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Parathyroid hormone (PTH) is a key regulator of bone turnover. Depending on the duration of action, the hormone causes catabolic and anabolic effects by binding with specific receptors (PTHR1) in the bone. Various cells expressing PTHR1 on their surface are involved in the process – osteoblasts, osteocytes, bone marrow stromal cells, T-lymphocytes and macrophages. In physiological conditions PTH balances the bone metabolism. Intermittent pharmacological doses of PTH lead to the prevalence of bone formation and are used in the treatment of osteoporosis. Persistently elevated levels of PTH stimulate bone resorption by impacting mainly the cortical bone. New imaging and analysis techniques show that high PTH levels can also have an adverse effect on trabecular microarchitecture. Primary hyperparathyroidism (PHPT) is a disease characterized by increased bone metabolism, decreased bone mineral density (BMD), inadequate osteoid mineralization and an increased risk of fractures. Prolonged overproduction of PTH leads to stimulation of bone resorption and defects in bone formation, mainly causing loss of cortical bone mass, while in the trabecular bone predominate demineralization processes. One explanation of these findings is the enhanced stimulation of RANKL expression by osteoblasts with decreased OPG expression and bone formation at the same time.

BACKGROUND Thyroid nodules are common ultrasound findings with malignancy rate 7%-15%. Our objective was to assess the relative expression of the tissue inhibitor of metalloproteinase-1 gene (TIMP1) and chitinase-3-like protein 1 gene (CHI3L1) in fine-needle aspiration biopsy (FNAB) washouts and the serum levels of their protein products (TIMP-1 and chitinase-3-like protein 1 known as YKL-40) in patients with papillary thyroid cancer (PTC) and patients with benign nodules. Furthermore, the correlation between gene expression and circulating protein product was evaluated. METHODS Eighty patients who underwent FNAB in one tertiary center were recruited in the study. Forty with Bethesda V and VI nodules were operated and PTC was confirmed. The other 40 patients were with Bethesda II nodules. TIMP-1 and YKL-40 serum levels were measured in all subjects. The TIMP1 and CHI3L1 expression was assessed in FNAB washouts from 20 PTC patients and 20 benign cases using quantitative PCR. RESULTS The relative expression of TIMP1 and CHI3L1 was significantly higher in the PTC group than in the benign group (p

Purpose: Some interleukins (ILs) play an important role in Graves’ orbitopathy (GO) pathogenesis. We aimed to compare serum IL-6, IL-8 and IL-10 in GO patients, patients with Graves’ disease (GD) w...

Background: Several thyroid societies have endorsed ultrasound (US) malignancy risk stratification systems for thyroid nodules and the recently released European Thyroid Imaging Reporting and Data System (EU-TIRADS) needs large prospective studies for validation. Objective: The purpose of our study was to evaluate the performance of EU-TIRADS in identifying thyroid nodules for fine-needle aspiration biopsy (FNAB) and its ability to reduce the number of unnecessary biopsies. Methods: This was a single-center prospective study. From August 2017 to September 2018, 783 consecutive patients with 1,000 thyroid nodules underwent US examination and US-guided FNAB. A total of 741 patients (median age 50 years; range, 15–87 years; 649 females, 92 males) with 942 nodules (median largest diameter 14 mm; range, 4–96 mm) met the following inclusion criteria: (1) nodules with benign or malignant cytology – categories II and VI of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC); (2) nodules with non-diagnostic and indeterminate cytology (BSRTC I, BSRTC III, and BSRTC IV), or suspicious for malignancy (BSRTC V), if postoperative histology was present; (3) nodules classified as BSRTC I and BSRTC III with a repeat FNAB and conclusive cytology. Results: Of 942 nodules, 839 (89.1%) were benign and 103 (10.9%) were malignant. Nodules were classified as follows: EU-TIRADS 2 – 4.8%, EU-TIRADS 3 – 37.4%, EU-TIRADS 4 – 25.2%, and EU-TIRADS 5 – 32.6%. The malignancy rate in categories 2 to 5 was 0, 0, 3.8, and 30.6%, respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EU-TIRADS with a cut-off set at category 5 were 91.3, 74.6, 30.6, 98.6, and 76.4%, respectively. Diagnostic performance other than sensitivity and NPV was superior in nodules ≥10 mm. FNAB number would be reduced by 53.4% if FNAB criteria were strictly applied. When the indication for FNAB was applied as test positivity, the estimated sensitivity, specificity, PPV, and NPV of EU-TIRADS were 69.9, 56.3, 16.4, and 93.8%, respectively. Conclusion: EU-TIRADS provides effective malignancy risk stratification that can guide the selection of thyroid nodules for biopsy. The application of the guidelines criteria for FNAB in the clinical practice might reduce significantly the number of unnecessary FNAB.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors associated with high cardiovascular morbidity and mortality. The MetS and its elements have been linked to anxiety and depressive disorders. The aim of the current cross-sectional study was to assess the prevalence of depression and anxiety, measured by the Zung Self-Rating Scale in subjects with and without the metabolic syndrome and diabetes.A total of 2111 adults were included, 1155 female, age 47.6 (13.7) and 956 male, age 45.2 (13.5). All participants filled questionnaires covering current and past disorders and medication, smoking and family history. Zung self-rating depression and anxiety scales were completed. Body weight, height and waist circumference were measured, BMI was calculated, serum glucose and lipids were measured.Depression (SDSi) and anxiety scores (SASi) were higher in the females and increased with age (p 0.001). SDSi was higher in the females and males with metabolic syndrome (MetS) (50.9 ± 9.8 vs. 45.9 ± 8.9, p 0.001 and 42.7 ± 9.2 vs. 40.5 ± 7.9 p 0.001, respectively). SASi was higher in the MetS subjects (females 50.59 ± 11.35 vs. 45.97 ± 10.58, p 0.001; males 40.48 ± 10.1 vs. 38.04 ± 8.42, p 0.001). Both SDSi and SASi were higher in the subjects with known diabetes than in those with normal glucose tolerance (Mann-Whitney both p 0,001). Positive depressive scores were more prevalent in subjects with MetS than those without (females 54% vs. 31.6%, p 0.001; males 22.7% vs. 12.3%, p 0.001). Depression and anxiety were more prevalent in the subjects with known diabetes than in those with normal glucose tolerance but not in the newly-diagnosed diabetes. The OR for depressiveness was 2.0 (1.3; 2.6) in subjects with MetS and 4.2 (2.3; 7.8) in those with known diabetes.In conclusion, depressiveness and anxiety were associated positively with age and female gender and were more prevalent among subjects with MetS and known diabetes mellitus.

Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Aim The aim of this study was to compare two nationwide cross-sectional studies of diabetes prevalence in Bulgaria (2006 and 2012) and to assess its dynamics. Material and Methods The two studies included 2396 and 2033 subjects, respectively. The International Diabetes Federation (IDF) diagnostic criteria were applied, and the data were weighed for type of settlement and age. Results Diabetes prevalence was found to be 7.9% in 2006 and 9.55% in 2012, P = 0.06, showing an increase of 20.9%. The absolute increase was 0.9% in the females and 2.3% in the males ( P < 0.09). The increase was the largest in those aged 50–59: [9.4%, 2006 vs. 15.7%, 2012, P < 0.01]. Diabetes prevalence increased in the 20–60-year olds by 6.8% and decreased in the elderly by 6.1%. Obesity increased from 26.7 to 32.7%, P < 0.02. Conclusions A significant increase in diabetes prevalence was found that necessitates healthcare measures and resources for community-based awareness and prevention programs.

To investigate the long-term efficacy and safety of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) treatment in patients with primary hyperparathyroidism (PHPT). In our prospective study, 13 of 72 screened patients with PHPT were eligible for HIFU treatment, which was performed in one or two sessions. Parathyroid adenoma size and function were evaluated at baseline, 1, 3, 6, 9, and 12 months after the final HIFU session. In 11 females and 2 males, mean age 55.2 ± 12.41 years, the mean applied energy was 15.2 ± 7.7 kJ. Parathyroid size and parathyroid hormone decreased significantly one month after HIFU therapy (p

The aim of this study was to determine the prevalence of thyroid dysfunction and its association with cardiovascular risk factors in an adult Bulgarian population. 2402 subjects were studied, 1347 female, 20–94y (median: 48.0y) and 1055 male, 20–91y (median: 45.5y). Body weight, height, waist circumference, arterial blood pressure, TSH, FT4 and lipids were measured. Known hypothyroidism was reported by 53 subjects (2.2%) and hyperthyroidism by 20 (0.8%). New hypothyroidism was found in 98 (4.1%), [subclinical (3.2%), overt (0.9%)]. New hyperthyroidism was found in 68 (2.9%), [subclinical (2.5%), overt (0.4%)]. New diagnosis of hypothyroidism and hyperthyroidism was entered in 84% and 87% in male subjects and 60% and 65% in the females respectively. Arterial hypertension was present in 40% of the women and in 47% of the men (p

To assess the short-term efficacy and safety of ultrasonographically (US)-guided high-intensity focused ultrasound (HIFU) ablation for treatment of benign solid thyroid nodules.This prospective study was approved by the institutional ethics committee, and written informed consent was acquired. HIFU ablation was performed in one session with US guidance and conscious sedation in 20 euthyroid patients (mean age, 44.5 years) with a benign solitary or dominant thyroid nodule. Thyroid nodule volume, US structure, and Doppler pattern were assessed at baseline, at 1 week, and at 1, 3, and 6 months after treatment. Adverse events associated with HIFU were evaluated. Statistical analysis was conducted by using repeated measures analysis of variance, the Student t test, χ(2) test, and correlation analysis.The mean ± standard deviation nodule volume was 4.96 mL ± 2.79 at the start of the study. Nodule volume had decreased to 3.05 mL ± 1.96 at the 3-month follow-up examination (n = 20, P.001), and reached 2.91 mL ± 2.43 by the 6-month follow-up examination (n = 16, P.001). By then, the mean volume reduction was 48.7% ± 24.3 (P.001). Isoechoic nodules showed greater reduction at 1 month than did hypoechoic nodules (31.6% ± 18.1 vs 16.4% ± 8.6, P = .053). Nodules with markedly increased blood flow showed smaller volume reduction at 3 months than did less-vascularized nodules (10.9% ± 14.5 vs 41.5% ± 20.3, P = .054). Minor transient complications (eg, subcutaneous edema, mild skin redness) were observed in two patients.Early data suggest that US-guided HIFU ablation is an effective and safe procedure for treatment of benign solid thyroid nodules. Initial US echogenicity and vascularization influence the ablation outcome.

Osteoprotegerin (OPG) and osteocalcin (OC) are essential bone proteins. Recent studies have demonstrated that they are not secreted solely by bone cells; they play roles in the vascular function and energy metabolism, and they are influenced by multiple factors. The aim of the current study was to investigate the influence of menopause and age on OPG and OC in women with different thyroid-stimulating hormone (TSH) levels. Material and Methods We studied 49 women with elevated TSH, 26 with suppressed TSH, and 67 age-matched euthyroid controls. Of them 64 were menstruating and 78 postmenopausal. Body weight, height, waist circumference (WC), body mass index (BMI), serum TSH, free thyroxin (FT4), OPG, and OC were measured. Results Generally, both OPG and OC were higher in the postmenopausal women than in the menstruating subjects (OPG 3.85 ± 1.49 pmol/L vs. 5.84 ± 2.42 pmol/L, P < 0.001; OC 8.84 ± 3.70 ng/dL vs. 12.87 ± 6.45 ng/dL, P < 0.001), and within the two thyroid dysfunction subgroups and the controls (all P < 0.05). OPG correlated with age (postmenopausal rho = 0.57, P < 0.001; premenopausal rho = 0.31, P = 0.015). Among the premenopausal subjects, OPG was higher in those with low TSH than in the controls ( P = 0.048). OC correlated negatively with BMI and WC in the postmenopausal group (Spearman rho = –-0.25, P = 0.03 and rho = –-0.42, P < 0.001 respectively). OC was higher in the postmenopausal subjects with low TSH than in those with elevated TSH ( P = 0.024), and correlated positively with FT4 (rho = 0.40, P = 0.002) and negatively with TSH (rho = -0.29, P = 0.013). CONCLUSIONS In women, OPG and OC depended differently on age and menopause and, to a lesser extent, on the thyroid function and body composition.

Background. The recently developed non-invasive high-intensity focussed ultrasound (HIFU) technique for the destruction of parathyroid adenomas could also be of interest for the treatment of secondary hyperparathyroidism (SHP) in patients with chronic kidney disease (CKD). We conducted a pilot study using this method. Methods. Five chronic haemodialysis patients with severe SHP underwent one to three HIFU treatments, respectively. They had at least one or two enlarged parathyroid glands, which were accessible to this technique. Results. In Patients 1-I and 5-V, serum intact parathyroid hormone (iPTH) could be successfully reduced in the long run. In Patient 3-N, serum iPTH decreased dramatically down to the normal range but increased again subsequently. In Patients 2-E and 4-D, transient reductions in serum iPTH were also obtained but HIFU failed to correct SHP during follow-up. Serum total calcium and phosphorus decreased in four among the five patients, either transiently or permanently. Serum total alkaline phosphatases were reduced in four of five patients. Side effects included local oedema, transient impairment of vocal cord mobility and bitonal voice. Conclusions. HIFU treatment may be of help in controlling SHP in selected patients with CKD. Further experience is clearly needed.

Many patients with primary hyperparathyroidism either decline or are not candidates for surgical parathyroidectomy. There are drawbacks to medical therapy as well as percutaneous ethanol injection as alternative therapies for primary hyperparathyroidism. Therefore, in this pilot study, our aim was to test the feasibility, safety, and efficacy of a newly developed noninvasive high-intensity focused ultrasound (HIFU) technique for the nonsurgical management of primary hyperparathyroidism.We treated four menopausal women with biochemical, sonographic, and cytologic evidence of benign primary hyperparathyroidism. HIFU treatment was performed in two sessions using TH-One under sonographic guidance and with the patient under conscious sedation. Parathyroid volume and function were evaluated at baseline and repeatedly until 12 months after the second HIFU session.Serum parathyroid hormone levels decreased in all four patients and normalized 1 and 8 months after the second HIFU session in two patients. Serum calcium levels decreased in all patients and normalized in three patients. Three of four parathyroid tumors had decreased in size by 11%, 43%, and 79%, respectively, 12 months after the second HIFU session. All adverse events related to HIFU were transient: mild subcutaneous edema in three patients and impaired vocal cord mobility in one patient that resolved 40 days later.HIFU is a promising procedure for patients with primary hyperparathyroidism that may become an alternative to established options, especially in elderly patients with comorbidities, or in patients who decline surgery. Large-scale long-term studies including patients with secondary and tertiary hyperparathyroidism are warranted.

OBJECTIVES: To observe changes in the parathyroid tissue treated by extracorporeal HIFU. MATERIAL AND METHODS: 5 patients were treated for primary hyperparathyroidism by thermally ablating enlarged parathyroid glands using an external HIFU applicator. The treated glands were visualized with B‐Mode and contrast enhanced ultrasonography (CEUS) before, 1 week and 4 weeks post HIFU. Serum iPTH, calcium, and phosphorus levels were monitored before and after the treatment. RESULTS: The initial results showed a correlation between contrast agent uptake of treated parathyroid tissue, the reduction of volume of the gland and the decrease of iPTH levels. CONCLUSIONS These results show it is possible to use CEUS to monitor the thermal ablation of parathyroid glands.

Objectie: The psychoemotional and sexual status of Bulgarian urban postmenopausal women 10 years after the beginning of the period of extensive political, social, economic and cultural transitions was studied. Subjects and Methods: Three hundred and thirty-two postmenopausal women (83.5% in natural menopause and 16.5% in surgical menopause) and 295 women with normal menstrual cycle in several Bulgarian cities and the capital were studied. A campaign for free-of-charge bone density measurement was announced and the examined subjects filled in an individual anonymous questionnaire. SPSS for Windows version 8.0 was used for the statistical processing of the results. The comparison was made between normally menstruating women (n= 295), postmenopausal women on hormone replacement therapy (HRT) (n=36) and postmenopausal subjects without HRT (n= 296). Results :A significant correlation was observed between depression and sexual aversion, depression and pain with intercourse, depression and the change in the sexual life after menopause. The correlation between self-esteem and sexual thoughts, self-esteem and sexual desire, self-esteem and the arousal from the partner, self-esteem and orgasm also proved important. About 20% of the studied subjects reported depressive thoughts, 50% reported anxiety and the self-esteem was very low in 13%. These results can be explained in part with the economic stagnation in the country, the unemployment and uncertainty. However, 94% of Bulgarian women believe that they do well in life and rely on their professionalism and social positions. All parameters of sexual life are significantly lower in the postmenopausal group without HRT as compared both with menstruating women and postmenopausal women on HRT. Marital status influences them too. Conclusion: The change in the sexuality is related to the decline in the estrogen activity, the influence of the psychosocial factors, the lack of a permanent intimate partner, and the derogatory attitude of the society towards the sexuality of postmenopausal women. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

Sexual dysfunction is frequently observed in postmenopausal women but there are few epidemiological studies of the relationship between the menopause and sexual functioning. An epidemiological study of sexual function was performed among 619 Bulgarian women aged between 40 and 58 years. Two hundred and eighty-five (46%) had a normal menstrual cycle (group A) and 334 (54%) were postmenopausal. Of these, 302 (group C) did not use hormone replacement therapy (HRT) and 32 were on HRT (group B). Many women feel uneasy and are unwilling to talk about their sexual problems even with medical professionals. This fact warranted the implementation of an anonymous questionnaire. There were significant differences in all sexual function parameters reported between groups C and A (p < 0.001), as well as between groups C and B (p < 0.05). These results suggest that HRT restores the dynamics of sexual life in postmenopausal women and brings them closer to those of normally menstruating middle-aged women.

To assess the long term efficacy and tolerability of one or two ultrasound (US)-guided high-intensity focused ultrasound (HIFU) treatment in patients with breast fibroadenoma (FA). Twenty patients with 26 FA were selected for US-guided HIFU. The therapy was performed in one or two sessions. FA volume was assessed before and followed up to 24 months after the last HIFU. After each treatment, adverse events were evaluated. In 19/26 FA (73.1%) one HIFU was performed (group 1), whereas 7/26 FA (26.9%) received second HIFU (group 2) 6-9 months (median, 7 months) after the first session. In group 1 and 2, FA volume decreased significantly at 1-month (p

Background The aim of our multicenter study was to assess the clinical outcome and safety of ultrasound (US)-guided high-intensity focused ultrasound (HIFU) in patients with breast fibroadenoma (FA). Methods From May 2011 to February 2013, 42 women with 51 FA in one or both breasts were selected for treatment with US-guided HIFU. Eight of 51 FA were treated twice. Patients’ age ranged from 16 to 52 years (mean 32 years). All patients with FA underwent core needle biopsy with histological confirmation. HIFU treatment was performed as an outpatient procedure under conscious sedation. Exclusion criteria were pregnant or lactating women, microcalcifications within the lesion at mammogram, history of breast cancer, previous laser or radiation therapy, and breast implant in the same breast. All patients signed written informed consent. After the treatment, follow-up US with volume evaluation was performed at 2, 6, and 12 months. Results The FA mean baseline volume was 3.89 ml (0.34–19.66 ml). At 2-month follow-up, the mean volume reduction was 33.2% ± 19.1% and achieved significance at 6-month (59.2% ± 18.2%, p