstimulation of adrenal glands. Clinical spectrum may range from asymptomatic cases to severe cases of mineralocorticoid and/or androgen excess. At present time, primary generalized glucocorticoid resistance has been exclusively associated with defects in the NR3C1 gene. Here, we present a case report of an adolescent patient with clinical presentation of glucocorticoid resistance confirmed by detailed endocrinologic evaluation but no confirmed mutations in the NR3C1 gene.

[Prepubertal gynecomastia at the debut of hereditary tumors predisposition syndrome (clinical case reports)].

Peutz-Jeghers Syndrome (Peutz-Jeghers Syndrome, PJS) refers to syndromes of hereditary tumor predisposition and is caused by pathological variants of the STK11 gene, leading to a defect in the synthesis of serine/threonine kinase 11 protein, which acts as a tumor suppressor.Clinical symptoms of the syndrome are combination of hamartomatous polyposis of the gastrointestinal tract and specific skin-mucosal hyperpigmentation. Also, this disease is characterized by a high risk of developing gastrointestinal and extra-intestinal tumors, including benign or malignant tumors of the reproductive system.One of the first signs of the disease in male patients may be prepubertal gynecomastia associated with large-cell calcifying Sertoli cells tumors expressing aromatase. In contrast to from pubertal gynecomastia, prepubertal is extremely rare, and it is often based on pathological causes. Early diagnosis of patients with pre-pubertal gynecomastia, including Peitz-Jaegers syndrome, defines the tactics of gynecomastia management and protocols for monitoring the development of other components of the disease in the future.This article describes two patients with pre-pubertal gynecomastia and Peitz-Jaegers syndrome with different molecular genetic defects: in one case associated with duplication of the STK11 gene site, in the other - with microdeletion of the short arm of chromosome 19 containing this gene.

[Puberty induction in boys with congenital isolated hypogonadotropic hypogonadism].

BACKGROUND: Gonadotropin therapy in boys with congenital isolated hypogonadotropic hypogonadism helps to increase testes volume and induce spermatogenesis in comparison with testosterone therapy. However, difficulties with dose titration, partial therapy success, absence of generally accepted regimen protocols don't allow to use this therapy in order to induce puberty in adolescents with Kallmann syndrome or normosmic hypogonadotropic hypogonadism. AIM: To assess the effectiveness of combination hormonal replacement therapy via human chorionic gonadotropin and recombinant follicle stimulation hormone in adolescents with congenital isolated normosmic hypogonadotropic hypogonadism and with Kallmann syndromeMATERIALS AND METHODS: This is an open single-center prospective non-controlled study. Boys with hypogonadotropic hypogonadism were receiving hormonal replacement therapy for 12 months. Initial dose of human chorionic gonadotropin was 500 IU per week. Initial dose of recombinant follicle stimulation hormone was 37.5 IU per week. Doses were doubled in 6 months. Antropometric data, Tanner stage, testes volumes, inhibin B and anti-Mullerian hormone (AMH) levels were evaluated in all the patients before the treatment, after 6 and 12 months of the therapy. RESULTS: 8 boys with hypogonadotropic hypogonadism were included into the study. Median age before therapy initiation was 15.7 years [15.33; 16.41]. In 12 months after the therapy initiation puberty development, testosterone increase from 0.44 [0.34;0.62] to 4.39 [0.88;10.51] nmol/l (p=0.012), AMH decrease from 35.70 [18.00;59.00] to 14.41 [11.60;16.65] ng/ml were noted in all the patients (p=0.017). Testes volumes increase and inhibin B level increase were not statistically significant. CONCLUSION: Gonadotropin therapy is effective in order to puberty initiation in adolescents with congenital hypogonadotropic hypogonadism. In helps to achieve not only androgenization, but also to Sertoli cells maturation.

Course of Cushing`s disease and treatment outcomes in correlation with pituitary MRI in children.

BACKGROUND: Cushing's disease (CD) is a rare disorder of a persistent cortisol excess caused by ACTH-secreting pituitary tumor (corticotropinoma). Transsphenoidal surgery (TSS) is a treatment of choice for СD, which effectiveness range is from 70 to 90%. Recurrence rate after successful treatment is about 25%. If surgical treatment is unsuccessful or recurrence appear, radiation treatment is the next therapeutic option, which effectiveness range is also 90%, but the hypopituitarism rate as side effect of treatment is higher. Preoperative predictors of remission and recurrence are still unexplored what leads to further investigations. AIM: Analysis of remission and recurrence rates of pediatric CD after successful treatment according to preoperative MRI and therapeutic option. MATERIALS AND METHODS: We conducted a retrospective analysis of 90 pediatric patients with CD who were observed between 1992 and 2020 at the Endocrinology Research Centre. RESULTS: The most common clinical symptoms of CD were weight gain [94%] and growth retardation [72%]. Pituitary tumor was detected on radiological imaging in 53/90 patients [59%], there were no signs of visible adenoma in 37/90 of patients [41%]. 63 of 90 patients underwent TSS (70%), 27 patients underwent radiosurgery (30%). Remission rate after TSS was 71% [45/63], after radiosurgery - 85% [23/27]. There were no significant differences in remission rates after radical treatment according to preoperative MRI results (P=0.21 after TSS and P=0.87 after radiosurgery, х2 analysis). Recurrence after successful treatment was diagnosed in 10 patients. There were no significant differences in time to recurrence according to preoperative MRI results (P=0.055, х2 analysis). Time to recurrence was statistically different after TSS compared to radiosurgery (P=0.007, Kaplan-Meier analysis) and in the group with developed adrenal insufficiency in the early postoperative period (P=0.04, Kaplan-Meier analysis). Analysis of side effect of treatment showed that the frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery (р<0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.>< 0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.

[Steroid profiling characteristics in pediatrc adrenal diseases].

BACKGROUND: Adrenocortical adenomas are often followed with steroid hormones hyperproduction, and therefore determination of their concentration plays an important role in the differential diagnosis of adrenal diseases. Steroid profiling by tandem mass spectrometry is one of the main diagnostic methods in steroidogenesis characterization. Currently plasma and urinary steroid profiling is of particular interest in differential diagnosis and subtyping patients with adrenocortical adenomas. AIM: Steroid profiling of pediatric patients with adrenal diseases (incidentalomas, ACTH-secreting pituitary adenoma, ACTH-independent Cushing syndrome, premature adrenarche). MATERIALS AND METHODS: We conducted a retrospective analysis of steroid profile of 41 pediatric patients with adrenal diseases who were observed between 2005 and 2020 at the Endocrinology Research Centre. RESULTS: All patients were divided into groups due to diagnosis: with ACTH-secreting pituitary adenoma [n=7], ACTH-independent Cushing syndrome (autonomous cortisol secretion by an adrenal adenoma) [n=4], with incidentaloma [n=7] and premature adrenarche [n=23]. In group of patients with ACTH-independent Cushing syndrome identified statistically significant higher levels of 11-deoxycortisol (р=0, 0035) and significant lower levels of 17-hydroxypregnenolone (р=0, 0026) and DHEA (р=0, 0047) compared to other groups. Statistically significant differences in steroid profiles between other groups were not identified. CONCLUSION: Results of our study steroid profiling can be used as additional differential diagnosis method in patients with adrenocortical adenomas with or without hormonal hyperproduction (ACTH-independent Cushing syndrome and incidentaloma). Further studies are needed to identify steroid markers for subtyping pediatric adrenal diseases.

[Congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency: late diagnosis and gender reassignment in a two-year-old child].

11ß-hydroxylase deficiency is a rare autosomal recessive disorder due to impaired steroidogenesis in the adrenal cortex caused by pathogenic mutations in the CYP11B1 gene. The main clinical manifestations are determined by a deficiency of cortisol, ACTH hyperproduction, excessive androgens secretion and the accumulation of 11-deoxycorticosterone, which leads to the development of arterial hypertension. In the diagnostic search, it is important to take into account the ethnicity of the patient, since the frequency of the disease and the prevalence of mutations differ between ethnic groups. The article presents a clinical case of 11ß-hydroxylase deficiency as the result of compound heterozygous mutations in the CYP11B1 gene in a patient of Turkic origin. This case shows the clinical manifestations and the development of complications of 11ß-hydroxylase deficiency, the stages of differential diagnosis of patients with 21-hydroxylase deficiency.

[Clinical guidelines «Precocious puberty¼].

The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target indicators of final growth and prevent social deprivation. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of рrecocious puberty, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

[Early manifestation and progressive multicomponent current of McCune-Albright-Braitsev syndrome in a girl 9 years old: a clinical case and literature review].

McCune-Albright-Braitsev Syndrome (MAB syndrome) is a very rare multisystem disease manifested by fibrous bone dysplasia, coffee-and-milk colored spots, hyperfunction of various endocrine glands and a number of pathologies of other body systems. We present a description of a clinical case of a severe progressive course of MAB Syndrome in a nine-year-old girl. With this diagnosis, the girl is observation of the girl began when she was 2.5 years old, when spots of coffee-and-milk, polyosseous fibrous dysplasia, peripheral premature sexual development against a backdrop of estrogen--secreting ovarian cysts, multinodular goiter were detected. In the process of dynamic observation, it was noted that the child's active growth stopped against a backdrop of deformities of the skeletal system with multiple repeated fractures of the extremities; progression of skull deformity with stenosis of the optic nerve canals and deterioration of visual acuity; development of STH hypersecretion, hypophosphatemic rickets, tachycardia. Appropriate suppressive / replacement therapy was prescribed for each of the endocrine dysfunctions. The article presents algorithms for examining a girl in dynamics, criteria for choosing a component-wise management tactics and a discussion of the features of the course of all manifestations of the Syndrome.

[Laparoscopic adrenalectomy for benign adrenal tumors in pediatric surgical practice]. / Laparoskopicheskaya adrenalektomiya pri dobrokachestvennykh novoobrazovaniyakh nadpochechnikov v praktike detskogo khirurga.

OBJECTIVE: To estimate the results of minimally invasive adrenalectomy in children and compare our data with worldwide results. MATERIAL AND METHODS: There were 65 patients aged from 3 months to 17 years with different organic diseases of adrenal glands. Children have undergone surgery for the period since 2003 to 2018. RESULTS: Incidentalomas accounted 33.8% of all resected tumors. Bilateral lesion was diagnosed in 12% of patients. The largest neoplasm (12 cm) was diagnosed in a 9-year-old child. Intraoperative bleeding occurred in 2 patients. Endoscopic surgery did not require conversion in any case. CONCLUSION: We accumulated unique experience of laparoscopic resection of benign lesions of adrenal glands. Our results are satisfactory and comparable with data of other national and foreign colleagues. Only close collaboration of pediatric surgeons and endocrinologists could lead to successful and safe treatment of these patients. Patients with suspected malignancies should receive treatment at special hospitals with oncological service.

[Clinical polymorphism of congenital X-linked adrenal hypoplasia].

Congenital adrenal hypoplasia is a rare clinical variant of primary adrenal insufficiency. Two forms of this disease are known, one of which is inherited in an autosomal recessive manner (including IMAGe syndrome - a combination of adrenal hypoplasia with intrauterine growth retardation, metaphysical dysplasia and abnormal genital structure, OMIM 300290), and the other has X-linked nature of inheritance (DAX-1 gene defect). X-linked adrenal hypoplasia is relatively more common and studied in more detail.Congenital X-linked adrenal hypoplasia is manifested by a combination of primary adrenal insufficiency and hypogonadotropic hypogonadism and is caused by defects in the DAX-1 gene (measurement-sensitive sex reversal, adrenal hypoplasia congenital, critical region on the X chromosome, gene-1).

[Lipoid adrenal hyperplasia caused by earlier unknown 21STAR gene mutations].

Lipoid adrenal hyperplasia (LAH) is a most severe type of congenital adrenal cortical dysfunction (CACD). In this type of CACD, there is defect in the conversion of cholesterol to pregnenolone, as a consequence the production of all steroid hormones was impaired in both the adrenals and gonads. Defects of the STAR gene encoding for a steroidogenic acute regulatory (StAR) protein underlie the disease in most cases. Until the present time, there have been no reports on cases of LAH in the Russian literature. The diagnosis of LAH was established by the authors in three genetic girls aged 2.3 years, 6 and 7 months who had a normal structure of the external genitalia and in whom the disease was marked by manifestations of primary hypoadrenocorticism at the age of 21, 2, and 10 days, respectively. A hormonal study failed to show elevated levels of Cortisol and 17-hydroxyprogesterone in response to adrenocorticotropic hormone stimulation. A molecular genetic study revealed the following STAR gene defects: P129AC/W250X, IVS5-1G, and W147X, respectively. Р129ЛС, IVSS, and W147X mutations have not been earlier described. The data of the observation emphasizes the need of including LAH into the algorithm of differential diagnosis of CACD in children with the normal female structure of the external genitalia. The molecular genetic analysis should be prominent in diagnosing LAH, by taking into account the lack of hormonal markers of the disease.

[The nonclassical form of congenital adrenal cortical dysfunction in adolescent girls].

The study was undertaken to define the frequency of nonclasslcal 21-hydroxylase deficiency confirmed by CYP21 gene mutations in girls with pubertal hyperandrogenlsm, to estimate the value of clinical and hormonal markers of nonclasslcal 21-hydroxylase deficiency. Eighty-five girls aged 5-17 years who had hyperandrogenlsm (pubertas precox, hirsutism, acne vulgaris). All the examinees underwent adrenocorticotropic hormone (ACTH) (Synacthen-depot) test. After detecting the hormonal markers oj"nonclassical21-hy-droxylase deficiency (the baseline level of 17- О HP being was above 9 nmol/l and/or above 45 nmol/l after A CTH stimulation), the authors analyzed the most common CYP21 gene mutations. The frequency of nonclassical 21-hydroxylase deficiency supported by CYP21 mutations In the girls with hyperadrogenlsm was 8.3%. There were no clinical differences between the nonclassical form of 21-hydroxylase deficiency and other forms of hyperandrogenlsm. The high baseline 17-OHP ( > 20 nmol/l) is the most specific hormonal marker of nonclasslcal 21-hydroxylase deficiency. Glucocorticoid therapy is indicated for patients with substantially accelerated growth and bone maturation and in those with menstrual irregularities as oligomenorrhea or amenorrhea.

[Effects of carnitine and cobamamide on the dynamics of mental work capacity in patients with anorexia nervosa]. / Vliianie karnitina i kobalamina na dinamiku umstvennoi raboto- sposobnosti bol'nykh nervnoi anoreksiei.

The authors relate the results of studying intellectual work fitness in patients with anorexia nervosa (in the stage of cachexia) receiving the vitamin-like drugs carnitine and cobamamide. It has been shown that the long-term food deprivation leads to a reduction of intellectual work fitness, lability of productivity, fluctuations in the work quality, appearance of latent fatigue. In spite of the fact that standard nonspecific treatment ameliorates intellectual work fitness, it does not lead to its normalization. The use of carnitine and cobamamide in the course of nonspecific treatment results in the reduction of the time spent on task implementation, a rise of the work rate as compared to the control group. However, this does not fully remove latent fatigue and does not bring about complete recovery to normal of intellectual work fitness. The combined use of carnitine and cobamamide eliminates fluctuations in the work rate and normalizes the scope and productivity of intellectual work.

Anorexia nervosa as manifested in Russia.

The authors describe current theoretical and clinical conceptualizations and treatment of anorexia nervosa in Russia, based on their experience in the follow-up of 800 patients. Three-quarters of the patients exhibited anorexia nervosa linked with a border-line state, and one-quarter associated with schizophrenia. Different relationships to dysmorphophobic fears were observed in the different anorexic groups. In the border-line group, follow-up study indicated that the clinical symptoms of anorexia nervosa were significantly reduced. However, the disorder preserved its connection with dysmorphophobic fears even in the remote stages of the disease, and in later stages there was an occurrence of pathological personality changes. In the second group, from the very beginning, anorexia nervosa in schizophrenia was closely connected with affective disorders, pathological body sensations, hypochondriacal complaints, and a gradual personality deterioration. As the schizophrenic defect increased, anorexia nervosa was reduced to an exhausted form of vomiting behaviour, and lost its connection with dysmorphophobic experiences.

[Characteristics of families of patients with anorexia nervosa (psychocorrective measures)]. / Kharakteristika semei bol'nykh nervnoi anoreksiei (psikhokorrektsionnye meropriiatiia).

The paper is concerned with an examination of the families of patients suffering from anorexia nervosa and the role they play in rehabilitation and resocialization of patients. 103 families (103 patients and 268 persons from their family environment) were examined. 65 patients suffered from anorexia nervosa of schizophrenic etiology and 38 from anorexia nervosa as a borderline disease. Among blood relatives of patients with schizophrenia, there predominated subjects with pathology of schizophrenic nature and those with schizoid disorders. The relatives of patients with borderline disease mostly had diverse anomalies of the character, largely hysteric accentuation. The common traits characteristic of the families of anorexia nervosa patients were delineated. Based on the parents' personality traits, the nature of family relations, the type of children's education, attitude toward the sick child and preparedness for cooperation with the treating physician and medical personnel, five types of the families could be distinguished: harmonious one and 4 types of disharmonic families (non-harmonious, symbiotic, rigid pseudosolidary and destructive (conflicting]. The first two family types are more characteristic of patients suffering from borderline anorexia nervosa, the remainder three of schizophrenic patients with the syndrome of anorexia nervosa. The family types have been thus characterized; a complex of psychocorrective measures have been worked out both for patients themselves and their relatives with regard to the specific features of each family type.

[Bulimic disorders in anorexia nervosa]. / Bulimicheskie rasstroistva pri nervnoi anoreksii.

As many as 108 patients with anorexia nervosa were examined. Of these, 83 patients manifested bulimic symptomatology. In all the examined patients, the formation of bulimic symptomatology was preceded by the typical dynamics of the syndrome of anorexia nervosa in the form of the stage of dysmorphophobia-dysmorphomania, of the stage of looks correction with the aid of different methods of weight reduction, and of the stage of an appreciable body weight decrease with marked secondary ++somato-endocrine abnormalities up to cachexia. Three types of bulimic disorders associated with anorexia nervosa were distinguished: bulimia as a symptom of anorexia nervosa, bulimia s a stage of anorexia nervosa, and the bulimic variety of anorexia nervosa. Each of these types of pathology is depicted clinically.

[Association of schizophrenia and Recklinghausen's disease]. / Sochetanie shizofrenii s bolezn'iu Reklingkhauzena.

Two cases of associated Recklinghausen's disease and different forms of schizophrenia (sluggish psychopathlike and shift-like paranoid) are described. Of special interest was the fact that such association was observed in two brothers. Based on the clinical material suggested, the conclusion was made about the modifying influence of the organism process in Recklinghausen's disease (brain gliosis) on the schizophrenic process, thereby creating certain difficulties in the diagnosis. It is also assumed that the age of the onset of Recklinghausen's disease may determine the clinical picture of the mental pathology.

[Clinico-psychological correlations of mental rigidity in anorexia nervosa]. / Kliniko-psikhologicheskie korreliatsii psikhicheskoi rigidnosti pri nervnoi anoreksii.

A study was made of mental rigidity in patients suffering from anorexia nervosa and their relatives using the Tomsk rigidity questionnaire. Based on examinations of 40 patients with anorexia nervosa, 22 of whom suffered from schizophrenia, 18 with borderline pathology (16 with an active method of weight losing, 24 with the bulimic variant of anorexia nervosa) and of 58 close relatives (mothers, fathers, sisters) the data were obtained on the level of mental rigidity. In the patients' group, it was found to depend to a greater measure on the stage of anorexia nervosa, whereas in the relatives, on the nosological appurtenance of the syndrome in their children.