Dynamic Evaluation of Vitamin D Metabolism in Post-Bariatric Patients.

BACKGROUND: findings from the previously conducted studies indicate altered regulatory mechanisms of calcium and vitamin D metabolism in obese patients and a role for bariatric surgery in regulating vitamin D metabolism; however, the available data is controversial and does not provide an adequate understanding of the subject. METHODS: we evaluated serum parameters of vitamin D and mineral metabolism (vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3), vitamin D-binding protein (DBP), free 25(OH)D, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), total calcium, albumin, phosphorus, creatinine, magnesium) in 30 patients referred for bariatric surgery in comparison with 30 healthy volunteers of similar age, sex and baseline 25(OH)D3. Patients were also followed up with repeated laboratory assessments 3 months and 6 months after surgery. During the first 3 months, patients were prescribed high-dose cholecalciferol therapy (50,000 IU per week), with subsequent correction based on the results of the 3-month visit examination. RESULTS: Preoperatively, patients with morbid obesity were characterized by a high prevalence of vitamin D deficiency (median 25(OH)D3 level 11.9 (6.8; 22.2) ng/mL), significantly lower levels of active vitamin D metabolite 1,25(OH)2D3 (20 (10; 37) vs. 39 (33; 50) pg/mL, p < 0.001), lower serum albumin-adjusted calcium levels (2.24 (2.20; 2.32) vs. 2.31 (2.25; 2.35) mmol/L, p = 0.009) and magnesium levels (0.79 (0.72; 0.82) vs. 0.82 (0.78; 0.85) mmol/L, p = 0.043) with simultaneous similar PTH levels (p = 0.912), and higher DBP levels (328 (288; 401) vs. 248 (217; 284) mg/L, p < 0.001). The 25(OH)D3 levels remained suboptimal (24.5 (14.7; 29.5) ng/mL at the 3-month visit and 17.9 (12.4; 21.0) ng/mL at the 6-month visit, p = 0.052) despite recommended high-dose cholecalciferol supplementation. Patients also demonstrated an increase in 1,25(OH)2D3 levels (38 (31; 52) pg/mL at the 3-month visit and 49 (29; 59) pg/mL at the 6-month visit, p < 0.001) without a change in PTH or calcium levels during the follow-up. CONCLUSION: our results of a comprehensive laboratory evaluation of vitamin D status and mineral metabolism in patients undergoing bariatric surgery highlight the importance of improving current clinical guidelines, as well as careful monitoring and education of patients.

Parameters of Vitamin D Metabolism in Patients with Hypoparathyroidism.

Only a few studies evaluating the metabolism of vitamin D in patients with hypoparathyroidism (HypoPT) have been performed thus far, and, in particular, they mainly investigated the process of vitamin D activation (specifically, 1α-hydroxylation). This study, therefore, aimed to evaluate the extended spectrum of vitamin D metabolites in patients with HypoPT compared to healthy individuals. We examined 38 adult patients with chronic HypoPT in comparison to 38 healthy adults. The assessment included biochemical parameters (total calcium, albumin, phosphorus, creatinine, and magnesium), parathyroid hormone (PTH), and vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, and 24,25(OH)2D3) in serum. Our data show that an adequate level of 25(OH)D3 (median 35.3 (29.6; 42.0) ng/mL) is achieved with standard doses of cholecalciferol (median 2000 (2000; 2500) IU per day) in HypoPT patients. They also presented with supraphysiological levels of 1,25(OH)2D3 (median 71 (47; 96) vs. 40 (34; 59) pg/mL, p < 0.001) and the increased production of inactive metabolite (median 24,25(OH)2D3 3.8 (3.0; 5.1) vs. 1.9 (1.3; 2.7) ng/mL, p < 0.001; median 25(OH)D3/24,25(OH)2D3 ratio 8.9 (7.6; 11.1) vs. 13.5 (11.1; 17.0), p < 0.001) as compared to the control group. This might be a consequence of the therapy received (treatment with activated vitamin D) and the pathophysiology of the disease (lack of PTH). The abnormality of vitamin D metabolism does not seem to interfere with the achievement of hypoparathyroidism compensation.

Impaired Vitamin D Metabolism in Hospitalized COVID-19 Patients.

There is increasing data regarding the association between vitamin D and COVID-19. This study aimed to reveal the alterations of vitamin D metabolism in the setting of COVID-19. We examined 119 adult COVID-19 inpatients and 44 apparently healthy adult individuals with similar serum 25OH-D3 levels as a reference group. The assessment included serum biochemical parameters (total calcium, albumin, phosphorus, creatinine), parathyroid hormone (PTH), vitamin D-binding protein (DBP), vitamin D metabolites (25OH-D3, 25OH-D2, 1,25(OH)2D3, 3-epi-25OH-D3, 24,25(OH)2D3 and D3) and free 25OH-D. COVID-19 patients had in general very low vitamin D levels (median 25OH-D3 equals 10.8 ng/mL), accompanied by an increased production of the active vitamin D metabolite (1,25(OH)2D3), estimated as higher 1,25(OH)2D3 serum levels (61 [44; 81] vs. 40 [35; 50] pg/mL, p < 0.001) and lower 25OH-D3/1,25(OH)2D3 ratio (175 [112; 260] vs. 272 [200; 433], p < 0.001) which is presumably aimed at preventing hypocalcemia. Patients with COVID-19 also had elevated DBP (450 [386; 515] vs. 392 [311; 433] mg/L, p < 0.001) and low free 25OH-D levels (

Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment.

PURPOSE: To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment. METHODS: The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics. RESULTS: Patients with acromegaly had tendency to lower baseline 25(OH)D3 levels (p = 0.05) and lower 25(OH)D3 levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH)2D3 and lower 24,25(OH)2D3 levels with corresponding lower 25(ОН)D3/1,25(ОН)2D3 and higher 25(ОН)D3/24,25(ОН)2D3 ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D3 was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05). CONCLUSION: Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН)2D3, lower 24,25(ОН)2D3 and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations. TRIAL REGISTRATION: NCT04844164 (release date: April 9, 2021; retrospectively registered).

Assessment of Vitamin D Metabolism in Patients with Cushing's Disease in Response to 150,000 IU Cholecalciferol Treatment.

In this study we aimed to assess vitamin D metabolism in patients with Cushing's disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Serum circulating miRNA-342-3p as a potential diagnostic biomarker in parathyroid carcinomas: A pilot study.

OBJECTIVE: To compare the serum miRNA expression profiles between patients with benign and malignant parathyroid tumours. BACKGROUND: Despite recent advances in molecular biology, a histological tissue biopsy is still the method of choice used to diagnose most cancers. The preoperative cytology is not an applicable method for diagnosis of parathyroid cancer (PC); therefore, huge interest exists in terms of finding alternative methodologies to seek specific cancer biomarkers. DESIGN: A retrospective cross-sectional study. PATIENTS AND METHODS: Serum samples of patients with PC (n = 13) and parathyroid adenoma (PA) (n = 11), age (p = .999) and sex (p = .999) were matched and examined via the simultaneous comparative expression analysis of 754 microRNAs (miRNAs). The «TaqMan OpenArray Human MicroRNA Panel¼ (Applied Biosystems) was used to conduct real-time PCRs using the «QuantStudio 12К Flex¼ station (Life Technologies). RESULTS: According to the results of a pilot study, significant changes in expression levels between the PC group and the PA group (control) (p < .05) were observed for 17 miRNAs. Among them, the downregulation of miRNA-342-3p met the Benjamini-Hochberg adjustment criteria for multiple comparisons (p = .02). CONCLUSIONS: Serum miRNA-342-3p could be a promising biomarker for PC to improve diagnosis and prognosis.

Evaluation of Vitamin D Metabolism in Patients with Type 1 Diabetes Mellitus in the Setting of Cholecalciferol Treatment.

In this prospective controlled study, we examined 25 adults with adequately controlled (HbA1c level < 8.0%) type 1 diabetes mellitus (T1DM) and 49 conditionally healthy adults, intending to reveal the diversity of vitamin D metabolism in the setting of cholecalciferol intake at a therapeutic dose. All patients received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. The studied groups had no significant differences in baseline parameters except that the patients with diabetes showed higher baseline levels of free 25(OH)D (p < 0.05). They also lacked a correlation between the measured and calculated free 25(OH)D in contrast to the patients from the control group (r = 0.41, p > 0.05 vs. r = 0.88, p < 0.05), possibly due to the glycosylation of binding proteins, which affects the affinity constant for 25(OH)D. The elevation of vitamin D levels after the administration of cholecalciferol was comparable in both groups, with slightly higher 25(OH)D3 levels observed in the diabetes group throughout the study since Day 1 (p < 0.05). Overall, our data indicate that in patients with adequately controlled T1DM 25(OH)D3 levels and the therapeutic response to cholecalciferol is similar to that in healthy individuals.

[COVID-19 pandemic and endocrinopathies].

Many endocrinopathies have chronic course; patients with endocrinopathies (above all diabetes mellitus and thyroid diseases) who receive outpatient care on a regular basis amount up to 80% of patients with chronic diseases. Endocrinologists most likely play the role of general practitioners for these patients; therefore, they should quickly and efficiently explain the patients with diabetes, thyroid, hypophysis and adrenal diseases how to behave in new setting of COVID19 pandemic (coronavirus infection). The most severe course of the infection can be observed in patients older than 65 years with chronic diseases, especially endocrinopathies. This review sums up the currently available data on the disease pathogenesis and progression. It also provides information about patient responsibility to prevent infection, special aspects of communication between the patient and the physician in the setting of self-isolation and quarantine, additional care needed in case of COVID19 in patients with most severe endocrinopathies.

[Epidemiology, clinical manifestations and efficiency of different methods of treatment of acromegaly according to the United Russian Registry of Patients with Pituitary Tumors].

BACKGROUND: The registry is the main source of information about patients with acromegaly for assessing the quality of medical care, effectiveness of treatment, determining the compliance of real clinical practice with existing standards and patient management protocols. AIMS: To evaluate epidemiological, demographic and clinical characteristics of acromegaly in Russian Federation and effectiveness of treatment modalities. MATERIALS AND METHODS: The object of the study was the database of the united Russian registry of patients with pituitary tumors with specific analysis of patients with acromegaly only. We analyzed the data of 4114 patients with acromegaly stored on the online system in February 2019. RESULTS: Based on the data 32% of patients had complete clinical and laboratory remission of acromegaly; the percentage of patients with no remission was 68%, among them 22.5% had significant improvements in clinical symptoms and a decrease in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) without IGF-1 normalization. The average age of patients at the onset of the disease was 42.7 years and at diagnosis – 45.8 years. The ratio of men to women was 1:2.6. In patients with acromegaly hypopituitarism was registered in 14.7% of cases and among them hypothyroidism (66%) and hypogonadism (52%) were registered more often. Among other complications the leading were diabetes mellitus (15.7%) and acromegalic arthropathy (15%). The proportion of patients receiving neurosurgical treatment increased from 35.7% to 49.6% in 2012–2019; the portion of patients undergoing radiation therapy decreased significantly from 17.7% in 2012 to 0.8% in 2019. Remission was achieved in 40.47% after neurosurgery and 28.95% after medical treatment as a first line therapy p<0.01. The number of patients receiving medical treatment at the time of the study was 1209. Among them 51% of patients treated with long-acting lanreotide and 24% receiving long-acting octreotide achieved remission (p<0.0001) CONCLUSIONS: The remission rate of acromegaly remains suboptimal despite increased surgical activity, which corresponds to global trends. Long-acting lanreotide was significantly superior versus long-acting octreotide in the rate of acromegaly remission, which does not correspond with clinical trials.

[Vitamin D metabolism in hypercorticism and acromegaly].

Due to the high prevalence of low vitamin D levels in the overwhelming majority of regions of the world and discovery of extra-skeletal effects of vitamin D, the issue of maintaining adequate levels of vitamin D in the blood remains extremely relevant, especially in people with high risk of severe deficiency. To date, few studies have been performed on the features of vitamin D metabolism in disorders such as hypercorticism and acromegaly. However, vitamin D deficiency in such patients, according to available literature, may be more widespread and more pronounced than in general population. It is now recommended to use standard prophylactic and therapeutic doses of vitamin D for the treatment of these diseases, which may not satisfy the therapeutic goals specific to each disease. This review provides information on normal vitamin D metabolism, as well as literature data on the possible relationship and mutual influence between these endocrinopathies and vitamin D metabolism.

[Organization, problems and development prospects of endocrinology care and specialist training].

Currently, among the priority tasks of the health care system is to improve the quality of medical care provided to the population and the accessibility of services. Incomplete staffing is a serious slowdown to the provision of quality care. The shortage of medical personnel is widespread in medicine, which is especially pronounced in primary health care, and endocrinology is no exception. The shortage of personnel is directly related to the problems of accessibility and quality of medical care. Reorganizing the system of professional training, retraining and continuing medical education in a volume that allows eliminating quantitative and qualitative defects in providing care for people with endocrine diseases, as well as analyzing staffing needs and planning based on the real needs of the population, will help to achieve the solution to the set tasks of the healthcare system.

A registry for patients with chronic hypoparathyroidism in Russian adults.

Hypoparathyroidism and pseudohypoparathyroidism are rare endocrine disorders, characterized by low serum calcium due to inappropriate parathyroid hormone (PTH) levels or resistance to its action. There is little epidemiological information regarding chronic hypoparathyroidism in Russia. This study aims to build a registry database of Russian patients with chronic hypoparathyroidism who were referred for hospital treatment in order to conduct initial analysis of clinical presentations and hospital management. The Italian registry model was taken to be able to integrate our data in the future. Two hundred patients with hypoparathyroidism (n = 194) and pseudohypoparathyroidism (n = 6) were enrolled over 2 years (2017-2019). The most frequent cause of hypoparathyroidism was neck surgery (82.5%, mostly females), followed by idiopathic hypoparathyroidism (10%), syndromic forms of genetic hypoparathyroidism (4.5%) and forms of defective PTH action (3%). Calcium supplements and alfacalcidol were prescribed in most cases. However, a minority of patients (n = 6) needed to receive teriparatide as the only way to maintain calcium levels and to prevent symptoms of hypocalcemia. Consequently, substitution treatment with parathyroid hormone should be available in certain cases of hypoparathyroidism. This database will be useful to estimate the potential requirement for recombinant PTH in Russia and standards for clinical and therapeutic approaches.

Primary hyperparathyroidism in young patients in Russia: high frequency of hyperparathyroidism-jaw tumor syndrome.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial. OBJECTIVE: To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age. DESIGN: We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had MEN1 mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome. METHODS: The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). In cases suspicious for gross CDC73 deletions multiplex ligation-dependent probe amplification was performed. RESULTS: NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in CDC73 c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in CASR c.3145G>T (p.Glu1049*) and one in MEN1 c.784-9G>A. In two patients, MLPA confirmed gross CDC73 deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom CDC73 mutations were found in 5/8. CONCLUSIONS: Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with CDC73 mutations.

Diagnosis and treatment challenges of parathyroid carcinoma in a 27-year-old woman with multiple lung metastases.

SUMMARY: Parathyroid carcinoma is an extremely rare disorder with little treatment options. It could be misdiagnosed in medical centers with little experience in management of such cases. Our clinical case shows that the initial misdiagnosis of a parathyroid carcinoma in a young woman has led to the development of multiple lung metastases, thus making its treatment hardly possible. Initiation of treatment with sorafenib - a multi-kinase inhibitor approved for treatment of different types of cancer but not parathyroid carcinoma - has led to a significant decrease in the size of lung metastases and has prevented the progression of hyperparathyroidism, which is usually severe in cases of parathyroid carcinoma. The detection of a germline CDC73 mutation in this patient has raised additional concerns about the necessity of periodic screening for early detection of renal, jaw and uterine lesions. LEARNING POINTS: Diagnosis of parathyroid carcinoma may be challenging due to the absence of reliable diagnostic criteria. Thus, thorough histological examination is needed using immunohistochemical staining of resected tissue in suspicious cases. CDC73 genetic testing should be considered in patients with parathyroid carcinoma.Sorafenib may be a promising treatment of patients with parathyroid carcinoma with distant metastases.