Hiperkalijemija izazvana nebivololom: prikaz slučaja

In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation. Our patient, a 47-year-old woman taking nebivolol for hypertension developed persistent hyperkalemia, with serum potassium levels up to 6.4 mmol/L. After extensive diagnostic evaluation and exclusion of other known conditions leading to hyperkalemia, its cause remained occult. Since hyperkalemia coincided with increased doses of nebivolol, dose reduction and discontinuation were attempted, resulting in normalized serum potassium. Poor drug metabolism could not explain this adverse effect, since pharmacogenetic testing showed no relevant aberrations. In conclusion, hyperkalemia is a harmful adverse event with possible lethal outcome, and it may be caused by nebivolol. Therefore, medical professionals have to be aware of this side effect and hyperkalemia should be listed as an adverse event in nebivolol SmPC.U ovom članku je po prvi put u poznatoj medicinskoj literaturi dokumentiran slučaj hiperkalijemije izazvane nebivololom. Hiperkalijemija je povezana s ozbiljnim stanjima kao što su srčane aritmije i iznenadna srčana smrt. Za nebivolol dosad nije bilo poznato da može uzrokovati hiperkalijemiju pa ona nije navedena u sažetku opisa svojstava lijeka. Za starije beta blokatore hiperkalijemija je poznata kao rijetka nuspojava lijeka vezana uz polimorfizam citokroma P450 2D6 (CYP2D6) i slabiju razgradnju lijeka. Nebivolol je uzimala i naša 47-godišnja bolesnica zbog hipertenzije, s posljedičnim razvojem refraktorne hiperkalijemije, s razinama serumskog kalija do 6,4 mmol/L. Nakon opsežne dijagnostičke evaluacije i isključenja drugih poznatih uvjeta koji dovode do hiperkalijemije njen uzrok nije razjašnjen. Pojava hiperkalijemije se podudarala s povećanjem doze nebivolola, a smanjenje doze i prekid terapije doveli su do normalizacije serumskog kalija. Ova nuspojava nije se mogla objasniti usporenim metabolizmom lijeka budući da farmakogenetičko testiranje nije pokazalo relevantnih aberacija. U zaključku napominjemo da je hiperkalijemija štetan događaj s mogućim smrtnim ishodom koja može biti uzrokovana nebivololom. Stoga liječnici moraju biti svjesni ove nuspojave i hiperkalijemija treba biti navedena kao moguća nuspojava u sažetku opisa svojstava ovoga lijeka

Functioning pituitary gonadotroph microadenoma responding to GnRH antagonist therapy: a case report

Functioning pituitary gonadotropinomas are rarely described and comprise only a small portion of pituitary adenomas. Most of them are macroadenomas and cause endocrine dysfunctions usually presenting as either ovarian hyperstimulation, testicular enlargement or precocious puberty. Transsphenoidal resection is currently regarded as the treatment of choice, while other treatment options are considered ineffective and are rarely used

Utjecaj stresne hiperglikemije u akutnom infarktu miokarda na klinički ishod u bolesnika bez šećerne bolesti [Influence of stress hyperglycaemia in acute myocardial infarction on clinical outcomes in patients without diabetes mellitus]

The aim of this study was to investigate the long term impact of stress hyperglycemia in nondiabetic patients with acute myocardial infarction on the incidence of major adverse cardiovascular and cerebrovascular events and new onset type 2 diabetes mellitus. There were 239 consequetive patients with first acute myocardial infarction included into the study after signing the informed consent. All of them were hospitalized in the Coronary Care Unit of the University hospital „Sestre milosrdnice“ in Zagreb from 1. 1. 2005. to 31. 12. 2005. Patients were grouped due to their admission glycemia ( or = 7,8 mmol/L ), and history of diabetes, and followed up for a period of 4 years. The incidence of major adverse cardiovascular and cerebrovascular events was noted, as well as new onset type 2 diabetes mellitus. If after 4 years type 2 diabetes mellitus was not detected, an oral glucose tolerance test was performed. Fisher exact test, Mann – Whitney U test and Cox regression were used for statistical analysis. Statistical significant differences were found for all cause mortality ( p = 0,003 ), both cardiac ( p = 0,034 ) and non-cardiac mortality ( p = 0,017 ), incidence of combined TIA and stroke ( p = 0,024 ), incidence of heart failure ( p < 0,001 ), combined incidence of all MACCE ( p < 0,001 ), and new onset type 2 diabetes mellitus ( p = 0,008 ). There was no difference in the incidence of myocardial reinfarction, cardiac surgery and nontraumatic lower extremity amputation between groups. Independent influence of stress hyperglycemia was found for the incidence of cardiac mortality, combined TIA and stroke, heart failure, and combined incidence of all MACCE. In conclusion, stress hyperglycemia in nondiabetic patients with acute myocardial infarction is related to an increased number of MACCE and new onset diabetes mellitus

Management of Cushing’s disease when surgery is a tricky option – a case report

Cushing’s disease, a form of Cushing’s syndrome, is caused by excess ACTH production, a hormone that regulates cortisol production, by a benign tumor in the pituitary gland. As a result, cortisol levels are elevated, while ACTH levels are not suppressed due to autonomous secretion. The primary treatment option is surgery. Other therapeutic modalities include drug therapy, radiation, and bilateral adrenalectomy in selected cases

Poremećaji metabolizma glukoze u bolesnika s akutnim koronarnim sindromom

Glucose metabolism disorders in acutely ill patients include oscillations in plasma glucose concentration outside the range of reference values. These disorders include both hyperglycemia and hypoglycemia, regardless of previous diagnosis of diabetes in a particular patient. Hyperglycemia is frequent in acute patients due to the increased release of stress hormones such as catecholamines and cortisol, but also as an effect of a cascade of proinflammatory cytokines in emergencies such as acute coronary syndrome, pulmonary edema, pulmonary embolism, injuries, severe infections and sepsis. Hyperglycemia occurs often even in patients in whom diabetes was not previously diagnosed, and in diabetic patients requirement for hypoglycemic medication may be temporarily increased. Hyperglycemia in cardiac emergencies is associated with more frequent adverse major cardiovascular events and worse prognosis. Hypoglycemia occurs seldom in these patients, its origin is almost always iatrogenic, and it worsens the patient’s prognosis even more than moderate hyperglycemia. Good regulation of glycemia is necessary in the management of these patients; therefore plasma glucose determination and close monitoring are obligatory, and therapy with short acting insulin should be introduced if plasma glucose concentration exceeds 10 mmol/L, regardless of the risk of hypoglycemia. It is also useful to determine the acid-base status and blood or urine ketones.Poremećaji metabolizma glukoze u akutnih bolesnika uključuju poremećaje poput hiperglikemije i hipoglikemije, odnosno odstupanja koncentracija glukoze u plazmi izvan referentnih raspona. Pritom je nevažno boluje li bolesnik od ranije dijagnosticirane šećerne bolesti. Hiperglikemija je česta kod ovakvih bolesnika zbog prolazno povišenih koncentracija kateholamina i kortizola, kao i niza proupalnih citokina, a može se javiti kod bolesti poput akutnog koronarnog sindroma, plućnog edema, plućne embolije, povreda, te teških infekcija i sepsa. Često se javlja kod bolesnika bez šećerne bolesti, kod dijabetičara može zahtijevati prolazno povišenje doza antidijabetičnih lijekova. Hipoglikemija se javlja mnogo rjeđe, po svom postanku je gotovo uvijek jatrogena. Hiperglikemija i hipoglikemija pogoršavaju prognozu akutnih bolesnika, te je u bolničkim uvjetima praćenje razine glukoze u krvi obvezno, uz uvođenje terapije kratkodjelujućim inzulinom kod hiperglikemije iznad 10 mmol/L. Dodatne informacije pruža određivanje acidobaznog statusa i ketona

Tumor Sertoli-Leydigovih stanica kao uzrok hiperandrogenemije

Postmenopausal hyperandrogenemia presents with virilization symptoms. Determining the etiology of virilization and planning a treatment plan requires a thorough diagnostic workup. Among other causes, ovarian and adrenal tumors come into consideration in the differential diagnosis.Hiperandrogenemija u postmenopauzi prezentira se simptomima virilizacije. Navedeno stanje zahtijeva pomnu dijagnostičku obradu radi pronalaženja uzroka povišenih vrijednosti androgenih hormona te planiranja ade- kvatnog liječenja. Diferencijalno dijagnostički između ostalog u obzir dolaze tumori nadbubrežnih žijezda i jajnika

Glukagonu sličan peptid-1 različito utječe na percepciju okusa u žena: randomizirana, placebom kontrolirana ukrižena studija

Gastrointestinal tract is an important connector between food intake and body weight, it senses basic tastes in a similar manner as the tongue. The aim of the study was to find out how gut hormone glucagon-like peptide-1 (GLP-1) influences taste preference. Fourteen healthy participants (six male and eight female) were included in this double-blind, placebo-controlled crossover study. After overnight fast and salty fluid (oral sodium load), participants were randomized to receive placebo (500 mL of 0.9% saline) or GLP-1 infusion (1.5 pmol/kg/min) over a 3-hour period. At the end of infusion, participants chose food preferences from illustrations of food types representing 5 tastes. After 7 days, the protocol was repeated, this time those that had received placebo first got GLP-1 infusion, and those having received GLP-1 first got placebo. Change of taste preference after GLP-1 infusion but not after placebo was reported as response, and non-response was reported in case of taste persistence. A statistically significant difference in response type was found between genders, with women being more likely to change their taste preference after GLP-1 than men. The change of taste upon GLP-1 infusion observed in women might be ascribed to estrogen weight-lowering effects accomplished by receptor-mediated delivery.Probavni sustav povezuje unos hrane i tjelesnu masu razlikujući osnovne okuse sličnim mehanizmima kao i jezik. Cilj ove studije bio je istražiti kako glukagonu sličan peptid-1 (GLP-1) utječe na sklonost određenom okusu. Četrnaestoro zdravih ispitanika (šest muškaraca i osam žena) uključeno je u randomiziranu, placebom kontroliranu ukriženu studiju. Ispitanicima koji su bili natašte dana je slana tekućina (oralno opterećenje solju), nakon čega su randomizirani za placebo (500 mL 0.9% fiziološke otopine) ili infuziju GLP-1 (1.5 pmol/kg/min) tijekom 3 sata. Na kraju infuzije ispitanicama su predočene slike hrane koje predstavljaju 5 osnovnih okusa pa su birali okus kojem su najviše skloni. Nakon 7 dana postupak se ponovio; onima kojima je prvi puta dan placebo primijenjen je GLP-1, a onima koji su prvi put dobili GLP-1 primijenjen je placebo. Promjena sklonosti određenom okusu nakon infuzije GLP-1, no ne i nakon placeba, smatrala se pozitivnim odgovorom, a negativan je bila nepromijenjena sklonost okusu. Analizirajući ispitanike prema spolu nađeno je da žene imaju veću vjerojatnost promjene sklonosti okusa nakon GLP-1 nego muškarci, što je bilo statistički značajno. Navedeno opažanje promjeni okusa nakon infuzije GLP-1 u ispitanica može se objasniti učinkom estrogena na gubitak tjelesne mase koji se objašnjava receptorski posredovnim prijenosom

Recidivirajući hiperparatiroidizam: prikaz slučaja

A 57-year-old man with a history of primary hyperparathyroidism, consequential chronic renal failure and associated chronic Hashimoto.s thyroiditis presented with recurrent hypercalcemia. Hypercalcemia persisted despite three resections of enlarged parathyroid glands and multiple sclerosations of the remaining parathyroid tissue. The possible causes of persisting hypercalcemia include unrecognized asymmetric parathyroid hyperplasia, multiple parathyroid adenomas, however, parathyromatosis as a complication of parathyroid resection could not be ruled out. Dispersion of parathyroid tissue and growth of multiple parathyroid nodules could lead to primary hyperparathyroidism. With intermittent parenteral pamidronate normocalcemia was temporarily achieved, although fourth resection of parathyroid tissue and subtotal thyroidectomy eventually led to normocalcemia and normal parathyroid hormone levels in this patient.Prikazuje se 57-godišnji bolesnik s recidivirajućim primarnim hiperparatiroidizmom i posljedičnom kroničnom bubrežnom insuficijencijom.U tri navrata učinjena je ekstirpacija povećanih paratiroidnih žlijezda i višekratna sklerozacija preostalog paratiroidnog tkiva, uz i dalje prisutnu hiperkalcemiju. Moguća objašnjenja su da se kod bolesnika radilo o višestrukim adenomima paratiroidnih žlijezda koji su se razvili metakrono ili se od samog početka radilo o neprepoznatoj asimetričnoj hiperplaziji svih paratiroidnih žlijezda. Ne može se, međutim, isključiti niti paratiromatoza kao posljedica poslijeoperacijske rupture kapsule adenoma, što je dovelo do rasapa i ponovnog rasta višestrukih paratiroidnih čvorova i recidiva primarnog hiperparatiroidizma. Bolesnik je uz intermitentnu parenteralnu terapiju pamidronatom bio u prolaznoj normokalcemiji, a nakon ponovne pojave hiperparatiroidizma učinjena je radikalna disekcija paratiroidnog tkiva i subtotalnalna resekcija štitne žlijezde, čime je uspostavljena normokalcemija i postignuta uredna razina paratiroidnog hormona