This descriptive clinical case series analyzes five cases of destructive thyrotoxicosis associated with Hashimoto's thyroiditis, historically referred to as hashitoxicosis, initially misdiagnosed as Graves' disease, highlighting a persistent diagnostic challenge in autoimmune thyroid disorders. The series includes four published cases reported between 2000 and 2025 and one unpublished case contributed by the authors. The cohort comprised three females and two males, with a mean age of 55.4 years (range: 21-69). Clinical presentations were heterogeneous, most commonly fatigue (80%), palpitations (60%), and weight changes (40%), while two patients exhibited no overt hyperthyroid symptoms.Biochemical evaluation demonstrated suppressed thyroid-stimulating hormone (TSH) levels in all cases (range: <0.000-0.13 µIU/mL), elevated anti-thyroid peroxidase (anti-TPO) antibodies in 80% (range: 41->1,000 IU/mL), and initially negative thyroid-stimulating hormone receptor antibodies (TRAb/TSI) in 60% of patients. Seroconversion to positive TRAb/TSI was observed in two cases during follow-up, suggesting autoimmune overlap rather than definitive disease transition. Imaging findings, including thyroid ultrasonography and radioiodine uptake (RAI) studies, consistently favored destructive thyroiditis over stimulatory hyperthyroidism, with heterogeneous echotexture observed in 75% of assessed cases and low or normal RAI uptake in all evaluated patients.Misdiagnosis occurred in 80% of cases, predominantly due to reliance on suppressed TSH levels without TRAb confirmation, resulting in inappropriate antithyroid drug administration in 80% and accelerated hypothyroidism in 60%. Immunopathological interpretation based on existing literature supports a predominantly Th1-mediated destructive process, in contrast to the Th2-driven antibody-mediated stimulation characteristic of Graves' disease, with rare Th1-to-Th2 immune shifts reported. Clinical outcomes ranged from spontaneous resolution to surgical intervention.This case series underscores the importance of mandatory TRAb testing, adherence to American and European Thyroid Association guidelines, and early specialist referral to reduce iatrogenic harm and improve diagnostic precision in autoimmune thyroid disease.
Primary aldosteronism (PA) is the most common curable cause of secondary hypertension and an independent risk factor for chronic kidney disease (CKD). This review focuses on the pathophysiological mechanisms of aldosterone-induced renal injury, including mineralocorticoid receptor activation, nongenomic signaling via GPER, oxidative stress, and the upregulation of profibrotic and inflammatory mediators such as TGF-β1, NF-κB, and NLRP3. Chronic aldosterone excess leads to podocyte injury, microvascular dysfunction, and interstitial fibrosis, resulting in decreased glomerular filtration rate and CKD progression. Genetic mutations (KCNJ5, ATP1A1, CACNA1D) and tubular stress biomarkers (L-FABP, KIM-1, microalbuminuria) are discussed as key factors of early nephron injury. Comparative clinical data show that adrenalectomy provides superior nephroprotection compared to pharmacological blockade, while long-term therapy with mineralocorticoid receptor antagonists requires careful renal monitoring. Emerging therapeutic strategies, including nonsteroidal MR antagonists and aldosterone synthase inhibitors (baxdrostat), offer new prospects for targeted nephroprotection. By integrating molecular and clinical evidence, this review highlights the central role of aldosterone in renal pathology and emphasizes early detection and personalized treatment approaches to prevent CKD progression in patients with PA.
BACKGROUND:Vitamin D deficiency is one of the most common endocrine disorders and plays a significant role in the pathogenesis of carbohydrate metabolism disturbances. Low serum 25(OH)D levels are associated with the development of insulin resistance, metabolic syndrome, prediabetes, and type 2 diabetes mellitus (T2DM). However, data on the prevalence of vitamin D deficiency and its age-related characteristics in the population of Uzbekistan remain limited. OBJECTIVE:To investigate the prevalence of vitamin D deficiency in individuals with prediabetes and newly diagnosed T2DM based on screening data from the city of Andijan and the Markhamat district of the Andijan region, Uzbekistan. MATERIALS AND METHODS:A total of 3,400 individuals over 40 years of age were screened (1,800 in Markhamat district, 1,600 in Andijan city) using the FINDRISC questionnaire. Serum 25(OH)D levels, carbohydrate and lipid metabolism parameters, and HOMA-IR index were assessed in 205 subjects with prediabetes, 102 patients with newly diagnosed T2DM, and 60 controls. Prediabetes and T2DM were diagnosed according to WHO criteria. RESULTS:Mean vitamin D levels were significantly lower in patients with prediabetes and T2DM compared to the control group (p<0.05). The most severe deficiency was observed in patients with T2DM, especially among women and individuals aged 45-59 and 60-74 years. In Andijan city, vitamin D deficiency was detected in 100% of T2DM patients, while in Markhamat district the prevalence reached 40.3%. CONCLUSIONS:Vitamin D deficiency is highly prevalent among patients with prediabetes and T2DM, with severity increasing with age and more pronounced in women. These findings highlight the need for routine monitoring of serum 25(OH)D and preventive strategies in high-risk groups.
Gluconeogenesis, a dual-purpose pathway in type 2 diabetes mellitus (T2DM), not only synthesizes glucose but also clears metabolic waste via the Cori cycle (lactate recycling through LDH, PC, PEPCK) and Alanine cycle (nitrogen disposal via ALT, GDH, urea cycle), preventing acidosis, ROS accumulation, and ammonia toxicity. Metformin, the cornerstone T2DM therapy, inhibits gluconeogenesis by targeting mitochondrial complex I, elevating AMP/ATP ratios, and activating AMPK-PKCι/λ signaling to repress CREB-CRTC2-driven PEPCK/G6Pase expression, disrupting these cycles. This leads to lactate, pyruvate, and ammonia buildup, triggering pro-inflammatory cascades: HIF-1α stabilization induces IL-6/VEGF, ROS from pyruvate excess activates NF-κB for TNF-α, and ammonia primes NLRP3 inflammasome for IL-1β/IL-18 release, fostering chronic inflammation. Multisystem consequences include musculoskeletal fatigue from ATP deficits, cognitive fog via neuroinflammation, atherosclerosis from endothelial dysfunction, hepatic fibrosis from urea cycle stress, and immune inflammaging impairing macrophage function. Clinical evidence reveals short-term anti-inflammatory benefits (reduced IL-6, CRP) via AMPK and microbiota effects, contrasted by long-term risks like lactic acidosis and neurodegeneration in renal-impaired or elderly patients. This review integrates physiological roles, molecular mechanisms, inflammatory pathways, systemic impacts, and clinical findings, highlighting metformin’s dual-edged profile glycemic efficacy versus “inflammatory debt.” Researchers are urged to explore precision interventions, such as antioxidants or biomarker-guided dosing, to optimize metformin’s pleiotropic potential in T2DM and inflammaging-related disorders, redefining therapeutic paradigms.
BACKGROUND:Differentiated thyroid carcinoma (DTC) in children is a rare malignancy characterized by a high propensity for regional and distant metastases yet generally associated with a favorable long-term prognosis. Radioiodine-refractory (RAIR) disease represents a distinct clinical challenge, accounting for approximately 10-30% of pediatric DTC cases, and warrants comprehensive investigation of its clinical course, prognostic factors, and therapeutic options. This study aimed to perform an integrated assessment of treatment outcomes in children undergoing combined therapy for DTC (surgery and radioiodine therapy, RAI), with a particular focus on advanced and RAIR disease. MATERIALS AND METHODS:We retrospectively analyzed medical records of 278 patients aged 5-18 years who underwent primary surgical treatment between 2008 and 2022, followed by one or more courses of RAI at the Endocrinology Research Centre (Moscow, Russia) from December 2015 to March 2024. The study included patients with advanced disease (high risk of recurrence at diagnosis) fulfilling at least one RAIR criterion, with a median follow-up of 48.0 months [21.5; 62.0]. RESULTS:Among 278 patients, 39 (14%) were diagnosed with advanced disease. Of these, 4 achieved remissions, 29 had stable disease, and 6 experienced biochemical and/or structural progression. Progression-free survival in the RAIR cohort was 85%, while the 5-year overall survival reached 100%. CONCLUSION:Based on study findings, we propose a novel classification system integrating both the baseline ability of metastases to accumulate ¹³¹I and the dynamic response to RAI (progression vs. stabilization). This framework is designed to optimize treatment and follow-up algorithms. The management of RAIR pediatric DTC should remain balanced: avoiding overtreatment in stable disease, while ensuring timely initiation of modern systemic therapies in patients with risk factors for progression.
Microcephalic osteodysplastic primary dwarfism type II (MOPDII) is a form of primordial nanism characterized by extreme short stature, microcephaly, specific phenotype, maxillofacial dysmorphisms, skeletal dysplasia, disorders of carbohydrate metabolism, and neurovascular abnormalities. This article describes a patient with a Seckel syndrome phenotype presenting with left internal carotid artery aneurysms with intracerebral hemorrhages, thrombocytosis, arterial hypertension, and diabetes mellitus due to insulin resistance confirmed by a low Matsuda index. Target carbohydrate metabolism values were achieved on metformin therapy. Clinical exome sequencing revealed two rare heterozygous variants in the PCNT gene: c.6220C>T (p.Gln2074*) and c.4564-12T>A. Comparison of the results of the molecular genetic study and the patient's phenotype allowed us to verify the diagnosis of MOPDII. Hypergonadotropic hypogonadism was described for the first time in this syndrome.
The clinical practice guidelines for congenital adrenal hyperplasia (CAH) in children clearly and systematically present the key information on the epidemiology, etiology, pathogenesis, and diagnostic methods for all forms of the disease. Protocols for glucocorticoid and mineralocorticoid replacement therapy, as well as follow-up regimens for patients in different age groups, are provided. These clinical guidelines were developed and approved by the expert community of pediatric endocrinologists from the Russian Association of Endocrinologists and endorsed by the council of the Russian Federation Ministry of Health. The guidelines are based on systematic reviews, meta-analyses, original articles, and scientific studies on this pathology conducted in the Russian Federation and other countries. This article provides updated author comments and clarifications on the most critical aspects of the diagnosis and treatment of congenital adrenal hyperplasia in childhood.
RELEVANCE:Primary hyperparathyroidism is one of the most common endocrine diseases characterized by impaired calcium-phosphorus metabolism due to hypersecretion of parathyroid hormone. GOAL:Assessment of the epidemiological situation with parathyroid gland diseases in the Chuvash Republic based on data from the All-Russian Registry of Patients with primary hyperparathyroidism. To analyze the data of patients with primary hyperparathyroidism in a retrospective cohort study from 2014 to 2025 at the clinical base of the Republican Clinical Hospital for War Veterans of the Ministry of Health of Chuvashia. MATERIALS AND METHODS:The data on the Chuvash Republic from the All-Russian Registry of patients with primary hyperparathyroidism are analyzed. In the course of a retrospective cohort study (2014-2025), a cohort of patients registered at the Republican Clinical Hospital for War Veterans of the Ministry of Health of Chuvashia was analyzed. For statistical data processing, a descriptive method was used with the calculation of absolute and relative values (percentages). RESULTS:It was found that the prevalence of parathyroid gland pathology in the region is 73.4 cases per 100,000 population. Key epidemiological features were identified: a pronounced predominance of women (88.9%) in the older age group, an uneven geographical distribution with a concentration of cases in urbanized areas (Cheboksary, Novocheboksarsk), as well as a significant increase in detection in recent years. The data obtained indicate the influence of both organizational factors (availability of specialized care) and possible environmental risks (imbalance of trace elements in water sources) on the prevalence of pathology. CONCLUSION:The implemented electronic registry has proven its effectiveness for monitoring morbidity, planning medical care and conducting scientific research, which determines the prospects for its further development to optimize the system of endocrinological care in the region.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide have transformed type 2 diabetes mellitus (T2DM) management, yet emerging concerns highlight potential risks of accelerated sarcopenia and subsequent metabolic disruptions. This case-driven hypothesis explores a 53-year-old male with T2DM diagnosed in 2014, who experienced progressive glycemic failure despite standard therapies, including metformin, glipizide, sitagliptin, and empagliflozin. Transition to dulaglutide 1.5 mg for 1.5 years followed by semaglutide (titrated from 0.25 to 1 mg weekly starting September 2024) resulted in weight loss from 84 kg to 70 kg by September 2025, accompanied by sarcopenic symptoms (muscle weakness, reduced mobility) and refractory hyperglycemia (fasting glucose 300 mg/dL, HbA1c 9%), persisting post-discontinuation on September 1, 2025, despite metformin and empagliflozin. We posit that semaglutide may precipitate acute sarcopenia via unexpected GLP-1R-mTOR-satellite cells axis crosstalk, disrupting AMPK-mTOR balance to suppress anabolic mTORC1/IGF-1 signaling (potentially by 25-35%) while enhancing catabolic FOXO/ubiquitin-proteasome and excessive autophagy pathways. This could extend to myokine reprogramming (elevated myostatin/GDF15, reduced irisin/IL-15), glucagon/α-cell compensation inducing hyperglucagonemia (15-25% rise), microbiome-bile acid shifts fostering low-grade inflammation (IL-6/TNF-α upregulation by 10-15%), mitochondrial mass reduction (20-25% via AMPK), and NMJ disassembly, collectively impairing muscle as the primary glucose sink (reducing GLUT4-mediated uptake by 35-45%) and initiating a «muscle-glucose feedback loop» with hepatic gluconeogenesis amplification, yielding treatment-resistant hyperglycemia. Supporting evidence from cohorts (e.g., 24-month study showing ASMI/grip strength declines in 432 patients), longitudinal analyses (NMJ degradation with CAF22/NfL elevations in 141 men), secondary trials (9.3% psoas volume loss in 51 MASLD cases), and case reports (fatigue in a 74-year-old, rhabdomyolysis in a 47-year-old) aligns with this framework, as does in vitro data linking GLP-1 excess to kinesin-1/GLUT4 inhibition and ATP depletion (20-30%). This novel hypothesis underscores sarcopenia’s role in GLP-1RA-induced metabolic paradoxes, urging prospective studies on muscle-preserving interventions like resistance training or GLP-1R modulators to refine T2DM paradigms and inspire multidisciplinary research into endocrine-muscle interactions.
During the first quarter of the 21st century, iodized salt became available almost everywhere, and only isolated pockets of iodine deficiency remain in the world. By 2024, 126 countries had introduced mandatory iodine fortification of salt, 89% of the world’s population consumes iodized salt, and 101 countries have achieved adequate iodine status among their populations, whereas in 1993, low iodine intake was observed in 113 countries. This is why iodine fortification of salt is recognized as one of the greatest achievements in public health. The new recommendations reviewed in this paper update existing guidelines regulating salt fortification programs, their monitoring and evaluation, and propose using new approaches in combination with maintaining and strengthening measures that have proven effective and sustainable. Of the six "analytical notes" included in the guidelines, the section on improving the availability of data on the iodine status of the population may be of greatest interest to readers. According to the authors, the effectiveness of salt iodization programs should be assessed by integrating iodine status surveys into more comprehensive health and nutrition surveys of the population or through sentinel epidemiological monitoring in areas at high risk of iodine deficiency. Collecting urine samples in antenatal clinics during routine visits by pregnant women is likely to be a less resource-intensive approach than representative cross-sectional surveys of iodine status.
On December 3, 2025, a meeting of the expert working group was held in Moscow. The discussion focused on the safety and personalized use of tirzepatide (Tirzetta®) and semaglutide (Velgia® eco) in patients with overweight and obesity. Following the meeting, a consensus position was developed on the optimal use of incretin receptor agonists in real-world clinical practice.
Congenital Adrenal Hyperplasia (CAH) is a group of diseases with an autosomal recessive inheritance pattern, which are caused by a defect in the enzymes involved in steroidogenesis in the adrenal cortex. Depending on the enzyme block variant, the spectrum of clinical manifestations of CAH varies from mild symptoms to potentially fatal disorders. The review provides a detailed analysis of the six main forms of CAH (lipoid hyperplasia, HSD3B2, CYP17A1, CYP21A2, CYP11B1, POR) with an in-depth description of their molecular basis, pathogenesis, and clinical and laboratory manifestations. Particular attention is paid to modern methods of genetic diagnosis of CAH, including analysis of the highly homologous CYP21A2 locus, prenatal and preimplantation diagnosis. Not only modern approaches to replacement therapy are described in detail, but also promising methods of treatment: corticotropin-releasing hormone receptor antagonists, gene- and cellbased technologies. The study's strength lies in its comprehensive analysis of the disease, spanning fundamental research to practical patient management, as applied to the realities of clinical practice in Russia.
Neonatal screening for congenital adrenal hyperplasia (CAH) has been conducted in Russia since 2006. An analysis of results from 2015-2025, covering 15,546,274 newborns, identified 1,871 children with classic forms of 21-hydroxylase deficiency. The average detection rate was 1:8,309 (0.012% or 1,20 per 10 000 per year) with annual variations ranging from 1.03 to 1.48 per 10,000 newborns per year. Significant interregional variability in incidence was observed, with the highest rates recorded in the Karachay-Cherkess Republic (6.16/10,000 per year), Leningrad Oblast (4.04/10,000 per year), and Primorsky Krai (3.07/10,000 per year). Among federal districts, the Urals Federal District ranked highest. The timing of diagnosis leads to critical differences in outcomes, including the risk for adrenal crisis. Newborn screening confirms its high efficiency, and the identified regional variations underscore the need for further population genetic studies to optimize medical genetic counseling.
BACKGROUND:Hypoparathyroidism (HypoPT) and pseudohypoparathyroidism (PHP) are rare, predominantly genetically determined diseases in children with similar complications, characterized by hypocalcemia and hyperphosphatemia. PHP and HypoPT have similar complications: brain and lens calcification. In HypoPT, there is also an increased risk of developing nephrocalcinosis. Data on the frequency and structure of complications in affected children in Russia are limited, and comparative studies are lacking. AIM:To compare the prevalence of chronic complications and to identify factors associated with their development in children with PHP and congenital forms of HypoPT. MATERIALS AND METHODS:A retrospective study with a prospective component included 135 children with PHP and congenital forms of HypoPT. The results of laboratory and instrumental studies were evaluated. RESULTS:At least one complication associated with HypoPT/PHP was identified in 82% of children. Nephrocalcinosis was most frequently detected in patients with autoimmune polyendocrine syndrome type 1 (APS-1) (67%) and autosomal dominant hypocalcemia type 1 (ADH1), and much less often in patients with PHP (22%) and unspecified forms of HypoPT (18%). Disease duration, as well as the duration of therapy with active vitamin D analogs and calcium supplements, was significantly longer in patients with nephrocalcinosis (p < 0.001). An association between nephrocalcinosis and cataracts was established (p=0.005). Hypercalciuria persisted in 60% of patients despite medical compensation, was most prevalent in APS-1 and ADH1, and was not observed in PHP (p < 0.001). No statistically significant relationship was identified between hypercalciuria and the development of nephrocalcinosis (p=0.567). A decrease in eGFR corresponding to CKD stage 2 was observed in 48.9% of patients. Fahr's syndrome was detected in 76% of cases, predominantly involving the basal ganglia, and the presence of mineral deposits was associated with hyperphosphatemia (p=0.010). Cataract and micronephrolithiasis were less frequent (18.6% and 3.9%, respectively), with no significant differences between nosological groups. The most common lens opacities observed were cortical (68%) and posterior subcapsular (41%). The duration of the disease was longer in patients with cataracts (p = 0.018). CONCLUSION:Among the complications observed in children, nephrocalcinosis, hypercalciuria, and Fahr's syndrome were the most frequent. Renal complications predominated in patients with APS-1 and ADH1. Hypercalciuria persisted despite optimal serum calcium levels in most patients.
Graves' orbitopathy (GO) is a progressive autoimmune disorder of visual organ, mostly associated with Graves' disease (GD). Although rituximab has been used as an off-label therapy for steroid-resistant GO, paradoxical immune reactivation has also been reported. We present a rare case of GO that developed after bendamustine-rituximab (BR) therapy for chronic lymphocytic leukemia (CLL). A 73-year-old male with a 3-year history of GD, presented with new onset of bilateral proptosis, diplopia, and decreased visual acuity, that happened two weeks after his second BR cycle for CLL. The anamnesis was negative for both smoking, and radioiodine therapy. Laboratory studies showed persistently elevated thyrotropin receptor antibodies levels in plasma, and extraocular muscle enlargement on orbital MRI. The active phase (CAS 6/6) of moderate-to-severe (EUGOGO) GO was diagnosed. Despite two courses of intravenous methylprednisolone (cumulative dose - 12.2 g) and 10 retrobulbar dexamethasone injections, the patient progressed to dysthyroid optic neuropathy. Although the patient had a predisposing autoimmune background, the close temporal association with BR therapy, progressive disease course, and glucocorticoid resistance suggest that chemotherapy-induced immune dysregulation played a critical role in triggering GO. Rituximab-related B-cell depletion and cytokine release syndrome may have facilitated T-cell-mediated orbital inflammation, while bendamustine-induced lymphopenia further disrupted immune tolerance. This case illustrates the potential for paradoxical autoimmune activation following BR therapy in a predisposed patient. Clinicians should monitor for GO signs, and symptoms before, during, and after BR therapy in patients with underlying thyroid autoimmunity. Further clinical trials are needed to verify this phenomenon.
BACKGROUND:Obesity and type 2 diabetes (T2D) are common metabolic disorders. Oxytocin, a hypothalamic neuropeptide, has recently been recognized as a potential regulator of energy balance, appetite, and insulin sensitivity. OBJECTIVE:To investigate the relationship between circulating oxytocin levels and metabolic parameters in individuals with obesity and newly diagnosed T2D. MATERIALS AND METHODS:A total of 96 participants were enrolled, including 48 with normal glucose tolerance (NGT) and 48 with newly diagnosed T2D, each subdivided into normal-weight and obese groups. Anthropometric indices, glucose and lipid parameters, insulin, HbA1c, and high-sensitivity C-reactive protein were measured. Insulin resistance and β-cell function were assessed using the HOMA model. RESULTS:Circulating oxytocin levels were significantly lower in patients with T2D compared to NGT (p < 0.01), and in obese compared to normal-weight participants (p < 0.01). Low oxytocin was negatively correlated with BMI, waist circumference, HbA1c, glucose, insulin, lipids, and hs-CRP, but positively with β-cell function. Multiple regression analysis identified 2-hour glucose, BMI, and total cholesterol as independent predictors of oxytocin levels. CONCLUSION:Patients with obesity and newly diagnosed T2D exhibit markedly reduced circulating oxytocin levels, associated with adverse metabolic profiles. These findings highlight oxytocin as a potential biomarker of early metabolic dysregulation and suggest new therapeutic perspectives.
In recent decades, the Russian government has been committed to improving the country's demographic situation. Therefore, obstetricians and gynecologists pay special attention to women of reproductive age, whose reproductive system disorders can lead to infertility and the inability to conceive. Menstrual cycle disorders (MCDs) are a manifestation of various pathological conditions associated not only with disorders of the female reproductive system but also with general systemic and endocrine diseases. Since the 1980s, the incidence of MCDs has increased more than sevenfold. MCDs are characterized by changes in the cycle frequency, duration, and volume of menstrual blood loss. An obstetrician/gynecologist who initially consults a woman of reproductive age with MCDs should not only develop an examination plan for the patient, but most importantly, collect a detailed medical history, including a description of her physical condition, sports history, dietary habits, medication intake, including vitamins and dietary supplements, and analyze the relationship between MCDs and epigenetic factors in the woman's life. The incidence of NMC in the presence of an endocrine disease is up to 35% and requires referral of the patient to an endocrinologist to compensate for the endocrinopathy.
Congenital Adrenal Hyperplasia (CAH) is a group of diseases with an autosomal recessive inheritance pattern, which are caused by a defect in the enzymes involved in steroidogenesis in the adrenal cortex. Depending on the enzyme block variant, the spectrum of clinical manifestations of CAH varies from mild symptoms to potentially fatal disorders. The review provides a detailed analysis of the six main forms of CAH (lipoid hyperplasia, HSD3B2, CYP17A1, CYP21A2, CYP11B1, POR) with an in-depth description of their molecular basis, pathogenesis, and clinical and laboratory manifestations. Particular attention is paid to modern methods of genetic diagnosis of CAH, including analysis of the highly homologous CYP21A2 locus, prenatal and preimplantation diagnosis. Not only modern approaches to replacement therapy are described in detail, but also promising methods of treatment: corticotropin-releasing hormone receptor antagonists, gene- and cellbased technologies. The study's strength lies in its comprehensive analysis of the disease, spanning fundamental research to practical patient management, as applied to the realities of clinical practice in Russia.
BACKGROUND:The paradigm of combined treatment for differentiated thyroid cancer has been in use since the mid-20th century. This approach involves thyroidectomy, followed by radioactive iodine therapy, and after patients may be prescribed suppressive therapy. Combined treatment improves outcomes, particularly in cases of high risk of recurrence. However, it can also lead to a range of secondary complications, including those affecting the reproductive system. AIM:Assessment and comparative analysis of ovarian function and ovarian reserve (OR) using anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2) and estrone (E1) in the early follicular phase in women of reproductive age who received combined treatment for DTC, and in healthy women of the same age. MATERIALS AND METHODS:In a single-center, comparative cross-sectional study, clinical and morphological, anamnestic and laboratory parameters were analyzed in patients who underwent thyroidectomy and one course of radioiodine therapy for DTC, and in healthy women. RESULTS:The study enrolled 90 women aged 18 to 40 years: 67 women with DTC with a median age of 31 years [26; 36] who underwent combined treatment, and 30 healthy women with a median age of 30 years [28; 35]. The frequency of menstrual cycle disorders over the past year was 33% in women with DPT and 13% in healthy women.When comparing the results of hormonal examination, it was revealed that the levels of FSH, LH, PRL, E1 and E2 did not differ significantly between the groups. The level of AMH was the only parameter that significantly differed in patients with DTC receiving combined treatment and in healthy women - 2.49 ng/ml [1.1; 3.3] and 3.6 ng/ml [2.62; 4.18], respectively (P < 0.004). In 18 (27%) patients with DTC, the level of AMH was < 1.2 ng/ml, in the group of healthy women low level of AMH was found only in one case. Only patient's age at the time of RAIT and age at the time of examination on the background of thyroid stimulating hormone suppression were associated with diminished ovarian reserve, using the Juden index, the cut-off points of 31 years and 33 years were determined, respectively. CONCLUSION:The level of AMH in patients with DTC who undergo combined treatment is significantly lower compared to healthy women of the same age. Only patient's age at the time of RAIT and age at the time of examination on the background of thyroid stimulating hormone suppression were associated with diminished ovarian reserve.
Type 2 diabetes mellitus (T2DM), projected to affect 700 million individuals by 2045, may be driven by a hypothesized physiological axis where impaired hepatic insulin clearance, mediated by CEACAM1 endocytosis, links proinsulin misfolding to chronic hyperinsulinemia, exacerbating T2DM, obesity, and non-alcoholic fatty liver disease (NAFLD). Approximately 50–80% of proinsulin, synthesized at ~6000 molecules per second, undergoes 5–10% misfolding due to disrupted disulfide bonds (B7-A7, B19-A20, A6-A11) under endoplasmic reticulum (ER) stress, compounded by glutathione (GSH) depletion, which primarily impairs protein disulfide isomerase (PDI) function critical for insulin synthesis. Hepatic clearance involves CEACAM1 binding, insulin receptor isoform B (IR-B) tyrosine 960 autophosphorylation, AP-2/clathrin/dynamin vesicle formation, Rab5-mediated acidification (pH 5.5), Rab7 trafficking, and lysosomal cathepsin B/D hydrolysis, supported by IR-B–IRS-1 tyrosine 608–PI3K–PDK1–Akt (Ser473)–GSK3β signaling. ER stress activates the unfolded protein response (UPR: IRE1α-XBP1, PERK-eIF2α, ATF6), increasing clearance demand. When clearance fails, misfolded proinsulin accumulates, driving hyperinsulinemia, which promotes insulin resistance, activates mTORC1–SREBP-1c-mediated lipogenesis and VLDL export, and contributes to NAFLD and obesity, as observed in CEACAM1 knockout models. The Hepatic Insulin Clearance Index (HICI), derived from a 50-g glucose challenge yielding a C-peptide/insulin ratio <1, may diagnose impaired clearance with greater sensitivity than HOMA-IR. Emerging tools, such as cryo-EM and portal vein proteomics, could quantify misfolded aggregates and elucidate NAFLD connections. Potential therapeutic strategies, including CEACAM1 enhancers and IR-B agonists, may target this clearance axis. This hypothesis underscores hepatic insulin clearance as a potential mediator of insulin resistance and its role in diseases linked to chronic hyperinsulinemia.
