Camurati-Engelmann disease in a family from Croatian Island: an old bone scan confirmed pattern of inheritance.

34-year old patient had history of muscular wasting, easy fatigability, pain in extremities and waddling gait since age of four. During the time, neuromuscular disease was suspected, but not confirmed. Elevated bone alkaline phosphatase as well as other bone turnover markers (osteocalcin, procollagen, telopeptide) indicated further skeletal evaluation. Symmetrical enhanced uptake on technetium methylene diphosphonate [99mTc]MPD bone scintigraphy at diaphyses of longitudinal bones and scull matched cortical thickening of long bones and sclerosis of the scull seen at radiograms. Those findings pointed to Camurati-Engelmann disease misdiagnosed for the long time. This rare genetic autosomal dominant disorder was retrospectively diagnosed in asymptomatic father too on the basis of bone scans done long time ago. Old family member scans confirmed heredity pattern of the disease.

Simultaneous analysis of mitotane and its main metabolites in human blood and urine samples by SPE-HPLC technique.

Adrenocortical carcinoma (ACC) is a rare malignancy with an incompletely understood pathogenesis and a poor prognosis. The adrenalytic activity of mitotane has made it the most important single drug in the treatment of ACC. Unfortunately, the exact mechanism of mitotane action is still unknown. It is believed that mitotane belongs to the class of drugs that require metabolic transformation by cytochrome P450 for therapeutic action; therefore determination of plasma levels of not only mitotane but also its metabolites would help in carrying out the treatment. The objective of this work was to develop and validate an SPE-HPLC method for simultaneous determination of mitotane and its metabolites in different biological fluids. The sample preparation consisted of a solid-phase extraction on a Discovery DSC(18) cartridge, while analysis of extracts was performed on a Symmetry C(18) column. The usefulness of the proposed method was confirmed by analysis of plasma, red cell and urine samples from patient chronically treated with 1.5 g of mitotane. The patient involved in this study had a high plasma concentration of mitotane and none of the investigated metabolites were found. In order to investigate whether the polymorphism of CYP2C9 and CYP2C19 enzymes could be related to the metabolism of mitotane, RT-PCR analysis was performed.

Prevalence and five-year cumulative incidence of abdominal obesity in Croatian women of childbearing age: the CroHort study.

Generalised obesity is increasing in prevalence globally, however trends in abdominal obesity are less well known. In 2003, 1,999 women of childbearing age participated in the Croatian Adult Health Survey, of whom 598 (29.9%) participated in the second cycle in 2008. For 2008, the prevalence of abdominal obesity using the International Diabetes Federation (IDF) criterion (waist circumference > or = 80 cm) was estimated at 70.3% (95% CI 61.8% to 75.7%), whereas the prevalence of abdominal obesity using the National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP III) criterion (waist circumference > or = 88 cm) was estimated at 48.6% (42.6% to 54.7%). The preceding five-year cumulative incidence was 54.3% (44.5% to 64.2%) and 35.2% (28.0% to 42.4%) using the IDF and NCEP ATP III criteria, respectively. The burden of abdominal obesity is high and rapidly increasing in Croatian women of childbearing age, the key population subgroup for obesity control.

[Croatian Society of Endocrinology guidelines for the diagnosis and treatment of acromegaly]. / Smjernice Hrvatskoga endokrinoloskog drustva za dijagnostiku i lijecenje akromegalije.

The working group of the Croatian Society of Endocrinology met in September 2011 to discuss the diagnostic and therapeutic dilemmas in patients with acromegaly. The group comprised 9 pituitary specialists including endocrinologists, neurosurgeons, and medical biochemistry specialist. After a critical analysis of published scientific papers the group has developed guidelines for the diagnosis and treatment of acromegaly.

[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.

[Vitamin D: vitamin from the past and hormone of the future]. / Vitamin D: vitamin proslosti, hormon buducnosti.

In the last decade there has been a rising recognition of potential clinical significance of the vitamin D. Vitamin D regulates about 3% of the human genome. Thus, vitamin D deficiency is common and high in various populations across the world including Croatia. In this paper vitamin D metabolism and up to date knowledge of vitamin D function in calcium metabolism, muscular function and in prevention of infection, malignancy, autoimmune and cardiovascular diseases is presented. Reasons for pandemic vitamin D deficiency and guidelines for vitamin D supplementation are given.

Health-related quality of life among patients with postmenopausal osteoporosis treated with weekly and monthly bisphosphonates.

OBJECTIVE: The present study was designed to assess the effect of monthly ibandronate on health-related quality of life (HR-QoL) in patients with postmenopausal osteoporosis previously treated with weekly bisphosphonates. METHODS: HR-QoL was assessed by Euroqol (EQ-5D) and Osteoporosis Targeted Quality of Life (OPTQoL) questionnaires. RESULTS: The EQ-5D questionnaire showed significant improvement associated with ibandronate treatment, occurring in mobility (p < 0.01), usual activity (p < 0.01), pain/discomfort (p < 0.05), and anxiety/depression (p < 0.05). In addition, ibandronate treatment considerably improved patients' perceived health on a visual analog scale (p < 0.001). For the OPTQoL questionnaire, patients reported less physical difficulty (p < 0.001), fewer adaptations in their lives (p < 0.001), and less fear (p < 0.001) with ibandronate than with weekly bisphosphonates. CONCLUSION: The study demonstrated that patients who were transferred from weekly bisphosphonates to a monthly ibandronate experienced improved HR-QoL.

[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.

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 (T(4)) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T(4) and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively. RESULTS: Hypothyroid patients had significantly higher TSH, significantly lower T(4) 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 T(4) 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.

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.

[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.

[Croatian Thyroid Society guidelines for rational detection of thyroid dysfunction]. / Smjernice hrvatskog drustva za stitnjacu za racionalnu dijagnostiku poremecaja funkcije stitnjace.

Thyroid dysfunction is common in the population, especially in women, and thyroid diagnostic tests are among the most often used diagnostic procedures nowadays. Many thyroid societies developed guidelines for the detection of thyroid dysfunction. An interdisciplinary team of experts from the Croatian Thyroid Society studied guidelines of other thyroid societies and international publications, and according to our tradition and clinical practice developed guidelines for rational detection of thyroid dysfunction; hypothyroidism and hyperthyroidism. The aim of these guidelines is to recommend evidence-based and rational approach to the detection of thyroid dysfunction.

Ibandronate: is there an effect on nonvertebral fractures?

Although ibandronate improves suboptimal compliance in patients receiving weekly bisphosphonates, there is a concern about its effect on the reduction of nonvertebral fractures. In the era of evidence-based medicine, randomized clinical trials are considered the highest quality evidence which guide us to the best clinical decision. Nevertheless, if level 1 evidence is not available, as is the case with ibandronate, evidences of lower levels could be used to draw relevant clinical decision. In this article, we discussed data from clinical trials (subgroup analyses of high-risk patients, meta-analysis of clinical trials) which suggested significant effect of ibandronate on the risk reduction of nonvertebral fractures.

Non-hip peripheral osteoporotic fractures: epidemiology and significance.

Fractures are the most serious consequence of osteoporosis. Non-vertebral and non-hip fractures are seldom recognised as important, even though they account for the majority of all fractures. The most prevalent localisations are distal radius, proximal humerus, ribs, clavicle, and the pelvis. According to the results from large phase III clinical trials for placebo groups, their incidence ranges from 4.9 % to 12.0 %. Hospital morbidity data in Croatia in 2006 show that peripheral non-hip fractures ranked among the leading fifteen injuries, accounting for 23.7 % of all injuries in patients aged 60 years and above. Risk factors for non-hip and non-vertebral fractures are similar to other osteoporotic fractures, and the main are low bone mineral density and earlier fractures. Quality of life is considerably affected by these fractures, and medical costs are very high, soaring as high as 36.9% of all national medical costs in the USA. Non-vertebral non-hip fractures need more attention, which was also recognised by the European regulatory bodies that approve use of anti-osteoporotic drugs.

[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.

Metabolic syndrome and schizophrenia from integrative medicine perspective.

BACKGROUND: There has been a growing interest in the effect that comorbid schizophrenia and metabolic syndrome may have on each other. OBJECTIVE: To examine metabolic syndrome from integrative medicine point of view including prevalence of metabolic syndrome in patients with schiziphrenia compared to their first-degree relatives, healthy volunteers without schizophrenia in close family, and patients with PTSD, as well as the percentage patients with schizophrenia without any component of metabolic syndrome. METHOD: Metabolic syndrome according to NCEP/ATP III criteria and number of its components were analysed in 205 patients with schizophrenia, 140 healthy volunteers and 105 patients with combat PTSD. RESULTS: Metabolic syndrome was identified in 45.9% of the patients with schizophrenia, 38.1% of the war veterans with PTSD, 36.7% of the first-degree relatives of patients with schizophrenia and 16.2% of the healthy volunteers without schizophrenia in close family. Only 21.5% of the patients with schizophrenia were without any metabolic syndrome component. CONCLUSION: The comorbidity of schizophrenia and metabolic syndrome is very important for theory and practice of integrative medicine. Almost 80% of the patients with schizophrenia have increased risk or developed cardiovascular disorders,.

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.

High prevalence rate of pituitary incidentaloma: is it associated with the age-related decline of the sex hormones levels?

Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of pituitary incidentaloma, and finally, is there any correlation between pituitary tumours incidence and serum concentrations of LH, FSH, bioavailable testosterone or estradiol.

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.

[Epidemiology of osteoporosis]. / Epidemiologija osteoporoze.

In many countries, including Croatia, there is no disease registry for osteoporosis and osteoporotic fractures. Epidemiological data show that the prevalence of osteoporosis is much higher in Asian people than in white European or North American populations, where the prevalence ranges between 10% and 15%. Epidemiological characteristics of osteoporosis in Croatia are similar to other European countries, though the incidence of osteoporotic fractures is somewhat higher. According to the annual report of registered diseases, the number of patients with osteoporosis and osteoporotic fractures increased during the last 10 years. In 2004, 0.70 % of all registered diseases in Croatia referred to osteoporosis and osteomalacia. The most important risk factors for osteoporosis are age, heredity, lifestyle, chronic diseases, hormonal abnormalities and physical characteristics of bone. Like in other chronic diseases, prevention measures are most important for disease control.