Trismus due to myotonia associated with hyperadrenocorticism in a dog.

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.

Old Problem, New Concerns: Hypercortisolemia in the Time of COVID-19.

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.

Thrombin Generation Assay and Hemostatic Profile for Elucidating Hypercoagulability in Endogenous Canine Hyperadrenocorticism.

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.

Emphysematous Cystitis and Pneumoperitoneum in a Dog with Escherichia coli Urinary Tract Infection and Hyperadrenocorticism.

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.

A preliminary evaluation of the circulating leptin/adiponectin ratio in dogs with pituitary-dependent hyperadrenocorticism and concurrent diabetes mellitus.

Leptin and adiponectin are thought to modulate insulin sensitivity and pancreatic ß-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 ß-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)-1ß, 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-1ß 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 HOMAß-cell function was significantly lower in PDH dogs with DM than in normoglycemic PDH dogs, while HOMAinsulin 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 ß-cell function might predispose PDH dogs to DM. Further longitudinal study will be necessary to confirm this result.

Neumonía bilateral en un paciente con un síndrome de Cushing / Bilateral pneumonia in a patient with Cushing's syndrome

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Prevalence and risk factors associated with systemic hypertension in dogs with spontaneous hyperadrenocorticism.

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 × 103 /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.

Surgical Approach to Endocrine Hypertension in Patients with Adrenal Disorders.

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.

[Hypercorticism during streptozotocin diabetes and mifepristone administration: the role of cyclic adenosine monophosphate]. / Giperkortitsizm pri streptozototsinovom diabete i vvedenii mifepristona: rol' tsiklicheskogo adenozinmonofosfata.

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.

Novel GC-MS/MS Technique Reveals a Complex Steroid Fingerprint of Subclinical Hypercortisolism in Adrenal Incidentalomas.

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-3ß,17ß-diol, and conjugated 5α-androstane-3α,17ß-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.

Evaluation of Hypertriglyceridemia as a Mediator Between Endocrine Diseases and Pancreatitis in Dogs.

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.

Physiolgic hypercortisolism at onset of celiac disease in a girl: A case report.

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.

Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease.

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.

Recurrent pyoderma and its underlying primary diseases: a retrospective evaluation of 157 dogs.

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.

Management and closure of multiple large cutaneous lesions in a juvenile cat with severe acquired skin fragility syndrome secondary to iatrogenic hyperadrenocorticism.

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.

Punctate retinal hemorrhage and its relation to ocular and systemic disease in dogs: 83 cases.

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.

Concurrent hyperadrenocorticism and diabetes mellitus in dogs.

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.

Development of a plasminogen activator inhibitor (PAI-1) assay and comparison of plasma PAI-1 activity in hyperlipidemic/dyslipidemic dogs with either hyperadrenocorticism or diabetes mellitus, and healthy dogs.

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.

"Nonfunctional" Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes: A Cohort Study.

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.