Congenital hypothalamic hypogonadism — a Kallmann syndrome in boys. Clinical cases

Central hypogonadism (CH) is a rare disease that occurs with a frequency of 1 : 8000 in women and 1 : 4000 in men. In 60 % of cases of CH, it is caused by Kallmann syndrome (KS) — a disease in which hypogonadotropic hypogonadism is combined with olfactory disorders (hyposmia or anosmia).Aim — to study clinical features, principles of diagnosis of CH/KS and evaluation of the effectiveness of various treatment. Materials and methods. 4 cases with CH/KS from three families had been described. Laboratory and instrumental investigations were used to confirm the KS; genetic diagnosis was performed using targeted next-generation sequencing (tNGS hypogonadotropic panel).Results. Patients with CH/KS had a wide spectrum of genital disorders (micropenia, cryptorchidism, microorchidism), which appeared at different age. Extragenital pathology was found in three of four patients: namely disorders of kidney, eye, respiratory system, hypoparathyroidism, hypothyroidism and epilepsy. It should be noted that all patients had olfactory disorders, which appeared in two of them only during a detailed survey after receiving genetic testing. In all patients, the diagnosis of CH was confirmed by the test with triptorelin 0.1. Also, all patients who underwent densitometry were found to have significant osteoporosis. In three patients, genetic testing confirmed hemizygous pathogenic variants in ANOS1 gene, while in one patient a heterozygous variant in FGFR1 gene was confirmed. After treatment with chorionic gonadotropin (HCG), two patients responded positively, with a descent of the testicles into the scrotum and an increase of testosterone level and testicular volume. However, in the other two patients there was no positive trend in treatment with HCG, therefore, the use of recombinant human FSH (r-FSH) in the form of priming and then further — in combination with HCG may be considered. Although the presence of severe microorchidism, cryptorchidism, low levels of AMH, inhibin B, and an unsatisfactory response to the previous treatment with HCG indicates extremely unfavorable prognosis. Therefore, in order to achieve the fertility in some patients with CH/KS, the most likely attempt is the use of assisted reproductive technologies.Conclusions. The leading problem in the treatment of patients with KS is their different response to hormone therapy, including different manifestations of the disease.

Predictive indicators of an unfavorable prognosis for the restoration of laryngeal functions in unilateral lesions of the recurrent laryngeal nerve in thyroid surgery

Recurrent laryngeal nerve (RLN) damage in thyroid surgery is a very dangerous complication. An otolaryngologist, especially at pri­mary care institutions,should administer conservative or surgical treatment in a timely manner and depending on the type of nerve damage (transient, permanent), i. e., to analyze possible prognosis of the disease. Only few studies to predict disease developmentin RLN have been performed. One of the most modern and informative methods is laryngeal electromyography using needle electrodes, but despite the sufficient number of patients with this pathology, in most medical institutions in Ukraine it is not performed, given the technical difficulties of implementation, invasiveness and difficulty in interpreting the results of this method.Aim — to analyze the laryngoscopic signs of paresis and paralysis of the larynx in thyroid surgery and to identify the most significant from them, which together can serve as prognostic criteria of the lack of recovery of laryngeal mobility (paralysis).Materials and methods. A single-site prospective study was conducted in the years 2018—2021 that involved 164 patients with postoperative laryngeal movement disorders, who were divided into two groups: subjects with laryngeal paralysis (n = 33) and patients with laryngeal paresis (n = 131). All patients underwent phoniatric examination. The following signs have been identified: general signs, including age, number of operations, scope of surgical intervention, and 18 laryngoscopicsigns, each of them had two to seven grades. For the convenience, the grades were coded with numbers and, if possible, arranged in ascending order of severity. The obtained results were processed with Fisher angular transformation.Results. Among 18 laryngoscopic and general signs, 10main (predictors) were identified, that affect the absence or presence of laryngeal paralysis. They included:elements of mobility of the paralyzed vocal cords (VC) (absent), flotation of the «paralyzed» VC (insignificant and pronounced), mobility of the arytenoid cartilage (absent), closure of the VC (complete non-closure), synchronicity of oscillations VC (absence of movement of the paralyzed VC), restriction of the movement of the «paralyzed» VC (absent (the GE is motionless), level of the VC in the vertical plane (not on the same level), the tension of the median edge of the VC (incurvate), patient’s age > 45 years, the position of the «paralyzed» VC (median and intermedian). The mathematical analysis showed that none of the isolated laryngoscopic signs can be used as an independent criterion in assessing the predictions of the laryngeal mobilityrestoration.Conclusions. Prognostic laryngoscopic signs of recurrent laryngeal nerve damage in the thyroid surgery allow to create a prognostic model of recovery or lack of recovery of laryngeal motility, which is important for the appointment of timely adequate treatment.

Surgical treatment of unilateral nodular goiter with compression syndrome in patients with autoimmune thyroiditis

Aim — todetermine indications for the choice of the surgery scope in patients with unilateral nodular goiter with compression syndrome against the background of autoimmune thyroiditis (AIT) and possibility of prognosis of the long-term results of surgical treatment.Materials and methods. The analysis has been performed for the long-term results of hemithyroidectomy in 101 femalepatients aged 23 to 72 years with unilateral nodular goiter against the background of AIT (NGAIT) with compression syndrome. The pre-operational levels of the following parameters, definingsatisfactory and unsatisfactory treatment results, have been analyzed: volume of the lobe of the gland, blood levels of thyroid stimulating hormone, free thyroxine and triiodothyronine, antibodies to thyroid peroxidase, indices of apoptosisand proliferation, variants ofechostructure.Results. Satisfactory results have been established in 75 patients based on the following results of examinations 3 years after hemithyroidectomy: no violations of thyroid gland functional state, andno progression of preoperative AIT signs or progression without hypothyroidism and changesin ultrasound picture in the parenchymaof the remaining lobe of the gland according to the data of ultrasound investigation.Unsatisfactory results were definedin 26 subjects: an increase in the volume of the remaining thyroid gland and the progression of autoimmune process with the development of hypothyroidism. A satisfactory result of hemithyroidectomy in the treatment of patients with NGAIT with compression syndrome can be expected in cases where at the time of surgery the volume of the lobe was not more than 12.7 cm3, its echostructure corresponded to hypoechoic and heterogeneous and pseudomicronodular variants, and the following blood levels were established: thyroid stimulating hormone < 2.85 IU/L, free thyroxine > 16.7 pmol/l, free triiodothyronine > 5.3 pmol/l, antibodies to thyroid peroxidase < 137 IU/ml.Conclusions. One of the possible options for surgical treatment of patients with unilateral nodular goiter against the background of AIT with compression syndrome may be hemithyroidectomy in conditions of preserved hormonal function of the gland with moderately pronounced processes of proliferation and apoptosis, structural changes in the parenchyma at the level of hypoechoic and heterogeneous and pseudomicro-nodal echostructural variants. The use of hemithyroidectomy is contraindicatedin cases of pseudo-large-nodular and more severe variants of the echostructure of the thyroid parenchyma, regardless of the indicators of hormone-producing function, antibodies to thyroid peroxi­dase, proliferation and apoptosis.

Laser doppler flowmetry as the advanced non-invasive method of evaluation оf microcirculation status in patients with diabetes mellitus

Currently, the problem of diabetes mellitus (DM) is one of the most important medical and social challenges worldwide. This is primarily due to the widespread prevalence of the disease and tendency to further increase in the incidence of diabetes mellitus.Systemic microcirculatory disorders play an impor­tant role in the pathogenesis of DM complications. They lead to the development of microangiopathy and neuropathy through the primary lesion of vessels involved in the blood supply of the peripheral parts of the nervous system. Currently, less than one-third of physicians recognize signs of peripheral neuropathy associated with diabetes. Untimely diagnosis contributes significantly to high morbidity, disability, and mortality.The authorinvestigates the experience of the use of laser Doppler flowmetry (LDF) in clinical practice as a method of studying the state of the microcirculatory bed in patients with diabetes mellitus.LDF is a non-invasive quantitative method of microcirculation assessment; its capabilities include the analysis of microcirculatory rhythms and functional testing with different types of provocative effects, which provides with investigating the state of regulatory mechanisms of microcirculation. The prevention and treatment of various microcirculatory disorders is one of the most important problems of medical practice. The difficulties of studying the microcirculation are caused by the very small size of microvessels and strong ramification of intra-organic vascular networks. The use of LDF in scientific research will make it possible toreveal the DM-specific changes in microcir­culatory bed functioning. The findings of some studies suggest that microcirculatory disorders are not only a pathogenetic link in the development of complications, but they are also observed in patients with early disorders of carbohydrate metabolism and may precede the manifestation of diabetes. However, the method has not yet become widespread in clinical practice.

Risk factors and prognosis of metabolic syndrome in perimenopausal women with hypothyroidism

One of the main problems is that the metabolic syndrome (MS) is not clinically manifested until thesignificant carbohydrate and lipid metabolism violations, that initiate a pathological range of symptoms, leading to cardiovascular disease, diabetes mellitus, non-alcoholic steatohepatosis, impairment of reproductive function and other diseases. Conco­mitant endocrine disorders create a background on which dyshormonal and metabolic factors are superimposed. Therefore, an urgent and important task is the correct, and most importantly timely, interpretation of existing risk factors for metabolic disorders in women of perimenopausal age with concomitant hypothyroidism (HT), purposed on their correction to prevent or slowdown the development of complications.Aim — to develop a mathematical model for assessing the prognostic value of risk factors for investigation ofMSdevelopment and progression in perimenopausal women with HT.Materials and methods. 146 perimenopausal women with HT were examined to predict the MS development. Multiple regression analysis was used to construct prognostic model of MS risk.Results. With the help of logistic regression analysis, the following significant multicollinear risk factors for MS have been identified: triglycerides, thyroid-stimulating hormone, vitamin D, and waist circumference. A correlation matrix with the calculation of regression coefficients and coefficient of determination was constructed, and mathematical model was created to determine the coefficient of the MSprogression. The developed mathematical model for predicting of MSdevelopment had a high predictive accuracy, which confirms the compliance of the predicted results with the theoretically expected. The probability that patients will develop MS with a previously predicted risk of MS was 96.1 % (p < 0.05).Conclusions. The developed mathematical model of the predictionof metabolic syndromedevelopment against the background of hypothyroidism is highly informative and allows to determine in advance the contingent of women with high probability of MS development for the timely implementation of appropriate preventive measures.

Calcitonin level in the postoperative period as a risk factor for persistence of medular thyroid cancer

Aim — to evaluate the possibility of using basal calcitonin levels in the postoperative period to assess the effectiveness of surgical treatment of medullary thyroid cancer and the likelihood of its persistence (recurrence). Materials and methods. A single-site retrospective study was conducted to assess results of surgical treatment of 194 patients (74.2 % women and 25.8 % men), from them148 (76.3 %) patients had primary forms of the disease (group 1) and 46 (23.8 %) the recurrent form (group 2). Primary surgery included thyroidectomy, supplemented with thecentral and lateral dissection of the neck. Patients in group 1 were divided into two subgroups depending on the postoperative calcitoninlevels: group 1A with normal calcitonin levels (≤ 18 pg/ml)and group 1B with hypercalcitoninemia (> 18 pg/ml). The quantitative­determination of blood serum calcitonin levels was performed using automatic immunochemiluminescent analyzer «MAGLUMI» («Snibe Diagnostic», China) in 1 week and 1 year after surgery. Accumulation and primary data processing were performed in MS Excel 2013, statistical processing was performed using StatPlus programs with descriptive statistics, parametric and nonparametric methods for testing statistical hypotheses (Student’s criteria, Mann-Whitney, Fisher angular transformation), analysis of conjugation tables, ROC-analysis. The results were considered statistically significantat p < 0.05. Results. The average duration of follow-up was 67.5 months. The results of surgery were analyzed in terms of absence or presence of clinical recurrence, calcitoninlevels in the early postoperative period (5 days) were used as a predictor. After 2 years of follow-up,normocalcitoninemiawas accompanied by recurrence in almost 2 % of cases, while hyper­calcitoninemia — in 61 % to 74 %, depending on the stage and frequency of the disease. The correlationsbetween postoperative calcitonin levels and presence of recurrence (persistence) of medullary thyroid cancer has been established: AUC = 0.928 (0.867; 0.989, Juden index (J) = 0.429, threshold (cut-off point) ≥ 28.1 pg/ml, sensitivity = 0.938 (0.854; 1,000), specificity = 0.855 (0.789; 0.920), predictive value of positive result(PPV) = 0.699, predictive value of negative resultPNV = 0.991. Moreover, countersensitivity scores and incidence of negative test results in patients with relapse depending on the level of postoperative calcitonin were calculated. Conclusions. Postoperative calcitonin levels in 5 days after surgery can be used for assessment of efficacy of the surgical treatment (AUC — 0,928 (0,867; 0,989), Juden index — 0,429)). The prognosis of recurrence-free disease does not depend on the disease stage. At calcitonin levels < 18 pg/ml, clinical signs of the disease persistence (recurrence) were detected in 1.5 % of cases (PNV = 0.991). The reliability of predicting the disease recurrence depended on the stage and frequency of surgery: PRV = 0.612 in primary forms without metasta­­ses, PRV = 0.825 in recurrent forms. Calcitonin values < 28.1 pg/ml can be considered a relatively «safe» level.

Glycemic control in children and young adults with different types of diabetes mellitus in Ukraine

Introduction. Until recently, glycated hemoglobin (HbA1c) has not been studied in children with different types of diabetes mellitus (DM). With the development of molecular genetics, new types of diabetes have been diagnosed, including neonatal (ND) and maturity onset diabetes of the young (MODY), which usually require specific pathogenetic therapy, including sulfonylureas (SU), which improve glycemic control in patients with certain mutations. The aim of this study, which was conducted for the first time in Ukraine, was to analyze glycemic control in patients with different types of DM, including ND and MODY and changing their treatment after genetic testing. Materials and methods. We studied conducted the analysis of glycemic control in patients depending on the type of diabetes, namely: type 1 diabetes (n = 9282), type 2 diabetes (n = 23), ND (n = 16) with mutations KCNJ11, ABCC8 and MODY (n = 16) with mutations in HNF1A/HNF4A and ABCC8 genes. To confirm the nature of monogenic diabetes, targeting next-generation sequencing (tNGS) of all known neonatal and monogenic diabetes genes was performed. Results. According to the Register in 2018, in Ukraine the average age of children with type 1 DM was 11.5 ± 1.4 years, and the level of HbA1c was unsatisfactory (8.8 ± 2.01 %). The proportion of children who had ideal or optimal glycemic control (HbA1c

Non-alcoholic fatty liver disease and diabetes mellitus: bidirectional relationship

To date, nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic diffuse liver disease. Under adverse conditions, its natural course involves progression from simple steatosis and nonalcoholic steatohepatitis (NASH) to the development of liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, there has been much convincing evidence that NAFLD is a multisystem disease that contributes to damage to extrahepatic organs and systems, primarily increasing the risk of cardiovascular diseases, type 2 diabetes, chronic kidney disease and other diseases. In particular, numerous studies in recent years indicate that NAFLD increased the risk of diabetes by at least twice. Currently, the complex and bidirectional relationship between NAFLD and type 2 diabetes are well studied. NAFLD, hepatic and systemic insulin resistance, gut dysbiosis and lipotoxicity are the main factors determining the development of diabetes mellitus in predisposed individuals. Once type 2 diabetes manifests clinically, the likelihood of progressive liver damage increases. Non-alcoholic fatty liver disease, which is associated with type 2 diabetes, is thought to be a sign of a severe clinical course with serious clinical consequences in the form of NASH, liver cirrhosis and HCC. This combination requires a more aggressive therapeutic strategy, HCC screening, and long-term follow-up. A vicious circle is formed, which leads to adverse clinical consequences, worsens the prognosis and requires an active diagnostic and treatment strategy.