Somatic Activating ESR1 Mutation in an Aggressive Prolactinoma.

CONTEXT AND OBJECTIVE: The genetic profile of prolactinomas remains poorly understood. Our objective is to identify somatic genetic alterations associated with prolactinomas and to report the identification of an activating ESR1 mutation (ESR1Y537S) in an aggressive prolactinoma. SETTING: Brigham and Women's Hospital. DESIGN: Massively parallel-sequencing panel (OncoPanel) was performed in a cohort of patients with prolactinomas to identify mutations and copy number variation (CNV). RESULTS: Twenty subjects (mean age 38.6 years; 12 women and 8 men) were included in this study. A somatic ESR1Y537S mutation was identified in an aggressive prolactinoma in a post-menopausal woman. No SF3B1 or other somatic mutations were identified. The median number of CNV events identified in our samples was 46; the prolactinoma with ESR1Y537S had the highest number with 233 events. In breast cancer, ESR1Y537S has been shown to activate estrogen receptor alpha independent of ligand binding. In patients with resistant breast cancer and ESR1Y537S, elacestrant, a second-line ER degrader, improves progression-free survival. Therefore, given the lack of response to multimodality therapies, elacestrant was initiated in this patient after the third cycle of radiotherapy. Elacestrant, along with radiotherapy, controlled tumor growth and significantly reduced prolactin levels. CONCLUSION: Molecular profiling allowed the identification of ESR1Y537S, in an aggressive prolactinoma. ESR1Y537S was not detected early in the course of the disease and is likely conferring tumor aggressiveness. This finding emphasizes the significance of estrogen receptor signaling in prolactinomas. It also allowed the use of targeted therapy with successful control of disease progression.

Prolactinoma: Navigating the Dual Challenge of Side Effects and Treatment Strategies - A Comprehensive Review.

This narrative review provides a succinct exploration of prolactinoma, the most common pituitary adenoma, focusing on its epidemiology, clinical manifestations, and therapeutic interventions. Beginning with an overview of its prevalence and aetiology, the review delves into the gender distribution and familial associations of prolactinoma. Clinical presentations, including endocrine disruptions, reproductive health issues, and metabolic disturbances, are examined, emphasizing their impact on hormonal regulation and cardiovascular health. The narrative then navigates through pharmacological treatments, surgical interventions, and radiation therapy, highlighting their efficacy, side effects, and long-term management challenges. Strategies to mitigate side effects and optimize treatment outcomes are discussed, emphasizing the importance of multidisciplinary collaboration in prolactinoma management. This review is a concise yet comprehensive resource for healthcare professionals and researchers, providing insights into prolactinoma's clinical complexities and therapeutic nuances to guide optimal patient care strategies.

Visual morbidity in macroprolactinoma: A retrospective cohort study.

OBJECTIVE: The management of visual field damage in patients with macroprolactinomas is a major therapeutic challenge. We aimed to study the visual morbidity associated with macroprolactinoma and its outcomes following medical and surgical treatment. We aimed to identify predictors of visual recovery. METHODS: We retrospectively reviewed patient's data including clinical presentation, serial pituitary magnetic resonance imaging, laboratory tests, visual symptoms and neuro-ophthalmologic examination, visual field tests and optical coherence tomography tests. The main outcome was complete visual field recovery. Descriptive analyses were conducted. Predictors of visual recovery were investigated. PATIENTS: The study cohort included 150 patients with macroprolactinoma [median follow-up, 6.0 years (interquartile range (IQR) 2.9-10.6)]. RESULTS: At diagnosis, visual field defects were evident in 40 patients (26.7%). At the end of follow-up, 24 out of 39 available visual field tests (61.5%) exhibited complete recovery. Patients that achieved complete visual recovery had smaller macroadenomas at diagnosis [30.5 mm (15.0-80.0) vs. 42.0 mm (30.0-85.0), p < .01], lower baseline serum prolactin levels [1414 mcg/L (489-3586) vs. 4119 mcg/L (2715-6315), p < .01], lower rates of central hypogonadism (78.3% vs. 93.3%, p = .05) and central hypothyroidism (20.8% vs. 53.3%, p = .04), lower rates of compressive optic neuropathy (35.3% vs. 87.5%, p = .02) and a better visual acuity (better than 6/8 in both eyes, 93.7% vs. 28.6%, p < .01). CONCLUSIONS: In our cohort of 150 patients with macroprolactinoma, 40 patients (26.7%) presented with visual field defects, of which 61.5% achieved complete visual recovery with treatment. Patients that achieved complete visual recovery presented with smaller macroadenomas, lower serum prolactin levels, lower rates of central hypogonadism and central hypothyroidism, lower rates of compressive optic neuropathy and better visual acuity.

Recovery from hypogonadism in men with prolactinoma treated with dopamine agonists.

PURPOSE: In men with prolactinoma treated with dopamine agonists (DA), the extent, timeline, and predictive factors of gonadotropic axis recovery are still unclear. METHODS: We analyzed data of 97 men with a prolactinoma treated with DA (77/97 macroprolactinomas). We excluded patients with primary hypogonadism, surgery < 12 months after DA initiation, and patients with tumors < 5 mm or prolactin < 45 µg/l at diagnosis. RESULTS: Among the 97 patients, 12 had normal total testosterone (NT group) and 85 had low testosterone at diagnosis (LT group). In the NT group, testosterone rose from a mean of 13.5 nmol/l to 17.1nmol/l at 6 months (n = 11; p < 0.05) then remained stable at 12 months (n = 8). In the LT group, testosterone rose from a mean of 5.2 nmol/l to 9.6 nmol/l at 6 months (n = 66; p < 0.001) and further to 13.1nmol/l at 12 months (n = 40; p < 0.001) then remained stable. Recovery from hypogonadism occurred in 43%, 50%, and 54% of patients at 6, 12 and 24 months, respectively (61%, 69 and 69% if prolactin was normal). Factors independently associated with persistent hypogonadism at 12 months were at baseline the presence of visual field deficit and lower testosterone levels, while the most significant independent predictor of persistent hypogonadism at one year was a testosterone level < 7.4 nmol/l at 6 months, with 91% sensitivity and 94% specificity. CONCLUSION: Testosterone levels recover in a small majority of men with prolactinoma mostly during the first year of DA treatment. However, testosterone replacement could be considered earlier in patients with large and compressive tumors, and in whom testosterone remains below 7.4 nmol/l after 6 months of DA treatment.

An Overview of Cardiovascular Risk in Pituitary Disorders.

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.

Feasibility of Early Surgical Treatment for Adolescent Patients with Prolactinoma: A Case Report and Literature Review.

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.

Granulomatous Mastitis: An Initial Presentation of Undiagnosed Prolactinoma.

Granulomatous lobular mastitis (GLM) is a rare, benign inflammatory disease of the breast that shares some physical diagnostic features with breast cancer. GLM has been rarely reported to be associated with prolactinoma. In this report, we present a case of undiagnosed prolactinoma in a 37-year-old woman with its initial presentation as GLM. We discuss the underlying pathophysiologic mechanisms for the development of GLM and the potential immunomodulatory role of prolactin in the development of GLM. We also highlight the need to assess for possible prolactinoma in GLM, which might go undiagnosed as in the case of our patient who did not seek medical attention for her amenorrhea, which is likely due to hyperprolactinemia that might also have other clinical implications on cardiovascular and bone health due to consequent estrogen deficiency.

Characteristics and outcomes of men with erectile dysfunction as the presenting symptom due to a lactotroph adenoma.

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.

Preoperative treatment with dopamine agonist therapy influences surgical outcome in prolactinoma: a retrospective single-center on 159 patients.

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.

Clinical use of [18F]fluoro-ethyl-L-tyrosine PET co-registered with MRI for localizing prolactinoma remnants.

PURPOSE: To assess the utility of [18F]fluoroethyl-L-tyrosine PET co-registered with magnetic resonance imaging ([18F]FET-PET/MRICR) in patients with difficult-to-localize prolactinoma to inform clinical decision-making and (surgical) treatment planning. METHODS: Retrospective cohort study of 17 consecutive patients with prolactinoma undergoing [18F]FET-PET/MRICR between October 2020 and September 2022 for either (1) additional information in case of difficult-to-visualize remnants after prior transsphenoidal surgery (TSS), or pharmacological treatment, or (2) radiological diagnosis in absence of a (clear) adenoma on diagnostic/post-treatment conventional MRI. RESULTS: [18F]FET-PET/MRICR identified a lesion in 14/17 patients, yet failed to identify active lesions in 2 patients with negative conventional MRI despite prolactin > 7.5 times upper limit of normal. [18F]FET-PET/MRICR results were inconclusive in 1 patient due to diffuse tracer uptake 10 weeks post-surgery. [18F]FET-PET/MRICR was completely concordant with a suspected lesion on conventional MRI in 10/17 patients, and partially concordant in 3/17 patients. New foci were identified in 4/17 patients. The [18F]FET-PET/MRICR conclusions influenced clinical shared decision-making in 15/17 patients, of whom 7 patients underwent TSS and 8 refrained from TSS. One patient underwent TSS despite negative [18F]FET-PET/MRICR, and one patient underwent additional imaging. Intraoperative findings corresponded with [18F]FET-PET/MRICR in 5/8 patients, and immunohistochemistry was positive in 5/8 patients. The treatment goal was achieved in 7/8 patients, and remission was achieved in 5/7 patients in whom total resection was considered feasible. CONCLUSION: [18F]FET-PET/MRICR can be of added value in the preoperative decision-making process for selected patients with difficult-to-localize prolactinoma (remnants), or patients lacking a substrate on conventional MRI.

Network pharmacology analysis and molecular mechanism of paeoniflorin and its metabolite in prolactinoma cells.

Prolactinoma was the most common functional pituitary neuroendocrine tumor tissue type, which was caused by excessive proliferation of pituitary prolactin (PRL) cells. Drug therapy of dopamine receptor agonists was generally considered as the prior treatment for prolactinoma patients. However, there were still prolactinoma patients who were resistant to dopamine agonists. Studies have been reported that paeoniflorin can inhibit the secretion of PRL in prolactinoma cells lacking dopamine D2 receptor (D2R) expression, and paeoniflorin can be metabolized into albiflorin by intestinal flora in rats. The effect of albiflorin on prolactinoma has not been reported yet. In this study, network pharmacology was used to analyze the mechanism of paeoniflorin and its metabolite albiflorin as multi-target therapy for prolactinoma, and the experimental verification was carried out. In order to clarify the complex relationship among paeoniflorin, albiflorin and prolactinoma, we constructed a component-target-disease network, and further constructed interaction network, MMP9, EGFR, FGF2, FGFR1 and LGALS3 were screened as the core targets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that paeoniflorin and albiflorin may be involved in various pathways in the treatment of prolactinoma, included relaxin signaling pathway and PI3K-Akt signaling pathway. Molecular docking analysis showed that paeoniflorin and albiflorin had good binding activity with MMP9. Western blotting results showed that paeoniflorin and albiflorin could significantly reduce the expression of MMP9, and ELISA results showed that paeoniflorin and albiflorin could significantly reduce the concentration of PRL in GH3 cells, and the reduce degree of albiflorin was stronger than paeoniflorin at 50 µM, which indicated that albiflorin might be a potential drug to treat prolactinoma, which can regulate prolactinoma through MMP9 and reduce the concentration of PRL. Our study provided a new therapeutic strategy for prolactinoma.

Impulse Control Disorders in Southern Iraqi Patients Medicated With Cabergoline for Prolactinoma.

BACKGROUND: Among the patient population in Basrah, Iraq, prolactinoma is the most commonly found pituitary tumor. Impulse control disorders (ICDs) were reportedly associated with these patients being treated with cabergoline. This study aimed to assess the prevalence of ICDs in cabergoline-treated prolactinoma patients versus healthy, matched controls. METHODS: This cross-sectional case-control study was conducted at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah, southern Iraq, from January 2023 to May 2023. It included 30 cabergoline-treated prolactinoma patients and 30 healthy, matched controls. The questionnaire for ICDs in Parkinson's disease was used as a screening tool. Following this, positively screened patients were evaluated using validated criteria accordingly to diagnose impulse control disorders. RESULTS: The ICDs were diagnosed in nine (30%) cabergoline-treated prolactinoma patients versus two (6.7%) in control (p = 0.02). The most frequent ICD types were hypersexuality and binge eating, while no patient reported pathological gambling. Three patients reported multiple types of ICDs. The patients' sociodemographic characteristics, prolactinoma duration and size, and cabergoline dose did not correlate significantly with ICD diagnosis. CONCLUSIONS: Treatment with cabergoline is associated with the development of ICDs. Therefore, clinicians should be aware of this disabling side effect to ensure its early detection and treatment.

Ectopic Sphenoid Sinus Prolactinoma Associated With Empty Sella and Recurrent Meningitis Treated Successfully With Cabergoline.

Ectopic pituitary adenomas (EPA) are tumors that reside outside the sella turcica and are not connected to the pituitary gland. We present a case of a 62-year-old female who was hospitalized for recurrent meningitis. Workup, including magnetic resonance imaging (MRI) of the brain, computed tomography (CT) of the sinuses, and follow-up MRI of the sella turcica, revealed an 8 millimeter (mm) mass in the right posterior sphenoid sinus with an empty sella turcica and no evidence of a sellar mass. The mass was biopsied, with pathology results showing findings of a pituitary adenoma staining positive for prolactinoma. Subsequent hormonal workup revealed an elevated prolactin level of 128.4 nanograms per milliliter (ng/mL) without evidence of additional hormonal co-secretion or hypopituitarism. The patient was started on cabergoline with eventual normalization of the prolactin level and regression of the adenoma on follow-up imaging. EPAs are rare and thus treatment guidelines have not been established. Our case report not only highlights a case of successful treatment of ectopic prolactinoma with dopamine agonist therapy but also calls attention to the uncommon co-existence of EPAs and empty sella turcica and meningitis as an extremely uncommon presentation of EPAs.

Prolactinomas: Preconception and During Pregnancy.

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.

Bromocriptine sensitivity in bromocriptine-induced drug-resistant prolactinomas is restored by inhibiting FGF19/FGFR4/PRL.

PURPOSE: At present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment. METHODS: In our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice. RESULTS: Consistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels. CONCLUSION: Overall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas.

Paradoxical effect of dopamine-agonists on IGF-1 in patients with prolactinoma: the role of weight.

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.

Apoplexy of a giant clival ectopic prolactinoma: A very rare case report.

INTRODUCTION AND IMPORTANCE: Ectopic pituitary neuroendocrine tumor (EPNET) is a very rare entity, seldom with apoplexy evolution. Only three cases of intracranial ectropic pituitary neuroendocrine tumor apoplexy were reported in the literature. CASE PRESENTATION: We report the case of a 45-year-old woman with a history of amenorrhea, and headaches. Neuroimaging showed a very aggressive giant mass within the clivus with the invasion of the sphenoidal sinus and encasement of internal carotid arteries with an empty sella. Endocrinology work-up revealed an exceedingly high level of prolactin surprisingly without galactorrhea. Immunohistochemical analysis after an endonasal biopsy confirmed the diagnosis of prolactinoma. One month after Cabergoline initiation, an apoplexy of the ectopic pituitary neuroendocrine tumor occurred. Conservational management with a decrease in cabergoline dose was performed. DISCUSSION: This article highlights data from various cases reported in the literature in addition to our case to confirm the extreme rarity of apoplexy as a complication of EPNET. CONCLUSION: Pituitary apoplexy in ectopic pituitary neuroendocrine tumor is extremely rare. Therefore, in case of unusual localization of pituitary neuroendocrine tumor, a thorough follow-up is necessary to detect complications and ensure early management.

The research trend of hyperprolactinemia from 2011 to 2023 was analyzed by bibliometrics.

The objective of this study is to conduct a bibliometric analysis of research trends in hyperprolactinemia from 2011 to 2023. This analysis aims to provide researchers with insights into the current hotspots and frontiers related to hyperprolactinemia. It is worth noting that there are currently no existing reports on bibliometric analyses of hyperprolactinemia. The Social Science Citation Index (SSCI) and Science Citation Index Expanded (SCIE) databases of the Web of Science Core Collection were systematically searched for "articles" and "review articles" related to the topic of hyperprolactinemia from 2011 to 2023. VOSviewer was employed to conduct bibliometric analysis, aiming to analyze the research trends in hyperprolactinemia over the past 13 years. A total of 1865 eligible articles were retrieved, with contributions from 9544 scholars representing 83 countries in the field of research. The United States had the highest number of publications, followed by China. The keywords were categorized into six clusters: (1) etiology of hyperprolactinemia and other related endocrine and metabolic diseases. (2) Hyperprolactinemia and mental illness. (3) Diagnosis and management of hyperprolactinemia. (4) Treatment of hyperprolactinemia and prolactinoma. (5) Detection of macroprolactin and macroprolactinemia. (6) Symptoms of male hyperprolactinemia. Over the past 13 years, there has been a consistent and slightly increasing trend in the number of research papers focusing on hyperprolactinemia. The primary areas of research focus are centered around the diagnosis and treatment of hyperprolactinemia caused by antipsychotic drugs or prolactinoma.

[Clinically active pituitary tumors]. / Klinisch aktive Hypophysentumoren.

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.

Muscle function, exercise capacity, physical activity level and cardiovascular disease risk factor knowledge in patients with prolactinoma.

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).