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Objectives Surgery of pheochromocytomas (PCs) still carries a high risk of haemodynamic complications during the perioperative period. We aimed to evaluate the influence of their secretory phenotype and preoperative alpha-blocker treatment on surgical outcome. Design A retrospective monocentric study at a tertiary medical centre. Patients In this study, 80 consecutive patients operated by the same team for a PC between 1988 and 2018. Results Diagnosis was based on typical symptoms and signs in 58 patients, genetic testing in 12 and work-up of an adrenal incidentaloma in 9. It was made during surgery in one patient. A genetic predisposition was found in one-third of index cases (21/62). The majority of the patients (73/79) had a secreting PC; more than 2/3 had an adrenergic phenotype and less than 1/3 a noradrenergic phenotype. The rate of perioperative haemodynamic complications was not influenced by the secretory phenotype, but persistent hypertension after surgery, recurrence and malignancy were more frequently observed in patients with a noradrenergic tumour. Preoperative alpha-blocker treatment was given for ≥ 14 days in 29 patients and, although being more symptomatic at diagnosis, these patients had less haemodynamic complications (3/29 vs 12/51 non-treated patients, P = 0.05). Conclusions The occurrence of haemodynamic complications during surgery was not significantly affected by the secretory phenotype in our study, but noradrenergic tumours show a worse post-surgical outcome. Our data also provide additional support in favour of a sufficient preoperative alpha-blockade in patients with pheochromocytoma.

Summary Primary aldosteronism (PA) is more common than expected. Aberrant adrenal expression of luteinizing hormone (LH) receptor in patients with PA has been reported; however, its physiological role on the development of PA is still unknown. Herein, we report two unique cases of PA in patients with untreated Klinefelter’s syndrome, characterized as increased serum LH, suggesting a possible contribution of the syndrome to PA development. Case 1 was a 39-year-old man with obesity and hypertension since his 20s. His plasma aldosterone concentration (PAC) and renin activity (PRA) were 220 pg/mL and 0.4 ng/mL/h, respectively. He was diagnosed as having bilateral PA by confirmatory tests and adrenal venous sampling (AVS). Klinefelter’s syndrome was suspected as he showed gynecomastia and small testes, and it was confirmed on the basis of a low serum total testosterone level (57.3 ng/dL), high serum LH level (50.9 mIU/mL), and chromosome analysis. Case 2 was a 28-year-old man who had untreated Klinefelter’s syndrome diagnosed in his childhood and a 2-year history of hypertension and hypokalemia. PAC and PRA were 247 pg/mL and 0.3 ng/mL/h, respectively. He was diagnosed as having a 10 mm-sized aldosterone-producing adenoma (APA) by AVS. In the APA, immunohistochemical analysis showed co-expression of LH receptor and CYP11B2. Our cases of untreated Klinefelter’s syndrome complicated with PA suggest that increased serum LH levels and adipose tissues, caused by primary hypogonadism, could contribute to PA development. The possible complication of PA in hypertensive patients with Klinefelter’s syndrome should be carefully considered. Learning points: The pathogenesis of primary aldosteronism is still unclear. Expression of luteinizing hormone receptor has been reported in aldosterone-producing adenoma. Serum luteinizing hormone, which is increased in patients with Klinefelter’s syndrome, might contribute to the development of primary aldosteronism.

Introduction This randomized controlled study aims to investigate the prophylactic effect of tamsulosin on the development of postoperative urinary retention (POUR) in men undergoing elective open inguinal hernia (IH) repair under spinal anesthesia. The study also focused on potentially predisposing factors for POUR. Methods 100 eligible patients were randomized into two groups. Patients in the experimental group were given two doses of tamsulosin 0.4 mg orally 24 hours and 6 hours before surgery. In the control group, two doses of placebo were administered, in the same manner as the study group. The following parameters were also recorded: the International Prostate Symptom Score (IPSS) questionnaire scores, the presence of scrotal hernia, operation duration, perioperative administration of IV opioids and/or atropine, postoperative pain, and preoperative anxiety. Results Overall, the incidence of POUR was 37% (37/100) with no difference between the two groups. Among patients receiving tamsulosin, 39.2% (20/51) developed POUR, compared to 34.7% (17/49) in the control group. Preoperative patients' high anxiety visual analog scale (VAS) score (>51mm) (P=0.007) and the intraoperative use of atropine (P=0.02) were detected as risk factors for POUR. Conclusion This interim analysis of our prospective randomized trial showed no benefit from the prophylactic use of tamsulosin in preventing POUR after IH repair under spinal anesthesia. This type of anesthesia was also correlated with an overall high incidence of POUR. Preoperative anxiety and administration of atropine were identified as statistically significant factors for POUR. In patients with preoperative high anxiety, VAS score a different type of anesthesia may be used.

Objectives To identify non-invasive predictors of response to tamsulosin 0.4 mg in patients with benign prostatic obstruction (BPO). Methods Males ≥ 50 years of age with lower urinary tract symptoms (LUTS) suggestive of BPO for over three months were included in the study. We assessed change in the mean International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) after six weeks of medical therapy. Clinical and uroflowmetry parameters were compared between two groups of patients with >25% vs.

Представлены результаты последних исследований о препаратах, используемых в лечении симптомов нижних мочевых путей при доброкачественной гиперплазии предстательной железы, а также механизмы возникновения резистентности к терапии данного заболевания., This literature review presents the results of recent studies on drugs used in the treatment of lower urinary tract symptoms in benign prostatic hyperplasia, as well as the mechanisms of the emergence of resistance to therapy of this disease., Вестник Национального медико-хирургического Центра им. Н.И. Пирогова, Выпуск 4 2021, Pages 102-106

Introduction Medical treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) targets prostate size, to prevent disease progression, and prostate smooth muscle tone for rapid relieve of LUTS. Holmium laser enucleation of the prostate (HoLEP) is a size-independent method for surgical treatment of LUTS/BPO in medication-refractory patients and offers durable long-term results with reduced perioperative morbidity. As up to 50% of patients receive medical treatment for LUTS/BPO prior to surgery, we analyzed the impact of alpha-blockers and 5-alpha reductase inhibitors (5-ARI) on outcomes and perioperative morbidity in patients undergoing HoLEP for LUTS. Material and methods We retrospectively gathered data of 1,057 patients, who underwent HoLEP for LUTS/BPO from 2013-2018, and divided patients into group 1 (no medication), group 2 (α-blockers), and group 3 (5-ARI and α-blockers). Perioperative parameters, short-term functional outcomes and safety were assessed and statistical analysis was performed using SPSS V26.0 software. Results Even though preoperative LUTS profile was significantly different between groups, all patients improved significantly after HoLEP, irrespective of preoperative LUTS medication. Median improvement of IPSS was 9, 8 and 7 points, of Qmax was 10, 12 and 9.5 ml/s, with significant improvement of quality of life (QoL) and reduction of post-void residual volume (PVR) for groups 1-3, respectively, 30 days after surgery. With only 4.0% (42/1,057) of patients experiencing a Clavien-Dindo grade ≥II complication, there was no difference in prevalence of perioperative complications between groups (p = 0.943). Conclusions Although preoperative LUTS medication does not impair efficacy of HoLEP with acceptable perioperative morbidity, the time gap between medical therapy and surgical treatment may favor an earlier response.

Summary A 29-year-old primigravida woman with a known history of primary aldosteronism due to a right aldosteronoma presented with uncontrolled hypertension at 5 weeks of estimated gestation of a spontaneous pregnancy. Her hypertension was inadequately controlled with pharmacotherapy which lead to the consideration of surgical management for her primary aldosteronism. She underwent curative right unilateral adrenalectomy at 19 weeks of estimated gestational age. The procedure was uncomplicated, and her blood pressure normalized post-operatively. She did, however, have a preterm delivery by cesarean section due to intrauterine growth retardation with good neonatal outcome. She is normotensive to date. Learning points: Primary aldosteronism is the most common etiology of secondary hypertension with an estimated prevalence of 5–10% in the hypertensive population. It is important to recognize the subtypes of primary aldosteronism given that certain forms can be treated surgically. Hypertension in pregnancy is associated with significantly higher maternal and fetal complications. Data regarding the treatment of primary aldosteronism in pregnancy are limited. Adrenalectomy can be considered during the second trimester of pregnancy if medical therapy fails to adequately control hypertension from primary aldosteronism.

Summary We report the case of a 76-year-old male with a remote history of papillary thyroid cancer who developed severe paroxysmal headaches in the setting of episodic hypertension. Brain imaging revealed multiple lesions, initially of inconclusive etiology, but suspicious for metastatic foci. A search for the primary malignancy revealed an adrenal tumor, and biochemical testing confirmed the diagnosis of a norepinephrine-secreting pheochromocytoma. Serial imaging demonstrated multiple cerebral infarctions of varying ages, evidence of vessel narrowing and irregularities in the anterior and posterior circulations, and hypoperfusion in watershed areas. An exhaustive work-up for other etiologies of stroke including thromboembolic causes or vasculitis was unremarkable. There was resolution of symptoms, absence of new infarctions, and improvement in vessel caliber after adequate alpha-adrenergic receptor blockade for the management of pheochromocytoma. This clinicoradiologic constellation of findings suggested that the etiology of the multiple infarctions was reversible cerebral vasoconstriction syndrome (RCVS). Pheochromocytoma remains a poorly recognized cause of RCVS. Unexplained multifocal cerebral infarctions in the setting of severe hypertension should prompt the consideration of a vasoactive tumor as the driver of cerebrovascular dysfunction. A missed or delayed diagnosis has the potential for serious neurologic morbidity for an otherwise treatable condition. Learning points: The constellation of multifocal watershed cerebral infarctions of uncertain etiology in a patient with malignant hypertension should trigger the consideration of undiagnosed catecholamine secreting tumors, such as pheochromocytomas and paragangliomas. Reversible cerebral vasoconstriction syndrome is a serious but reversible cerebrovascular manifestation of pheochromocytomas that may lead to strokes (ischemic and hemorrhagic), seizures, and cerebral edema. Alpha-adrenergic receptor blockade can reverse cerebral vasoconstriction and prevent further cerebral ischemia and infarctions. Early diagnosis of catecholamine secreting tumors has the potential for reducing neurologic morbidity and mortality in patients presenting with cerebrovascular complications.

Objective To evaluate the efficacy and safety of adjunctive alpha-blocker therapy before ureteroscopy in the management of ureteral stones. Methods The databases MEDLINE®, EMBASE and The Cochrane Controlled Trail Register of Controlled Trials were searched between January 1980 and June 2019 to identify randomized controlled trials (RCTs) that referred to the use of alpha-blockers as adjunctive therapy before ureteroscopy for the treatment of ureteral stones. Odds ratios (ORs) with 95% confidence intervals (CIs) were used for dichotomous outcomes; and mean difference (MD) with 95% CIs were used to report continuous outcomes. Results The analysis included five RCTs with a total of 557 patients. Compared with placebo, patients that received adjunctive alpha-blockers had significantly higher successful access to the stone (OR 5.44; 95% CI 2.99, 9.88), a significantly higher stone-free rate at the end of week 4 (OR 3.75; 95% CI 2.20, 6.39), significantly less requirement for balloon dilatation (OR 0.26; 95% CI 0.15, 0.44) and a significantly lower risk of complications (OR 0.25; 95% CI 0.15, 0.42). There was no significant difference in the operation time between the two groups (MD –3.33; 95% CI –7.03, 0.37). Conclusions Adjunctive alpha-blocker therapy administered before ureteroscopy was effective in the management of ureteral stones with a lower risk of complications than placebo treatment.

Summary Ectopic adrenocorticotropic hormone (ACTH) production is an uncommon cause of Cushing’s syndrome and, rarely, the source can be a phaeochromocytoma. A 55-year-old man presented following an episode of presumed gastroenteritis with vomiting and general malaise. Further episodes of diarrhoea, joint pains and palpitations followed. On examination, he was hypertensive with no clinical features to suggest hypercortisolaemia. He was subsequently found to have raised plasma normetanephrines of 3.98 nmol/L (NR Learning points: Phaeochromocytomas are a rare source of ectopic ACTH secretion. A high clinical index of suspicion is therefore required to make the diagnosis. Ectopic ACTH secretion from a phaeochromocytoma can rapidly progress to severe Cushing’s syndrome, thus complicating tumour removal. Removal of the primary tumour often leads to full recovery. The limited literature suggests that the presence of ectopic Cushing’s syndrome does not appear to have any long-term prognostic implications.

Summary Parathyroid-independent hypercalcaemia of pregnancy, due to biallelic loss of function of the P450 enzyme CYP24A1, the principal inactivator of 1,25(OH)2D results in hypervitaminosis D, hypercalcaemia and hypercalciuria. We report two cases of this disorder, with intractable hypercalcaemia, one occurring during gestation and into the postpartum, and the other in the postpartum period. Case 1, a 47-year-old woman with a twin pregnancy conceived by embryo transfer, presented with hypercalcaemia at 23 weeks gestation with subnormal serum parathyroid hormone (PTH) and normal serum 25-OH D levels. She was admitted to hospital at 31 weeks gestation with pregnancy-induced hypertension, gestational diabetes and increasing hypercalcaemia. Caesarean section at 34 weeks gestation delivered two healthy females weighing 2.13 kg and 2.51 kg. At delivery, the patient’s serum calcium level was 2.90 mmol/L. Postpartum severe hypercalcaemia was treated successfully with Denosumab 60 mg SCI, given on two occasions. CYP24A1 testing revealed she was compound heterozygous for pathogenic variants c.427_429delGAA, (p.Glu143del) and c.1186C>T, (p.Arg396Trp). Case 2, a 36-year-old woman presented 4 days after the delivery of healthy twins with dyspnoea, bradycardia, severe headaches, hypertension and generalized tonic-clonic seizures after an uneventful pregnancy. She was hypercalcaemic with a suppressed PTH, normal 25(OH)D, and elevated 1,25(OH)2D levels. Her symptoms partially responded to i.v. saline and corticosteroids in the short term but bisphosphonates such as Pamidronate and Zoledronic acid did not result in sustained improvement. Denosumab 120 mg SCI successfully treated the hypercalcaemia which resolved completely 2 months post-partum. CYP24A1 testing revealed she was homozygous for the pathogenic variant c.427_429delGAA, (p.Glu143del). Learning points: Hypercalcaemia in pregnancy can be associated with considerable morbidity with few options available for management. In non-PTH-related hypercalcaemia the diagnosis of CYP24A1 deficiency should be considered. Making a definitive diagnosis of CYP24A1 deficiency by genetic testing delays the diagnosis, while the availability of serum 24,25-dihydroxyvitamin D (24,25(OH)2D) will expedite a diagnosis. In pregnant women with CYP24A1 deficiency hypercalcaemia can worsen in the post-partum period and is more likely to occur with twin pregnancies but generally resolves within 2–3 months. Therapeutic alternatives are limited in pregnancy and their effectiveness is short-lived and mostly ineffective. Denosumab used in both our patients after delivery was the most effective agent normalizing calcium and may have benefit as a long-term therapeutic agent in preventing complications in patients with CYP24A1 deficiency.

We describe two cases of SGLT2i-induced euglycaemic diabetic ketoacidosis, which took longer than we anticipated to treat despite initiation of our DKA protocol. Both patients had an unequivocal diagnosis of type 2 diabetes, had poor glycaemic control with a history of metformin intolerance and presented with relatively vague symptoms post-operatively. Neither patient had stopped their SGLT2i pre-operatively, but ought to have by current treatment guidelines. Learning points: SGLT2i-induced EDKA is a more protracted and prolonged metabolic derangement and takes approximately twice as long to treat as hyperglycaemic ketoacidosis. Surgical patients ought to stop SGLT2i medications routinely pre-operatively and only resume them after they have made a full recovery from the operation. While the mechanistic basis for EDKA remains unclear, our observation of marked ketonuria in both patients suggests that impaired ketone excretion may not be the predominant metabolic lesion in every case. Measurement of insulin, C-Peptide, blood and urine ketones as well as glucagon and renal function at the time of initial presentation with EDKA may help to establish why this problem occurs in specific patients. Patient Demographics: Adult, Female, Male, White, Ireland Clinical Overview: Adrenal, Kidney, Diabetes, Insulin, Diabetes mellitus type 2, Diabetic ketoacidosis, Euglycemic diabetic ketoacidosis*, Metabolic acidosis Diagnosis and Treatment: Diabetic ketoacidosis, Diabetes mellitus type 2, Euglycemic diabetic ketoacidosis*, Ketonuria, Metabolic acidosis, Nausea, Fatigue, Myasthaenia, Anorexia, Tachycardia, Tachypnoea, Dehydration, Glucosuria, Dry mucous membranes*, Acanthosis nigricans, Acrochorda, Syncope, Hypoglycaemia, Haemoglobin A1c, Glucose (blood), Urinalysis, Bicarbonate, pH (blood), Ketones (urine), Ketones (plasma), Lactate, Anion gap, BMI, Creatinine (serum), Estimated glomerular filtration rate, Electrolytes, Fluid repletion, SGLT2 inhibitors, Glucose, Atorvastatin, Canagliflozin, Dulaglutide*, Ezetimibe, Empagliflozin, Insulin glargine, Duloxetine*, Lercanidipine*, Doxazosin, Ramipril, Alpha-blockers, Pregabalin*, Insulin Aspart, Gliclazide, Sitagliptin Related Disciplines: Cardiology, Nephrology, Surgery Publication Details: Unusual effects of medical treatment, September, 2019 Background Sodium glucose-like transporter-2 inhibitor (SGLT2i) drugs have become widely prescribed for patients with type 2 diabetes (T2DM) because of their efficacy in improving glycaemic control (1), reducing cardiovascular and all-cause mortality (1) as well as improving renal (2) and cardiac (3) function in patients with chronic kidney disease and heart failure, respectively. Moreover, SGLT2is do not cause hypoglycaemia or weight gain, unlike some other diabetes medications. They inhibit the reabsorption of glucose from the renal filtrate, thus inducing glycosuria (4), which can commonly lead to genitourinary infections. In 2015, the first description of a rare and unanticipated complication of SGLT2i use, euglycaemic diabetic ketoacidosis (EDKA) was described, whereby patients with an unequivocal diagnosis of type 2 diabetes developed metabolic acidosis with very high levels of ketones consistent with DKA, but with normal glucose levels. While EDKA has been well described, with an incidence of approximately 0.1% in the EMPAREG (1) and CANVAS (5) randomised controlled trials (1, 5), its mechanistic basis is still not well established. It has been observed predominantly in hospitalised patients. Whether the duration of the metabolic acidosis is different from hyperglycaemic ketoacidosis has not been well described previously. We sought to describe our experience of the management of two patients with EDKA in whom the metabolic derangement took longer than expected to reverse.

OBJECTIVE: To develop an evidence-based recommendation concerning the use of α-blockers for uncomplicated ureteric stones based on an up-to-date Cochrane review, as the role of medical expulsive therapy for uncomplicated ureteric stones remains controversial in the light of new contradictory trial evidence. METHODS: We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice-changing evidence with recommendations developed according to standards for trustworthy guidelines. RESULTS: The panel suggests the use of α-blockers in addition to standard care over standard care alone in patients with uncomplicated ureteric stones (weak recommendation based on low-quality evidence). The panel judged that the net benefit of α-blockers was small and that there was considerable uncertainty about patients' values and preferences. This means that the panel expects that most patients would choose treatment with α-blockers but that a substantial proportion would not. This recommendation applies to both patients in whom the presence of ureteric stones is confirmed by imaging, as well as patients in whom the diagnosis is made based on clinical grounds only. CONCLUSION: The Rapid Recommendations panel suggests the use of α-blockers for patients with ureteric stones. Shared decision-making is emphasised in making the final choice between the treatment options. ispartof: Bju International vol:122 issue:6 pages:924-931 ispartof: location:England status: published

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are widely presented, particularly among elderly men. It was commonly accepted that LUTS are directly or indirectly connected with the prostate. Recent studies have shown that mild andsevere forms of LUTS may have a different etiology, such as, bladder related problems: overactive bladder (OAB)/detrusor overactivity or, conversely, an underactive bladder due to compromised contractions of the detrusor. There are three main groups of LUTS: storage symptoms, voiding symptoms and post-micturition symptoms. Patients with LUTS/BPH who are not sufficiently respond to monotherapy with alpha-blockers should receive additional treatment with M‑anticholinergics in accordance with the European urological guidelines. Current studies show that up to 65% of patients with LUTS/BPH with symptoms of urgency and frequency do not have sufficient reduction of symptoms after 3 months of treatment with alphablocker as monotherapy. Until recently, alpha-blockers and M‑anticholinergic medications were prescribed in combination therapy as a two separate pills. Vesomni is a combination of antimuscarinic drug solifenacin 6 mg with α1‑blocker tamsulosin OCAS 0.4 mg in one tablet. It is developed to relieve storage (urgency and frequency) and voiding symptoms in men with LUTS/BPH. Solifenacin suppresses the overactivity of the detrusor and reduces storage symptoms. Tamsulosin OCAS relaxes smooth muscle of the prostate, prostatic urethra and bladder neck, and eliminates most voiding symptoms and, to a lesser extent, storage symptoms.

Summary We report a case of elderly Chinese lady with neurofibromatosis type-1 presenting with longstanding palpitation, paroxysmal hypertension and osteoporosis. Biochemical testing showed mild hypercalcaemia with non-suppressed parathyroid hormone level suggestive of primary hyperparathyroidism, and mildly elevated urinary fractionated normetanephrine and plasma-free normetanephrine pointing to a catecholamine-secreting pheochromocytoma/paraganglioma. Further scintigraphic investigation revealed evidence of a solitary parathyroid adenoma causing primary hyperparathyroidism and a left pheochromocytoma. Resection of the parathyroid adenoma and pheochromocytoma resulted in normalization of biochemical abnormalities and hypertension. The rare concurrence of primary hyperparathyroidism and pheochromocytoma in neurofibromatosis type-1 is discussed. Learning points: All NF-1 patients who have symptoms suggestive of a pheochromocytoma/paraganglioma (PPGL), even remotely, should undergo biochemical testing. The initial biochemical tests of choice for PPGL in NF-1 are either plasma-free metanephrines or urinary fractionated metanephrines. Any elevations of metanephrines should be carefully evaluated for the presence of PPGLs in NF-1 patients. Primary hyperparathyroidism (PHPT) is described in subjects with NF-1. Due to the lack of epidemiological and functional studies, their association is yet to be substantiated. Meanwhile, PHPT may further exacerbate the metabolic bone defect in these patients and should be treated when present according to published guidelines. Coexistence of PPGL and PHPT can occur in subjects with NF-1, mimicking multiple endocrine neoplasia type 2 (MEN2).

Background To investigate the efficacy of tamsulosin in patients with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) with intravesical prostatic protrusion (IPP). Ultrasound measurement of the IPP has been previously described as an effective instrument for the evaluation of benign prostatic obstruction (BPO) and could help in clarifying the role of alpha-blockers in patients with (BPE). Methods Patients with BPE and LUTS were enrolled in this observational study. Intravesical prostatic protrusion was graded as grade 1 ( 10 ml). Patients were treated with tamsulosin for twelve weeks. Evaluation was performed before and at the end of treatment by means of International Prostate Symptom Score (IPSS) and uroflowmetry. Patients were considered responders if a reduction of IPSS > 3 points was reported. Results One hundred forty-two patients were enrolled. Twelve patients were excluded because of incomplete data. Fifty patients showed an IPP grade 1 (group A), 52 a grade 2 (group B) and 28 a grade 3 (group C). Treatment success was obtained in 82%, 38,5% and 7,1% of patients respectively; these differences (group A vs B-C and group B vs C) were highly significant. The odd ratio to obtain a treatment success was of 59 and 8.1 in group A and group B respectively, in comparison to group C. After a multivariate regression, the relationship between IPP grade and treatment success remained significant. Improvement of uroflowmetry parameters has been reported in all the groups especially in patients with a low grade IPP (p value = 0,016 group A vs group B; p value = 0,005 group A vs group C). Prostate volume seems not to influence this relationship. Conclusions Intravesical prostatic protrusion has found to be significantly and inversely correlated with treatment success in patients with LUTS and BPE under alpha-blockers therapy. Alpha blockers odd ratio of success is 59 times higher in patients with a low grade IPP in comparison to patients with a high grade.

The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects. ispartof: Journal of Hypertension vol:28 issue:9 pages:1796-1803 ispartof: location:Netherlands status: published

Lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in adult men. Several drugs used for LUTS/BPO may strongly affect sexual function and bother. The aim of this systematic review and meta-analysis was to evaluate the impact of combination therapy with alpha-blockers (AB), 5-alpha reductase inhibitors (5-ARI) on the risk of erectile dysfunction(ED) and libido alterations (LA) from randomized clinical trial (RCT). Based on the inclusion and exclusion criteria, five RCTs involving 6131 patients were included in the analysis. According to the analysis, the overall prevalence of ED and LA were significantly greater in the combination treatment group than in the AB group (7.93% versus 4.66%; OR 1.81; p 0.0001 and 3.69% versus 2.36%; OR 1.58; p = 0.003, respectively). The combination therapy increased the risk of ED compared to monotherapy with 5-ARI (7.93% versus 6.47%; OR 1.25; p = 0.04) but not the risk of LA (3.51% versus 3.37; OR 1.03; p = 0.84). In our systematic meta-analysis, we demonstrated that combination therapy with ABs and 5-ARIs was associated with significantly higher risk of ED and LA compared with single monotherapy. Combination therapy showed similar risk of LA compared with 5-ARI monotherapy.

Background: The Prostate Cancer Prevention Trial has shown a protective effect of finasteride on prostate cancer in low-risk men. It is uncertain whether similar results can be expected when finasteride is used to treat benign prostatic hyperplasia. Methods: We performed an observational cohort study within the Finnish Prostate Cancer Screening Trial. Using a comprehensive prescription database on medication reimbursements during 1995–2004 of men using finasteride or alpha-blockers for benign prostatic hyperplasia, we evaluated prostate cancer incidence among 23 320 men screened during 1996–2004. Results: Compared to medication non-users, overall prostate cancer incidence was not significantly affected in finasteride users (hazard ratio 0.87; 95% CI 0.63–1.19). Incidence of Gleason 2–6 tumours, however, was decreased among finasteride users (HR 0.59; 95% CI 0.38–0.91), whereas incidence of Gleason 7–10 tumours was unchanged (HR 1.33; 95% CI 0.77–2.30). The protective effect concerned mainly screen-detected tumours. Overall prostate cancer risk was not significantly reduced among alpha-blocker users relative to non-users, but decreased incidence of high-grade tumours was observed (0.55; 95% CI 0.31–0.96). Conclusions: The detection of low-grade, early-stage tumours is decreased among men who use finasteride for symptomatic BPH. The protective effect of finasteride can also be expected in men with benign prostatic hyperplasia.

Summary A 55-year-old female patient presented to the endocrine clinic with Grave's disease. She was initially treated with carbimazole. After an early relapse, a decision was made to proceed with radioactive iodine therapy. Four days after radioiodine administration, she presented to the emergency department with chest tightness and dyspnea due to heart failure. Biochemistry revealed thyrotoxicosis and significantly elevated Troponin-T. There was ST segment elevation on electrocardiography. However, coronary angiography was normal. Ventricular function was fully restored after 6 weeks of supportive medical management. A diagnosis of stress cardiomyopathy following radioactive iodine therapy was made. This is the second case reported in the literature so far to the best of our knowledge. Learning points Stress cardiomyopathy in the context of radiation thyroiditis is a rare complication following radioiodine therapy. A degree of awareness is essential because the approach is multidisciplinary. Management is mainly supportive and cardiac dysfunction is completely reversible in most cases. The pathogenesis of this condition remains unclear. Post-menopausal women and susceptible individuals appear to be pre-disposed.

To perform a systematic review and meta-analysis of randomized clinical trials (RCTs) reporting the efficacy and safety of silodosin in the treatment of non-neurogenic male LUTS suggestive of benign prostatic enlargement. A systematic review searching multiple dataset for the term "silodosin". A meta-analysis was conducted using Review Manager software (Cochrane Collaboration, Oxford, UK). Our systematic search retrieved four studies summarizing the data of five RCTs. Silodosin was more effective than placebo with regard to mean change in all the parameters related to the IPSS and Q(max) (all p values < 0.0003). Adverse events (AE), abnormal ejaculation (AEj), and withdrawal due to AE were all more common with silodosin (all p values < 0.001). The prevalence of dizziness and adverse events other than AEj was similar with silodosin and placebo. Silodosin was more effective than tamsulosin 0.2 mg with regard to some IPSS-related parameters and Q(max) (p a parts per thousand currency sign 0.05). Silodosin and tamsulosin 0.4 mg were similarly effective in all the efficacy analyses. AEj was less common with tamsulosin 0.2 and 0.4 mg (p values < 0.00001); adverse events other than AEj were more common with tamsulosin 0.2 and 0.4 mg (p values a parts per thousand currency sign0.05). Silodosin was significantly more effective than placebo and tamsulosin 0.2 mg in improving symptoms and as effective as tamsulosin 0.4 mg. With regard to adverse events, AEj was more common with silodosin. All the adverse events other than AEj were significantly more common with tamsulosin 0.2 and 0.4 mg and as frequent with silodosin and placebo.

AIMS: To determine whether α1-blocker treatment, in chronic bladder outlet obstruction (BOO), influences bladder tissue ischemia. MATERIALS AND METHODS: This prospective study included 60 patients with BOO, of which 40 were under α1-blocker medication and 20 without treatment. Patients underwent transurethral resection of the prostate (TURP) or suprapubic prostatectomy (SPP). Ten patients with non-muscle invasive bladder cancer underwent transurethral resection of the bladder tumor and served as the control group. Tissue specimens were immunohistochemically stained for hypoxia inducible factor-1α (HIF-1α). RESULTS: Bladder tissue from obstructed subjects showed high immunoreactivity to HIF-1α. The specimens from the control group, showed no or weak, mainly cytoplasmic immunoreactivity to HIF-1α. Patients under α -blocker treatment did not differ in the number of HIF-1α positive cells compared to subjects with no treatment (median number 86.8 [20-150] and 88.6 [0-175], respectively) (p > 0.05). The lowest bladder pressure at which HIF-1α was up regulated, was detected at detrusor pressure Qmax (PdetQmax) = 60 cm H2O. CONCLUSIONS: Treatment with α-blockers in obstructed patients considered as non-responders, does not result in HIF-1α down regulation, thus bladder continues to be under chronic stress.

Primary bladder neck obstruction (PBNO) was first described in men by Marion in 1933. The precise cause of PBNO has not been clearly elucidated. This paper review the theories on etiology, clinical presentation, diagnostic evaluation and treatments for PBNO. Also this paper focuses on management of patients with complications like acute urine retention, hydroureteronephrosis and severe renal failure. The treatment options for men and women with PBNO include careful clinical evaluation, pharmacotherapy with alpha-blockers and surgical intervention.

Maximal hyperaemia is paramount in the diagnosis of patients with coronary artery disease. However in these patients, enhanced α-adrenergic microvascular vasoconstriction may preclude adenosine to induce maximal hyperaemia. To assess the presence and the clinical relevance of residual microvascular resistance after administration of adenosine. Fractional flow reserve (FFR, calculated by coronary pressure measurements during adenosine-induced hyperaemia) was assessed in 85 patients with an intermediate coronary stenosis (mean diameter stenosis of 50 ± 1%) and normal left ventricular function which were divided into the following three groups: (a) 33 patients before and after IC bolus of phentolamine, an α 1-, α 2-adrenergic blocker; (b) 32 patients before and after IC bolus of urapidil, a selective α 1-adrenergic blocker; (c) 20 patients before and after IC bolus of saline. Since minimal luminal diameter remained unchanged before and after phentolamine (1.46 ± 0.06 vs. 1.47 ± 0.06 mm, ns), urapidil (1.46 ± 0.06 vs. 1.39 ± 0.08, ns), and saline (1.56 ± 0.08 vs. 1.55 ± 0.08, ns), changes in FFR reflects changes in microvascular resistance. Overall, phentolamine and urapidil induced a slight but significant decrease in FFR (phentolamine: 0.79 ± 0.02 vs. 0.77 ± 0.02, p < 0.05; urapidil: 0.78 ± 0.02 vs. 0.75 ± 0.02, p < 0.05). However, only 6 patients showed a change in FFR from ≥0.75 to