Dopamine Agonists Research Articles

Modern approach to bone comorbidity in prolactinoma.

Prolactinomas account for more than half of pituitary adenomas, and besides their clinical impact on fertility and gonadal function, they lead to detrimental effects on bone. Patients with prolactinoma are prone to deterioration of bone structure caused not only by prolactin (PRL) induced hypogonadism but also by its direct actions on bone cells and calcium metabolism. However, clinical studies have shown inconsistent evidence regarding whether PRL could have a deleterious effect independently from gonadal insufficiency on skeletal integrity. Seminal studies from our group reported an increased prevalence of vertebral fractures (VFs) in both female and male patients with prolactinoma. Treatment of prolactinoma with dopamine agonists can restore gonadal function and improve bone mineral density. Since the presence of VFs may be related to more aggressive disease, bone comorbidities in prolactinoma should be managed by a multidisciplinary team in line with the recent concept of 'pituitary tumors centers of excellence'. The review aims to evaluate the mechanism of PRL actions on bone, as well as to provide practical indications for a modern approach to the management of skeletal complications of patients with prolactin-secreting adenoma considering different clinical characteristics and outcomes.

Efficacy and safety of safinamide in Parkinson's disease patients with motor fluctuations without levodopa dosage escalation over 18 weeks: KEEP study.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with≥1.5 h of "off" time daily, who took levodopa≥3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily "off" time (-1.3±2.4 h, p<0.001) and quality of life (QoL) based on PDQ-39 summary index (-2.7±10.3, p<0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily "on" time without dyskinesia (all p<0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022.

The Present Difficulties and Potential Benefits of Dopaminergic Agents in Parkinson's Disease Treatment

Parkinson's disease (PD) is a progressive neurological condition characterized by bradykinesia, rigidity, tremors, and impaired balance, among other motor impairments. The issue arises from dopaminergic neurons located in the spinal column of the brain. This research report examines the therapeutic potential of dopaminergic medications in the management of Parkinson's disease. The central concept of Parkinson's disease (PD) revolves around the notion that dopaminergic pathways exert significant influence over the regulation of movement. The book examines various dopaminergic medications, elucidating their mechanisms of action and the impact they exert on dopamine signaling. Examples of these medications include levodopa, dopamine agonists, and monoamine oxidase-B (MAO-B) inhibitors. Although dopaminergic medicines initially aid in the treatment of Parkinson's disease (PD), prolonged usage of these medications gives rise to several complications. Experiencing dyskinesias and motor fluctuations, characterized by episodes of involuntary movements and behaviors that are undesired, is a significant challenge. This study investigates the underlying causes of these difficulties and explores potential treatment options, including the use of controlled-release formulations and further therapy. The book discusses the non-motor symptoms of Parkinson's disease (PD), as well as the use of dopaminergic medications to treat mood disorders, autonomic dysfunction, and cognitive loss. Dopaminergic medications remain crucial in reducing motor symptoms and enhancing the quality of life for those with Parkinson's disease. Parkinson's disease (PD) is a complex condition with multiple distinct variations. In order to address its existing challenges and explore its potential implications for future Parkinson's disease medications, a comprehensive and effectively coordinated strategy is required.

EHospitals and Parkinson’s disease care: audit insights from an EPIC-integrated Hospital

Abstract Introduction Parkinson’s disease (PD) is a neurodegenerative condition that affects approximately 145,000 individuals in the UK. PD symptoms are managed primarily through medications such as levodopa and dopamine agonists. Delays or omissions in administering these medications is the primary reason for increased length of stay in up to 73% of emergency admissions.1 This audit investigated the management of PD medications at Cambridge University Hospitals to identify areas for improvement in clinical practice. Aim This audit aimed to evaluate the pharmacological management of PD patients admitted to Cambridge University Hospitals NHS Trust. Specifically, it sought to assess the accuracy of drug histories, the quality of medication administration, and adherence to standards set by Parkinson’s UK ‘Get it on Time’ campaign and NICE.2,3 Methods A cross-sectional audit was conducted, reviewing the records of PD patients admitted over a three-month period. The sample included patients with a confirmed diagnosis of idiopathic PD who were prescribed at least one PD medication. Data were collected retrospectively from the electronic patient records, focusing on ten performance standards. Ethical approval was not required as the study involved a retrospective review of existing clinical records. Results The audit included 63 admissions, predominantly male (65%) with a mean age of 78.5 years. A significant portion of patients (81%) had their drug histories completed by a doctor after clerking, and 90% had orders for their regular treatment generated immediately post-clerking. Pharmacy staff completed drug histories within 24 hours for 81% of patients, though discrepancies between medical and pharmacy histories were noted in 70% of cases. Medication reconciliation within 24 hours was achieved for 83% of patients, yet only 29% received their PD medications on time for every dose. Additionally, 76% did not miss a dose or had a valid reason recorded for missed doses. 83% had PD listed in their electronic problem list after clerking. Alarmingly, just 5% were assessed for Self-Administration of Medicines (SAM), and 76% were assessed by a PD specialist during their stay. Discussion and conclusion The audit revealed substantial gaps in PD medication management, particularly regarding discrepancies between medical and pharmacy drug histories and delays in medication administration. The low rate of SAM assessments and inconsistent PD specialist consultations were also significant concerns. These findings highlight the need for improved documentation practices, such as standardized templates within the EPIC system, and increased pharmacy involvement during early stages of admission. Appropriate staffing levels and better interdisciplinary coordination are essential. The audit identified critical areas for improvement, emphasizing the need for better documentation, timely administration, and enhanced interdisciplinary coordination. Future audits should aim to randomize patient selection over a longer period to minimize bias and provide a more comprehensive assessment of medication management practices. The audit was limited by its retrospective design and the specific three-month timeframe, which may not fully represent broader trends. The exclusion of admissions shorter than 24 hours and the focus on a single hospital trust also limit the generalizability of the findings. Future studies should consider a larger, more randomized sample to validate and expand upon these results.

Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular Reactive Oxygen Species in Prolactin-Secreting Pituitary Adenoma.

Aims: Dopamine agonists (DAs) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. Results: Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to bromocriptine (BRC) both in vitro and invivo. Mechanistically, we demonstrated that intracellular reactive oxygen species (ROS) function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NFE2-like bZIP transcription factor 2 (NRF2) expression, which regulates intracellular ROS levels, thereby enhancing cell viability and conferring DA resistance to pituitary adenoma (PA) cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. Conclusion and Innovation: We demonstrated that AR plays a crucial role in mediating DA resistance in PRL adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas. Antioxid. Redox Signal. 00, 000-000.

Cephalgic syndrome in patients with acromegaly

The aim of this review is to summarize the data available in the literature on the causes of headache in patients with acromegaly, as well as on the effect of various methods of acromegaly treatment on headache. Publications were searched in the PubMed database using the keywords «Headache in patients with acromegaly», «Headache in patients with pituitary adenomas», «Tension-type headache», «Migraine». Headache in patients with pituitary adenomas secreting somatotropic hormone (STH) is not uncommon: according to various authors, cephalgic syndrome occurs in 30-70% of patients with acromegaly and can worsen their quality of life, along with other factors, up to disability. By the nature of development, headache with acromegaly is classified into primary (migraine, tension headache, trigeminal autonomic cephalgia, for example, SUNCT syndrome and cluster headaches), and can also be caused by various causes directly related to the tumor. All this requires differential diagnosis. The factors causing headaches in somatotropinomas have not yet been well studied and require further research. These include the mass effect of the tumor, hormonal hypersecretion, pathology of the temporomandibular joint, sodium and fluid retention in the body, psychological factors, etc. The authors evaluated the effect on headache of various methods of acromegaly treatment: transnasal transsphenoidal adenomectomy, radiation therapy and drug therapy with somatostatin analogues, dopamine agonists and growth hormone receptor antagonist. However, even when normal levels of STH and insulin-like growth factor 1 (IGF-1) are reached, cephalgic syndrome may persist, therefore patients should be warned about this in advance and referred to a cephalgologist to select adequate headache therapy.

Evaluating efficacy and safety of Saffron add-on treatment in improvement of motor and depressive symptoms of patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial

AimEvidence has highlighted neuroprotective effects of saffron in animal models of Parkinson’s disease (PD). The present study investigated the efficacy and safety of add-on saffron on motor and depressive symptoms of patients with PD. MethodsThis study was an 8-week, randomized, double-blind, and parallel-group clinical trial. Known cases of PD with depression were randomized to receive either a routine treatment (levodopa or levodopa-equivalent dose of a dopamine agonist) plus saffron capsule (15 mg bid) or routine treatment plus placebo. All participants were assessed using the Hamilton Depression Rating Scale (HAMD), Geriatric Depression Scale-30 (GDS-30), item 3 of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 1, MDS-UPDRS part 3, and H and Y scale at baseline and at week 8. ResultsA total of 52 patients (25 in saffron and 27 in placebo groups) were included. Our results demonstrated that saffron could not improve motor symptoms of PD patients (F=0.53, df=1, p=0.424). However, repeated-measures analysis showed a significant effect of time × treatment (F=8.24, df=1, p=0.006) on HAMD scores, indicating a greater improvement of depressive symptoms in saffron compared to placebo groups. Our study showed nonsignificant findings regarding the secondary outcome measures (GDS-30, item 3 of MDS-UPDRS part 1, and H and Y scale). We showed that treatment with saffron is safe in PD. ConclusionWe substantiated that add-on treatment with saffron significantly improved depression, but not motor symptoms, in PD. Further trials with larger sample sizes and longer follow-ups are needed to confirm our findings.

Effects of puerarin on gait disturbance in a 6-hydroxydopamine mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by dopamine (DA) neuronal dysfunction. Although DA agonists and N-methyl-D-aspartate receptor (NMDAR) antagonists are used to treat PD, chronic use causes severe side effects. Puerarin (PUE) is a natural bioactive compound that affects the DA system; however, its effect on PD-associated motor functions is unknown. Therefore, we investigated whether PUE treatment in a 6-hydroxydopamine (6-OHDA) PD mouse model affects motor dysfunction. Adult male ICR mice received unilateral 6-OHDA microinfusion into the right medial forebrain bundle. After a 2-week recovery period, PUE (20 or 50mg/kg) or the vehicle (saline, VEH) was administered intraperitoneally once daily for 21 days. Motor dysfunction was assessed using the locomotion, gait cycle, and rotation tests. Local field potentials (LFPs) were measured in the substantia nigra compacta (SNc), striatum (STR), subthalamic nucleus (STN), and primary motor cortex. 6-OHDA-lesioned PD mice showed increased gait cycle disturbance and unidirectional rotation. PUE treatment ameliorated the gait cycle disturbance, but not unidirectional rotation of PD mice. These effects differed with DA agonist treatment (which improved PD symptoms) and NMDAR antagonist treatment (which aggravated PD symptoms). Moreover, locomotion was increased only in NMDAR antagonist treatment. PUE treatment induced no changes in the attenuated LFP of the beta wave in the STR and STN, and SNc-STN delta-wave coherence was shown in PD animals. This study suggests that PUE is a beneficial co-therapeutic agent for alleviating gait cycle disturbance in PD symptoms.

Prescription trends in Japanese advanced Parkinson's disease patients with non-motor symptoms: J-FIRST.

Non-motor symptoms (NMS) are important factors when selecting treatments for patients with advanced Parkinson's disease (PD). We sought to elucidate the prescribing practices for advanced PD patients with NMS in Japanese clinical practice. We examined the prescription rates and doses of anti-PD drugs, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) in post hoc analyses of a 52-week observational study of 996 PD patients with wearing-off on levodopa-containing therapy and ≥1 NMS. Dopamine agonists were the most frequently prescribed drugs combined with levodopa-containing drugs, followed by entacapone, zonisamide, istradefylline, selegiline, and amantadine. The daily dose of levodopa-containing drugs, rotigotine, entacapone, istradefylline, and droxidopa, and the levodopa-equivalent dose increased during the observation period. In a subgroup analysis of patients stratified by NMS status (improved/unchanged/deteriorated), the deteriorated group had higher prescription rates of entacapone and istradefylline, whereas the improved group had higher prescription rates of NSAIDs and zonisamide at Week 52. Prescriptions varied by geographical region for anti-PD drugs and by NMS status for NSAIDs. There were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region.

Risk factors and evolution of weight loss in Parkinson's disease: A 9-year population-based study

IntroductionWeight loss is considered a common complication of Parkinson's disease (PD), but there are few prospective longitudinal studies on weight loss in patients followed from time of PD diagnosis. We sought to determine the frequency, evolution and risk factors of weight loss in a representative incident PD cohort. MethodsIn this prospective population-based observational study, we followed 180 newly-diagnosed, initially drug-naïve PD patients and 161 controls with repetitive weight examinations over 9 years. We used Cox regression models with adjustment for potential confounders to identify independent risk factors of clinically significant (>10 %) weight loss. ResultsMean % weight change during follow-up was −3.9 (±11.2) in patients and −1.4 (±8.1) in controls (p = 0.016). Clinically significant weight loss was observed in 26.7 % of patients and 10.6 % of controls (RR 2.53; 95 % CI 1.52–4.21; p < 0.001). Age was the only independent baseline risk factor for weight loss (HR 1.06 per year; 95 % CI 1.03–1.10; p < 0.001). Additional time-dependent risk factors were presence of olfactory impairment (HR 2.42; 95 % CI 1.14–5.15; p = 0.021), presence of dyskinesias (HR 3.14; 95 % CI 1.58–6.23; p = 0.001), and cognitive impairment (HR per MMSE unit 0.90; 95 % CI 0.82–0.99; p = 0.036). Dopamine agonist use reduced the risk of weight loss during follow-up (HR 0.44; 95 % CI 0.24–0.82; p = 0.007). ConclusionThe risk of weight loss is more than doubled in the general PD population and associated with both disease-related features and drug-related complications. This suggests a multifactorial nature of weight loss in PD, which is important to consider in research and clinical practice.

Prevalence and features of headache in Parkinson's disease: the role of dopamine.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, but dopamine also plays a role in the pathophysiology of migraine. The aim of this study is to assess lifetime and previous year prevalence rates of headache in PD patients compared with controls. We enrolled 101 patients (57M and 44W) and 101 controls (62M and 39W), comparable for age and gender, who underwent a semi-structured questionnaire to assess the occurrence and the features of headache, and Beck Depression Inventory (BDI). We did not find any significant differences in the overall prevalence of lifetime and last 12-month headache between the two groups, as well as lifetime and last year tension-type headache (TTH) and migraine. Patients, especially those suffering from migraine and treated with dopamine agonists (DA), more frequently showed headache remission after the onset of motor symptoms compared to the age-related remission observed in controls(p = 0.001). Patients affected by headache were less frequently treated with DA in comparison with those without (p = 0.051). Depression of mood was more severe among PD patients with migraine than with TTH (p = 0.021). PD patients with headache exhibiting the akinetic-rigid subtype more frequently reported motor fluctuations than those presenting with tremor-dominant disease (p = 0.040). The prevalence of headache in PD follows that described in the general population, but dopaminergic pathway degeneration, loss of dopamine activation on the trigeminal-vascular system, and DA treatment might favor migraine improvement and remission in PD patients.

What do we know about abnormally low prolactin levels in polycystic ovary syndrome? A narrative review.

Hyper and hypoprolactinemia seem to be related to the occurrence of metabolic alterations in PCOS patients. In contrast, between significantly elevated and significantly low, prolactin levels seem to be protective against metabolic consequences. In the present review, we found 4 studies investigating hypoprolactinemia in patients with PCOS. We also identified 6 additional studies that reported low levels of PRL in PCOS patients. Although its prevalence is not considered high (13.2-13.9%), its contribution is certainly significant to the metabolic alterations observed in PCOS (insulin resistance, obesity, diabetes mellitus, and fatty liver disease). Dopamine inhibits the secretion of prolactin and GnRH. If dopamine levels are low or the dopamine receptor is less expressed or mutated, the levels of prolactin and GnRH increase, and consequently, LH also increases. On the other hand, hyperprolactinemia, in prolactinomas-typical levels, acting through kisspeptin inhibition causes GnRH suppression and hypogonadotropic hypogonadism. In situations of hypoprolactinemia due to excessive dopamine agonist treatment, dosage reduction is important to minimize the decrease in prolactin levels. Nevertheless, there is a lack of prospective studies confirming these hypotheses, as well as randomized clinical trials with appropriate drugs targeting both hyperprolactin and hypoprolactin in patients with PCOS.

Elucidating Clinical Queries for Tailored Therapy in Patients with Prolactinoma.

Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy-a patient-focused, multidisciplinary approach- we aim to improve the management of prolactinoma patients.

Efficacy of Aerobic and Stretching Exercises in Managing Willis-Ekbom Disease (Restless Leg Syndrome) Among Hemodialysis Patients.

Restless legsyndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs, particularly during rest. It significantly affects the quality of life of hemodialysis patients with high prevalence in this population. While pharmacological treatments, especially dopamine agonists (DAs), are commonly used, they often come with side effects and augmentation phenomena. This systematic review examines the effectiveness of exercise interventions in managing RLS among hemodialysis patients. Eight studies, including randomized controlled trials and quasi-experimental studies, were analyzed. The interventions primarily consisted of aerobic exercises (cycling) and stretching exercises, with durations ranging from eight weeks to six months. The primary outcome measure was RLS severity, assessed using validated scales such as the International Restless Legs Syndrome Study Group (IRLSSG) scale or the Restless Legs Syndrome Questionnaire (RLSQ). Secondary outcomes included sleep quality, depression, and physical performance. The results consistently demonstrated that both aerobic and stretching exercises significantly reduced RLS severity and improved related outcomes. The intradialytic nature of some interventions offered a practical approach to incorporating exercise into patient routines. While exercise showed comparable efficacy to DAsin reducing RLS symptoms and improving depression scores, only DAs significantly enhanced sleep quality in one comparative study. These findings suggest that exercise interventions may be a viable non-pharmacological approach to managing RLS in hemodialysis patients, potentially complementing or reducing reliance on pharmacological treatments.

The use of CRISPR-Cas9 technology for targeted gene therapy in Parkinson's disease focusing on LRRK2 and SNCA genes

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to the start of motor and non-motor symptoms. These include bradykinesia, resting tremor, rigidity, and postural instability, alongside cognitive impairments, mood disorders, and autonomic dysfunctions. The hallmark of PD is the accumulation of α-synuclein protein aggregates, forming Lewy bodies within the neurons. Given the numerous causes of Parkinson’s, involving genetic, epigenetic, and environmental factors, therapeutic treatments are hard to come by. Traditional pharmacological treatments, such as levodopa and dopamine agonists, primarily offer symptomatic relief and are associated with diminishing efficacy over time. Therefore, there is a need for new therapeutic approaches that target the disease at its roots. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, with the RNA-guided Cas9 endonuclease enables precise, targeted modifications at the genomic level. This technology offers potential for terminating the genetic factors causing parkinsons and aid in developing gene-based therapies. By attempting to regulate gene expression, CRISPR holds promise for addressing the fundamental causes of neurodegeneration in Parkinsons. One of the key genetic targets in PD is the leucine-rich repeat kinase 2 (LRRK2) gene, where specific gain-of- function mutations, such as G2019S, lead to hyperactivation of its kinase activity, contributing to neurotoxicity. CRISPR-Cas9 can be employed to introduce precise double-strand breaks at the mutation site, followed by homology-directed repair (HDR) to restore the wild-type sequence, thereby normalizing LRRK2 function and preventing neuronal death. Similarly, CRISPR technology can target the SNCA gene, which encodes α-synuclein. Pathogenic duplicates or triplicates of SNCA result in overproduction of α-synuclein and subsequent aggregation. Utilizing CRISPR to disrupt these extra copies can reduce α-synuclein levels, alleviating its toxic effects.CRISPR activation (CRISPRa) and interference (CRISPRi) systems enable fine-tuned upregulation or downregulation of gene expression, offering strategies to increase the expression of neuroprotective factors or suppress the expression of deleterious genes.

Long term outcomes of pituitary adenomas in Multiple Endocrine Neoplasia type 1: a nationwide study.

Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.

Acromegalia em felinos

Acromegaly in felines occurs mainly due to a pituitary adenoma of somatotropic cells, and presents slow and progressive evolution, responsible for increasing the production and secretion of growth hormones (GH). This condition is common in senile or adult male domestic cats, neutered and with short hair. The pathophysiology is due to the excessive release of GH in the adenohypophysis region, whose synthesis is regulated by growth hormone-releasing hormone (GHRH) and somatostatin, responsible for stimulating or inhibiting the secretory axis, respectively. The anabolic action of GH is responsible for increasing the secretion of IGF-1, which is mainly responsible for the clinical signs of acromegaly, such as body growth and organomegaly. The catabolic effect refers to insulin resistance. Clinical signs may be associated with secondary diabetes mellitus (DM), weight gain, exacerbated growth of various tissues and neurological signs as the tumor mass grows. The diagnosis of the disease can be performed through laboratory, imaging and endocrine tests such as the specific immunoassay for GH and/or insulin-like growth factor 1 (IGF-1). Treatment is based on controlling the DM that develops secondary to it, as well as on attempts to reduce or even inhibit the excess release of GH. Treatment can be performed with somatostatin analogues and dopamine agonists. The use of stereotactic radiotherapy can also be recommended, with favorable results for tumor reduction, as well as the surgical technique of transsphenoidal hypophysectomy, which presents better results than other techniques but is a complex surgical procedure. This project aims to inform veterinarians of this endocrine disease and its main currently recognized diagnoses and treatments, emphasizing the need to establish a differential diagnosis for difficult-to-control DM.

7220 Menopause Has a Beneficial Influence on the Evolution of Prolactinomas: a Study in 95 Patients

Abstract Disclosure: S. Constantinescu: None. C. Nava: None. F. Chasseloup: None. P. Chanson: Consulting Fee; Self; Eli Lilly &amp; Company, Recordati, Ipsen, Novo Nordisk. O. Alexopoulou: None. D.M. Maiter: Consulting Fee; Self; Ipsen, Recordati, Pfizer, Inc. The natural occurrence of menopause is considered to have beneficial effects in women with a prolactinoma and represents a window of opportunity for successful dopamine agonist (DA) withdrawal. Strong evidence for these effects remains however scarce. We retrospectively analyzed data from 95 women undergoing menopause (Mp) (FSH&amp;gt;35 U/L) while still treated with DA (cabergoline (CAB) in 82) for a prolactinoma diagnosed at a mean age of 38.0 ± 8.0 years. The pituitary tumor was a microadenoma in 66 and a macroadenoma in 29 (invasive in 12). Our objectives were to identify the influence of menopause on the evolution of treated prolactinomas and on the risk of recurrence after DA withdrawal. In post-menopausal women still treated with DA (median dose of 0.50 mg CAB/week or equivalent), a significant decrease in median prolactin (PRL) was observed from a premenopausal value of 15.1 µg/L to 10.7 µg/L 3-6 months after Mp (n=64, P=0.05) and to 7.7 µg/L 24 months after Mp (n=43, P &amp;lt; 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p &amp;lt; 0. 01). DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262). Strict criteria for discontinuation were fulfilled in 52 of them: a normal PRL for at least 24 months under a cabergoline dose ≤ 0.50 mg/week and a more than 50%-reduction in tumor surface area for macroadenomas. Among them, 37 women (71%) remained in remission during a median follow-up period of 26 months (range: 6-176), while 15 (29%) had an asymptomatic biological recurrence after a median duration of 6 months (range: 2-47). Only one woman showed minimal tumor regrowth. 12/15 of the biological recurrences of hyperprolactinemia occurred within the first year after withdrawal and the estimated probability of remission at 5 years was 66%. Multivariate analysis showed that the only independent predictor of recurrence was the PRL value observed 3 to 6 months after DA discontinuation (p = 0.028). Estrogen-progestin replacement therapy, given in 21 women, did not influence these outcomes. In conclusion, we confirm that menopause has a beneficial effect on the evolution of treated and untreated prolactinomas. When using strict criteria for DA withdrawal in the post-menopausal period, a sustained clinical and biological remission can be expected in two-thirds of women, and when recurrence occurs, it is usually mild and asymptomatic. Presentation: 6/2/2024

9281 Menopause Has a Beneficial Influence on the Evolution of Prolactinomas: a Study in 95 Patients

Abstract Disclosure: S. Constantinescu: None. C. Nava: None. F. Chasseloup: None. P. Chanson: Consulting Fee; Self; Eli Lilly &amp; Company, Recordati, Ipsen, Novo Nordisk. O. Alexopoulou: None. D.M. Maiter: Consulting Fee; Self; Ipsen, Recordati, Pfizer, Inc. The natural occurrence of menopause is considered to have beneficial effects in women with a prolactinoma and represents a window of opportunity for successful dopamine agonist (DA) withdrawal. Strong evidence for these effects remains however scarce. We retrospectively analyzed data from 95 women undergoing menopause (Mp) (FSH&amp;gt;35 U/L) while still treated with DA (cabergoline (CAB) in 82) for a prolactinoma diagnosed at a mean age of 38.0 ± 8.0 years. The pituitary tumor was a microadenoma in 66 and a macroadenoma in 29 (invasive in 12). Our objectives were to identify the influence of menopause on the evolution of treated prolactinomas and on the risk of recurrence after DA withdrawal. In post-menopausal women still treated with DA (median dose of 0.50 mg CAB/week or equivalent), a significant decrease in median prolactin (PRL) was observed from a premenopausal value of 15.1 µg/L to 10.7 µg/L 3-6 months after Mp (n=64, P=0.05) and to 7.7 µg/L 24 months after Mp (n=43, P &amp;lt; 0.001). There was also a significant reduction in median coronal tumor surface at 24 months, from 12.6 to 7.1 mm² (p &amp;lt; 0. 01). DA treatment was withdrawn in 53 women (56%) after a median interval of 26 months after menopause (range: 3-262). Strict criteria for discontinuation were fulfilled in 52 of them: a normal PRL for at least 24 months under a cabergoline dose ≤ 0.50 mg/week and a more than 50%-reduction in tumor surface area for macroadenomas. Among them, 37 women (71%) remained in remission during a median follow-up period of 26 months (range: 6-176), while 15 (29%) had an asymptomatic biological recurrence after a median duration of 6 months (range: 2-47). Only one woman showed minimal tumor regrowth. 12/15 of the biological recurrences of hyperprolactinemia occurred within the first year after withdrawal and the estimated probability of remission at 5 years was 66%. Multivariate analysis showed that the only independent predictor of recurrence was the PRL value observed 3 to 6 months after DA discontinuation (p = 0.028). Estrogen-progestin replacement therapy, given in 21 women, did not influence these outcomes. In conclusion, we confirm that menopause has a beneficial effect on the evolution of treated and untreated prolactinomas. When using strict criteria for DA withdrawal in the post-menopausal period, a sustained clinical and biological remission can be expected in two-thirds of women, and when recurrence occurs, it is usually mild and asymptomatic. Presentation: 6/2/2024

12612 Chiasmal Herniation - A Rare Complication Of Prolactinoma Treatment

Abstract Disclosure: A. Syeda: None. V. Kantorovich: None. Introduction: Primary treatment of symptomatic prolactinomas is medical therapy with dopamine agonists (DA). Herniation of optic chiasm is a rare complication of tumor shrinkage induced by DA therapy which causes secondary deterioration in visual fields. Case:A 26-year-old man presented to our hospital after a syncopal episode. He had headaches and blurry vision in the left eye for the past 4 months. He was diagnosed with a 4 cm x 3.6 cm x 2.6 cm pituitary macroprolactinoma compressing the optic chiasm, his prolactin (PRL) was 4700 ng/mL (N: 4.0-15.2 ng/mL) and testosterone was suppressed to 10 ng/dL (N: 249-836 ng/dL). Other hormonal workup was unremarkable. Ophthalmologic evaluation was consistent with left optic nerve pallor and neural rim thinning suggestive of a guarded prognosis. Immediate neurosurgical intervention was deemed unnecessary. Cabergoline 0.25 mg twice a week was initiated. Subsequently, the PRL levels improved but remained elevated to 414.2 ng/mL and cabergoline dose was increased to 0.5 mg twice a week. MRI Brain after 10 months revealed significant tumor reduction to 2.1 cm x 2.1cm x 1.2 cm. He was inconsistent with his endocrinology follow up appointments and was also non-adherent to cabergoline intermittently. After 14 months of starting DA therapy, he presented with worsening blurriness in his left eye. A repeat brain MRI showed stable appearance of the large pituitary macroadenoma with inferior bowing of the optic chiasm. Significant distortion, tented appearance, and attenuation of the left prechiasmatic optic nerve was also noted. He was evaluated by neuro ophthalmology and a diagnosis of secondary visual deterioration due to optic chiasmal herniation was made. Cabergoline therapy was promptly discontinued. Two weeks post-cabergoline cessation, he underwent trans-sphenoidal resection reporting vision improvement pre-surgery. Post-operative MRI depicted changes with no residual tumor and improved optic chiasm position. Discussion:Various theories explain chiasmal herniation with dopamine agonist (DA) treatment for prolactinomas. Pre-existing chiasm-tumor tethering may exacerbate downward pull during tumor reduction caused by DA therapy. Some case series have suggested that not all patients with chiasmal herniation have visual field defects and that despite improvement in visual fields with decrease in DA dosage, there are no appreciable radiographic changes/reversal of chiasmal herniation. One of the explanations for this lack of correlation is that visual impairment is rather a consequence of vascular compression. This case underscores the need for regular perimetry in macroprolactinoma patients on medical treatment. Adjusting dopamine agonist dosage to allow controlled tumor regrowth, monitored closely with frequent visual field and prolactin assessments, is crucial for relieving optic chiasm tension. Presentation: 6/3/2024