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Objective: Thromboelastography (TEG) is a whole blood assay that yields global assessment of hemostasis, as it evaluates clot time, strength, and kinematics of clot formation and lysis. The main objective was to describe preoperative TEG findings in dogs that had an adrenalectomy performed and, secondarily, to describe TEG findings in the dogs with or without hyperadrenocorticism (HAC)., Animals: 30 dogs that had preoperative TEG and adrenalectomy performed., Methods: Medical records between 2018 and 2022 were reviewed. Signalment, diagnostic data, and perioperative treatment were abstracted., Results: 53% (16/30) of the dogs were hypercoagulable, and none were hypocoagulable. Based on histopathology, 6 of 9 dogs with adenocarcinoma were hypercoagulable, 4 of 8 with pheochromocytoma were hypercoagulable, and 6 of 10 with adenoma were hypercoagulable. None of the 3 dogs with other histopathologic diagnoses or combinations of diagnoses (adrenocortical hyperplasia, poorly differentiated sarcoma, and both adrenocortical adenocarcinoma and pheochromocytoma) were hypercoagulable. Of the 14 dogs tested preoperatively for HAC, 4 of 8 HAC dogs were hypercoagulable and 2 of 6 non-HAC dogs were hypercoagulable., Clinical Relevance: The present report describes for the first time TEG findings for dogs undergoing adrenalectomy and suggests that the majority of dogs with adrenal neoplasia are hypercoagulable based on TEG results.

We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years and 9 months old, presented with stiff gait and trismus as well as polyuria and polydipsia. Abdominal ultrasonography showed enlarged adrenal glands. An adrenocorticotropic hormone stimulation test revealed an exaggerated response. Based on these findings, this case was diagnosed with hyperadrenocorticism. Electromyography revealed myotonic discharge in the temporalis muscle and limbs. Therefore, trismus was considered to be caused by hyperadrenocorticism-associated myotonia, and the case was treated with oral trilostane (1.3 mg/kg, once daily). During the 4-month follow-up period, despite the partial improvement in stiff gait, trismus did not recover. Long-term data on more cases are warranted to assess the prognosis and clinical characteristics of trismus due to hyperadrenocorticism-associated myotonia.

Canine hyperadrenocorticism is a common endocrine disorder caused by chronic secretion of glucocorticoid, often associated with hypercoagulability and secondary thrombosis. The thrombin generation assay (TGA) evaluates hemostasis globally by measuring endogenous thrombin potential. We aimed to determine whether TGA is suitable for assessing hypercoagulability in dogs with endogenous hyperadrenocorticism (HAC), and to correlate TGA with coagulation markers including fibrinogen, antithrombin (AT), D-dimer, prothrombin time (PT) and activated partial thromboplastin time (aPTT), and with routine laboratory tests for elucidating prothrombotic mechanisms and evaluating their utility as hypercoagulability screening tests. Thrombin generation performed with high activator concentration showed significantly higher endogenous thrombin potential (ETP) (P = .0239) and peak thrombin (P = .0281) in Cushing patients. Fibrinogen (P = <.0001) and AT (P = .0444) activities were significantly higher in the HAC group, while those of PT (P = .0046) and aPTT (P = .0002) were lower. Basal cortisol levels correlated positively with fibrinogen (r = 0.4503; P = .0355) and negatively with AT activity (r = -0.4580; P = .0280). Fibrinogen and hematocrit values were inversely correlated (r = -0.4853; P = .0076). Our study confirmed the presence of higher thrombin generation in dogs with HAC. However, TGA performed with lower activator concentrations was unsuitable for detecting hypercoagulability. Higher AT and fibrinogen levels and lower aPTT activity were identified in dogs with HAC relative to controls suggesting a potential role for the combined use of these assays when assessing hypercoagulability in canine hyperadrenocorticism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The ongoing coronavirus disease 2019 (COVID-19) pandemic forced a change in the way we provide medical treatment. Endocrinology in the era of COVID-19 had to transform and reduce its vast potential to the absolute necessities. Medical professionals needed to update their clinical practice to provide their patients as much support and as little harm as possible in these increasingly difficult times. International expert statements were published to offer guidance regarding proper care. It was suggested to simplify the diagnostic scheme of hypercortisolemia and to modify the approach to treatment. Hypercortisolemic patients with COVID-19 and iatrogenic hypercortisolemia due to glucocorticoid use are important clinical scenarios - we aimed to provide a cohesive summary of issues to consider., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Berlińska, Świątkowska-Stodulska and Sworczak.)

A 9 yr old male neutered Staffordshire bull terrier with a history of poorly controlled hyperadrenocorticism, urinary tract infections, and emphysematous cystitis (EC) was presented to a veterinary referral teaching hospital for vomiting. Abdominal radiographs revealed EC and a pneumoperitoneum. The urinary bladder was found to be intact based on ultrasound and a pre- and postiohexol contrast computed tomography study with retrograde contrast cystogram. Urine culture confirmed the presence of a recurrent Escherichia coli urinary tract infection. The patient was managed medically, primarily as an outpatient, and had complete resolution of all problems. This case represents an extremely rare form of EC with pneumoperitoneum, without evidence of concurrent urinary bladder rupture. Only six similar cases have been reported in humans, with no previous cases reported in veterinary medicine. This case demonstrated that surgery is not necessarily indicated in all cases of pneumoperitoneum. The patient remained alive at 2 mo follow-up, with no evidence of recurrence of EC., (© 2021 by American Animal Hospital Association.)

Leptin and adiponectin are thought to modulate insulin sensitivity and pancreatic β-cell function, but there is limited information regarding the adipokine status of hyperglycemic dogs with hyperadrenocorticism. This study aimed to determine whether alterations in the leptin/adiponectin ratio, insulin sensitivity, and/or pancreatic β-cell function are associated with diabetes mellitus (DM) in dogs with pituitary-dependent hyperadrenocorticism (PDH). A total of 48 client-owned dogs were included in this prospective observational study: 20 dogs with PDH (10 normoglycemic and 10 with DM), 15 dogs with DM, and 13 healthy dogs. The serum concentrations of leptin, adiponectin, resistin, interleukin (IL)-1β, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF)-α were measured, and homeostatic model assessment indices (HOMAs) were calculated and compared among the groups. Serum leptin was significantly higher in PDH dogs with and without DM than in healthy and DM dogs, and it was lower in DM dogs than in PDH dogs without DM. Serum adiponectin was significantly lower in PDH dogs with DM than in healthy and PDH dogs, and it was significantly lower in DM dogs than in healthy dogs. Serum IL-10 was significantly higher in PDH dogs with DM than in healthy and PDH dogs without DM. The leptin/adiponectin ratio was significantly higher in PDH dogs with DM than in normoglycemic PDH dogs. Serum IL-6 concentrations were significantly higher in DM dogs than in healthy dogs. Serum IL-1β concentration was significantly higher in DM dogs than in healthy dogs and PDH dogs with DM and without DM. Serum TNF-α and IL-18 concentrations were not different among groups. The HOMA β-cell function was significantly lower in PDH dogs with DM than in normoglycemic PDH dogs, while HOMA insulin sensitivity was significantly lower in PDH dogs with DM than in healthy dogs. These results suggest that adipokine dysregulation, a reduction in insulin sensitivity, and a further impairment in pancreatic β-cell function might predispose PDH dogs to DM. Further longitudinal study will be necessary to confirm this result., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Systemic hypertension (SH) is common in dogs with hyperadrenocorticism (HAC) however there are not many studies assessing its prevalence and risk factors., Objectives: To determine the prevalence and severity of SH in dogs with HAC and its association with clinical and laboratory findings to identify potential risk factors., Animals: Sixty-six client owned dogs with spontaneous HAC., Methods: Retrospective cross-sectional study. Medical records of dogs with HAC were reviewed. Systolic blood pressure (SBP) was measured using Doppler ultrasonography. Clinical signs, physical examination findings and clinicopathologic data (CBC, serum biochemistry and electrolytes, urinalysis and urinary culture, and adrenal function tests) were reviewed for analysis., Results: Prevalence of SH (≥150 mm Hg) was 82% (54/66) and prevalence of severe SH (≥180 mm Hg) was 46% (30/66). All dogs with thrombocytosis had SH (P = .002), and a platelet count ≥438 × 10 3 /μL was 100% specific and 61.1% sensitive to predict SH (AUC = .802, P = .001). Median potassium levels were lower in hypertensive dogs (4.1 mEq/L, range 3.1-5.4 mEq/L) than in normotensive ones (4.5 mEq/L, range 4.0-5.0 mEq/L) (P = .007). Dogs with UPC ≥ 0.5 had higher median SBP than those without proteinuria (P = .03). Dogs with concurrent diabetes mellitus seemed to have a reduced risk of SH (OR = .118, 95%CI = .022-.626, P = .02)., Conclusions and Clinical Importance: Systemic hypertension is common in dogs with HAC and is frequently severe. Blood pressure should be routinely assessed in these dogs, especially if thrombocytosis, proteinuria or low potassium concentrations are present., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Increased hormonal secretion of aldosterone, cortisol, or catecholamines from an adrenal gland can produce a variety of undesirable symptoms, including hypertension, which may be the initial presenting symptom. Consequences of secondary hypertension can result in potential cardiovascular and cerebrovascular complications at higher rates than in those with essential hypertension. Once a biochemical diagnosis is confirmed, targeted pharmacotherapy can be initiated to improve hypertension and may be corrected with surgical intervention. Adrenalectomy can be curative and can reverse the risk of cardiovascular sequelae once blood pressure control is achieved. This article discusses perioperative and operative considerations of adrenal causes of hypertension., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: Improvement of imaging methods has led to more incidental adrenal tumor findings, especially adenomas. Routine hormonal evaluation uses only a few steroids to evaluate possible hormonal hypersecretion of these adenomas, but a wide spectrum of serum steroid hormone changes has not been published., Objective: To measure the serum levels of 83 steroids from patients with unilateral and bilateral adrenal incidentalomas to uncover full steroid profile changes in patients with subclinical hypercortisolism (SH)., Design: Cross-sectional study., Setting: The study was conducted at a tertiary inpatient clinic., Patients: Fifty-two patients with adrenal incidentalomas (unilateral, n = 29; bilateral, n = 23), including nonfunctioning (n = 11) vs SH (n = 41), and 26 age- and sex-matched controls from the general population were included., Main Outcome Measures: Eighty-three serum steroids were measured by gas chromatography-tandem mass spectrometry (GC-MS/MS) before and after 1 mg dexamethasone, ACTH, midnight serum cortisol, and urinary free cortisol/24 hour., Results: Of 83 measured steroids, 10 were significantly decreased in patients with SH, including dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate, epiandrosterone sulfate, androstenediol sulfate, conjugated 5α-androstane-3β,17β-diol, and conjugated 5α-androstane-3α,17β-diol. This finding was observed even when unilateral, bilateral, male, and female subgroups were analyzed separately. When we compared routine clinical methods and GC-MS/MS‒measured steroids, the most discriminatory was DHEAS followed by midnight serum cortisol, epiandrosterone sulfate, androsterone sulfate, ACTH, and 16α-hydroxypregnenolone., Conclusions: SH was associated with decreased levels of adrenal androgens, their metabolites, and pregnenolone metabolite. GC-MS/MS is a powerful tool for measuring serum levels of these undescribed changes in steroid metabolism, which are characteristic of SH in adrenal incidentalomas., (Copyright © 2019 Endocrine Society.)

It was studed basal and ACTH-stimulated production of cyclic adenosine monophosphate (cAMP) and corticosteroid hormones (progesterone and corticosterone) in rat adrenals in vitro under streptozotocin diabetes, in conditions of mifepristone administration and their combination. It was shown that in streptozotocin diabetes animals, both the basal and adrenocorticotropic hormone (ACTH) stimulated cAMP production significantly increased; this was accompanied by the increase in basal and ACTH-stimulated progesterone and corticosterone production in rat adrenals in vitro. Repeated administration of mifepristone to control and diabetic rats caused an increase mainly in ACTH-stimulated production of the main glucocorticoid hormone, corticosterone, without additional changes in the cAMP level. The results obtained suggest activation of two mechanisms of steroidogenesis enhancement in experimental animals. In rats with streptozotocin diabetes, both basal and ACTH-stimulated activity of all stages of steroidogenesis increase, which is mediated by the increased formation of cAMP as second messenger mediating the ACTH action on adrenocortical cells. Prolonged administration of mifepristone to control and diabetic rats resulted in increased activity of only late stages of steroidogenesis with predominant elevation of synthesis of physiologically active hormone corticosterone without additional changes in cAMP production level.

The role of hypertriglyceridemia (HTG) secondary to endocrine diseases in the occurrence of pancreatitis in dogs has not been fully investigated. The objective of the present study was to evaluate HTG as a mediator between endocrine diseases and pancreatitis in dogs. The study design was a retrospective case-control study. Medical records of dogs newly diagnosed with acutely presenting pancreatitis between 2012 and 2014 were reviewed for the presence or absence of hyperadrenocorticism (HAC), diabetes mellitus (DM), and hypothyroidism. A matched case-control analysis was performed, and the association between endocrine diseases and pancreatitis was evaluated using multiple logistic regression analysis. In dogs with pancreatitis, the odds of HAC (P < .001) and DM (P < .001) were 4.5 and 12.4 times that of dogs without pancreatitis, respectively. HTG significantly mediated the association between DM and pancreatitis but not between HAC and pancreatitis. Additional studies will be necessary to confirm these findings and to further elucidate the associations between endocrine diseases and pancreatitis.

Rationale: Celiac disease (CD) is an autoimmune disorder induced by dietary gluten in genetically predisposed subjects. Activation of the hypothalamic-pituitary-axis (HPA) can occur in patients with CD; however, this condition has never been described in overweight/obese CD children., Patient Concerns: A 12-year-old girl with CD was admitted with mild acanthosis nigricans of the armpits, groin and neck. Recently, extra fat appeared around the neck, and moon face was observed. The abdomen was globular and meteoric, treatable and not aching. She weighed 64 kilos (75°-97° percentile) and was 146 centimeters tall (3°-25° percentile) with a body mass index of 30 kg/mq. Laboratory tests revealed hypertriglyceridemia and positive anti-transglutaminase IgA. Cortisoluria was determined. Serum ACTH was normal., Diagnoses: This paper reports a case of a girl with CD in which both obesity and activation of HPA activity were noted., Interventions: During follow-up, anti-transglutaminase IgA increased to 201.5 UI/mL. The patient was positive for anti-endomysium antibodies, and the HLA DQ2 haplotype was identified, confirming a diagnosis of CD., Outcomes: Despite a gluten-free diet, obesity and hyperadrenalism persisted, and anti-transglutaminase antibodies remained elevated. In addition, high cortisoluria persisted. A high-dose suppression dexamethasone test (8 mg) produced negative results with a morning cortisol value of 1 ng/mL, suggesting the diagnosis of pseudo-Cushing's syndrome., Lessons: This case highlights that the first manifestation of CD could be being overweight, and this finding seems to support the need to prescribe laboratory tests for CD not only to children with failure to thrive, as commonly recommended, but also to those with increased body weight.

Objective: To describe clinical aspects of dogs with punctate retinal hemorrhage (PRH)., Animals Studied: 83 dogs (119 eyes) with PRH., Procedures: Medical records of dogs evaluated by the Cornell University ophthalmology service with a clinical diagnosis of PRH between 2006 and 2015 were reviewed. For this study, PRH was defined as retinal hemorrhages ≤ 1 optic disk diameter in size and dogs with other posterior segment ocular diseases were excluded. Signalment and clinical features of the dogs were recorded, including concurrent ocular and systemic diseases., Results: Punctate retinal hemorrhage was identified in 119 eyes of 83 dogs. The mean (±standard deviation) age of dogs was 10.0 (±3.8) years. Mixed-breed dogs, Golden Retrievers, Jack Russell Terriers, and English Springer Spaniels were statistically overrepresented relative to the ophthalmology service canine referral population during the same period. Hemorrhages were found in all retinal locations and varied in number. Concurrent ocular disease was present in 78 eyes (66%) including keratoconjunctivitis sicca, uveitis, and cataracts. Fifty dogs (60%) suffered from concurrent systemic disease and diabetes mellitus, multiple myeloma, and systemic hypertension were statistically overrepresented in the PRH population. Less frequently, other serious systemic diseases were present in dogs with PRH including immune-mediated thrombocytopenia, leptospirosis, metastatic neoplasia, and thromboembolic disease., Conclusions: The risk of PRH in dogs may be increased by certain ocular and systemic diseases. As the presence of PRH can be associated with underlying systemic disease in dogs, it may prompt further clinical investigation and diagnostics., (© 2017 American College of Veterinary Ophthalmologists.)

A 12-year-old female Shih-Tzu with hyperadrenocorticism and hypothyroidism developed concurrent refractory generalized demodicosis that did not respond to doramectin treatment. Although amitraz treatment was effective, the dog developed severe diabetes, which resulted in the cessation of amitraz and trilostane. Attempts to control the diabetes were unsuccessful, and its hyperadrenocorticism was left untreated, leading to the recurrence of demodicosis. However, demodicosis went into complete remission with a single dose of fluralaner. Transient erythematous papules appeared on the trunk three days after the administration of fluralaner, but no other adverse reactions were noted. We demonstrated that fluralaner is a potent treatment for demodicosis, and skin eruptions are possible after the first dose of the drug.

Bacterial pyoderma is common in small animal practice. Usually there is an associated underlying disease, but little is known about the prevalence of underlying diseases in dogs with recurrent pyoderma. The aim of this study was to analyse the frequency of the different underlying diseases in dogs with recurrent pyoderma. In total, 157 animals with recurrent pyoderma were identified in hospital records from 2008 to 2013 and the data analysed for primary diseases. The time between recurrences, the type of clinical signs and the age at pyoderma onset were also evaluated. At least one primary disease was found in 107 dogs. Allergies were the primary cause in 63 dogs, environmental allergy was the most frequent (n=45) and was often associated with other allergies, followed by hypothyroidism (n=12) and hyperadrenocorticism (n=6). Sixteen dogs with recurrent pyoderma suffered from demodicosis. In young dogs with recurrent pyoderma an allergy work-up combined with deep skin scrapings should lead to a diagnosis of the underlying disease in most of the cases. In dogs in which pyoderma began in middle or old age, hormonal testing and ruling out a possible flea infestation should be the first steps., Competing Interests: Competing interests: None declared., (© British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

CASE DESCRIPTION A 13-month-old castrated male cat was evaluated for a large, spontaneously developed cutaneous laceration over the left scapular region. The cat had a history of severe gingivostomatitis, conjunctivitis, giardiasis, and feline herpesvirus infection and had received systemic glucocorticoid treatment for 7 weeks prior to evaluation. CLINICAL FINDINGS Physical examination revealed a 10 × 7-cm full-thickness cutaneous laceration over the left scapular region, extremely thin skin, crusts over the dorsal aspect of the neck and base of the skull, medially curling pinnae, and moderate gingivostomatitis. TREATMENT AND OUTCOME Staged wound closure was performed with a combination of daily wound cleaning and debridement, tension and appositional sutures, and wet-to-dry and nonadherent dressings initially with a bacitracin, neomycin, and polymyxin B ointment and then with a 30:1 mixture of silver sulfadiazine and insulin. Multiple additional lesions developed and were treated in the same manner. Complete closure and resolution of all cutaneous lesions was achieved in 9 weeks. CLINICAL RELEVANCE Cats are fairly resistant to the adverse effects of glucocorticoid treatment, and iatrogenic hyperadrenocorticism is rarely reported. This case demonstrated that acquired skin fragility syndrome secondary to iatrogenic hyperadrenocorticism can develop following short-term systemic glucocorticoid administration and that large cutaneous wounds associated with this condition can be successfully managed and closed by means of the reported methods. The prognosis for skin recovery in cats with acquired skin fragility syndrome may be more favorable than previously reported.

Hyperadrenocorticism (HAC) and diabetes mellitus (DM) are two diseases that can occur concurrently in dogs. The objective of this study was to evaluate the coexistence of HAC and DM, and the risk factors involved that could contribute to the development of DM in dogs with HAC. A total of 235 dogs with HAC were studied and, according to their fasting glycemia, they were divided into three groups: <5.6mmol/L, between 5.6 and 10.08mmol/L and >10.08mmol/L. The following parameters were evaluated: age, gender, cause of HAC, body condition, glycemia, total cholesterol, triglycerides, urinary cortisol:creatinin ratio (UCCR) and survival time. A 13.61% concurrence of HAC and DM was observed. Dogs with a fasting glycemia >5.6mmol/L, with dislipemia, with Pituitary-Dependent Hyperadrenocorticism, UCCR >100×10 -6 and non-castrated females showed a higher risk of developing DM. The development of DM in dogs with HAC reduces the survival time., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Thrombosis is a serious complication of many canine diseases and may be related to decreased fibrinolytic potential. Plasminogen activator inhibitor-1 (PAI-1) is the key regulator of fibrinolysis with increased levels demonstrated in states of pro-thrombosis and abnormal lipid metabolism. Our objective was to develop and validate a canine PAI-1 activity assay and test whether dogs with hyperadrenocorticism or diabetes mellitus that are hyperlipidemic/dyslipidemic have increased plasma PAI-1 activity. Functionally active PAI-1 in the plasma sample was incubated with recombinant tissue plasminogen activator (tPA), allowing the formation of a 1:1 stoichiometric inactive complex. Residual unbound tPA was then reacted with excess plasminogen in the presence of a colorimetric plasmin substrate. Plasmin production is quantified by computing the area under the curve of time (x) vs optical density (y) plot and converted to tPA IU/mL by comparison to a calibration curve of tPA standards. PAI-1 activity was determined by calculating the proportion of exogeneous tPA suppressed by PAI-1 in plasma. Assay verification included assessment of linearity, specificity, precision, sensitivity, and stability. PAI-1 activity was increased in hyperlipidemic compared to healthy dogs, but there was no significant difference between dogs with hyperadrenocorticism and diabetes mellitus. A near significant decrease in activity was detected in thawed plasma stored for 20h at 4°C. Our successfully validated assay offers a new tool for investigating fibrinolysis in dogs. Investigation of PAI-1 activity in dogs with other diseases associated with an increased risk of thrombosis would be valuable. Future studies of PAI-1 activity should consider its lability., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Benign adrenal tumors are commonly discovered on abdominal imaging. Most are classified as nonfunctional and are considered to pose no health risk, but some are considered functional because they secrete hormones that increase risk for metabolic and cardiovascular diseases., Objective: To evaluate the hypothesis that nonfunctional adrenal tumors (NFATs) increase risk for cardiometabolic outcomes compared with absence of adrenal tumors., Design: Cohort study., Setting: Integrated hospital system., Participants: Participants with benign NFATs ("exposed"; n = 166) and those with no adrenal tumor ("unexposed"; n = 740), with at least 3 years of follow-up., Measurements: Medical records were reviewed from the time of abdominal imaging for development of incident outcomes (hypertension, composite diabetes [prediabetes or type 2 diabetes], hyperlipidemia, cardiovascular events, and chronic kidney disease) (mean, 7.7 years). Primary analyses evaluated independent associations between exposure status and incident outcomes by using adjusted generalized linear models. Secondary analyses evaluated relationships between NFATs and cortisol physiology., Results: Participants with NFATs had significantly higher risk for incident composite diabetes than those without adrenal tumors (30 of 110 [27.3%] vs. 72 of 615 [11.7%] participants; absolute risk, 15.6% [95% CI, 6.9% to 24.3%]; adjusted risk ratio, 1.87 [CI, 1.17 to 2.98]). No significant associations between NFATs and other outcomes were observed. Higher "normal" postdexamethasone cortisol levels (≤50 nmol/L) were associated with larger NFAT size and higher prevalence of type 2 diabetes., Limitation: Potential bias in the selection of participants and ascertainment of outcomes., Conclusion: Participants with NFATs had a significantly higher risk for diabetes than those without adrenal tumors. These results should prompt a reassessment of whether the classification of benign adrenal tumors as "nonfunctional" adequately reflects the continuum of hormone secretion and metabolic risk they may harbor., Primary Funding Source: National Institutes of Health and Doris Duke Charitable Foundation.

Context: Subtle hypercortisolism is associated with an increased risk of vertebral fracture (VFx)., Objective: The objective was to determine the best parameters of cortisol secretion for detecting the VFx risk in patients with adrenal incidentalomas (AI)., Design: This was a retrospective (cross-sectional arm) and prospective (longitudinal arm) design. In the cross-sectional arm, we assessed the accuracy of the cortisol secretion indexes in identifying the patients with VFx (prevalent VFx). In the longitudinal arm, we tested the cortisol secretion parameters, which were able to identify the prevalent VFx, for the prediction of the occurrence of a new VFx (incident VFx) in AI patients followed-up for at least 2 years., Setting: Four referral Italian endocrinology units participated in this study., Patients: A total of 444 and 126 AI patients without symptoms of hypercortisolism enrolled in the cross-sectional arm and longitudinal arm, respectively., Main Outcome Measures: Serum cortisol after a 1-mg dexamethasone suppression test (1 mg DST), urinary free cortisol, ACTH, bone mineral density at lumbar spine and femoral neck (by dual-energy x-ray absorptiometry), and the VFx presence (by x-ray)., Results: The cortisol levels after 1 mg DST that were greater than 2.0 μg/dl (55 nmol/liter) were the best criteria for detecting patients with both prevalent (73.6% sensitivity, 70.5% specificity) and incident VFx (80% sensitivity, 68.8% specificity) and were associated with a 10-fold increased risk of a new VFx (odds ratio,10.27; 95% confidence interval, 3.39-31.12; P < .0001), regardless of age, gender, bone mineral density at lumbar spine, and prevalent VFx., Conclusions: In AI patients without symptoms of overt hypercortisolism, the cortisol levels after 1 mg DST greater than 2.0 μg/dl (55 nmol/liter) represent the best criterion for detecting prevalent and incident VFx.

Arterial hypertensions (HTA) of endocrine origin are a rare cause of hypertension; HTA overall prevalence don't exceed 4% of hypertensive patients. Research interest in endocrine HTA is due to the severity of some life-threatening, potentially curable and reversible forms of HTA. The aim of our study was to determine the clinical, paraclinical, etiological and therapeutic profile of secondary HTA of endocrine origin in patients treated in endocrinology department at the University Hospital Mohamed VI in Marrakech. We conducted a prospective, descriptive study spanned 4 years, enrolling 45 patients with endocrine HTA. The average age was 44.89 years, with a clear predominance of women (sex ratio 0.49). Etiology of endocrine HTA was dominated by pheochromocytoma (17 cases), hypercorticism (11 cases) and acromegaly (8 cases). HTA were paroxysmal in 24.4%. HTA were immediately classified as grade 3 severe in 40% of cases. HTA were complicated by heart disease in 24% of cases and by renal disease in 20% of cases. Curative treatment cleared up HTA in 60% of cases (27 cases). The diagnosis of secondary endocrine HTA is sometimes difficult because of the lack of clinical specificity. It is not unusual for HTA to be the only manifestation of the disease. In our study we noted the paroxysmal and severe nature of HTA. The potentially curable nature of HTA in more than two thirds of cases, demostrates the importance of early diagnosis of each severe HTA resistant to treatment or in the presence of suggestive clinical, biological or radiological signs.

Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in diabetes mellitus-associated late-onset hypogonadism., (© Georg Thieme Verlag KG Stuttgart · New York.)

Two dogs were diagnosed with myotonia associated with hyperadrenocorticism and treated with trilostane. One dog showed temporary improvement, but the other dog showed no improvement. The dogs survived 2383 and 1902 days, respectively. Findings suggest that myotonia persists despite treatment, but this condition is not associated with a poor prognosis for survival.

Objectives: Hyperadrenocorticism has been reported to cause left ventricular (LV) structural and functional abnormalities in human patients. The purpose of the present study was to assess the incidence and features of LV structural and functional changes in dogs with hyperadrenocorticism., Animals: Twenty-two client-owned dogs with pituitary-dependent hyperadrenocorticism (n = 15) and cortisol-secreting adrenocortical tumors (n = 7) and 6 control dogs were enrolled in this study., Methods: Echocardiographic examinations were performed and non-invasive measurements of systolic blood pressure (SBP) were obtained., Results: The normalized LV wall thickness and LV mass index of the affected dogs differed significantly from those of control dogs. Using a published reference value for M-mode measurements, 15 of the 22 dogs (68%) were found to have increased LV wall thickness. Eleven of the 15 (73%) dogs with increased LV wall thickness were normotensive, and no significant correlation between LV wall thickness and SBP was found., Conclusions: Regardless of the presence of systemic hypertension, hyperadrenocorticism should be included in the differential diagnosis of underlying disorders that may cause LV hypertrophy in dogs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To study the impact of adrenal hyperandrogenism (AH; defined as DHEAS concentration >95th percentile of a healthy female control population) on cardiometabolic risk factors associated with polycystic ovary syndrome (PCOS)., Design: Cross-sectional study., Setting: Academic hospital., Patient(s): Two-hundred ninety-eight consecutive women with PCOS, of whom 120 were obese (body mass index [BMI] ≥30 kg/m(2)) and 178 nonobese (BMI <30 kg/m(2))., Intervention(s): None., Main Outcome Measure(s): Comprehensive evaluation of cardiovascular risk factors, including 75-g oral glucose tolerance test, office blood pressure, lipid profile, and low-grade inflammatory markers., Result(s): Patients with AH (AH-PCOS) had higher insulin circulating levels and lower insulin sensitivity than their counterparts without AH (non-AH-PCOS). Obesity, but not AH, was the main contributor to the presence of glucose tolerance disorders. Both obesity and AH increased the prevalence of prehypertension and hypertension. AH diminished high-density lipoprotein (HDL) levels in nonobese PCOS women in parallel with a decrease in total cholesterol levels, leading to a total to HDL cholesterol ratio similar to that of nonobese non-AH-PCOS patients. Furthermore, AH blunted the deleterious effect of obesity on the total cholesterol/HDL ratio, with the ratio of obese AH-PCOS patients being similar to that of nonobese PCOS patients with or without AH., Conclusion(s): The presence of AH in women with PCOS is associated with reduced insulin sensitivity and increased blood pressure but may have beneficial impact on the lipid profile. Obesity is the main determinant of the clustering of cardiovascular risk factors in PCOS women., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

In neurosurgery practice glucocorticoids are commonly used. Steroids may have central nervous system side effects affecting whole body, including steroid-induced mental agitation and psychosis. In experimental and clinical studies conducted by using dexamethasone (DEX), it has been reported that DEX adversely affects learning and memory skills. Unfortunately, there are yet no clinically accepted clinical approaches to prevent DEX-induced cognitive dysfunction. In this experimental study it was aimed to investigate the effect of chronic DEX administration on learning-memory and locomotor behaviors in adult male Sprague Dawley rats. In addition, it was also aimed to explore the potential favorable contribution of melatonin (MEL) and vitamin C (Vit C) having antioxidant and neuroprotective properties to the effects of DEX on learning-memory and locomotor behaviors. For this purpose, rats were injected 10mg/kg DEX intraperitoneally, both alone and in combination with MEL (40 mg/kg) and Vit C (100mg/kg), for 9 days, and the animals were tested using the radial arm maze and open field apparatus. The test results revealed that DEX caused a significant decrease in spatial memory and locomotor activities and MEL and Vit C failed to reverse losses in these activities. Furthermore, DEX led to a gradual weight loss that reached 30% of the initial weight at 9th day of the injection. DEX administration causes a generalized loss of behavioral activity of rats. Experimental studies devised to investigate effects of DEX should take into account this DEX-induced generalized behavioral loss when assessing the effects of DEX on learning and memory skills. This article is part of a Special Issue entitled SI: Brain and Memory., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Hyperadrenergic postural tachycardia syndrome (POTS) is the main phenotype of POTS. The aim of this study was to present our single-center experience of hyperadrenergic POTS in children and adolescents., Methods: Thirty-seven patients who met the diagnostic criteria for POTS were enrolled in our study. Their orthostatic serum norepinephrine levels were determined by high-performance liquid chromatography. In a retrospective analysis, based on clinical and serum norepinephrine criteria, we analyzed the clinical features of POTS cases between the POTS-alone group and the hyperadrenergic POTS group., Results: Nineteen patients (51.35%) met the diagnostic criteria for hyperadrenergic POTS and 18 patients were assigned to the POTS-alone group. Compared with the POTS-alone patients, dizziness, headache and tremulousness were more frequent in patients with hyperadrenergic POTS (P < 0.05). During the tilt table test, children with hyperadrenergic POTS had a greater increment of systolic blood pressure and heart rate than POTS-alone patients., Conclusion: Patients with hyperadrenergic POTS should be identified and differentiated from those with neuropathic POTS. Hyperadrenergic POTS in children and adolescents should be considered when POTS patients suffer from frequent dizziness, headache, and tremulousness. In head-up tilt testing, children and adolescents with hemodynamic characteristics of hyperadrenergic POTS had greater increments of systolic blood pressure and heart rate., (© 2014 Japan Pediatric Society.)

A 13-year-old female domestic shorthair cat presented with polyphagia and weight loss. Marked systolic hypertension was found on examination. Elevated total thyroxine levels confirmed hyperthyroidism, and hypokalaemia was also documented. A euthyroid state and normotension were achieved following 4 weeks of treatment with carbimazole and amlodipine. Despite potassium supplementation, the hypokalaemia worsened. Abdominal ultrasonography revealed left adrenomegaly. Plasma aldosterone concentrations were initially in the lower half of the reference interval and, when repeated 2 months later, were undetectable. Urea and creatinine remained in the lower half of the reference interval throughout treatment, and urine specific gravity suggested good urine concentrating ability. The fractional excretion of potassium confirmed a renal source of potassium loss. Blood gas analysis was unremarkable. It was theorised that an aldosterone precursor was causing signs of mineralocorticoid excess and undetectable plasma aldosterone levels. Treatment with an aldosterone receptor antagonist successfully increased the serum potassium concentration. Owing to difficulties administering medication and associated effects on life quality the cat was euthanased. Adrenal hyperplasia was apparent on post-mortem histopathology., (© ISFM and AAFP 2014.)

Background: Specificity of canine pancreatic lipase immunoreactivity (cPLI) assays in dogs with hyperadrenocorticism (HAC) is unknown., Hypothesis: Results of cPLI assays differ for clinically healthy dogs and dogs with HAC., Animals: Seventeen healthy dogs and 20 dogs with HAC diagnosed by ACTH stimulation test results without evidence of clinical pancreatitis., Methods: Dogs were enrolled between December 2009 and November 2010. Serum cPLI concentrations were determined by quantitative (Spec cPL test, SPEC) and semiquantitative (SNAP cPL test, SNAP) assays. Results were categorized as normal, equivocal, or abnormal (SPEC) or negative or positive (SNAP). Associations between group and cPLI were assessed using Fisher's exact test or the Mann-Whitney U-test. Spearman rank correlation coefficients (ρ) were determined for SNAP and SPEC results. Significance was set at P < .05., Results: Spec cPL test concentrations were significantly (P < .001) higher in dogs with HAC (491.1 μg/L) than in healthy dogs (75.2 μg/L), with more abnormal SPEC results in HAC dogs (P < .001). There were more (P = .002) positive SNAP results in dogs with HAC (55%) than in healthy dogs (6%). SNAP and SPEC results were highly correlated (ρ = 0.85; P < .001)., Conclusions and Clinical Importance: Dogs with HAC had higher SPEC concentrations and more positive SNAP results than clinically healthy dogs with normal ACTH stimulation test results. Specificity of SPEC and SNAP assays in HAC dogs without clinical pancreatitis were 65 and 45%, respectively. Pending further study, SNAP and SPEC results should be interpreted cautiously in dogs with HAC to avoid false diagnosis of concurrent pancreatitis., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

A 13 yr old castrated male vizsla was referred to the authors' institute because of polyuria, polydipsia, polyphagia, and weight loss. Pituitary-dependent hypercortisolism (PDH) was diagnosed by hormone testing and adrenal and pituitary imaging. Computed tomography (CT) revealed a pituitary mass measuring 21 mm in width. Medical therapy was initiated with trilostane. Despite adequate control of the hypercortisolemia, the polyuria and polydipsia persisted and the dog developed neurologic signs due to the pituitary mass effect. Pituitary transsphenoidal debulking surgery was performed and immunocytochemistry confirmed a corticotroph adenoma. The dog survived for 13 mo after surgery. Postmortem examination revealed an empty fossa without pituitary remnants and the presence of a malignant pheochromocytoma in the right adrenal gland. This case report demonstrates, for the first time, that a large pituitary adenoma in the dog may be treated successfully by pituitary surgery.

Background: Thrombosis has been associated to some diseases like hyperadrenocorticism (HAC). Several drugs can alter the balance, such as the corticosteroid prednisone, used mainly for its anti-inflammatory and immunosuppressive effects. It is known that hypercortisolism can stimulate thrombi formation by increasing coagulation factors and decreasing fibrinolysis. However it is not known how prednisone administration affects hemostasis in dogs and if it is dose dependent. The aim of this study, therefore, was to demonstrate the effects of prednisone administration on dogs' hemostatic profile., Results: Significant decrease of antithrombin levels was observed in both groups (anti-inflammatory and immunosuppressive doses) after 15 days of treatment. An increase of platelet aggregation was observed in dogs receiving immunosuppressive doses of prednisone (Group II)., Conclusions: From the results obtained in our study, it is not possible to infer that hypercortisolism can increase the thromboembolic risk, despite the decreased anticoagulant factors (antithrombin levels).

Background: Anecdotal accounts and limited research suggest that dogs with spontaneous hyperadrenocorticism (HAC) are at risk of developing thromboembolic complications. Detailed description of coagulation status and identification of subsets of dogs at greatest risk would impact therapeutic recommendations for these patients., Hypothesis: A subset of dogs with HAC will have a hypercoagulable tendency as identified by increased procoagulant activity, decreased fibrinolysis, or both. Objective 1: To document the existence of this hypercoagulable tendency in HAC dogs using assays of individual coagulation factors, fibrinolytic activity, and systemic coagulation. Objective 2: To evaluate clinical and biochemical markers in HAC dogs to identify a subset of HAC patients at increased risk of this hypercoagulable tendency., Animals: Seventeen dogs newly diagnosed with HAC., Methods: Prospective study. Medical history, physical examination findings, routine diagnostic tests, and comprehensive coagulation testing were performed at the time of HAC diagnosis. Coagulation parameters were assessed individually and as panels for each dog. Historical and clinical variables were correlated with coagulation parameters to identify risk factors., Results: The majority (88.2%) of HAC dogs exhibited a hypercoagulable tendency. Abnormalities in 1 coagulation assay did not predict abnormalities in others. Duration of clinical signs of HAC did not predict hypercoagulability. Comorbid conditions or abnormal clinicopathologic parameters that predicted hypercoagulability were not identified., Conclusions and Clinical Importance: Although HAC dogs may demonstrate a hypercoagulable tendency individually and as a group, comorbid conditions or biochemical variables that would predict more severe coagulation abnormalities were not identified., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Background: Canine generalized demodicosis associated with hyperadrenocorticism is often problematic and might be intractable. The aim of this study was to report the efficacy of a weekly application of spot-on moxidectin/imidacloprid in dogs with hyperadrenocorticism and secondary generalized demodicosis., Methods: Dogs with hyperadrenocorticism and secondary generalized demodicosis were included. The condition of hyperadrenocorticism was treated and stabilized with trilostane before and throughout the study period in all dogs., Results: Average total live adult mite counts before treatment and after four, eight and 12 weeks of spot-on moxidectin/imidacloprid (2.5/10 mg/kg) applications were 20.1±6.3 (range, 13-33), 0.5±0.7 (range, 0-2; 6/11 were negative), 0.2±0.4 (range, 0-1; 9/11 were negative), 0.2±0.4 (range, 0-1; 9/11 were negative) and 0.1±0.3 (range, 0-1; 10/11 were negative) respectively; this difference was significant (P<0.001). Ten of 11 dogs (90.1%) achieved clinical remission, as demonstrated by the absence of demodectic mites at any life stage at monthly scrapings for eight consecutive weeks, and maintained remission throughout the 12-month follow-up period., Conclusion: The weekly application of spot-on moxidectin/imidacloprid appeared to be effective and safe against generalized adult onset canine demodicosis associated with hyperadrenocorticism.

When confronted with a diabetic cat in clinical practice, it is tempting to assume it has a form of diabetes mellitus akin to human type 2 diabetes mellitus (diabetes). For most diabetic cats examined, this will indeed be justified. Nevertheless, a significant proportion have other specific types of diabetes with distinctly different etiologies. This article discusses the concept of other specific types of feline diabetes caused by endocrinopathies, and more specifically feline hypersomatotropism, acromegaly, and hyperadrenocorticism, including relevance, presentation, diagnosis, and therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Hyperadrenocorticism (HAC) has been associated with thrombotic disease in dogs., Hypothesis: The purpose of this study was to use thromboelastography (TEG) and measurement of thrombin generation (TG) to characterize the hypercoagulable state in dogs with HAC. We hypothesized that dogs with HAC would have a hypercoagulable profile on TEG tracings and an increase in thrombin generation as measured by endogenous thrombin potential (ETP)., Animals: Sixteen dogs with HAC. Dogs were compared with a population of normal dogs used to obtain reference intervals., Methods: TEG tracings on citrated whole blood were obtained from 15 dogs, and TG measurements on frozen-thawed platelet-poor plasma (PPP) were obtained from 15 dogs., Results: For the TEG analysis, when results of individual dogs were compared with the reference interval, 12/15 dogs had at least 1 parameter associated with hypercoagulability. When the population of HAC dogs was compared with a population of healthy dogs, HAC dogs had decreases in R and K and increases in α and MA values. The ETP was increased when the HAC group was compared with a population of normal dogs. However, only 3/15 dogs had an ETP above reference interval, and 1/15 had a decreased lag time., Conclusion and Clinical Importance: Of 16 dogs with HAC, 12/15 had evidence of hypercoagulability when evaluated by TEG, 4/15 when evaluated by TG, and 2 dogs had increases in ETP and MA., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1-mg dexamethasone suppression test (1-mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X-ray absorptiometry and TBS was assessed in the region of LS-BMD; BMD and TBS data were reported as Z-scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS-BMD (-0.31 ± 1.17), FT-BMD (-0.29 ± 0.91), and TBS (-3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; -1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; -1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1-mg DST (β = -0.26, t = -2.79, p = 0.006) regardless of age, LS-BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85-12.42, p = 0.001) and with the cluster low TBS plus low LS-BMD (OR, 4.37; 95% CI, 1.71-11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS-BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > -1.5) plus normal LS-BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71-71.41, p = 0.012) regardless of LS-BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures., (Copyright © 2012 American Society for Bone and Mineral Research.)

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects β-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83 mmol/L and two groups with glycaemia >5.83 mmol/L and <9.35 mmol/L, one of which received insulin detemir during 4 months. Dogs with glycaemia <5.83 mmol/L and those with glycaemia >5.83 mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83 mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83 mmol/L could prevent progression to diabetes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We present a 16-year-old boy with weakness, hypercortisolemia, and markedly elevated adrenocorticotropic hormone. Computed tomographic imaging revealed hepatic lesions and a calcified pancreatic mass. Biopsy of the hepatic lesions revealed moderately differentiated neuroendocrine carcinoma. The primary tumor could not be determined. The patient received neoadjuvant chemotherapy with carboplatin and etoposide followed by therapeutic bilateral adrenalectomy and tumor debulking. Despite significant clinical improvement, restaging revealed progressive hepatic disease. The patient died 9 months after diagnosis. Autopsy revealed disseminated neuroendocrine carcinoma. The rarity of this tumor compels a cooperative investigational model involving pediatric and adult oncologists.

Objective: The purpose of our study was to clarify whether subtle cortisol-producing tumors, such as not only subclinical Cushing's syndrome (SubCS) but also subclinical hypercortisolism (SH), influence the prevalence of hypertension, since numerous basic research studies have noted that glucocorticoid excess influences blood pressure., Methods: 80 patients with adrenocortical adenomas (39 women and 41 men; mean age 62.1 years) were enrolled. SubCS was diagnosed using a diagnostic criteria, and SH was diagnosed as the presence of a serum cortisol level greater than 50 nmol/L following 1-mg dexamethasone suppression test (DST)., Results: SubCS, SH, or non-functioning adrenocortical adenoma (NF) was diagnosed in 14, 13, or 53 patients, respectively. The prevalence of hypertension differed significantly among the diagnoses (SubCS, 78.6%; SH, 84.6%; NF, 39.6%; P=0.002), whereas no differences in other clinical characteristics such as age, sex, or waist girth were observed. The patients with SH had an 11.7-fold increased risk (95% confidence interval: 1.9-72.7, P=0.009) and those with SubCS had a 9.5-fold increased risk (95% confidence interval: 1.9-48.3, P=0.007) for hypertension compared to those with NF using a multivariate analysis., Conclusion: We demonstrated that subtle cortisol-producing tumors, such as SH as well as SubCS, were an independent risk factor for hypertension. The cut-off value of the 1-mg DST would be appropriate to predict the development of hypertension., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

We recently implicated two recurrent somatic mutations in an adrenal potassium channel, KCNJ5, as a cause of aldosterone-producing adrenal adenomas (APAs) and one inherited KCNJ5 mutation in a Mendelian form of early severe hypertension with massive adrenal hyperplasia. The mutations identified all altered the channel selectivity filter, producing increased Na(+) conductance and membrane depolarization, the signal for aldosterone production and proliferation of adrenal glomerulosa cells. We report herein members of four kindreds with early onset primary aldosteronism of unknown cause. Sequencing of KCNJ5 revealed that affected members of two kindreds had KCNJ5(G151R) mutations, identical to one of the prevalent recurrent mutations in APAs. These individuals had severe progressive aldosteronism and hyperplasia requiring bilateral adrenalectomy in childhood for blood pressure control. Affected members of the other two kindreds had KCNJ5(G151E) mutations, which are not seen in APAs. These subjects had easily controlled hypertension and no evidence of hyperplasia. Surprisingly, electrophysiology of channels expressed in 293T cells demonstrated that KCNJ5(G151E) was the more extreme mutation, producing a much larger Na(+) conductance than KCNJ5(G151R), resulting in rapid Na(+)-dependent cell lethality. We infer that this increased lethality limits adrenocortical cell mass and the severity of aldosteronism in vivo, accounting for the milder phenotype among these patients. These findings demonstrate striking variations in phenotypes and clinical outcome resulting from different mutations of the same amino acid in KCNJ5 and have implications for the diagnosis and pathogenesis of primary aldosteronism with and without adrenal hyperplasia.

A seven-year-old Burmese cat was presented with sudden onset blindness. On physical examination, the cat had bilateral retinal detachment and severe systemic hypertension. Further clinical investigations revealed pituitary-dependent hyperadrenocorticism. Antihypertensive therapy was discontinued when the hypertension resolved after bilateral adrenalectomy. Systolic blood pressure remained normal until 19 months post-operatively when systemic hypertension recurred and was attributed to chronic kidney disease. The cat was euthanased 47 months after initial presentation. A pituitary adenoma was identified at post-mortem examination. This case illustrates that systemic hypertension can occur secondary to hyperadrenocorticism in the cat., (© 2011 British Small Animal Veterinary Association.)

Ten dogs that had skin lesions as the only presenting signs of hyperadrenocorticism (HAC) and as the owners' primary complaint are described. Dogs were included if the initial examination was for skin disease, there were no signs of systemic illness on initial presentation and there was a confirmed diagnosis of HAC by specific screening tests. Dogs were excluded if they had a severe disease that might interfere with screening tests for HAC or if the screening tests were not diagnostic. There were five males and five females; six dogs were intact. Nine dogs were diagnosed at ≥7 years. Eight dogs weighed ≤10 kg. Alopecia was present in nine dogs. Eight dogs had bacterial pyoderma, five had hyperpigmentation, and four had thin skin. One dog had unresolved dermatophytosis. Skin lesions resolved after treatment in eight dogs. One dog was not treated and one was lost to follow-up. This study showed that skin lesions may be the only clinical signs of HAC. The presence of the more common clinical signs of HAC, such as a non-pruritic, truncal alopecia and/or thin skin, without any systemic signs of HAC and/or the presence of poorly responsive skin infections warrant screening for this disease.

We report the case of a young patient who had a past history of HSV encefalitis and presented for decreased vision in her left eye associated with pain and red eye.

An aim of the study was to optimize the diagnosis and treatment of epilepsy in women of reproductive age with concomitant disturbances of menstrual cycle. One hundred and thirty-two women, aged from 18 to 35 years, were studied. Menstrual dysfunction was found in 47,7% (n = 63): oligomenorrhea--in 68,3% (n = 43), amenorrhea--in 9,5% (n = 6) and dysfunctional metrorrhagia--in 22,2% (n = 14). Based on the character of hormone and ovarian dysfunction, the following syndromes were singled out: polycystic ovaries--54% (n = 34), isolated hypoprogesteronemia--23,8% (n = 15), hypercorticism--14,3% (n = 9), hypogonadotropic hypogonadism--7,9% (n = 5). Different hormonally-active drugs that allowed to normalize the menstrual cycle were used, along with basic antiepileptic drugs, to treat these hormonal dysfunctions and improve the course of epilepsy.

Background: Oxidative stress, an excessive production of reactive oxygen species (ROS) outstripping antioxidant defense mechanisms, occurs in cardiovascular pathologies, including hypertension. In the present study, we used biochemical, physiological, and pharmacological approaches to explore the role of derangements of catecholamines, ROS, and the endothelium-derived relaxing factor nitric oxide (NO(•)) in the development of a hyperadrenergic model of hereditary hypertension: targeted ablation (knockout [KO]) of chromogranin A (Chga) in the mouse., Methods and Results: Homozygous ⁻(/)⁻ Chga gene knockout (KO) mice were compared with wild-type (WT, +/+) control mice. In the KO mouse, elevations of systolic and diastolic blood pressure were accompanied by not only elevated catecholamine (norepinephrine and epinephrine) concentrations but also increased ROS (H₂O₂) and isoprostane (an index of lipid peroxidation), as well as depletion of NO(•). Renal transcript analyses implicated changes in Nox1/2, Xo/Xdh, and Sod1,2 mRNAs in ROS elevation by the KO state. KO alterations in blood pressure, catecholamines, H₂O₂, isoprostane, and NO(•) could be abrogated or even normalized (rescued) by either sympathetic outflow inhibition (with clonidine) or NADPH oxidase inhibition (with apocynin). In cultured renal podocytes, H₂O₂ production was substantially augmented by epinephrine (probably through β₂-adrenergic receptors) and modestly diminished by norepinephrine (probably through α₁-adrenergic receptors)., Conclusions: ROS appear to play a necessary role in the development of hyperadrenergic hypertension in this model, in a process mechanistically linking elevated blood pressure with catecholamine excess, renal transcriptional responses, ROS elevation, lipid peroxidation, and NO(•) depletion. Some of the changes appear to be dependent on transcription, whereas others are immediate. The cycle could be disrupted by inhibition of either sympathetic outflow or NADPH oxidase. Because common genetic variation at the human CHGA locus alters BP, the results have implications for antihypertensive treatment as well as prevention of target-organ consequences of the disease. The results document novel pathophysiological links between the adrenergic system and oxidative stress and suggest new strategies to probe the role and actions of ROS within this setting.

A 12-year-old female neutered cat presented with acute onset unilateral vestibular syndrome, a spontaneous cutaneous wound, polyuria, polydipsia, and diabetes mellitus. Hyperadrenocorticism was demonstrated by means of hyper-responsiveness to adrenocorticotropic hormone stimulation, elevated urine cortisol-to-creatinine ratio, bilaterally enlarged adrenal glands on abdominal ultrasound, and pituitary enlargement on computed tomography imaging. The cat was euthanased and post-mortem histological examination revealed feline skin fragility syndrome; confirmed a pituitary cromophobe macroadenoma; and generalised toxoplasmosis with tachyzoites in the pancreas, bowel and brain. This report is the first to describe the concurrence of macroadenoma pituitary-dependent hyperadrenocorticism and generalised toxoplasmosis in a cat with central vestibular syndrome., (Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine causes of hyperphosphatasemia (high serum alkaline phosphatase [ALP] activity) in apparently healthy Scottish Terriers., Design: Prospective case-controlled study., Animals: 34 apparently healthy adult Scottish Terriers (17 with and 17 without hyperphosphatasemia)., Procedures: Serum activities for 3 isoforms (bone, liver, and corticosteroid) of ALP were measured. Concentrations of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, and aldosterone were measured before and after cosyntropin administration (ie, ACTH; 5 microg/kg [2.27 microg/lb], IM). Liver biopsy specimens from 16 dogs (11 with and 5 without hyperphosphatasemia) were evaluated histologically., Results: In dogs with hyperphosphatasemia, the corticosteroid ALP isoform comprised a significantly higher percentage of total ALP activity, compared with the percentage in dogs without hyperphosphatasemia (mean +/- SE, 69 +/- 5.0% and 17 +/- 3.8%, respectively). In 6 dogs with hyperphosphatasemia, but none without, serum cortisol concentrations exceeded reference intervals after ACTH stimulation. Six dogs with and 15 without hyperphosphatasemia had increased concentrations of >or = 1 noncortisol steroid hormone after ACTH stimulation. Serum ALP activity was correlated with cortisol and androstenedione concentrations (r = 0.337 and 0.496, respectively) measured after ACTH stimulation. All dogs with and most without hyperphosphatasemia had abnormal hepatocellular reticulation typical of vacuolar hepatopathy. Subjectively, hepatocellular reticulation was more severe and widespread in hyperphosphatasemic dogs, compared with that in nonhyperphosphatasemic dogs., Conclusions and Clinical Relevance: Hyperphosphatasemia in apparently healthy Scottish Terriers was most likely attributable to hyperadrenocorticism on the basis of exaggerated serum biochemical responses to ACTH administration and histologic hepatic changes, but none of the dogs had clinical signs of hyperadrenocorticism.