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Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow‐up exist. However, not all recommendations are strictly evidence‐based. To evaluate consensus on the treatment and follow‐up of patients with acromegaly in the Nordic countries. Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow‐up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert‐type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert‐type scale. Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first‐generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first‐generation SSA and pegvisomant as second‐ or third‐line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence‐based data. [ABSTRACT FROM AUTHOR]

Introduction and purpose Cariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use. Methods and materials A review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist. Conclusions Cariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change sleep parameters, thus having adverse effects on patient condition. This meta-analysis clarified the effects of DAs used in RLS treatment on the sleep architecture. PubMed, Embase, and Cochrane Central databases were searched for randomized control trials (RCT) (up to October 2023) that discussed the effects of DAs on sleep architecture in patients with RLS. A meta-analysis employing a random-effects model was conducted. The patients were divided into subgroups according to individual DAs and treatment duration (1 day or ≥4 weeks). Thirteen eligible randomized placebo-controlled trials were included in the assessment. The effects of three DAs (i.e., pramipexole, ropinirole, and rotigotine) on rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were analyzed. Overall, pramipexole significantly improved SE but decreased the percentage of REM sleep among treated patients. Ropinirole also enhanced SE compared with the placebo group. Rotigotine did not affect SE and REM sleep. Subgroup analysis found that pramipexole used for 1 day and ≥4 weeks significantly diminished the percentage of REM sleep. Ropinirole used for 1 day showed similar REM sleep patterns. Finally, none of the three DAs affected SWS. This meta-analysis demonstrated that DAs significantly affect sleep parameters. • A meta-analysis examined the effects of pramipexole, ropinirole, and rotigotine on sleep structure. • Pramipexole improved sleep efficiency (SE) but decreased the percentage of rapid eye movement (REM) sleep. • Ropinirole enhanced sleep efficiency. • None of the three DAs had any effect on slow-wave sleep (SWS). [ABSTRACT FROM AUTHOR]

Real world clinical practice frequently poses the question on the advisability of diagnostic and/or treatment interventions for increased prolactin levels of below 2500 mU/mL (100 ng/mL), which is commonly considered as mild and not unequivocally indicating a prolactinoma. The aim of the review is to critically analyze the body of literature within the last 10 years on clinical and biochemical particulars of patients with mildly increased prolactin levels. We performed the search in Pubmed and RISC (Russian Index of Science Citation) databases with the keywords of “mild hyperprolactinemia” and “women” (or their Russian equivalents). After exclusion of the studies in patients with primary hypothyroidism or treatment with agents inducing prolactin secretion, as well as of clinical case descriptions, we selected 21 original papers with clinical and biochemical data of female patients with mild hyperprolactinemia (prolactin levels of less than 2500 mU/mL or less than 100 ng/mL). Symptoms of mild hyperprolactinemia include menstrual cycle disorders, anovulatory infertility and/or early pregnancy losses, breast disorders, psychoemotional and sexual disorders, and metabolic abnormalities. Repeated testing of prolactin levels to exclude potential stress related to the vein puncture allows for exclusion of 27% to 28% of the patients from further diagnostic work up. Confirmation of persistently increased prolactin levels warrants a magnetic resonance imaging study of the pituitary. Most patients with persistently increased prolactin levels by repeated tests would have pituitary abnormalities (in most cases, pituitary microadenoma). Taking into account the data on negative effects of even mildly increased prolactin levels on reproductive and metabolic health, it is reasonable to administer a first line agent cabergoline at doses ensuring normoprolactinemia. The results of studies indicate that treatment with cabergoline at doses necessary to normalize prolactin levels would lead to regression of menstrual dysfunction, decrease the probability of early pregnancy losses, improve metabolic parameters, promotes restoration of the sexual function, and diminishes the level of depression. This is especially important when planning pregnancy in patients with menstrual cycle disorders, infertility and/or early pregnancy losses.

Objective The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). Design This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. Methods Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. Results Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P <.01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P =.03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P <.01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P =.04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. Conclusion In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients. [ABSTRACT FROM AUTHOR]

Background: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. Objective: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). Methods: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. Result: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88–0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03–0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37–42.97, p 0.021). Conclusion: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder. [ABSTRACT FROM AUTHOR]

Pramipexole, a dopaminergic agonist, has rarely been implicated as a cause of hyponatremia in patients with Parkinson’s disease (PD). Pramipexole-induced stimulation of anti-diuretic hormone results in euvolemic hyponatremia. This is often neglected, and hyponatremia may lead to worsening of the motor symptoms with PD and an unnecessary increase in dopaminergic medications, causing disabling dyskinesias. This case report describes a patient with young-onset PD who developed newonset hyponatremia due to pramipexole-induced syndrome of inappropriate anti-diuretic hormone within 3 months of starting the drug.

Background/Objective: To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy. Case Report: A 35-year-old woman with a history of Graves’ disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis. Discussion: Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function. Conclusion: We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.

Characterised by fever, altered mental status, muscle rigidity and autonomic dysfunction, neuroleptic malignant syndrome is a life-threatening idiosyncratic reaction to antipsychotic medication; around one in 10 cases end in cardiac arrest. The primary cause of neuroleptic malignant syndrome is dopamine receptor blockade, and the standard causative agent is an antipsychotic drug. While first-generation (typical) neuroleptics such as haloperidol, fluphenazine, trifluoperazine and prochlorperazine pose the greatest risk, neuroleptic malignant syndrome has been reported with second-generation (atypical) neuroleptics such as risperidone, clozapine, olanzapine and ziprasidone. Paramedic awareness of neuroleptic malignant syndrome as a neuropsychiatric emergency is paramount to reducing serious morbidity and even death in patients presenting with symptoms and a history of antipsychotic use. Treatment is individualised and based on clinical presentation, with supportive medical therapy being a key intervention. [ABSTRACT FROM AUTHOR]

Background and purpose: Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. Methods: Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive‐Compulsive Disorders in Parkinson's Disease–Rating Scale. Those who scored above the cut‐off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge‐eating) were compared in a case–control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. Results: Forty‐six patients were included: 19 ICD‐positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. Conclusions: The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD. [ABSTRACT FROM AUTHOR]

Context Treatment of hyperprolactinemia with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. Objective This study examines the efficacy and tolerability of the nonergot DA ropinirole for the long-term treatment of hyperprolactinemia. Methods Twelve hyperprolactinemic women were treated with ropinirole in a 6-month, open-label, dose-escalation trial; 7 of the 12 continued treatment in an extension study for up to 17 months. Ropinirole doses were uptitrated to achieve normal prolactin (PRL) levels, restore menses, and eliminate galactorrhea. Results Two of the 12 participants were DA naive; 6 of 12 were ergot DA intolerant; and 1 of 12 had known ergot DA resistance. Baseline PRL levels were 126.2 ± 41.4 ng/mL (SEM). Ropinirole was uptitrated from 0.125 to 0.25 mg/h to a median total daily dose (TDD) of 2 mg/d (1-4 mg/d [interquartile range]). PRL normalization was achieved in 50% of the participants (5 with microadenomas and 1 with idiopathic hyperprolactinemia) at a median effective TDD of 1 mg/d. Of the patients achieving PRL normalization, 83% were ergot DA intolerant. A persistent partial biochemical response (PRL reduction >50% from baseline) was achieved in 17% of the participants. During treatment, menses resumed in 67% of amenorrheic patients; galactorrhea resolved in 67%. Mild adverse effects were reported in 92% of participants; however, ropinirole was not discontinued because of intolerance even among the 50% of individuals with a prior history of ergot DA intolerance and resultant medication discontinuation. Conclusion These data demonstrate the efficacy and tolerability of ropinirole for the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia and suggest ropinirole may represent a novel therapeutic alternative for treating hyperprolactinemic disorders in patients with ergot DA intolerance. [ABSTRACT FROM AUTHOR]

Although some studies have examined the impact of short-term dopamine agonist treatment on altered central sensory processing in patients with restless legs syndrome (RLS), there is a scarcity of research investigating the effect of long-term treatment with these drugs. The aim of this study is to investigate the long-term impact of dopamine agonist treatment on altered central sensory processing in RLS patients using current perception threshold (CPT) testing. We conducted a study of 24 RLS patients, measuring their CPT values before and after dopamine agonist treatment for at least 2 months. Patients were classified as responders or non-responders based on their decrease in International Restless Legs Syndrome (IRLS) score. Clinical parameters were collected and compared pre- and post-treatment. The mean duration of treatment with dopamine agonist was 13.6 ± 11.0 months. Our results showed that dopamine agonist treatment significantly improved clinical parameters, including the IRLS score, Visual Analogue Scale, and RLS Quality of Life questionnaire. However, CPT values did not show significant changes for all stimulus frequencies after treatment. Furthermore, we did not find any difference in CPT values before and after treatment in both responders and non-responders. Our study demonstrated that long-term treatment with dopamine agonists effectively reduces RLS symptoms, but does not reverse the altered central sensory processing observed on CPT testing in RLS patients. These results support the notion that the pathophysiology of RLS is multifactorial and not solely driven by dopaminergic dysfunction. • Dopamine agonist treatment effects on central sensory processing in RLS patients may vary with treatment duration. • Long-term dopamine agonist treatment does not reverse altered CPT-measured central sensory processing in RLS patients. • These findings support the notion that RLS pathophysiology is multifactorial and not solely dopaminergic. [ABSTRACT FROM AUTHOR]

Objective This study aimed to elucidate the efficacy (as per current biochemical criteria) of cabergoline monotherapy or as addition to long-acting somatostatin receptor ligand (SRL) in patients with acromegaly and no previous pituitary radiotherapy. Design Multi-centre, retrospective, cohort study (four UK pituitary centres: Birmingham, Bristol, Leicester, and Oxford). Methods Clinical, laboratory, and imaging data were analysed. Results Sixty-nine patients on cabergoline monotherapy were included (median insulin-like growth factor 1 [IGF-1] × upper limit of normal [ULN] pre-cabergoline 2.13 [1.02-8.54], median treatment duration 23 months, and median latest weekly dose 3 mg); 31.9% achieved normal IGF-1 (25% growth hormone [GH]-secreting and 60% GH+prolactin co-secreting tumours); median weekly cabergoline dose was similar between responders and non-responders. Insulin-like growth factor 1 normalization was related with GH+prolactin co-secreting adenoma (B 1.50, P =.02) and lower pre-cabergoline IGF-1 × ULN levels (B −0.70, P =.02). Both normal IGF-1 and GH < 1 mcg/L were detected in 12.9% of cases and tumour shrinkage in 29.4% of GH-secreting adenomas. Twenty-six patients on SRL + cabergoline were included (median IGF-1 × ULN pre-cabergoline 1.7 [1.03-2.92], median treatment duration 36 months, and median latest weekly dose 2.5 mg); 23.1% achieved normal IGF-1 (15.8% GH-secreting and 33.3% GHprolactin co-secreting tumours). Normal IGF-1 and GH < 1 mcg/L were detected in 17.4%. Conclusions In non-irradiated patients, cabergoline normalizes IGF-1 in around one-third and achieves both IGF-1 and GH targets in approximately one out of ten cases. SRL + cabergoline is less efficient than previously reported possibly due to differences in study methodology and impact of confounding factors. [ABSTRACT FROM AUTHOR]

ABSTRACT Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (

ABSTRACT: Drying off dairy cows may challenge animal welfare due to high milk yields. A total of 111 loose-housed Holstein cows yielding >15 kg/d of milk were included in a 2 × 2 × 2 factorial design during dry-off to investigate the effects of reduced feeding level (normal vs. reduced energy density), reduced milking frequency (twice vs. once daily), and administration of a dopamine agonist (saline i.m. injection vs. cabergoline i.m. injection) on behavior in the home pen. During the 7 d before dry-off, cows were fed and milked according to 1 of the 4 feeding level and milking frequency combinations. Within 3 h after the last milking, cows were injected i.m. with 5 mL of either saline or a dopamine agonist (5.6 mg of cabergoline; Velactis, Ceva Santé Animale, Libourne, France; labeled for use only with abrupt dry-off, i.e., no preceding reduction in feeding level or milking frequency before last milking). Cows' behavior during d −1, 0, and +1 relative to the last milking was recorded via video and leg-attached sensors. Cows on the reduced energy density diet spent more time feeding and showed more attempts to feed from other cows' bins on d −1. Throughout the period of observations, cows on the reduced diet spent a lower percentage of lying time with their head raised, a higher percentage of lying time with their legs bent, and less time standing in a vigilant posture than did cows on the normal lactation diet. Reducing the daily milking frequency from 2 to 1 did not result in any clear behavioral signs of discomfort. On d 0, cows injected with cabergoline lay down longer but had their head raised for a shorter percentage of time while lying, compared with cows injected with saline. Cows injected with cabergoline also spent less time feeding than cows injected with saline on d 0, and reduced the time spent drinking from d −1 to d 0. Finally, fewer cabergoline-injected cows used the brush for self-grooming, and, among cows that did use the brush, the cows injected with cabergoline reduced the time spent using the brush from d −1 to d 0. In conclusion, cows injected with cabergoline showed several behavioral changes compared with control cows injected with saline. The behavioral changes shown by cows injected with cabergoline may be indicative of malaise during the first 24 h after injection, raising concern for animal welfare. No behavioral evidence for reduced udder pain in cows injected with cabergoline compared with control cows injected with saline was found. Drying off by reducing the energy density of the diet caused behavioral changes indicative of hunger before dry-off, whereas reducing the milking frequency had no clear effects on behavior.

Objective: To summarize the clinical characteristics of 4 male prolactinoma patients with severe obesity. Methods: The clinical data of all the patients were retrospectively analyzed. Results: All the patients visited our hospital for severe obesity at the age of 16-30 years old with their body mass index (BMI) of 37.9-55.9 kg/m². All the patients were obese since childhood, even at birth. Hyperprolactinemia (72.3-273.0 ng/ml) was found during the etiological screening of obesity and MRI revealed pituitary adenomas. Additionally, all of them had multiple obesity related complications, such as hyperinsulinemia and dyslipidemia. Treatment of dopamine agonists (DAs) effectively normalized their prolactin level and the pituitary MRI reexamination after 6 months of DAs treatment showed the shrinkage of the pituitary adenomas in 3 patients. Their weight also decreased in different degrees (2.70~19.03% lower than the baseline) with improved metabolic profiles. Conclusion: Serum prolactin level should be screened in obese patients, especially those with severe obesity. [ABSTRACT FROM AUTHOR]

Background: Vitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome. Methods: We have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia. Results: Some evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure. Conclusion: It appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it. [ABSTRACT FROM AUTHOR]

Drying off dairy cows may challenge animal welfare due to high milk yields. A total of 111 loose-housed Holstein cows yielding >15 kg/d of milk were included in a 2 × 2 × 2 factorial design during dry-off to investigate the effects of reduced feeding level (normal vs. reduced energy density), reduced milking frequency (twice vs. once daily), and administration of a dopamine agonist (saline i.m. injection vs. cabergoline i.m. injection) on behavior in the home pen. During the 7 d before dry-off, cows were fed and milked according to 1 of the 4 feeding level and milking frequency combinations. Within 3 h after the last milking, cows were injected i.m. with 5 mL of either saline or a dopamine agonist (5.6 mg of cabergoline; Velactis, Ceva Santé Animale, Libourne, France; labeled for use only with abrupt dry-off, i.e., no preceding reduction in feeding level or milking frequency before last milking). Cows' behavior during d −1, 0, and +1 relative to the last milking was recorded via video and leg-attached sensors. Cows on the reduced energy density diet spent more time feeding and showed more attempts to feed from other cows' bins on d −1. Throughout the period of observations, cows on the reduced diet spent a lower percentage of lying time with their head raised, a higher percentage of lying time with their legs bent, and less time standing in a vigilant posture than did cows on the normal lactation diet. Reducing the daily milking frequency from 2 to 1 did not result in any clear behavioral signs of discomfort. On d 0, cows injected with cabergoline lay down longer but had their head raised for a shorter percentage of time while lying, compared with cows injected with saline. Cows injected with cabergoline also spent less time feeding than cows injected with saline on d 0, and reduced the time spent drinking from d −1 to d 0. Finally, fewer cabergoline-injected cows used the brush for self-grooming, and, among cows that did use the brush, the cows injected with cabergoline reduced the time spent using the brush from d −1 to d 0. In conclusion, cows injected with cabergoline showed several behavioral changes compared with control cows injected with saline. The behavioral changes shown by cows injected with cabergoline may be indicative of malaise during the first 24 h after injection, raising concern for animal welfare. No behavioral evidence for reduced udder pain in cows injected with cabergoline compared with control cows injected with saline was found. Drying off by reducing the energy density of the diet caused behavioral changes indicative of hunger before dry-off, whereas reducing the milking frequency had no clear effects on behavior. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder in premenopausal women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Patients frequently present comorbidities, including obesity, insulin resistance, and impaired glucose and lipid metabolism. The diverse clinical presentation may mimic various endocrine disorders, making the diagnosis challenging in some clinical circumstances. Prolactin (PRL) is a recommended biomarker in the initial diagnostic workup to rule out hyperprolactinemia (HPRL). The traditional role of PRL is linked to lactation and the reproductive system. Recent research highlights PRL's emerging role in metabolic homeostasis. PRL influences metabolism directly by interacting with the pancreas, liver, hypothalamus, and adipose tissue. Its influence on an individual's metabolism is intricately tied to its serum concentration. While deficient and very high levels of PRL can negatively affect metabolism, intermediate–normal to moderately high levels may promote metabolic health. In women with PCOS, PRL levels may be altered. Research results on different aspects of the relationship between PCOS and the impact of various levels of PRL on metabolic homeostasis are limited and inconsistent. In this narrative literature review, we comprehensively examined data on serum PRL levels in PCOS patients. We investigated the correlation between a favorable metabolic profile and serum PRL levels in this population. Furthermore, we explored the concept of beneficial PRL effects on metabolism and discussed the potential therapeutic application of dopamine agonists in PCOS treatment. Lastly, we emphasized several promising avenues for future research in this field. [ABSTRACT FROM AUTHOR]

Dopamine agonist-induced cerebrospinal fluid (CSF) rhinorrhea is an uncommon treatment-related complication arising in 6.1% of prolactinoma patients treated with dopamine agonists. Locally invasive prolactinomas may create CSF fistulae through formation of dural and osseous skull base defects. Tumor shrinkage secondary to dopamine agonist therapy unmasks skull base defects, thus inducing CSF rhinorrhea. In these cases, repair of the leak may be achieved through collaborative surgical intervention by rhinologists and neurosurgeons. Multiple variables have been investigated as potential contributors to the risk of CSF rhinorrhea development in medically treated prolactinoma patients, with little consensus. The primary aim of our study was the characterization of risk factors for CSF rhinorrhea development following dopamine agonist treatment. A systematic review of the literature was conducted to identify cases of CSF rhinorrhea following dopamine agonist treatment of prolactinoma. The clinical history, radiographic findings and treatment outcomes are discussed. Fifty-four patients with dopamine agonist-induced CSF rhinorrhea were identified across 23 articles published from 1979 to 2019. Description of diagnostic imaging [computed tomography (CT)/magnetic resonance imaging (MRI)] was not provided for 18/54 subjects. For the 36 cases that described prolactinoma appearance on CT or MRI, invasion of the cavernous sinuses was reported in 13 (36.1%) and invasion of the sphenoid sinus was reported in 18 (50%). Based on our systematic review, we propose that CT findings of osseous erosion of the sella or the anterior skull base may predict dopamine agonist-induced CSF rhinorrhea. We recommend obtaining a thin-slice CT of the sinuses in cases with MRI evidence of sphenoid involvement. [ABSTRACT FROM AUTHOR]

• A total of 99,118 PD patients who were prescribed levodopa or DAs alone as initial anti-parkinsonian drugs between 2011 and 2020 were eligible for inclusion in the analysis. • The decline in levodopa prescriptions reversed in 2012, and the prescription rate has been increasing until recently. • The odds ratio of levodopa prescription increased for elderly and Alzheimer's disease patients, and decreased for patients with Medicaid insurance and gastrointestinal disease. Parkinson's disease (PD) is a common neurodegenerative disorder typically treated with dopamine replacement therapy and dopamine agonists (DAs) to alleviate symptoms and minimize dyskinesia. Optimal treatment strategies for patients newly diagnosed with PD have been a topic of debate for many years. We conducted a 10-year descriptive study of drug prescription trends and factors affecting prescription choices for newly diagnosed drug-naïve PD patients using data from the National Health Insurance program in Korea. To identify statistically significant differences in yearly trends, we employed the Cochran-Armitage trend test. Additionally, we utilized multiple logistic regression analysis to investigate the factors associated with the selection of levodopa and DAs as initial anti-parkinsonian drugs. A total of 99,118 patients with PD who were prescribed levodopa or DAs alone as initial anti-parkinsonian drugs between 2011 and 2020 were eligible for inclusion in the analysis. The prescription rate of DAs increased until 2012, and then steadily decreased annually. The likelihood of levodopa prescription increased with age and at higher-level hospitals. In terms of comorbidities, patients with Alzheimer's disease and cerebrovascular diseases were more likely to be prescribed levodopa than those with peptic ulcer disease and dyslipidemia. The decline in levodopa prescriptions was reversed in 2012, and the prescription rate has continued to increase until recently. The odds ratio of levodopa prescription increased in elderly patients with Alzheimer's disease and decreased in patients with Medical aid insurance and peptic ulcer disease. [ABSTRACT FROM AUTHOR]

Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson's disease, suggesting a potential role of these lipids as biomarkers. This project's objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson's patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson's patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography-mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson's groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson's and GBA1-mutation-carrier Parkinson's patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson's. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson's groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson's patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients.

Abstract Background Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control with drugs may reduce long-term CVD risk. Bromocriptine has been in clinical use for over 30 years, but the utility of bromocriptine in the treatment of diabetes patients has been proposed more recently. Objective To summarize the available data regarding the effect of bromocriptine in T2DM management. Method A systematic literature search was conducted in the electronic databases, including Google Scholar, PubMed, Medline, and Science Direct, to locate studies that meet the objectives of this systematic review. Additional articles were included by conducting direct Google searches of the references cited by eligible articles located by the database search. The following search terms were used on PubMed “bromocriptine OR dopamine agonist AND diabetes mellitus OR hyperglycemia OR obese”. Result Eight studies were included in the final analysis. 6210 of the 9391 study participants received bromocriptine treatment, while 3183 received a placebo. The studies demonstrated that patients who took bromocriptine treatment had significantly reduced blood glucose and BMI, which is the main cardiovascular risk factor in T2DM patients. Conclusion Based on this systematic review, bromocriptine may be used for T2DM treatment for its cardiovascular risk reduction effect, especially body weight reduction. However, advanced study designs might be warranted.

This commentary discusses a study on male prolactinoma patients with severe obesity and their response to dopamine agonist therapy. The study found that treatment with dopamine agonists resulted in the control of prolactin levels and improvements in metabolic profiles. The authors suggest that dopamine agonists may explain the weight loss observed and emphasize the importance of screening prolactin levels in men with severe obesity. They also discuss the potential role of prolactin in obesity and metabolic syndrome and the possibility of considering surgical intervention as an alternative to dopamine agonist therapy. The authors commend the original study and call for further research on the relationship between obesity and hyperprolactinemia. The article provides valuable insights for individuals researching the impact of prolactinoma on body weight and metabolic health. [Extracted from the article]

Pramipexole, a dopaminergic agonist, has rarely been implicated as a cause of hyponatremia in patients with Parkinson's disease (PD). Pramipexole-induced stimulation of anti-diuretic hormone results in euvolemic hyponatremia. This is often neglected, and hyponatremia may lead to worsening of the motor symptoms with PD and an unnecessary increase in dopaminergic medications, causing disabling dyskinesias. This case report describes a patient with young-onset PD who developed newonset hyponatremia due to pramipexole-induced syndrome of inappropriate anti-diuretic hormone within 3 months of starting the drug. [ABSTRACT FROM AUTHOR]

ABSTRACT: This study aimed to investigate the effect of the different dry-off strategies based on reducing feeding level (normal vs. reduced energy density), reducing milking frequency (twice vs. once daily), and administration of a dopamine agonist after last milking (i.e. saline vs. cabergoline injection) on blood metabolites, hormones, and minerals around dry-off. In this experiment, 119 Holstein dairy cows were used in a 2 × 2 × 2 factorial arrangement. In the last week before dry-off, cows were allocated to 1 of the 4 possible dry-off strategies based on feeding level and milking frequency. Within 3 h after last milking, cows were injected with either saline or a D2 dopamine agonist (cabergoline; Velactis, Ceva Santé Animale, Libourne, France; labeled for use only with abrupt dry-off, e.g., no preceding reduction in feeding level or milking frequency before last milking). After dry-off, all cows were fed the same dry cow diet and data collection continued for a week. Blood samples were collected from the coccygeal vein on d −9, −6, −5, −2, 1, 2, 5, and 7 relative to dry-off. Additionally, blood was sampled at 0, 3, and 6 h relative to injection of either cabergoline or saline, equivalent to d 0.125, 0.250, and 0.375 relative to last milking (dry-off). The reduced feeding level before dry-off caused reduced glucose and insulin concentrations as well as increased free fatty acid concentrations, particularly when reduced feeding level was combined with milking the cows 2× daily. The intramuscular injection of cabergoline caused the expected reduction in circulating prolactin concentrations. In addition, dopamine-agonist cabergoline induced an atypical simultaneous pattern of plasma metabolites (i.e., increased glucose and free fatty acid concentrations), hormones (i.e., reduced insulin and increased cortisol concentrations), and minerals (i.e., reduced calcium concentration), indicating that normal metabolic and mineral homeostatic regulations were hindered after the injection of ergot alkaloid cabergoline. In conclusion, reducing milking frequency seems the best management strategy to reduce milk production at dry-off among those tested in this study.

Excessive daytime sleepiness is a symptom experienced by more than one-third of patients with Parkinson's disease and is associated with disease duration and severity, dopaminergic therapy, and several non-motor symptoms. In recent years, growing evidence has been suggesting “primary” sleepiness as a symptom in Parkinson's disease due to common pathophysiological features: for this reason, it is crucial to recognize sleepiness in these patients and to investigate and exclude other conditions possibly leading to sleepiness (e.g., heavy dopaminergic therapy or breathing disorders during sleep). For both inpatients and outpatients, the key to a correct diagnosis is a structured clinical interview, together with questionnaires, for a better characterization of symptoms and the use of objective measures as the most precise method to assess excessive daytime sleepiness. Finally, there are some therapeutical approaches that may be attempted for these patients, and although there is still no consensus on a standardized therapy, clinical trials with new drugs are currently persevered on.

BackgroundVitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome.MethodsWe have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia.ResultsSome evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure.ConclusionIt appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it.

Introduction: Prolactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar). Methods: We compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13)withunselectedhospital-treated prolactinomas ("unselected", n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39). Results: AIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p<0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p<0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p<0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p<0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA- induced macroadenoma shrinkage (>50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p<0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p<0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups. Discussion: AIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically- negative tumors. [ABSTRACT FROM AUTHOR]

Purpose: Treatment with dopamine agonists (DAs) has been the first-line standard treatment for prolactinoma, and surgery has been reserved for drug intolerance and resistance for several decades. We evaluated whether surgery plays a primary role in prolactinoma management. Materials and Methods: We conducted a retrospective study of 210 prolactinoma patients who had received surgical treatment at our institution. We analyzed the treatment outcomes according to tumor extent, sex, and preoperative DA medication. Results: Overall hormonal remission was achieved in 164 patients (78.1%), and complete removal was achieved in 194 patients (92.4%). When the tumors were completely removed, the remission rate increased to 84.5%. Anterior pituitary function was normalized or improved in 94.6% of patients, whereas only 4.1% of patients showed worsening of hormone control. Hormonal remission was higher in patients who had not received DA preoperatively than in those who had received preoperative DA treatment. Smaller tumor size (<1 cm), no invasion into the cavernous sinus, and female sex were predictors of good surgical outcomes. Conclusion: Although DAs remain the first-line standard treatment for prolactinomas, surgery can be an excellent option and should be considered as an alternative primary treatment modality when patients are predicted to achieve a good surgical outcome. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control with drugs may reduce long-term CVD risk. Bromocriptine has been in clinical use for over 30 years, but the utility of bromocriptine in the treatment of diabetes patients has been proposed more recently. Objective: To summarize the available data regarding the effect of bromocriptine in T2DM management. Method: A systematic literature search was conducted in the electronic databases, including Google Scholar, PubMed, Medline, and Science Direct, to locate studies that meet the objectives of this systematic review. Additional articles were included by conducting direct Google searches of the references cited by eligible articles located by the database search. The following search terms were used on PubMed "bromocriptine OR dopamine agonist AND diabetes mellitus OR hyperglycemia OR obese". Result: Eight studies were included in the final analysis. 6210 of the 9391 study participants received bromocriptine treatment, while 3183 received a placebo. The studies demonstrated that patients who took bromocriptine treatment had significantly reduced blood glucose and BMI, which is the main cardiovascular risk factor in T2DM patients. Conclusion: Based on this systematic review, bromocriptine may be used for T2DM treatment for its cardiovascular risk reduction effect, especially body weight reduction. However, advanced study designs might be warranted. [ABSTRACT FROM AUTHOR]

Dopamine replacement therapy for Parkinson's disease is achieved using L-DOPA or dopamine D2/3 agonists, such as ropinirole. Here, we compare the effects of L-DOPA and ropinirole, alone or in combination, on patterns of glial and microvascular reactivity in the striatum. Rats with unilateral 6-hydroxydopamine lesions were treated with therapeutic-like doses of L-DOPA (6 mg/kg), an equipotent L-DOPA-ropinirole combination (L-DOPA 3 mg/kg plus ropinirole 0.5 mg/kg), or ropinirole alone. Immunohistochemistry was used to examine the reactivity of microglia (ionized calcium-binding adapter molecule 1, IBA-1) and astroglia (glial fibrillary acidic protein, GFAP), as well as blood vessel density (rat endothelial cell antigen 1, RECA-1) and albumin extravasation. L-DOPA monotreatment and L-DOPA–ropinirole cotreatment induced moderate-severe dyskinesia, whereas ropinirole alone had negligible dyskinetic effects. Despite similar dyskinesia severity, striking differences in perivascular microglia and astroglial reactivity were found between animals treated with L-DOPA vs. L-DOPA–ropinirole. The former exhibited a marked upregulation of perivascular IBA-1 cells (in part CD68-positive) and IBA-1–RECA-1 contact points, along with an increased microvessel density and strong perivascular GFAP expression. None of these markers were significantly upregulated in animals treated with L-DOPA–ropinirole or ropinirole alone. In summary, although ropinirole cotreatment does not prevent L-DOPA-induced dyskinesia, it protects from maladaptive gliovascular changes otherwise associated with this disorder, with potential long-term benefits to striatal tissue homeostasis. [ABSTRACT FROM AUTHOR]

Background. Dopamine agonists (DA) are first line treatment for prolactinomas. Optic chiasm herniation can rarely occur during therapy, while brain herniation is very uncommon. Case Reports. A 34 yo woman presented with headaches and vision changes. Prolactin (PRL) was 4300 ng/mL. MRI showed a 4.5 cm pituitary adenoma with chiasm compression. After 3 months, PRL decreased to 201 ng/mL while patient was taking CAB 0.75 mg twice a week. MRI showed ~30% tumor reduction with medial temporal lobe herniation and encephalocele. CAB was stopped and she underwent surgical debulking and encephalocele repair. Histopathology confirmed prolactin tumor. CAB 0.75 mg twice a week was resumed. A 50 yo man had incidental detection of a sellar mass after trauma. MRI showed 3.6 cm tumor with minimal contact of right optic nerve, and PRL 3,318 ng/ml. He received CAB 0.5mg twice a week with PRL improvement to 26 ng/mL after 1 month. After 2 months ophthalmology exam showed new left superotemporal depression. PRL was 68 ng/mL and MRI showed 35% mass reduction and new inferior displacement tethering of the chiasm. CAB dose was decreased to 0.25 mg twice a week. Conclusion. Our cases illustrate that rapid biochemical and radiographic response to DA therapy in large prolactinomas warrants close clinical and neuroophthalmologic follow-up. We recommend repeating the MRI 3 months after initiation of DA therapy or sooner in case of new mass effect manifestations. Decision regarding DA dose reduction or chiasmopexy for visual field deficits needs to be multi-disciplinary and on a case-to-case basis. [ABSTRACT FROM AUTHOR]

Context: Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database. Objective: We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline. Design: Observational, retrospective, and cross-sectional study. Setting: This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center. Patients and Methods: Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed. Results: We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P=0.015), higher serum PRL levels (P=0.007), larger tumors (P=0.001), and cabergoline resistance (P< 0.001). Conclusions: The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Cabergoline-associated valvulopathy (CAV) is defined by the echocardiographic triad of moderate or severe regurgitation, valvular thickening and restricted valvular motion. While it is a well-described complication of dopamine agonist therapy in Parkinson’s disease, only three convincing cases of CAV have previously been described in the treatment of prolactinoma, with none involving the tricuspid valve. We describe a case of CAV affecting the tricuspid valve, ultimately resulting in the patient’s death. The novel finding of CAV affecting the tricuspid valve suggests a possible link between confirmed cases of CAV and the echocardiographic surveillance studies of cabergoline-treated prolactinoma patients which have mostly demonstrated subclinical tricuspid valve changes. The risk of CAV, although small, prompts a mindful prescription of dopamine agonist therapy for prolactinomas and consideration of measures to minimise cabergoline exposure. The cumulative cabergoline doses and duration of therapy associated with CAV in published cases exceed what has been evaluated in case series and surveillance studies, underscoring the importance of case reports in understanding CAV.

A recent study published in the Journal of Clinical Endocrinology & Metabolism examined the impact of tumor fibrosis on surgical outcomes for patients with prolactinomas. The study found that patients who were pretreated with dopamine agonists (DAs) had more extensive tumor fibrosis, higher rates of surgical complications, and lower rates of surgical remission for microadenomas. While DAs are effective in treating prolactinomas, they can induce tumor fibrosis, making surgical removal more challenging and reducing the chances of surgical cure. The study suggests that upfront surgical resection may be a better alternative in certain cases, but patient choice should also be considered. [Extracted from the article]

IntroductionProlactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar).MethodsWe compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas (“unselected”, n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39).ResultsAIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p

Objective: There has been increasing awareness that micro-vascular alteration or vascular inflammation has been associated with levodopa-induced dyskinesia in PD. Vascular endothelial function assessed by flow mediated dilation (FMD) is known to reflect early microvascular change. We compare the impact of levodopa or dopamine agonist treatment on the change of FMD in de novo PD patients. Methods: This retrospective study used a selected sample from registry. We identified de-novo PD patients who underwent FMD at baseline, and follow-up FMD after 1 year (± 2 month) of levodopa (n = 18) or dopamine agonist (n = 18) treatment. Results: FMD decreased after levodopa (8.60 ± 0.46 to 7.21 ± 0.4, p = 0.002) but there were no significant changes after DA treatment (8.33 ± 0.38 to 8.22 ± 0.33, p = 0.26). Homocysteine rose (11.52 ± 0.45 to 14.33 ± 0.68, p < 0.05) during levodopa treatment, but dopamine agonist had no effect (10.59 ± 0.38 to 11.38 ± 0.67, p = 0.184). Correlation analysis revealed that the changes in homocysteine level had non-significant correlation with FMD change (r = − 0.30, p = 0.06). FMD change was not associated with age (p = 0.47), disease duration (p = 0.81), baseline motor UPDRS (p = 0.43), motor UPDRS change (p = 0.64), levodopa equivalent dose change (p = 0.65). Conclusions: We found that 1-year levodopa treatment may adversely affect vascular endothelial function in de novo PD. Further studies are needed to clarify the exact pathogenesis and clinical implication of levodopa-induced endothelial dysfunction in PD. [ABSTRACT FROM AUTHOR]

Context: Dopamine agonist (DA)--induced impulse control disorder (ICD) represents a group of behavioral disorders that are increasingly recognized in patients with prolactinoma. Objective: We aimed to examine the genetic component of the underlying mechanism of DA-induced ICD. Methods: Patients with prolactinoma receiving dopamine agonist (cabergoline) treatment were included in the study. These patients were divided into 2 groups: patients who developed ICD due to DA and patients who did not. Patients were evaluated for polymorphisms of the DRD1, DRD3, COMT, DDC, GRIN2B, TPH2, OPRK1, OPRM1, SLC6A4, SLC6A3, HTR2A genes. Results: Of the 72 patients with prolactinoma using cabergoline, 20 were diagnosed with ICD. When patients with and without ICD were compared according to genotype frequencies, OPRK1/rs702764, DRD3/rs6280, HTR2A/rs6313, SLC6A4/rs7224199, GRIN2B/rs7301328, TPH2/rs7305115, COMT/rs4680, DRD1/rs4532 polymorphisms significantly increased in patients with DA-induced ICD. Conclusion: Our results show that multiple neurotransmission systems affect DA-induced ICD in patients with prolactinoma. [ABSTRACT FROM AUTHOR]

Background: The monoamine neurotransmitter disorders are neurometabolic syndromes caused by disturbances in the synthesis, transport and metabolism of the biogenic amines (the catecholamines dopamine, norepinephrine and epinephrine; serotonin), which are increasingly recognized as an expanding group of inherited neurometabolic syndromes. Case Description: A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was diagnosed with infantile parkinsonism-dystonia-2 (MIM: 618049). The whole-exome sequencing identified a homozygous c.710C > T (p.Pro237His) transition in the monoamine transporter gene SLC18A2, which was due to paternal uniparental disomy (UPD) of chromosome 10p15.3q26.3, resulting in brain dopamine-serotonin vesicular transport disease. Sanger sequencing confirmed that his unaffected father carried the same mutation in the heterozygous state, while his mother did not carry the same mutation. Autosomal recessive gene mutations in SLC18A2 has been identified in three families in different countries. The infant was treated with pramipexole, a dopamine agonist, and the static tremor was better compared with that before treatment, but the movement disorder was not significantly improved. Conclusion: This case confirmed the causal mutation of SLC18A2 gene and brain dopamine-serotonin vesicular transport disease, which suggested the mechanism of UPD homozygous formation, and confirmed that dopamine agonist treatment could improve some symptoms in affected individuals. [ABSTRACT FROM AUTHOR]

Purpose: The dopamine agonists (DA) have been used widely to treat prolactinomas. However, it is difficult to predict whether the patient will be responsive to DA treatment. Methods: We aimed to investigate whether the in vivo expression of DRD2 based on 18F-fallypride PET/MR could predict the therapeutic effect of DA on prolactinomas. Seven patients with prolactinomas completed 18F-fallypride PET/MR. Among them, three patients underwent surgery and further tumor immunohistochemistry. Imaging findings and immunohistochemical staining were compared with treatment outcomes. Results: 18F-fallypride PET/MR was visually positive in 7 of 7 patients, and DRD2 target specificity could be confirmed by immunohistochemical staining. A significantly lower tracer standard uptake value (SUV) could be detected in the resistant patients (n = 3) than in the sensitive patients (n = 4; SUVmean, 4.67 ± 1.32 vs. 13.57 ± 2.42, p < 0.05). DRD2 expression determined by 18F-fallypride PET/MR corresponded with the DA treatment response. Conclusion: 18F-fallypride PET/MR may be a promising technique for predicting DA response in patients with prolactinoma. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effect of the different dry-off strategies based on reducing feeding level (normal vs. reduced energy density), reducing milking frequency (twice vs. once daily), and administration of a dopamine agonist after last milking (i.e. saline vs. cabergoline injection) on blood metabolites, hormones, and minerals around dry-off. In this experiment, 119 Holstein dairy cows were used in a 2 × 2 × 2 factorial arrangement. In the last week before dry-off, cows were allocated to 1 of the 4 possible dry-off strategies based on feeding level and milking frequency. Within 3 h after last milking, cows were injected with either saline or a D 2 dopamine agonist (cabergoline; Velactis, Ceva Santé Animale, Libourne, France; labeled for use only with abrupt dry-off, e.g., no preceding reduction in feeding level or milking frequency before last milking). After dry-off, all cows were fed the same dry cow diet and data collection continued for a week. Blood samples were collected from the coccygeal vein on d −9, −6, −5, −2, 1, 2, 5, and 7 relative to dry-off. Additionally, blood was sampled at 0, 3, and 6 h relative to injection of either cabergoline or saline, equivalent to d 0.125, 0.250, and 0.375 relative to last milking (dry-off). The reduced feeding level before dry-off caused reduced glucose and insulin concentrations as well as increased free fatty acid concentrations, particularly when reduced feeding level was combined with milking the cows 2× daily. The intramuscular injection of cabergoline caused the expected reduction in circulating prolactin concentrations. In addition, dopamine-agonist cabergoline induced an atypical simultaneous pattern of plasma metabolites (i.e., increased glucose and free fatty acid concentrations), hormones (i.e., reduced insulin and increased cortisol concentrations), and minerals (i.e., reduced calcium concentration), indicating that normal metabolic and mineral homeostatic regulations were hindered after the injection of ergot alkaloid cabergoline. In conclusion, reducing milking frequency seems the best management strategy to reduce milk production at dry-off among those tested in this study. [ABSTRACT FROM AUTHOR]

Purpose: Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline. Methods: We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal. Results: Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases. Conclusions: Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue. [ABSTRACT FROM AUTHOR]