Cardiovascular disease and risk factors in adult hypopituitarism

Recent retrospective studies suggest that hypopituitary patients on routine replacement therapy suffer a higher cardiovascular morbidity and mortality. The aim of this study was to compare a group of adult hypopituitary patients on adequate replacement therapy (n=34) with a group of healthy volunteers (n=39) matched for age, sex, body mass index and smoking habits. Vascular status was studied with high resolution B-mode ultrasonic imaging of both and femoral arteries, resting cardiograms and exercise testing, and ankle/brachial pressure index at rest and after walking on a treadmill. The presence of risk factors for vascular disease was sought with anthropometric techniques, study of carbohydrate and lipid metabolism, along with clotting methods. Statistical analysis was performed with unpaired two-tailed Student's t-test, Mann-Whitney U test and linear regression analysis. Patients had higher intima-media thickness (IMT) values in their carotid arteries (0.74±0.16 vs 0.65±0.13 mm, p<0.02). This difference was seen in middle-aged and elderly patients. More patients and a higher percentage of their individual arteries had an atheromatous plaque (65% vs 41%, p<0.05). Patients had also reduced compliance (CC: 5.00 (0.90-3.40) vs 6.63 (2.15-14.80) 10⁻⁷m²kPa¹, p<0.05) and distensibility (DC: 20.85 (17.90-71.40) vs 28.50 (11.00-64.00) 10⁻³kPa⁻¹, p<0.02 and increased stiffness (Beta: 7.43 (2.20-49.01) vs 5.30 (2.60-13.30), p<0.02) in their carotid arteries. Resting cardiograms, exercise testing and ankle/brachial pressure index were within normal limits, in both groups. Patients (21/34) were obese and the males had increased percentage of body fat (27.8±2.2 vs 20.2±1.8%, p=0.01). Female patients had central adiposity (waist-hip ratio: 0.84±0.09 vs 0.77±0.05, p=0.002). A higher percentage of patients had abnormal glucose tolerance (44% vs 15% p<0.01). Glucose area under the curve was higher in patients and there was hyperinsulinemia, though not significantly different from controls. Patients had higher levels of total (292.2±72.9 έναντι 235.3±64.0 mg/dl, p<0.02), while triglyceride levels were higher in female patients (158.8±82.0 έναντι 107.9±42.35 mg/dl, p<0.02). Plasminogen activator inhibitor levels (PAI-1) were slightly increased in patients. In conclusion, this study presents evidence that symptom-free adults treated for hypopituitarism have signs of premature atherosclerosis in their peripheral vessels. Various risk factors for vascular disease are also present. The role of growth hormone deficiency in the vascular disease of hypopituitarism remains speculative.Πρόσφατες αναδρομικές μελέτες έδειξαν ότι ασθενείς που θεραπεύονται για υποφυσιακή ανεπάρκεια παρουσιάζουν αυξημένη καρδιαγγειακή νοσηρότητα και θνητότητα. Σκοπός της εργασίας αυτής ήταν να μελετήσει μία ομάδα ασθενών με υποφυσιακή ανεπάρκεια που βρισκόταν σε επαρκή θεραπεία υποκατάστασης (n=34) και να τους συγκρίνει με μία ομάδα υγιών μαρτύρων (n=39) παρόμοιας ηλικίας, κατανομής φύλου, δείκτη μάζας σώματος και βαρύτητας καπνίσματος. Η κατάσταση του αγγειακού συστήματος ελέγχθηκε με υπερηχογράφημα υψηλής αναλύσεως των καρωτίδων και μηριαίων αρτηριών, ηλεκτροκαρδιογράφημα ηρεμίας και δοκιμασία κόπωσης, και μέτρηση του λόγου πιέσεων κάτω/άνω άκρων σε ηρεμία και μετά άσκηση. Η παρουσία προδιαθετικών παραγόντων για αγγειακές παθήσεις ελέγχθηκε με ανθρωπομετρικές τεχνικές, μελέτη του μεταβολισμού υδατανθράκων και λιπιδίων, όπως και του πηκτικού μηχανισμού. Η επεξεργασία των αποτελεσμάτων έγινε με χρήση των δοκιμασιών t-test, Mann-Whitney U test και της ανάλυσης εξαρτήσεως. Οι ασθενείς είχαν μεγαλύτερο πάχος έσω-μέσου χιτώνα (ΙΜΤ) καρωτίδων (0.74±0.16 έναντι 0.65±0.13 mm, p<0.02. Η διαφορά εντοπιζόταν στα άτομα μέσης και τρίτης ηλικίας. Περισσότεροι ασθενείς, και σε μεγαλύτερο ποσοστό των αρτηριών τους, έφεραν μικρές αθηρωματικές πλάκες (65% έναντι 41%, p<0.05. Επίσης οι ασθενείς είχαν ελαττωμένη ευενδοτότητα (CC: 5.00 (0.90-3.40) έναντι 6.63 (2.15-14.80) 10⁻⁷m²kPa¹, p<0.05) και διατασιμότητα (DC: 20.85 (17.90-71.40) έναντι 28.50 (11.00-64.00) 10⁻³kPa⁻¹, p<0.02 και αυξημένη ακαμψία (Beta: 7.43 (2.20-49.01) έναντι 5.30 (2.60- 13.30), p<0.02) των καρωτίδων τους. Δεν βρέθηκαν παθολογικά ευρήματα στις δύο ομάδες από τον ηλεκτροκαρδιογραφικό έλεγχο, τη δοκιμασία κοπώσεως και τη μέτρηση του λόγου των πιέσεων κάτω/άνω άκρων. Οι ασθενείς (21/34) παρουσίαζαν παχυσαρκία και οι άνδρες είχαν αυξημένο ποσοστό λίπους σώματος (27.8±2.2 έναντι 20.2±1.8%, p=0.01). Οι γυναίκες ασθενείς είχαν κεντρικού τύπου κατανομή του λίπους (λόγος περιμέτρων μέσης/γλουτών: 0.84±0.09 έναντι 0.77±0.05, p=0.002). Μεγαλύτερο ποσοστό ασθενών είχε ανώμαλη ανοχή γλυκόζης (44% έναντι 15%, p<0.01). Η περιοχή κάτω από την καμπύλη γλυκόζης ήταν μεγαλύτερη στους ασθενείς, ενώ υπήρχε και υπερινσουλιναιμία, αλλά όχι σημαντικά διάφορη των μαρτύρων. Οι ασθενείς είχαν υψηλότερα επίπεδα ολικής (292.2±72.9 έναντι 235.3±64.0 mg/dl, p<0.02), ενώ τα τριγλυκερίδια ήταν υψηλότερα στους θήλεις ασθενείς (158.8±82.0 έναντι 107.9±42.35 mg/dl, p<0.02). Τα επίπεδα του αναστολέα του ενεργοποιητή του πλασμινογόνου (ΡΑΙ-1) ήταν οριακά αυξημένα στους ασθενείς. Συμπερασματικά, η μελέτη αυτή έδειξε ότι ασυμπτωματικοί ασθενείς που θεραπεύονται για υποφυσιακή ανεπάρκεια έχουν σημεία πρώιμης αθηρωμάτωσης στα περιφερικά αγγεία τους. Επίσης στην ομάδα αυτή εντοπίστηκαν αρκετοί προδιαθετικοί παράγοντες για αγγειακή νόσο. Ο ρόλος της έλλειψης αυξητικής ορμόνης στην παθογένεια του φαινομένου παραμένει αδιευκρίνιστος

Androgen deprivation monotherapy usage in non-metastatic prostate cancer: Results from eight European countries

Introduction The aim of this study was to investigate the attitudes towards use of androgen deprivation therapy (ADT) as monotherapy for localized or locally advanced prostate cancer (PC). Material and methods A survey using a 28-item, structured, quantitative questionnaire about the management of patients with PC was conducted in eight European countries between February and May 2018. Survey recipients were selected from a private database of healthcare providers. Results Overall, 375 physicians completed the survey (response rate, 58%). Participants were urologists (71.2%) or medical oncologists (28.8%), with a mean practice duration of 19.9 years and with university hospital or cancer center (41.6%), non-teaching hospital (38.4%) or private-sector clinic (20.0%) affiliations. Median proportions of physicians considering ADT as monotherapy to treat patients with PC in different risk groups varied between countries, but overall were: high/very high-risk, 60%; intermedi-ate-risk, 30%; low-risk, 7.5%. The use of ADT monotherapy in the different risk groups also varied by medical specialty and type of affiliation. Proportions of participants applying different target thresh-olds for testosterone (T) levels also varied by country, but overall were: &lt;50 ng/dL, 29.9%; &lt;32 ng/dL, 4.8%; &lt;20 ng/dL, 54.3%; castration but no specific target, 11%. More than half of participants (58.7%) determined target T levels only when prostate-specific antigen level was increased. Conclusions Our multinational survey provides evidence that PC management varies across European countries and with clinical context, and frequently diverges from European Association of Urology (EAU) – European Society for Radiotherapy and Oncology (ESTRO) – European Society of Urogenital Radiology (ESUR) – International Society of Geriatric Oncology (SIOG) guidelines. Strategies for effective implementation of evidence-based recommendations in clinical practice may be needed to optimize patient outcomes. © 2021, Polish Urological Association. All rights reserved

Association of Pathology Markers with Somatostatin Analogue Responsiveness in Acromegaly

Background. Somatotroph adenomas (SAs) exhibit a variable responsiveness to somatostatin analogue (SS-a) treatment, a process that is not well understood. We investigated established and novel histological markers as predictors of SS-a responsiveness. Methods. We retrospectively investigated pathology samples from 36 acromegalic patients that underwent transsphenoidal surgery. Clinical, hormonal, and imaging data were available in 24/36 patients, before and after SS-a treatment. Specimens were semiquantitatively analyzed with immunocytochemistry for Ki-67, KER, SSTR-2, SSTR-5, ZAC-1, E-cadherin, and AIP. Results. Collectively, 18 (50%) adenomas were each classified as densely/sparsely granulated somatotroph adenomas (DGSAs/SGSAs), respectively. Patients that received preoperative SS-a had lower expression of SSTR-2 compared to those that did not (2.0 (1.0, 3.0) vs. 3.0 (3.0, 3.0), p = 0.042). Compared with DGSAs, SGSAs had higher Ki-67 labeling index (LI) (1.0 (0.5, 1.0) vs. 2.0 (1.0, 3.5), p = 0.013), and a higher proportion of high MR T2 signal (1 (6%) vs. 6 (33%), p = 0.035), and tended to express less ZAC-1 (p = 0.061) and E-cadherin (p = 0.067). In linear regression corrected for baseline growth hormone (GH), ZAC-1 immunostaining was significantly associated with a decrease in GH levels after SS-a treatment (beta (95% confidence interval): -1.53 (-2.80, -0.26), p = 0.021). No markers were associated with changes in circulating insulin-like growth factor-I (IGF-I) after treatment with SS-a. Conclusion. The novel marker ZAC-1 was associated with GH response to medical treatment with SS-a. The SGSA cases were characterized by higher Ki-67 values and MR T2 signals indicative of an inferior response to SS-a. These findings improve our understanding of the mechanisms underlying SA response to medical treatment. © 2022 George Kontogeorgos et al