Long-term use of clomiphene in male macroprolactinomas with persistent hypogonadism.

BACKGROUND: Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy. METHODS: This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC. RESULTS: The median age at diagnosis of prolactinomas was 34 (range, 26-60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1-7) mg/week, with a median time of treatment of 8.5 (2-15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported. CONCLUSION: CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism.

Contralateral suppression in adrenal venous sampling predicts clinical and biochemical outcome in primary aldosteronism.

CONTEXT: The role for hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcome remains controversial. OBJECTIVE: To investigate the impact of hormone parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcome. METHODS: We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. Bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index (LI), aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 - nondominant RASI) *100. RESULTS: A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had a worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure were significantly more frequent in the patients with CS >50% [98.41% vs. 42.86% (p < 0.001) and 41.94% vs. 0% (p < 0.001)]. CS correlated with high aldosterone at diagnosis (p < 0.001) and low postoperative aldosterone levels at 1 month (p = 0.019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs. 16.67%, p = 0.014). In multivariable analysis, a CS >50% was associated with complete biochemical cure (OR 125, 95%CI 11.904-5,000; p = 0.001) and hypertension remission (OR 12.19, 95%CI 2.074-250; p = 0.023). CONCLUSION: A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral PA and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.

The impact of obesity in hospitalized patients with COVID-19: a retrospective cohort study.

BACKGROUND: Obesity is believed to be a risk factor for COVID-19 and unfavorable outcomes, although data on this remains to be better elucidated. OBJECTIVE: To evaluate the impact of obesity on the endpoints of patients hospitalized due to SARS-CoV-2. METHODS: This retrospective cohort study evaluated patients hospitalized at a tertiary hospital (Hospital das Clínicas da Faculdade de Medicina da USP) from March to December 2020. Only patients positive for COVID-19 (real-time PCR or serology) were included. Data were collected from medical records and included clinical and demographic information, weight and height, SAPS-3 score, comorbidities, and patient-centered outcomes (mortality, and need for mechanical ventilation, renal replacement therapy, or vasoactive drugs). Patients were divided into categories according to their BMI (underweight, eutrophic, overweight and obesity) for comparison porpoise. RESULTS: A total of 2547 patients were included. The mean age was 60.3 years, 56.2% were men, 65.2% were white and the mean BMI was 28.1 kg/m2. SAPS-3 score was a risk factor for all patient-centered outcomes (HR 1.032 for mortality, OR 1.03 for dialysis, OR 1.07 for vasoactive drug use, and OR 1.08 for intubation, p < 0.05). Male sex increased the risk of death (HR 1.175, p = 0.027) and dialysis (OR 1.64, p < 0.001), and underweight was protective for vasoactive drug use (OR 0.45, p = 0.027) and intubation (OR 0.31, p < 0.003). CONCLUSION: Obesity itself was not an independent factor for worse patient-centered outcomes. Critical clinical state (indirectly evaluated by SAPS-3) appears to be the most important variable related to hard outcomes in patients infected with COVID-19.

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

Down the rabbit hole: reviewing the evidence for primary prevention of cardiovascular disease in people with obesity.

Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low- or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic.

Treatment with Antiobesity Drugs in Weight Regain After Bariatric Surgery: a Retrospective Cohort Study.

BACKGROUND: Bariatric surgery is the most efficient treatment for obesity. However, in some cases, weight regain can occur. Currently, it is unknown the best antiobesity medication (AOM) for such clinical situation. This study aims to evaluate the effect of AOM in patients with weight regain after bariatric surgery. METHODS: A retrospective cohort study from December 2010 to July 2019 with patients submitted to bariatric surgery that had weight regain and received AOM for at least 2 years. RESULTS: Of 96 patients that had weight regain in the analyzed period and received AOM, 16 were excluded from the analysis due to non-compliance (n = 7), treatment failure (n = 5), intolerable side effects with all available AOM (n = 2), or interaction with other medications (n = 2). Eighty patients were included in the analysis. The mean age was 59.0 ± 10.1 years, 88.8% were female, 91.2% white, and most of them were submitted to gastric bypass (87.6%). The mean preoperative and nadir weight after surgery were 127.9 ± 25.5 kg and 84.7 ± 22.8 kg, respectively. At the initiation of AOM, the mean baseline weight was 99.4 ± 23.1 kg. After 2 years of follow-up, there was significant weight loss in the groups treated with topiramate-alone (- 3.2 kg), topiramate plus sibutramine (- 6.1kg), and orlistat-alone or in combination (- 3.9kg). No statistical difference was observed in the sibutramine-alone group. CONCLUSION: Topiramate (alone or associated with sibutramine) and orlistat (alone or in combination) promoted significant weight loss after 2 years of use in patients submitted to bariatric surgery with weight regain.

Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do Brasil / Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do BrasilClinical and therapeutic profile of patients with hyperthyroidism in an outpatient endocrine clinic at a university hospital in southern Brazil

.Introdução: O hipertireoidismo decorre da elevação sérica dos hormônios tireoidianos, secundária à hiperfunção da glândula tireoide, sendo as principais causas a Doença de Graves (DG) e os Bócios Nodulares Tóxicos (BNT). Objetivos: Avaliar o perfil clínico e modalidades terapêuticas aplicadas em pacientes com diagnóstico de hipertireoidismo acompanhados em um Hospital Universitário no Sul do Brasil. Métodos: Estudo observacional, transversal e descritivo, com inclusão de pacientes com diagnóstico de hipertireoidismo por DG e BNT; foram coletados dados epidemiológicos, clínicos, laboratoriais e de tratamento. Resultados: A maioria dos pacientes foi referenciada pela atenção primária e encontrava-se em uso prévio de droga antitireoidiana (DAT). A variável idade obteve diferença estatisticamente significativa entre as etiologias de DG e BNT; em ambas houve predomínio de incidência no sexo feminino. A DG apresentou maior frequência de sinais e sintomas de tireotoxicose, ao passo que o BNT mostrou mais sinais e sintomas de compressão. Houve remissão da doença em 23,2% dos pacientes com DG tratados com DAT; em 23,2% dos pacientes optou-se pela manutenção de metimazol em baixa dose por mais de 36 meses e em 16,1% foi realizado tratamento definitivo. No BNT foram preferidas terapias definitivas, principalmente a tireoidectomia, em 27,5% dos pacientes. Doses baixas de metimazol por mais de 36 meses foram utilizados também no BNT, em 22,5% dos pacientes. Conclusão: O hipertireoidismo é uma doença heterogênea, desde a clínica inicial até a terapêutica, entre suas etiologias mais prevalentes. Observou-se uma tendência de priorizar as terapias medicamentosas em longo prazo com baixas doses, tanto na DG quanto no BNT. (AU)

Perfil clínico e terapêutico dos pacientes com hipertireoidismo do ambulatório de endocrinologia de um hospital universitário do sul do BrasilClinical and therapeutic profile of patients with hyperthyroidism in an outpatient endocrine clinic at a university hospital in southern Brazil ARTIGO ORIGINALRafael Antonio Parabocz1, Renata Soares Carvalho1, Gianna Carla Alberti Schrut1, Ana Claudia Garabeli Cavalli Kluthcovsky1, Matheo Augusto Morandi Stumpf1Introduction: Hyperthyroidism results from the serum elevation of thyroid hormones, secondary to hyperfunction of the thyroid gland. The main causes are Graves' disease (DG) and Toxic Nodular Goiters (BNT). Objectives: Evaluate the clinical profile and therapeutic modalities applied in patients diagnosed with hyperthyroidism followed up at a University Hospital in Southern Brazil. Methods: Observational, cross-sectional and descriptive study, including patients diagnosed with hyperthyroidism by DG and BNT; epidemiological, clinical, laboratory and treatment data were collected. Results: Most patients were referred by primary care and had been using antithyroid drugs (DAT). The age variable obtained showed a statistically significant difference between the etiologies of DG and BNT; in both, there was a predominance of incidence in females. DG showed a higher frequency of signs and symptoms of thyrotoxicosis, while BNT showed more signs and symptoms of compression. There was remission of the disease in 23.2% of patients with DG treated with DAT; in 23.2% of the patients, low-dose methimazole was maintained for more than 36 months and in 16.1%, definitive treatment was performed. In BNT, definitive therapies were preferred, mainly thyroidectomy, in 27.5% of patients. Low doses of methimazole for more than 36 months were also used in BNT in 22.5% of patients. Conclusion: Hyperthyroidism is a heterogeneous disease, from initial clinic to therapy, among its most prevalent etiologies. There was a tendency to prioritize long-term drug therapies with low doses, both in DG and BNT. (AU)

Acute Kidney Injury with Neurological Features: Beware of the Star Fruit and its Caramboxin.

Star fruit (Averrhoa carambola) is a well-known product in tropical countries. There are few reports published in literature with acute kidney injury due to oxalate induced nephropathy. However, none of them have an important neurological feature. We present a case of a 51-year-old male with paresis and altered mental status. Screening for neurological diseases such as stroke, Guillain-Barre, meningitis and encephalitis were negative. In the evolution, he developed acute kidney failure and was submitted to 4 dialysis sessions. After talking to the family, we discovered he had ingested over 50 star fruits prior to the acute neurologic deficits. He recovered renal function so a renal biopsy was not required. Physicians should actively look for star fruit ingestion history in patients presenting with unexplained acute kidney injury with or without neurological features. Besides, taking star fruit in a large amount, accompanied by an empty stomach and dehydrated state, is a risk factor for neurotoxicity.