Adrenal incidentaloma: Do patients with apparently nonfunctioning mass or autonomous cortisol secretion have similar or different clinical and metabolic features?

OBJECTIVE: Although there is growing evidence associating nonfunctioning adrenal incidentalomas (NFAI) with cardiovascular risk factors, there are limited data whether NFAI and autonomous cortisol secretion (ACS) groups have similar or different clinical and metabolic features. The aim of this study is to compare cardiometabolic clinic parameters among patients with ACS and NFAI, as well as controls. DESIGN: Cross-sectional study. PATIENTS: Eighty nine NFAI, 58 ACS and 64 controls were evaluated. MEASUREMENTS: Diagnosis of NFAI (1 mg dexamethasone suppression test [1 mg-DST] ≤50 nmol/L [≤1.8 µg/dl]) and ACS (1 mg-DST > 50 nmol/L [> 1.8 µg/dl]) was established according to current guidelines. The control group was selected based on a normal adrenal imaging exam. RESULTS: There were no differences between groups regarding age, gender, ethnicity, menopause or body mass index. Patients with adrenal incidentaloma presented higher frequency of hypertension (74.1 vs. 57.8%; p = .02), resistant hypertension (45.4 vs. 9.4%; p < .001), dyslipidemia (80.1 vs. 63.9%; p = .01), as well as metabolic syndrome (84.2 vs. 61.7%; p = .001) compared to the controls, respectively. NFAI and ACS patients presented similar frequency of arterial hypertension (70.8 vs. 79.3%) and resistant hypertension (41.3 vs. 51.1%), dyslipidemia (79.3 vs. 81.5%) and metabolic syndrome (83.3 vs. 85.7%); also, levels of HbA1c were similar between the groups. Binary logistic regression showed that NFAI (p = .004) and ACS (p = .001) were independent predictors for resistant hypertension (p = .003); also, ACS was an independent predictor for metabolic syndrome (p = .04). CONCLUSIONS: NFAI and ACS presented a higher frequency of cardiometabolic morbidities in comparison with individuals with normal adrenal glands. Additionally, we demonstrated that both ACS and NFAI groups have similar cardiometabolic conditions.

No association between psychiatric symptoms and doses of anabolic steroids in a cohort of male and female bodybuilders.

The use of androgenic-anabolic steroids (AAS) can be associated with psychiatric symptoms such as insomnia, anxiety and increased aggressiveness. Although dose-dependent effects have been observed in some controlled studies, this association is not always seen in the ecological use of AAS. This study utilized WADA's steroid profile of suspicious use of AAS, urinary detection of AAS metabolites and measurement of sexual hormones to confirm recent use of AAS in a cohort of 103 bodybuilders (75 males, 28 females). The majority of participants (61.2%) presented symptoms of agitation, insomnia, increased aggressiveness or depression in the last 3 months. About one-third of participants presented scores on the HAM-A anxiety scale equivalent to moderate to severe symptoms of anxiety. A minority of participants (12.6%) presented high to moderate scores on the BPQ aggressiveness scale. The majority of participants (73.8%) presented hyperthymic temperament in the BRIEF-TEMPS scale. There was no significant difference in the presence of psychiatric symptoms between males and females and no association between psychiatric symptoms and estimated weekly doses of AAS. A negative association was observed between scores on the BPQ scale (verbal aggression, anger and total score) and the time of AAS use. We discuss differences of AAS use between male and female bodybuilders and the screening of AAS use in the general population. Our findings highlight the importance of mental health awareness among people using AAS.

Colonic tuberculosis presenting as intestinal subocclusion in a patient with neuroendocrine tumor: a case report.

Extra-pulmonary tuberculosis (EPT) is responsible for approximately 14% of all tuberculosis cases in Brazil. The incidence of EPT is increasing slightly and is often associated with human immunodeficiency virus infection and other causes of immunosuppression. The association of EPT and cancer is poorly documented. Here we present a rare case of intestinal subocclusion that was supposed to be caused by cancer and was caused by colonic tuberculosis (CT) in a patient with metastatic neuroendocrine tumor (NET). A 61-year-old woman presented with one-year history of abdominal pain, diarrhea and weight loss. An abdominal CT scan (ACTS) showed liver, peritoneal and lymph nodes metastasis. Colonoscopy revealed a subocclusive lesion in the descendent colon. She underwent an urgent laparoscopy and transverse colostomy. The liver biopsy revealed a well differentiated grade 2 NET and the mycobacterial culture confirmed tuberculosis in the colonic lesion. Anti-tuberculosis was prescribed, and somatostatin analogue therapy was introduced one month later. The tuberculosis treatment was finished, and the patient remained on somatostatin analogue for 21 months. During this time the symptoms of abdominal pain and diarrhea disappeared and her body weight increased 35% over her baseline weight. Then, diarrhea, flushing and abdominal pain returned, and a new ACTS confirmed progressive disease. Interferon was added to her treatment with satisfactory control of symptoms. She was forwarded to another hospital to be treated with 177Lu-DOTATOC. The symptoms improved and the patient remained symptom free for more than a year, and now she has a new disease progression. The patient will be evaluated for retreatment with 177Lu-DOTATOC. Advanced NET may be a devastating disease enough to predispose the patient to EPT. We must keep this hypothesis in the differential diagnosis of our patients since symptoms of CT are usually nonspecific. At colonoscopy, radiological features are strictures, colitis and polypoidal lesions and complications such as bowel perforation or fistula must be in mind. It is particularly important those with advanced disease in endemic areas of tuberculosis.

Use of aromatase inhibitors in patients with breast cancer is associated with deterioration of bone microarchitecture and density

ABSTRACT Objective: To evaluate changes in bone density and architecture in postmenopausal women with breast cancer (BC) and use of aromatase inhibitor (AI). Subjects and methods: Thirty-four postmenopausal women with BC, without bone metastasis, renal function impairment and who were not receiving bone-active drugs were selected from a population of 523 outpatients treated for BC. According to the presence of hormonal receptors, HER2 and Ki67, seventeen had positive hormonal receptors and received anastrozole (AI group), and seventeen were triple-negative receptors (non-AI group), previously treated with chemotherapy. Areal bone mineral density (aBMD) and vertebral fracture assessment (VFA) analyses were performed by DXA; vBMD and bone microarchitecture were evaluated by HR-pQCT. Fracture risk was estimated using the FRAX tool. Results: No patient referred previous low-impact fracture, and VFA detected one moderate vertebral fracture in a non-AI patient. AI patients showed lower aBMD and BMD T-scores at the hip and 33% radius and a higher proportion of osteoporosis diagnosis on DXA (47%) vs non-AI (17.6%). AI group had significantly lower values for vBMD at the entire, cortical and trabecular bone compartments, cortical and trabecular thickness and BV/TV. They also had a higher risk for major fractures and for hip fractures estimated by FRAX. Several HR-pQCT parameters evaluated at distal radius and distal tibia were significantly associated with fracture risk. Conclusion: AI is associated with alterations in bone density and microarchitecture of both the cortical and trabecular compartments. These findings explain the overall increase in fracture risk in this specific population.

Effective treatment and prevention of attempted suicide, anxiety, and aggressiveness with fluoxetine, despite proven use of androgenic anabolic steroids.

The treatment of a man who attempted suicide after experiencing symptoms of anxiety and aggressiveness associated with the use of androgenic-anabolic steroids (AAS) is described. This report includes 30 days of inpatient treatment and a 6-month follow-up. Regular use of fluoxetine apparently prevented the onset of anxiety, depression, aggressiveness, and suicide ideation, even with the concurrent use of AAS. The urinary concentration of androgens, metabolites of AAS, and fluoxetine were monitored through analysis of urinary samples by the Brazilian Laboratory of Doping Control. Our results are congruent with previous findings describing the risk of suicide prompted by AAS use as well as the efficacy of fluoxetine in the treatment of mood disorders associated with the use of anabolic steroids.

Multiple endocrine neoplasia type 1 in patients with gastroenteropancreatic neuroendocrine tumors: An opportunity for early diagnosis and appropriate management.

Gastroenteropancreatic neuroendocrine tumors (GEPNET) are rare tumors that may be sporadic or develop as part of multiple endocrine neoplasia type 1 syndrome (MEN1). The aim of the present study was to report the experience of a Brazilian multidisciplinary outpatient neuroendocrine tumor clinic regarding the clinical diagnosis of MEN1 in a cohort of GEPNET patients. Patient data, including clinical characteristics and the lag time from the onset of symptoms to diagnosis of the first tumor, and further lag time until the diagnosis of MEN1, were retrospectively reviewed. Among 44 GEPNET patients, 6 had a clinical diagnosis of MEN1. Primary hyperparathyroidism and GEPNET were present in all patients in the cohort, and pituitary neuroendocrine tumors were present in 33.3%. The median time interval from the onset of initial symptoms to the diagnosis of the first tumor was 42 months (range, 0-204 months). The median time interval between the diagnosis of the first tumor and the diagnosis of MEN1 was 22 months (range, 1-109 months). The prolonged lag time between the onset of initial symptoms and MEN1 diagnosis may result in substantial morbidity and loss of opportune interventions for the patients. Therefore, greater efforts should be made to shorten these times and improve the care of patients with MEN1.

Bone Evaluation by High-Resolution Peripheral Quantitative Computed Tomography in Patients With Adrenal Incidentaloma.

CONTEXT: Data regarding high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with adrenal incidentaloma (AI) are unknown. PURPOSE: To evaluate the areal bone mineral density (aBMD), microstructure, and fractures in patients with nonfunctioning AI (NFAI) and autonomous cortisol secretion (ACS). METHODS: We evaluated 45 patients with NFAI (1 mg dexamethasone suppression test [DST] ≤1.8 µg/dL) and 30 patients with ACS (1 mg DST 1.9-5.0 µg/dL). aBMD was measured using dual-energy X-ray absorptiometry; vertebral fracture by spine X-ray; and bone geometry, volumetric bone mineral density (vBMD), and microstructure by HR-pQCT. RESULTS: Patients with ACS showed lower aBMD values at the spine, femoral neck, and radius 33% than those with NFAI. Osteoporosis was frequent in both groups: NFAI (64.9%) and ACS (75%). Parameters at the distal radius by HR-pQCT were decreased in patients with ACS compared to those with NFAI: trabecular vBMD (Tb.vBMD, P = 0.03), inner zone of the trabecular region (Inn.Tb.vBMD, P = 0.01), the bone volume/tissue volume ratio (BV/TV, P = 0.03) and trabecular thickness (P = 0.04). As consequence, a higher ratio of the outer zone of the trabecular region/inner zone vBMD (Meta/Inn.vBMD, P = 0.003) was observed. A correlation between the cortisol levels after 1 mg DST and Meta/Inn.vBMD ratio was found (r = 0.29; P = 0.01). The fracture frequency was 73.7% in patients with ACS vs 55.6% in patients with NFAI (P = 0.24). CONCLUSION: Our findings point to an association between trabecular bone microarchitectural derangement at the distal radius and ACS. Our data suggest that AI have a negative impact on bone when assessed by HR-pQCT, probably associated to subclinical hypercortisolism.

Body self-image disturbances in women with prolactinoma

Objective: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. Methods: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. Results: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. Conclusion: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Body self-image disturbances in women with prolactinoma.

OBJECTIVE: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. METHODS: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. RESULTS: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. CONCLUSION: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Adrenal Venous Sampling in Primary Aldosteronism: The Usefulness of Contralateral Suppression Index.

Adrenal venous sampling (AVS) is the gold standard test to differentiate the unilateral from the bilateral form in patients with primary aldosteronism (PA) although it may be a difficult procedure, especially the successful cannulation of the right adrenal vein. In this report, we describe a 49-year-old female patient diagnosed with PA, after investigating resistant hypertension and refractory hypokalemia. Abdominal computed tomography scan revealed a 2.5 cm adenoma on the right adrenal vein. AVS was performed under cosyntropin infusion. Aldosterone and cortisol concentrations were obtained from the right and left adrenal veins and inferior vena cava (IVC). Cortisol on each adrenal vein divided by cortisol on IVC confirmed successful cannulation of the left side only, which makes it impossible to calculate the lateralization index (LI). From the data on the left adrenal vein and IVC, the aldosterone-to-cortisol ratio divided by the IVC aldosterone-to-cortisol ratio was less than 1.0, suggesting that the left adrenal vein was suppressed with the excess aldosterone originating from the contralateral side (contralateral suppression index (CSI)). Right adrenalectomy was performed; postoperative hypoaldosteronism was confirmed. This report highlights the importance of CSI obtained in AVS when technical difficulties occur making it impossible to obtain LI, which is most commonly used to decide between surgical and clinical management of PA.

Gastrinoma of Cystic Duct: A Rare Association With Multiple Endocrine Neoplasia Type 1.

Neuroendocrine tumors (NETs) of cystic duct are extremely rare, accounting for less than 2% of NET cases. The association of biliary tree NET and multiple endocrine neoplasm type 1 (MEN1) are even more rare. In this report, we described a case of a 65-year-old woman who was referred to our neuroendocrine outpatient clinic to investigate MEN1 after an incidental diagnosis of gastrinoma. Her medical history initiated 7 years earlier with severe peptic disease not responsive to proton pump inhibitor therapy. Endoscopic study revealed erosive antral gastritis, erosive duodenitis, bulbar ulcer and pyloric deformity. During follow-up she presented with abdominal pain, chronic diarrhea and weight loss; an ultrasonography was performed and showed only a cholelithiasis. She underwent a video laparoscopic cholecystectomy and all her symptoms were solved. Histopathological study found a 1.0 cm well differentiated NET (Ki-67 labeling index < 2%) located in cystic duct infiltrating the entire wall and subserosa. The MEN1 investigation revealed a primary hyperparathyroidism with a brown tumor in right iliac bone; the patient was referred to a total parathyroidectomy with autotransplantation. No evidence of pituitary tumor was found. The patient remains asymptomatic 24 months after surgery. To conclude, this case highlights an unusual presentation of a cystic duct primary NET gastrinoma in a MEN1 context.

Nonfunctioning adrenal incidentaloma: A novel predictive factor for metabolic syndrome.

CONTEXT: Although metabolic syndrome has been studied in patients with autonomous cortisol secretion, there are limited data for those with nonfunctioning adrenal incidentaloma (NFAI). OBJECTIVE: To assess metabolic syndrome frequency in NFAI patients and controls without adrenal adenoma according to World Health Organization (WHO), National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) and International Diabetes Federation (IDF) criteria. DESIGN: Retrospective and transversal study. PATIENTS: Seventy-four NFAI and 90 controls were evaluated. NFAI diagnosis was established according to current guidelines. The control group was selected based on normal adrenal imaging examinations. MEASUREMENTS: Subjects were categorized by metabolic syndrome presence according to WHO, NCEP-ATP III, AACE/ACE and IDF. RESULTS: Age, gender, ethnicity, body mass index, smoking, menopause, statin and fibrate use were comparable between patients and controls. The frequency of prediabetes, dyslipidaemia and hypertension as well as waist circumference were significantly higher in the NFAI patients compared to the controls. The metabolic syndrome frequency in the NFAI group was significantly higher compared to the normal adrenal group: WHO: 69.2% × 31.0% (P < 0.001); NCEP-ATP III: 81.7% × 44.9% (P < 0.001); AACE/ACE: 77.1% × 31.9% (P < 0.001); IDF: 78.6% × 45.5% (P < 0.001). Logistic regression analysis showed that NFAI was a predictor of metabolic syndrome according to WHO (P = 0.001), NCEP-ATP III (P = 0.005) and AACE/ACE (P = 0.007). CONCLUSIONS: Metabolic syndrome is frequently found in patients with NFAI, and this frequency is higher in NFAI patients than in those with normal adrenal imaging.

Alkaline phosphatase: reference interval transference from CALIPER to a pediatric Brazilian population / Fosfatase alcalina: transferência de intervalos de referência do CALIPER para uma população pediátrica brasileira

ABSTRACT Introduction: Interpreting laboratory tests requires reference intervals (RI) that may vary between different populations. For the diagnosis of hypophosphatasia (HPP), lower limits of alkaline phosphatase (ALP) levels must be determined. Objective: To transfer the RI findings for ALP obtained by the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER) in children and adolescents, adjusted for the Brazilian population. Methods: The ALP measures from 1690 subjects (aging from 1-18 years) were analyzed. The CALIPER subgroups and the Clinical and Laboratory Standards Institute (CLSI) guideline were used for validation. Inclusion criteria were patients with normal range of hepatic and renal function, bone metabolism, and blood counts. Exclusion criteria were hospitalization, low weight, and use of drugs that could interfere in the ALP measurement and patients in with more than three orders for ALP measuring test. The RI obtained were considered valid if more than 90% of patients were whitin of the CALIPER RI. Results: The ALP RI results (IU/l) obtained were: 149-301 for both sexes aged 1-9 years; 127-326 for both sexes aged 10-12 years; 62-212 for girls and 129-437 for boys aged 13-14 years; 52-120 for girls and 78-268 for boys aged 15-16 years; 45-97 for girls and 40-129 for boys aged 17-18 years. In 92.4% of the patients, the results were comparable with those of the CALIPER study. Conclusion: The results demonstrated that the ALP RI for Brazilian children and adolescents are comparable to the CALIPER study in 92.4% of the patients and can be used for this population.

RESUMO Introdução: A interpretação de exames laboratoriais necessita de intervalos de referência (IR) que podem variar entre diferentes populações. Para o diagnóstico de hipofosfatasia, deve-se determinar limites inferiores do IR da fosfatase alcalina (FA). Objetivo: Transferir os resultados de IR da FA obtidos pela Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER) em crianças e adolescentes, ajustados para a população brasileira. Métodos: Analisaram-se as dosagens de FA de 1690 indivíduos (1 a 18 anos). Subgrupos do CALIPER e diretrizes do Clinical and Laboratory Standards Institute (CLSI) foram utilizados. Os critérios de inclusão foram pacientes com função hepática, renal, exames do metabolismo ósseo e hemograma normais; já os de exclusão, hospitalização, baixo peso, uso de drogas interferentes na dosagem de FA e pacientes com mais de três solicitações de FA. Os IR seriam considerados válidos se mais de 90% dos pacientes se encontrassem dentro dos IR do CALIPER. Resultado: Os resultados dos IR de FA (UI/l) obtidos foram: 149-301 para ambos os sexos entre 1-9 anos; 127-326 para ambos os sexos entre 10-12 anos; 62-212 para meninas e 129-437 para meninos entre 13-14 anos; 52-120 para meninas e 78-268 para meninos entre 15-16 anos; 45-97 para meninas e 40-129 para meninos entre 17-18 anos de idade. Em 92,4% dos pacientes os resultados eram comparáveis com os do CALIPER. Conclusão: Os resultados demonstraram que os IR de FA para crianças e adolescentes brasileiras são comparáveis com o estudo CALIPER em 92,4% dos pacientes e podem ser utilizados para essa população.

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism.

The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.

A review of Cushing's disease treatment by the Department of Neuroendocrinology of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT The treatment objectives for a patient with Cushing's disease (CD) are remission of hypercortisolism, adequate management of co-morbidities, restoration of the hypothalamic-pituitary-adrenal axis, preservation of fertility and pituitary function, and improvement of visual defects in cases of macroadenomas with suprasellar extension. Transsphenoidal pituitary surgery is the main treatment option for the majority of cases, even in macroadenomas with low probability of remission. In cases of surgical failure, another subsequent pituitary surgery might be indicated in cases with persistent tumor imaging at post surgical magnetic resonance imaging (MRI) and/or pathology analysis of adrenocorticotropic hormone-positive (ACTH+) positive pituitary adenoma in the first procedure. Medical treatment, radiotherapy and adrenalectomy are the other options when transsphenoidal pituitary surgery fails. There are several options of medical treatment, although cabergoline and ketoconazole are the most commonly used alone or in combination. Novel treatments are also addressed in this review. Different therapeutic approaches are frequently needed on an individual basis, both before and, particularly, after surgery, and they should be individualized. The objective of the present review is to provide the necessary information to achieve a more effective treatment for CD. It is recommended that patients with CD be followed at tertiary care centers with experience in treating this condition.

HR-pQCT detects alterations in bone microstructure in men with CKD stages 3 and 4, which are influenced by hormonal changes and body composition
.

INTRODUCTION: Factors associated with osteodystrophy in predialysis patients are poorly understood. In the present study, we attempted to evaluate the impact of body composition and hormonal regulatory factors on the bone microstructure in a group of men with chronic kidney disease (CKD) stages 3 and 4. MATERIALS AND METHODS: 46 men, aged 50 - 75 years, with previously unrecognized CKD were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and dual-energy X-ray absorptiometry (DXA). HR-pQCT parameters were correlated with estimated glomerular filtration rate (eGFR), age, body mass index (BMI), muscle mass index (MMI), and biochemistry. RESULTS: As compared to patients in stage 3 CKD, those with stage 4 CKD showed lower serum 25-hydroxyvitamin D (25(OH)D) and bicarbonate levels, and higher serum fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH) levels. They also exhibited lower total, trabecular, and cortical volumetric bone mineral density, lower trabecular bone volume/tissue volume, trabecular number, trabecular and cortical thickness, and increased heterogeneity of the trabecular network. In the whole cohort, cortical bone density and thickness were negatively associated with age, PTH, and FGF-23, and positively with BMI. Trabecular bone parameters were positively associated with MMI and 25(OH)D. After simultaneously adjusting for age and eGFR, BMI, and MMI remained significantly associated with bone microstructural variables. CONCLUSION: HR-pQCT showed significant differences in bone microstructure in stage 4 vs. stage 3 CKD patients. Increased BMI, probably due to increased muscle mass, may favorably affect bone architecture in predialysis CKD patients.
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The presence of nonfunctioning adrenal incidentalomas increases arterial hypertension frequency and severity, and is associated with cortisol levels after dexamethasone suppression test.

There are limited data regarding the frequency of hypertension in nonfunctioning adrenal incidentaloma (NFAI). Our objectives were to investigate rates of hypertension and resistant hypertension in NFAI patients, and compare them to a control group without adrenal adenoma. We also aimed to evaluate the relationship between cortisol levels after 1 mg-dexamethasone suppression test (DST) and hypertension in NFAI patients. We selected 40 patients with NFAI and 40 control patients over the age of 18 without adrenal lesions on abdominal imaging. Data regarding hypertension, resistant hypertension, number, and type of antihypertensive drugs were collected from each subject. Blood samples for C-reactive protein (CRP), plasma adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) were also collected from the patients. Age, gender, race, smoking status, menopause status and BMI were comparable between patient and control groups. Patients with NFAI had a higher frequency of hypertension (72.5 vs. 47.5%; p = 0.04), resistant hypertension (37.9 vs. 11.1%; p = 0.04) and took three or more antihypertensive drugs (33.3 vs. 5.2%; p = 0.002) when compared to the controls, respectively. NFAI patients with hypertension had higher mean cortisol levels after 1 mg-DST when compared to NFAI patients without hypertension (1.3 ± 0.3 vs. 1.0 ± 0.4; p = 0.03, respectively). We found a negative correlation between cortisol levels after 1 mg-DST DHEA-S levels (r = -0.61; p < 0.001) and a positive correlation with CRP levels (r = 0.44; p = 0.02). In conclusion, NFAI patients presented a higher frequency of hypertension, resistant hypertension and used more antihypertensive medications when compared to the control group. We found an association between hypertension in NFAI patients and cortisol levels after 1 mg-DST.

Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?

PURPOSE: Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed. METHODS: The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands. The association of EMT and EMT-TFs with clinical outcomes and pathology features were also evaluated. RESULTS: Cytoplasmic vimentin expression was increased among CAT samples when compared to ACC, ACA, and normal adrenal samples (p < 0.001). There was no difference in e-cadherin and fibronectin expression observed between groups. Nuclear and cytoplasmic expression of TWIST1 and SIP1 was stronger in CAT and ACC vs. ACA and normal tissue samples (all, p < 0.05). ACT, regardless of classification, exhibited increased SNAIL expression when compared to normal tissue (p < 0.05). A significant correlation was observed between vimentin and TWIST1 (r s = 0.44, p < 0.001); SIP1 (r s = 0.51, p < 0.001); and SNAIL (r s = 0.23, p < 0.05). TWIST1 and SIP1 expressions demonstrated a significant correlation (r s = 0.56, p < 0.001). High SIP1 expression was associated with a lower survival rate among ACC cases (p < 0.05). CONCLUSIONS: Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.

A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma.

Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT) transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to poorer outcomes in other malignancies, but their role in ACC is unknown. We describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at age 76. After primary tumor resection, mitotane therapy was started as palliation to low-volume liver metastasis. After a 2-year period of stable disease, the patient died due to brain metastasis. Somatic gene sequencing revealed a novel TP53 mutation in DNA extracted from paraffin-embedded tissue, a deletion of 8bp in exon 8 (c.811_818del8; GAGGTGCG/-) in homo or hemizygosis causing a subsequent frameshift and premature stop codon at position 302. Immunohistochemistry of P53 and p-Ser-15 P53 showed absent tumoral staining. In addition, immunohistochemical analysis showed an increased expression of the mesenchymal markers vimentin and fibronectin. At last, EMT transcription factors TWIST1 and SIP1 were also overexpressed in tumoral cells. This case report describes an aggressive ACC with not only a novel somatic mutation, but also a novel International Agency for Research on Cancer database 8 base-pair deletion in TP53 exon 8. In addition, the expression of EMT inducers TWIST1 and SIP1 have been reported for the first time in an ACC case. Further investigation is needed to clarify the biologic significance of this new TP53 mutation and its role in the EMT process.

A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Clinically nonfunctioning pituitary adenomas (NFPA) are the most common pituitary tumors after prolactinomas. The absence of clinical symptoms of hormonal hypersecretion can contribute to the late diagnosis of the disease. Thus, the majority of patients seek medical attention for signs and symptoms resulting from mass effect, such as neuro-ophthalmologic symptoms and hypopituitarism. Other presentations include pituitary apoplexy or an incidental finding on imaging studies. Mass effect and hypopituitarism impose high morbidity and mortality. However, early diagnosis and effective treatment minimizes morbidity and mortality. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism is to provide a review of the diagnosis and treatment of patients with NFPA, emphasizing that the treatment should be performed in reference centers. This review is based on data published in the literature and the authors’ experience. Arch Endocrinol Metab. 2016;60(4):374-90.