AMIODARONE AND THYROID DYSFUNCTION.

Thyroid gland has a key role in maintaining the body homeostasis. Thyroxine is the main hormone secreted from the thyroid gland, its effect being predominantly achieved after the intracellular conversion of thyroxine to triiodothyronine, which exhibits a higher affinity for the receptor complex, thus modifying gene expression of the target cells. Amiodarone is one of the most commonly used antiarrhythmics in the treatment of a broad spectrum of arrhythmias, usually tachyarrhythmias. Amiodarone contains a large proportion of iodine, which is, in addition to the intrinsic effect of the medication, the basis of the impact on thyroid function. It is believed that 15%-20% of patients treated with amiodarone develop some form of thyroid dysfunction. Amiodarone may cause amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT). AIT is usually developed in the areas with too low uptake of iodine, while AIH is developed in the areas where there is a sufficient iodine uptake. Type 1 AIT is more common among patients with an underlying thyroid pathology, such as nodular goiter or Graves' (Basedow's) disease, while type 2 mostly develops in a previously healthy thyroid. AIH is more common in patients with previously diagnosed Hashimoto's thyroiditis. Combined types of the diseases have also been described. Patients treated with amiodarone should be monitored regularly, including laboratory testing and clinical examinations, to early detect any deviations in the functioning of the thyroid gland. Supplementary levothyroxine therapy is the basis of AIH treatment. In such cases, amiodarone therapy quite often need not be discontinued. Type 1 AIT is treated with thyrostatic agents, like any other type of thyrotoxicosis. If possible, the underlying amiodarone therapy should be discontinued. In contrast to type 1 AIT, the basic pathophysiological substrate of which is the increased synthesis and release of thyroid hormones, the basis of type 2 AIT is destructive thyroiditis caused by amiodarone, desethylamiodarone as its main metabolite, and an increased iodine uptake. Glucocorticoid therapy is the basis of treatment for this type of disease.

Hypertriglyceridemia-induced pancreatitis treated with continuous insulin infusion-Case series.

OBJECTIVE: There are no definitive treatment guidelines for hypertriglyceridemia (HTG)-induced acute pancreatitis (AP). The aim of this retrospective study was to evaluate the efficacy of insulin in decreasing triglyceride (TG) levels in patients with HTG-induced AP. DESIGN: We included 17 cases of HTG-induced AP treated with continuous insulin aspart for 4 days. PATIENTS: Fifteen patients were male, two were female. The mean TG level at admission was 56.53 ± 25.29 mmol/L. The mean APACHE II score was 10.2 ± 5.7, Ranson 4.2 ± 1.7 and Balthazar 6.5 ± 2.6, implying a severe form of the disease. METHODS: In an 8-year period, 17 patients with a diagnosis of HTG-induced AP were treated with a continuous infusion of 5% dextrose and insulin aspart in an attempt to lower TG levels. TG levels were assessed on admission, the second and fourth day of therapy. The patient outcome, complications and recurrence of AP were monitored. RESULTS: A significant reduction of TG levels was observed in all patients on Day 4. All patients survived, with one forming a giant pseudocyst as a disease complication, one needing haemodialyses treatment due to an acute kidney injury, and one developing acute respiratory distress syndrome that required mechanical ventilation for 4 days. All patients recovered completely. CONCLUSION: Our study showed that continuous insulin aspart infusion decreases TG levels in HTG-induced AP from a mean TG level of 56.53 mmol/L on Day 1 to 21.75 mmol/L on Day 2 and finally to 6.86 mmol/L on Day 4. We consider this therapy very efficient, safe, simple to administer and monitor.

Analysis of Fatty Acid Esters of Hydroxyl Fatty Acid in Selected Plant Food.

Metabolic syndrome, characterized by obesity, low-grade inflammation, insulin resistance, hyperglycemia, dyslipidemia and hypertension, is a major risk factor for cardiovascular mortality. Preclinical studies on recently discovered classes of lipids - fatty acid esters of hydroxy fatty acids (FAHFA) have revealed their anti-inflammatory and insulin-sensitizing potential. The FAHFA levels are significantly decreased in insulin-resistant individuals, their application exhibited anti-inflammatory effects and restoring the glucose-insulin homeostasis. The aim of our research was to analyze the overall FAHFA composition in a common diet, as only a partial FAHFA composition has been revealed so far (only the PAHSA subclass was analyzed in a few foods). A new approach to the FAHFAs analysis includes nano-LC and post-column modifier followed by negative ion mass spectrometry, in order to obtain maximum sensitivity. Analysis of different foods - oat (whole grain, coarse flakes and fine flakes), apple, clementine, lemon, strawberry, blueberry, mango, kiwi, avocado, pineapple, banana, onion, garlic, cherry tomato, carrot, parsley root, pepper and radish - exhibited wide inter-food variation in the FAHFA profiles. Sixteen analyzed FAHFAs (palmitic, oleic, palmitoleic and stearic hydroxy-esters) showed microgram to low nanogram levels (0.165 ng/g - 32 µg/g FW), with the highest abundancy in oat, clementine, garlic and pineapple. Stearic acid hydroxy stearic acid (SAHSA) was the most abundant FAHFA, especially in the food with antioxidative, anti-inflammatory and beneficial metabolic effects. In contrary, the PAHSA - previously proven to have the strongest antihyperglycemic and insulin-sensitizing effects, was not present in some foods (radish, avocado, mango, lemon, cherry tomato, kiwi). Our study proves the importance of overall FAHFA analysis in food (especially in a functional food), because of their potential metabolic benefits and possible future incorporation in special diets.

Effect of timing of levothyroxine administration on the treatment of hypothyroidism: a three-period crossover randomized study.

AIM: Hypothyroidism is a common clinical problem that is successfully treated with hormone substitutes in the form of levothyroxine (LT4). LT4 is a drug with a narrow therapeutic index and is usually administered by strict rules, standardly at least half an hour before breakfast. The aim of this study was to investigate a possible effect of different timings of administration on thyroid function status and lipid profile. METHODS: The study included patients with the diagnosis of primary hypothyroidism, which were using a stable dose of levothyroxine. They were randomized into three different groups regarding the timing of LT4 administration in a crossover fashion. Each timing regimen lasted for at least 8 weeks; timing regimen A-half an hour before breakfast; timing regimen B-an hour before the main meal of the day; timing regimen C-at bedtime (minimally 2 h after dinner). The hormones (TSH, fT3, fT4) and lipid profile (triglycerides, HDL-, LDL-, and total cholesterol) were measured before the study, at the beginning of every timing regimen and at the end of the study. RESULTS: Altogether, 84 patients finished the study. Different timings of LT4 administration were non-inferior in comparison to the standard one and between each other. Median differences in TSH level between baseline and timing regimens were: baseline vs. A = -0.017 95% C.I. (-0.400-0.192); baseline vs. B = -0.325 95% C.I. (-0.562-0.023); baseline vs. C = -0.260 95% C.I. (-0.475-0.000). There were no statistically significant differences in either TSH, fT4, or fT3 when compared between all three timing regimens of LT4 administration and the baseline. There were no statistically significant differences in any of the lipid profile parameters (triglycerides, HDL-, LDL-, and total cholesterol) when compared between all three timing regimens of LT4 administration and the baseline. CONCLUSION: The three investigated timing regimens of LT4 administration were equally efficient and offer additional options regarding the treatment individualization.

Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review.

PURPOSE: Levothyroxine (LT4) is a drug with a narrow therapeutic index, applied in small amounts (micrograms), which makes interactions in the absorption phase clinically significant. The main aim of this article was to review and present the latest information on factors that affect the gastrointestinal absorption of this drug. METHODS: Relevant data were collected by using the MEDLINE, PubMed, EMBASE, Web of Science, Science Direct, and Scopus databases with the key words levothyroxine and absorption. Searches were not limited to specific publication types, study designs, dates, or languages. The reports were highly variable in the amount of information provided regarding study design and methods. Because of the heterogeneity of studies, no statistical analysis was performed. FINDINGS: Many gastrointestinal disorders, such as celiac disease, atrophic gastritis, lactose intolerance, and Helicobacter pylori infection, may impede the absorption of levothyroxine. During treatment of these disorders, it is necessary to monitor serum thyroid-stimulating hormone and free T4 values to reduce the risk of developing iatrogenic hyperthyroidism. Soybeans and coffee have the greatest impact on the reduction of absorption, whereas vitamin C has the ability to increase it. Conversely, the effect of dietary fiber on the absorption of LT4 is not yet fully understood; further research is needed on this topic. A decrease in the absorption of LT4 is established and clinically significant when administered concomitantly with cholestyramine, colesevelam, lanthanum, calcium carbonate, calcium citrate, calcium acetate, iron sulfate, ciprofloxacin, aluminum hydroxide, sevelamer, or proton pump inhibitors. This effect should be taken into consideration when prescribing these drugs concomitantly with LT4. The effects of Giardia lamblia infection and the influence of orlistat, polystyrene sulfonate, raloxifene, and simethicone on absorption of LT4 have been poorly documented. For bariatric surgery, sucralfate and H2-antagonist interactions are not well founded or contradictory evidence is available regarding their existence; additional research should be conducted. IMPLICATIONS: The majority of the interactions are clinically significant. They are based on the LT4 adsorption on interfering substances in the digestive tract, as well as a consequently reduced amount of the drug available for absorption. These interactions can be avoided by separating the administration of LT4 and the interfering substance.

[CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES]. / HRVATSKE SMJERNICE ZA FARMAKOLOSKO LIJECENJE SECERNE BOLESTI TIPA 2.

INTRODUCTION: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. PARTICIPANTS: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. EVIDENCE: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. CONCLUSIONS: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

Kinetics of Ischemia-Modified Albumin Following Exercise-Induced Myocardial Ischemia.

BACKGROUND: Ischemia-modified albumin (IMA) is a potentially valuable biochemical marker of myocardial ischemia. The aim of our study was to define the kinetics and to determine the diagnostic value of IMA in detection of myocardial ischemia by using a model of exercise-stress induced transitory ischemia. METHODS: The study included 43 consecutive patients with positive exercise stress test and coronary artery disease confirmed by coronary angiography (ischemic group) and 22 healthy volunteers with negative exercise stress test (control group). IMA plasma levels were measured before and at nine time points after exercise over a 6-hour period. RESULTS: IMA kinetics was significantly different between the ischemic and control group (p = 0.03). In the ischemic group, IMA plasma levels peaked between the 3rd and 4th hour after exercise. However, due to large interindividual differences in the time-to-peak IMA values, a standard IMA kinetics curve could not be defined for the patients with transitory myocardial ischemia. On the other hand, with the cutoff value of a 10.6% relative increase, sensitivity and specificity of IMA for the detection of myocardial ischemia were sufficiently high at 81% and 82%, respectively. CONCLUSIONS: Although an optimum time for the detection of recent myocardial ischemia by a single IMA sampling could not be defined, serial measurements of IMA can be a useful biochemical tool for the detection of myocardial ischemia in patients with doubtful exercise stress test results.

Monthly or weekly bisphosphonate? Evaluation of satisfaction in patients with postmenopausal osteoporosis using OPSAT-Q questionnaire during the BOOSTER study in Croatia.

A prospective, open-labelled, multicentre 6-month study was designed to assess three categories that have high impact on Health-Related Quality of Life (HR-QoL). These categories were: satisfaction, preference and drug tolerability in postmenopausal patients with osteoporosis in Croatia, at first treated with weekly oral bisphosphonates, followed by monthly oral ibandronate. Three hundred eighty-five postmenopausal women who were treated with one of the weekly bisphosphonates for at least 6 months were included into the study and after they had signed written informed consent, the therapy was changed to monthly ibandronate. Satisfaction with the treatment was assessed with the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q). Patients completed OPSAT-Q at the baseline visit before the change of therapy (visit 1) and 6 months after the change of therapy (visit 2). Following 6 months ibandronate therapy, the values in all four domains of the OPSAT-Q (convenience, confidence with daily activities, overall satisfaction, side effects) as well as in the Composite Satisfaction Score were higher in visit 2 (p < 0.001). Values in subjects enrolled into the patient assistance programme did not differ significantly from the values in subjects that were not (p = 0.399) except for the domain convenience (p = 0.026). This study demonstrates significantly higher satisfaction in patients who switched from the weekly bisphosphonate therapy regimen to monthly ibandronate in all observed aspects of treatment. Patients expressed preference for monthly bisphosphonate (ibandronate) in comparison with weekly bisphosphonates and found it to be a more convenient method of treatment. At the time of study, however, it was not known that the anti-fracture effect of ibandronate was smaller for hip fractures than with other bisphosphonates.

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.

Obstruction of left ventricular outflow tract by a calcified mass at mitral valve.

A case of an unusual left ventricular outflow tract obstruction by mitral valve pathology in a 35-year old female with diabetes and end-stage renal disease is presented in the study. The patient suffered from fever of an unknown origin after lower-leg amputation. Although the wound healed well, fever persisted for three weeks despite a triple antibiotic treatment until the infection was resolved with vancomycin. Three months later echocardiography displayed a floating mass attached to mitral valve, producing a newly developed systolic murmur and a mild haemodynamic obstruction of the left ventricular outflow tract. The calcified vegetation was probably formed during an unrecognized subacute infective endocarditis.

Successful conversion of recent-onset atrial fibrillation by sequential administration of up to three antiarrhythmic drugs.

BACKGROUND: Short-term conversion attempt of recent-onset atrial fibrillation (AF) in the emergency room fails too often. Many patients and doctors still prefer pharmacological to electrical solutions in such cases. HYPOTHESIS: Sequential administration of up to 3 antiarrhythmic drugs of different classes of action (amiodarone, propafenone, and quinidine) may achieve conversion in such patients. METHOD: One hundred and forty consecutive patients with recent-onset AF were transferred to the intensive cardiac care unit after a failed 2-h conversion attempt in the emergency room. First-line drug for conversion was continued up to a full dose, and was chosen by AF etiology, or in recurrent AF episodes, empirically. In nonresponders, the failed drug was replaced by a drug of another class, and if the second-line drug failed it was replaced by a drug of the third-line. Electrical cardioversion was the final solution for nonresponders. RESULTS: Sixty percent of patients reached sinus rhythm by the first-line drug therapy, 34% by the second-line, and 4% by the third-line. Seventy-five percent of patients achieved conversion within 26 h, and 95% of patients achieved conversion within 40 h. Three patients were electrically cardioverted due to hemodynamical instability. Two episodes of Torsade de Pointes ventricular tachycardia were self-terminated. CONCLUSION: Sequential usage of up to 3 antiarrhythmic drugs of different classes of action provides almost complete success in conversion of recent-onset AF in patients refractory to short-term conversion attempt in the emergency room.