ANDREA GLEZER
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
42 resultados
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- Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment(2017) BUENO, C. B. F.; TRARBACH, E. B.; BRONSTEIN, M. D.; GLEZER, A.Background About 80% of prolactinomas respond to dopamine agonists (DA) with hormonal normalization and tumor shrinkage. Mechanisms of DA resistance include reduction of dopamine receptor subtype 2 (DRD2) expression, short and long isoform ratio and post-receptor mechanisms. It was suggested that polymorphisms in the gene encoding dopamine receptor subtype 2 gene (DRD2) could be associated with variable effectiveness of cabergoline (CAB). Objective To assess the influence of DRD2 polymorphisms in responsiveness of CAB treatment in patients with prolactinoma. Study design and patients Cross-sectional retrospective case-control study analyzing the frequency of five DRD2 polymorphisms in 148 patients with prolactinoma and 349 healthy subjects. The association of genetic variants and clinical characteristics with CAB responsiveness was performed in 118 patients (mean age at diagnosis 29 years; range 11-61 years) with hormonal evaluation. Patients with prolactin (PRL) normalization were considered as responders. Results No association in genotypes and allele proportions was found comparing patients and controls. On pharmacogenetic study, 118 patients on CAB were included and 20% were non-responders. No association was found between clinical characteristics (gender, age, PRL level and tumor size at diagnosis) and polymorphisms of DRD2 with CAB responsiveness. Otherwise, there was association between polymorphisms rs1076560 (allele A) and rs1800497 (allele T) and the presence of macroadenomas. Conclusion No correlation was found between DRD2 polymorphisms and CAB responsiveness in patients with prolactinoma. More data are necessary in order to assess the influence of DRD2 genotyping on DA treatment response.
- Prolactinomas in pregnancy: considerations before conception and during pregnancy(2020) GLEZER, Andrea; BRONSTEIN, Marcello D.Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.
- Penetrance of Functioning and Nonfunctioning Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 in the Second Decade of Life(2014) GONCALVES, Tatiana D.; TOLEDO, Rodrigo A.; SEKIYA, Tomoko; MATUGUMA, Sergio E.; MALUF FILHO, Fauze; ROCHA, Manoel S.; SIQUEIRA, Sheila A. C.; GLEZER, Andrea; BRONSTEIN, Marcelo D.; PEREIRA, Maria A. A.; JUREIDINI, Ricardo; BACCHELLA, Telesforo; MACHADO, Marcel C. C.; TOLEDO, Sergio P. A.; LOURENCO JR., Delmar M.Context: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. Apotential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. Objective: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. Design: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. Patients: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. Methods: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. Results: The overall penetrance of PETs during the second decade of life was42%(8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67 < 2%). Conclusions: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.
- Apoplexy in nonfunctioning pituitary adenomas(2018) WILDEMBERG, Luiz Eduardo; GLEZER, Andrea; BRONSTEIN, Marcello D.; GADELHA, Monica R.Pituitary apoplexy is an uncommon event, occurring due to the infarction and/or haemorrhage usually of a previously unknown pituitary adenoma. It can occur in all adenoma subtypes but is more common in nonfunctioning pituitary adenomas. The physiopathology is not completely clear, and precipitating factors, such as major surgeries, anticoagulant use or pituitary dynamic tests, can be found in up to 40% of patients. The clinical presentation is characterized by a rapid onset with a headache as the main symptom, but visual disturbances can also be present as well as meningism and intracranial hypertension. The diagnosis is based on imaging evaluations, mainly using magnetic resonance imaging, which can show various patterns depending on the timeframe following the occurrence of the apoplectic event. Pituitary hormonal deficits are also common, and the evaluation of hormonal levels is mandatory. Pituitary apoplexy can be managed by surgery or conservative treatment, and a multidisciplinary team is essential for the decision-making process. The outcome is usually positive with both surgical and conservative approaches, but surveillance is needed due to the risk of re-bleeding or tumour recurrence.
bookPart Regulação Hipotálamo-hipofisária(2016) GLEZER, Andrea; BRONSTEIN, Marcelo Delano- Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas(2016) SHIMON, Ilan; SOSA, Ernesto; MENDOZA, Victoria; GREENMAN, Yona; TIROSH, Amit; ESPINOSA, Etual; POPOVIC, Vera; GLEZER, Andrea; BRONSTEIN, Marcello D.; MERCADO, MoisesProlactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size a parts per thousand yen40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter a parts per thousand yen60 mm) are rare, and their management outcomes have not been well characterized. We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size a parts per thousand yen60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment. Mean age was 36.3 +/- 13.5 years (range 12-59 years). Mean adenoma size was 71.8 +/- 10.2 mm (60-92 mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78 %) had visual field defects. Mean PRL at presentation was 28,465 ng/ml (range 1300-270,000). All patients were treated with cabergoline (3.9 +/- 2.0 mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20 months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8 +/- 5.1 years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRL < 3 x ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints. These enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.
- The Pituitary Gland in Pregnancy(2022) GLEZER, A.; BRONSTEIN, M. D.During pregnancy, pituitary morphology and function are modified by placental hormonal secretion. Pituitary volume is increased due to lactotroph hypertrophy and hyperplasia. Placental sex steroids inhibit GnRH and gonadotropin secretion. The placenta secretes a variant isoform of GH, increasing IGF-1 levels. TSH secretion decreases in the first trimester, secondary to thyroid stimulation by human chorionic gonadotropin. Hepatic production of thyroid-binding globulin is stimulated by estrogens, increasing total T4 and T3. Placental CRH stimulates pituitary and placental ACTH, increasing cortisol levels throughout pregnancy. Infertility is common in patients harboring pituitary tumors. Pathophysiology includes hormonal hypersecretion and tumoral mass effect. Hypopituitarism can also result from surgery and/or radiotherapy for pituitary adenoma treatment. Hyperprolactinemia, occurring in prolactinomas, the most common subtype of pituitary adenomas, and other pituitary tumors, inhibits GnRH pulsatility. Different mechanisms seem to play a role in hypogonadism of patients harboring acromegaly: tumoral gonadotroph compression, hyperprolactinemia, and GH/IGF-1 excess disrupting gonadal axis. In Cushing's disease, hypogonadism is mainly due to the negative impact of hypercortisolism and hyperandrogenism in the gonadotrophic axis. Clinically nonfunctioning pituitary tumors seldom are associated with pregnancy. In pituitary adenomas, treatment is often necessary to control hormonal hypersecretion and tumor mass effect related to infertility. Other causes of infertility include lymphocytic hypophysitis and Sheehan's syndrome. This chapter reviews the pathophysiology, diagnosis, and therapeutic approaches for women with pituitary diseases, before and during pregnancy, in order to induce fertility and avoid the deleterious effects of hormonal hyper- or hyposecretion. © 2022 Elsevier Inc. All rights reserved.
- Pituitary autoimmune disease: nuances in clinical presentation(2012) GLEZER, A.; BRONSTEIN, M. D.Pituitary autoimmune disease is considered an autoimmune organ-specific disorder, characterized by a pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be secondary to systemic diseases or infections. Primary pituitary hypophysitis is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous), necrotizing and IgG4 plasmacytic, according to the histological findings. Concerning lymphocytic hypophysitis (LH), it is characterized by lymphocytic infiltration and can be subclassified according to the affected area on: lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis and lymphocytic panhypophysitis. LH had always been considered a rare disease. Nevertheless, with improved imaging techniques, especially magnetic resonance imaging (MRI), LH diagnosis has been increased. This disease usually affects young women during pregnancy or postpartum period with headache, visual impairment, ACTH deficiency and a homogenous sellar mass with thickening of pituitary stalk in MRI. Definitive diagnosis depends on histopathological evaluation; nevertheless, a presumptive diagnosis could be done in a typical case. As no specific autoantigen was identified in LH, there is no antipituitary antibody (APA) method available for helping diagnosis. However, APA used in some centers for research could support an autoimmune origin for some hypopituitarism previously named as idiopathic, confirming nuances in clinical presentation of pituitary autoimmune disease. Therapeutic approach should be based on the grade of suspicious and clinical manifestations of LH.
bookPart Síndrome da sela vazia e apoplexia hipofisária(2017) CUNHA NETO, Malebranche Berardo Carneiro da; MUSOLINO, Nina Rosa Castro; TOSCANINI, Andrea Cecília; GLEZER, Andreaarticle 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.