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Biomedical subjects

M Korsić

Publications and source records attributed to M Korsić.

At least 19 recordsLinked to original sources

Diagnostic value of thyrotropin releasing hormone test in 129 patients with suspected tumoral hyperprolactinemia.

In 129 hyperprolactinemic (PRL > or = 100 ng/mL) and 100 normoprolactinemic patients (PRL 0-25 ng/mL), delta max. PRL (the difference between maximal prolactin (PRL) after thyrotropin releasing hormone (TRH) injection and basal value) was compared with basal PRL and computed tomography (CT) of the sellar region. In 122 hyperprolactinemic patients delta max. PRL was < 100%, while tumor was found in 106 of them. In the remainder seven hyperprolactinemic patients delta max. PRL was > or = 100% and CT showed no tumor. A significant difference in delta max. PRL between hyperprolactinemic patients without and those with verified adenoma was found and showed a significant negative correlation with basal PRL. Between 122 hyperprolactinemic patients with delta max. PRL < 100%, mean basal PRL and duration of clinical symptoms were significantly lower in 16 patients with normal CT compared to 106 patients with tumor. All normoprolactinemic patients showed delta max. PRL > or = 100% and no tumor on CT. PRL stimulation disturbance precedes tumor visualization and represents a decisive diagnostic parameter in hyperprolactinemic patients with no tumor signs.

Adult↗

Vertebral osteophytosis and vertebral deformities in an elderly population sample.

AIM OF THE STUDY: We investigated the association between vertebral osteophytosis and vertebral deformities in an elderly population sample, and the influence of some risk factors on spinal osteophytosis and deformities. SUBJECTS AND METHODS: A population sample of 280 women and 263 men, all Zagreb residents older than 45 years, participated in the study. Radiographs of the thoracic and lumbar spine were evaluated for the presence of osteophyte formation and vertebral deformities. Osteophyte size was graded on a scale from 0 to 4. Vertebral deformities were determined by the semiquantitative method of McCloskey. The chi-square test was used to analyse the association between vertebral osteophytes and deformities, and the influence of several risk factors was investigated by discriminate analysis. RESULTS: The prevalence of vertebral osteophytosis was 47.9% in men (36.5% in the thoracic and 21.3% in the lumbar spine) and 56.0% in women (36.0% in the thoracic and 23.9% in the lumbar spine). The prevalence of vertebral deformities was 8.3% in men (5.3% in the thoracic and 3.4% in the lumbar spine) and 12.5% in women (7.9% in the thoracic and 5.4% in the lumbar segment). There was a significant association between deformities and osteophytosis on the lumbar segment of the spine (P = 0.0240 men, P = 0.0152 women). Analysing the influence of several risk factors, age was found to be the most associated with both vertebral deformities and osteophytosis. Obesity was significantly associated with osteophytosis. CONCLUSIONS: We found a significant association between vertebral osteophytosis and deformities in the lumbar segment and no relationship in the thoracic segment. This implicates different etiologies of vertebral deformities in the thoracic and lumbar spine.

Age Distribution↗

Genotyping of CYP2D6 in Parkinson's disease.

Parkinson's disease is characterized by progressive degradation of dopaminergic neurons. Cytochrome P450 CYP2D6 enzyme is one of the most investigated and highly polymorphic isoforms, which metabolizes many drugs and is also involved in the metabolism of dopamine. Using allele-specific multiplex PCR, we genotyped 186 subjects for CYP2D6 *3, *4, *6, *7, and *8 alleles in order to estimate allelic, genotype and predicted phenotype frequencies in the control and patient groups, and to investigate the possible statistical difference between Parkinson's disease patients (n=41) and healthy controls (n=145). Parkinson's disease patients were further divided into two subgroups according to Hoehn and Yahr staging of the disease (HY), i.e. groups with HY stage less than 2.5 (HY <2.5; n=27) and more than 2.5 (HY >2.5; n=14). A subgroup of Parkinson's disease patients exhibiting side effects such as "on-off" phenomenon and dyskinesia (both suggesting favorable response to therapy) were compared with a subgroup of patients showing no such response. The preliminary results of this study showed that only the prevalence of CYP2D6 *4 allele differed significantly between the PD patients and control group (20.7% vs. 11.0%; p=0.027; RR=2.1, 95%CI 1.113-3.994). In the HY >2.5 subgroup, the CYP2D6*4 allelic difference was even greater (25.0% vs. 11.0% in controls; p=0.062, RR=2.69, 95%CI 1.090-6.624). Genotype frequencies differed only in the HY >2.5 subgroup, however with a level of significance of p=0.095.

Adult↗

Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

Adenoma↗

[The diabetic foot. The Croatian model--national consensus (clinical recommendations for diagnosis, prevention and therapy)].

Diabetic foot occurs due to the loss of protective sense and circulation disorder and a marked proneness to infections. Mechanical stress of bone growths frequently leads to ulcerations. The prevention and timely treatment of diabetic foot requires the participation of both patients and all health care levels. This consensus is given for the purpose of procedure standardization. Education is the basis of prevention and should be carried out with every patient suffering from diabetes mellitus and those with a sensory defect in particular. Appropriate footwear significantly contributes to prevention and treatment of ulcers. As regards the treatment, the necessity of surgical approach with a long term and often manifold antibiotic therapy should be pointed out. Infections are usually mixed. The deeper the ulceration, the more likely the infection with anaerobes and Gram-negative bacteria occurs in addition to Gram-positive ones which are normally present in surface lesions. Strict metabolic control is a precondition for successful treatment. In conclusion, diabetic foot is a major health problem which requires multidisciplinary approach with permanent patient education as its essential part, and a specific cooperation of all levels and different health care specialties.

Diabetic Foot↗

Massive osteolysis in a girl with agenesis of thyroid C cells.

A rare case of massive osteolysis affecting the pelvis of a young girl is presented. The clinical, radiographic, and histopathological features are described in detail. Septicemia complicated the clinical course and the patient eventually died. Histopathological examination of the pelvic lesion revealed massive osteolysis characterized by prominent osteoclastic activity with extensive bone resorption. A thorough post-mortem histological examination of the thyroid gland showed no C cells. This is an interesting observation, since it is known that thyroid C cells are the primary source of calcitonin. Since the main biological effect of calcitonin is to inhibit osteoclastic bone resorption, there is a possibility that massive osteolysis in our case could have been related to the lack of this hormone. There is a clear need for further investigation regarding the role of thyroid C cells and calcitonin in this puzzling disease.

Bone Resorption↗

[Bone mineral density in patients on long-term therapy with levothyroxine].

The aim of the study was to determine the influence of replacement and suppressive thyroxine therapy on bone mineral density (BMD). 30 postmenopausal women; 19 on replacement therapy (dose 1.22 +/- 0.35 micrograms/kg; duration 11.4 +/- 7.2 years) and 11 on suppressive therapy (dose 1.45 +/- 0.71 micrograms/kg; duration 9.5 +/- 7.2 years). Controls were 60 healthy women matched for age and menopausal status. BMD at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter was measured by dual-energy absorptiometry. Forearm BMD at distal site was measured by single-photon absorptiometry. Mean thyroid hormone values and TSH were within normal limits, although the patients on suppressive therapy had significantly higher T3 (p < 0.05) than the patients on replacement therapy. BMD on each site was significantly lower in the replacement treated group than in controls. BMD in patients on suppressive therapy was lower, but not significantly, compared to controls. Thyroxine therapy could have an adverse effect on BMD. The magnitude of bone loss depends on the serum level of thyroid hormones and on the functional state of thyroid hormone receptor in bone tissue, as well.

Absorptiometry, Photon↗

Effects of combined treatment with etidronate, nandrolone-decanoate and calcium on bone mineral density in postmenopausal women.

The objective of this retrospective study was to see whether the effect on bone mineral density (BMD) and response to the intermittent cyclic treatment with etidronate (E) + nandrolone-decanoate (ND + calcium (Ca) (group A--combined regimen--400 mg E daily for 2 weeks, followed by 500 mg Ca daily for the next 10 weeks + 50 mg ND once a month i.m., for 3 months in every other E cycle) was of greater benefit than cyclic E + Ca treatment (group B--standard regimen--E + Ca given in the same manner as in group A) or Ca treatment alone (group C--calcium regimen--500 mg Ca daily, continuously for 1 year). Group A comprised 30, group B 27 and group C 26 postmenopausal women with spinal BMD > or = 1 standard deviation below young adult mean (T score < or = -1) without vertebral fractures. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck before (baseline values) and after one year treatment period. A similar, statistically significant increase in BMD was noted at lumbar spine in groups A and B (3.6% and 3.8%, respectively) and at femoral neck in groups A and B (1.7% and 2.5%, respectively). In group C, the bone loss at lumbar spine was prevented but no significant increase was recorded (0.3%) and at femoral neck an insignificant decrease in BMD was recorded (-0.3%). Percentages of change from baseline were significantly higher in groups A and B in respect to those in group C but there were no significant differences between groups A and B either at lumbar spine or at femoral neck. In about 30% of women from groups A and B, spinal BMD increased by more than 4.2% ("real" responders to the given therapy). A femoral BMD increase of more than 5.6% was recorded in about 13% of women from groups A and B. In group C, no such increase was recorded. In conclusion, combined intermittent cyclical regimen of E + ND + Ca has not proven to be superior to the intermittent cyclic regimen of E + Ca.

Anabolic Agents↗

Analysis of the in vitro secretory activity of human pituitary adenomas: modification of corticotropin release from adenoma tissue explant cultures by addition of a human plasma ultrafiltrate bioactive fraction.

The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Cushing's disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/l in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.

Adenoma↗

[Epidemiology, classification and clinical aspects of hyperandrogenemia].

Hyperandogenemia in women is manifested typically by clinical features that may include hirsutism, acne, central obesity, male pattern baldness, increased waist-to-hip ratio, clitoral hypertrophy and deepening of the voice. The differential diagnosis include Cushing syndrome, PCO and iatrogenic hirsutism. Complications include cardiovascular disease, intravascular disease and insulin resistance. An interdisciplinary approach to management is strongly recommended. Risk reduction strategies include correction of dyslipidemias, low-dose aspirin for primary prevention of myocardial infarction, maintenance of ideal weight, smoking cessation, use of oral contraceptives with low progestin, and postmenopausal estrogen replacement.

Diagnosis, Differential↗

[Clinical significance of testosterone and dihydrotestosterone metabolism in women].

Hyperandrogenism in women refers to both excess androgen production and clinical manifestations of androgen excess. Clinical evaluation of women with hyperandrogenism is complex. The synthesis and release of androgenic steroid in women are normal part of adrenal and ovarian steroidogenesis. One of the classic questions concerning androgenic disorders concerns the source of circulating androgens. Relative roles of adrenal and ovary vary greatly, both can be involved. The use of gonadal or adrenal steroid administration can sometimes be used to distinguish the source of androgen excess. In many cases of hyperandrogenism no laboratory diagnosis of adrenal and ovarian androgen overproduction can be made. These patients may have increased androgen sensitivity due to increased enzyme 5 alpha-reductase activity in the skin. To be active in the skin, testosterone (T) must be converted to dihydrotestosterone (DHT) by the 5 alpha-reductase. The increase in DHT production is a localized phenomenon and there is no generalized increase in enzyme activity in women with hyperandrogenism. DHT is rapidly converted to other steroid metabolites including androsteron, androstanediol and their glucuronide and sulfate conjugates. Although once thought to be specific for skin conversion of T to DTH these androgen conjugates reflect adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the most effective therapeutic modalities of cutaneous hyperandrogenism. Clinical trials are in progress to determine efficacy of finasteride for the treatment of hirsutism and androgenetic alopecia. Finasteride is the first available medication of a new class of drugs that is an competitive inhibitor of 5 alpha-reductase and therefore should be beneficial for medical treatment of cutaneous hyperandrogenism.

Androgen Antagonists↗

[National consensus on hyperandrogenemia].

Croatian Endocrine Society and Croatian Academy of Medical Sciences organized Symposium on Hyperandrogenaemia on March 22nd, 1996. Different aspects of this syndrome were discussed: epidemiology, classification and clinical features, steroid biosynthesis in the adrenal gland and ovarium, the genetics of polycystic ovarian syndrome (PCOS), clinical significance of testosterone and dihydrotestosterone metabolism, androgen excess and metabolic syndrome (syndrome X), insulin disturbances in PCOS, increased risk for development of non insulin dependent diabetes mellitus, androgen effects on serum lipoproteins, insulin like growth factors and function of ovarium, Doppler parameters in PCOS, treatment of hyperandrogenaemia, skin changes in PCOS, tests for adrenal and ovarial function, arterial hypertension and hyperinsulinism. National Board of Hyperandrogenaemia has been elected.

Adult↗

Effects of ritanserin, a specific serotonin-S2 receptor antagonist, on the release of anterior pituitary hormones during insulin-induced hypoglycemia in normal humans.

The role of serotonin in the insulin hypoglycemia (IH) stimulated secretion of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and cortisol (F) was studied in a group of 12 normal subjects during the control period after placebo and a consecutive six-day treatment with 20 mg ritanserin (RIT) per day. RIT failed to affect the baseline levels of all the four hormones as well as the PRL response to IH (p > 0.5). The serum GH response to IH was moderately diminished after RIT, the reduction of integrated trapezoidal area under hormone curves (nAUC) being 50.7% +/- 6.9% (p < 0.005). Furthermore, RIT was found to slightly decrease the plasma ACTH response to IH, the reduction of nAUC being 36.3% +/- 2.6% (p < 0.005). Decrease in the corresponding plasma F response to IH was accompanied by 29.1% +/- 2.4% reduction of nAUC (p < 0.005). According to our results, serotonin-S2 receptors appeared to be moderately involved in IH-induced release of GH, but slightly in that of ACTH, leaving unaffected that of PRL.

Adult↗

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)

Adolescent↗

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.

Adolescent↗

Measurement of salivary insulin-like growth factor-I in acromegaly: comparison with serum insulin-like growth factor-I and growth hormone concentrations.

The aim of this study was to establish the concentration of insulin-like growth factor-I (IGF-I) in saliva of acromegalic patients, and to compare it with the basal levels of serum IGF-I and growth hormone. IGF-I was determined in extracted serum or neat saliva by a disequilibrium RIA using antibodies and iodinated ligand from Amersham and WHO 87/518 as standard. The detection limit of the assay was 0.5 microgram/l, and the intra- and interassay coefficients of variations were 7.9% and 15% respectively. Our study included 13 healthy adult individuals and 17 acromegalics. Compared with healthy adult subjects, acromegalics had significantly higher salivary IGF-I concentrations (mean +/- SEM 5.4 +/- 2.64 vs. 10.5 + -5.69 micrograms/l; p < 0.01), as well as serum IGF-I (176 +/- 42.9 vs. 520 +/- 98.8 micrograms/l; p < 0.0001) and somatotropin levels (1.2 +/- 1.02 vs. 15.4 +/- 9.89 micrograms/l; p < 0.0001). However, 47.1% patients (8 out of 17) with active acromegaly had salivary IGF-I concentrations within the normal range. Serum IGF-I and somatotropin concentrations were found to follow more closely the disease activity after adenomectomy, compared with the concentrations of salivary IGF-I. These results suggest that the IGF-I levels in serum and saliva are somatotropin-dependent. According to our results, measurement of IGF-I in saliva cannot be considered as an additional measure for evaluation of the disease activity in acromegaly, being less reliable than the determination of IGF-I and somatotropin in serum.

Acromegaly↗