Response to Osilodrostat Therapy in Adrenal Cushing's Syndrome.

Cushing's disease (CD) is the most common cause of endogenous hypercortisolism. Osilodrostat was demonstrated to be efficient in treating CD, and the mean average dose required for CD control was <11 mg/day. Potential differences in osilodrostat treatment between cortisol-producing adenoma (CPA) and CD have not been reported. The aim of this study was to present two patients with CPA in whom significant differences in the response to therapy compared to CD were found. We demonstrated a case of inverse response of cortisol levels with adrenal tumor progression during the initial dose escalation (Case 1). Simultaneously, severe exaggeration of hypercortisolism symptoms and life-threatening hypokalemia occurred. A further rapid dose increase resulted in the first noticeable cortisol response at a dose of 20 mg/day, and a full response at a dose of 45 mg/day. We also present a case that was initially resistant to therapy (Case 2). The doses required to achieve the first response and the full response were the same as those for Case 1. Our study demonstrated that osilodrostat therapy in patients with CPA may require a different approach than that in CD, with higher doses, faster dose escalation, and a possible initial inverse response or lack of response.

Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing's disease receiving pasireotide treatment: post hoc analyses from the SOM230B2219 study.

Introduction: Pasireotide, a somatostatin receptor ligand, is approved for treating acromegaly and Cushing's disease (CD). Hyperglycemia during treatment can occur because of the drug's mechanism of action, although treatment discontinuation is rarely required. The prospective, randomized, Phase IV SOM230B2219 (NCT02060383) trial was designed to assess optimal management of pasireotide-associated hyperglycemia. Here, we investigated predictive factors for requiring antihyperglycemic medication during pasireotide treatment. Methods: Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 µg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks. Those who required additional/alternative antihyperglycemic medication to metformin were randomized to incretin-based therapy or insulin for an additional 16 weeks. Logistic-regression analyses evaluated quantitative and qualitative factors for requiring antihyperglycemic medication during pre-randomization. Results: Of 190 participants with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication; most were aged <40 years (acromegaly 62.5%, CD 86.7%), with baseline glycated hemoglobin (HbA1c) <6.5% (<48 mmol/mol; acromegaly 98.9%, CD 100%) and fasting plasma glucose (FPG) <100 mg/dL (<5.6 mmol/L; acromegaly 76.1%, CD 100%). By logistic regression, increasing baseline HbA1c (odds ratio [OR] 3.6; P=0.0162) and FPG (OR 1.0; P=0.0472) and history of diabetes/pre-diabetes (OR 3.0; P=0.0221) predicted receipt of antihyperglycemic medication in acromegaly participants; increasing baseline HbA1c (OR 12.6; P=0.0276) was also predictive in CD participants. Investigator-reported hyperglycemia-related adverse events were recorded in 47.9% and 54.2% of acromegaly and CD participants, respectively, mainly those with diabetes/pre-diabetes. Conclusion: Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.

Obesity-Related Hemodynamic Alterations in Patients with Cushing's Disease.

Background: Cushing's disease (CD) is associated with a specific form of metabolic syndrome that includes visceral obesity, which may affect cardiovascular hemodynamics by stimulating hypercortisolism-related metabolic activity. The purpose of this study was to evaluate the relationship between obesity and the hemodynamic profile of patients with CD. Methods: This prospective clinical study involved a hemodynamic status assessment of 54 patients newly diagnosed with CD with no significant comorbidities (mean age of 41 years). The assessments included impedance cardiography (ICG) to assess such parameters as stroke index (SI), cardiac index (CI), velocity index (VI), acceleration index (ACI), Heather index (HI), systemic vascular resistance index (SVRI), and total arterial compliance index (TACI) as well as applanation tonometry to assess such parameters as central pulse pressure (CPP) and augmentation index (AI). These assessments were complemented by echocardiography to assess cardiac structure and function. Results: Compared with CD patients without obesity, individuals with CD and obesity (defined as a body mass index ≥ 30 kg/m2) exhibited significantly lower values of ICG parameters characterizing the pumping function of the heart (VI: 37.0 ± 9.5 vs. 47.2 ± 14.3 × 1*1000-1*s-1, p = 0.006; ACI: 58.7 ± 23.5 vs. 76.0 ± 23.5 × 1/100/s2, p = 0.005; HI: 11.1 ± 3.5 vs. 14.6 ± 5.5 × Ohm/s2, p = 0.01), whereas echocardiography in obese patients showed larger heart chamber sizes and a higher left ventricular mass index. No significant intergroup differences in blood pressure, heart rate, LVEF, GLS, TACI, CPP, or AI were noted. Conclusions: Hemodynamic changes associated with obesity already occur at an early stage of CD and manifest via significantly lower values of the ICG parameters illustrating the heart's function as a pump, despite the normal function of the left ventricle in echocardiography.

Pituitary apoplexy as the first manifestation of non­functioning pituitary neuroendocrine tumour.

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Ectopic ACTH syndrome in the course of ACTH-secreting pancreatic neuroendocrine tumour in a patient with a pituitary lesion - diagnostic challenges and individual approach.

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Relevance of mutations in protein deubiquitinases genes and TP53 in corticotroph pituitary tumors.

Introduction: Corticotroph pituitary neuroendocrine tumors (PitNETs) develop from ACTH-producing cells. They commonly cause Cushing's disease (CD), however, some remain clinically silent. Recurrent USP8, USP48, BRAF and TP53 mutations occur in corticotroph PitNETs. The aim of our study was to determine frequency and relevance of these mutations in a possibly large series of corticotroph PitNETs. Methods: Study included 147 patients (100 CD and 47 silent tumors) that were screened for hot-spot mutations in USP8, USP48 and BRAF with Sanger sequencing, while 128 of these patients were screened for TP53 mutations with next generation sequencing and immunohistochemistry. Results: USP8 mutations were found in 41% CD and 8,5% silent tumors, while USP48 mutations were found in 6% CD patients only. Both were more prevalent in women. They were related to higher rate of biochemical remission, non-invasive tumor growth, its smaller size and densely granulated histology, suggesting that these mutation may be favorable clinical features. Multivariate survival analyses did not confirm possible prognostic value of mutation in protein deubiquitinases. No BRAF mutations were found. Four TP53 mutations were identified (2 in CD, 2 in silent tumors) in tumors with size >10mm including 3 invasive ones. They were found in Crooke's cell and sparsely granulated tumors. Tumors with missense TP53 mutations had higher TP53 immunoreactivity score than wild-type tumors. Tumor with frameshift TP53 variant had low protein expression. TP53 mutation was a poor prognostic factor in CD according to uni- and multivariate survival analyses in spite of low mutations frequency. Conclusions: We confirmed high prevalence of USP8 mutations and low incidence of USP48 and TP53 mutations. Changes in protein deubiquitinases genes appear to be favorable prognostic factors in CD. TP53 mutations are rare, occur in both functioning and silent tumors and are related to poor clinical outcome in CD.

Prolactin-secreting pituitary adenomas: male-specific differences in pathogenesis, clinical presentation and treatment.

Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex.

The Heart's Function as a Pump Assessed via Impedance Cardiography and the Autonomic System Balance in Patients with Early-Stage Acromegaly.

BACKGROUND: Acromegaly is a rare, chronic disease that involves structural and functional abnormalities of the cardiovascular system. Acromegaly likely affects interactions between the cardiovascular system and the autonomic nervous system (ANS). Therefore, assessing the relationship between sympathetic-parasympathetic balance by analyzing heart rate variability (HRV) and the hemodynamic profile via impedance cardiography (ICG) may be useful in learning the exact nature of interactions between the ANS and the cardiovascular system. The purpose of this study was to assess a possible association between HRV and ICG-based parameters of cardiac function in patients newly diagnosed with acromegaly. METHODS: This observational cohort study was conducted on 33 patients (18 men, mean age of 47 years) newly diagnosed with acromegaly and no significant comorbidities. A correlation analysis (Spearman's rank coefficient R) of the parameters assessed via ICG and the HRV assessed via 24 h ambulatory electrocardiography was performed. ICG assessments included the following parameters: stroke volume index (SI), cardiac index (CI), acceleration index (ACI), velocity index (VI), and Heather index (HI). The analysis of HRV included both time-domain parameters (pNN50, SDNN, SDSD, rMSSD) and frequency-domain parameters (total power (TP) and its individual frequency bands: low-frequency (LF day/night), high-frequency (HF day/night), and the LF/HF ratio (day/night)). RESULTS: Frequency-domain HRV analysis showed the following correlations: (1) lower nighttime LF values with higher ACI (R = -0.38; p = 0.027) and HI (R = -0.46; p = 0.007) values; (2) higher nighttime HF values with higher ACI (R = 0.39; p = 0.027) and HI (R = 0.43; p = 0.014) values; (3) lower nighttime LF/HF values with higher ACI (R = -0.36; p = 0.037) and HI (R = -0.42; p = 0.014) values; (4) higher nighttime TP values with higher SI values (R = 0.35; p = 0.049). Time-domain parameters of HRV showed a significant correlation only between the nighttime values of SDSD and SI (R = 0.35; p = 0.049) and between the daytime and nighttime values of SDNN and HR (R = -0.50; p = 0.003 and R = -0.35; p = 0.046). In multivariate regression, only ACI was revealed to be independently related to HRV. CONCLUSIONS: In patients newly diagnosed with acromegaly, the relationship between the sympathetic-parasympathetic balance assessed via HRV and the hemodynamic profile assessed via ICG was revealed. Better function of the left ventricle was associated with a parasympathetic shift in the autonomic balance.

Cushing's Disease: Long-Term Effectiveness and Safety of Osilodrostat in a Polish Group of Patients with Persistent Hypercortisolemia in the Experience of a Single Center.

Osilodrostat is a potent oral steroidogenesis inhibitor that has emerged as the new medical agent for patients with Cushing's disease (CD) requiring long-term medical therapy for hypercortisolemia control. Its efficacy and safety have been assessed in clinical trials; however, real-world evidence is still scarce. This study aimed to investigate the long-term treatment (156 weeks) clinical and biochemical effect of osilodrostat in six patients with CD at a single center in Poland, initially participating in the LINC4 study. At week 36, all six patients met the key secondary endpoint of the LINC4 trial, achieving normalization of median urinary free cortisol. Osilodrostat treatment allowed for complete disease control in all patients and none of the patients was excluded due to the lack of treatment effectiveness in 156 weeks of follow-up. All patients demonstrated significant improvement from baseline on most metabolic and cardiovascular parameters, which was most evident at week 36 and sustained throughout the study period. This study supports and strengthens the role of osilodrostat as an effective long-term medical treatment in patients with CD. We also present three patient case histories in detail to highlight the clinical situations that endocrinologists might face during osilodrostat therapy.

The patient's sex determines the hemodynamic profile in patients with Cushing disease.

Background: Cushing disease (CD) may lead to accelerated cardiovascular remodeling and increased mortality. There are suspected differences in the mechanism of cardiovascular dysfunction between males and females with CD. The purpose of this study was to assess the effect of patient sex on the hemodynamic profile assessed via impedance cardiography and echocardiography in patients newly diagnosed with CD. Material and methods: The 54 patients newly diagnosed with CD (mean age 41 years; 77.8% of females) who were included in this prospective clinical study underwent impedance cardiography to assess specific parameters (including systemic vascular resistance index [SVRI], total arterial compliance index [TACI], Heather index [HI], stroke index [SI], cardiac index [CI], velocity index [VI], and acceleration index [ACI]) and transthoracic echocardiography to assess heart chamber diameters and left ventricular systolic and diastolic function. Results: Males with CD exhibited higher afterload, with higher SVRI (3,169.3 ± 731.8 vs. 2,339.3 ± 640.8 dyn*s*cm-5*m² in males and females, respectively; p=0.002), lower TACI (0.80 ± 0.30 vs. 1.09 ± 0.30 mL/mmHg*m2; p=0.008), and lower hemodynamic parameters of left ventricular function, with lower HI (9.46 ± 2.86 vs. 14.1 ± 5.06 Ohm/s2; p=0.0007), lower VI (35.1 ± 11.9 vs. 44.9 ± 13.1 1*1000-1*s-1; p=0.009), lower SI (36.5 ± 11.7 vs. 43.6 ± 9.57 mL/m2; p=0.04), lower CI (2.36 ± 0.46 vs. 3.17 ± 0.76 mL*m-2*min-1; p=0.0009), and lower ACI (50.4 ± 19.8 vs. 73.6 ± 25.0 1/100/s2; p=0.006). There were no significant differences between the sexes in left ventricular systolic or diastolic function assessed by echocardiography. Conclusion: In comparison with females with CD, males with CD have a less favorable hemodynamic profile, with higher afterload and worse left ventricular function. Sex differences in cardiovascular system function should be taken into consideration in designing personalized diagnostic and therapeutic management of patients with CD.

Progression of a corticotroph tumour during durable medical therapy with osilodrostat in a patient with persistent Cushing's disease.

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Long-term efficacy and safety of osilodrostat in patients with Cushing's disease: results from the LINC 4 study extension.

Objective: To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushing's disease. Methods: The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first. Study outcomes assessed in the extension included: mean urinary free cortisol (mUFC) response rates; changes in mUFC, serum cortisol and late-night salivary cortisol (LNSC); changes in cardiovascular and metabolic-related parameters; blood pressure, waist circumference and weight; changes in physical manifestations of Cushing's disease; changes in patient-reported outcomes for health-related quality of life; changes in tumor volume; and adverse events. Results were analyzed descriptively; no formal statistical testing was performed. Results: Of 60 patients who entered, 53 completed the extension, with 29 patients receiving osilodrostat for more than 96 weeks (median osilodrostat duration: 87.1 weeks). The proportion of patients with normalized mUFC observed in the core period was maintained throughout the extension. At their end-of-trial visit, 72.4% of patients had achieved normal mUFC. Substantial reductions in serum cortisol and LNSC were also observed. Improvements in most cardiovascular and metabolic-related parameters, as well as physical manifestations of Cushing's disease, observed in the core period were maintained or continued to improve in the extension. Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports. Conclusion: Osilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of hypercortisolism. Osilodrostat is an effective long-term treatment for patients with Cushing's disease. Clinical trial registration: ClinicalTrials.gov, identifier NCT02180217.

Corrigendum: Diabetes as a risk factor of death in hospitalized COVID-19 patients - an analysis of a National Hospitalization Database from Poland, 2020.

[This corrects the article DOI: 10.3389/fendo.2023.1161637.].

Medical treatment of Cushing's disease with concurrent diabetes mellitus.

Cushing's disease (CD) is a severe endocrine disorder characterized by chronic hypercortisolaemia secondary to an overproduction of adrenocorticotropic hormone (ACTH) by a pituitary adenoma. Cortisol excess impairs normal glucose homeostasis through many pathophysiological mechanisms. The varying degrees of glucose intolerance, including impaired fasting glucose, impaired glucose tolerance, and Diabetes Mellitus (DM) are commonly observed in patients with CD and contribute to significant morbidity and mortality. Although definitive surgical treatment of ACTH-secreting tumors remains the most effective therapy to control both cortisol levels and glucose metabolism, nearly one-third of patients present with persistent or recurrent disease and require additional treatments. In recent years, several medical therapies demonstrated prominent clinical efficacy in the management of patients with CD for whom surgery was non-curative or for those who are ineligible to undergo surgical treatment. Cortisol-lowering medications may have different effects on glucose metabolism, partially independent of their role in normalizing hypercortisolaemia. The expanding therapeutic landscape offers new opportunities for the tailored therapy of patients with CD who present with glucose intolerance or DM, however, additional clinical studies are needed to determine the optimal management strategies. In this article, we discuss the pathophysiology of impaired glucose metabolism caused by cortisol excess and review the clinical efficacy of medical therapies of CD, with particular emphasis on their effects on glucose homeostasis.

Diabetes as a risk factor of death in hospitalized COVID-19 patients - an analysis of a National Hospitalization Database from Poland, 2020.

Introduction: Diabetes is one of the comorbidities associated with poor prognosis in hospitalized COVID-19 patients. In this nationwide retrospective study, we evaluated the risk of in-hospital death attributed to diabetes. Methods: We analyzed data from discharge reports of patients hospitalized with COVID-19 in 2020 as submitted to the Polish National Health Fund. Several multivariate logistic regression models were used. In each model, in-hospital death was estimated with explanatory variables. Models were built either on the whole cohorts or cohorts matched with propensity score matching (PSM). The models examined either the main effects of diabetes itself or the interaction of diabetes with other variables. Results: We included 174,621 patients with COVID-19 who were hospitalized in the year 2020. Among them, there were 40,168 diabetic patients (DPs), and the proportion of DPs in this group was higher than in the general population (23.0% vs. 9.5%, p<0.001). In this group of COVID-19 hospitalizations, 17,438 in-hospital deaths were recorded, and the mortality was higher among DPs than non-diabetics (16.3% vs. 8.1%, p<0.001). Multivariate logistic regressions showed that diabetes was a risk factor of death, regardless of sex and age. In the main effect analysis, odds of in-hospital death were higher by 28.3% for DPs than for non-diabetic patients. Similarly, PSM analysis including 101,578 patients, of whom 19,050 had diabetes, showed that the risk of death was higher in DPs regardless of sex with odds higher by 34.9%. The impact of diabetes differed among age groups and was the highest for patients aged 60-69. Conclusions: This nationwide study confirmed that diabetes was an independent risk factor of in-hospital death in the course of COVID-19 infection. However, the relative risk differed across the age groups.

The expression of glucocorticoid and mineralocorticoid receptors in pituitary tumors causing Cushing's disease and silent corticotroph tumors.

Objective: Pituitary neuroendocrine corticotroph tumors commonly cause Cushing's disease (CD) that results from increased adrenocorticotropic hormone (ACTH) secretion by the pituitary tumor and consequent increase of cortisol levels in blood. However, in some patients, corticotroph tumors remain clinically non-functioning. Cortisol secretion is regulated by the hypothalamic-pituitary-adrenal axis and includes a negative feedback between cortisol and ACTH secretion. Glucocorticoids reduce ACTH level both by hypothalamic regulation and acting on corticotrophs via glucocorticoid (GR) and mineralocorticoid (MR) receptors. The aim of the study was to determine the role of GR and MR expression at mRNA and protein levels in both functioning and silent corticotroph tumors. Methods: Ninety-five patients were enrolled, including 70 with CD and 25 with silent corticotroph tumors. Gene expression levels of NR3C1 and NR3C2 coding for GR and MR, respectively, were determined with qRT-PCR in the two tumor types. GR and MR protein abundance was assessed with immunohistochemistry. Results: Both GR and MR were expressed in corticotroph tumors. Correlation between NR3C1 and NR3C2 expression levels was observed. NR3C1 expression was higher in silent than in functioning tumors. In CD patients NR3C1 and NR3C2 levels were negatively correlated with morning plasma ACTH levels and tumor size. Higher NR3C2 was confirmed in patients with remission after surgery and in densely granulated tumors. Expression of both genes and GR protein was higher in USP8-mutated tumors. Similar relationship between USP8 mutations and expression levels were observed in analysis of silent tumors that also revealed a negative correlation between GR and tumor size and higher NR3C1 expression in densely granulated tumors. Conclusions: Although the associations between gene/protein expression and patients clinical features are not strong, they consistently show an evident trend in which higher receptor expression corresponds to more favorable clinical characteristics.

Characteristics, Mortality, and Clinical Outcomes of Hospitalized Patients with COVID-19 and Diabetes: A Reference Single-Center Cohort Study from Poland.

Background: Diabetes is a risk factor for a severe course of COVID-19. We evaluated the characteristics and risk factors associated with undesirable outcomes in diabetic patients (DPs) hospitalized due to COVID-19. Materials and Methods: The data analysis of patients admitted between March 6, 2020, and May 31, 2021, to the University Hospital in Krakow (Poland), a reference center for COVID-19, was performed. The data were gathered from their medical records. Results: A total number of 5191 patients were included, of which 2348 (45.2%) were women. The patients were at the median age of 64 (IQR: 51-74) years, and 1364 (26.3%) were DPs. DPs, compared to nondiabetics, were older (median age: 70 years, IQR: 62-77 vs. 62, IQR: 47-72, and p < 0.001) and had a similar gender distribution. The DP group had a higher mortality rate (26.2% vs. 15.7%, p < 0.001) and longer hospital stays (median: 15 days, IQR: 10-24 vs. 13, IQR: 9-20, and p < 0.001). DPs were admitted to the ICU more frequently (15.7% vs. 11.0%, p < 0.001) and required mechanical ventilation more often (15.5% vs. 11.3%, p < 0.001). In a multivariate logistic regression, factors associated with a higher risk of death were age >65 years, glycaemia >10 mmol/L, CRP and D-dimer level, prehospital insulin and loop diuretic use, presence of heart failure, and chronic kidney disease. Factors contributing to lower mortality were in-hospital use of statin, thiazide diuretic, and calcium channel blocker. Conclusion: In this large COVID-19 cohort, DPs constituted more than a quarter of hospitalized patients. The risk of death and other outcomes compared to nondiabetics was higher in this group. We identified a number of clinical, laboratory, and therapeutic variables associated with the risk of hospital death in DPs.

Assessment of the spectrum of depression and bipolarity in patients with type 1 diabetes.

AIMS: The aim of the study was to check the prevalence of unipolarity (depression), bipolarity, as well as the quality of sleep and temperament traits in patients with type 1 diabetes (T1DM) who are provided with optimal conditions of diabetes care and to identify possible risk factors connected with affective traits. MATERIALS AND METHODS: Out of the 107 T1DM patients, 78 (54 females, 24 males) were included for the analysis (HbA1c [%] 7.11 ± 1.0, BMI [kg/m2 ] 25.3 ± 5.6; Years of disease duration [N] 13.7 ± 8.3). The patients filled in a set of questionnaires during their regular visit to the outpatient clinic. Three patients from the whole group were on intensive insulin therapy with Multiple Daily Injections (MDI) and Self-Monitoring of Blood Glucose (SMBG), all the rest were on various types of personal insulin pumps (years on insulin pump [N] 9.1 ± 4.5). All the patients were on regular diabetologist care, with regular visits in a Centre for Advanced Technologies in Diabetes (at least every 6 months). RESULTS: In QIDS-S (full explanation and abbreviation 26 patients (33.8%) were screened positive for depression, in PHQ (full explanation and ab 57.7% of the patients (45 patients) had symptoms of depression (age was negatively correlated with PHQ score [r = -0.26; p = 0.023]). In CES-D 16 (20%) of the patients assessed their present affect as depressed. None of the analysed clinical variables correlated with depression scores. In the Mood Disorder Questionnaire (MDQ), 16 patients reported having symptoms of bipolarity (20.5% vs. 79.5%). Hypomania Checklist (HCL) analysis indicated 10 patients with bipolar traits (>14) (14.9% vs. 85.1%). None of the analysed clinical variables correlated with HCL results. 11.5% of patients were indicated to be of morning type. Morningness was more often seen in younger patients (r = 0.39; p = 0.001). As many as 46.6% declared that they had poor sleep quality. The temperament traits analysis correlated with clinical parameters: Cyclothymic temperament trait was negatively correlated with age (r = -0.30; p = 0.007) and positively with HbA1c level (r = 0.30; p = 0.025). Hyperthymic temperament was positively correlated with (BMI r = 0.28; p = 0.016). Quality of sleep was highly correlated with depressive symptoms CESD (r = 0.61, p = 0.001), PHQ Score (r = 0.62; p = 0.001), QISD (r = 0.68; p = 0.001) and bipolarity MDQ (p = 0.50, p = 0.001) and HCL (r = 0.42, p = 0.001). In addition, QIDS was shown to be correlated with the following features of temperament: depressive factor (r = 0.41; p = 0.001), irritable factor (r = 0.53; p = 0.001), cyclothymic factor (r = 0.59; p = 0.001), anxious factor (r = 0.58, p = 0.001). CONCLUSIONS: The prevalence of affective disorders and poor sleep quality in the examined T1DM patients was much higher than in the general population. Even if the patients have in general good glycaemic control, their mental health condition should not be neglected. Well organised cooperation between patients, diabetologists, psychiatrists and psychotherapists is needed (Clinical Trials Identifier: NCT04616391).

Type 1 diabetes outpatient care and treatment effectiveness during COVID-19: A single-center cohort study.

PURPOSE: COVID-19 has brought many challenges for providing quality healthcare for type 1 diabetes (T1DM). We evaluated the impact of the COVID-19 pandemic on the medical care, glycemic control, and selected outcomes in T1DM patients. METHODS: We retrospectively analyzed medical records from 357 T1DM adults enrolled in the Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow, and assessed differences in patient data from before the COVID-19 period (March 2019-February 2020) and after it started COVID-19 (March 2020-February 2021). RESULTS: The median HbA1c levels and the percentage of patients within the HbA1c target of <7 % (53 mmol/mol) were similar in both periods: before and after the beginning of the pandemic (6.86 % [51.5 mmol/mol], IQR 6.23-7.58 % [44.6-59.3 mmol/mol] vs. 6.9 % [51.9 mmol/mol], IQR 6.2-7.61 % [44.3-59.7 mmol/mol]; p = 0.50 and 56.3 % vs. 57.1 %, p = 0.42, respectively). However, we observed a rise in BMI and body weight (median 24.25, IQR 21.97-27.05 vs. 24.82, IQR 22.17-27.87 and median weight 71.0 IQR 61-82 vs. 72.55, IQR 55-85; p < 0.001 for both comparisons). There was no reduction in the numbers of total diabetes-related visits (median 4, IQR 4-5 vs. 5, IQR 4-5; p = 0.065), but the frequency of other specialist consultations decreased (2, IQR 0-2 vs. 1, IQR 0-2). During the pandemic, telehealth visits constituted of 1191 out of 1609 (71.6 %) total visits. CONCLUSIONS: In this single-center observation, the COVID-19 pandemic did not have a negative impact on glycemic control in T1DM patients, but the patients' weight did increase. Telemedicine proved to be a valuable tool for T1DM care.

Increased Thoracic Fluid as the Most Distinctive Cardiovascular Hemodynamic Alteration in Men with Prolactinoma.

Hyperprolactinemia in males with prolactin-secreting adenomas, or prolactinomas, may be associated with endothelial dysfunction and co-existing cardiovascular risk factors. As a noninvasive technique of assessing cardiac function, impedance cardiography (ICG) may be useful in the early detection of hemodynamic dysfunction. The aim of the present study was to analyze and compare the hemodynamic profiles of patients with prolactinoma versus controls. A total of 20 men with prolactinoma (PR group) (mean age 43 years) and 20 men from the control group (CG) were evaluated in this prospective, observational comparative clinical study. The study subjects were propensity score-matched in terms of clinical characteristics­age, mean blood pressure [MBP], arterial hypertension [AH] rates, and body mass index [BMI]. ICG assessments of hemodynamic profiles were conducted with the use of a Niccomo™ device and included stroke volume index (SI), cardiac index (CI), systemic vascular resistance index (SVRI), velocity index (VI), acceleration index (ACI), Heather index (HI), and thoracic fluid content (TFC). AH was well-controlled in both study groups (116/76 mmHg PR vs. 119/76 mmHg CG). In comparison with CG patients, ICG revealed PR group patients to have higher rates of high thoracic fluid content (TFC) (>35 1/kOhm; p = 0.035) and lower SI values (<35 mL/m2, p = 0.072). There was a convergent tendency towards lower values of other cardiac function parameters (SI, CI, VI, ACI, and HI). Prolactinoma-associated endocrine abnormalities are related to hemodynamic profile alterations, including higher rates of increased TFC and the risk of worsened cardiac function.