Background Graves’ orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves’ Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. Methods Prospective observational multicentre study. All new referrals with diagnosis of GO within September–December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. Results Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0–350) vs 6 (0–552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). Conclusion GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Obesity has more than doubled since 1980 all over the world, and in the European perspective it does not seem to be better. Obesity-related diseases like diabetes, hypertension, coronary heart disease, stroke and hyperlipidemia are the main cause of mortality and morbidity in developed countries. These are the reasons for continuous search for efficient treatment of obesity. One of the options is medical therapy. Over history, many anti-obesity drugs were introduced and subsequently removed from the market due to various side effects. Unfortunately, there is still no ideal drug for the treatment of obesity, and the current ones are very strictly evaluated. The anti-obesity drug should target patients that have previously failed to lose weight with lifestyle interventions, with body mass index (BMI) ≥30, or those with BMI ≥27 plus concomitant obesity-related risk factors or diseases. The only drug currently approved in Europe is orlistat, a pancreatic lipase inhibitor. Sibutramine, an appetite suppressant (serotonin-norepinephrine reuptake inhibitor), has been off the market since 2010 due to cardiovascular side effects. There is a large group of drugs used for other indications with weight loss effects, e.g. incretin mimetics or analogues used in the treatment of diabetes type 2, topiramate used as an anticonvulsant, and fluoxetine and sertraline used in the treatment of depression.

A 24-year-old female patient with parathyroid carcinoma, the rarest endocrine malignancy, had two pregnancies. In the first pregnancy, she had severe nausea and fatigue. Hypercalcemia and hyperparathyroidism were diagnosed in the postpartum period. Hyperemesis gravidarum masked a diagnosis of hypercalcemia. Neck ultrasound and Tc-99m sestamibi found an enlarged lower right parathyroid gland. The gland was surgically removed, and an initial pathology report described atypical adenoma. Shortly afterward, she became pregnant again. During the second pregnancy, her calcium level was frequently controlled but was always in the normal range. Normocalcemia is explained by the specific physiology of pregnancy accompanied by hemodilution, hypoalbuminemia and maternal hypercalciuria (mediated by increased glomerular filtration). During lactation, calcium levels rose, and a new neck ultrasound showed a solitary mass in the area of prior surgery and an enlarged pretracheal lymph node. Fine needle aspiration of the solitary mass and node showed parathyroid carcinoma cells. The tumor mass was resected en bloc with the contiguous tissues and surrounding lymph nodes (pathology report; parathyroid carcinoma with metastases). Over the next five years, four consecutive surgeries were performed to remove malignant parathyroid tissue, lymph nodes and local metastases. Following the surgical procedures, no hypocalcemia was observed. More serious hypercalcemia recurred; the calcium level was difficult to control with a combination of pamidronate, cinacalcet and loop diuretic. No elements of multiple endocrine neoplasia were present.

Introduction Glucagon-like peptide-1 (GLP-1) has many effects on the human body, but its glucose-lowering effect through its stimulation of insulin secretion is the most significant. GLP-1 also acts on renal function and hemodynamics. The antihypertensive and renoprotective effects of GLP-1 receptor agonists are partly explained by their vasoactive effect and increased natriuresis, but their positive influences on blood pressure and the development and progression of kidney disease are attributed to many effects beyond glycemic control. The aim of this study was to determine how the native gut hormone GLP-1 influences the renin–angiotensin–aldosterone system (RAAS). Methods Fourteen healthy participants (6 males and 8 females) were included in a double-blind, placebo-controlled crossover study. After overnight fasting and oral sodium loading, participants were randomly assigned to receive either placebo (500 ml of 0.9% saline) or GLP-1 infusion (1.5 pmol/kg/min dissolved in 500 ml of 0.9% saline) over a 3-h period. After 3 and 6 h, the following parameters were measured: glucose, insulin, plasma renin activity, aldosterone, GLP-1, and antidiuretic hormone. After 7 days, the protocol was repeated, except that those who had previously received placebo now received GLP-1 infusion, and those who had previously received GLP-1 now received placebo. Results Three hours after GLP-1 infusion, aldosterone had decreased by a statistically significant amount (p < 0.008) compared to the baseline level. Conclusion The present study showed that native GLP-1 can decrease aldosterone secretion in a group of healthy individuals, supporting the idea of beneficial outcomes of GLP-1-activating agents on blood pressure and the RAAS. Trial Registration ClinicalTrials.gov Identifier: NCT02130778.

Background: Hypoglycemia in type 2 diabetes mellitus (T2DM) is still unsolved issue. The aim of this study was to investigate hypoglycemia in T2DM in participants treated with oral antihyperglycemic agents using different glucose cut-off values and to explore influence of different therapies. Methods: This multi-center prospective observational study included participant with T2DM from primary care offices across Croatia treated with antihyperglycemic agents who were monitored using professional continuous glucose monitoring (CGM) device (iPro™2). Hypoglycemia was defined as at least 1% of the monitored period spent in the hypoglycemic range and/or area under the curve of glycemia registered ever under the defined cut-off value. The higher upper limit of blood glucose cut-off value was 3.9 mmol/L (70 mg/dL) and the lower one 3.0 mmol/L (54 mg/dL). Results: Study included 94 participants. Median hemoglobin A1C levels, age, T2DM duration, body mass index, and CGM use duration were 7 (5.8–11.5) %, 65 (40–86) years, 7 (1–36) years, 30.4 (21.3–41.5) kg/m² and 6 (1–7) days, respectively. Fifty participants were treated with sulfonylurea, primarily gliclazide (84%). The percentage of participant with hypoglycemia based on the higher cut-off value was 42.6% vs. 16% based on the higher cut-off value. The percentage of participant with nocturnal hypoglycemia (23 PM to 06 AM) was significantly lower among participant with hypoglycemia based on the higher cut-off value compared to lower one (7.8% vs. 22.9%). Sulfonylurea treatment did not influence the occurrence of hypoglycemia. Analysis of the data from participants having hypoglycemia based on the lower cut-off value pointed to other possible risk factors for hypoglycemia like prolonged overnight fasting, physical activity, alcohol consumption, and concomitant therapy with angiotensin-converting enzyme inhibitors. Conclusions: In participant with T2DM treated with oral antihyperglycemic agents hypoglycemia based on the blood glucose cut-off value of 3.9 mmol/L was more prevalent, but with less nocturnal hypoglycemia. Sulfonylurea therapy was not risk factor for hypoglycemia regardless of cut-off value. In participants having hypoglycemia based on the blood glucose cut-off value of 3.0 mmol/L some other possible factors were identified related to concomitant therapy, nutrition and daily habits. Trial registration: ClinicalTrials.gov Identifier: NCT03253237.