The phenotype of Graves' orbitopathy is associated with thyrotropin receptor antibody levels.

PURPOSE: Graves' orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO. METHODS: Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively. RESULTS: Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis. CONCLUSIONS: TSH-R-Ab were significantly associated with GO's phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.

Health care access of thyroid disease patients in Serbia during the COVID-19 pandemic.

PURPOSE: The aim of this study was to assess the impact of repurposing health care facilities in response to COVID-19 on the access of patients with thyroid disease to health care. METHODS: This study consisted of a web-based survey. The survey was anonymous and consisted of forty questions. RESULTS: This survey included 206 respondents. 91.3% of the respondents had health insurance through the Republic Fund of Health Insurance, 9.7% had private or both health insurances, and 3.4% did not have any health insurance. A significant proportion of respondents (60.4%) had to switch from public to private health care to reach a physician and 73.8% had to switch from public to private laboratories. For the 91.9%, this was perceived as a financial burden. Before the pandemic, 83.1% of respondents reported regular follow-up by physicians, which decreased to 44.9% during the pandemic (p < 0.01). 76.3% of the respondents regarded that their thyroid disease was managed optimally before the pandemic, while this figure declined to only 48% during the pandemic (p < 0.01). CONCLUSIONS: The COVID-19 pandemic disrupted the medical care of thyroid patients in Serbia. For the patients treated in the public health care system, access to general practice was hindered, while access to specialist care was disrupted. It led to a switch from public to private health care, which was perceived as a financial burden for almost all the respondents. However, private health care proved to be an important safety net when the public system was overwhelmed.

Clinical value of functional thyrotropin receptor antibodies in Serbian patients with Graves' orbitopathy.

PURPOSE: Thyrotropin receptor autoantibodies (TSH-R-Ab) are heterogeneous in their biological function and play a significant role in the pathophysiology of both Graves' disease and Graves' orbitopathy (GO). The clinical significance and utility of determining functional TSH-R-Ab in a Serbian collective were evaluated. METHODS: 91 consecutive patients with GO were included in this study. Total TSH-R-Ab concentration, referred to as TSH-R binding inhibitory immunoglobulins (TBII) was detected using a competitive-binding immunoassay. Stimulating and blocking TSH-R-Ab (TSAb and TBAb) were measured with cell-based bioassays. RESULTS: Stimulating TSAb activity and TBII positivity were detected in 85 of 91 (93.4%) and 65 of 91 (71.4%) patients with GO (P < 0.001). Blocking TBAb activity was observed in only one patient who expressed dual stimulating and blocking TSH-R-Ab activity. The sensitivity rates for differentiating between clinically active versus inactive and mild versus moderate-to-severe GO were 100% and 100% for TSAb, respectively. In contrast, these were 82% and 87% only for TBII. Seven of eight (87.5%) and one of eight (12.5%) euthyroid patients with GO were TSAb and TBII positive, respectively (P < 0.031). TSAb serum levels significantly predicted GO activity compared to TBII (odds ratio, OR, 95%CI: 3.908, 95%CI 1.615-9.457, P = 0.003; versus 2.133, 0.904-5.032, P = 0.084, univariate analysis; and OR 4.341, 95%CI 1.609-11.707, P = 0.004; versus 2.337, 0.889-6.145, P = 0.085 multivariate analysis). CONCLUSION: Stimulating TSAb are highly prevalent in patients with GO and show superior clinical characteristics and predictive potential compared to the traditionally used TBII.

Antithyroid drugs in Graves' hyperthyroidism: differences between "block and replace" and "titration" regimes in frequency of euthyroidism and Graves' orbitopathy during treatment.

PURPOSE: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves' hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether 'Block and Replace' (B + R) and 'Titration' (T) regimes are equivalent in terms of frequency of euthyroidism and Graves' Orbitopathy (GO) during ATD therapy. METHODS: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution's policy. RESULTS: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27-0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. CONCLUSION: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

Production of levan by Bacillus licheniformis NS032 in sugar beet molasses-based medium.

The production of levan by Bacillus licheniformis NS032 in a medium based on sugar beet molasses was studied. High polysaccharide yields were produced by using diluted molasses (100-140 g/L of total sugars) with the addition of commercial sucrose up to 200 g/L of total sugars, as well as K2HPO4. A levan yield of 53.2 g/L was obtained on a medium optimized by response surface methodology, containing 62.6% of sugar originating from molasses, and 4.66 g/L of phosphate, with initial pH value of 7.2. In comparison to the media with 200 and 400 g/L sucrose, in the molasses optimized medium, the observed bacterial growth was faster, while the maximum production of polysaccharide was achieved over a shorter time interval (48 h). The polysaccharide produced in molasses medium had a weight average molecular weight of 5.82 × 106 Da, degree of branching 12.68%, viscosity of 0.24 dL/g, and based on methylation analysis and NMR data, it did not significantly differ from levan obtained in the medium with 200 g/L sucrose.

Autoimmunity and thyrotropin level in developing thyroid malignancy.

OBJECTIVE: Malignancies and autoimmune thyroid disease are still controversial, but recent studies prove that a long lasting thyroid disease may be linked with malignancy, e.g. papillary thyroid carcinoma in patients with Hashimoto thyroiditis. Having in mind that thyrotropin is a thyroid growth factor, the relationship between its serum values, as well as the levels of anti-peroxidase and anti-thyroglobulin antibodies and thyroid malignancy in patients with nodular thyroid goiter was examined. PATIENTS AND METHODS: Six-hundred-thirty-seven medical records, which included the thyroid fine-needle aspiration cytology were retrospectively evaluated. Patients were grouped regarding the levels of thyrotropin, anti-peroxidase and anti-thyroglobulin antibodies (in or out of the reference ranges) and compared with cytology findings for establishing their prognostic potential for malignancy. RESULTS: Elevated serum thyrotropin (≥ 4.5 mIU/L) was found in 27.3% of patients with thyroid malignancy compared with 10.8% with benign and 16.1% with unspecified cytology finding (p < 0.01). In the group of patients with malignant cytology findings 7.0% of them had elevated anti-peroxidase antibodies level, and 1.4% had anti-peroxidase antibodies level in reference range. In the group of patients with malignant cytology findings 4.2% of them had elevated anti-thyroglobulin antibodies level, and 1.4% had anti-thyroglobulin antibodies level in reference range. CONCLUSIONS: In patients with elevated serum thyrotropin concentration and/or chronic thyroiditis the occurrence of thyroid malignancy is increased.

Impact of anesthetic regimen on the respiratory pattern, EEG microstructure and sleep in the rat model of cholinergic Parkinson's disease neuropathology.

OBJECTIVES: We hypothesized that the impact of distinct anesthetic regimens could be differently expressed during anesthesia and on post-anesthesia sleep in the neurodegenerative diseases. Therefore, we followed the impact of ketamine/diazepam and pentobarbital anesthesia in a rat model of the severe Parkinson's disease cholinergic neuropathology on the electroencephalographic (EEG) microstructure and respiratory pattern during anesthesia, and on the post-anesthesia sleep. METHODS: We performed the experiments on adult, male, spontaneously breathing Wistar rats chronically instrumented for sleep recording. The bilateral pedunculopontine tegmental nucleus (PPT) lesion was done by ibotenic acid microinfusion. Following postoperative recovery, we recorded sleep for 6h, induced anesthesia 24h later using ketamine/diazepam or pentobarbital, and repeated sleep recordings sessions 48h and 6days later. During 20min of each anesthesia we recorded both the EEG and respiratory movements. For sleep and EEG analysis, Fourier analysis was applied on 6-h recordings, and each 10-s epoch was differentiated as a state of wakefulness (Wake), non-rapid eye movement (NREM) or rapid eye movement (REM). Additionally, the group probability density distributions of all EEG frequency band relative amplitudes were calculated for each state, with particular attention during anesthesia. For respiratory pattern analysis we used Monotone Signal Segments Analysis. The PPT lesion was identified through nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. RESULTS AND CONCLUSIONS: Our data show that the ketamine/diazepam anesthetic regimen in the PPT-lesioned rats induces more alterations in the EEG microstructure and respiratory pattern than does the pentobarbital anesthesia. In addition, the equal time required to establish an anesthetized state, and the long-term effect on post-anesthesia sleep in the PPT-lesioned vs. control rats suggest this anesthetic regimen as potentially more beneficial both for anesthesia induction and for post-anesthesia sleep in the surgical procedures of the elderly, and Parkinson's, and Alzheimer's patients.

Further studies on delineating thyroid-stimulating hormone (TSH) reference range.

The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.

Glucocorticoid effect on insulin sensitivity: a time frame.

It is well known that glucocorticoids induce insulin resistance, but the exact time scale in humans is not well known. The aim of the study was to determine the time scale of effects of pharmacologic doses of glucocorticoids on insulin sensitivity. Subjects were treated with repeated methylprednisolone infusions and oral prednisone for Graves' orbitopathy. Insulin sensitivity was determined using euglycemic hyperinsulinemic clamp (EHGC) before, during the first glucocorticoid infusion and after 2 months of treatment. EHGC started 2 h after the start of the glucocorticoid infusion, and lasted for 2 h. In another group of patients, insulin sensitivity was determined by short insulin tolerance test (SITT) before and during the first glucocorticoid infusion. SITT started 15 min after the start of the glucocorticoid infusion and lasted for 15 min. Ten subjects were included in each protocol. All were euthyroid during the study period. Four hours after the start of the glucocorticoid infusion significant reduction of insulin sensitivity was observed, which did not change for a further 2 months of glucocorticoid treatment [before 7.82 (95% confidence interval (CI) 5.35-10.29), first infusion, 4.93 (95% CI 2.99-6.87), after 2 months 5.36 (95%CI 3.91-6.81) mg/kg/min]. No significant change in insulin sensitivity occurred during the first 30 min of glucocorticoid infusion [before 139.7 (95%CI 94.1-185.3), during 146.7 (95%CI 106.3-187.1) mumol/l/min]. In humans, glucocorticoid- induced insulin resistance develops quickly, in about 4 h, and does not change during further glucocorticoid treatment.

Temporal coupling of luteinizing hormone and follicle stimulating hormone secretion in polycystic ovary syndrome.

The aim of this study was to assess the luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile secretion and their temporal relation (concordance) in subjects with polycystic ovary syndrome (PCOS). Fifteen subjects were included in the study (age 17-30 years, body mass index (BMI) 19.38-33.46 kg/m2). For the LH and FSH determinations, blood sampling started at 23.00 and lasted for 6 h with an intersample interval of 10 min. Pulse analysis was carried out using the PulsDetekt program. LH/FSH pulse concordance was calculated using the specific concordance index. Gonadotropin co-pulsatility was found in six subjects who were significantly younger than the others (median 18.5 vs. 22.5 years, p = 0.036). BMI, hirsutism grade, insulin sensitivity, estradiol, progesterone, testosterone, prolactin, cortisol and results obtained from the pulsatility analysis did not significantly differ between the groups. A serum cortisol concentration was correlated with the increased LH/FSH lag time (p = 0.851, p = 0.036) all subjects were included. In conclusion, two distinct LH/FSH secretory patterns were found in PCOS patients, manifested by the presence or absence of the concordance of gonadotropin secretion. In the group where LH/FSH co-pulsatility was present, correlation was found between the serum cortisol and the LH/FSH lag. We also confirmed the finding of previous studies that LH and FSH secretion are regulated by two different mechanisms.

[Diffuse and binodular goiter in a patient with tuberous sclerosis]. / Difuzna i binodozna struma kod bolesnice sa tuberoznom sklerozom.

Tuberous sclerosis complex is hereditary multisystemic, neurocutaneous disorder characterized by hamartomatous lesions mainly involving the brain, skin and viscera. Thyroid gland is rarely affected in these patients. Case history of a patient with tuberous sclerosis complex and diffuse and binodular goiter was presented. No epileptic seizures occurred despite multiple intracranial calcifications, cortical and subependimal tubers, revealed by neuroimaging. Borderline intellectual functioning was determined. Ultrasonographic findings of the heart, abdomen and pelvis were normal. Bone radiographs revealed multiple cystic lesions of the metacarpal, metatarsal and terminal phalanges. Clinical, endocrine and metabolic evaluations were performed because of anxiety, mild weight loss, transient problems of swallowing and breathing complaints, developing when she was 39 years old. Palpable diffuse and asymmetric thyroid enlargement was found. Laboratory tests of thyroid function, ultrasonographic examination and scintiscanning of the thyroid gland and patohistological analysis of fine-needle aspiration biopsy revealed the euthyroid, inactive, diffuse and binodular goiter. Unusual association of goiter and tuberous sclerosis was discussed.

[Treatment of Grave's ophthalmopathy with high doses of corticosteroids]. / Lecenje Grejvsove oftalmopatije visokim dozama kortikosteroidnih lekova.

UNLABELLED: Severe ophthalmopathy with sight impairment and double vision due to a compressive optic neuropathy, extraocular muscle thickness and corneal exposure occurs in 3-5% of all patients with Graves' hyperthyroidism [1]. Steroids are the choice of treatment for ophthalmopathy in more than 50%, and with orbital radiotherapy or surgical decompression in more than 70% of cases [2]. In severe ophthalmopathy steroids are effective in more than 60% of patients [1, 3], but to be effective high dosage is necessary [1, 4-6]. High-dose intravenous steroid pulse therapy is probably preferable to oral steroids giving a better response with fewer adverse effects [6]. The aim of the study was to evaluate the efficacy of high-dose intravenous methylprednisolone pulse therapy followed by oral steroids in the treatment of patients with severe Graves' ophthalmopathy. PATIENTS AND METHODS: Fourteen euthyroid patients with severe Graves' ophthalmopathy were treated with high-dose intravenous methylprednisolone during 6 months and followed-up for 24-48 months by clinical and ophthalmological assessment. During three days two doses of methylprednisolone were given as 500 mg in 500 ml isotonic saline infusion. The treatment was followed by oral prednisone 40 mg daily and tapered off to 10 mg in four weeks when next course of therapy started. There were no contraindications for steroid treatment. Characteristics of the group are presented in Table 1. Ophthalmological assessment relating to the status of cornea, extraocular muscles, eyelids, proptosis and optic nerve function was done during the study. It provides the measurement of visual acuity, intraocular pressure, visual evoked potentials, palpebral apertures and proptosis, fundoscopy, the assessment of ocular motility, visual fields, color vision, lagophthalmos and corneal changes. For better evaluation of eye disease clinical activity score and patients self-assessment were used. Thyroid hormones and thyroid microsomal antibodies were measured during the study. All patients were photographed before and after treatment. Orbital computed tomograms were performed before and after treatment for extraocular muscles assessment. Data were analyzed by Wilcoxon test. RESULTS: Clinical activity score fell significantly within the first week of therapy in all patients and remained stable during the follow-up period (before treatment: mediana 5, min 3, max 7 and after: mediana 2, min 1, max 4, p < 0.01). Proptosis (Table 2, Figure 1) was significantly reduced (mean values before and after treatment were 24.15 mm and 22.75 mm respectively, the difference was 1.40 mm; p = 0.014). Visual acuity was improved in 2 of 5 patients (Table 3). Ophthalmological assessment of color vision, fundal changes, visual fields and intraocular pressure is presented in Table 4. Five of 9 patients experienced loss or amelioration of diplopia after a 3-6 month treatment. The ocular motility was normalized or improved in 9 of 10 patients. The extraocular muscle enlargement on orbital CT scans decreased in 10 patients (mean score before and after treatment was 6.9 and 3.8 respectively). Minimal and transient side effects were observed during treatment. DISCUSSION: The best parameters of severity of the disease and of response to treatment are those related to assessment of optic nerve function, ocular motility and corneal status [6, 10]. In this series of 14 patients treated with high-dose steroids we found an improvement in visual acuity and color vision and normalization of visual fields, intraocular pressure, visual evoked potentials and fundal changes within a few days of treatment. Clinical activity score (CAS) was significantly and promptly reduced by therapy as most reports revealed [3, 5, 8]. CAS has a high predictive value for the outcome of treatment since it is based on signs of inflammation. The low score level, however, does not preclude a therapeutic success [9]. A mean value of proptosis was significantly reduced by thera

Effect of weight loss on the pulsatile insulin secretion.

The aim of the study was to assess whether pulsatile insulin secretion is variable in the same individual and is related to changes in insulin sensitivity. Insulin sensitivity and pulsatility were measured before and after weight reduction in nine obese subjects. A pulsatility analysis was done using the PulsDetekt program. Blood was sampled every 2 min over a period of 90 min. The secretion randomness was quantified using approximate entropy (ApEn), and ApEn normalized by SD of the insulin time series (nApEn). Lower values indicate more regular secretion. Insulin sensitivity was measured using the homeostasis model assessment. Data are presented as median, minimum-maximum. After weight loss insulin sensitivity was increased (12.16, 7.60-76.70 vs. 38.96, 19.88-74.96%), the number of insulin pulses was reduced (11, 8-16 vs. 9,6-12), and they were more regular (ApEn, 0.92, 0.53-133 vs. 0.69,0,40-1.27; nApEn, 1.07, 0.74-1.33 vs. 0.97, 0.54-1.42). Before and after the weight loss there was a correlation between ApEn and nApEn and insulin sensitivity. Therefore, insulin secretion regularity is variable in the same individual and is related to insulin sensitivity.

Effect of insulin sensitivity on pulsatile insulin secretion.

OBJECTIVE: The aim of the study was to determine whether derangements in insulin pulsatility are related to the presence of insulin resistance or whether these changes occur only in non-insulin-dependent diabetes mellitus (NIDDM). DESIGN AND METHODS: The study included 26 obese, 11 NIDDM and 10 control subjects. The obese group was divided into a low insulin (plasma insulin <20 mU/l, OLI, 14 subjects) and a high insulin (OHI, 12 subjects) group. For pulsatility analysis blood was sampled every 2 min for 90 min. Pulsatility analysis was carried out using the PulsDetekt program. The insulin secretion randomness was quantified using interpulse interval deviation (IpID) and approximate entropy (ApEn). ApEn and ApEn normalized by s.d. of the individual insulin time series (nApEn) were calculated. Lower values of ApEn and IpID indicate more regular secretion. Homeostasis model assessment (HOMA) was used to quantify insulin sensitivity. RESULTS: Insulin pulses were significantly less regular in the OHI and the NIDDM groups compared with the control and the OLI groups (control: ApEn 0.54+/-0.16, nApEn 0.69+/-0.19, IpID 2.53+/-0.99; OLI: ApEn 0.64+/-0.12, nApEn 0. 79+/-0.15, IpID 2.92+/-1.09; OHI: ApEn 0.88+/-0.07, nApEn 0.92+/-0. 07, IpID 3.95+/-0.84; NIDDM: ApEn 0.92+/-0.16, nApEn 0.99+/-0.09, IpID 4.41+/-0.53; means +/- s.d.). There was no difference in the pulse regularity between the OHI and the NIDDM groups. CONCLUSIONS: Decrease in insulin sensitivity was correlated with the reduction of insulin secretion regularity. Therefore irregular insulin secretion is related to a reduction in insulin sensitivity, and it is not unique to NIDDM.

Optimizing the diagnostic criteria for standard (250-microg) and low dose (1-microg) adrenocorticotropin tests in the assessment of adrenal function.

ACTH stimulation is the standard test for assessment of adrenal function. It was suggested that the low dose (1 microg) would be more sensitive for detecting mild secondary adrenal insufficiency than the usual dose of 250 microg. The aim of this study was to find the optimal diagnostic criteria and to compare standard dose test (SDT) with the low dose test (LDT). A group of patients treated with corticosteroids for the 6 months was considered to have hypothalamo-pituitary-adrenal impairment. Studies were performed in 14 corticosteroid-treated and 28 control subjects in random order on 2 consecutive days. Tests were analyzed using the receiver operating characteristic curve method. The best test was cortisol increment at 15 min of the LDT. It was significantly better than the cortisol concentration at 15 min of the SDT, the best test during the SDT (receiver operating characteristic curve area and 95% confidence interval: LDT, 0.997 and 0.956-0.999; SDT, 0.827 and 0.662-0.929; P = 0.0113). For the cortisol increment at 15 min of the LDT at 100% sensitivity, the diagnostic value was 100 mmol/L, and the specificity was 96%. Therefore, the LDT is superior to the standard dose test in the assessment of secondary adrenal insufficiency.

Microalbuminuria is associated with salt sensitivity in hypertensive patients.

We have investigated 59 patients with mild-to-moderate uncomplicated essential hypertension in order to estimate whether salt sensitivity is associated with greater urinary albumin excretion. Patients whose average mean blood pressure (BP) value on day 5 of the high-sodium regimen (300 mmol/l NaCl) exceeded 10 mm Hg or more than that on day 5 of the low-sodium regimen (40 mmol/l NaCl) were classified as salt sensitive. We have demonstrated that salt sensitive patients (n = 29) manifest greater urinary albumin excretion than salt resistant patients (51.5 +/- 15 vs 11.5 +/- 12.8 mg/24h). Hypertensive patients selected as salt sensitive had a longer duration of hypertension (87 +/- 62 vs 41.5 +/- 33.6 months); greater body mass index (BMI) (29.0 +/- 4.7 vs 24.7 +/- 3.6 kg/m2); lower urinary excretion of sodium after 3 days of sodium loading (172.1 +/- 23.3 vs 245.8 +/- 21.6 mmol/day); and slightly, but significantly higher mean BP (121.3 +/- 7.4 vs 115.3 +/- 5.3 mmHg) than salt resistant patients (n = 29). Nevertheless, there was no significant correlation between duration of hypertension and the degree of urinary albumin excretion in salt sensitive patients. On the other hand, a significant correlation was demonstrated in a group of salt resistant hypertensive patients, suggesting that salt sensitivity could be linked with an early tendency to abnormal albumin excretion, while in salt resistant patients it may depend on hypertension-related renal disfunction. Therefore, measurement of microalbuminuria in patients with essential hypertension can be a useful marker for salt sensitivity.

The Vogt-Koyanagi-Harada syndrome: association with autoimmune polyglandular syndrome type 1.

We describe a young woman with primary adrenal insufficiency, hypoparathyroidism (autoimmune polyglandular syndrome type 1), Graves disease, vitiligo, and alopecia universalis. Five years after the diagnosis, she presented with recurrent ophthalmological and neurological disorders as features of Vogt-Koyanagi-Harada syndrome. A marked therapeutic response was noted on systemic high-dose corticosteroid treatment. To the best of our knowledge, such a spectre of autoimmune diseases has not been reported previously.

Influence of three-week fasting on gonadotropin pulsatility in obese menstruating women.

OBJECTIVE: To evaluate the influence of three-week fasting on gonadotropin pulsatility in extremely obese women of reproductive age. DESIGN: Prospective study of 21-day fasting (400 kcal/day), under medical supervision. SUBJECTS: 20 females, average age of 35.1 +/- 5.9 y, and average BMI of 41.19 +/- 8.39 kg/m2, with regular menstrual cycles (26-34 days). The mean weight loss was 12.5 +/- 3.23 kg. MEASUREMENTS: Blood samples for LH and FSH were taken between 4th and 7th day of the menstrual cycle, before and in the first cycle immediately after weight reduction, for 6 h, starting at 09.00 with 10 min intersample intervals. Pulsatility analysis was done using Pulsar program. Statistical analysis was done using Wilcoxon's matched pairs signed ranking test and McNemar's test. RESULTS: There was no statistically significant difference (p > 0.05) in LH and FSH pulsatile secretion before and after diet including the number of pulses, amplitudes, interpulse intervals and peak lengths. There were no disturbances of menstrual cycle during or after the diet. CONCLUSION: These results suggest that a 21-day fast, accompanied with significant weight loss, does not affect gonadotropin pulse pattern in follicular phase and normal menstrual cycle length in extremely obese females of reproductive age, compared with the pattern before diet.

[The circadian rhythm of serum aldosterone in the diagnostics of primary aldosteronism]. / Dnevni ritam aldosterona u serumu u dijagnostici primarnog aldosteronizma.

Diagnosis of primary aldosteronism should be easy in patients with unprovoked hypokaliemia and hypertension. However, it is more difficult to differentiate patients with primary normokaliemic aldosteronism from those with essential hypertension with low plasma renin activity. The aim of this study was to evaluate the appropriate testing of diagnosis and differential diagnosis of primary aldosteronism. The study group consisted of 17 patients with primary aldosteronism (12 with aldosteronoma and 5 with bilateral hyperplasia) and 20 patients with essential hypertension. The finding of increased serum aldosterone level using a single measurement, without anti-hypertensive therapy and on normal sodium intake is sufficient to confirm the diagnosis of primary aldosteronism with specificity of 95% and sensitivity of 94%. Upright posture test is shown to be fairly good tool in differentiation aldosteronoma and bilateral adrenal hyperplasia. Specificity of this test is 100% and sensitivity 88%. Although primary aldosteronism is not a common cause of hypertension it is reasonable to screen for this disorder because complete cure can be provided in a large percentage of patients.

[The effect of cilazapril and prazosin on insulin sensitivity in patients with essential hypertension]. / Uticaj cilazaprila i prazosina na insulinsku senzitivnost u bolesnika s esencijalnom hipertenzijom.

Two groups of drugs are actual for improving effects of insulin in vivo: alpha-1-adrenergic blockers and angiotensin-converting-enzyme-inhibitors. The objective of this study was to examine short-term effects of cilazapril and prazosin therapy on insulin sensitivity assessed by a 15' test of insulin tolerance of obese hypertensive persons. In groups of 8 patients insulin tolerance was tested prior to and 7 days after therapy by cilazapril dosed to 2.5 mg a day and prazosin 3 mean 1-2 mg a day. In this way satisfactory control of arterial tension was achieved. No significant changes of coefficient which enable assessment of insulin effects in vivo were established. However, in the group treated with cilazapril there were 6 out of 8 patients in whom coefficient increase was registered, so that among groups there was a significant difference in coefficient change in regard to therapy with better cilazapril effects.