Thyroiditis in children are important issues of pediatric endocrinology due to their widespread occurrence. They differ in etiology, pathogenesis, and their clinical manifestations. Updated clinical guidelines in 2024 are the main working tool of physicians. They briefly and structurally present the main information about epidemiology and modern classification of thyroiditis, methods of diagnosis and treatment based on the principles of evidence-based medicine.

The syndrome of apparent mineralocorticoid excess (AME) is a rare genetic disease characterized by juvenile hypertension, hypokalemia, suppression of renin and aldosterone. AME syndrome is caused by a mutation in the HSD11B2 gene, which encodes 11ß-hydroxysteroid dehydrogenase type 2, that converts cortisol into cortisone.The purpose of the article is to describe a clinical case of genetically confirmed (mutation C.911A>G of the HSD11B2 gene) AME syndrome. The disease manifested in the first years of life; the patient was prescribed mineralocorticoid receptor antagonists, potassium preparations, potassium-sparing diuretics, and other antihypertensive therapy. Due to the absence of normotonia and normokalemia, dexamethasone has been prescribed since the age of 12. Due to uncontrolled arterial hypertension and hypokalemia, complications developed (medullary nephrocalcinosis, myocardial remodeling), and prolonged dexamethasone intake led to a slowdown in puberty and a decrease in bone mineral density.

Введение. Синдром Клайнфельтера (СК) – аномалия половых хромосом, характеризующаяся высокой распространенностью в различных популяциях, гипергонадотропным гипогонадизмом и мужским бесплодием, выраженной клинической вариабельностью симптомов и часто поздней диагностикой. Причины фенотипической вариабельности СК, в том числе роль генетических, эпигенетических и средовых факторов, до сих пор недостаточно изучены. Цель: исследование влияния CAG-полиморфизма гена андрогенового рецептора (AR) и родительского происхождения дополнительной Х-хромосомы на клинико-лабораторные показатели у пациентов с СК. Методы. Обследованы 34 пациента с СК от 5 до 18 лет, имеющие кариотипы 47,XXY (n=32); 48,XXYY (n=1) и mos 47,ХХY[22]/46,XY[8] (n=1). Два пациента являлись монозиготными близнецами, остальные не были родственниками. Родительское происхождение Х-хромосом определяли путём генотипирования пациентов и родителей по (CAG)n-полиморфному локусу гена AR и (GAAA)n полиморфному локусу, расположенному вблизи гена RP2. Влияние родительского происхождения дополнительной хромосомы Х и количества CAG-повторов на клинико-лабораторные показатели оценено у 22 подростков с кариотипом 47,ХХY, достигших стадии полового развития по Таннеру ≥2, не получавших заместительную терапию препаратами тестостерона на момент обследования. Результаты. Количество CAG-повторов в гене AR у пациентов с СК варьировало от 16 до 27, 22 аллеля (32,4%) содержали 20 или 21 повтор. По числу CAG-повторов группа из 22 подростков с СК была разделена на 3 подгруппы: носители «коротких» аллелей ((CAG)n ≤19; 6 пациентов), «средних» аллелей ((CAG)n=20–25; 12 пациентов) и «длинных» аллелей ((CAG)n ≥26; 4 пациента). Сравнительный анализ данных антропометрии (SDS роста и ИМТ, ΔSDS сегментов тела) не выявил статистически значимых различий между подгруппами. В группе носителей «длинных» аллелей отмечены более высокие уровни тестостерона и инсулина, больший объем тестикул по сравнению с носителями «средних» и «коротких» аллелей. По уровням гонадотропинов (ЛГ, ФСГ), показателям метаболического профиля (ХС общего, ЛПНП, ЛПВП, ТГ), исследуемые группы также не различались. Родительское происхождение дополнительной Х-хромосомы установлено у 33 пациентов, из них у 22 (67%) выявлено материнское происхождение (Хm), у 11 (33%) – отцовское (Хр). Анализ влияния происхождения хромосомы Х на показатели антропометрии, гормонального и липидного профиля у отобранных для исследования 22 подростков (из них 15 с дополнительной Хm, 7 с дополнительной Хр) не выявил статистически значимых различий между подгруппами. Таким образом, существенного влияния родительского происхождения дополнительной Х-хромосомы на клинические и гормонально-метаболические показатели в исследованной выборке пациентов с СК не выявлено. Introduction. Klinefelter syndrome (KS) is a sex chromosome abnormality characterized by high prevalence in various populations, hypergonadotropic hypogonadism, male infertility, pronounced clinical variability of symptoms and commonly late diagnosis. The causes of phenotypic variability of KS, including the influence of genetic, epigenetic and environment factors on it, is still not well understood. Aim: evaluation of the CAG polymorphism of androgen receptor (AR) gene and the parental origin of the X chromosomes on clinical and laboratory parameters in Klinefelter syndrome patients. Methods. We examined 34 KS patients 5-18 years of age with following karyotypes: 47,XXY (n=32); 48,XXYY (n=1) и mos 47,ХХY[22]/46,XY[8] (n=1). Two patients were monozygotic twins, the other patients were unrelated. Parental origin of the X chromosomes was determined by genotyping for (CAG)n polymorphism of the AR gene and (GAAA)n polymorphism, near to the RP2 gene, in patients and parents. The influence of the origin of the additional X chromosome and CAG-repeats of AR gene on the clinical and laboratory parameters was assessed in 22 adolescents with a karyotype 47,XXY, who had reached the Tanner stage of sexual development ≥2, and not received testosterone replacement therapy at the time of examination. Results. The number of CAG repeats of the AR gene in KS patients was ranged from 16 to 27, and 22 alleles (32.4%) contained from 20 or 21 repeats. According to CAG-repeats, a group of 22 adolescents with KS was divided into 3 subgroups: carriers of “short” alleles ((CAG) n ≤19; 6 patients), “medium” alleles ((CAG)n=20–25; 12 patients) and “long” alleles ((CAG)n ≥26; 4 patients) alleles. Comparative analysis of anthropometric data (SDS of height and BMI, ΔSDS of body segments) did not reveal statistically significant differences between subgroups. In the group of carriers of “long” alleles, higher levels of testosterone and insulin and a larger testicular volume were noted compared to carriers of “medium” and “short” alleles. The study groups also did not differ in the levels of gonadotropins (LH, FSH) and metabolic profile indicators (total cholesterol, LDL, HDL, TG). The parental origin of the additional X chromosome was established in 33 patients, of which 22 (67%) patients had maternal origin (Xm), and 11 (33%) individuals had paternal origin (Xp). Analysis of the influence of the origin of the X chromosome on anthropometric indicators, hormonal and lipid profiles in 22 adolescents selected for the study (additional Xm, n=15; additional Xp, n=7) did not reveal statistically significant differences between the subgroups. No significant influence of the parental origin of the additional X chromosome and the CAG polymorphism of the androgen receptor gene on clinical and hormonal-metabolic parameters in our sample of KS patients, was found.

Osteomalacia is a systemic disease of the skeleton, accompanied by the formation of an unmineralized or poorly mineralized osteoid instead of full-fledged bone tissue. The most common cause is severe vitamin D and calcium deficiency, phosphorus deficiency (kidney pathology, mesenchymal tumors secreting an excess of FGF23, genetic diseases). Among inherited pathologies, X-linked dominant hypophosphatemic rickets (XLHR, gene PHEX, OMIM: 307800) is the most frequent form, while autosomal dominant hypophosphatemic rickets (ADHR, gene FGF23, OMIM: 193100) and autosomal recessive hypophosphatemic rickets 1,2 (ARHR1-2, genes DMP1, ENPP1, FAM20C, OMIM: 241520, OMIM: 613312) are much less common. ADHR is an extremely rare form of genetic rickets caused by mutations in the FGF23 gene. It can manifest at any age. About 50 cases of this disease have been reported in the literature. This article presents the first clinical case of ADHR in an adult in the Russian Federation. Severe vitamin D deficiency, renal tubular disorders and tumor-induced osteomalacia were excluded in differential diagnosis. The patient underwent a genetic test, which revealed a mutation in the FGF23 gene and confirmed the diagnosis of ADHR. Therapy with an active vitamin D analog and phosphate supplement was initiated, after which the patient noticed decreased pain when walking and increased muscle strength.Difficulties in diagnosing osteomalacia are due to the lack of routine determination of serum phosphate and low awareness of doctors about this disease. In some cases, genetic tests make it possible to confirm hereditary forms, which prevents unnecessary surgical treatment, ensures timely prescription of therapy and significantly improves the quality of patients’ lives.

Ежегодно в Институт детской эндокринологии ГНЦ ФГБУ «НМИЦ эндокринологии» Минздрава России госпитализируется более 5,5 тысяч детей и подростков из всех регионов РФ с различными эндокринными заболеваниями. С целью аккумуляции уникальных данных для дальнейшего клинико-эпидемиологического мониторинга этих пациентов разработана структура единой ЭНДОКАРТЫ учета 7 нозологий, внедренная в медицинскую информационную систему (МИС) ГНЦ ФГБУ «НМИЦ эндокринологии»: опухоли гипоталамо- гипофизарной области, первичный гиперпаратиреоз, хронический гипопаратиреоз, гипогликемический синдром, гонадотропинзависимое преждевременное половое развитие, низкорослость и врожденная дисфункция коры надпочечников (ВДКН). ЦЕЛЬ: оценить структуру патологии редких эндокринных заболеваний у лиц детского возраста (менее 18 лет), госпитализированных в ГНЦ ФГБУ «НМИЦ эндокринологии». МАТЕРИАЛЫ И МЕТОДЫ: объект исследования - база данных ГНЦ ФГБУ «НМИЦ эндокринологии» Минздрава России детей в возрасте от 0 до 18 лет. Детская Эндокарта начала функционировать с декабря 2020 года. Анализ выполнен по данным выгрузки от 15.01.2023. РЕЗУЛЬТАТЫ: регистр первичного гиперпаратиреоза включает 18 детей (8 мальчиков, 10 девочек), средний возраст составляет 16 лет. При первичном обращении у 8 детей (44,5%) наблюдалось мани- фестное течение первичного гиперпаратиреоза, у 10 (55,5%) пациентов мягкое течение. В группе па- циентов в активной фазе заболевания медианы паратгормона и общего кальция составили 131,7 пг/мл и 2,89 ммоль/л соответственно. Всем детям было проведено хирургическое лечение и достигнута ремиссия. Регистр опухолей гипоталамо-гипофизарной области включает данные о 38 детях (17 мальчиков, 21 де- вочка), средний возраст 14 лет. Болезнь Иценко-Кушинга имелась у 11 (29%) пациентов, другие аденомы гипофиза (пролактиномы, СТГ-продуцирующие аденомы и другие) встречались у 27 (71%) пациентов, из них большая часть составили пролактиномы – 22 ребенка. Регистр хронического гипопаратиреоза содержит сведения о 19 пациентах (12 мальчиков, 7 девочек), средний возраст 11 лет, из данной группы пациентов АПС 1 типа имелся у 5 (26%) детей, послеоперацион- ный гипопаратиреоз и наследственный гипопаратиреоз (за исключением АПС 1 типа) - у 4 (21%) пациентов и 3 (16%) пациентов соотвественно . Регистр детей с гипогликемиями включает сведения о 192 ребенке (106 мальчиков, 86 девочек), сред- ний возраст 4 года. Из них у 107 (56%) пациентов имелся врожденный гиперинсулинизм, подтвержденный молекулярно-генетическим исследованием. Регистр гонадотропинзависимого преждевременного полового развития включает данные 130 детей (28 мальчика, 102 девочки), средний возраст 8 лет. Средний возраст начала заболевания - 6 лет. Терапию аналогами ЛГ-РГ получают 76 детей (58,6 %), костный возраст которых статистически значимо опережал хронологический (10 лет vs. 6 лет, p<0,001). Регистр низкорослости включает данные о 354 пациентах (240 мальчик, 114 девочек), средний возраст 11 лет. Структура нозологии: гипопитуитаризм – 217 (61%) пациентов, другие варианты низкорослости (в том числе идиопатическая задержка роста, синдром Шерешевского-Тернера и другие синдромальные формы) – 137 (39%) пациент. Регистр пациентов с ВДКН включает 82 ребенка (29 мальчиков, 53 девочки), средний возраст 5 лет. В 80,5 % (n = 66) заболевание связано с дефицитом 21-гидроксилазы, у 19,5 % (n = 16) детей ВДКН ассоциирована с нарушением синтеза других ферментов стероидогенеза (11b-гидроксилазы, 3b-гидроксистероиддегидрогеназы и пр.).ВЫВОДЫ: ГНЦ ФГБУ «НМИЦ эндокринологии» Минздрава России аккумулирует экспертное мне- ние по проблеме орфанных эндокринных заболеваний детского возраста в Российской Федерации. Организация структуры системы учета редких эндокринопатий позволит оценить структуру и клинико- эпидемиологические характеристики данных нозологий, распределение по регионам РФ, провести ана- лиз эффективности терапии, что послужит научно-практической основой совершенствования оказания помощи по профилю «детская эндокринология».

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 syndrome MATERIALS 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.

BACKGROUND: The majority of Kallmann patients have anosmia or hyposmia. This is how the disease is diagnosed. Some of them don’t have such complaints but olfactory dysfunction is diagnosed via olfactometry. Nowadays there is the lack of information about correlation between olfactometry results and subjective complaints. Correlation between olfactory bulbs size and olfactory dysfunction has been little studied. AIM: To explore olfactory bulb size and olfactory function in patients with congenital isolated hypogonadotropic hypogonadism. To correlate olfactory bulb sizes and smell test scores. MATERIALS AND METHODS : Single-centre comparative study. 34 patients were included. The main group consisted of 19 patients with hypogonadotropic (15 –with Kallmann syndrome, 4 — with normosmic hypogonadism). Olfactory bulbs MRI were provided to all the patients, olfactory test (Sniffin’ Sticks Test) and molecular-genetic studies were provided in all patients with hypogonadism. Control group consisted of 15 patients who were provided with orbits MRI. Olfactory bulbs were evaluated additionally in them. RESULTS: Normal size of olfactory bulbs were only in 1 patient with hypogonadism. Olfactory bulbs height and width were significantly smaller in patients with hypogonadism in comparison with control group (p<0.01). Height median of right bulb was 1.0 mm [0.2; 1.8] in patients from the main group vs. 3.0 [2.5; 3.2] in controls, width median of right bulb was 1.0 mm [0.2; 1.9] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Height median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 3.0 [2.7; 3.2] in controls, width median of left bulb was 0.8 mm [0.0; 1.2] in patients from the main group vs. 2.5 [2.0; 3.0] in controls. Correlation has been established between left bulb height (r=0.59) and width (r=0.67) and olfactometry results (p<0.05). 4 patients had no anosmia complaints but had olfactory dysfunction according to Sniffin’ Sticks Tests. CONCLUSION: Olfactometry was able to diagnose olfactory dysfunction in 78.5% (i.e. in 15 out of 19 patients with congenital isolated hypogonadotropic hypogonadism. However, anosmia complaints had only 11 out of 19 patients. It is the first results of olfactory bulb sizes in patients with hypogonadotropic hypogonadism in Russia. Uni — or bilateral hypoor aplasia were diagnosed in 94.7% patients with hypogonadism regardless of olfactory dysfunction. Bilateral olfactory bulbs hypoplasia were the most common MRI-finding (36.8%). Unilateral hypoor aplasia was diagnosed in 31.6% patients.

BACKGROUND:X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative metabolic disease with a frequency 1:17,000 in newborn boys. Being a major part of X-ALD with an incidence of 70-80% of patients, adrenal insufficiency (AI) is a life-threatening condition without timely treatment. The possibility of developing AI during the whole disease duration and the absence of any predictive factor for AI joining shows the necessity of studying AI in X-ALD patients to optimize current diagnostic and treatment algorithms. AIM:To study diagnostic and therapeutic features of primary adrenal insufficiency due to X-ALD. MATERIALS AND METHODS:A retrospective observational comparative study was conducted in 66 male patients, examined and treated in the Pediatric endocrinology department of Endocrinology Research Centre, Research Centre for Medical Genetics, Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University Detached Structural Unit Russian Children's Clinical Hospital (Moscow, Russia) for 2014-2022. All of patients were diagnosed with primary AI and a genetically confirmed X-ALD. RESULTS:The median age of X-ALD manifestation was 6.6 years [4.7; 11.1]. The earliest age of AI diagnosis was 1.5 years at the preclinical stage and 1 year 8 months with clinical symptoms. The renin level was studied in 22.7% at the manifestation of AI (15/66 patients), mineralocorticoid deficiency was found in 7 patients. Family history was positive in 39.4% of patients (n=66), only in 15.1% (10/66 patients) of patients the disease was established at the preclinical stage. In 59.1% (n=66) the cerebral form of the disease (cALD) was established, in 16.6% - adrenomyeloneuropathy (AMN), and in 24.2% - isolated adrenal insufficiency (PAI). Age of AI establishment in the group of patients with AMN (15.6 years) significantly differs from the establishment of AI in patients with cALD (7.4 years, p=0.001) and PAI (5.6 years, p = 0.000). Mineralocorticoid therapy was prescribed simultaneously with glucocorticoid therapy in patients with cALD, in AMN and PAI patients it was added after 11 and 7 months, respectively (the differences between AMN and PAI groups were insignificant). Combined hormonal therapy receive 41% of patients with cALD, 54.5% of patients with AMN and 60% of patients with PAI. CONCLUSION:It is necessary to examine all male patients with AI regardless of the manifestation age to exclude adrenoleukodystrophy, and it is also important to examine patients for the presence of AI regardless of X-ALD manifestation age. The assessment of renin level in the manifestation of AI is also needed to prescribe mineralcorticoid therapy timely. Studying family history is the main method to detect X-ALD at the preclinical stage.

ОБОСНОВАНИЕ ОБОСНОВАНИЕ. В подавляющем большинстве пациенты с синдромом Кальмана отмечают неспособность различать запахи, что помогает своевременно установить диагноз. Некоторые из пациентов с синдромом Кальмана не предъявляют подобных жалоб, но при помощи ольфактометрии с использованием специальных наборов пахучих веществ у них выявляются нарушения обоняния. Нарушения обоняния часто отмечаются у пациентов с гипоплазией или аплазией одной или обеих обонятельных луковиц (ОЛ). Характер взаимосвязи размеров обонятельных луковиц и гипоили аносмии по результатам ольфактометрии у пациентов с ВИГГ в настоящее время мало изучен. ЦЕЛЬ ЦЕЛЬ. Изучить размеры ОЛ и обонятельную функцию у детей с ВИГГ. Установить наличие взаимосвязи между размерами ОЛ и обонятельной функцией. МАТЕРИАЛЫ И МЕТОДЫ МАТЕРИАЛЫ И МЕТОДЫ. Одноцентровое одномоментное сравнительное исследование. В исследование включены 34 пациента. Основную группу составили 19 детей с гипогонадотропным гипогонадизмом (15 — с синдромом Кальмана, 4 — с нормосмическим гипогонадотропным гипогонадизмом). Всем пациентам проводилась МРТ головного мозга с оценкой размеров ОЛ, ольфактометрический тест (Sniffin’ Sticks Test) и молекулярно-генетические исследования. Контрольную группу составили 15 детей, у которых при проведении МРТ орбит дополнительно оценивали размеры ОЛ. РЕЗУЛЬТАТЫ РЕЗУЛЬТАТЫ. Из 19 пациентов с ВИГГ нормальные размеры ОЛ имелись только у 1 пациента. У детей с гипогонадизмом высота и ширина ОЛ оказались достоверно меньше (p<0,01) в сравнении с контролем. Медиана высоты правой луковицы (ПЛ) у пациентов с ВИГГ составила 1,0 мм [0,2; 1,8] против 3,0 [2,5; 3,2] в контрольной группе, медиана ширины ПЛ — 1,0 мм [0,2; 1,9] против 2,5 [2,0; 3,0], медиана высоты левой луковицы (ЛЛ) у пациентов с ВИГГ — 0,8 мм [0,0; 1,2] против 3,0 [2,7; 3,2], медиана ширины ЛЛ — 0,8 мм [0,0; 1,2] против 2,5 [2,0; 3,0]. Выявлена корреляция между высотой (r=0,59) и шириной (r=0,67) левой ОЛ и результатами ольфактометрического теста (p<0,05). У 4 пациентов субъективная оценка обонятельной функции не совпала с данными ольфактометрического исследования. ЗАКЛЮЧЕНИЕ ЗАКЛЮЧЕНИЕ. Ольфактометрия позволила выявить нарушения обоняния у 78,5% пациентов с изолированным гипогонадотропным гипогонадизмом (15 из 19 пациентов), при этом субъективно на нарушения обоняния жаловались только 11 из 19 пациентов. Впервые в РФ представлены размеры ОЛ у пациентов с изолированным гипогонадотропным гипогонадизмом. У 94,7% пациентов вне зависимости от нарушения обонятельной функции отмечалась гипоплазия и/или аплазия одной или обеих ОЛ. Чаще всего встречалась гипоплазия обеих луковиц (36,8%), изменения ольфакторных луковиц (гипоплазия или аплазия) с одной стороны имелись у 31,6% пациентов.

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.

Primary adrenal insufficiency (PAI) is a rare pathology with a prevalence of 100 to 140 cases per one million. X-linked adrenoleukodystrophy (X-ALD) and X-linked congenital adrenal hypoplasia (X-CAH) are the leading pathologies among boys (after congenital cortical dysfunction adrenal glands) and account for 3.1% and 2.0% of all PAI, respectively. Establishing the PAI etiology is necessary to predict the course of the disease and adhere to special protocols for examining patients. The purpose of this research was to compare the PAI course in diseases with an X-linked type of inheritance. Materials and methods used: a single-center, one-stage observational comparative retrospective study was conducted in 25 male patients with genetically confirmed diagnoses of X-ALD, X-CAH and who had PAI as a component of the disease. The study was conducted at the Pediatric Endocrinology Institute with the Endocrinology Research Centre of the Ministry of Healthcare of Russia (Moscow, Russia) in 2019-2022 as well as based on the patients’ medical records that have been forwarded for a genetic search for the causes of adrenal insufficiency under the “Alfa-Endo” Charity Program for children with endocrine diseases in the same period of time. Results: X-ALD was detected in 11/25 (44%) patients, median age of manifestation was 6.2 [4.5; 7.2] y/o and 2 y/o was the earliest. A single patient with X-ALD was found to have TARTs (testicular adrenal rest tumors). X-CAH was diagnosed in the remaining 14/25 (56%) patients, median age of manifestation was 1.9 [0.04; 3.9] y/o, p=0.015. The oldest age of manifestation was 14 y/o. A single patient was found to have hypogonadotropic hypogonadism (HH) and another one had bilateral cryptorchidism. There were no statistically significant differences in symptoms, adrenocorticotropic hormone (ACTH), cortisol levels during the manifestation of PAI and doses of replacement therapy (p=0.756 for ACTH, p=0.591 for cortisol, p=0.825 for hydrocortisone and p=0.148 for fludrocortisone). Conclusion: it is necessary to exclude X-ALD and X-CAH when diagnosing PAI in boys regardless of the age of the disease manifestation. It is highly recommended to conduct a genetic study of a panel of genes responsible for the development of PAI in order to establish the PAI etiology, and regardless of the established PAI etiology it is necessary to perform an ultrasonic study of the testicles with the purpose of excluding the space-occupying formations. It is necessary to evaluate ACTH levels in patients with testicular masses for timely diagnosis of PAI and optimal treatment.

СОВЕРШЕНСТВОВАНИЕ АЛГОРИТМА ЭТИОЛОГИЧЕСКОЙ ДИАГНОСТИКИ И ПОДХОДОВ К ТЕРАПЕВТИЧЕСКОЙ ТАКТИКЕ ПРИ ВРОЖДЕННОМ ГИПОТИРЕОЗЕ У ДЕТЕЙСловак М .А . 1 , Кияев А .В . 1,2, Сумина М

Congenital isolated hypogonadotropic hypogonadism includes a group of diseases related to the defects of secretion and action of gonadotropin-releasing hormone (GNRH) and gonadotropins. In a half of cases congenital hypogonadism is associated with an impaired sense of smell. It's named Kallmann syndrome. Now 40 genes are known to be associated with function of hypothalamus pituitary gland and gonads. Phenotypic features of hypogonadism and therapy effectiveness are related to different molecular defects. However clinical signs may vary even within the same family with the same molecular genetic defect. Genotype phenotype correlation in patients with congenital malformations prioritizes the search for mutations in candidate genes. There are data of significant contribution of oligogenicity into the phenotype of the disease are presented in the review. Moreover, an issue of current isolated hypogonadotropic hypogonadism definition and classification revision is raised in the review due to hypogonadotropic hypogonadism development while there are mutations in genes not associated with GNRH neurons secretion and function.