[Fatty tissue and bone]. / Masno tkivo i kost.

Obesity is one of leading public health issues. Along with genetic predisposition it is the main risk factor for osteoarthritis and it also has an influence on rheumatoid arthritis. Fatty tissue acts on arthritic joints through a biomechanical and humoral mechanisms. The humoral mechanism is complex and the role of adipokines in the pathogenesis of arthritis is still not entirely clear. It is assumed that no adipokine can cause joint damage on its own, but only a dysfunction in a relationship between leptine and other adipokines can cause inflammatory-destructive processes. It remains unclear whether the involvement of adipokines is primary or secondary in the process ofjoint inflammation. The relative influence of visceral fatty tissue adipokines as compared to that of locally synthesised adipokines from various joint structures is unclear. Adipokines have a predominantly pro-inflammatory action and destroy the cartilage, although they can also have a protective action. A better knowledge of the role adipokines play not only allows for a better knowledge of pathophysiological processes in osteoarthritis and rheumatoid arthritis, but it also opens possibilities for development of new therapies.

[Visceral obesity]. / Visceralna debljina.

Some studies indicate that visceral obesity may be a better predictor of morbidity and mortality related to cardiovascular diseases and type 2 diabetes than general obesity measured by the body mass index. A causal relationship seems to exist between the accumulation of visceral fat and occurence of cardiovascular diseases and type 2 diabetes. Assessment of cardiometabolic risk comprises information on intra-abdominal obesity, as well as traditional risk factors. Visceral fat acts as a large endocrine gland, excreting cytokines and adipokines which leads to insulin resistance and proinflammatory state, whereas subcutaneous fat may act as a protective metabolic sink. Of anthropometric measures, waist circumference seems to best correlate with visceral fat.

[Influence of obesity on fracture risk in osteoporosis]. / Utjecaj debljine na rizik od osteoporotskih prijeloma.

The skeleton is part of the locomotor system which has a static and a dynamic biomechanical function. Bone mass, bone shape and bone structure influence these skeleton functions and also determine bone strength, an important determinant of fracture risk. They are mostly genetically determined and linked with body shape, structure and weight. This relationship is also genetically determined. Changes in body weight, structure and shape through biomechanical and humoral mechanisms cause changes in the bone mass, shape and structure. These processes also lead to changes in neuromuscular system to occur which influence the risk of fall and bone strength. As long as the changes in body weight and body structure are within the physiological range, the fracture risk does not change significantly. Low body weight increases the risk of fracture. In obesity pathophysiological processes develop, some of which could negatively influence the fracture risk. The results of studying the influence of obesity on fracture risk have been contradictory. Based on the current knowledge, we may conclude that obesity probably does not protect from fracture.

[4th guidelines on diagnosis and treatment of obesity]. / 4. Smjernice o dijagnostici i lijecenju debljine.

Obesity is one of the leading public health problems in today's world. The situation is not significantly better in our country. The Republic of Croatia is among the countries with highest prevalence of obesity in the world. All attempts to stop the progression of obesity pandemic have not given satisfactory results up to date. On the other hand, the treatment of obesity is a long-term, exhausting and very complicated process with modest results. From 15th to 18th April 2010 the 4th Croatian Congress on Obesity with international participation was held in Umag with the aim of furthering knowledge about epidemiology, etiopathogenesis, complications and obesity treatment and to provide doctors who treat obesity with opportunity to share insights and experience. The Congress was attended by 200 doctors. At the Congress the Guidelines on Obesity Diagnostics and Treatment were adopted, which will provide practical help to doctors treating patients with obesity.

[Management of adrenal incidentaloma: the position statement of the Croatian referral center for adrenal gland disorders]. / Dijagnostika i lijecenje incidentaloma nadbubrezne zlijezde: preporuke referentnog centra ministarstva zdravstva za bolesti nadbubrezne zlijezde.

Adrenal incidentalomas are tumours of adrenal glands discovered during diagnostic workup for other clinical condition unrelated to adrenal glands. Improvement in imaging techniques and their widespread use in everyday practice have increased detection of adrenal incidentalomas making their management one of the most important challenges of modern endocrinology. Based on the relevant medical literature and guidelines of other international societies a panel of Croatian leading experts in adrenal gland disorders provide practical recommendations for the diagnostics and treatment of adrenal incidentaloma.

[Obesity as a medical and public health problem]. / Debljina, medicinski i javnozdravstveni problem.

Obesity is one of the leading public health problems. Fat tissue is an organ with intensive metabolic activity whose function is to store unused energy. At the same time, it is a gland with internal secretion which secretes cytokines (adipokines) which have an endocrine, paracrine and autocrine function. Receptors for numerous hormones and cytokines are found on adipocytes. In such a way a functional connection between fat tissue and other tissues and organs is ensured. Fat tissue is part of a system of neuroendocrine regulation of body mass and metabolism. An increase in fat tissue, especially in visceral fat tissue, leads to an increase in adipokine blood concentration, which results in changes in the functioning of distant tissues and organs with which fat tissue is hormonally linked. The consequent comprehensive changes in the metabolism are termed metabolic syndrome, and are linked with further complications. The consequences of these complications are a diminished quality of life and a rise in mortality. The treatment of obesity is a long term and often unsuccessful process. Better results of treatment are achieved by a multidisciplinary approach.

[Comment on Croatian National Consensus on Diagnosis and Treatment of Obesity]. / Osvrt na Nacionalni konsenzus o dijagnostici i lijecenju debljine.

Obesity is a chronic endocrine-metabolic disease with a multifactorial etiology and a polygenetic basis, whose complex patophysiologic mechanism causes numerous complications. Fat tissue is a gland which "communicates" intensively with the whole organism. It secretes adipokines which have an endocrine, paracrine and autocrine function. In obesity, adipokine synthesis, secretion into the blood and effect on the target tissues and organs is impaired, leading to development of complications in all organic systems. Pandemic levels of obesity and overweight are such that both in developed and developing countries only a small part of the population has normal body weight. In Croatia every fifth adult is obese, and overall 2/3 of men and little more than 1/2 of women have body weight greater than normal. Mortality rises with BMI >25 kg/m2 and in obese persons it is 1.5-2 times greater, while in persons with morbid obesity (BMI >40 kg/m2) the life expectancy is 5-15 years shorter. Treatment of obesity is a long-term endeavor and requires the participation of physicians of various specialties. The Croatian Obesity Society held the 3d Croatian Congress on Obesity with international participation in Opatija from 4-6 April. The main topics of discussion were obesity epidemiology and diagnostics, patophysiologic mechanisms, complications, mortality and disease treatment. The National Programe for Countering the Obesity Epidemic was presented. At the end of the Congress the 3d National Consensus on Diagnostics and Treatment of Obesity was adopted. It incorporated some changes compared to the previous 2006 Consensus. The new obesity treatment guidelines take individual needs and capabilities more into account, with the aim of increasing the success of the treatment.

Bone properties in patients with acromegaly: quantitative ultrasound of the heel.

Growth hormone (GH) deficiency and acromegaly serve as good models for investigating the effects of GH on bone remodeling. However, the results from various studies are rather conflicting. The aim of our study was to estimate the potential role of gender, disease activity, and duration on both calcaneus quantitative ultrasound (QUS) parameters and bone turnover markers in patients with acromegaly. Thirty-six acromegalic patients (17 men, 19 women) and 3 age- and gender-adjusted controls for every patient were included in the study. The disease was active in 22 patients, and was considered cured in 14 of them. In each subject, QUS of the heel and parameters of bone turnover (bone alkaline phosphatase, beta-crosslaps, and osteocalcin) were measured. The results demonstrated lower QUS values in acromegalic patients compared with the controls. When stratified by gender, the differences in QUS parameters were significant in men, but not in women. Male patients with active disease had significantly lower QUS values than those in remission. Such differences were not observed among women. Multiple regression model indicated strong association between disease activity and the QUS parameters. The group of patients with active disease had a higher level of serum beta-crosslaps, whereas osteocalcin concentration was significantly increased only in male patients with active disease. The results of our study suggest significantly lower QUS values and increased bone turnover in male patients with active acromegaly. The disease activity is the strongest predictor of the QUS parameters in acromegalic patients.

The effects of the level of physical activity on calcaneal ultrasound measurements: bone properties of medical and physical education students.

The aim of the study was to compare bone properties of two groups of students which strongly differ in the level of their everyday physical activity; the School of Medicine (SM) students and the Faculty of Physical Education (FPE) students, University of Zagreb. Quantitative ultrasound parameters--broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured. Quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were calculated by the device software. The final study sample consisted of 165 students from SM (94 males and 71 females) and 215 students from the FPE (164 males, 51 females). Sixty eight percent of FPE students and 21% of SM students reported a high level of everyday physical activity (P < 0.001). All ultrasound parameters were significantly higher in FPE students than in SM students (at the P < 0.001 level). The multiple regression model of the QUI confirmed that the school students attended was the single significant predictor variable for both genders. Our data indirectly showed the beneficial role of physical activity on bone properties.

[Croatian National Consensus on diagnosis and treatment of obesity]. / Hrvatski nacionalni konsenzus o dijagnostici i lijecenju debljine.

Obesity is one of the leading public health problems. Over half of women and two thirds of men in Croatia are either overweight or obese, and about one fifth is overweight. Especially worrying is the rising prevalence of obesity in children and adolescents. Obesity is a chronic disease characterised by metabolic and endocrine disorders, resulting in serious chronic complications. The Croatia Obesity Society was founded in 2002 under the umbrella of the Croatian Medical Association and has so far organised two national congresses on obesity. At each congress a national consensus on diagnosing and treating obesity was adopted. Taking into account that treating obesity only with recommendations about dieaty modification and increased physical activity has not given satisfactory results, the 2006 Congress Consesus recommends an earlier start of pharmacologic therapy and surgical treatment of obesity compared to 2003 Congress Consensus. We expect that the new recommendations will improve diagnostics and treatment of obesity in Croatia.

[Osteoporosis prevalence in Croatian males--the results of calcaneus ultrasound]. / Ucestalost osteoporoze u muskaraca u hrvatskoj--rezultati ultrazvucne denzitometrije petne kosti.

The aim of the study was to establish the normative QUS data in a healthy sample of Croatian males and estimate the prevalence of osteoporosis. A total of 1002 male participants, aged 20-99, were recruited in seven study centers (Zagreb, Ivanic-grad, Koprivnica, Sibenik, Pula, Slavonski Brod, Vukovar). In each subject broadband ultrasound attenuation (BUA), speed of sound (SOS) and quantitative ultrasound index (QUI) of the calcaneus were measured using the Sahara ultrasound device. Significant declining with age was found for all three parameters (p < 0.001). The peak SOS (1562.8 +/- 28.5 m/s) 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 of life. Using the World Health Organization diagnostic criteria for DXA the rates of osteoporosis in the males aged 50 and older were 5.8%, 3.4 and 4.2% for QUI, BUA, and SOS respectively. However, when we used the cut-off value of the T < or = -l.8, prevalence of osteoporosis in Croatian males older than 50 years was 16.2%, 11.7% and 17.2%.

Higher prevalence of FTO gene risk genotypes AA rs9939609, CC rs1421085, and GG rs17817449 and saliva containing Staphylococcus aureus in obese women in Croatia.

Obesity is composed of multifunctional interactions of eating habits, behaviors, microbiota, genetics, and other unknown factors. We hypothesize that correlations occur between the fat mass and obesity-associated single nucleotide polymorphisms (FTO SNPs), the composition of microorganisms in the saliva, and life habits in obese women from Zagreb County. Our results of the analysis of 3 FTO SNPs showed a statistically significant positive correlation among the frequencies of the high-risk genotypes AA rs9939609 (P = .0367), CC rs1421085 (P = .0367), and GG rs17817449 (P = .0065) of the FTO gene in obese cases. Interestingly, 39.13% of obese women were triple homozygous for all 3 risk alleles. Furthermore, the composition of the oral microbiota in the obese group showed a higher occurrence of a major human pathogen, bacterium Staphylococcus aureus, but a significantly low presence of bacteria Streptococcus oralis, Streptococcus mitis, and Serratia ureilytica compared with the control group. The investigation also revealed that obese women prefer to consume candy and snacks and more meat and meat-derived products, sleep less than 6 hours per day, and had higher hypertension in comparison with the control group. These results support the hypothesis that female obesity is strongly related to all 3 variants of the FTO gene and perhaps a specific composition of microbiota in saliva due to dietary habits. Considering the bimodal distribution of the SNPs and bacterial content of saliva in obese women taken together are factors to consider for risk of obesity.

Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers.

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome.

Severe postoperative hypoglycemia in a patient with pheochromocytoma and preclinical Cushing's syndrome.

BACKGROUND: Postoperative hypoglycemia is not a common complication following the removal of a pheochromocytoma. Although the mechanism of hypoglycemia is not fully understood, it seems that it is caused by excessive rebound secretion of insulin after surgical resection of pheochromocytoma. CASE REPORT: We report a 43-year-old woman with a very rare association of pheochromocytoma and preclinical Cushing's syndrome (PCS) in the same adrenal gland who developed severe postoperative hypoglycemia. Pheochromocytoma was diagnosed by high serum and urine metanephrine and normetanephrine levels. PCS was characterized by blunted cortisol diurnal rhythm, low ACTH level, and failure of cortisol suppression by dexamethasone without any clinical signs of cortisol excess. In the early postoperative period after surgical removal of right adrenal gland, the patient lapsed into a stuporous state. The blood glucose level was 0.7 mmol/l. During the next 48 hours, normoglycemia was maintained with a continuous infusion of 20% glucose. On the third postoperative day, infusion was discontinued, oral feeds were introduced, and the plasma glucose level normalized. The patient did not have further episodes of hypoglycemia. Pathology revealed medullary pheochromocytoma and a cortical tumor of right adrenal gland. During the fifth postoperative day, plasma metanephrine and normetanephrine were 0.13 nmol/l and 0.30 nmol/l, respectively. Urinary metanephrine decreased to 0.5 pmol/24 h and normetanephrine to 2.8 micromol/24 h. CONCLUSIONS: This report indicates the importance of close monitoring of blood glucose level in a patient with pheochromocytoma after removal of an adrenal gland.