Moderate dietary salt restriction improves blood pressure and mental well-being in patients with primary aldosteronism: The salt CONNtrol trial.

BACKGROUND: Primary aldosteronism (PA) is a frequent cause of hypertension. Aldosterone excess together with high dietary salt intake aggravates cardiovascular damage, despite guideline-recommended mineralocorticoid receptor antagonist (MRA) treatment. OBJECTIVES: To investigate the antihypertensive impact of a moderate dietary salt restriction and associated physiological changes, including mental well-being. METHODS: A total of 41 patients with PA on a stable antihypertensive regimen-including MRA-followed a dietary salt restriction for 12 weeks with structured nutritional training and consolidation by a mobile health app. Salt intake and adherence were monitored every 4 weeks using 24-h urinary sodium excretion and nutrition protocols. Body composition was assessed by bioimpedance analysis and mental well-being by validated questionnaires. RESULTS: Dietary salt intake significantly decreased from 9.1 to 5.2 g/d at the end of the study. In parallel, systolic (130 vs. 121 mm Hg) and diastolic blood pressure (BP) (84 vs. 81 mm Hg) improved significantly. Patients' aptitude of estimating dietary salt content was refined significantly (underestimation by 2.4 vs. 1.4 g/d). Salt restriction entailed a significant weight loss of 1.4 kg, improvement in pulse pressure (46 vs. 40 mm Hg) and normalization of depressive symptoms (PHQD scale, p < 0.05). Salt restriction, cortisol after dexamethasone suppression test and dosage of renin-angiotensin-aldosterone-system (RAAS) blockers were independently associated with BP reduction. CONCLUSION: A moderate restriction of dietary salt intake in patients with PA substantially reduces BP and depressive symptoms. Moreover, the findings underline that a sufficient RAAS blockade seems to augment the effects of salt restriction on BP and cardiovascular risk.

[Conn's syndrome-Frequent and still too rarely diagnosed to underdiagnosed]. / Das Conn-Syndrom ­ häufig, und immer noch zu selten diagnostiziert.

Conn's syndrome represents the most common cause of endocrine hypertension and is associated with an increased cardiovascular risk, a series of comorbidities (including type 2 diabetes mellitus) and with their frequent occurrence. Therefore, a correct and rapid diagnosis is of essential importance. Measurement of the aldosterone-renin ratio is used as a first screening test for primary aldosteronism. This should ideally be evaluated under optimized conditions (e.g. at rest), after adjustment of the blood pressure medication and with an equilibrated potassium balance. In cases of elevated aldosterone to renin ratio, further confirmatory testing as well as imaging of the adrenal glands is needed. After confirmation of Conn's syndrome a differentiation between a unilateral and bilateral adrenal disease is necessary for further treatment planning. The current gold standard is still selective adrenal vein catheterization. Promising alternatives to an adrenal vein catheter, such as functional imaging techniques and measurement of steroid profiles are currently being investigated in clinical trials. In cases of lateralization of aldosterone production, unilateral laparoscopic adrenalectomy of the affected side is the treatment of choice. In contrast, patients with bilateral disease or patients with contraindications for adrenalectomy should receive life-long treatment with mineralocorticoid receptor antagonists.

Atherosclerotic Burden and Arterial Stiffness are Not Increased in Patients with Milder Forms of Primary Aldosteronism Compared to Patients with Essential Hypertension.

Patients with primary aldosteronism (PA) are at increased cardiovascular risk, compared to patients with essential hypertension (EH). Cardiovascular damage could depend on PA phenotype, potentially being lower in milder forms of PA. Our aim was to assess atherosclerotic burden and arterial stiffness in 88 prospectively recruited patients, including 44 patients with mild PA and EH respectively. All patients underwent a structured study program, including measurements of ankle-brachial index, oscillometric measurement of central pulse wave velocity (cPWV) and vascular ultrasound examination of the supraaortic arteries, the abdominal aorta, and the femoropopliteal arteries. A plaque score was calculated to estimate atherosclerotic burden for each patient. This is a prospective case-control study set at a tertiary care hospital. Patients with PA and EH matched well for age, gender, blood pressure, BMI, and cardiovascular risk factors such as diabetes mellitus and smoking status. Common carotid intima-media thickness (0.77 vs. 0.75 mm; p=0.997) and cPWV (7.2 vs. 7.1 m/s; p=0.372) were comparable between patients with PA and EH. The atherosclerotic burden, as expressed by the plaque score, did not differ between the two groups (p=0.159). However, after initiation of treatment cPWV was significantly decreased in patients with PA (p=0.017). This study shows that subclinical atherosclerotic burden and arterial stiffness in patients with milder forms of PA is comparable to patients with EH. Nevertheless, specific treatment for PA significantly improved cPWV, which argues for a more liberal use of mineralocorticoid receptor antagonists in patients with arterial hypertension.

Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism.

First described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is well established as a relevant cause of secondary hypertension and accounts for about 5-10 % of hypertensives. The importance of considering PA is based on its deleterious target organ damage far beyond the effect of elevated blood pressure and on PA being a potentially curable form of hypertension. Aside the established contributory role of high dietary salt intake to arterial hypertension and cardiovascular disease, high salt intake is mandatory for aldosterone-mediated deleterious effects on target-organ damage in patients with primary aldosteronism. Consequently, counselling patients on the need to reduce salt intake represents a major component in the treatment of PA to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is high and far beyond the target values of 5 g per day, recommended by the World Health Organization. Insufficient patient motivation for lifestyle interventions can be further complicated by enhancing effects of aldosterone on salt appetite, via central and gustatory pathways. In this context, treatment for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake and might therefore provide further reduction of cardiovascular risk in PA than specific medical treatment alone. Furthermore, there is evidence from clinical studies that even after sufficient treatment of PA dietary salt intake remains a relevant prognostic factor for cardiovascular risk. This review will focus on the synergistic benefits derived from both blockade of aldosterone-mediated effects and reduction in dietary salt intake on cardiovascular risk.

The Impact of Glucocorticoid Co-Secretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease.

Excess aldosterone is associated with the increased risk of cardio-/cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects. The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation. Ninety-seven PA patients (43 unilateral, 54 with bilateral PA) from the database of the German Conn's Registry were included. Anti-TPO and anti-TG levels were measured pre and 6-12 months post therapeutic intervention. Patients were assessed for ACS according to their 24- hour urinary cortisol excretion, late night salivary cortisol and low-dose dexamethasone suppression test. Abnormal test results in line with ACS were identified in 74.2% of patients with PA. Following adrenalectomy, significant increases in anti-TPO levels were observed in patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy (MRA). Our data are in line with an immunosuppressive effect of mild glucocorticoid excess in PA on thyroid autoantibody titers. This effect is uncovered by adrenalectomy, but not by MRA treatment.

Steroid Profiling and Immunohistochemistry for Subtyping and Outcome Prediction in Primary Aldosteronism-a Review.

PURPOSE OF REVIEW: Steroid profiling and immunohistochemistry are both promising new tools used to improve diagnostic accuracy in the work-up of primary aldosteronism (PA) and to predict treatment outcomes. Herein, we review the recent literature and present an outlook to the future of diagnostics and therapeutic decision-making in patients with PA. RECENT FINDING: PA is the most common endocrine cause of arterial hypertension and unilateral forms of the disease are potentially curable by surgical resection of the overactive adrenal. Recent studies have shown that adrenal steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be helpful for subtyping unilateral and bilateral forms of PA, classifying patients with a unilateral aldosterone-producing adenoma (APA) according to the presence of driver mutations of aldosterone production in APAs, and potentially predicting the outcomes of surgical treatment for unilateral PA. Following adrenalectomy, immunohistochemistry of aldosterone synthase (CYP11B2) in resected adrenals is a new tool to analyze "functional" histopathology and may be an indicator of biochemical outcomes after surgery. Biochemical and clinical outcomes of therapy in PA vary widely among patients. Peripheral venous steroid profiling at baseline could improve diagnostic accuracy and help in surgical decision-making in cases of a suspected APA; results of "functional" histopathology could help determine which patients are likely to need close post-surgical follow-up for persistent aldosteronism.

Spurious hyperbicarbonatemia and a negative anion gap in a cat and a dog with severe rhabdomyolysis.

A 3-year-old male neutered domestic shorthair cat and a 2-year-old male neutered Labrador-mix dog were separately presented to the Veterinary Medical Center for evaluation after sustaining significant muscle trauma due to a dog attack and seizure activity, respectively. In both cases, biochemical analysis was consistent with rhabdomyolysis. Additionally, a markedly increased measured serum bicarbonate concentration and negative calculated anion gap were observed. As these biochemical abnormalities were not expected and deemed incompatible with life, an interference with the analyzer measurement of bicarbonate involving marked increases in pyruvate and lactate dehydrogenase (LDH) following myocyte injury was suspected. Venous blood gas analysis calculated bicarbonate concentration and anion gap were within reference interval, while measured LDH activity was markedly increased. These findings supported an analyzer-generated interference. This is the first published report of a previously described chemistry analyzer interference of markedly increased LDH activity with serum bicarbonate concentration measurement in dogs and cats. Awareness of this interference is important, particularly in the emergency setting, as it may influence case management.

Hepatic insufficiency in two juvenile dogs with histoplasmosis.

A 9-month-old female intact toy poodle and a 1-year-old female intact Labrador retriever mix presented to separate teaching hospitals for chronic histories of malaise and clinicopathologic evidence of hepatic dysfunction. The signalment and clinical histories of these dogs prompted consideration of a congenital portosystemic shunt as a primary differential. However, microscopic evaluation of peritoneal effusion, pleural effusion, and peripheral blood samples from the dogs revealed round to ovoid yeast organisms morphologically most compatible with Histoplasma capsulatum. Additional testing confirmed histoplasmosis in each case. The poodle underwent a computed tomography (CT) study, which showed hepatomegaly with a spleno-gonadal shunt, pancreatic and gastric wall edema, and marked peritoneal effusion, findings compatible with portal hypertension and secondary acquired shunt formation. The dog was later humanely euthanized due to clinical deterioration, and on necropsy hepatic histoplasmosis was verified, with additional affected tissues comprising lungs and spleen. The Labrador Retriever mix responded clinically and clinicopathologically to antifungal therapy, though no abdominal imaging was performed to definitively exclude the possibility of a congenital portosystemic shunt. In retrospect, several features were more compatible with histoplasmosis than portosystemic shunt in these cases, including hyperbilirubinemia, effusion, and hepatomegaly. These findings serve as a reminder of the need to interpret serum biochemical findings in the context of the totality of the clinicopathologic data and imaging findings, as well as the diagnostic value of microscopy in the evaluation of hematologic and body cavity fluid samples.

Assessing Lateralization Index of Adrenal Venous Sampling for Surgical Indication in Primary Aldosteronism.

BACKGROUND: Clinical practice guidelines recommend the Lateralization Index (LI) as the standard for determining surgical eligibility in primary aldosteronism (PA). Our goal was to identify the optimal LI cut-offs in adrenal venous sampling (AVS) for diagnosing PA that is amenable to surgical cure. METHODS: We conducted a retrospective international cohort study across 16 institutions in 11 countries, including 1,550 patients with PA who underwent AVS, with and/or without ACTH stimulation. The establishment of optimal cut-offs was informed by a survey of 82 PA patients in Japan, aimed at determining the LI cut-off aligned with patient expectations for a surgical cure rate. RESULTS: The survey revealed that a median cure rate expectation of 80% would motivate PA patients towards undergoing adrenalectomy. The optimal LI cut-offs achieving an adjusted positive predictive value (PPV) of 80% were identified as 3.8 for unstimulated AVS and 3.4 for ACTH-stimulated AVS. Furthermore, a contralateral ratio of less than 0.4 and the detection of an adrenal nodule on CT imaging were identified as independent predictors of surgically curable PA. Incorporating these factors with the optimal LI cut-offs, the adjusted PPV increased to 96.6% for unstimulated AVS and 89.6% for ACTH-stimulated AVS. No clear differences in predictive ability between unstimulated and ACTH-stimulated LI were found. CONCLUSIONS AND RELEVANCE: The present study clarified the optimal LI cut-offs for without and with ACTH stimulation. The presence of contralateral suppression and adrenal nodule on CT imaging seems to provide additional available information besides LI for surgical indication.

Postoperative ACTH-stimulated aldosterone predicts biochemical outcome in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is the most common surgically curable cause of hypertension. Unilateral aldosterone-producing adenoma can be treated with adrenalectomy. Clinical and biochemical outcomes are assessed 6-12 months after adrenalectomy according to primary aldosteronism surgical outcome (PASO) consensus criteria. Earlier prediction of biochemical remission would be desirable as it could reduce cumbersome follow-up visits. We hypothesized that postoperative adrenocorticotropic hormone (ACTH) stimulated plasma aldosterone concentrations (PAC) measured shortly after adrenalectomy can predict PASO outcomes. DESIGN: Retrospective cohort study. METHODS: We analyzed 100 patients of the German Conn's registry who underwent adrenalectomy and postoperative ACTH stimulation tests within the first week after adrenalectomy. Six to twelve months after adrenalectomy we assessed clinical and biochemical outcomes according to PASO criteria. Serum cortisol and PAC were measured by immunoassay at baseline and 30 min after the intravenous ACTH infusion. We used receiver operating characteristics (ROC) curve analysis and matched the parameters to PASO outcomes. RESULTS: Eighty-one percent of patients had complete, 13% partial, and 6% absent biochemical remission. Complete clinical remission was observed in 28%. For a cut-off of 58.5 pg/mL, stimulated PAC could predict partial/absent biochemical remission with a high sensitivity (95%) and reasonable specificity (74%). Stimulated PAC's area under the curve (AUC) (0.89; confidence interval (CI) 0.82-0.96) was significantly higher than other investigated parameters. CONCLUSIONS: Low postoperative ACTH stimulated PAC was predictive of biochemical remission. If confirmed, this approach could reduce follow-up visits to assess biochemical outcome.

Red cell distribution width is a predictor of all-cause mortality in hospitalized dogs.

OBJECTIVE: To determine whether RBC distribution width (RDW) is associated with an increased odds of mortality in hospitalized dogs and cats. DESIGN: Retrospective, single-center study; data collected from 2007 to 2017. SETTING: University teaching hospital. ANIMALS: Six thousand six hundred and sixty-one animals (5183 dogs and 1478 cats). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were identified from animals presented to the emergency service and admitted to the ICU with a CBC and serum biochemistry performed on admission. Patients were stratified into quintiles based upon presenting RDW, and logistic regression modeling was performed to evaluate the relationship between RDW and in-hospital mortality. Canine patients with a presenting RDW in the upper fourth and fifth quintiles had an increased odds of all-cause in-hospital mortality (p < 0.0001). Specifically, dogs in the upper fifth quintile had a 2.1-fold greater odds of death compared to dogs in the first quintile, and dogs in the upper fourth quintile had a 1.9-fold greater odds of death compared to dogs in the first quintile. This relationship remained significant after adjusting for age, sex, key laboratory values excluding HCT, medical versus surgical disease, and diagnosis category. This relationship was no longer significant with the inclusion of HCT. No significant association was identified between presenting RDW and in-hospital mortality in cats. CONCLUSIONS: Hospitalized dogs with higher RDW on presentation to the emergency service have greater odds of all-cause in-hospital mortality compared to dogs with a lower RDW. A similar association between RDW and mortality was not found in cats. Further studies are warranted to assess the usefulness of this biomarker for specific diseases in dogs and to better understand the mechanisms driving the association between increased RDW and mortality in canine patients.

Retrospective evaluation of fluid production at the time of thoracostomy tube removal following elective and emergency surgery in dogs (2010-2017): 185 cases.

OBJECTIVE: To report the rate of fluid production at the time of removal of thoracostomy tubes placed intraoperatively and to determine the association of this rate with specific patient factors, surgical factors, or clinical diagnosis. The secondary objective was to determine whether identification of pleural effusion within 2 weeks of thoracostomy tube removal was associated with the same variables. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: One hundred eighty-five client-owned dogs with thoracostomy tubes placed intraoperatively between January 2010 and March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thoracostomy tubes were removed at a median fluid production of 0.09 mL/kg/h (range, 0-7.0 m L/kg/h). Median fluid production at the time of thoracostomy tube removal was significantly higher in dogs with preoperative pleural effusion compared to dogs without preoperative pleural effusion (0.21 vs 0.05 mL/kg/h; P = 0.0001) and in dogs that had a median sternotomy compared to dogs that had a lateral thoracotomy (0.14 vs 0.09 mL/kg/h; P = 0.04). Of the 169 dogs available for follow-up, 12 (7.1%) had pleural effusion within 2 weeks of removal of the thoracostomy tube. Detection of pleural effusion during the follow-up period was significantly associated with the presence of preoperative pleural effusion (P = 0.0019) and the diagnosis (P = 0.01). A greater proportion of dogs with a lung lobe torsion (4/9, 44.4%) and idiopathic chylothorax (2/7, 28.5%) had pleural effusion within 2 weeks compared to other diagnoses. Reintervention was performed in 4.7% of dogs. CONCLUSIONS: Thoracostomy tubes were removed at pleural fluid production rates that frequently exceeded current veterinary guidelines. However, the fluid production rate at the time of thoracostomy tube removal was not associated with the detection of pleural effusion within 2 weeks of thoracostomy tube removal, and the overall need for reintervention following thoracostomy tube removal was low (4.7%).

A mixed-methods approach to understanding domestic dog health and disease transmission risk in an indigenous reserve in Guyana, South America.

Domestic dogs (Canis lupus familiaris) can transmit a variety of pathogens due to their ubiquitousness in urban, rural and natural environments, and their close interactions with wildlife and humans. In this study, we used a mixed-methods approach to assess the role of domestic dogs as potential intermediaries of disease transmission from wildlife to humans among indigenous Waiwai in the Konashen Community Owned Conservation Area, Guyana. To address these objectives we 1) performed physical examinations and collected biological samples to assess Waiwai domestic dog health, and 2) administered questionnaires to characterize the role of dogs in the community and identify potential transmission pathways between wildlife, dogs, and humans. We observed ectoparasites on all dogs (n = 20), including: fleas (100%), ticks (15%), botflies (30%), and jigger flea lesions (Tunga penetrans) (80%). Ten percent of dogs were seropositive for Ehrlichia canis/ewingii, 10% were positive for Dirofilaria immitis, and one dog was seropositive for Leishmania infantum. All dogs (n = 20) were seronegative for: canine distemper virus, Brucella canis, Leptospira serovars, Trypanosoma cruzi, Anaplasma phagocytophilum/platys and Borrelia burgdorferi. Our questionnaire data revealed that the Waiwai remove ectoparasites from their dogs, clean up dog feces, and administer traditional and/or Western medicine to their dogs. White blood cell, strongyle-type ova, and eosinophil counts were lower in dogs that were not frequently used for hunting, dogs that did receive traditional and/or western medicine, and dogs that were frequently kept in elevated dog houses, although differences were not statistically significant. While our results suggest that the Waiwai have developed cultural practices that may promote dog health and/or prevent zoonotic disease transmission, more research is necessary to determine the efficacy of these practices. Our study provides important data on the health of dogs and the potential for disease transmission to humans in a zoonotic hotspot.

Targeted sequencing of candidate gene regions for myelofibrosis in dogs.

BACKGROUND: Myelofibrosis often lacks an identifiable cause in dogs. In humans, most primary myelofibrosis cases develop secondary to driver mutations in JAK2, CALR, or MPL. OBJECTIVES: To determine the prevalence of variants in JAK2, CALR, or MPL candidate regions in dogs with myelofibrosis and in healthy dogs. ANIMALS: Twenty-six dogs with myelofibrosis that underwent bone marrow biopsy between 2010 and 2018 and 25 control dogs matched for age, sex, and breed. METHODS: Cross-sectional study. Amplicon sequencing of JAK2 exons 12 and 14, CALR exon 9, and MPL exon 10 was performed on formalin-fixed, decalcified, paraffin-embedded bone marrow (myelofibrosis) or peripheral blood (control) DNA. Somatic variants were categorized as likely-benign or possibly-pathogenic based on predicted impact on protein function. Within the myelofibrosis group, hematologic variables and survival were compared by variant status (none, likely-benign only, and ≥1 possibly-pathogenic). The effect of age on variant count was analyzed using linear regression. RESULTS: Eighteen of 26 (69%) myelofibrosis cases had somatic variants, including 9 classified as possibly-pathogenic. No somatic variants were detected in controls. Within the myelofibrosis group, hematologic variables and survival did not differ by variant status. The number of somatic variants per myelofibrosis case increased with age (estimate, 0.69; SE, 0.29; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Somatic variants might initiate or perpetuate myelofibrosis in dogs. Our findings suggest the occurrence of clonal hematopoiesis in dogs, with increasing incidence with age, as observed in humans.

Differential central regulatory mineralocorticoidreceptor systems for anxiety and depression - Could KCNJ5 be an interesting target for further investigations in major depression?

The mineralocorticoid receptor (MR) is suggested to play a role in the pathophysiology of depression and anxiety. Main support comes from studies in patients with primary aldosteronism (PA) which suggested different central pathways for depression and anxiety mediated via the MR and gender differences. We investigated 118 patients with PA over 3 years using self-rating questionnaires for anxiety (GAD-7) and depression (PHQD) at baseline and once a year under specific treatment with adrenalectomy (ADX; n = 48) or a MR antagonist (MRA; n = 70). Genotyping for KCNJ5 mutation was performed in resected tumors. At baseline, patients treated by ADX or MRA had comparable scores for anxiety and depression. Females showed a better metabolic profile but higher scores of depression and anxiety, compared to males. Initiation of specific treatment for PA resulted in a better response in depressive symptoms after ADX and of anxiety under MRA treatment. However, GAD-7 and PHQD remained high in women over the three-year follow-up. KCNJ5 mutation, linked to co-secretion of hybrid steroids as 18-oxocortisol and 18-hydroxycortisol, was detected in 10 female and 2 male patients. They tended to have higher GAD and PHQD scores at baseline compared to patients without KNCJ5 mutation, but showed a significant better reduction in symptoms of anxiety during the 3-year follow up compared to patients without this mutation (all p < 0.05). These data support a differentiated regulation of depression and anxiety by the MR. Moreover, genetic mutations such as KCNJ5 could affect the pathophysiology of these disorders by impacting in adrenal steroidogenesis.

Lymphocyte populations in joint tissues from dogs with inflammatory stifle arthritis and associated degenerative cranial cruciate ligament rupture.

OBJECTIVE: To evaluate lymphocyte populations in stifle synovium and synovial fluid of dogs with degenerative cranial cruciate ligament rupture (CCLR). STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n=25) with stifle arthritis and CCLR, 7 dogs with arthritis associated with cartilage degeneration (osteoarthritis [OA]), and 12 healthy Beagle dogs with intact CCL. METHODS: Arthritis was graded radiographically in CCLR dogs. After collection of joint tissues, mononuclear cells were isolated and subsequently analyzed using flow cytometry for expression of CD3, CD4, CD8, and CD21. RESULTS: The proportions of CD4(+) T helper lymphocytes, CD8(+) cytotoxic T lymphocytes, and CD3(+) CD4(-) CD8(-) T lymphocytes were increased in synovium from dogs with CCLR compared with synovium from healthy Beagle dogs (P<.05). The proportion of CD3(+) CD4(-) CD8(-) T lymphocytes in synovial fluid was increased in dogs with CCLR compared with dogs with OA (P<.05). In dogs with CCLR, the proportion of CD3(+) CD4(-) CD8(-) T lymphocytes in synovial fluid was inversely correlated with radiographic arthritis (S(R) =-0.68, P<.005). CONCLUSION: Lymphocytic inflammation of stifle synovium and synovial fluid is an important feature of the CCLR arthropathy. Lymphocyte populations include T lymphocytes expressing CD4 and CD8, and CD3(+) CD4(-) CD8(-) T lymphocytes. Presence of CD3(+) CD4(-) CD8(-) T lymphocytes was associated with development of stifle synovitis. Further work is needed to fully identify the phenotype of these cells.

Characteristics of preoperative steroid profiles and glucose metabolism in patients with primary aldosteronism developing adrenal insufficiency after adrenalectomy.

Treatment of choice in patients with unilateral aldosterone producing adenoma (APA) is adrenalectomy. Following surgery, most patients retain normal adrenal function, while some develop adrenal insufficiency (AI). To facilitate early detection and treatment of AI, we aimed to identify variables measured pre-operatively that are associated with post-operative AI. Variables obtained from 66 patients before and after surgery included anthropometrical data, clinical chemistry, endocrine work-up. LC-MS/MS steroid hormone profiles from tests before surgery (ACTH-stimulation, saline infusion, dexamethasone suppression) were obtained. Based on 78 variables, machine-learning methods were used in model fitting for classification and regression to predict ACTH-stimulated cortisol after surgery. Among the 78 variables, insulin concentration during pre-operative oral glucose tolerance test (OGTT) correlated positively, and dexamethasone suppressed glucocorticoids correlated negatively with ACTH-stimulated cortisol after surgery. Inclusion of LC-MS/MS measurements allowed construction of better models associated with the occurrence of AI in the training data, but did not allow reliable prediction in cross-validation. Our results suggest that glucocorticoid co-secretion (low insulin during pre-operative OGTT and insufficient suppression of glucocorticoids following dexamethasone) are correlated with the development of post-operative AI. Addition of steroid profiles improved the accuracy of prediction, but cross validation revealed lack of reliability in the prediction of AI.

Autonomous Cortisol Secretion Influences Psychopathological Symptoms in Patients With Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is associated with impaired quality of life (QoL). Autonomous cortisol cosecretion (ACS) is a relevant phenotype of PA, which could contribute to depression and anxiety disorders. This has not been investigated so far. OBJECTIVE: To evaluate the prevalence of depression and anxiety in PA patients according to ACS. METHODS: We performed testing for hypercortisolism and evaluated anxiety, depression and QoL by self-rating questionnaires in newly diagnosed PA patients of the German Conn's Registry; 298 patients were reevaluated at follow-up. RESULTS: In the overall cohort, scores for anxiety (P < .001), depression (P < .001), and QoL (mental P = .021; physical P = .015) improved significantly at follow-up. This improvement was seen in both subgroups of patients with and without ACS, with the exception of the mental subscore in no-ACS patients. Analysis for sex differences showed that anxiety decreased significantly in females with ACS and no-ACS, whereas males with no-ACS failed to improve. Depression improved significantly in males and females with ACS (P = .004, P = 0.011 respectively), but not in those with no-ACS. Physical subscore of QoL improved significantly (P = .023) in females with ACS and mental subscore (P = .027) in males with ACS, whereas no differences were seen for the no-ACS groups. CONCLUSION: Improvement in depression and anxiety scores in response to treatment of PA is more pronounced in patients with ACS in contrast to no-ACS suggesting a role of ACS in the psychopathological symptoms of patients with PA. Furthermore, we observed significant differences in depression and anxiety scores between the sexes.

Altered Taste Perception for Sodium Chloride in Patients With Primary Aldosteronism: A Prospective Cohort Study.

[Figure: see text].