Self-Administration of Long-Acting Somatostatin Analogues in NET Patients-Does It Affect the Clinical Outcome?

Background and Objectives: Long-acting somatostatin analogues (SSA) (octreotide LAR and lanreotide Autogel) are recommended as first line treatment of locally advanced or metastatic well-differentiated neuroendocrine tumors (NETs) with a good expression of somatostatin receptor (SSTR). Both of these SSAs are usually administered via injections repeated every 4 weeks. The purpose of the study was to compare the route of SSA administration (injection performed by professional medical staff and self-administration of the drug) with progression-free survival. Materials and methods: 88 patients in 2019 and 96 patients in 2020 with locally advanced or metastatic well-differentiated NETs were included in the study. All patients had a good expression of SSTR type 2 and had been treated for at least 3 months with a stable dose of long-acting somatostatin analogue every 4 weeks. All of them had received training on drug self-injections from professional NET nurses at the beginning of the COVID-19 epidemic. Results: The rate of NET progression in the study group in 2020 was higher than in 2019 29.1% vs. 18.1% (28 vs. 16 cases), p = 0.081. Conclusions: The method of administration of long-acting SSA injection performed by professional medical staff vs. self-injection of the drug may significantly affect the risk of NET progression. The unequivocal confirmation of such a relationship requires further observation.

Determinants of weight outcomes in type 2 diabetes prevention intervention in primary health care setting (the DE-PLAN project).

BACKGROUND: Real life implementation studies performed in different settings have proved that lifestyle interventions in the prevention of type 2 diabetes (DM2) can be effective, although the weight reduction results are typically modest compared to randomized control trials. Our objective was to identify the factors that predict successful weight loss in a less intensive, lower budget, real life setting lifestyle diabetes prevention intervention. METHODS: Study participants (n = 175) with increased DM2 risk (Finnish Diabetes Risk Score (FINDRISC) > 14) but no diabetes at baseline received ten group lifestyle counselling sessions, physical activity and motivation sessions during a ten-month intervention. Stepwise regression analysis was used to determine demographic, clinical, and lifestyle predictors of successful weight reduction defined as a reduction of ≥5% of the initial body weight. RESULTS: At 12 months following the initiation of the intervention, 23.4% of study participants lost ≥5% weight (mean loss of 7.9 kg, SD = 5.8). Increased physical activity (44% vs 25%, p = 0.03), decreased total fat consumption (88% vs 65%, p = 0.006) and adherence to four-five lifestyle goals (71% vs 46%, p = 0.007) were more often reported among those who managed to lose ≥5% weight versus those who did not. In a multivariate analysis, meeting the ≥5% weight loss goal was most effective in individuals with a higher baseline BMI (OR 1.1, 95%CI 1.0-1.2), baseline and medium versus higher education (OR 5.4, 95% CI 1.2-24.7) and a history of increased glucose (OR 2.6, 95%CI 1.1-1.3). A reduction of total fat in the diet was an independent lifestyle predictor, increasing the probability of successful weight loss by 3.8 times (OR 3.8, 95% CI 1.2-11.4). CONCLUSION: Baseline higher BMI, lower education and a history of increased glucose predicted the successful weight loss among individuals with a high risk for the DM2 following lifestyle intervention in a real life primary health care setting. People who manage to lose weight more often adhere to lifestyle changes, while the reduction of total fat in diet independently predicts successful weight loss. Further studies exploring the predictors of success in implementation studies in DM2 prevention should help health care providers redesign interventions to improve their effectiveness and outcomes. TRIAL REGISTRATION: ISRCTN, ID ISRCTN96692060 , registered 03.08.2016 retrospectively.

Sustained diabetes risk reduction after real life and primary health care setting implementation of the diabetes in Europe prevention using lifestyle, physical activity and nutritional intervention (DE-PLAN) project.

BACKGROUND: Real life implementation studies performed in different settings and populations proved that lifestyle interventions in prevention of type 2 diabetes can be effective. However, little is known about long term results of these translational studies. Therefore, the purpose of this study was to examine the maintenance of diabetes type 2 risk factor reduction achieved 1 year after intervention and during 3 year follow-up in primary health care setting in Poland. METHODS: Study participants (n = 262), middle aged, slightly obese, with increased type 2 diabetes risk ((age 55.5 (SD = 11.3), BMI 32 (SD = 4.8), Finnish Diabetes Risk Score FINDRISC 18.4 (SD = 2.9)) but no diabetes at baseline, were invited for 1 individual and 10 group lifestyle counselling sessions as well as received 6 motivational phone calls and 2 letters followed by organized physical activity sessions combined with counselling to increase physical activity. Measurements were performed at baseline and then repeated 1 and 3 years after the initiation of the intervention. RESULTS: One hundred five participants completed all 3 examinations (baseline age 56.6 (SD = 10.7)), BMI 31.1 (SD = 4.9)), FINDRISC 18.57 (SD = 3.09)). Males comprised 13% of the group, 10% of the patients presented impaired fasting glucose (IFG) and 14% impaired glucose tolerance (IGT). Mean weight of participants decreased by 2.27 kg (SD = 5.25) after 1 year (p = <0.001). After 3 years a weight gain by 1.13 kg (SD = 4.6) (p = 0.04) was observed. In comparison with baseline however, the mean total weight loss at the end of the study was maintained by 1.14 kg (SD = 5.8) (ns). Diabetes risk (FINDRISC) declined after one year by 2.8 (SD = 3.6) (p = 0.001) and the decrease by 2.26 (SD = 4.27) was maintained after 3 years (p = 0.001). Body mass reduction by >5% was achieved after 1 and 3 years by 27 and 19% of the participants, respectively. Repeated measures analysis revealed significant changes observed from baseline to year 1 and year 3 in: weight (p = 0.048), BMI (p = 0.001), total cholesterol (p = 0.013), TG (p = 0.061), fasting glucose level (p = 0.037) and FINDRISC (p = 0.001) parameters. The conversion rate to diabetes was 2% after 1 year and 7% after 3 years. CONCLUSIONS: Type 2 diabetes prevention in real life primary health care setting through lifestyle intervention delivered by trained nurses leads to modest weight reduction, favorable cardiovascular risk factors changes and decrease of diabetes risk. These beneficial outcomes can be maintained at a 3-year follow-up. TRIAL REGISTRATION: ISRCTN, ID ISRCTN96692060 , registered 03.08.2016 retrospectively.

Abnormal glucose metabolism in men with alcohol withdrawal syndrome.

UNLABELLED: The aim of the study was to evaluate the glucose metabolism in patients suffering from ethanol withdrawal syndrome. The study group comprised 88 alcohol dependent men aged 21- 50 y (mean 39.18 years, SD ±7.78), treated at the Clinical Toxicology Ward. Alcohol dependence was diagnosed accord- ing to the criteria of the International Statistical Classification of Diseases and Related Human Problems (ICD-10). The degree of alcohol withdrawal syndrome was assessed according to the scale CIWA-Ar. The blood ethanol concentration, and glucose serum concen- tration were measured on admission. On the next post-admission day blood glucose were determined after fasting and at the 0, 60th and 120th minute of an oral glucose tolerance test (OGTT) using 75 g glucose. Basing on the recommendations of Polish Diabetes Association (2013y) the patients were classified into one of groups according to their glucose tolerance test results. RESULTS: Mean duration of alcohol dependence was 10.56 years ± 7.78. A mean CIWA-Ar scale score was 23.95 points ± 2.81. Mean BMI was 24.65 ±3.74, overweight and obesity were determined in 35.22% examined men. Normal glucose tolerance were found in 54.55%, abnormal fasting glucose and/or abnormal glucose tolerance were noted in 23.87%, diabetes in 10.23%, and hypoglycemia in 11.36% of examined patients. Intensity of withdrawal syndrome according to the CIWA- Ar (OR -1.59, p= 0.05) and duration of alcohol consumption (OR -1.01, p=0.03) were the risk factors of diabetes type 2 in examined group. Greater BMI was a protective factor against diabetes type 2 in the study group. There was no significant correlation between risk of hypoglycemia and age, BMI, duration of alcohol consumption, alcohol blood concentration on admission, intensity ofwithdrawal syndrome according to the CIWA- Ar scale. A higher frequency of hypoglycemia was found in patients who declared vodka drinking in interview (at the borderline of statistical significance OR - 7.43, p=0.06). CONCLUSIONS: 1. In the study group of alcohol-dependent men, the risk of diabetes was inversely proportional to BMI value. 2. The risk factors of type 2 diabetes in the alcohol-dependent group included the duration of lasting alcohol drinking and the intensity of withdrawal symptoms according to the CIWA- Ar scale. 3. According to the preference of alcohol type, a higher frequency of hypoglycemia was confirmed only in persons preferring to drink vodka.

Patients with Cushing's syndrome suffer from provoked venous thromboembolism and are anticoagulated in various patterns.

Objective: Cushing's syndrome (CS) is associated with an 18-fold greater risk of venous thromboembolism (VTE). We aimed to identify factors which provoke VTE among patients with CS and VTE and to describe the anticoagulant regimen used in these cases. Methods: In this retrospective observational study, patients included in the European Registry on CS (ERCUSYN) in Krakow center, Poland, were followed for the occurrence of VTE and anticoagulant treatment. We identified factors provoking VTE according to the International Society of Thrombosis and Hemostasis (ISTH), along with factors included in the Padua score and CS-VTE score. Results: Of the 128 patients followed for a median of 4.3 years, there were nine patients who experienced ten VTE episodes (prevalence of 7.8% and incidence of 13.4 per 1000 patient-years). All VTEs were classified as provoked according to the ISTH guidance, predominantly due to the transient major and minor (50% and 20%, respectively) factors, while they were less commonly due to persistent (30%) factors. In 2/9 patients, we could not identify any risk factor for VTE according to the Padua score, while in 2/6 patients according to the CS-VTE score. Patients were mostly anticoagulated with vitamin K antagonists (4/8 patients), followed by direct oral anticoagulants (3/8) and low-molecular-weight heparin (1/8). The median duration of anticoagulation was 2.75 years and exceeded beyond the primary treatment in 28% of episodes provoked by transient factors. Conclusion: Further, multicenter studies are required to create a validated thrombotic risk score and guidelines regarding VTE treatment in CS patients.

Tall stature and gigantism in adult patients with acromegaly.

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess. We established three categories for height for patients with acromegaly: normal stature, tall stature (TS, height above the 97th percentile (1.88 standard deviations (SD)) to <3 SD for gender- and country-specific data or as a height which was greater than 1.5 SD but less than 2 SD above the MPH) and gigantism (height which was greater than 3 SD) above the gender- and country-specific mean or greater than 2 SD above MPH). RESULTS: Thirteen percent (17/135) of patients (53% females) met the criteria for gigantism, 10% (14/135) fulfilled the criteria for TS (57% females). Parents and adult siblings were not taller than the population mean. CONCLUSION: In a group of 135 consecutive adult patients with acromegaly, 23% had increased height based on country-specific and MPH data: 13% presented with gigantism while 10% had TS. The frequency of gigantism and TS in patients diagnosed with GH excess as adults is not higher in males than in females. Patients with acromegaly come from normal-stature families.

Increased incidence of myxedema coma during the COVID-19 pandemic and in the post pandemic era: a single-center case series.

The COVID-19 pandemic was a major challenge for all health care employees, but it was also difficult for patients to gain access to health care services. Myxedema coma (MC) is an extremely rare but potentially fatal endocrine emergency. The aim of the study was to report an increased incidence of life-threatening myxedema coma that occurred in relation to the COVID-19 pandemic. In this paper, we report a cohort of 11 patients with MC who were treated at the University Hospital in Krakow, Poland, in the period from 2015 to 2023. Only 1 case of MC was recorded in the period from 2015 to 2019, and, in the same area, 10 cases of MC were recorded after the start of COVID-19 pandemic until present. Hypothyroidism was diagnosed de novo in 2 (18%) patients; the remaining patients were severely hypothyroid due to therapy non-compliance. Nine patients had primary hypothyroidism, and 2 had central hypothyroidism. Besides longstanding hypothyroidism, an additional precipitating factor for MC was identified in 4 (36%) of the patients. Due to the inaccessibility of parenteral levothyroxine, patients were treated with oral, mostly liquid, form of levothyroxine. The mortality rate in this cohort was 27.2%. In conclusion, the increase of the incidence of MC, which is a life-threatening complication of inadequately treated hypothyroidism, during the COVID-19 pandemic, when resources were limited, and in the post-pandemic era, underlines the importance of adequate communication with patients and of long-term availability of primary care for patients with thyroid disease.

Comparison of clinical characteristics of a pediatric cohort with combined pituitary hormone deficiency caused by mutation of the PROP1 gene or of other origins.

The most commonly identified genetic cause of combined pituitary hormone deficiency (CPHD) is PROP1 gene mutations. The aim of the study was to compare selected clinical features of patients with CPHD caused by variants of the PROP1 gene (CPHD-PROP1) and patients with inborn CPHD of other etiology (CPHD-nonPROP1). MATERIAL AND METHODS: The retrospective analysis included childhood medical records of 74 patients (32 female) with CPHD, including 43 patients (23 female) with the mutation in the PROP1 gene. RESULTS: Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with the following: significantly higher median birth weight (0.21 vs. - 0.29 SDS, p = 0.019), lower growth velocity within 3 years preceding growth hormone administration (- 2.7 vs. - 0.8 SDS, p < 0.001), higher mean maximal blood concentration of growth hormone within the stimulation process (1.2 vs. 1.08 ng/mL, p = 0.003), lower TSH (1.8 vs. 2.4 µIU/mL, p < 0.001), significantly lower prolactin concentrations (128 vs. 416.3 µIU/mL, p < 0.001), and less frequent typical signs of hypogonadism at birth in boys (n = 6; 30% vs. n = 12, 54%, p < 0.001). Secondary adrenal insufficiency was less frequent in CPHD-PROP1 (20 vs. 25 cases, p = 0.006) and occurred at a later age (13.4 vs. 10.4 years). MRI of the pituitary gland in CPHD-PROP1 revealed a small pituitary gland (21 cases), pituitary gland enlargement (eight cases), and one pituitary stalk interruption and posterior lobe ectopy, while it was normal in nine cases. CONCLUSION: Patients with the PROP1 mutations present a clinical picture significantly different from that of other forms of congenital hypopituitarism. Certain specific clinical results may lead to the successful identification of children requiring diagnostics for the PROP1 gene mutation.

The thrombotic risk in Cushing's syndrome-questions, answers, and the algorithm to consider in its assessment: part I-thrombotic risk not related to surgery.

Introduction: Recently, it has been reported that there is a great diversity in strategies used for thromboprophylaxis in patients with Cushing's syndrome (CS). An aim of this review was to discuss these practices in light of the existing data on the thrombotic risk in patients with CS and guidelines for medically ill patients. Methods: The four relevant topics and questions on thrombotic risk in CS were identified. The current guidelines on prevention and diagnosis of venous thromboembolism (VTE) were reviewed for the answers. An algorithm to consider in the assessment of the thrombotic risk in patients with CS was proposed. Results: To address both generic and CS-specific risk factors for VTE, the algorithm includes the stepwise approach consisting of Padua Score, urine free cortisol, and CS-VTE score, with no indication for routine thrombophilia testing in the prediction of an index VTE episode. Having confirmed VTE, selected patients require thrombophilia testing to aid the duration of anticoagulant treatment. The separate part of the algorithm is devoted to patients with ectopic adrenocorticotropic hormone syndrome in whom exclusion of VTE precedes introducing routine thromboprophylaxis to prevent VTE. The cancer-related VTE also prompts thromboprophylaxis, with the possible vessel invasion. The algorithm presents a unifactorial and multifactorial approach to exclude high-bleeding risks and safely introduce thromboprophylaxis with low-molecular-weight heparin. Summary: Our article is the first to present an algorithm to consider in the thrombotic risk assessment among patients with Cushing's syndrome as a starting point for a broader discussion in the environment. A plethora of factors affect the VTE risk in patients with CS, but no studies have conclusively evaluated the best thromboprophylaxis strategy so far. Future studies are needed to set standards of care.

Life-threatening amiodarone-induced thyrotoxicosis - Personalized approach to radical treatment.

Objective: Amiodarone is an iodine-rich molecule and an effective antiarrhythmic drug. It is a first-line treatment for patients with life-threatening ventricular arrhythmias and for prevention in patients at high risk. The use of amiodarone may cause serious adverse effects such as pharmacotherapy-resistant, life-threatening amiodarone-induced thyrotoxicosis (AIT)leading to rapid deterioration of the patient's condition.According to the European Thyroid Association (ETA) guidelines, emergency thyroidectomy is the first-line treatment option in these cases. ; however, is not always feasible in the clinical setting due to the high anesthetic risk.We aimed to assess the clinical course and results of urgent thyroidectomy and 131-I therapy in patients with severe AIT with worsening of cardiac status. Methods: Retrospective analysis of the clinical course and outcomes of life-threatening AIT refractory to pharmacotherapy in patients hospitalized at a tertiary endocrinology center between 2014 and 2022. Results: An electronic database search identified 75 patients hospitalized for severe AIT. At the time of AIT diagnosis, median Thyroid-stimulating hormone (TSH) concentration was 0.001 mIU/L (range 0.001-0.35), fT4 63.2 pmol/L (range 9.0 - >100), and fT3 10.2 pmol/L (range 3.8-49.3). All patients received optimal conservative treatment. Among them, 20 required urgent radical therapy due to worsening arrhythmias and/or AIT-related heart failure. In this group, 6 patients died before any radical treatment was applied, 6 underwent total thyroidectomy, while 8 patients were successfully treated with 131-I (in 6 cases after rhTSH stimulation). The median dose of 131-I used for the therapy was 784MBq (range 627-860). The decision to treat with 131-I despite low but detectable 131-I uptake (median value 6 %) was made in cases of significant contraindications to anesthesia due to refractory ventricular arrhythmias, exacerbation of severe heart failure unresponsive to cardiac treatment, myocardial infarction during AIT course, massive pulmonary embolism. Conclusion: The decision regarding the optimal time and type of radical treatment of AIT refractory to pharmacotherapy is critical for patients management and should not be delayed. Urgent therapy with 131-I may be an effective therapeutic option in patients who are unsuitable for thyroidectomy due to the high risk of anesthesia.

Glucagon-like peptide-1 receptor imaging with [Lys40(Ahx-HYNIC- 99mTc/EDDA)NH2]-exendin-4 for the detection of insulinoma.

PURPOSE: The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4. METHODS: Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed. RESULTS: Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis. CONCLUSION: [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.

COVID-19 infection in a patient with Cushing's disease on osilodrostat treatment.

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Liquid levothyroxine in the treatment of myxoedema coma.

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Differences in clinical characteristics, treatment, and outcomes of sporadic and MEN-1-related insulinomas.

INTRODUCTION: Although in most cases insulinomas are small, benign, sporadic tumours, they can also be associated with hereditary syndromes, most commonly multiple endocrine neoplasia type 1 (MEN-1). Such a diagnosis significantly affects patient management. The objective was to elucidate the clinical differences between sporadic and MEN-1-linked insulinoma. MATERIAL AND METHODS: Comparison of clinical and histopathological characteristics, types of surgery, and outcomes of patients with sporadic and MEN-1-related insulinoma diagnosed between 2015 and 2022. RESULTS: There were 17 cases of insulinomas that underwent MEN-1 genetic testing (10 women and 7 men). In 7 cases, the mutation in the menin gene was confirmed. The median age at the time of diagnosis of sporadic insulinoma related to MEN-1 was 69 years (range 29-87) and 31.5 years (16-47), respectively. Primary hyperparathyroidism (PHP) was found in 6 of 7 patients with MEN-1-related insulinoma, while in none of the patients without MEN-1 mutations. Multifocal pancreatic NETs were found in 3 patients with MEN-1 syndrome, while in all sporadic cases there was a single pancreatic tumour. Two patients with insulinoma related to MEN-1 had a positive familial history of MEN-1-related diseases, while none with sporadic form. Dissemination at diagnosis was found in 4 cases, including 3 patients with insulinoma related to MEN-1-related insulinoma. Patients with sporadic and MEN-1-related insulinoma did not differ in tumour size, Ki-67 proliferation index, and outcome. CONCLUSIONS: Of all the features evaluated, only the multifocal nature of pancreatic neuroendocrine tumour (PanNET) lesions and a positive family history differentiated between patients with sporadic and MEN-1-related insulinomas. An age of insulinoma diagnosis of less than 30 years may be a strong indicator of an increased risk of MEN-1 syndrome.

Basics of prevention and management of iodine-based contrast media-induced thyroid dysfunction - position paper by the Polish Society of Endocrinology.

Medical practice involves a high number of radiological examinations using iodinated contrast media (ICM). Therefore, it is crucial for doctors of different specialties to be aware of possible adverse effects associated with ICM use. The most common and well characterized adverse effect is contrast-induced nephropathy, whereas thyroidal adverse reactions remain a diagnostic and therapeutic dilemma. ICM-induced thyroid dysfunction represents a highly heterogenous group of thyroid disorders. Due to supraphysiological iodine concentration, ICM can induce both hyper- and hypothyroidism. In most cases, the ICM-induced thyroid dysfunction is oligo- or asymptomatic, mild, and transient. In rare cases, however, the ICM-induced thyroid dysfunction may be severe and life threatening. Recently, the European Thyroid Association (ETA) Guidelines for the Management of Iodine-Based Contrast Media-Induced Thyroid Dysfunction were published. The authors advise an individualized approach to prevention and treatment of ICM-induced thyroid dysfunction, based on patient's age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities, and iodine intake. There is a geographic variation of ICM-induced thyroid dysfunction prevalence, which is linked to iodine intake. The prevalence of ICM-induced hyperthyroidism, which may pose a serious therapeutic challenge, is greater in countries with iodine deficiency. Poland is a region with a history of iodine deficiency, contributing to an increased prevalence of nodular thyroid disease, especially in the elderly. Therefore, the Polish Society of Endocrinology has proposed national, simplified principles of ICM-induced thyroid dysfunction prevention and treatment.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes. METHODS: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 µSiemens) and estimated glomerular filtration rate (eGFR). RESULTS: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin (p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo (p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo (p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo (p = 0.0002). CONCLUSIONS: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

[Symptoms and early diagnostic possibilities of pancreatic endocrine cells hyperplasia (nesidioblastosis)]. / Symptomatologia i mozliwosci wczesnej diagnostyki hiperplazji kom6rek dokrewnych trzustki (nesidioblastosis).

Nesidioplastosis in adults is one of a rare causes of hyperinsulinemic hypoglycemia. Symptoms include chronic or recurrent hypoglycemias, often with neurological signs. Due to the looses of consciousness with coexisting seizures, in many cases patients are treated on epilepsy. Right diagnosis is usually late established, when the damages in the central nervous system (CNS) are irreversible. Early diagnosis of the disease and appropriate treatment might help to avoid serious disability in these patients. The aim of the study was to asses modern diagnostics of the nesidioblastosis with an emphasis on the biochemical and hormonal tests and imaging modalities. Patients enrolled to the study were aged between 18 and 72 years of age, and had chronic or recurrent hypoglycemia caused by hyperinsulinemia. In all patients fasting glucose and fasting insulinemia tests were performed, as well as the fasting blood test or in the 24-hour profile tests. Several techniques were used including ultrasound (US), abdominal computer tomography (CT), in two patients magnetic resonance imaging, scintigraphy of somatostatin receptors in seven patients, and in two patients scintigraphy with glucagone-like peptide-1 (GLP-1) analogue-labeled marker was done. In the performed tests low values of the blood glucose were found, whereas insulin levels, however not adequate to the blood glucose, were nearly always within the normal range. In the standard imaging only in one patient tumor lesion in the pancreatic tail was revealed, though not confirmed in the intraoperative histology. In the scintigraphy examination with the somatostatin analogue in one patient slightly increased collection of the marker in whole pancreas was reported and in the other patient focal collection in the pancreatic tail was observed. Scintigraphy with GLP-1 analogue revealed focal collection of the marker in one case. Five patients were underwent surgical treatment. In the histopathology in all operated patients hyperplasia of the endocrine pancreatic cells with positive immuno. histochemic reaction on the insulin was found. In the three cases despite hyperplasia of pancreatic islets, small sizes insulinomas were detected as well. 1. The diagnosis of nesidioblastosis should be taken into consideration in all patients with unclear-cause hypoglycemias, in whom simultaneously insulin blood level is inadequate to the level of glucose. 2. Widely available imaging examinations: US, CT, MRI are useless in the diagnosis of nesidioblastosis. 3. Among the imaging methods in preoperative diagnostics of hypoglycemia with concomitant hyperinsulinemia somatostatin receptor scintigraphy seems to have specific, though limited role - it is valuable only in the severe, diffused lesions. 4. Recurrent hypoglycemias after 70% excision of the pancreas may indicate the possibility of coexistence of pancreatic islets hyperplasia and insulin secreting insulinoma.

[Pulmonary embolism as the first manifestation of Cushing syndrome in a young woman].

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Sex and age differences among patients with acromegaly.

INTRODUCTION: Acromegaly is a chronic, slowly progressive disorder caused mostly by growth hormone (GH)-producing pituitary neuroendocrine tumors (PitNETs). Recently, the associations between sex and age at the time of diagnosis and the course of acromegaly have been a focus of debate. OBJECTIVES: The aim of our study was to evaluate the association between sex and age at the time of diagnosis of acromegaly and the clinical features, biochemical status, severity of the disease, and comorbidities. PATIENTS AND METHODS: This was a single­center study conducted in a group of consecutive patients with acromegaly and no family history of PitNETs. The participants were divded into 2 subgroups according to sex (male, female) and 3 subgroups according to age at the time of diagnosis: i) younger (≤40 years), ii) middle­aged (41-59 years), and iii) elderly patients (≥60 years). RESULTS: Our study included 101 patients (41 men, 60 women) who met the eligibility criteria. The mean (SD) age at the time of diagnosis was 47.3 (14.1) years and the median diagnostic delay was 5 years (interquartile range, 3-10). Age at the time of diagnosis and diagnostic delay were not statistically different in men and women. Levels of insulin­like growth factor 1 (IGF­1) above the upper limit of age­adjusted normal range (%ULN IGF­1) were greater in men than in women (mean [SD], 174.8% [98.9%] vs 109.4% [66.6%]; P = 0.002), while there was no significant difference in terms of %ULN IGF­1 between the age groups. Median basal and nadir GH levels did not differ between the sexes. Men presented with hypogonadism more frequently than women (54% vs 26%; P = 0.005). Hyperprolactinemia, hypogonadism, and macroadenoma were more frequently observed in the younger patients than in the middle­aged and elderly individuals (all P <0.05). CONCLUSIONS: According to our results, hypogonadism and greater IGF­1 values were more frequently observed in men with acromegaly. Hyperprolactinemia, hypogonadism, and macroadenoma were more frequent in patients with acromegaly aged 40 years or younger.

Individualized medical treatment options in Cushing disease.

Cushing disease (CD) is caused by a pituitary tumor which oversecretes adrenocorticotropic hormone (ACTH). It is a serious endocrine disease associated with increased mortality and impaired quality of life. The management of CD remains challenging. Although transsphenoidal surgery is the treatment of choice in most cases, in approximately half of CD patients, second or third-line treatment options are needed. Currently, new medical therapies are available which target adrenal steroidogenesis, pituitary somatostatin and dopamine receptors, and glucocorticoid receptors. Selection of which medication to use should be individualized and is determined by many factors including severity of the disease, possible side effects, patients preferences and local availability. The aim of this article is to describe currently available medical therapy to help clinicians individualize the treatment options in the context of recently updated Pituitary Society recommendations.