RESUMO
Introduction: Prolactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar). Methods: We compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas ("unselected", n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39). Results: AIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p<0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p<0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p<0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p<0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (>50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p<0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p<0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups. Discussion: AIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Humanos , Masculino , Agonistas de Dopamina , Células Germinativas , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/terapia , Prolactina , Prolactinoma/tratamento farmacológico , Prolactinoma/genética , Receptores de Hidrocarboneto ArílicoRESUMO
Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.
Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Endocrinologia/organização & administração , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/terapia , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/epidemiologia , Carcinoma Adrenocortical/terapia , Endocrinologia/normas , Europa (Continente) , Medicina Baseada em Evidências/organização & administração , Medicina Baseada em Evidências/normas , Medicina Baseada em Evidências/tendências , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Rede SocialAssuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Humanos , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Clinically relevant pituitary adenomas are present in about 1 per 1,000 of the general population and prolactinomas are by far the most common clinical subtype of pituitary adenomas. Usually prolactinomas affect premenopausal women and present with typical symptoms of menstrual disturbance and/or galactorrhea. They are generally managed with dopamine agonists to restore fertility and to control symptoms and tumor size. In a subset of prolactinomas, however, management remains challenging. Studies in recent years have identified the factors related to dopamine agonist resistance, such as male sex, genetic features, and aggressive tumor behavior. Certain other patient groups represent particular challenges for management, such as pediatric patients and pregnant women. Treatment with dopamine agonists is usually safe and effective, and adverse effects such as clinically relevant cardiac valvular complications and impulse control disorders may occur in isolated instances. A number of important disease characteristics of prolactinomas remain to be explained, such as the difference in sex prevalence before and after menopause, the higher prevalence of macroadenomas in older males, and the biochemical mechanisms of resistance to dopaminergic agonists.
Assuntos
Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/terapia , Prolactinoma/epidemiologia , Prolactinoma/terapia , Feminino , Humanos , MasculinoRESUMO
Background: Up to 7% of all adrenal incidentalomas (AIs) are pheochromocytomas (PCCs). In the evaluation of AI, it is generally recommended that PCC be excluded by measurement of plasma-free or 24-hour urinary fractionated metanephrines. However, recent studies suggest that biochemical exclusion of PCC not be performed for lesions with CT characteristics of an adrenocortical adenoma (ACA). Aim: To determine the proportion of PCCs with ACA-like attenuation or contrast washout on CT. Methods: For this multicenter retrospective study, two central investigators independently analyzed the CT reports of 533 patients with 548 histologically confirmed PCCs. Data on tumor size, unenhanced Hounsfield units (HU), absolute percentage washout (APW), and relative percentage washout (RPW) were collected in addition to clinical parameters. Results: Among the 376 PCCs for which unenhanced attenuation data were available, 374 had an attenuation of >10 HU (99.5%). In the two exceptions (0.5%), unenhanced attenuation was exactly 10 HU, which lies just within the range of ≤10 HU that would suggest a diagnosis of ACA. Of 76 PCCs with unenhanced HU > 10 and available washout data, 22 (28.9%) had a high APW and/or RPW, suggestive of ACA. Conclusion: Based on the lack of PCCs with an unenhanced attenuation of <10 HU and the low proportion (0.5%) of PCCs with an attenuation of 10 HU, it seems reasonable to abstain from biochemical testing for PCC in AIs with an unenhanced attenuation of ≤10 HU. The assessment of contrast washout, however, is unreliable for ruling out PCC.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Feocromocitoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: MDH2 (malate dehydrogenase 2) has recently been proposed as a novel potential pheochromocytoma/paraganglioma (PPGL) susceptibility gene, but its role in the disease has not been addressed. This study aimed to determine the prevalence of MDH2 pathogenic variants among PPGL patients and determine the associated phenotype. METHODS: Eight hundred thirty patients with PPGLs, negative for the main PPGL driver genes, were included in the study. Interpretation of variants of unknown significance (VUS) was performed using an algorithm based on 20 computational predictions, by implementing cell-based enzymatic and immunofluorescence assays, and/or by using a molecular dynamics simulation approach. RESULTS: Five variants with potential involvement in pathogenicity were identified: three missense (p.Arg104Gly, p.Val160Met and p.Ala256Thr), one in-frame deletion (p.Lys314del), and a splice-site variant (c.429+1G>T). All were germline and those with available biochemical data, corresponded to noradrenergic PPGL. CONCLUSION: This study suggests that MDH2 pathogenic variants may play a role in PPGL susceptibility and that they might be responsible for less than 1% of PPGLs in patients without pathogenic variants in other major PPGL driver genes, a prevalence similar to the one recently described for other PPGL genes. However, more epidemiological data are needed to recommend MDH2 testing in patients negative for other major PPGL genes.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Malato Desidrogenase/genética , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Paraganglioma/patologia , Feocromocitoma/patologia , Isoformas de ProteínasRESUMO
Context: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine, usually benign, tumors. Currently, the only reliable criterion of malignancy is the presence of metastases. Objective: The aim of this study was to identify genes associated with malignancy in PPGLs. Design: Transcriptomic profiling was performed on 40 benign and 11 malignant PPGLs. Genes showing a significantly different expression between benign and malignant PPGLs with a ratio ≥4 were confirmed and tested in an independent series by quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed for the validated genes on 109 benign and 32 malignant PPGLs. Functional assays were performed with hPheo1 cells. Setting: This study was conducted at the Department of Pathology of the Erasmus MC University Medical Center Rotterdam Human Molecular Genetics laboratory of the de Duve Institute, University of Louvain. Patients: PPGL samples from 179 patients, diagnosed between 1972 and 2015, were included. Main outcome measures: Associations between gene expression and malignancy were tested using supervised clustering approaches. Results: Ten differentially expressed genes were selected based on messenger RNA (mRNA) expression array data. Contactin 4 (CNTN4) was overexpressed in malignant vs benign tumors [4.62-fold; false discovery rate (FDR), 0.001]. Overexpression at the mRNA level was confirmed using qRT-PCR (2.90-fold, P = 0.02; validation set: 4.26-fold, P = 0.005). Consistent findings were obtained in The Cancer Genome Atlas cohort (2.7-fold; FDR, 0.02). CNTN4 protein was more frequently expressed in malignant than in benign PPGLs by immunohistochemistry (58% vs 17%; P = 0.002). Survival after 7 days of culture under starvation conditions was significantly enhanced in hPheo1 cells transfected with CNTN4 complementary DNA. Conclusion: CNTN4 expression is consistently associated with malignant behavior in PPGLs.
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Neoplasias das Glândulas Suprarrenais/diagnóstico , Biomarcadores Tumorais/metabolismo , Contactinas/metabolismo , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , RNA Mensageiro/metabolismo , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/metabolismo , Biomarcadores Tumorais/genética , Contactinas/genética , Perfilação da Expressão Gênica , Humanos , Paraganglioma/genética , Paraganglioma/metabolismo , Feocromocitoma/genética , Feocromocitoma/metabolismo , Prognóstico , RNA Mensageiro/genéticaRESUMO
Genetic diagnosis is recommended for all pheochromocytoma and paraganglioma (PPGL) cases, as driver mutations are identified in approximately 80% of the cases. As the list of related genes expands, genetic diagnosis becomes more time-consuming, and targeted next-generation sequencing (NGS) has emerged as a cost-effective tool. This study aimed to optimize targeted NGS in PPGL genetic diagnostics. A workflow based on two customized targeted NGS assays was validated to study the 18 main PPGL genes in germline and frozen tumor DNA, with one of them specifically directed toward formalin-fixed paraffin-embedded tissue. The series involved 453 unrelated PPGL patients, of whom 30 had known mutations and were used as controls. Partial screening using Sanger had been performed in 275 patients. NGS results were complemented with the study of gross deletions. NGS assay showed a sensitivity ≥99.4%, regardless of DNA source. We identified 45 variants of unknown significance and 89 pathogenic mutations, the latter being germline in 29 (7.2%) and somatic in 58 (31.7%) of the 183 tumors studied. In 37 patients previously studied by Sanger sequencing, the causal mutation could be identified. We demonstrated that both assays are an efficient and accurate alternative to conventional sequencing. Their application facilitates the study of minor PPGL genes, and enables genetic diagnoses in patients with incongruent or missing clinical data, who would otherwise be missed.
Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Análise Mutacional de DNA/métodos , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paraganglioma/diagnóstico , Feocromocitoma/diagnósticoAssuntos
Cardiopatias Congênitas/fisiopatologia , Paraganglioma/fisiopatologia , Feocromocitoma/fisiopatologia , Neoplasias das Glândulas Suprarrenais , Adulto , Idoso , Bélgica , Cardiologia , Feminino , Cardiopatias Congênitas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Paraganglioma/complicações , Paraganglioma/epidemiologia , Feocromocitoma/complicações , Feocromocitoma/epidemiologia , Prevalência , Estudos RetrospectivosRESUMO
Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology.
Assuntos
Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Valvas Cardíacas/efeitos dos fármacos , Hiperprolactinemia/tratamento farmacológico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adulto , Cabergolina , Agonistas de Dopamina/farmacologia , Ecocardiografia , Ergolinas/farmacologia , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/diagnóstico por imagem , Humanos , Hiperprolactinemia/etiologia , Masculino , Pessoa de Meia-Idade , Prolactinoma/complicações , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Evaluation of patient characteristics and mitotane use in the treatment of adrenocortical carcinoma (ACC) over a 4-year period in Belgium. MATERIAL AND METHODS: This was a multicentre retrospective review of the outcome of 34 patients treated with mitotane for ACC during the period [01/2008-12/2011] (12 diagnosed before and 22 diagnosed during the study period) and evaluated up to 06/2013. RESULTS: Patient and tumour characteristics were consistent with those generally described for ACC. Mean age at diagnosis was 46.5 years, most patients were female (62%), had functioning ACC (65%) and advanced tumours (ENSAT stages III or IV: 82%). Therapeutic mitotane plasma levels (14-20 mg/L) were achieved at least once in 70% of the cohort, after a median of 4 months, and were maintained for more than 2 months in 61% of evaluable patients. Mitotane-related adverse effects were observed in 66% of patients, were never serious, and included gastrointestinal, neurological, neuropsychological, hormonal, dermatologic and metabolic effects. Most patients (88%) discontinued mitotane, mainly due to tumour progression. Multivariate analysis showed that ENSAT stage was a prognostic factor for overall (OS) and disease-free survival (DFS); OS was also influenced independently by achievement of therapeutic mitotane plasma levels for at least two consecutive months. CONCLUSION: Patient and tumour characteristics were consistent with previously published data. OS and DFS were mostly influenced by ENSAT stage at diagnosis. Achieving therapeutic levels of mitotane for at least two consecutive months seemed to positively influence OS, but such levels were not reached or sustained in some patients.
Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Mitotano/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Bélgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitotano/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Clinical presentations of prolactinomas are quite different between genders. In comparison with women's prolactinoma, those in men showed predominance of large tumors with high prolactin (PRL) levels. This preponderance could be attributed to a greater proliferative potential of the tumors. Differences in magnetic resonance imaging (MRI) signal at diagnosis have not been yet clearly evaluated. METHODS: We conduct a retrospective study comparing MRI signal intensity (SI) on T2-weighted images (T2-WI) between 41 men and 41 women to investigate whether or not men prolactinoma present specific features. RESULTS: In addition to the size of the adenoma and PRL levels (P < 0001), prolactinomas in men also exhibit differences from those in women in signal on T2-WI on MRI (P < 0001). Women's prolactinomas are mostly of high SI on T2-WI while men's prolactinomas exhibit a more heterogeneous pattern of SI on T2-WI. Prolactinomas presenting with low SI on T2-WI are almost exclusively encountered in men. CONCLUSIONS: Presence of T2-WI hypointensities in pituitary adenoma can be predictive of a different subtype of prolactinoma almost encountered in men and possibly translate the presence of spherical amyloid deposits, in agreement with the literature.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Prolactinoma/diagnóstico por imagem , Prolactinoma/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Placa Amiloide/diagnóstico por imagem , Placa Amiloide/patologia , Prolactina/sangue , Prolactinoma/sangue , Radiografia , Estudos Retrospectivos , Fatores SexuaisRESUMO
BACKGROUND: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by second-generation PTH assays, the normal 3rd/2nd generation PTH ratio (<1) is inverted in PCa (ie, >1). OBJECTIVE: The objective of the investigation was to study the utility and advantages of automated 3rd/2nd generation PTH ratio measurements using the Liaison XL platform over existing manual techniques. SETTING: The study was conducted at a tertiary-referral academic center. DESIGN: This was a retrospective laboratory study. SUBJECTS: Eleven patients with advanced PCa (mean age 56.0 y). The controls were patients with primary-hyperparathyroidism (n = 144; mean age 53.8 y), renal transplantation (n = 41; mean age 50.6 y), hemodialysis (n = 80; mean age 65.2 y), and healthy elderly subjects (n = 40; mean age 72.6 y). RESULTS: The median (interquartile range) 3rd/2nd generation PTH ratio was 1.16 (1.10-1.38) in the PCa group, which was significantly higher than the control groups: hemodialysis: 0.74 (0.71-0.75); renal transplant: 0.77 (0.73-0.79); primary hyperparathyroidism: 0.76 (0.74-0.78); healthy elderly: 0.80 (0.74-0.83). An inverted 3rd/2nd-generation PTH ratio (>1) was seen in 9 of 11 PCa patients (81.8%) and in 7 of 305 controls (2.3%): 3 of 80 hemodialysis (3.8%), and 4 of 144 primary-hyperparathyroidism patients (2.8%). Of four PCa patients who had a normal PTH ratio with the manual method, two had an inverted 3rd/2nd-generation PTH ratio with the automated method. CONCLUSIONS: Study of the 3rd/2nd-generation PTH ratio in large patient populations should be feasible using a mainstream automated platform like the Liaison XL. The current study confirms the utility of the inverted 3rd/2nd-generation PTH ratio as a marker of PCa (sensitivity: 81.8%; specificity: 97.3%).
Assuntos
Biomarcadores Tumorais/análise , Hormônio Paratireóideo/análise , Neoplasias das Paratireoides/diagnóstico , Adulto , Idoso , Automação Laboratorial , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Medições Luminescentes/instrumentação , Medições Luminescentes/métodos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Estudos RetrospectivosRESUMO
Recent studies have reported a higher prevalence of pituitary tumors than previously thought. Among these tumors, prolactinomas occur in up to 66% of cases. Since the mid-1980s, the widespread use of dopamine agonists has facilitated the management of the majority of prolactinomas, allowing biological and tumoral control in most cases. The less frequent cases of resistant prolactinomas remain challenging despite a multimodal therapy approach. The understanding of genetic alterations in familial and aggressive pituitary tumors provides new perspectives in the management of some prolactinomas. Genetic screening should be considered, particularly in familial cases but also in young patients with macroprolactinomas, as some mutations can predict potential aggressiveness.
RESUMO
BACKGROUND: Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. DESIGN AND METHODS: A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB ≥2.0 mg weekly. RESULTS: Ninety-two patients (50 F, 42 M) were analyzed. At diagnosis, most had macroprolactinomas (82.6%); males were significantly older than females (P=0.0003) and presented with a more aggressive disease. A genetic basis was identified in 12 patients. Thirty-six patients (39.1%) received only medical therapy, most underwent surgery (60.9%, including multiple interventions in 10.9%), and 14.1% received postoperative radiotherapy. Eight patients developed late CAB resistance (8.7%). The median maximal weekly dose of CAB (CAB(max/w)) was 3.5 mg (2.0-10.5). Despite a higher CAB(max/w) in patients treated with multimodal therapy (P=0.003 vs exclusive pharmacological treatment), a debulking effect of surgery was shown in 14 patients, with a higher rate of PRL control (P=0.006) and a significant reduction in CAB(max/w) (P=0.001) postoperatively. At last follow-up (median 88 months), PRL normalization and tumor disappearance were achieved in 28 and 19.9% of the patients respectively, with no significant sex-related difference observed in CAB(max/w) or disease control. Mortality was 4.8%, with four patients developing aggressive tumors (4.3%) and three a pituitary carcinoma (3.3%). CONCLUSION: CAB-resistant prolactinomas remain a serious concern. Surgical debulking, newer therapeutic strategies, and early diagnosis of genetic forms could help to improve their outcome.
Assuntos
Antineoplásicos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Ergolinas/administração & dosagem , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cabergolina , Quimioterapia Adjuvante , Criança , Esquema de Medicação , Feminino , Humanos , Hiperprolactinemia/etiologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Prolactinoma/complicações , Prolactinoma/diagnóstico , Prolactinoma/genética , Prolactinoma/patologia , Prolactinoma/cirurgia , Proteínas Proto-Oncogênicas/genética , Estudos Retrospectivos , Falha de TratamentoRESUMO
BACKGROUND: Impotence and decreased libido are the cardinal features of prolactinomas in males. We describe the unusual clinical, pathological and biochemical features in a male patient with a giant prolactinoma and normal gonadal function. CASE REPORT: A 57 year-old man presented with visual symptoms related to a 30x25x60mm tumor of the sella and skull base. Biopsy revealed a pituitary adenoma and subsequent hormone profiles demonstrated grossly elevated serum prolactin (131,412ng/ml), LH at the upper limit of normal and normal testosterone. The patient had no symptoms of decreased libido or impotence related to this giant prolactinoma. Immunohistochemistry revealed a tumor that was positive for prolactin, alpha-subunit and LH. Cabergoline greatly reduced prolactin levels but these remained above normal. LH, testosterone and alpha-subunit levels were decreased in parallel. Loss of libido and impotence became apparent when testosterone fell below normal, a situation that resolved with further cabergoline treatment and prolactin inhibition and testosterone therapy. CONCLUSIONS: Sexual dysfunction is a hallmark of prolactinomas in males. Tumors that co-secrete prolactin and LH are extremely rare and this is the first such case reported in an adult male. In this case, normal testosterone was maintained by intact LH levels even in the face of the highest prolactin level reported to date.