Mirko Koršić

Effects of Sertraline Treatment on Plasma Cortisol, Prolactin and Thyroid Hormones in Female Depressed Patients

The aim of the study was to evaluate the effects of 4 and 24 weeks of sertraline treatment (average dose 42.5 mg/day) on plasma hormone levels in 15 female patients with major depression. Baseline levels of triiodothyronine (T3) were lower, while cortisol, prolactin (PRL), thyroid-stimulating hormone (TSH), and thyroxin (T4) levels did not differ from the values in 16 female controls. There was a positive correlation between the scores on the Montgomery-Asperg Depression Rating Scale and baseline cortisol levels. Treatment with sertraline for 4 weeks increased plasma cortisol levels, while 24 weeks of sertraline treatment increased plasma T3 levels in depressed patients. Neither 4, nor 24 weeks of sertraline treatment affected PRL, T4 and TSH levels in depressed patients. The data show different and time-dependent effects of sertraline treatment on plasma cortisol, PRL and thyroid hormones in female depressed patients.

Changes of the corrected Q-T interval in the electrocardiogram of patients with anorexia nervosa

Thirty patients with anorexia nervosa and 30 controls had an electrocardiogram with the corrected Q-T interval. The aim of the study was to analyse the corrected Q-T interval in patients with anorexia nervosa compared with the findings in the control group, to compare the body mass index between two groups and to measure underlying dispersion of the corrected Q-T interval in each of the 12 ECG leads in both groups. All corrected Q-T intervals were measured in each of the 12 ECG leads and the longest values of three consecutive intervals were used for this analysis. The prolonged corrected Q-T interval was found in 12 out of 30 patients with anorexia nervosa (40%), with the longest mean values of 0.421 s (range, 0.334-0.500 s), and in 2 out of 30 patients of the controls (7%), with the longest mean values of 0.390 s (range, 0.343-0.444 s). The difference was statistically significant (t = 4.453, P < 0.001). Relative risk for prolongation of the corrected Q-T interval in patients with anorexia nervosa was high: 12 compared with control subjects. The longest values of the corrected Q-T interval in both groups, and the longest values of the prolonged corrected Q-T interval in both groups were observed in the anteroseptal leads of the electrocardiograms. The mean serum potassium level in the group with anorexia nervosa was 3.97 and in the control group was 4.15 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Proinflammatory cytokines and receptor activator of nuclear factor kappaB-ligand/osteoprotegerin associated with bone deterioration in patients with Crohn´s disease

Objectives The high incidence of bone disease and the increasing evidence of Crohns disease (CD) bone decline in corticosteroid users and nonusers suggest that bone metabolism is affected by inflammatory process. The aim of the study was to compare serum levels of proinflammatory cytokines, markers of bone turnover and regulatory molecules of osteoclast biogenesis, receptor activator of nuclear factor κB-ligand (RANKL) and osteoprotegerin (OPG), between naïve and long-standing CD patients. Methods The study included 95 CD patients, 15 of them with newly diagnosed and previously untreated CD. The spine and hip bone mineral density was measured by dual-energy X-ray absorptiometry. Biochemical markers were determined by immunoassay. Results Osteopenia was recorded at diagnosis in 53% of naïve patients and osteoporosis was found in 26% of long-standing CD patients. The newly diagnosed patients showed correlation between TNF-&agr; and soluble RANKL (sRANKL) (r=0.5; P=0.04), and this positive relationship characterized the study population as a whole (r=0.3; P=0.003). Analysis of the OPG and sRANKL relationship showed absence of correlation in patients with healthy skeleton, whereas an inverse correlation was found in those with osteopenia (r=−0.31; P=0.033) and osteoporosis (r=−0.48; P=0.028). In naïve patients with reduced T score, the correlation between sRANKL and OPG was highly inverse (r=−0.8; P=0.02) and these patients were characterized by lower BMI, significantly higher level of proinflammatory cytokines, elevated C-reactive protein, and increased activity of free sRANKL and OPG. Conclusion Bone disease that accompanies CD at diagnosis suggests that bone metabolism is affected by the underlying inflammatory process per se, as probably confirmed by our finding of the central proinflammatory cytokine TNF-&agr; being strongly associated with the osteoclastogenic mediator RANKL, and inversely with bone density.

Growth hormone and insulin growth factor-I levels in plasma and cerebrospinal fluid of patients with multiple sclerosis

Multiple sclerosis (MS) has several clinically different forms. Whereas the illness progresses slowly in most of the patients, 10% have an aggressively progressive course with fatal outcome without signs of remyelination capability. The process of remyelination depends on numerous interactive factors, including the presence of various growth factors, the most important of which in the adult is insulin growth factor-I (IGF-I). On the other hand, the most powerful postnatal regulator of IGF-I is growth hormone (GH), which also acts as a neuroprotective and an antiapoptotic agent, and has direct influence on myelination. Levels of these growth factors have never been examined in the cerebrospinal fluid (CSF) of patients with MS. The levels of IGF-I and GH were measured in serum and CSF of 46 MS patients and compared with those of 49 patients with no evidence of demyelinating disease. The only positive finding was a deficiency of GH in the CSF of MS patients. The possible implications of those findings in the etiopathogenesis of MS will be discussed.

Calcaneus ultrasound in males: Normative data in the Croatian population (ECUM study)

Limited number of dual X-ray absorptiometry (DXA) devices in Croatia makes this diagnostic technique unavailable to the majority of the population. Quantitative ultrasound (QUS) of the calcaneus could be an alternative tool for assessing fracture risk. However, age-specific normative data should be obtained before using the QUS in everyday clinical practice. The aim of our Epidemiology of Calcaneus Ultrasound in Males (ECUM) study is to establish the normative QUS data in a healthy sample of Croatian males. A total of 1002 male participants, aged 20–99, recruited in different Croatian counties, were included in the study. In each subject broadband ultrasound attenuation (BUA), speed of sound (SOS) and quantitative ultrasound index (QUI) of the left calcaneus were measured using the Sahara ultrasound device (Hologic).The coefficients of variation were 2.85 for BUA, 0.37 for SOS and 2.49 for QUI. Significant declining with age was found for all three parameters, BUA (p<0.001), SOS (p<0.001) and QUI (p<0.001), with respective r values 0.14, 0.27 and 0.23. The peak SOS (1562.8±28.5 m/sec) and QUI (103.6±16.5) values were observed in the third decade, whereas the peak BUA value (86.2±19.2 db/MHz) was observed in the fourth decade. A subgroup of 103 participants, aged 20–29, was used to estimate young adult mean and SD for QUI and calculate the T-scores. Using the World Health Organization diagnostic criteria the rates of osteoporosis (T-score50 yr was 16.2%. Although further studies might improve our understanding of the QUS role in the fracture prediction, we hope that the results presented here will improve the clinical management of osteoporosis in males. (J. Endocrinol. Invest. 29: 221–225, 2006)

Nutrition and lifestyle in relation to bone health and body weight in Croatian postmenopausal women.

The objective was to investigate the association of nutrients and lifestyle modifiers with bone mineral density (BMD) and weight and/or body mass index (BMI) in 120 healthy Croatian postmenopausal women. The hip and spine BMD was assessed by Lunar Prodigy (GE Medical Systems). Nutrient assessment from 3-day records was analyzed using the US Department of Agriculture Food Composition Tables and the Croatian National Institute of Public Health database. Subjects were asked to record the consumption of alcohol, coffee, tea and mineral waters, the amount of salt added to foods and smoking habits, as well as involvement in recreational activities, walking and heavy housework. Spot urine samples were analyzed for calcium, magnesium, sodium, potassium and zinc and were normalized by creatinine. Alcohol showed statistically significant positive association with femur and spine BMD and its consumption was higher in subjects without osteoporosis. Urinary sodium/creatinine was significantly positively associated with femoral neck and trochanter BMD, while urinary calcium/creatinine was significantly negatively associated with trochanter, total femur and spine BMD. Consumption of mineral waters was inversely associated with weight/BMI and so were dietary fiber and magnesium. In conclusion, moderate alcohol consumption and urinary sodium were positively associated while urinary calcium was negatively associated with either hip and/or spine BMD. Mineral waters, higher fiber and magnesium intake were beneficial for weight/BMI in this population of apparently healthy Croatian women.

A Novel AAAS Gene Mutation (p.R194X) in a Patient with Triple A Syndrome

Objective: The clinical and molecular data of a patient with triple A syndrome are reported. Patient: A 21-year-old male who was diagnosed for adrenal insufficiency at the age of 2 years after a severe attack of adrenal crisis. At the age of 4 years, achalasia and alacrima were diagnosed. Puberty started at the age of 17 years. At the same time, symptoms of central, peripheral, and autonomic nervous system dysfunction were noted. Later on, at the age of 20 years, a bone age delay of 6 years and severe osteoporosis was diagnosed. Results: A compound heterozygous AAAS mutation consisting of two mutations was found: a C > T transition in exon 7 resulting in a change of arginine at amino acid position 194 into a stop codon (Arg194X) at one allele, and a C > T transition in exon 12 resulting in a change of glutamine at amino acid position 387 into a stop codon (Gln387X) on the other allele. Conclusion: The mutation in exon 7 (p.R194X) of the AAAS gene is a novel mutation which has not been found in any other family so far, whereas the second was already found in some other families. This case adds to the clinical and molecular spectrum of triple A syndrome and may provide a new insight into the functions of AAAS gene.

Effects of ritanserin, a novel serotonin-s2 receptor antagonist, on the secretion of pituitary hormones in normal humans

The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and Cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline Cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans.

Clinical features and therapeutic outcomes of patients with acromegaly: Single-center experience

The aim of this study was to review the outcome of acromegaly treatment, as well as co-morbidity and mortality in a series of patients with acromegaly attending a single center in the last 10 yr. In that period, 53 patients were treated for acromegaly. Transsphenoidal operation was applied as the first-line therapy in 94.3% of patients and it led to disease remission in 59.2% of them. The remission criteria included a nadir GH<1 µg/l after glucose load, and normal age-related IGF-I levels. The remission rate after transsphenoidal surgery was significantly higher in the group of patients with microadenoma (76.9%), than in the group of patients with macroadenoma (52.8%). Patients with invasive tumors had remission rate of 16.7% after transsphenoidal surgery. There were no perioperative deaths. As the second-line treatment somatostatin analogues, radiotherapy, and dopaminergic agonists were used. Hypertension and diabetes were the most frequent co-morbidities in the group of patients. After successful treatment, 30% of patients with diabetes or impaired glucose tolerance had significant improvement of glycemic control. Transsphenoidal surgery is the appropriate first-line therapy in patients with somatotropinoma. Medical and radio-therapy should be reserved as the second-line therapy after surgery failure.

Platelet serotonin concentration and monoamine oxidase activity in hypothyroid patients

Background/Aim: The relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the serotonergic (5-hydroxytryptamine, 5-HT) system is not clear. The aim of the study was to determine platelet biochemical markers (5-HT concentration and monoamine oxidase B, MAO-B, activity) in hypothyroid patients. Methods: The study included 25 medication-free female hypothyroid patients in postoperative follow-up after total thyroidectomy due to papillary thyroid carcinoma, who had not been treated with synthetic thyroxine (T4) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T4 and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively. Results: Hypothyroid patients had significantly higher TSH, significantly lower T4 levels and platelet 5-HT concentrations, and unchanged platelet MAO-B activity than healthy subjects. A positive correlation was found between the 5-HT concentration and platelet MAO-B activity, and between the platelet MAO-B activity and T4 in control subjects. Conclusions: Reduced platelet 5-HT concentrations in hypothyroid patients suggests a complex interaction between the 5-HT system and HPT axis activity, which could be related to the frequent occurrence of depressive symptoms in hypothyroid patients. The determination of platelet 5-HT concentrations should be considered a diagnostic tool for the evaluation of depressive symptoms in hypothyroid patients during the hormone withdrawal procedure.