RAQUEL SOARES JALLAD
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Challenges in the diagnosis and management of acromegaly: a focus on comorbidities(2016) ABREU, Alin; TOVAR, Alejandro Pinzon; CASTELLANOS, Rafael; VALENZUELA, Alex; GIRALDO, Claudia Milena Gomez; PINEDO, Alejandro Castellanos; GUERRERO, Doly Pantoja; BARRERA, Carlos Alfonso Builes; FRANCO, Humberto Ignacio; RIBEIRO-OLIVEIRA JR., Antonio; VILAR, Lucio; JALLAD, Raquel S.; DUARTE, Felipe Gaia; GADELHA, Monica; BOGUSZEWSKI, Cesar Luiz; ABUCHAM, Julio; NAVES, Luciana A.; MUSOLINO, Nina Rosa C.; FARIA, Maria Estela Justamante de; ROSSATO, Ciliana; BRONSTEIN, Marcello D.Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.
article 13 Citação(ões) na Scopus Pregnancy and pituitary adenomas(2016) GLEZER, Andrea; JALLAD, Raquel S.; MACHADO, Marcio C.; FRAGOSO, Maria Candida; BRONSTEIN, Marcello D.Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition.- The interplay between prolactin and cardiovascular disease(2023) GLEZER, Andrea; SANTANA, Mariana Ramos; BRONSTEIN, Marcello D. D.; JR, Jose Donato; JALLAD, Raquel SoaresHyperprolactinemia can be caused by several conditions and its effects on the hypothalamic-pituitary-gonadal axis are understood in more detail. Nevertheless, in recent decades, other metabolic effects have been studied and data pointed to a potential increased cardiovascular disease (CVD) risk. A recent study showed a decrease in total and LDL- cholesterol only in men with prolactinoma treated with dopamine agonists (DA) supporting the previous results of a population study with increased CVD risk in men harboring prolactinoma. However, other population studies did not find a correlation between prolactin (PRL) levels and CVD risk or mortality. There is also data pointing to an increase in high-density lipoprotein levels, and decreases in triglycerides, carotid-intima-media thickness, C-reactive protein, and homocysteine levels in patients with prolactinoma on DA treatment. PRL was also implicated in endothelial dysfunction in pre and postmenopausal women. Withdrawal of DA resulted in negative changes in vascular parameters and an increase in plasma fibrinogen. It has been shown that PRL levels were positively correlated with blood pressure and inversely correlated with dilatation of the brachial artery and insulin sensitivity, increased homocysteine levels, and elevated D-dimer levels. Regarding possible mechanisms for the association between hyperprolactinemia and CVD risk, they include a possible direct effect of PRL, hypogonadism, and even effects of DA treatment, independently of changes in PRL levels. In conclusion, hyperprolactinemia seems to be associated with impaired endothelial function and DA treatment could improve CVD risk. More studies evaluating CVD risk in hyperprolactinemic patients are important to define a potential indication of treatment beyond hypogonadism.
- Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands(2021) WILDEMBERG, Luiz Eduardo; CAMACHO, Aline Helen da Silva; MIRANDA, Renan Lyra; ELIAS, Paula C. L.; MUSOLINO, Nina R. de Castro; NAZATO, Debora; JALLAD, Raquel; HUAYLLAS, Martha K. P.; MOTA, Jose Italo S.; ALMEIDA, Tobias; PORTES, Evandro; JR, Antonio Ribeiro-Oliveira; VILAR, Lucio; BOGUSZEWSKI, Cesar Luiz; TAVARES, Ana Beatriz Winter; NUNES-NOGUEIRA, Vania S.; MAZZUCO, Tania Longo; RECH, Carolina Garcia Soares Leaes; MARQUES, Nelma Veronica; CHIMELLI, Leila; CZEPIELEWSKI, Mauro; BRONSTEIN, Marcello D.; ABUCHAM, Julio; CASTRO, Margaret de; KASUKI, Leandro; GADELHA, MonicaContext: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. Objective: To develop a prediction model of therapeutic response of acromegaly to fg-SRL. Methods: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). Results: A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P=.014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. Conclusion: We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.
- Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors(2015) SHIMON, Ilan; JALLAD, Raquel S.; FLESERIU, Maria; YEDINAK, Chris G.; GREENMAN, Yona; BRONSTEIN, Marcello D.Objectives: Patients with acromegaly usually harbor macroadenomas measuring between 10 and 30 mm in maximal diameter. Giant (adenoma size >= 40 mm) GH-secreting pituitary tumors are rarely encountered and the aim of this study is to analyze different methods for managing them. Design and methods: We have identified 34 patients (15 men and 19 females) with giant adenomas among 762 subjects (4.5%) with acromegaly in our records, and characterized their clinical characteristics and response to treatment. Results: Mean age at diagnosis was 34.9 +/- 12.5 years (range, 16-67 years). Mean adenoma size was 49.4 +/- 9.4 mm (range, 40-80 mm); 30 adenomas showed cavernous sinus invasion and 32 had suprasellar extension. Twenty-nine (85%) patients had visual field defects. Mean baseline IGF1 was 3.4 +/- 1.8XULN. All patients except one underwent pituitary surgery (one to three procedures), but none achieved hormonal remission following first surgery. Among the 28 subjects with visual disturbances, 14 recovered post-operatively and 13 improved. Treatment with somatostatin analogs was given to all patients after surgical failure. Six achieved remission, nine others were partially controlled (IGF1<1.5XULN; 3/9 when combined with cabergoline), and 17 did not respond (two were lost). Nine patients were treated with pegvisomant, alone (n=4) or in combination with somatostatin analogs (n=5); five are in remission and two are partially controlled. Pasireotide-LAR achieved hormonal remission in one of the six patients. Currently, after a mean follow-up period of 8.9 years, 17 patients are in biochemical remission, eight are partially controlled, and seven are uncontrolled (two were lost to follow-up). Conclusions: Giant GH-secreting adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission.
- The place of medical treatment of acromegaly: current status and perspectives(2013) JALLAD, Raquel S.; BRONSTEIN, Marcello D.Introduction: Acromegaly is characterized by elevated growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels and by progressive somatic disfigurement and systemic manifestations, which lead to a mortality rate higher than the general population. Therefore, diagnosis and properly treatment should be performed as soon as possible. Areas covered: This article focuses on the state of the art of acromegaly medical treatment. Somatostatin analogs, dopamine agonists and GH receptor antagonist were reviewed. Somatostatin analogs, the first-choice pharmacotherapy, can be used as primary or pre-operative treatment or as secondary therapy after failed surgery. Dopamine agonists have been used in patients with slightly elevated hormone levels and/or mixed GH/prolactin adenomas. Pegvisomant is indicated for resistant to somatostatin analogs/dopamine agonists. Combined treatment is also an option for resistant cases. Other non-conventional therapies and perspectives of treatment were also been discussed. Expert opinion: The control of disease activity in acromegaly is of paramount importance. Medical treatment is an important option for cases in which surgery was unsuccessful or not indicated. Despite the achievements in medical treatment, somatotropic tumor aggressiveness and/or resistance to the drugs currently available remain a concern. Therefore, novel therapy targets based on molecular pathogenesis of GH-secreting tumors are currently in development, aiming at fulfilling this important gap.
- Pasireotide for treating acromegaly(2016) BRONSTEIN, Marcello D.; JALLAD, Raquel S.Introduction: Uncontrolled acromegaly can lead to serious illness and premature death. Currently, treatment options include surgery, medical therapy and radiotherapy. Somatostatin analogues (SAs) are the medical treatment of choice. Nevertheless, a percentage of patients do not adequately respond to first generation SAs, lanreotide and octreotide, monotherapy. In this context, the multi-ligand SA pasireotide, which has a broader binding profile, appears as an option. Areas covered: The aim of this paper is to review pasireotide as an option for acromegalic patients. It will provide an overview, emphasizing its mechanism of action, clinical efficacy, adverse effects and indications. In addition to Google Scholar, a PubMed search using key words was conducted, and relevant articles published in English peer-reviewed journals were retrieved. Only those papers that directly addressed pasireotide treatment for acromegaly were retained for extensive review. Expert opinion: Pasireotide has been shown to overcome resistance to the first generation SAs in a subset of acromegalic patients, becoming an important tool in the treatment algorithm of acromegaly. Nevertheless, due to the higher prevalence of hyperglycemia-related events under its use, in our opinion pasireotide treatment should be reserved for those acromegalic patients inadequately controlled by first generation SAs, lanreotide and octreotide.
- Brazilian multicenter study on pegvisomant treatment in acromegaly(2019) BOGUSZEWSKI, Cesar L.; HUAYLLAS, Martha Katherine P.; VILAR, Lucio; NAVES, Luciana Ansaneli; RIBEIRO-OLIVEIRA JUNIOR, Antonio; SOARES, Beatriz Santana; CZEPIELEWSKI, Mauro Antonio; ABUCHAM, Julio; CORREA-SILVA, Silvia Regina; BRONSTEIN, Marcello Delano; JALLAD, Raquel Soares; DUARTE, Felipe Gaia; MUSOLINO, Nina Rosa; KASUKI, Leandro; GADELHA, Monica RobertoObjective: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 mu g/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.