BACKGROUND:Hereditary hypoparathyroidism (hypoPT) is a rare endocrine disorder caused by absent or insufficient parathyroid hormone (PTH) secretion. Genetic forms are uncommon and frequently underdiagnosed, particularly when clinical onset is atypical. PURPOSE:We present a case series of three patients with genetic hypoPT caused by CASR, GNA11 and GATA3 mutations, highlighting atypical clinical presentation, diagnostic challenges and management approaches. METHODS:Clinical data, biochemical results, and genetic findings were analysed in a case of three female patients with early-onset, nonsurgical hypoPT, focusing on presentation patterns, diagnostic pathways, and choice of treatment. RESULTS:All patients exhibited chronic hypocalcemia, hyperphosphatemia, and low PTH without prior neck surgery, but had non-classical features leading to delayed diagnosis. Genetic testing identified pathogenic variants associated with autosomal dominant hypocalcemia types 1, 2, and Barakat syndrome. Age at symptom onset ranged from childhood to adolescence, whereas diagnosis was established only in late adolescence or adulthood. Major complications included intracranial calcifications (all cases), cataracts, and renal impairment. Initial presentations mimicked neurological, dermatological, and renal disorders, contributing to diagnostic delay. All patients required individualised therapy and multidisciplinary follow-up. CONCLUSION:Genetic causes of hypoPT should be suspected in patients with early-onset or atypical presentations in the absence of neck surgery. This case series illustrates that timely genetic testing confirms the diagnosis and determines personalised therapy. Management requires careful titration of calcium, active vitamin D medication to avoid complications and may benefit from emerging treatments (long-acting PTH analogues). Early recognition and tailored interventions can improve patient outcomes and quality of life.

Vitamin D plays an important role in the regulation of the «mother-placenta-fetus» system, participating in ensuring normal growth and development of the fetus, reducing the risks of hypocalcemia, muscle cramps, respiratory infections in childhood. To date, the existence of more than 50 metabolites of vitamin D has been established, of which the most studied are total 25-hydroxyvitamin D (25 (OH) D) and 1,25-dihydroxyvitamin D (1,25 (OH) 2D), which is due, first of all, to their importance for the endocrine regulation of calcium-phosphorus metabolism. The level of 25 (OH) D in the blood is an optimal, but not perfect marker of vitamin D status, and does not reflect the numerous effects of its metabolites. Taking into account the special metabolic adaptation of a woman’s body during gestation, the analysis of quantitative changes in various vitamin D metabolites is of particular relevance. This review summarizes the available data on the characteristics of vitamin D metabolism outside gestation and during pregnancy.

Background: Hereditary hypoparathyroidism (hypoPT) is a rare endocrine disorder caused by absent or insufficient parathyroid hormone secretion. Genetic forms are uncommon and frequently underdiagnosed, particularly when clinical onset is atypical.Purpose: We present three cases of genetic hypoPT caused by CASR, GNA11, and GATA3 mutations, highlighting diagnostic challenges and management approaches.Methods: Clinical data, biochemical results, and genetic findings were collected for three female patients with early-onset, nonsurgical hypoPT. Each case was evaluated for presenting symptoms, comorbidities, treatment responses, and outcomes. Relevant literature and guidelines were reviewed for context and management recommendations.Results: All patients exhibited chronic hypocalcemia, hyperphosphatemia, and low PTH without prior neck surgery. Initial manifestations were atypical, delaying diagnosis until adolescence or adulthood. Case 1 (CASR mutation) presented with seizure-like episodes misdiagnosed as epilepsy, and partial response to calcium–vitamin D therapy. Case 2 (GNA11 mutation) showed Raynaud’s phenomenon, dermatologic symptoms, and treatment intolerance without nephrocalcinosis. Case 3 (GATA3 mutation) had early deafness, later renal impairment, and fluctuating calcium levels. Genetic testing confirmed pathogenic variants, and individualized management with active vitamin D analogs achieved partial biochemical control. All patients remain under multidisciplinary follow-up with stabilization of neurological complications and monitoring of renal status. Conclusion: Genetic causes of hypoPT should be suspected in patients with early-onset or atypical presentations in the absence of neck surgery. Timely genetic testing confirms the diagnosis and determines personalized therapy. Management requires careful titration of calcium and active vitamin D to avoid complications and may benefit from emerging treatments (long-acting PTH analogs). Early recognition and tailored interventions can improve patient outcomes and quality of life.

Chronic liver disease is a significant public health problem worldwide, and its consequences lead to the development of various mineral disorders, which occur in 75% of patients. Osteoporosis (up to 30% of patients) has the greatest clinical significance among the mineral disorders that develop in chronic liver disease. Fractures occur, according to different data, in 7-35% of patients. There are number of mechanisms influencing the state of mineral metabolism in chronic liver diseases: from the disturbance of vitamin D metabolism to the synthesis of pro-inflammatory cytokines and the function of intestinal microbiota. To date, these processes remain insufficiently studied: for example, aspects concerning the functioning of parathyroid glands in chronic liver diseases are not completely clear; there is no clear idea about the predominant processes in bone tissue (anti- or proresorptive). This determines the imperfection of prophylactic and therapeutic approaches in mineral disorders due to chronic liver diseases and the need for further research in this direction. The first part of this review focuses on the epidemiology and pathophysiology of mineral metabolism disorders in these conditions; the second part of the review will focus on current therapeutic approaches

Sagliker syndrome (SS) is an extremely rare disorder that manifests in patients with advanced chronic kidney disease (CKD) undergoing programmed hemodialysis as a renal replacement therapy. Treatment of secondary hyperparathyroidism (SHPT) in these patients is still challenging. The main clinical manifestations of SS include craniofacial and fingertip deformities, dental anomalies, gingival hyperplasia, short stature, hearing loss, neurological and psychiatric impairment. The etiology and pathogenesis of SS in patients with SHPT require further clarification. However, mutations in the GNAS1, FGF23, and FGFR3 genes were described in some patients, suggesting a possible role of genetic predisposition to the syndrome. The preferred therapeutic approach for SS is surgery, but the volume of the operation is debated. The main surgical strategies include total, subtotal parathyroidectomy, or total parathyroidectomy with autotransplantation of the parathyroid gland (PG). Unfortunately, parathyroidectomy does not contribute to the regression of significant skeletal deformities. We present a unique clinical case of a patient with classical features of SS, recurrent tertiary hyperparathyroidism (THPT) after total parathyroidectomy due to intrathyroidal parathyroid carcinoma (PC).

BACKGROUND. Chronic hypoparathyroidism (HypoPT) is a relatively rare endocrine disorder. Adequate control of the disease requires the prescription of lifelong multicomponent therapy. Lack of sustained compensation of HypoPT is associated with the development of both early and delayed complications, including functional and structural renal pathology, cataracts, cerebral calcification, cardiac rhythm and/or conduction disorders, and others.AIM. To study the associations of clinical, laboratory and instrumental parameters, as well as the medical therapy, with long-term complications of chronic HypoPT.MATERIALS AND METHODS. The observational, continuous study was based on the data of the Russian Registry of Patients with Chronic Postoperative and Nonsurgical HypoPT; 1776 patients from 81 regions of the Russian Federation were included in the study.RESULTS. In the study population, 26,3% of patients (n=467) had at least one of the HypoPT complications, among them nephrolithiasis/nephromicrolithiasis was diagnosed in 33,4%. Nephrocalcinosis was observed in 10,7% and was more often bilateral (93,5%). In 17,4% of patients there was a significant decrease in GFR, corresponding to CKD stages 3a-5. Cataract was present in 34,7% of patients with chronic HypoPT. Statistically significant associations were found for disease duration with impaired renal filtration function (p<0,001), nephrocalcinosis/nephrolithiasis (p=0,001) and cataract (p<0,001). Patients with impaired renal function had higher serum ionized calcium level (p=0,0071) and lower phosphorus level (p=0,002). Cataract was predominantly diagnosed in patients of older age group (p<0,001), predominant in the presence of hypocalcemia by ionized calcium level (p=0,001). In patients undergoing brain MSCT for neurological symptoms, basal ganglia calcifications were detected in more than half of the cases (56,2%). Brain calcification was associated with younger patient age (p<0,001), hyperphosphatemia (p<0,001), hypomagnesemia (p=0,010). Statistically significant associations were observed between calcification of brain structures and higher doses of alfacalcidol and calcium carbonate (p=0,007).CONCLUSION. The analysis of the database revealed a number of associations between clinical, laboratory and instrumental parameters and long-term complications of HypoPT. The most significant factors in the development of renal pathology and cataracts are the duration of the disease, as well as off-target indicators of calcium-phosphorus metabolism.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Aim: to present disorders of mineral and bone metabolism in patients with chronic liver diseases through clinical observations.Key points. The liver plays an important role in mineral metabolism: metabolic activation of vitamin D, synthesis of vitamin D-binding protein and albumin, metabolism of parathyroid hormone, etc. However, data on the development of mineral metabolism disorders, particularly hyperparathyroidism, in this population are very limited. Bone diseases such as osteoporosis and osteomalacia are quite common in chronic liver disease, especially in cirrhosis and cholestatic diseases; however, the pathogenesis of these disorders and their relationship with mineral metabolism remain poorly understood. The article presents cases of severe primary hyperparathyroidism (PHPT) in patients with chronic liver disease. In one patient with a long history of viral hepatitis C and cirrhosis, PHPT manifested with severe bone complications, including multiple vertebral compression fractures and a subsequent femoral neck fracture. Imaging studies revealed lesions of all four parathyroid glands, and the removal of the largest lesion did not result in disease remission. In the second case described, PHPT was diagnosed in a patient with bone pain and osteoporosis following orthotopic liver transplantation for Budd — Chiari syndrome with cirrhosis. One year after the initial surgical treatment for PHPT, the patient experienced a recurrence of the disease, with confirmed multiglandular lesion.Conclusion. In patients with chronic liver diseases, disorders of mineral and bone metabolism remain a significant yet not fully understood problem. Further studies are needed to develop therapeutic approaches for this group of patients to prevent the onset of late, disabling complications.

BACKGROUND. Chronic hypoparathyroidism (HypoPT) is a rare endocrine disorder that requires lifelong multi-component therapy. The goal of HypoPT treatment is to reach the target values of the main indicators of calcium-phosphorus metab olism, first of all — calciemia, as well as to prevent acute and delayed complications, including pathology of kidneys, eyes, brain and other organs. One of the ways to improve the quality of medical care, determine optimal clinical and therapeutic management strategies, and find prognostic markers for HypoPT is to analyze large databases. This approach allows not only a better understanding of the peculiarities of disease progression, but also the evaluation of the efficacy of different therapeutic regimens.AIM. To evaluate the clinical and biochemical profile, medication therapy, and long-term complications in patients with chronic postoperative and nonsurgical HypoPT according to the data of the Russian Registry.MATERIALS AND METHODS. The observational, continuous study was based on the data of the Russian Registry of Patients with Chronic Postoperative and Nonsurgical HypoPT; 1776 patients from 81 regions of the Russian Federation were included in the study. RESULTS. In the study population, chronic HypoPT was predominant in women (86.5%), most patients had a postoperative etiology of the disease (70.1%), with the most common development of chronic postoperative HypoPT due to neck surgery for highly differentiated thyroid cancer (44.1%). Target calciemia was achieved in 44.6% of patients and target phosphatemia in 54.7%. Structural renal pathology (nephrocalcinosis/nephrolithiasis) was observed in 33.4% and 10.7% of patients, re spectively, and a decrease in glomerular filtration rate to chronic kidney disease stages 3a-5 in 17.4% of patients. Cataract occurred in 34.7%. In general, bone mineral density in the main zones (lumbar spine, femur, and radius) was within the values expected for the age of patients with both postoperative and nonsurgical HypoPT, and there was no evidence of high bone density phenomenon. The trabecular bone index corresponded to normal bone microarchitecture. 70.4% of patients re ceived classical HypoPT therapy — a combination of preparations of active metabolites of vitamin D and calcium. Additional medications (magnesium, potassium, recombinant human PTH, thiazide diuretics) were present in 5.9% of patients.CONCLUSION. Currently, there are limited epidemiologic data on the prevalence and morbidity of HypoPT in the Russian Federation, mainly due to the lack of nosology in the official statistical forms. The study of anamnestic, laboratory and in strumental characteristics of HypoPT in patients of the Russian population is an important step on the way to optimize the treatment and diagnosis of the disease. The analysis shows that the laboratory control of the disease is inadequate, as well as the coverage of patients with regard to the screening for long-term complications. Improving current clinical guidelines and raising awareness among physicians and patients can help overcome this problem.

Multiple endocrine neoplasia syndrome type 4 (MEN-4) is a rare autosomal dominant disease caused by mutation in the CDKN1B gene encoding the cell cycle regulator p27. Currently, a small number of clinical cases of patients with this pathology are known. Patterns of genotype-phenotype correlations in patients with CDKN1B mutations remains controversial and requires additional clarification. MEN-4 affects the same organs as MEN-1, however, the age of manifestation and the course of the disease may differ. We present the clinical case of a patient with MEN-4 with a new frame shift mutation in the CDKN1B gene caused PHPT with multiple parathyroid gland pathology and prolactin-secreting pituitary microadenoma. The first component of the disease diagnosed at the age of 37 was prolactinoma. Later, a visceral form of PHPT with isolated kidney complication was revealed. The patient has got the necessary treatment of the identified pathologies with satisfactory results. During a comprehensive examination, the involvement of other endocrine organs was not revealed. The limited number of case reports of patients with mutations in the CDKN1B gene currently does not allow us to determine the patterns of this syndrome’s course, and therefore a detailed description of the disease’s clinical presentation in a patient with a newly identified mutation makes a significant contribution to the study of this pathology.

One have described the clinical case of severe course of Trichinella infection. It has revealed some difficulties in diagnosis due to polymorphism of clinical picture, affection of different organs and systems by parasite. This demands the specialists of different profiles to be altered to this parasitic infection.

BACKGROUND: Primary hyperparathyroidism (PHPT), one of the most common endocrine pathologies, is associated with a higher incidence of cardiovascular diseases, in particular, those caused by endothelial dysfunction. Evaluation of endothelial dysfunction in patients with PHPT will predict the development of cardiovascular pathology and determine the optimal tactics for PHPT management.AIM: To evaluate the concentration of soluble endoglin and photoplethysmographic parameters as potential markers of endothelial dysfunction in patients with PHPT.MATERIALS AND METHODS: A single-center interventional single-stage study was carried out. 2 groups were formed. The first group included 50 patients with verified PHPT who did not have cardiovascular or other concomitant somatic pathologies in anamnesis. The comparison group included 21 healthy volunteers comparable in sex and age. All participants underwent a biochemical blood test (total calcium, ionized, albumin, lipidogram, urea, uricacid, glucose, creatinine, alkaline phosphatase), parathyroid hormone, 25 (OH) D and endoglin concentrations were evaluated. In addition, echocardiography, ultrasound of the brachiocephalic arteries and arteries of the lower extremities, as well as photoplethysmography were performed.RESULTS: The groups differed in mineral parameters associated with PHPT; no differences were found in parameters of lipid, uric acid and carbohydrate metabolism. Serum levels of endoglin were lower in PHPT patients (p=0.002). We found a negative correlation between the concentration of albumin-corrected calcium and PTH with endoglin (r1=-0.370, p1=0.003 and r2=-0.475, p2<0.001, respectively) and a positive correlation between the concentration of endoglin and phosphorus (r=0.363, p=0.003). These associations s were accompanied by changes in photoplethysmographic parameters that indicate an increase in the vascular wall stiffness.CONCLUSION: The serum level of soluble endoglin is lower in patients with PHPT than in healthy volunteers, negatively correlates with calcium and PTH concentrations and positively with serum phosphorus concentrations. Further studies will make it possible to establish the pathogenetic mechanism of the identified relationships and evaluate the role of endoglin as a potential predictor of cardiovascular pathology in PHPT population.

ЦЕЛЬ: исследовать патогенетические ассоциации между состоянием РААС и показателями минерального обмена, а также оценить частоту и характеристики артериальной гипертензии, в том числе, антигипертензивную терапию у пациентов с ПГПТ. МАТЕРИАЛЫ И МЕТОДЫ: были проведены проспективное исследование активности РААС при ПГПТ; анализ частоты АГ при ПГПТ и анализ антигипертензивной терапии на основании базы данных специализированного отделения. РЕЗУЛЬТАТЫ: в исследование РААС включены 37 пациентов в активной фазе ПГПТ и 29 сопоставимых здоровых добровольцев. У пациентов с ПГПТ активность ренина плазмы была значимо ниже, чем в группе сравнения (0,31 vs. 1,23 нг/мл*ч, р<0,001), а концентрация ангиотензина II - выше ( 40,2 vs. 23,7 пг/мл, р<0,001). На 3-и сутки после паратиреоидэктомии (ПТЭ) указанные изменения сохранялись. Через год после ПТЭ отмечалась нормализация всех показателей минерального обмена, отличий по показателям РААС между группами также не отмечалось. Из 585 пациентов с ПГПТ, госпитализированных в специализированное отделение НМИЦ эндокринологии, АГ диагностирована у 29,7% пациентов 18-49 лет, у 74% пациентов 50-65 лет и у 94% пациентов 66 лет и старше. Шанс наличия АГ у пациента с ПГПТ возрастает в 7 раз после 53 лет и при ИМТ более 28,3 кг/м2 , в 1,5 раза при концентрации фосфора более 0,91 ммоль/л, в 4 раза при СКФ менее 92 мл/мин/1,73 м2 и в 2 раза при концентрации бета-кросслапс менее 1,5 нг/мл. Пациенты, получавшие 3 и более антигипертензивных препарата, в отличии от лиц, не получавших антигипертензивную терапию, имели тенденцию к более высоким показателям кальциемии (2,69 vs. 2,61 ммоль/л, р = 0,03). У пациентов, принимавших ингибиторы РААС, показатели кальциемии были выше (2,68 vs. 2,62 ммоль/л, р=0,007), а СКФ ниже (80 vs. 84 мл/мин/1,73 м2 , р=0,002), чем у пациентов, не получавших данные препараты. ВЫВОДЫ: выявлена взаимосвязь между ПГПТ и компонентами РААС, также показана высокая частота АГ среди пациентов с ПГПТ, выявлена ассоциация между гиперкальциемией и интенсивностью и составом антигипертензивной терапии у пациентов с ПГПТ, патогенетические механизмы этих явлений требуют уточнения.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

IntroductionUntil recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation.Materials and methodsThe cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/).ResultsThe median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in MEN1, CDC73, RET genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol.ConclusionThe detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care.