Search Results (52)

Background: Central nervous system (CNS) tumors during pregnancy are rare but present significant diagnostic, therapeutic, and ethical challenges. These include both primary and metastatic lesions, which share overlapping clinical features and management complexities. Their clinical course is influenced by gestational physiological changes, which can mask symptoms and delay diagnosis, thereby increasing maternal and fetal risks. Objective: This review aims to synthesize current evidence on the epidemiology, pathophysiology, clinical presentation, diagnostic strategies, treatment options, prognosis, and ethical considerations related to CNS tumors in pregnant patients. Methods: A comprehensive literature review was conducted, including retrospective and prospective studies, clinical guidelines, and systematic reviews focusing on brain and spinal tumors diagnosed during pregnancy. Particular attention was given to the impact of gestational age, tumor histology, and maternal condition on treatment outcomes. Results: Hormone-sensitive tumors such as meningiomas and prolactinomas may exhibit accelerated growth during pregnancy due to elevated progesterone and prolactin levels. Diagnosis is often delayed due to symptom overlap with normal gestational changes. MRI without contrast remains the imaging modality of choice. Glucocorticoids and selected chemotherapy agents can be cautiously used depending on gestational age. Surgical resection, particularly in the second trimester, has been shown to be safe and effective in appropriate clinical scenarios. Multidisciplinary coordination is essential. Prognosis varies based on tumor type and timing of intervention, with maternal survival prioritized in high-risk situations. Ethical management hinges on patient autonomy, informed consent, and proportionality of medical interventions. Conclusions: CNS tumors during pregnancy require early recognition, individualized treatment planning, and ethical vigilance. Multidisciplinary collaboration is vital to optimizing outcomes for both mother and fetus. Future efforts should focus on developing standardized protocols and expanding evidence through multicenter studies. Full article

Background: Dopamine agonists (DAs) are first-line therapy for prolactin-secreting pituitary adenomas; however, a small proportion of tumors are resistant. Previous reports suggested that reduced D2R mRNA expression might cause resistance. This study aimed to determine if resistant prolactinomas express D2R protein. We also explored a role of estrogen receptor alpha (ERα) expression in DA resistance. Methods: We retrospectively selected 15 tumor specimens from 13 total patients (8 controls from 8 patients, 7 from 5 resistant patients) with resected lactotroph cell-type tumors. We reviewed age at diagnosis, tumor size, initial prolactin level, medical treatment, and reason for surgery. Immunohistochemistry was performed for D2R, prolactin, and ERα protein expression. Results: D2R expression was positive in seven of eight controls vs. two of seven in resistant tumors (p = 0.02). ERα expression did not significantly correlate with DA resistance. The two D2R expressing resistant tumors were ERα negative and both derived from a pre-pubertal female, supporting prior reports suggesting ERα may modulate DA therapy response. Conclusions: Our study introduces a reproducible method for assessing D2R protein expression in prolactinomas using commercially available D2R antibodies. Our findings align with current evidence indicating that lack of D2R expression, previously indicated by decreased mRNA levels, is common in DA-resistant prolactinomas and provide a basis for discontinuation of DA therapy to avoid potential harm to these patients. Full article

Background/Objectives: The management of pituitary adenomas involves balancing treatment efficacy with the risk of long-term morbidity, particularly treatment-induced hypopituitarism. While risk factors are qualitatively recognized, quantitative, individualized risk prediction tools for clinical practice are lacking. This study aims to evaluate and characterize the clinical features, hormonal profiles, and treatment outcomes of pituitary adenomas, and to develop and validate a pragmatic clinical prediction model for new-onset hypopituitarism. Methods: We conducted a retrospective cohort study of 215 patients diagnosed with pituitary adenomas, selected from 647 sellar lesions screened at a tertiary referral center between January 2010 and December 2020. Primary outcomes included adenoma size control, hormonal remission in functioning adenomas, and the development of new-onset hypopituitarism. A multivariable logistic regression model was developed to identify independent predictors of new-onset hypopituitarism, and its performance was assessed for discrimination and calibration. Results: The cohort consisted of 107 prolactinomas (49.8%), 77 non-functioning adenomas (35.8%), 18 GH-secreting (8.4%), and 8 ACTH-secreting (3.7%) adenomas, with a mean age of 43.2 ± 14.1 years and a female predominance (59.1%). At a median follow-up of 4.8 years, overall adenoma control was 92.1%. Radiotherapy achieved 100% adenoma control but was associated with the highest incidence of new hypopituitarism at 5 years (34.3%), significantly greater than medical therapy (5.6%, p < 0.001) and surgery (13.0%, p < 0.01). The final risk prediction model, incorporating treatment modality, baseline hypopituitarism, macroadenoma, age >50 years, and cavernous sinus invasion, demonstrated good discrimination (C-statistic = 0.82; 95% CI: 0.76–0.88) and excellent calibration (Hosmer–Lemeshow p = 0.42). Conclusions: Treatment modalities for pituitary adenomas have distinct risk–benefit profiles. Our validated, points-based risk model provides a transparent and clinically applicable tool to quantify an individual patient’s risk of developing hypopituitarism. This model can be integrated into clinical practice to facilitate shared decision-making and guide personalized surveillance strategies. Full article

The study aimed to analyze hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p expression in the serum of patients with invasive non-functioning pituitary adenomas (NFPAs) and prolactinomas, as candidates for non-invasive biomarkers. The study included 62 patients with NFPAs and 18 with macroprolactinoma who qualified for transsphenoidal surgical resection. MicroRNAs were isolated from serum samples. The expression levels of hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p were determined using TaqMan MicroRNA assays. The statistical analyses were performed with MedCalc. The total concentration of microRNA was significantly lower in NFPAs than in the CG (p = 0.0419). ROC curve analysis showed that the cutoff point of miRNA lower than 10.73 predicted the PA (sensitivity = 70.0%; specificity = 57.7%; AUC = 0.629; p = 0.052). No correlation between selected miRNAs and tumor type was found: hsa-miR-143-3p (p = 0.4610), hsa-miR-16-5p (p = 0.8767), and hsa-miR-423-5p (p = 0.1459). miRNA expression also did not correlate with invasiveness (cavernous or sphenoid sinus invasion, optic chiasm compression). Although the total expression of microRNA was significantly lower in NFPAs, hsa-miR-16-5p, hsa-miR-143-3p, and hsa-miR-423-5p are not useful as non-invasive biomarkers in patients with invasive non-functioning pituitary adenomas and prolactinomas. Full article

Issues: The clinical and paraclinical characteristics of prolactinomas differ mainly according to sex and tumor size. Drug treatment with dopamine agonists (ADs) has a crucial role in the management of prolactinomas. The use of surgery also has its indications. Purpose of the work: We aimed to establish the therapeutic strategy and the follow-up profiles of prolactinoma while analyzing the predictive factors of remission; we also looked for correlations between the size of the prolactinoma and the various clinical and paraclinical parameters. Materials and methods: This was a retrospective, descriptive, and analytical study of 77 cases of prolactinomas collected and monitored at the endocrinology and diabetology department of the Hedi Chaker CHU in Sfax between 2000 and 2017. Our patients were divided into three groups according to the size of their prolactinomas. Statistical correlations were sought between tumor size and clinical and biological parameters. Results: The mean age of our patients was 38.3 ± 14.2 years. The sample comprised 51 women (66.2%) and 26 men (33.7%). Anterior pituitary syndrome was observed in 75.3% of cases. The number of antehypophyseal deficits was significantly correlated with tumor size. Comparing the three groups, we noted that age, discovery circumstances, metabolic parameters, hypopituitarism, and pituitary extensions on imaging were significantly different. Therapeutically, our results showed that the favorable evolution of prolactinomas was correlated with tumor size and the duration of treatment. Conclusions: Tumor size appears to be a cornerstone in hormonal and radiological interpretation on the one hand and in the therapeutic decision on the other. Full article

Double pituitary neuroendocrine tumors (double PitNETs) are two distinct tumors in the same gland and are infrequent in clinical practice. In typical double PitNETs, an MRI detects two separate tumors that are diagnosed by pathology; they could also appear as a single tumor, and pathology would then identify the two independent tumors. A literature review was conducted, and 142 cases were analyzed to determine the characteristics of double PitNETs. Of these cases, acromegaly (45.5%) was the most common clinical feature, followed by Cushing’s disease (35.1%) and prolactinoma (17.9%), indicating that double PitNETs are usually noticed by hormonal excess symptoms due to at least one functional tumor. The pathological analysis of 284 tumors showed that somatotroph (28.9%) and corticotroph (26.8%) tumors were predominant, with a recent increase in the proportion of gonadotroph tumors. Regarding transcription factors, 51.1% were of GH-PRL-TSH PIT1-lineage, 26.1% ACTH TPIT-lineage, and 17.9% LH-FSH SF1-lineage. The radiological analysis of 82 cases revealed that double tumors (45.1%) and single tumors (47.6%) were comparable, suggesting that double PitNETs are often detected as a single tumor, and attention should be paid to hidden micro-tumors during surgery. Double PitNETs are complicated by a wide variety of clinical, radiological, and pathological findings, but diagnostic and therapeutic approaches are advancing. Full article

For several decades, dopamine agonist therapy has been the mainstay of treatment for prolactinomas, with surgery generally considered a second line for cases failing medical therapy due to intolerance or resistance. There is increasing recognition of the burden of long-term DA therapy; many patients experience debilitating side effects, and emerging evidence demonstrates that the prevalence of impulse control disorders has been vastly underreported. Long-term DA therapy is associated with significant costs to patients and healthcare systems, which is projected to exceed that of surgery in many circumstances. Recent advancements in surgical approaches, including endoscopic transsphenoidal surgery, have led to improved surgical outcomes (82–100% remission rates; serious complication rates < 2%), prompting a reappraisal of the role of surgery for prolactinoma. Favourable surgical outcomes have been observed in both remission and complication rates for microprolactinomas and well-circumscribed macroprolactinomas, leading to consideration of surgery as an earlier, or first-line, option in the treatment paradigm. Potential advantages of surgical management should be weighed against institutional case volume and expertise, the risk of perioperative complications, and the need for adjuvant medical therapy post-operatively. Ultimately, patients and care-providers should engage in shared decision-making following informed discussion about the risks and benefits of both medical and surgical approaches. Full article

Prolactinomas are commonly treated with dopamine receptor agonists (DAs), such as bromocriptine (BRC) and cabergoline (CAB). However, 10–30% of patients exhibit resistance to DA therapies. DA resistance is largely associated with reduced dopamine D2 receptor (DRD2) expression, potentially regulated by epigenetic modifications, though the underlying mechanisms are still unclear. Clinical samples were assessed for p300 expression. MMQ and AtT-20 cells were engineered to overexpress either wild-type p300 or a histone acetyltransferase (HAT) domain-mutant form of p300. Mechanistic studies included cell proliferation assays, flow cytometry, immunohistochemistry, immunofluorescence, co-immunoprecipitation, chromatin immunoprecipitation followed by quantitative PCR, reverse transcription quantitative PCR, and Western blotting. Additionally, an in vivo nude mouse xenograft model was used to confirm the in vitro findings. DAs downregulated p300 through the cAMP-PKA-CREB pathway. Activation of the HAT domain of p300 increased H3K18/27 acetylation, promoted DRD2 transcription, and worked synergistically with DA to exert anti-tumor effects both in vitro and in vivo. Tanshinone IIA (Tan IIA) upregulated p300 and DRD2, enhancing the therapeutic efficacy of BRC. These findings highlight the role of p300 in regulating DRD2 transcription in DA-resistant prolactinomas. Combining Tan IIA with BRC may offer a promising strategy to overcome DA resistance. Full article

Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical–pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n = 13) or metastatic (n = 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities. Full article

Background and Objectives: Prolactinomas are the most common pituitary adenomas, comprising 30–50% of such tumors. These adenomas cause hyperprolactinemia, leading to decreased fertility, reduced energy and libido, and galactorrhea. Diagnosing and treating prolactinomas in adolescents present unique challenges, as symptoms may be confused with age-related developmental variations. This case report explores the outcomes of early surgical intervention in an adolescent with a prolactinoma. Materials and Methods: A 14-year-old female presented delayed menarche and absent pubertal development. Initial evaluation revealed hyperprolactinemia (228.37 ng/mL) with normal estradiol levels. Initial management through observation was adopted, but persistent amenorrhea and severe headaches prompted further investigation. Magnetic resonance imaging revealed a cystic pituitary mass with apoplexy. Due to concerns regarding delayed puberty and the need for rapid normalization of prolactin levels, the patient underwent transsphenoidal surgery. Results: After operation, prolactin levels normalized, menarche occurred within three months, and secondary sexual characteristics developed within eight months. Pathology confirmed a pituitary adenoma with a high Ki-67 index (15%). Conclusions: Early surgical intervention for prolactinomas in adolescents can achieve successful biochemical remission and resolution of endocrine symptoms. Adolescents, particularly those with a high Ki-67 index and potential resistance to dopamine agonists, may benefit from prompt surgical management, resulting in improved clinical outcomes and complete tumor resection. Full article

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing’s Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as “acromegalic cardiomyopathy”. Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders. Full article

Antipsychotic medications are essential for managing severe mental illnesses like schizophrenia, which impacts about 1% of the global population. Despite efficacy, in some cases, they can induce hyperprolactinemia, affecting roughly half of the patients. The prevalence of this condition varies with the specific medication used. Although prolactinomas are rare among schizophrenia patients, treating them with dopamine agonists poses conflicts with antipsychotic medication, necessitating careful monitoring and adjustments. The aim of this study was to explore the presence of brain tumors, prolactinomas, and other structural brain changes in schizophrenia patients treated with second-generation antipsychotics using cerebral computed tomography (CT) scans. We conducted a cross-sectional study involving 152 hospitalized patients diagnosed between 1 January 2020 and 31 March 2024. Evaluations included cerebral CT scans, prolactin level assessments, and the monitoring of side effects. Patients, with an average age of 42.79 years and an illness duration of 17.89 years, predominantly received olanzapine (46.05%) and risperidone (36.84%). Side effects, reported by 61.78% of patients, included tremors, dizziness, and weight gain. Abnormal prolactin levels were observed in 53.95% of patients, more prevalent in females on risperidone and in both genders on olanzapine. No prolactinomas were detected on CT scans. Managing hyperprolactinemia in schizophrenia patients undergoing antipsychotic therapy is essential to prevent long-term complications and to ensure treatment compliance. Full article

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the “hook effect”), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL. Full article

This research investigates the utility of Chat Generative Pre-trained Transformer (ChatGPT) in addressing patient inquiries related to hyperprolactinemia and prolactinoma. A set of 46 commonly asked questions from patients with prolactinoma were presented to ChatGPT and responses were evaluated for accuracy with a 6-point Likert scale (1: completely inaccurate to 6: completely accurate) and adequacy with a 5-point Likert scale (1: completely inadequate to 5: completely adequate). Two independent endocrinologists assessed the responses, based on international guidelines. Questions were categorized into groups including general information, diagnostic process, treatment process, follow-up, and pregnancy period. The median accuracy score was 6.0 (IQR, 5.4–6.0), and the adequacy score was 4.5 (IQR, 3.5–5.0). The lowest accuracy and adequacy score assigned by both evaluators was two. Significant agreement was observed between the evaluators, demonstrated by a weighted κ of 0.68 (p = 0.08) for accuracy and a κ of 0.66 (p = 0.04) for adequacy. The Kruskal–Wallis tests revealed statistically significant differences among the groups for accuracy (p = 0.005) and adequacy (p = 0.023). The pregnancy period group had the lowest accuracy score and both pregnancy period and follow-up groups had the lowest adequacy score. In conclusion, ChatGPT demonstrated commendable responses in addressing prolactinoma queries; however, certain limitations were observed, particularly in providing accurate information related to the pregnancy period, emphasizing the need for refining its capabilities in medical contexts. Full article

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing’s disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients’ medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential. Full article