ContextHuman zonulin is a protein that regulates the intercellular tight junctions in various tis... more ContextHuman zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto’s thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied.Objective and designThis pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto’s thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics.Subjects and methodsA group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method.ResultsAge, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively).ConclusionsThere is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant.
Introduction: Thyroid dysfunction is often associated with disturbances in calcium-phosphorus met... more Introduction: Thyroid dysfunction is often associated with disturbances in calcium-phosphorus metabolism, but studies on the subject provide conflicting results. Aim: To study the parameters of calcium-phosphorus metabolism in women with newly diagnosed thyroid dysfunction, not receiving specific treatment, and to compare them with those of the control group healthy women. Patients and methods: The study included 119 women with newly diagnosed thyroid dysfunction- 51 with onset of Graves' disease and 68 with autoimmune thyroiditis. A comparison was made with the data of 75 age- matched euthyroid women. FT3, FT4, TSH, total and ionized serum calcium, inorganic phosphate, parathyroid hormone (PTH) were studied. Results: The results of the analysis showed statistically significant higher concentrations of total and ionized calcium in hyperthyroid women compared to the control group. However, no significant differences in parathyroid hormone values were found between the two groups....
UNLABELLED The purpose of this study was to analyze the relationship of the main hormonal and met... more UNLABELLED The purpose of this study was to analyze the relationship of the main hormonal and metabolic abnormalities in PCOS with different levels of TSH in the limits of its reference values. MATERIAL AND METHODS The study involved 70 women with PCOS aged 16 to 39 years and BMI between 18.3 and 39.5 kg/m2 and a control group of 22 clinically healthy women, corresponding to age and BMI. In all of the participating women fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, insulin, TSH, FT4, TPO-Ab and Tg-Ab, LH, FSH, estradiol, Androstenedione, testosterone, SHBG, DHEA-S, prolactin, 17-hydroxyprogesterone were assessed. BMI, LDL-cholesterol, LH/FSH ratio, FAI and HOMA-index were calculated. RESULTS In patients with PCOS, TSH levels > 2.0 mlU/L are associated with significantly higher levels of total and LDL-cholesterol. However, we did not find a direct dependency of TSH indicators of insulin resistance neither across the group of women with PCOS, nor with ...
vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary e... more vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours
OBJECTIVE The aim of the study was to establish whether a combi - nation of low dose estradiol va... more OBJECTIVE The aim of the study was to establish whether a combi - nation of low dose estradiol valerate (EV) and estriol (E3) is able to alleviate climacteric symptoms and preserve bone in early postmeno- pausal women. METHOD A one-year prospective non-randomized study was conducted of two groups of women: control group (n=31) and hormone replacement therapy (HRT) group (n=35), treated with 1 mg EV and 2 mg E3, combined with sequential levonorgestrel 0.25 mg. The criteria for inclusion were: 9-18 months after last menstru- al bleeding, FSH>25 IU/L, moderate climacteric symptoms, bone min- eral density (BMD) of less than 2.5 SD below peak adult bone mass. None of the women had any pre-existing medical condition which could affect bone metabolism. BMD was estimated by single-energy X-ray absorptiometry on the distal and ultradistal areas of the fore- arm at the start of the study and after 1 year. The Kupperman menopausal index (KI), Hamilton anxiety scale (HAMA), and adverse effec...
Experimental and Clinical Endocrinology & Diabetes, 2015
We described biochemical outcome in regards to different treatment modalities in patients with ac... more We described biochemical outcome in regards to different treatment modalities in patients with acromegaly in Bulgaria. It was a retrospective analysis using data from the Bulgarian Acromegaly Database. Patients with eligible data on at least one treatment modality were included in the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF-1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51) years after diagnosis. We identified 534 patients with interpretable data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with disease control achieved in 18.8% and 31.4% respectively. Patients without prior radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of response to dopamine agonist (DA) therapy were disease activity, radiotherapy and medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical control in 38.6% of 70 patients. Combination of SSA and cabergoline led to remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone or in combination resulted in remission in 61.5% of 13 patients. Approximately one third of the patients were cured median 10 years after irradiation. Overall disease control was observed in 51.4% of our patients increasing to 70.3% in the last 5 years of the study period. DAs are efficient in less than 20% of non-irradiated patients. They are a good cost-effective alternative for carefully selected patients.
Methods and Findings in Experimental and Clinical Pharmacology, 2008
In the present study, we assessed the levels of fasting homocysteine in patients with active Cush... more In the present study, we assessed the levels of fasting homocysteine in patients with active Cushing's syndrome using two different assay methods. To determine a possible link between homocysteine and renin-angiotensin-aldosterone system (RAAS), nine patients with Cushing's syndrome and nine patients with metabolic syndrome were given a 1-month treatment with angiotensin II (AII) receptor blocker valsartan. Plasma homocysteine, active renin and aldosterone did not differ significantly among patients with Cushing's syndrome, patients with metabolic syndrome and controls. As expected, active renin increased significantly during valsartan treatment in patients with Cushing's syndrome as well as in patients with metabolic syndrome. Plasma homocysteine did not change after valsartan treatment, suggesting a lack of direct relationship between homocysteine and RAAS. Our data suggest that homocysteine might not serve as a reliable marker of endogenous hypercortisolism or of cardiovascular risk associated with Cushing's syndrome and metabolic syndrome.
Methods and Findings in Experimental and Clinical Pharmacology, 2001
The aim of this study was to investigate the effect of short-term treatment with losartan, a sele... more The aim of this study was to investigate the effect of short-term treatment with losartan, a selective and competitive angiotensin II (AngII) receptor blocker, on vascular endothelial growth factor (VEGF), active renin and kallikrein activity (KA) in patients with essential hypertension and primary aldosteronism. Nine patients with primary aldosteronism (5 with Conn adenoma and 4 with idiopathic hyperaldosteronism) and 9 patients with essential hypertension were included in the study. Systolic and diastolic blood pressure decreased significantly after losartan treatment in both patient groups. Plasma and urinary Kallikrein activity were significantly higher in primary aldosteronism in comparison with essential hypertension. There were no significant changes in the active renin and aldosterone in patients with primary aldosteronism after treatment. Plasma and urinary KA decreased significantly after losartan administration in both groups. Serum VEGF levels in primary aldosteronism were not significantly different from those in essential hypertension and did not change significantly after treatment in either group. In conclusion, losartan, in usual therapeutic doses, lowers blood pressure in patients with primary aldosteronism and essential hypertension. This marked antihypertensive effect in primary aldosteronism could be explained predominantly by blockade of tissue renin-angiotensin system (RAS). The variations in KA could be due to hemodynamic changes. VEGF is not likely to be involved in the action of losartan.
Methods and Findings in Experimental and Clinical Pharmacology, 1998
Eleven patients with Cushing's syndrome were included in the study. They maintained their... more Eleven patients with Cushing's syndrome were included in the study. They maintained their usual sodium intake and received a single oral dose of 50 mg of the angiotensin II antagonist receptor losartan for 3 days. Losartan treatment resulted in stimulation of active renin and decrease of plasma and urinary kallikrein activity. Both systolic and diastolic blood pressure decreased independently of baseline level of active renin. The relationship between kallikrein and renin-angiotensin system are discussed.
There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arteria... more There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the present study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E2 (PGE2) in patients with endocrine hypertension. The study comprised: 30 patients with primary aldosteronism; 32 patients with active Cushing's syndrome; 19 patients with pheochromocytoma; 22 patients with essential hypertension and 24 healthy volunteers. VEGF was significantly elevated in all groups of patients as compared to the controls. VEGF levels in patients with Cushing's syndrome were significantly higher than those in patients with essential hypertension and primary aldosteronism. We did not find significant differences in VEGF levels between patients with Conn adenomas and idiopathic aldosteronism as well as between patients with Cushing's disease and Cushing's syndrome. PGE2 levels were not significantly different among the groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in those with pheochromocytoma compared to controls. The level of active renin in patients with primary aldosteronism was significantly lower than in patients with Cushing's syndrome and pheochromocytoma. In conclusion, VEGF levels were significantly elevated in patients with endocrine hypertension due to glucocorticoid, mineralocorticoid and/or catecholamine excess. The highest VEGF levels were detected in patients with Cushing's syndrome. The latter is associated with accelerated development of atherosclerosis and increased cardiovascular risk. VEGF might contribute to the cardiovascular risk in this disease. This effect was not likely to be PGE2 mediated.
The aim of this study was to follow up the effect of an 8-week treatment with amlodipine given al... more The aim of this study was to follow up the effect of an 8-week treatment with amlodipine given alone or in combination with hormone replacement therapy (HRT) on blood pressure and active renin in postmenopausal women with mild to moderate arterial hypertension using both conventional clinical blood pressure measurements and ambulatory blood pressure monitoring. Twenty-nine hypertensive menopausal women were divided randomly into two groups according to the treatment regimens: amlodipine and amlodipine plus HRT. The combination with HRT led to normalization of 24-h and daytime systolic and diastolic blood pressure. In contrast to the group treated with amlodipine alone, where a significant fall only of systolic night-time blood pressure was observed, in the group treated with amlodipine plus HRT both systolic and diastolic night-time blood pressure decreased significantly. Active renin did not change significantly after treatment in both groups. Triglycerides decreased significantly and high-density lipoprotein-cholesterol increased significantly only after amlodipine treatment. There were no significant differences in serum total cholesterol and low-density lipoprotein-cholesterol after HRT plus amlodipine. In conclusion, amlodipine is effective in reducing blood pressure in postmenopausal women. The maintenance of a normal circadian blood pressure pattern was influenced by HRT.
Experimental and Clinical Endocrinology & Diabetes, 2009
The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome w... more The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome with fatal consequences is described. Both the clinical and the biochemical findings were consistent with ectopic ACTH production. A computed tomographic (CT) scan revealed intact pituitary and enlarged adrenal glands. Liver metastases were seen but the primary neoplasm was not found. Treatment with aminoglutethimide and other therapeutic measures were unsuccessful. A carcinoma of the right ovary was discovered on autopsy. The tumour cells showed immunoreactivity for neuron-specific enolase (NSE), ACTH and beta-endorphin with differing degree of intensity.
ContextHuman zonulin is a protein that regulates the intercellular tight junctions in various tis... more ContextHuman zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto’s thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied.Objective and designThis pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto’s thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics.Subjects and methodsA group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method.ResultsAge, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively).ConclusionsThere is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant.
Introduction: Thyroid dysfunction is often associated with disturbances in calcium-phosphorus met... more Introduction: Thyroid dysfunction is often associated with disturbances in calcium-phosphorus metabolism, but studies on the subject provide conflicting results. Aim: To study the parameters of calcium-phosphorus metabolism in women with newly diagnosed thyroid dysfunction, not receiving specific treatment, and to compare them with those of the control group healthy women. Patients and methods: The study included 119 women with newly diagnosed thyroid dysfunction- 51 with onset of Graves' disease and 68 with autoimmune thyroiditis. A comparison was made with the data of 75 age- matched euthyroid women. FT3, FT4, TSH, total and ionized serum calcium, inorganic phosphate, parathyroid hormone (PTH) were studied. Results: The results of the analysis showed statistically significant higher concentrations of total and ionized calcium in hyperthyroid women compared to the control group. However, no significant differences in parathyroid hormone values were found between the two groups....
UNLABELLED The purpose of this study was to analyze the relationship of the main hormonal and met... more UNLABELLED The purpose of this study was to analyze the relationship of the main hormonal and metabolic abnormalities in PCOS with different levels of TSH in the limits of its reference values. MATERIAL AND METHODS The study involved 70 women with PCOS aged 16 to 39 years and BMI between 18.3 and 39.5 kg/m2 and a control group of 22 clinically healthy women, corresponding to age and BMI. In all of the participating women fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, insulin, TSH, FT4, TPO-Ab and Tg-Ab, LH, FSH, estradiol, Androstenedione, testosterone, SHBG, DHEA-S, prolactin, 17-hydroxyprogesterone were assessed. BMI, LDL-cholesterol, LH/FSH ratio, FAI and HOMA-index were calculated. RESULTS In patients with PCOS, TSH levels > 2.0 mlU/L are associated with significantly higher levels of total and LDL-cholesterol. However, we did not find a direct dependency of TSH indicators of insulin resistance neither across the group of women with PCOS, nor with ...
vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary e... more vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours
OBJECTIVE The aim of the study was to establish whether a combi - nation of low dose estradiol va... more OBJECTIVE The aim of the study was to establish whether a combi - nation of low dose estradiol valerate (EV) and estriol (E3) is able to alleviate climacteric symptoms and preserve bone in early postmeno- pausal women. METHOD A one-year prospective non-randomized study was conducted of two groups of women: control group (n=31) and hormone replacement therapy (HRT) group (n=35), treated with 1 mg EV and 2 mg E3, combined with sequential levonorgestrel 0.25 mg. The criteria for inclusion were: 9-18 months after last menstru- al bleeding, FSH>25 IU/L, moderate climacteric symptoms, bone min- eral density (BMD) of less than 2.5 SD below peak adult bone mass. None of the women had any pre-existing medical condition which could affect bone metabolism. BMD was estimated by single-energy X-ray absorptiometry on the distal and ultradistal areas of the fore- arm at the start of the study and after 1 year. The Kupperman menopausal index (KI), Hamilton anxiety scale (HAMA), and adverse effec...
Experimental and Clinical Endocrinology & Diabetes, 2015
We described biochemical outcome in regards to different treatment modalities in patients with ac... more We described biochemical outcome in regards to different treatment modalities in patients with acromegaly in Bulgaria. It was a retrospective analysis using data from the Bulgarian Acromegaly Database. Patients with eligible data on at least one treatment modality were included in the study. Disease control was assessed by both GH and IGF-1 values or by GH/IGF-1 alone in cases with one marker. Last follow-up was median 7.0 (range 0.5-51) years after diagnosis. We identified 534 patients with interpretable data, 65.4% of whom were females. Overall surgical cure rate was 28.8%. Adjuvant bromocriptine and cabergoline treatment was analyzed in 133 and 70 patients with disease control achieved in 18.8% and 31.4% respectively. Patients without prior radiotherapy had 16.3% and 18.2% control rates respectively. Predictors of response to dopamine agonist (DA) therapy were disease activity, radiotherapy and medication dose. Adjuvant somatostatin analog (SSA) treatment led to biochemical control in 38.6% of 70 patients. Combination of SSA and cabergoline led to remission in 25% of 20 patients. Growth hormone receptor antagonist (GHRA) alone or in combination resulted in remission in 61.5% of 13 patients. Approximately one third of the patients were cured median 10 years after irradiation. Overall disease control was observed in 51.4% of our patients increasing to 70.3% in the last 5 years of the study period. DAs are efficient in less than 20% of non-irradiated patients. They are a good cost-effective alternative for carefully selected patients.
Methods and Findings in Experimental and Clinical Pharmacology, 2008
In the present study, we assessed the levels of fasting homocysteine in patients with active Cush... more In the present study, we assessed the levels of fasting homocysteine in patients with active Cushing's syndrome using two different assay methods. To determine a possible link between homocysteine and renin-angiotensin-aldosterone system (RAAS), nine patients with Cushing's syndrome and nine patients with metabolic syndrome were given a 1-month treatment with angiotensin II (AII) receptor blocker valsartan. Plasma homocysteine, active renin and aldosterone did not differ significantly among patients with Cushing's syndrome, patients with metabolic syndrome and controls. As expected, active renin increased significantly during valsartan treatment in patients with Cushing's syndrome as well as in patients with metabolic syndrome. Plasma homocysteine did not change after valsartan treatment, suggesting a lack of direct relationship between homocysteine and RAAS. Our data suggest that homocysteine might not serve as a reliable marker of endogenous hypercortisolism or of cardiovascular risk associated with Cushing's syndrome and metabolic syndrome.
Methods and Findings in Experimental and Clinical Pharmacology, 2001
The aim of this study was to investigate the effect of short-term treatment with losartan, a sele... more The aim of this study was to investigate the effect of short-term treatment with losartan, a selective and competitive angiotensin II (AngII) receptor blocker, on vascular endothelial growth factor (VEGF), active renin and kallikrein activity (KA) in patients with essential hypertension and primary aldosteronism. Nine patients with primary aldosteronism (5 with Conn adenoma and 4 with idiopathic hyperaldosteronism) and 9 patients with essential hypertension were included in the study. Systolic and diastolic blood pressure decreased significantly after losartan treatment in both patient groups. Plasma and urinary Kallikrein activity were significantly higher in primary aldosteronism in comparison with essential hypertension. There were no significant changes in the active renin and aldosterone in patients with primary aldosteronism after treatment. Plasma and urinary KA decreased significantly after losartan administration in both groups. Serum VEGF levels in primary aldosteronism were not significantly different from those in essential hypertension and did not change significantly after treatment in either group. In conclusion, losartan, in usual therapeutic doses, lowers blood pressure in patients with primary aldosteronism and essential hypertension. This marked antihypertensive effect in primary aldosteronism could be explained predominantly by blockade of tissue renin-angiotensin system (RAS). The variations in KA could be due to hemodynamic changes. VEGF is not likely to be involved in the action of losartan.
Methods and Findings in Experimental and Clinical Pharmacology, 1998
Eleven patients with Cushing's syndrome were included in the study. They maintained their... more Eleven patients with Cushing's syndrome were included in the study. They maintained their usual sodium intake and received a single oral dose of 50 mg of the angiotensin II antagonist receptor losartan for 3 days. Losartan treatment resulted in stimulation of active renin and decrease of plasma and urinary kallikrein activity. Both systolic and diastolic blood pressure decreased independently of baseline level of active renin. The relationship between kallikrein and renin-angiotensin system are discussed.
There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arteria... more There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the present study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E2 (PGE2) in patients with endocrine hypertension. The study comprised: 30 patients with primary aldosteronism; 32 patients with active Cushing's syndrome; 19 patients with pheochromocytoma; 22 patients with essential hypertension and 24 healthy volunteers. VEGF was significantly elevated in all groups of patients as compared to the controls. VEGF levels in patients with Cushing's syndrome were significantly higher than those in patients with essential hypertension and primary aldosteronism. We did not find significant differences in VEGF levels between patients with Conn adenomas and idiopathic aldosteronism as well as between patients with Cushing's disease and Cushing's syndrome. PGE2 levels were not significantly different among the groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in those with pheochromocytoma compared to controls. The level of active renin in patients with primary aldosteronism was significantly lower than in patients with Cushing's syndrome and pheochromocytoma. In conclusion, VEGF levels were significantly elevated in patients with endocrine hypertension due to glucocorticoid, mineralocorticoid and/or catecholamine excess. The highest VEGF levels were detected in patients with Cushing's syndrome. The latter is associated with accelerated development of atherosclerosis and increased cardiovascular risk. VEGF might contribute to the cardiovascular risk in this disease. This effect was not likely to be PGE2 mediated.
The aim of this study was to follow up the effect of an 8-week treatment with amlodipine given al... more The aim of this study was to follow up the effect of an 8-week treatment with amlodipine given alone or in combination with hormone replacement therapy (HRT) on blood pressure and active renin in postmenopausal women with mild to moderate arterial hypertension using both conventional clinical blood pressure measurements and ambulatory blood pressure monitoring. Twenty-nine hypertensive menopausal women were divided randomly into two groups according to the treatment regimens: amlodipine and amlodipine plus HRT. The combination with HRT led to normalization of 24-h and daytime systolic and diastolic blood pressure. In contrast to the group treated with amlodipine alone, where a significant fall only of systolic night-time blood pressure was observed, in the group treated with amlodipine plus HRT both systolic and diastolic night-time blood pressure decreased significantly. Active renin did not change significantly after treatment in both groups. Triglycerides decreased significantly and high-density lipoprotein-cholesterol increased significantly only after amlodipine treatment. There were no significant differences in serum total cholesterol and low-density lipoprotein-cholesterol after HRT plus amlodipine. In conclusion, amlodipine is effective in reducing blood pressure in postmenopausal women. The maintenance of a normal circadian blood pressure pattern was influenced by HRT.
Experimental and Clinical Endocrinology & Diabetes, 2009
The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome w... more The case of a 60-year-old female with severe and rapidly progressing Cushing's syndrome with fatal consequences is described. Both the clinical and the biochemical findings were consistent with ectopic ACTH production. A computed tomographic (CT) scan revealed intact pituitary and enlarged adrenal glands. Liver metastases were seen but the primary neoplasm was not found. Treatment with aminoglutethimide and other therapeutic measures were unsuccessful. A carcinoma of the right ovary was discovered on autopsy. The tumour cells showed immunoreactivity for neuron-specific enolase (NSE), ACTH and beta-endorphin with differing degree of intensity.
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