Hypercoagulable state in Cushing's syndrome is reversible following remission.

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome (CS). The aim of this study was to assess the long-term effects of surgical remission from CS on serum levels of coagulation and fibrinolytic markers. DESIGN AND METHODS: Eighteen patients with active CS (16 women, 2 men; age: 38.6 ± 13.7 years) were enrolled in the study. We measured serum levels of coagulation and fibrinolytic markers during active CS and 6 months after remission. The control group comprised 18 age- and sex-matched healthy individuals. RESULTS: Six months after remission from CS, patients had lower levels of factors II (P < 0.001), V (P = 0.02), XI (P = 0.04) and XII (P < 0.001), protein C (P < 0.001), protein S (P = 0.002), antithrombin (P = 0.03), antithrombin Ag (P = 0.008), plasminogen (P = 0.03) and C1 inhibitor (P = 0.001), and aPTT was longer than at enrollment (P = 0.001). Levels of PAI-1 and factors VII, VIII and IX tended to normalize, but there were no significant differences in these parameters before and after surgery, nor were differences found in haemostatic and fibrinolytic markers between the patients in remission and control individuals, except for factor XII (P = 0.02) and protein C (P = 0.004), which were lower among patients in remission. CONCLUSION: Six months after remission from CS, patients' risk of thromboembolism is comparable to that of healthy individuals.

Health-related quality of life and fatigue in patients with adrenal incidentaloma.

The objective of the present study was to examine several dimensions of quality of life (QoL) and fatigue in patients with adrenal incidentaloma. This was a case-control study designed to analyze patient outcomes using three validated generic QoL questionnaires, EQ-5D, SF-36, and MFI-20, the results of which were compared to those obtained for age- and sex-matched controls. The study population comprised 139 consecutive patients with nonfunctioning adrenal masses (104 females, 35 males; age 59.1 ± 10.8) and 139 age- and sex-matched controls. Reduced QoL was found in patients with adrenal incidentaloma as compared to controls. Dimensions of QoL that were notably affected included mobility (P = 0.03), performance of usual activities (P = 0.002), and anxiety/depression (P = 0.04) as evaluated using the EQ-5D; physical functioning (P < 0.001), physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), social functioning (P = 0.001), and emotional role (P < 0.001) as evaluated using the SF-36; and physical fatigue (P = 0.04) as assessed using the MFI-20 questionnaire. In addition, perceived health on a visual analogue scale was also significantly lower in patients than in controls (64.8 ± 19.2 vs. 77.1 ± 15.1; P < 0.001). Patients with adrenal incidentaloma reported reduced QoL and a higher level of physical fatigue compared to age- and sex-matched controls. This subject will benefit from further studies comparing QoL outcomes of laparoscopic adrenalectomy versus no treatment in patients with adrenal incidentaloma.

[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.

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.

[Guidelines for diagnostics and treatment of arterial hypertension. Practical recommendations of the Croatian Working Group for Hypertension. Consideration on the ESH-ESC 2007 guidelines]. / Smjernice za dijagnosticiranje i lijecenje arterijske hipertenzije. Prakticne preporuke hrvatske radne skupine i osvrt na smjernice ESH/ESC 2007.

ESH/ECS guidelines for diagnostics and treatment of arterial hypertension 2007 is a basic paper for all physicians who treat hypertensive patients. Since publishing, this article has been the most cited medical paper. According to ESH/ECS guidelines some local peculiarities in each country should be considered when diagnosing and treating hypertensive patients. Practical recommendations of the Croatian working group for the diagnostics and treatment of hypertension are in agreement with ESH/ECS guidelines. However, few additional issues are added and further discussed in this paper (hypertensive crisis, treatment of hypertension in patients undergoing dialysis and in renal transplanted patients, role of family physicians, role of nurse). We believe that this paper will contribute better control of hypertension in Croatia. All medical societies and institutions that took part in writing this document, have to consider this paper as an official statement.

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.

[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%.

Screening for depression disorders in patients with chronic somatic illness.

Depression is one of the most common complications in patients with chronic somatic illnesses. Comorbidity of depression with physical illness often remains unrecognized and untreated, additionally aggravating the somatic illness itself, its treatment and prognosis. The aim of this study was to investigate the prevalence of depression in chronic somatic patients suffering from diabetes, epilepsy, asthma, chronic obstructive pulmonary disease (COPD) and hypothyroidism. Patients, who were regularly attending control examinations in neurological and internal medicine out-patient departments, were tested for the presence of depression with Beck Depression Inventory. The sample comprised 2153 chronic somatic patients aged between 18 and 80 years. Out of this total, 228 patients (10.6%) did not complete the study, (5.12%) refused to participate, and (5.5%) of the patients were technical failures. 1925 patients completed the study, and 1383 of them were not depressive. In 542 patients (28.5%) depression was confirmed, being almost twice more frequent in women, 346 (64%) vs. 196 (36%) male. Among these depressed examinees, mild depression was found in 284 (52.4%), major in 186 (34.3%) and severe in 72 (13.3%) chronic somatic patients. The majority of patients were aged over 55 yrs (49%). This population contained the largest number of depressed examinees (49.9%). The prevalence of depression with regard to subgroups shows that (25.6%) of asthma patients were depressed, as well as (26.6%) of those with COPD. These two groups did not present statistically significant differences regarding gender. The depression level of (32.2%) was found in patients with diabetes, of (29.6%) in patients with epilepsy and of (24.2%) among those with hypothyroidism. As for gender, statistically significant difference was found in the last three groups of patients (p < 0.001).

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.

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.

[Metabolic syndrome in patients with hypertension]. / Metabolicki sindrom u bolesnika s hipertenzijom.

Metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for the development of cardiovascular disease and type 2 diabetes. Together with obesity and dyslipidaemia, hypertension is one of the basic elements of the metabolic syndrome. Current guidelines do not provide specific recommendation for pharmacological management of the hypertensive patients with metabolic syndrome. Recent trials have consistently shown that therapy involving beta-blockers and diuretics may have some negative impact on metabolic and haemodynamic disorders present in metabolic syndrome. Several lines of evidence support the use of angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers as the appropriate first-line therapy and calcium channel blockers, as the second, in the patients with metabolic syndrome.

[Osteoporosis in men]. / Osteoporoza u muskaraca.

Male osteoporosis represents an important public health problem. According to NHANES III (National Health and Nutrition Examination Survey), 7% of white men aged 50 years and over have osteoporosis. One-third of all hip fractures occurred in men and prevalence of death after hip fracture is twice as high as in women. Hypogonadism, alcohol abuse and glucocorticoid excess are the most frequent causes of secondary osteoporosis in men, while in 30-50% of cases osteoporosis is idiopathic. In the article we discuss etiology, epidemiology, diagnostic procedure and treatment of osteoporosis in men.