Gordon Holmesov sindrom prvi put dijagnosticiran u Hrvatskoj

Prikazuje se 38-godišnja bolesnica koja se klinički prezentirala ataksijom, kognitivnom disfunkcijom i sekundarnom amenorejom, s izraženim hiperintenzivnim promjenama na magnetskoj rezonanciji mozga (MR). Klinički simptomi počeli su u dobi od 20 godina razvojem sekundarne amenoreje, nestabilnosti u hodu i kognitivnom disfunkcijom. Iako je ovakav skup povezanih simptoma ataksije, primarne/sekundarne amenoreje uslijed hipogonadotropnog hipogonadizma i kognitivne disfunkcije poznat kao Gordon Holmesov sindrom (GHS), takav do sada nije opisan u Hrvatskoj. Zbog navedenog, dotadašnja klinička dijagnostika u različitim neurološkim institucijama koja je bila u početku usmjerena primarno na ataksiju, kognitivni poremećaj te nalaz hiperintenzivnih promjena na MR-u mozga, zanemarujući sekundarnu amenoreju, bila je neuspješna. Analizom velike grupe autosomno-recesivnih cerebelarnih ataksija naša grupa uočila je podudarnost skupa kliničkih simptoma: cerebelarne ataksije, kognitivne disfunkcije i hipogonadotropnog hipogonadizma, uz karakterističan MR nalaz specifičnih subkortikalnih hiperintenzivnih promjena bijele tvari, talamusa i moždanog debla i cerebelarne atrofije, koji čine sindrom uzrokovan mutacijom gena ATM RNF216, Gordon Holmesov sindrom. Sekvencijska genomska analiza učinjena u Variantyx laboratoriju u SAD-u pokazala je u naše bolesnice složenu heterozigotnu mutaciju RNF216 što je potvrdilo dijagnozu GHS-a, prvi put dijagnosticiranog u Hrvatskoj

Glucagon-Like Peptide-1 Receptor Agonists and Dual Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity/Metabolic Syndrome, Prediabetes/Diabetes and Non-Alcoholic Fatty Liver Disease-Current Evidence

The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the "cardiometabolic continuum " and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm

Management of patients with adrenal incidentaloma – 2019 update

Zadnjih desetak godina došlo je do značajnih promjena u zdravstvenom zbrinjavanju bolesnika s incidentalomima nadbubrežne žlijezde koje su rezultirale novim preporukama za dijagnostiku i liječenje ovih bolesnika napravljenim u suradnji Europskoga endokrinološkog društva i Europske mreže za istraživanje tumora nadbubrežne žlijezde. Na temelju navedenih preporuka i višegodišnjega vlastitog iskustva Referentni centar Ministarstva zdravstva Republike Hrvatske za bolesti nadbubrežne žlijezde predlaže izmjene i dopune preporuka za dijagnostiku i liječenje ovih bolesnika objavljenih u Liječničkom vjesniku 2010. godine.In the last decade, the clinical care of patients with adrenal incidentaloma has been significantly changed which prompted the European Society of Endocrinology and European Network for the Study of Adrenal Tumors to develop an updated clinical practice guideline for the management of these patients. In accordance with the aforementioned recommendations and based on its own experience, the Croatian Referral Center for adrenal gland disorders provides an update of the previous guideline for the clinical management of patients with adrenal incidentaloma published in Liječnički vjesnik in 2010

PRECIPITATING FACTORS AND CLINICAL FEATURES OF DIABETIC KETOACIDOSIS

vod: Dijabetička ketoacidoza (DKA) jedna je od najozbiljnijih akutnih komplikacija šećerne bolesti (ŠB). Pojedina istraživanja su pokazala da su infekcije precipitirajući čimbenik u polovice ispitanika. Nekoliko novijih istraživanja naglašava da je loše pridržavanje liječenja također česti uzrok DKA. Cilj: Identifi cirati najčešće precipitirajuće čimbenike za DKA u Republici Hrvatskoj. Ispitanici i postupci: Ovo retrospektivno multicentrično istraživanje uključivalo je bolesnike sa ŠB-om tipa 1 ili tipa 2 s dijagnozom DKA između 1. siječnja 2014. i 31. prosinca 2018. i liječenih u 5 različitih središta za liječenje ŠB-a: Dubrovnik, Našice, Split, Zagreb i Osijek. U analizu je uključena samo prve epizoda DKA. Pacijenti koji boluju od steroidnog ŠB-a i ŠB-a zbog endokrinih poremećaja kao što su akromegalija i Cushingov sindrom bili su isključeni. Rezultati: Istraživanjem je obuhvaćeno 160 bolesnika (55 % muškaraca), od kojih je 68% imalo ŠB tip 1. Srednja dob ispitanika bila je 42 godine (od 18 do 89). Najčešći uzrok DKA bila je infekcija (57 %), zatim slabo kontrolirani ŠB (37 %) i prva prezentacija ŠB-a (9 %), dok je u 7% bolesnika DKA bila uzrokovana ostalim uzrocima kao što su kvar inzulinske pumpe, moždani ili srčani udar. U skupini bolesnika s infekcijama najčešće su bile infekcije mokraćnog sustava (30 %), probavne infekcije (30 %) i infekcije respiratornog trakta (19 %), dok je 21 % bolesnika imalo druge izvore infekcije. U 36 ovih bolesnika uz infekciju je bio prisutan i prethodno loše kontroliran ŠB, a u 12 % DKA uzrokovana infekcijom bila je prvo očitovanje bolesti. U bolesnika sa ŠB-om tipa 2 infekcije su češće bile uzrok DKA nego u bolesnika sa ŠB-om tipa 1 (P < 0,05). U bolesnika sa ŠB-om tipa 1, slabo regulirana glikemija je češće uzrok DKA (31%) nego u bolesnika sa ŠB-om tipa 2 (18 %). Zaključak: Najčešći precipitirajući čimbenici za razvoj DKA su infekcije i loša regulacija ŠB-a. Potrebna je bolja edukacija bolesnika o važnosti redovite primjene inzulina i korekcije terapije tijekom akutne bolesti.Introduction: Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus (DM). In some studies, infections have been found to be a precipitating factor in more than half of the subjects. On the other hand, several recent studies emphasize that poor treatment adherence is also a common cause of DKA. Objective: To identify the most common precipitating factors for DKA in Croatia. Patients and Methods: This retrospective, multicenter study included DM type 1 or DM type 2 patients diagnosed with DKA between January 1, 2014 and December 31, 2018, and treated in 5 different DM treatment centers, i.e., Dubrovnik, Našice, Split, Zagreb and Osijek. Only the fi rst episode of DKA was included in the analysis. Patients receiving steroids and DM due to endocrine disorders such as acromegaly and Cushing\u27s syndrome were excluded. Results: The study included 160 patients (55% of men), of whom 68% had DM type 1. The mean age of the respondents was 42 (18-89) years. The most common cause of DKA was infection (57%), followed by poorly controlled DM (37%) and fi rst presentation of DM (9%), while in 7% of patients DKA was due to other causes such as insulin pump failure, stroke or myocardial infarction. In the group of patients with infections, urinary tract infections (30%), gastrointestinal infections (30%) and respiratory tract infections (19%) were most common, whereas 21% of patients had other sources of infection. In 36% of these patients, the infection was associated with previously poorly controlled diabetes, and in 12% of them, DKA caused by the infection was the fi rst manifestation of the disease. In patients with type 2DM, infections were more often the cause of DKA than in patients with type 1DM (p<0.05).Poorly controlled glycemia appeared to be a more frequent cause of DKA in patients with type 1 DM (31%) than in patients with type 2 DM (18%). Conclusion: The most common precipitating factors for the development of DKA were infections and poor diabetes management. Better education of patients about the importance of regular insulin administration and correction of therapy in acute illness could reduce the risk of DKA

PRECIPITATING FACTORS AND CLINICAL FEATURES OF DIABETIC KETOACIDOSIS

vod: Dijabetička ketoacidoza (DKA) jedna je od najozbiljnijih akutnih komplikacija šećerne bolesti (ŠB). Pojedina istraživanja su pokazala da su infekcije precipitirajući čimbenik u polovice ispitanika. Nekoliko novijih istraživanja naglašava da je loše pridržavanje liječenja također česti uzrok DKA. Cilj: Identifi cirati najčešće precipitirajuće čimbenike za DKA u Republici Hrvatskoj. Ispitanici i postupci: Ovo retrospektivno multicentrično istraživanje uključivalo je bolesnike sa ŠB-om tipa 1 ili tipa 2 s dijagnozom DKA između 1. siječnja 2014. i 31. prosinca 2018. i liječenih u 5 različitih središta za liječenje ŠB-a: Dubrovnik, Našice, Split, Zagreb i Osijek. U analizu je uključena samo prve epizoda DKA. Pacijenti koji boluju od steroidnog ŠB-a i ŠB-a zbog endokrinih poremećaja kao što su akromegalija i Cushingov sindrom bili su isključeni. Rezultati: Istraživanjem je obuhvaćeno 160 bolesnika (55 % muškaraca), od kojih je 68% imalo ŠB tip 1. Srednja dob ispitanika bila je 42 godine (od 18 do 89). Najčešći uzrok DKA bila je infekcija (57 %), zatim slabo kontrolirani ŠB (37 %) i prva prezentacija ŠB-a (9 %), dok je u 7% bolesnika DKA bila uzrokovana ostalim uzrocima kao što su kvar inzulinske pumpe, moždani ili srčani udar. U skupini bolesnika s infekcijama najčešće su bile infekcije mokraćnog sustava (30 %), probavne infekcije (30 %) i infekcije respiratornog trakta (19 %), dok je 21 % bolesnika imalo druge izvore infekcije. U 36 ovih bolesnika uz infekciju je bio prisutan i prethodno loše kontroliran ŠB, a u 12 % DKA uzrokovana infekcijom bila je prvo očitovanje bolesti. U bolesnika sa ŠB-om tipa 2 infekcije su češće bile uzrok DKA nego u bolesnika sa ŠB-om tipa 1 (P < 0,05). U bolesnika sa ŠB-om tipa 1, slabo regulirana glikemija je češće uzrok DKA (31%) nego u bolesnika sa ŠB-om tipa 2 (18 %). Zaključak: Najčešći precipitirajući čimbenici za razvoj DKA su infekcije i loša regulacija ŠB-a. Potrebna je bolja edukacija bolesnika o važnosti redovite primjene inzulina i korekcije terapije tijekom akutne bolesti.Introduction: Diabetic ketoacidosis (DKA) is one of the most serious acute complications of diabetes mellitus (DM). In some studies, infections have been found to be a precipitating factor in more than half of the subjects. On the other hand, several recent studies emphasize that poor treatment adherence is also a common cause of DKA. Objective: To identify the most common precipitating factors for DKA in Croatia. Patients and Methods: This retrospective, multicenter study included DM type 1 or DM type 2 patients diagnosed with DKA between January 1, 2014 and December 31, 2018, and treated in 5 different DM treatment centers, i.e., Dubrovnik, Našice, Split, Zagreb and Osijek. Only the fi rst episode of DKA was included in the analysis. Patients receiving steroids and DM due to endocrine disorders such as acromegaly and Cushing\u27s syndrome were excluded. Results: The study included 160 patients (55% of men), of whom 68% had DM type 1. The mean age of the respondents was 42 (18-89) years. The most common cause of DKA was infection (57%), followed by poorly controlled DM (37%) and fi rst presentation of DM (9%), while in 7% of patients DKA was due to other causes such as insulin pump failure, stroke or myocardial infarction. In the group of patients with infections, urinary tract infections (30%), gastrointestinal infections (30%) and respiratory tract infections (19%) were most common, whereas 21% of patients had other sources of infection. In 36% of these patients, the infection was associated with previously poorly controlled diabetes, and in 12% of them, DKA caused by the infection was the fi rst manifestation of the disease. In patients with type 2DM, infections were more often the cause of DKA than in patients with type 1DM (p<0.05).Poorly controlled glycemia appeared to be a more frequent cause of DKA in patients with type 1 DM (31%) than in patients with type 2 DM (18%). Conclusion: The most common precipitating factors for the development of DKA were infections and poor diabetes management. Better education of patients about the importance of regular insulin administration and correction of therapy in acute illness could reduce the risk of DKA

Hypopituitarism after gamma knife radiosurgery for pituitary adenoma

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

Open vs laparoscopic adrenalectomy for localized adrenocortical carcinoma

Objective: The purpose of the study was to compare the long-term outcomes of patients with localized adrenocortical carcinoma (ACC) subjected to open vs laparoscopic surgery. ----- Design: Retrospective study. ----- Patients: This retrospective study included 46 patients with the ACC ENSAT stage I-stage III of whom 23 underwent open surgery (OA group), whereas 23 were subjected to laparoscopic adrenalectomy (LA group). The main outcomes analysed in the study were differences between the OA and LA groups in recurrence-free survival (RFS) and overall survival (OS). ----- Results: Patients in OA group had larger tumours (120 [70-250] mm vs 75 [26-110] mm; P < .001), higher Ki-67 index (16 [1-65] % vs 10 [1-25] %; P = .04) and higher disease stage (P = .01) compared with the patients in the LA group. The median duration of follow-up for patients underwent OA and LA was 51 (12-174) and 53 (5-127) months, respectively. Eight patients (5 OA and 3 LA) experienced recurrent disease, whereas six patients (3 OA and 3 LA) died during follow-up. No differences in RFS and OS were found between patients who underwent open or laparoscopic surgery. ----- Conclusion: The study demonstrated that in patients with localized ACC and without invasion of extra-adrenal tissues, LA is a plausible treatment option in terms of RFS and OS. However, our results are limited to referral centres with large experience in the management of patients with ACC and may not necessarily apply to nonspecialized centres

Open vs laparoscopic adrenalectomy for localized adrenocortical carcinoma

Objective: The purpose of the study was to compare the long-term outcomes of patients with localized adrenocortical carcinoma (ACC) subjected to open vs laparoscopic surgery. ----- Design: Retrospective study. ----- Patients: This retrospective study included 46 patients with the ACC ENSAT stage I-stage III of whom 23 underwent open surgery (OA group), whereas 23 were subjected to laparoscopic adrenalectomy (LA group). The main outcomes analysed in the study were differences between the OA and LA groups in recurrence-free survival (RFS) and overall survival (OS). ----- Results: Patients in OA group had larger tumours (120 [70-250] mm vs 75 [26-110] mm; P < .001), higher Ki-67 index (16 [1-65] % vs 10 [1-25] %; P = .04) and higher disease stage (P = .01) compared with the patients in the LA group. The median duration of follow-up for patients underwent OA and LA was 51 (12-174) and 53 (5-127) months, respectively. Eight patients (5 OA and 3 LA) experienced recurrent disease, whereas six patients (3 OA and 3 LA) died during follow-up. No differences in RFS and OS were found between patients who underwent open or laparoscopic surgery. ----- Conclusion: The study demonstrated that in patients with localized ACC and without invasion of extra-adrenal tissues, LA is a plausible treatment option in terms of RFS and OS. However, our results are limited to referral centres with large experience in the management of patients with ACC and may not necessarily apply to nonspecialized centres