Darko Kaštelan

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

Hypercoagulability is a commonly described complication in patients with Cushings 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.

Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN.

OBJECTIVEnTo evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushings syndrome (ERCUSYN), and to examine if their use differs from the current guidelines.nnnPATIENTS AND METHODSnWe analyzed data on the diagnostic tests performed in 1341 patients with Cushings syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS).nnnRESULTSnOf the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1u2009mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (Pu2009<u20090.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (Pu2009<u20090.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2u2009mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1u2009mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (Pu2009<u20090.05).nnnCONCLUSIONSnUse of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.

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 59.1xa0±xa010.8) 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 (Pxa0=xa00.03), performance of usual activities (Pxa0=xa00.002), and anxiety/depression (Pxa0=xa00.04) as evaluated using the EQ-5D; physical functioning (Pxa0<xa00.001), physical role (Pxa0<xa00.001), general health (Pxa0<xa00.001), vitality (Pxa0=xa00.001), social functioning (Pxa0=xa00.001), and emotional role (Pxa0<xa00.001) as evaluated using the SF-36; and physical fatigue (Pxa0=xa00.04) 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 (64.8xa0±xa019.2 vs. 77.1xa0±xa015.1; Pxa0<xa00.001). 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.

Advanced Age, High β-CTX Levels, and Impaired Renal Function are Independent Risk Factors for All-Cause One-Year Mortality in Hip Fracture Patients.

Risk factors for increased mortality in hip fracture patients include older age, male sex, fracture type, bone mineral density, and pre-existing co-morbidities. The role of biochemical and other anthropometric parameters on hip fracture mortality remains unclear. The aim of this study was to identify the risk factors for one-year mortality in patients with hip fractures. A total of 236 consecutive patients (59 males) with hip fractures were followed over a one-year period. Patient age, gender, type of fracture, type of treatment, time from admission to surgery, type of anesthesia, body mass index, and electrocardiograms were recorded. Complete blood counts, serum electrolytes, urea, creatinine, d-dimers, calcium, phosphate, osteocalcin, and beta-isomerised C-terminal telopeptide of collagen type I (β-CTX) were measured at admission and estimated glomerular filtration rate (eGFR) was calculated. Multivariate Cox regression models were used to analyze the association of these parameters with survival. One-year mortality rate was 28.4xa0%. Age was independently associated with mortality (HR 1.117, 95xa0% CI 1.062–1.174, Pxa0<xa00.001). In a multivariable model, mortality was increased in patients withxa0higher β-CTX (HR 4.63 95xa0% CI 1.87–11.45, Pxa0=xa00.001) and lower eGFR (HR 0.972, 95xa0% CI 0.956–0.987, Pxa0<xa00.001). Patients younger than 84xa0years, with eGFRxa0<xa055.4xa0ml/min had ten times higher mortality rates (3.2 vs. 24.5xa0%, HR 9.73, 95xa0% CI 2.06–45.93) as well as those with β-CTXxa0>xa00.276xa0g/L (3.5 vs. 25.7xa0%, HR 9.5, 95xa0% CI 2.11–42.76). Advanced age, high β-CTX levels, and impaired renal function are independent risk factors of mortality in patients with hip fractures.

New hopes in the treatment of osteoporosis in men

Darko Kastelan† & Mirko Korsic †Author for correspondence Medical University of Zagreb, Department of Endocrinology, University Hospital Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia Tel.: +385 12 421 867; Fax: +385 12 421 867; dkastelan@inet.hr ‘Recent discoveries of several new extracellular molecules have advanced our knowledge of osteoblast–osteoclast interaction and make them a promising target for developing new agents for managing osteoporosis.’

Epidemiology of Osteoporosis

Epidemiologija Osteoporoze U većini zemalja u svijetu, pa tako i u Hrvatskoj ne postoji jedinstveni sustav registriranja oboljelih od osteoporoze, kao ni osoba s osteoporotskim prijelomima. Podatci iz epidemioloških istraživanja pokazuju da je učestalost osteoporoze veća u azijskim zemljama u odnosu na europsko i sjevernoameričko stanovništvo bijele rase, u kojih prevalencija iznosi 10% do 15%. U Hrvatskoj je učestalost slična onoj u drugim europskim zemljama, dok je incidencija osteoporotskih prijeloma nešto veća od europskog prosjeka. Također je broj prijavljenih slučajeva osteoporoze i osteomalacije od primarne zdravstvene zaštite zadnjih 10 godina u stalnom porastu i u 2004. godini je iznosio 0,70% u odnosu na ukupan broj prijavljenih bolesti. Najvažniji rizični čimbenici bolesti su dob, naslijeđe, životne navike, postojanje kroničnih bolesti i hormonskih poremećaja te individualna fizikalna obilježja kosti. Kao u većine kroničnih bolesti, mjerama prevencije može se pravodobno spriječiti nastanak bolesti i njezinih komplikacija. Epidemiology of Osteoporosis 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.

Preoperative medical treatment in Cushing’s syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN

BACKGROUNDnSurgery is the definitive treatment of Cushings syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial.nnnOBJECTIVEn(1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS).nnnPATIENTS AND METHODSn1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS).nnnRESULTSnTwenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (Pu2009<u20090.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (Pu2009<u20090.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (Pu2009<u20090.01) and a lower remission rate (Pu2009<u20090.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups.nnnCONCLUSIONSnPMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results.

Hypopituitarism after gamma knife radiosurgery for pituitary adenoma

ABSTRACT Purpose: The aim of the study was to investigate the incidence of and risk factors for hypopituitarism after gamma knife radiosurgery (GKRS) for pituitary adenoma. Materials and Methods: We conducted a retrospective analysis of the pituitary function of 90 patients who underwent GKRS for pituitary adenoma at the University Hospital Centre Zagreb between 2003 and 2014. Twenty seven of them met the inclusion criteria and the others were excluded from the study due to pituitary insufficiency which was present before GKRS. Eighteen patients had non-functioning and 9 patients had secretory adenomas. Median patients’ age was 56 years (24–82). GKRS was performed using the Leksell gamma knife Model C. The median prescription radiation dose was 20 Gy (15–25) and the median tumor volume size was 3.4 cm3 (0.06–16.81). New onset hypopituitarism was defined as a new deficit of one of the three hormonal axes (corticotroph, thyreotroph, or gonadotroph) ≥3 months following GKRS. SPSS was used for statistical analysis, with the significance level at P<0.05. Results: During the median follow-up period of 72 months (range 6–144), 30% of patients developed new hypopituitarism after GKRS. This corresponds to incidence of one new case of hypopituitarism per 15 patient-years. Age, gender, tumor function, tumor volume, suprasellar extension, prescription dose of radiation, as well as dose-volume to the pituitary gland, stalk and hypothalamus were not predictive factors for the development of hypopituitarism. Conclusions: In our cohort of patients with pituitary tumors who underwent GKRS, 30% developed new hypopituitarism during the follow-up period.

Management of adrenal incidentaloma

The term adrenal incidentaloma covers a wide spectrum of adrenal pathologies sharing the method of discovery. The management of adrenal incidentaloma is controversial, and clinicians should determine whether the patient’s health is affected by the presence of a tumor. Critical points in management include differentiating benign from malignant and hormonally active from nonfunctional adrenal masses. The probability of malignancy is related to tumor size and imaging phenotype. Masses smaller than 4 cm in diameter that exhibit low attenuation by unenhanced CT scan and rapid contrast washout by delayed contrast-enhanced CT scan are probably benign. All patients with adrenal incidentaloma should undergo biochemical evaluations for pheochromocytoma and subclinical or overt Cushing’s syndrome, and hypertensive patients should undergo biochemical testing for hyperaldosteronism. Laparoscopic adrenalectomy is the treatment of choice in all hypersecretory tumors. If adrenocortical carcinoma is suspected, an open adrenalectomy is recommended. Patients who are not candidates for surgical resection of the tumor should be monitored radiographically for 2 years, and hormonal follow-up should be performed annually for 4 years.