RESUMEN
PURPOSE: Erectile dysfunction (ED) is frequently underreported in men suffering from prolactinomas and can be challenging to manage. Both dopamine agonists (DAs) and transsphenoidal surgery (TSS) correct hyperprolactinemia and restore gonadal function. However, there is scarce data regarding their effectiveness in correcting ED over the long term. METHODS: This study is a retrospective single-center comparative cohort study analyzing men diagnosed with prolactinomas, both with and without confirmed erectile dysfunction (ED) at diagnosis. Independent risk factors for persistent ED over the long term were examined using multivariate logistic regression. RESULTS: Among the 39 men with lactotroph adenomas, ED was one of the presenting symptoms in 22 (56%). The mean age at diagnosis was 45 ± 12 years. Surgery was the primary treatment in 6 (27%) ED patients and 8 (47%) non-ED patients. After a mean follow-up of 74 ± 48 months, remission from hyperprolactinemia was achieved in the majority (76%) of men: 71% in the non-ED cohort and 81% in the ED group (p = 0.70), regardless of the primary treatment strategy (surgical 84% versus medical 72%, p = 0.46). Long-term remission of ED was noted in 16 (73%) patients. Interestingly, high baseline BMI levels emerged as potential risk factors for persistent ED over the long term (OR 1.4, 95%CI 1.0-1.9; p = 0.04), while neither the initial adenoma size nor the primary treatment strategy (i.e., TSS vs. DAs) reached statistical significance. CONCLUSIONS: Correcting hyperprolactinemia and its associated hypogonadism significantly improves ED in the majority of men with prolactinomas over the long term, regardless of the primary treatment strategy employed. In addition to addressing endocrine deficiencies, the early initiation of weight control programs may be considered for men with lactotroph adenomas and ED. Although our study suggests an association between BMI and the risk of persistent ED, further research is needed to establish any causal relationships.
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Disfunción Eréctil , Neoplasias Hipofisarias , Prolactinoma , Humanos , Masculino , Persona de Mediana Edad , Prolactinoma/complicaciones , Prolactinoma/cirugía , Disfunción Eréctil/etiología , Estudios Retrospectivos , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/cirugía , Adulto , Resultado del Tratamiento , Hiperprolactinemia/etiología , Agonistas de Dopamina/uso terapéutico , Estudios de Cohortes , Factores de RiesgoRESUMEN
INTRODUCTION: Prolactinoma account to the most common pituitary adenomas and current therapy regime constitutes of dopamine agonist therapy (DA) and surgery in selected cases [17]. Due to tumor fibrosis induced by previous DA therapy, surgical removal can be challenging though. Therefore, this study investigates how preoperative DA usage influences perioperative treatment and surgical outcome in prolactinoma and aims to ascertain whether a specific subgroup of prolactinoma patients could derive greater benefit from exclusive surgical intervention. METHODS: We retrospectively analyzed n = 159 surgically treated and histologically confirmed prolactinomas in the sella region from 2013-2022 in our institution. Clinical, radiological and surgical features were analyzed. Univariate and multivariate analyses were performed. RESULTS: Out of total of 159 prolactinoma patients, 83.6% received previous treatment with DA followed by surgery, while only 16.4% received exclusive surgery. Both groups presented similar initial tumor volumes (1.9cm3 vs. 1.5cm3, p = 0.59) and equal preoperative prolactin levels (PRL) (199.7 µg/l vs. 191.0 µg/l, p = 0.44). Surgical procedures took significantly longer when patients received prior DA treatment (79 min. vs. 70 min., p = 0.0479). Six months after surgery, pretreated patients revealed significantly higher PRL compared to non-treated (107 g/l vs. 8.64 µg/, p = 0.0009). Additionally, untreated microprolactinoma presented a remission of 100%, whereas pretreated exhibited a remission rate of 88.75%. CONCLUSION: The current study demonstrates that prior DA treatment is associated with significantly longer surgeries, higher recurrence rates and lower rates of normalization of PRL levels after surgery, particularly in microprolactinomas and support the latest recommendations of the Pituitary Society's Consensus Statement 2023, which favors the option of surgery alone as first-line therapy for microprolactinomas.
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Agonistas de Dopamina , Neoplasias Hipofisarias , Prolactinoma , Humanos , Prolactinoma/tratamiento farmacológico , Prolactinoma/cirugía , Agonistas de Dopamina/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Adulto , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/patología , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Cuidados Preoperatorios/métodos , Anciano , Adolescente , Prolactina/sangreRESUMEN
Prolactinomas are a common cause of infertility in women. Medical treatment with dopamine agonists (DAs) has an excellent efficacy at restoring fertility and a reassuring safety profile in early pregnancy. Surgical treatment before conception is required in some cases of large macroadenomas and incomplete treatment response. In women with microprolactinomas, the pregnancy course is usually uneventful. In women with macroprolactinomas that are near/abut the optic chiasm, symptomatic tumor enlargement can occur during pregnancy and require a multidisciplinary team approach. This review provides an update regarding outcomes and management of prolactinomas before conception, during pregnancy, and postpartum.
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Neoplasias Hipofisarias , Complicaciones Neoplásicas del Embarazo , Prolactinoma , Humanos , Prolactinoma/terapia , Prolactinoma/tratamiento farmacológico , Embarazo , Femenino , Neoplasias Hipofisarias/terapia , Neoplasias Hipofisarias/complicaciones , Complicaciones Neoplásicas del Embarazo/terapia , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Agonistas de Dopamina/uso terapéutico , Agonistas de Dopamina/efectos adversos , Atención Preconceptiva/métodosRESUMEN
PURPOSE: An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index. METHODS: We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55). RESULTS: IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04). CONCLUSIONS: Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
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Agonistas de Dopamina , Factor I del Crecimiento Similar a la Insulina , Neoplasias Hipofisarias , Prolactinoma , Humanos , Prolactinoma/tratamiento farmacológico , Prolactinoma/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/análisis , Femenino , Masculino , Adulto , Estudios Retrospectivos , Agonistas de Dopamina/uso terapéutico , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/sangre , Persona de Mediana Edad , Cabergolina/uso terapéutico , Peso Corporal/efectos de los fármacos , Estudios de Seguimiento , Prolactina/sangre , Índice de Masa Corporal , PronósticoRESUMEN
The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary microadenomas. The most common clinically relevant pituitary adenomas are prolactin-secreting, followed by HI, and far less common are growth hormone (GH)-, adrenocorticotropic hormone (ACTH)- and thyroid-stimulating hormone (TSH)-secreting adenomas. Pituitary adenomas are usually benign, although aggressive growth and invasion occurs in individual cases. Very rarely, they give rise to metastases and are then termed pituitary carcinomas. All pituitary tumors require endocrine testing for pituitary hormone excess. In addition to the medical history and clinical examination, laboratory diagnostics are very important. Symptoms such as irregular menstruation, loss of libido or galactorrhea often lead to the timely diagnosis of prolactinomas, and hyperprolactinemia can easily confirm the diagnosis (considering the differential diagnoses). Diagnosis is more difficult for all other hormone-secreting pituitary adenomas (acromegaly, Cushing's disease, TSHoma), as the symptoms are often non-specific (i.e., headaches, weight gain, fatigue, joint pain). Furthermore, comorbidities such as hypertension, diabetes, and depression are such widespread diseases that pituitary adenomas are rarely considered as the underlying cause. Timely diagnosis and appropriate treatment have a significant impact on morbidity, mortality, and quality of life. Therefore, the role of primary care physicians is very important for achieving an early diagnosis. In addition, patients with pituitary adenomas should always be referred to endocrinologists to ensure optimal diagnosis as well as treatment.
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Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Diagnóstico Diferencial , Adenoma/metabolismo , Adenoma/patología , Adenoma/diagnóstico , Prolactinoma/diagnóstico , Prolactinoma/metabolismo , Prolactinoma/patologíaRESUMEN
OBJECTIVE: Prolactinomas-pituitary tumors that overproduce prolactin-can cause various troublesome symptoms. Dopamine agonists (DAs) reduce prolactin production in the prolactin pathway, making them the first-line treatment for prolactinomas. However, the main side effect of DA treatment, hyperdopaminergia, is an explicit etiology for psychiatric side effects. Psychiatric conditions are often treated with dopamine antagonists, which can induce hyperprolactinemia. This presents a challenge for patients with both a prolactinoma and a preexisting psychiatric condition, as treatment of one condition could worsen the other. This review seeks to identify an adequate therapeutic regimen for patients with coexisting prolactinomas and psychiatric symptoms. METHODS: This review examined PubMed citations from 1960 to 2023 published in English and involving human subjects. Case reports, case series, and cohort studies involving patients with concomitant prolactinomas and psychiatric symptoms, as validated by brain imaging, serologic prolactin levels, and medical history or chart reports of psychiatric symptoms, were included. RESULTS: Thematic analysis included 23 reports involving 42 participants; 27 of the 42 patients experienced a significant reduction in prolactin levels and psychiatric symptoms (64%). Treatment of those 42 patients included discontinuing or altering antipsychotic/dopamine antagonist therapy or discontinuing DA therapy to reduce psychiatric symptoms, with surgery or radiation postpharmacotherapy as a last-line strategy. However, in some cases (reported in Tables 2 to 4), either psychiatric or prolactin-related symptoms recurred despite adjustment. CONCLUSIONS: Clinicians may find it beneficial to prioritize specific antipsychotics (aripiprazole, olanzapine, ziprasidone, or clozapine) over others (risperidone, thioridazine, thiothixene, and remoxipride). Discontinuing DA medication at least periodically until the patient's condition improves may also be advisable. If these 2 initial approaches do not yield a significant improvement in symptom management, surgery or radiation therapy may be considered. As patients may respond differently to these therapies, our study still recommends a patient-centered approach.
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Agonistas de Dopamina , Trastornos Mentales , Neoplasias Hipofisarias , Prolactinoma , Humanos , Prolactinoma/tratamiento farmacológico , Prolactinoma/terapia , Neoplasias Hipofisarias/complicaciones , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/terapia , Agonistas de Dopamina/uso terapéutico , Agonistas de Dopamina/farmacología , Antipsicóticos/efectos adversos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Antagonistas de Dopamina/farmacologíaRESUMEN
We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.
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Antineoplásicos , Curcumina , MicroARNs , Neoplasias Hipofisarias , Prolactinoma , Curcumina/administración & dosificación , Prolactinoma/sangre , Prolactinoma/tratamiento farmacológico , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/tratamiento farmacológico , Autofagia/efectos de los fármacos , Regulación hacia Arriba , Regulación de la Expresión Génica , MicroARNs/sangre , MicroARNs/genética , Transducción de Señal , Antineoplásicos/administración & dosificación , Masculino , FemeninoRESUMEN
OBJECTIVE: Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to evaluate and compare muscle function, exercise capacity, physical activity (PA) level, CVD risk factor knowledge level, sleep quality, fatigue and quality of life between prolactinoma patients and healthy controls. METHODS: Nineteen female patients with prolactinomas and 19 healthy women were included in this study. Quadriceps muscle strength (QMS) was measured using a hand dynamometer, and muscular endurance was evaluated via the squat test. The 6-minute walking test (6MWT) distance was also measured. CVD risk factor knowledge levels were evaluated with the Cardiovascular Diseases Risk Factors Knowledge Level Scale (CARRF-KL), PA levels were assessed with the International Physical Activity Questionnaire-short form (IPAQ), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), fatigue was assessed with the Multidimensional Fatigue Rating Scale (MAF), and quality of life was assessed with the Short Form-36 questionnaire (SF-36). RESULTS: Patients with prolactinomas had significantly lower 6MWT distances; CARRF-KL total scores; SF-36 general health and physical limitation scores; and higher IPAQ-sitting scores than did healthy controls (p < 0.05). Moreover, there were no significant differences between the groups in terms of QMS score; number of squats; severity of IPAQ score; severity, moderate, or total walking score; total PSQI score; or total MAF score (p > 0.05). CONCLUSIONS: Exercise capacity and quality of life are adversely affected, and sedentary behavior is observed in prolactinomas. Patients with prolactinomas have less knowledge about CVD risk factors than healthy individuals. CVD incidence and knowledge and functional capacity should be improved in patients with prolactinomas by the use of a multidisciplinary team for cardiac rehabilitation. CLINICAL TRIAL REGISTRATION: This study is part of a larger clinical trial registered on ClinicalTrials.gov prior to participant enrollment (NCT05236829).
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Enfermedades Cardiovasculares , Tolerancia al Ejercicio , Ejercicio Físico , Fuerza Muscular , Neoplasias Hipofisarias , Prolactinoma , Calidad de Vida , Humanos , Femenino , Adulto , Prolactinoma/fisiopatología , Prolactinoma/complicaciones , Persona de Mediana Edad , Ejercicio Físico/fisiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/etiología , Tolerancia al Ejercicio/fisiología , Fuerza Muscular/fisiología , Neoplasias Hipofisarias/fisiopatología , Neoplasias Hipofisarias/complicaciones , Fatiga/fisiopatología , Factores de Riesgo de Enfermedad Cardiaca , Calidad del Sueño , Conocimientos, Actitudes y Práctica en Salud , Factores de RiesgoRESUMEN
OBJECTIVE: Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells. DESIGN AND METHODS: Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape. RESULTS: Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples. CONCLUSIONS: Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG.
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Cabergolina , Neoplasias Hipofisarias , Prolactinoma , Humanos , Cabergolina/farmacología , Cabergolina/uso terapéutico , Prolactinoma/tratamiento farmacológico , Prolactinoma/metabolismo , Masculino , Femenino , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/patología , Adulto , Persona de Mediana Edad , Fibrosis , Prolactina/metabolismo , Agonistas de Dopamina/farmacología , Agonistas de Dopamina/uso terapéutico , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Adulto Joven , Microambiente Tumoral/efectos de los fármacosRESUMEN
Purpose: The purpose of this study was to explore the factors influencing PRL levels in patients with prolactinoma and to investigate the correlations between anxiety, depression, sleep, self-efficacy, and PRL levels. Methods: This retrospective study included 176 patients with prolactinoma who received outpatient treatment at the Affiliated Hospital of Zunyi Medical University from May 2017 to August 2022. The general information questionnaire, Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and General Self-Efficacy Scale (GSES) were used for data collection. A generalized estimating equation (GEE) model was used to analyze the factors influencing PRL levels in patients with prolactinoma. GEE single-effect analysis was used to compare PRL levels at different time points between anxiety group and nonanxiety group, between insomnia group and normal group, and between low, medium, and high self-efficacy groups. Results: The median baseline PRL level and the PRL levels at 1, 3, 6, and 12 months of follow-up were 268.50 ng/ml, 122.25 ng/ml, 21.20 ng/ml, 19.65 ng/ml, and 16.10 ng/ml, respectively. Among patients with prolactinoma, 59.10% had anxiety (HADS-A score = 7.35 ± 3.34) and 28.98% had depression (HADS-D score = 5.23 ± 3.87), 9.10% had sleep disorders (AIS score = 6.10 ± 4.31) and 54.55% had low self-efficacy (GSES score = 2.13 ± 0.83). Educational level, tumor size, number of visits, sleep quality, anxiety level, and self-efficacy level were found to be factors influencing PRL levels in patients with prolactinoma (P<0.05). Higher PRL levels were observed in the anxiety group compared to the non-anxiety group (P<0.001), in the insomnia group compared to the normal group (P<0.05), and in the low self-efficacy group compared to the medium and high self-efficacy groups (P<0.05). Conclusion: PRL levels in patients with prolactinoma are related to education level, tumor size, number of visits, anxiety, self-efficacy, and sleep but not depression. PRL levels were higher in patients with anxiety, low self-efficacy, and sleep disorders.
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Neoplasias Hipofisarias , Prolactinoma , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Prolactinoma/complicaciones , Depresión , Estudios Retrospectivos , Autoeficacia , Prolactina , Sueño , Ansiedad , Neoplasias Hipofisarias/complicacionesRESUMEN
Background: Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory profiles in PRL patients, aiming to identify potential prognostic markers. Methods: The study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage. Results: The PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels. Conclusion: This study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices. However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients.
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Neoplasias Hipofisarias , Prolactinoma , Humanos , Prolactinoma/sangre , Prolactinoma/tratamiento farmacológico , Prolactinoma/patología , Femenino , Masculino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Resultado del Tratamiento , Inflamación/sangre , Centros de Atención Terciaria , Cabergolina/uso terapéutico , Prolactina/sangre , Pronóstico , Estudios de Seguimiento , Estudios de Cohortes , Adulto JovenRESUMEN
Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.
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Hiperprolactinemia , Neoplasias Hipofisarias , Prolactinoma , Embarazo , Humanos , Femenino , Hiperprolactinemia/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Brasil , Prolactina , Prolactinoma/diagnósticoRESUMEN
Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.
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Hiperprolactinemia , Neoplasias Hipofisarias , Prolactinoma , Embarazo , Humanos , Femenino , Hiperprolactinemia/tratamiento farmacológico , Prolactinoma/terapia , Agonistas de Dopamina/efectos adversos , Prolactina , Neoplasias Hipofisarias/terapia , BrasilRESUMEN
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.
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Cabergolina , Clomifeno , Hipogonadismo , Neoplasias Hipofisarias , Prolactinoma , Humanos , Masculino , Adulto , Prolactinoma/tratamiento farmacológico , Persona de Mediana Edad , Hipogonadismo/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Hipofisarias/tratamiento farmacológico , Cabergolina/uso terapéutico , Cabergolina/administración & dosificación , Clomifeno/uso terapéutico , Clomifeno/administración & dosificación , Resultado del Tratamiento , Testosterona/sangre , Moduladores Selectivos de los Receptores de Estrógeno/administración & dosificación , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Ergolinas/uso terapéutico , Ergolinas/administración & dosificación , Prolactina/sangreRESUMEN
BACKGROUND: Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma. METHODS: A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included. Bias and methodological rigour were assessed using the MINORS criteria. RESULTS: A total of 18 studies were identified studies were available for review, comprising 877 patients. Most were small cross-sectional studies at high risk of bias. Prolactinoma exhibit worse QOL than healthy controls, particularly mental and psychosocial wellbeing. QOL is also worse than patients with non-functional adenomas, but better than those with Cushing's disease and acromegaly. QOL correlates with prolactin levels, and approaches population baseline with prolonged biochemical control. Dopamine agonists and surgery both improve overall QOL, however improvements are more rapid with surgery. CONCLUSION: Poor quality of life in prolactinoma is multifactorial, related to biochemical control, side effects of therapy, and sellar mass effect. Targeting persistent symptoms, reducing healthcare costs, and reducing side-effects of therapy are avenues to improving QOL in patients with prolactinoma.
Asunto(s)
Neoplasias Hipofisarias , Prolactinoma , Calidad de Vida , Prolactinoma/tratamiento farmacológico , Humanos , Neoplasias Hipofisarias/psicología , Agonistas de Dopamina/uso terapéuticoRESUMEN
OBJECTIVE AND DESIGN: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years. PATIENTS AND MEASUREMENTS: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis. RESULTS: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference. CONCLUSIONS: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it.
Asunto(s)
Hiperprolactinemia , Prolactinoma , Adulto , Femenino , Humanos , Masculino , Hiperprolactinemia/diagnóstico , Prolactina , Prolactinoma/diagnósticoRESUMEN
OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.