The Russian registry of primary hyperparathyroidism, latest update.

Introduction: Until 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 methods: The 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/). Results: The 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. Conclusion: The 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.

Mathematical model for preoperative differential diagnosis for the parathyroid neoplasms.

Background and objective: Preoperative diagnosis of parathyroid carcinoma (PC) is critical for the determination of the scope of surgical intervention. Nowadays, specific diagnostic markers for differentiation of PC and benign tumors are unknown, and less than half of patients with PC undergo necessary en bloc surgery. The aim of this study was to develop the instrument for preoperative diagnosis of PC. Methods: A multi-center retrospective study included 242 patients with primary hyperparathyroidism: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands. Results: Patients with PC and AA had higher levels of PTH, ionized and albumin-corrected calcium, ALP, volume and the largest diameter of neoplasm, and the higher frequency of GFR decrease less than 60 ml/min/1.73 m2 compared to patients with adenoma. The frequency of low-energy fractures was higher in the carcinoma group versus the adenoma group (32% vs 8%). Heterogeneous structure and indefinite contour of glands detected by US were more typical for PC than for AA and adenomas. The mathematical model was developed using CatBoost gradient boosting algorithm for the noninvasive preoperative differential diagnosis of PC, AA, and adenoma. Conclusions: Model can predict adenoma with PPV 100% and PC with PPV 81-92%. Using model clinicians could plan extended en bloc resection for PC and selective parathyroidectomy for adenoma. If AA is predicted, he has to make a decision on the choice of the necessary volume of PTE based on his experience, because AA are the zone of uncertainty.

The Russian Registry of Chronic Hypoparathyroidism.

INTRODUCTION: Chronic hypoparathyroidism is a relatively rare disease associated with multicomponent medical therapy and various complications. The analysis of large databases of patients with chronic hypoparathyroidism is a necessary tool to enhance quality of medical care, as well as to determine the optimal clinical and therapeutic approaches, and prognostic markers of the disease. THE AIM: of this study is to estimate the clinical and biochemical profile, long-term complications, medical therapy and disease control of the patients with chronic postsurgical and non-surgical hypoparathyroidism. MATERIALS AND METHODS: the cross-sectional, observational, continuous study was based on the Russian Registry of patients with hypoparathyroidism. 544 patients from 63 regions of the Russian Federation were included in this study. RESULTS: The majority of cases had postsurgical etiology (88.4%). Postsurgical hypoparathyroidism prevailed in females (р<0.001). About a half of patients had blood calcium and phosphorus targets, 56 and 52% respectively. Nephrolithiasis was confirmed in 32.5%, nephrocalcinosis - in 12.3% of cases. The risk of nephrocalcinosis/nephrolithiasis increased by 1.85 times with disease duration more than 4.5 years. The cataract was found in 9.4%. The cut-off point for the development of cataracts was 9.5 years, with a 6.96-fold increased risk. The longer duration of hypoparathyroidism of any etiology was associated with more frequent cataract (p=0.0018).We found brain calcification in 4%, arrhythmias in 7.2% and neuropsychiatric symptoms in 5.15% of cases. Generally, the BMD in the studied group corresponded to age values, and there was no evidence for the phenomenon of high bone density. TBS was consistent with normal bone microarchitectonics. In our study, the majority of patients (83.5%) was treated with standard therapy of calcium and vitamin D supplements. 5 patients with severe disease course were treated with rhPTH (1-34). CONCLUSIONS: Analysis of the presented database indicates insufficient diagnosis of the complications associated with chronic hypoparathyroidism. Overall, hypoparathyroidism is associated with higher risks of renal stone formation, decreased GFR, cataract especially in patients with longer duration of disease.

[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.

[Changes in the morphological structure of giant prolactinoma during treatment with cabergoline].

Currently, cabergoline therapy is the main method of treatment with prolactin. The use of the drug in most cases leads to tumor regression, normalization of prolactin levels and restoration of gonadotropic function. The mechanism of its impact on tumor cells in vivo, which is dynamically traced in the same human tumor, is the case of considerable interest. We observed a 30-year-old patient who was operated on twice for a giant prolactinoma before and on treatment by cabergoline. The morphological study after the first surgery (before introducing of cabergoline therapy) revealed a prolactin-positive pituitary tumor with a Ki-67 labeling index of 8% and with strong expression of dopamine type 2 receptors (D2R), CD31 and CD34. After 4 months, during which the patient received cabergoline at a dose starting from 0.5 mg to 1.5 mg per week, a second transsphenoidal surgery was performed with subtotal removal of residual tumor tissue. During the morphological study of the second biopsy sample, the tumor retained a pronounced immunopositivity to prolactin and D2R, with a decrease in the labeling index Ki-67 to 2%, as well as a decrease in the expression of CD31 and CD34. Subsequent cabergoline therapyresulted in persistent normoprolactinemia, restoration of androgen (and reproductive) status, and no tumor recurrence over a 10-year period on cabergoline treatment. Thus, one of the mechanisms of effect of cabergoline that leads to tumor regression is a decrease in the proliferative index and angiogenesis of the tumor.

[The role of non-coding RNAs in the pathogenesis of multiple endocrine neoplasia syndrome type 1].

Changes in the expression of non-coding ribonucleic acids (ncRNAs) take part in the formation of various tumors. Multiple endocrine neoplasia syndrome type 1 (MEN1) is a rare autosomal dominant disease caused by mutations of the MEN1 gene encoding the menin protein. This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors, pituitary adenomas, as well as other endocrine and non-endocrine tumors. The pathogenesis of MEN-1 associated tumors due to MEN1 mutations remains unclear. In the absence of mutations of the MEN1 gene in patients with phenotypically similar features, this condition is regarded as a phenocopy of this syndrome. The cause of the combination of several MEN-1-related tumors in these patients remains unknown. The possible cause is that changes in the expression of ncRNAs affect the regulation of signaling pathways in which menin participates and may contribute to the development of MEN-1-related tumors. The identification of even a small number of agents interacting with menin makes a significant contribution to the improvement of knowledge about its pathophysiological influence and ways of developing tumors within the MEN-1 syndrome and its phenocopies.

[Androgens and Antiandrogens influence on COVID-19 disease in men].

The WHO has declared a SARS-CoV-2 pandemic. During a pandemic, the researches aimed at finding the new treatments for SARS-CoV-2 become relevant. The review focuses on studies of androgens and antiandrogens in this disease. Since the beginning of the COVID-19 epidemic, it has been noted that men have more severe forms of infection and higher mortality. The main cause of both the severity of the disease and the high mortality of men from COVID-19 are associated with androgens. It was found that patients receiving androgen deprivation are less likely to become infected and easily tolerate COVID-19. The researchers explain the effect of the therapy by the effect on the TMPRSS2 protein. It was found that both TMPRSS2 expression and a more severe course of coronavirus infection are observed in men with hyperandrogenism - androgenic alopecia, acne, excessive facial hair growth and increased skin oiliness. In this regard, some researchers suggest to use androgen deprivation for men at high risk of developing COVID-19. Steroid and non-steroidal antiandrogens are used for androgen deprivation. At the same time, obtaned scientific data on the relationship of severe forms and mortality of COVID-19 with low testosterone levels leads to a hypothesis about the possibility of a positive effect not of androgen devrivation therapy but of androgen replacement therapy in case of hypogonadism have diagnosed. These studies have not been completed recently, and data on the effectiveness and safety of antiandrogens and androgens in the treatment of a new coronavirus infection require clarification.

Bone Health TeleECHO: a Force Multiplier to Improve the Care of Skeletal Diseases in Underserved Communities.

PURPOSE OF REVIEW: This review describes the global development of a model of technology-enabled collaborative learning for healthcare professionals called Project ECHO (Extension for Community Healthcare Outcomes) and its applications for the management of patients with skeletal diseases. RECENT FINDINGS: The prototype Bone Health TeleECHO was established in 2015, with others now operational in the USA and other countries, and more expected to follow soon. Each teleECHO program, in the right language and convenient time zone, provides a virtual community of practice for healthcare professionals to benefit from real-time interactive case-based learning and brief didactic presentations on topics of interest. Bone Health TeleECHO elevates the level of knowledge of participants and improves self-confidence in managing patients with skeletal diseases. The development of many teleECHO programs worldwide serves as a force multiplier, with the potential to narrow the osteoporosis treatment gap and enhance the effectiveness of fracture liaison services.

Prediction of recurrence and remission within 3 years in patients with Cushing disease after successful transnasal adenomectomy.

BACKGROUND: Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. AIM: To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. METHODS: Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). RESULTS: Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. CONCLUSION: Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.

Diagnostic performance of osteocalcin measurements in patients with endogenous Cushing's syndrome.

The aim of this study was to evaluate the diagnostic performance of osteocalcin (OC), as measured by automated electrochemiluminescence immunoassay (ECLIA), in identifying Cushing's syndrome (CS) in two separate populations: among obese and overweight subjects and among women of postmenopausal age with osteoporosis. Among the 106 referral patients with obesity, CS was confirmed in 42 cases. The patients of the referred population provided late-night salivary cortisol (LNSC), underwent low-dose dexamethasone suppression testing (DST) and were further evaluated until CS was pathologically confirmed. A threshold of OC-8.3 ng ml(-1) differentiated CS among obese and overweight subjects with a sensitivity of 73.8% (95% confidence interval (CI) 58.9-84.7) and a specificity of 96.9% (95% CI 89.3-99.1). The total area under the receiver operating characteristic curve (AUC) was 0.859 (95% CI 0.773-0.945), which was lower than LNSC or DST (P=0.01). In the retrospective portion of the study, the OC levels were evaluated in 67 subjects with newly diagnosed postmenopausal osteoporosis and in 23 patients (older than 45) with newly diagnosed CS and osteoporosis (presence of low traumatic fractures or T-score P-2.5). The diagnostic performance of OC for osteoporosis due to CS was within an AUC of 0.959 (95% CI 0.887-1.00). A threshold for OC of 8.3 ng ml-1 yielded a sensitivity of 95.4% (95% CI 78.2-99.2%) and a specificity of 98.5% (95% CI 92.0-99.7%). Thus, osteocalcin could be used in the diagnostic testing for endogenous hypercortisolism in patients referred to exclude CS and to identify CS among patients of postmenopausal age with osteoporosis.

The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing's syndrome.

UNLABELLED: In a cohort study of 182 consecutive patients with active endogenous Cushing's syndrome, the only predictor of fracture occurrence after adjustment for age, gender bone mineral density (BMD) and trabecular bone score (TBS) was 24-h urinary free cortisol (24hUFC) levels with a threshold of 1472 nmol/24 h (odds ratio, 3.00 (95% confidence interval (CI), 1.52-5.92); p = 0.002). INTRODUCTION: The aim was to estimate the risk factors for fracture in subjects with endogenous Cushing's syndrome (CS) and to evaluate the value of the TBS in these patients. METHODS: All enrolled patients with CS (n = 182) were interviewed in relation to low-traumatic fractures and underwent lateral X-ray imaging from T4 to L5. BMD measurements were performed using a DXA Prodigy device (GEHC Lunar, Madison, Wisconsin, USA). The TBS was derived retrospectively from existing BMD scans, blinded to clinical outcome, using TBS iNsight software v2.1 (Medimaps, Merignac, France). Urinary free cortisol (24hUFC) was measured by immunochemiluminescence assay (reference range, 60-413 nmol/24 h). RESULTS: Among enrolled patients with CS (149 females; 33 males; mean age, 37.8 years (95% confidence interval, 34.2-39.1); 24hUFC, 2370 nmol/24 h (2087-2632), fractures were confirmed in 81 (44.5%) patients, with 70 suffering from vertebral fractures, which were multiple in 53 cases; 24 patients reported non-vertebral fractures. The mean spine TBS was 1.207 (1.187-1.228), and TBS Z-score was -1.86 (-2.07 to -1.65); area under the curve (AUC) was used to predict fracture (mean spine TBS) = 0.548 (95% CI, 0.454-0.641)). In the final regression model, the only predictor of fracture occurrence was 24hUFC levels (p = 0.001), with an increase of 1.041 (95% CI, 1.019-1.063), calculated for every 100 nmol/24-h cortisol elevation (AUC (24hUFC) = 0.705 (95% CI, 0.629-0.782)). CONCLUSIONS: Young patients with CS have a low TBS. However, the only predictor of low traumatic fracture is the severity of the disease itself, indicated by high 24hUFC levels.

Clinical significance of TSH circadian variability in patients with hypothyroidism.

OBJECTIVE: To investigate the clinical significance of thyroid-stimulating hormone (TSH) circadian variability in patients with hypothyroidism. DESIGN: A total of 20 women with subclinical hypothyroidism and 22 patients taking L-thyroxine replacement therapy for hypothyroidism were enrolled in the study. Measurements of serum TSH levels were done twice a day from 08.00 to 09.00 a.m. and from 2.00 to 4.00 p.m. RESULTS: The morning median TSH value in the patients with subclinical hypothyroidism was 5.83 mU/L; in the afternoon, it was 3.79 mU/L. The range of TSH circadian variability reached the level of 73%. According to the current TSH reference interval, hypothyroidism was not diagnosed in about 50% of the cases in the afternoon. The morning median TSH value in the patients taking l-thyroxine was 3.27 mU/L; it decreased to the value of 2.18 mU/L in the afternoon. The range of TSH circadian variability reached the level of 64.7%. Further analysis demonstrated inadequate compensation of hypothyroidism, which was defined in 45.5% of the morning samples and in 9% of the afternoon samples (p < 0.05). CONCLUSION: The time of blood sampling has an important role in the interpretation of TSH levels. Moreover, the high TSH circadian variability should be considered in discussions about the narrowing of its reference range.

Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing's syndrome.

This study estimates diagnostic performance of late-night salivary cortisol (LNSC) as measured by automated electrochemiluminescence immunoassay (ECLIA), evaluates the clinical implication of two consecutive LNSC measurements, and compares its accuracy with enzyme-linked immunosorbent assay (ELISA) and serum cortisol after low-dose dexamethasone suppression test (DST) in obese and overweight patients referred for suspected Cushing's syndrome (CS). One hundred twenty three consecutive obese and overweight referred patients and 98 healthy volunteers provided two saliva samples collected at 23:00 using a Salivette (Sarstedt, Germany), assayed by ECLIA (Cobas e601) and ELISA. The patients underwent DST and were further evaluated until CS was pathologically confirmed (n = 45) or excluded. Diagnostic performance of LNSC was evaluated by receiver operating characteristic (ROC) analysis. The total areas under the curve (AUC) were calculated to compare the different tests. We found that a cut-off value of 9.4 nmol/l can differentiate CS among obese and overweight patients with sensitivity of 84.4 % (95% CI 71.2-92.2), specificity of 92.3 % (95% CI 84.2-96.4), and diagnostic odds ratio of 65.1 (95% CI 20.4-207.6). No difference was found between AUCs from the first, second, and the mean from the two LNSC measurements (ECLIA), LNSC (ELISA), or DST. The single LNSC (ECLIA) and DST improved the sensitivity and specificity for concordant results up to 100 and 97.4 %, respectively. In conclusion, due to its automation and its comparable diagnostic performance, ECLIA is preferable as a first-line LNSC screening test for CS. The initial use of single LNSC followed by DST provides better diagnostic performance for concordant results.

Combined therapy with L-thyroxine and L-triiodothyronine compared to L-thyroxine alone in the treatment of primary hypothyroidism.

OBJECTIVE: The objective of this study was to compare various parameters in patients with hypothyroidism receiving either monotherapy with L-thyroxine (L-T4) or combination therapy with L-T4 and L-triiodothyronine (L-T3). DESIGN: We conducted a randomized, controlled trial in 36 premenopausal women with hypothyroidism. The patients were divided into two groups: Group A (n=20) received only L-T4, while Group B received the combination L-T4 and L-T3. The treatment period lasted for 6 months. RESULTS: At baseline, the various parameters examined did not differ in the two groups. No significant difference between monotherapy and combined therapy was demonstrated on TSH level, ECG monitoring, densitometry, or thyroid symptoms score. The lipid profile was better during combined treatment compared to L-T4 alone; in Group A during treatment with L-T4 the levels of cholesterol and low density lipoprotein (LDL) cholesterol were unchanged, while in group B total cholesterol and LDL decreased (p<0.05). The changes in osteocalcin levels did not differ in the two groups, whereas the levels of urine deoxypyridinoline at the end of therapy were higher in the group with combination therapy, compared to monotherapy. CONCLUSION: Compared with L-T4 alone, replacement therapy with the combination of L-T4+L-T3 shows favourable changes in serum lipid profile, but higher activation of bone resorption.

Effect on carbohydrate metabolism and analysis of acceptability (menstrual cycle control) of extended regimens of the vaginally inserted hormone-releasing system 'NuvaRing' as compared with the standard 21/7 regime in reproductive-age women with type 1 diabetes mellitus.

AIM: To evaluate the effect of the vaginally inserted hormone-releasing system 'NuvaRing' on carbohydrate metabolism and acceptability (menstrual cycle control) of extended regimens of using as compared with the standard regimen (21/7) in women with type 1 diabetes mellitus (DM) in reproductive period during 24 months. METHODS: The open randomised study included a total of 109 women with type 1 DM, using 'NuvaRing' in different regimens (21/7, 42/7, 84/7 and 357/7). Average daily insulin requirements, the levels of glycosylated haemoglobin were determined at baseline, after 6, 12, 18 and 24 months of contraception. The control group was composed of 22 age-matched women with type 1 DM using no methods of contraception. RESULTS: Using the contraceptive system 'NuvaRing' in type 1 DM women in the reproductive period has proved to exert no clinically significant effect on carbohydrate metabolism in prolonged regimens, as well as in standard regimen. The overall number of bleeding days and spotting days was comparable in different groups. Longer regimens with fewer breaks were associated with fewer days of bleeding but a larger number of spotting days as compared with the shorter regimens, with a tendency towards a gradual decrease in spotting days during a year. CONCLUSION: The releasing system 'NuvaRing' proved to be a reliable and safe means of contraception for late reproductive age women with type 1 DM.

Use of the NuvaRing hormone-releasing system in late reproductive-age women with type 1 diabetes mellitus.

AIM: To evaluate the effect of the vaginally inserted hormone-releasing system NuvaRing on carbohydrate and lipid metabolism and the hemostasis system, over 6 months of use, in late reproductive-age women with type 1 diabetes mellitus (DM). METHODS: The open randomized study included a total of 25 women with type 1 DM using NuvaRing. Average daily insulin requirements, levels of glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3 and 6 months of contraception. The control group was composed of 20 age-matched women with type 1 DM using no methods of contraception, as well as 20 apparently healthy women using the NuvaRing device. RESULTS: Use of the NuvaRing contraceptive system in type 1 DM women in the late reproductive period was shown to exert no clinically significant effect on carbohydrate and lipid metabolism on the background of persistent and satisfactory compensation of carbohydrate metabolism (HbA1c < or = 7.5%), with a neutral impact on the hemostasis system. CONCLUSION: The NuvaRing hormone-releasing system proved to be a reliable and safe means of contraception for late reproductive-age women with type 1 DM.

Subclinical hyperthyroidism of variable etiology and its influence on bone in postmenopausal women.

OBJECTIVE: To evaluate the effects of subclinical hyperthyroidism of variable etiology on bone mineral density (BMD) and bone metabolism in postmenopausal women. DESIGN: T he study included data of 88 postmenopausal women classified into four groups depending on the etiology of subclinical hyperthyroidism: (1) 20 with toxic multinodular goiter without history of clinical hyperthyroidism; (2) 25 on levothyroxine suppressive therapy after thyroidectomy due to differentiated thyroid cancer; (3) 21 with Graves' disease (GD) receiving antithyroid drugs; (4) 22 healthy women matched for age and duration of menopause. In all subjects biochemical markers of bone turnover and B MD were determined. RESULTS: Biochemical markers of bone turnover were significantly higher (p-value =0.001) in all patients with subclinical hyperthyroidism compared to the control group (group 4). T he women of group 1 had significantly lower B MD at all regions of the skeleton, whereas the women of group 3 had significantly lower B MD at Total Hip (p-value = 0.013) and Radius Total (p-value = 0.0003) compared to group 4. No significant differences in B MD between groups 2 and 4 were detected. CONCLUSION: The etiology of subclinical hyperthyroidism influences B MD in postmenopausal women. Endogenous subclinical hyperthyroidism might be considered as an additional risk factor for osteoporosis in postmenopausal women, especially for cortical bone, whereas exogenous subclinical hyperthyroidism has no effect on BMD.

Contraception in perimenopausal women with diabetes mellitus.

AIM: To assess the effect of combined oral contraceptives (COCs) and intrauterine devices (IUDs) on carbohydrate and lipid metabolism and hemostasis in perimenopausal diabetic women. METHODS: The open randomized study included a total of 113 diabetic women using COCs with different estrogen/progestogen profiles - ethinylestradiol (EE) 20 microg/desogestrel 150 microg, EE 30 microg/desogestrel 150 microg and EE 30 microg/gestodene 75 microg - and levonorgestrel-releasing or copper IUDs. Average daily insulin requirements, levels of glycosylated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, the state of coagulation hemostatis and fibrinolytic activity were determined at baseline and after 3, 6, 9 and 12 months of contraception. The control group was composed of 40 age-matched diabetic women who did not use any methods of contraception. RESULTS: Neither COCs nor IUDs influenced glycosylated hemoglobin and had little or no influence on the elevation in the requirements for insulin preparations. The majority of the preparations did not exert any unfavorable effect on the blood lipid profile. Taking COCs was accompanied by increased intravascular activation of blood platelets and to a lesser degree by alterations in parameters of hemostatic homeostasis. The use of IUDs had a neutral effect on blood coagulation and fibrinolysis systems. CONCLUSION: Comparing lipid levels and hemostatic variables as a function of glycosylated hemoglobin level, we conclude that diabetes control has greater influence on these parameters than the type and dose of steroids involved in the contraceptive devices.