Drug induced hypoprolactinemia.

Prolactin levels can be influenced by multiple medications primarily through the interaction with dopamine receptors which regulate its secretion. Unlike hyperprolactinemia which has a well-defined clinical phenotype, the effects of hypoprolactinemia beyond inability to lactate are incompletely understood. Recent studies have raised concerns regarding detrimental changes in glucose metabolism, sexual function and psychological profile in patients with low prolactin levels. In contrast with anatomic and genetic etiologies, drug-induced hypoprolactinemia is usually reversible after dose reduction of the offending medication. The most common clinical scenario of drug-induced hypoprolactinemia in the endocrine clinic pertains to patients treated with cabergoline or bromocriptine for prolactin-secreting or other types of pituitary adenomas. Also, data has accumulated regarding hypoprolactinemia in patients receiving aripiprazole for schizophrenia and other psychiatric disorders. These patients warrant careful evaluation for comorbidities. This review aims to increase awareness about the potentially detrimental effects of drug-induced hypoprolactinemia, which should be considered in clinical practice decisions.

Efficacy of Metformin-Cabergoline Compared to Metformin Monotherapy for Management of PCOS With Hyperprolactinemia: A Systematic Review and Meta-analysis.

Background: Metformin plays a major part in the treatment of polycystic ovarian syndrome .Trials are being conducted to compare the effectiveness of combination of metformin with cabergoline in the treatment of hyperprolactinemia and polycystic ovarian syndrome. Objectives: The purpose of this study is to compare the effectiveness of metformin monotherapy and combination therapy with cabergoline versus metformin for the management of polycystic ovarian syndrome with hyperprolactinemia. Methodology: An extensive search up until 31 May 2024 of electronic databases (PubMed, Registry of Controlled Clinical Trials, Web of Sciences, SCOPUS) to find pertinent studies. An analysis was conducted with both observational data and randomized clinical trials . To compute the standard mean difference, weighted mean difference, odds ratio, and 95% confidence interval, RevMan (v5.3) was utilized. Primary outcomes that were assessed included body-mass index, regular menstruation, weight change, prolactin, testosterone, and dehydroepiandrosterone-sulfate levels. Results: Three randomized controlled trials and 1 observational study, taking a total patient population of n = 535, were part of our final analysis. Prolactin (SMD = -3.23 95% CI: (-4.90, -1.55)) and dehydroepiandrosterone-sulfate levels (SMD = -0.27 95% CI: (-0.52, -0.01)) were significantly lower in the metformin and cabergoline combination therapy group; monthly regularity was also significantly higher (OR = 3.07 95% CI: (2.09, 4.51)). Statistically, there was no significant difference in weight, body-mass index, or testosterone levels. Conclusions: In the treatment of polycystic ovarian syndrome, the combination of metformin and cabergoline significantly lowers prolactin levels and encourages regular menstrual cycles. Although metformin has the potential to suppress testosterone levels, more investigation is required to determine how combination therapy affect dehydroepiandrosterone-sulfate and testosterone levels. It's interesting to note that while neither intervention had a substantial impact on weight or body-mass index, metformin and cabergoline combination therapy outperformed metformin monotherapy in terms of supporting regular menstrual cycles. Customized therapy approaches are essential, and large-scale trials involving a variety of groups are required to comprehend the safety and effectiveness of treatments.

Efficacy of metformin compared to metformin and cabergoline combination In this study, 2 therapies for women with high prolactin levels­a hormone associated with PCOS­were examined. Their goal was to determine which combination of metformin and cabergoline produced the best results.Observational data and randomized clinical trials were included while searching through several databases for pertinent studies. Researchers discovered that the combination of metformin and cabergoline was superior to using metformin alone in reducing prolactin and another hormone called DHEAS. The menstrual periods of women receiving the combined therapy were also more regular. However, there wasn't much difference in weight, body mass index (BMI), or testosterone levels between the 2 groups. In summary, it appears that the combination of cabergoline and metformin is a more effective way to treat the symptoms of PCOS, which include irregular periods and elevated prolactin levels. To find out how it impacts other hormones and whether it's long-term safe and effective, further research is still required.

The effect of intravenous Calcium gluconate on the prevention of Ovarian Hyperstimulation Syndrome. (A randomized clinical trial).

OBJECTIVE: Oral Cabergoline and intravenous Calcium have the potential to prevent Ovarian Hyperstimulation Syndrome (OHSS) in assisted reproductive technology by regulating the activity of the Vascular Endothelial Growth Factor (VEGF) receptor. The purpose of this study was to examine the effect of Cabergoline with intravenous Calcium versus oral Cabergoline alone on the overall rate of OHSS. METHODS: This study is a randomized clinical trial which was carried out in Milad Infertility Center affiliated with Mashhad University of Medical Sciences, Mashhad, Iran between April 2016 and January 2018. A total of 192 patients were randomly assigned into two groups. The control group received oral Cabergoline and the intervention group received Calcium gluconate in addition to Cabergoline. A total rate of OHSS, moderate and severe OHSS were measured in both groups. RESULTS: The demographic characteristics of the participants and the types of drugs used showed homogeneity between the intervention and control groups (p>.05). Furthermore, there was no significant difference between the two groups in terms of the number of the follicle, oocytes obtained, metaphase II oocytes, the number of embryos, and the rate of fertilization. Regarding the incidence of OHSS, 26.2% of participants in the control group experienced OHSS, while the occurrence rate was 15.7% in the intervention group (P =.401). The incidence of severe OHSS in the control group and intervention group was 7.1% and 3.6%, respectively. CONCLUSION: Intravenous injection of Calcium gluconate can be effective in preventing Ovarian Hyperstimulation Syndrome.

Pituitary apoplexy: a comprehensive analysis of 93 cases across functioning and non-functioning pituitary adenomas from a single-center.

INTRODUCTION: Pituitary apoplexy (PA) is a rare clinical syndrome due to acute/subacute pituitary hemorrhage and/or infarction; data on PA in functioning pituitary adenoma (FPA) is scarce. METHODS: A retrospective record-review of details of PA in non-functioning (NFPA) and FPA managed at tertiary endocrine center. RESULTS: 93 patients [56 males; 33.3% FPA: 5 acromegaly, 14 prolactinoma, and 12 Cushing's Disease (CD)] diagnosed with PA were included. Median age was 40 years, with younger age of presentation in FPA. Type A (acute) [49.5%] and headache (78.5%) were the commonest presentations, with PA being the initial manifestation in 98.4% of NFPA. Median (range) Pituitary Apoplexy Score (PAS) was 2 (0-8). Median tumor diameter was 2.5 cm, with larger tumors in FPA (3.2 cm vs. 2.3 cm). 29 (46.7%) NFPA-PA and 14 (45.2%) FPA-PA patients [71% prolactinoma, 33% in CD, and none in acromegaly] were conservatively managed. In the NFPA cohort, those managed surgically had significantly higher PAS (4 vs. 1) and larger tumor size (2.6 vs. 1.8 cm); however, both arms had comparable recovery of neuro-visual, radiological, and hormonal outcomes. In FPA cohort, CD and acromegaly required definitive treatment, whereas prolactinomas were effectively managed (clinical and biochemical recovery) with oral cabergoline and glucocorticoids. Matching PAS cohorts (to overcome allocation bias for management approach) in macroadenomas (excluding prolactinoma) showed comparable neuro-deficit and hormonal recovery between surgical and conservative approaches. CONCLUSION: PA in FPA has distinct features and management issues. Carefully selected patients (PAS guided) in NFPA with PA for conservative management have comparable outcomes to surgery.

A Peculiar Case of Cabergoline Response to a Non-functioning Cystic Pituitary Adenoma in a Young Adult Male.

We present an interesting case of a cystic, pituitary adenoma that showed up insidiously with non-traditional clinical symptoms. The standard of care for non-functioning pituitary adenomas is transsphenoidal surgery. However, with pharmacotherapy using cabergoline (a dopamine receptor agonist), the patient had a near disappearance of the tumor. This case report seeks to add to the medical literature the possibility of pharmacotherapy for treating non-functional pituitary adenomas.

Intraoperative Takotsubo Syndrome.

Takotsubo cardiomyopathy is a rare condition that presents a diagnostic challenge due to its close resemblance to acute myocardial ischemia and other cardiac disorders. The excessive production of catecholamines triggers abnormal and severe changes in the myocardium, typically resulting in significant dyskinesia of the left ventricle's apex, reduced ejection fraction, hypotension, and pulmonary edema. Recent reports suggest that potential risk factors may include postmenopausal syndrome and intense, unexpected stress, whether related to life events or medical conditions. Complications such as heart failure, thrombosis, and severe arrhythmias are infrequent and more likely to occur in patients with pre-existing cardiac conditions. We present the case of a 22-year-old woman who developed intraoperative Takotsubo cardiomyopathy during a transsphenoidal resection of a prolactin-secreting pituitary tumor under general anesthesia. Perioperative combination of cabergoline and oxymetazoline induced intraoperative hypertension, pulmonary edema, and Takotsubo stress cardiomyopathy. To our knowledge, this is the first reported case in the literature of intraoperative Takotsubo cardiomyopathy, potentially linked to the specific combination of intraoperative cabergoline and oxymetazoline.

Medical treatment of acromegaly - When the tumor size matters: A narrative review.

Medical treatment of acromegaly is generally positioned as a second line of treatment after pituitary adenoma surgery. With the rising availability and variety of medications for acromegaly increases our understanding of their effectiveness and safety. Volume of the published data on the impact of medical therapy on biochemical control of acromegaly, contrasts a relative lack of publications which comprehensively address pituitary tumor alterations under different drug modalities. Assessment of changes in GH-secreting adenoma volume is often overshadowed by clinicians' focus on GH and IGF-I levels during acromegaly treatment. Close analysis of studies published in the last two decades, reveals that both an increase and decrease in somatotropinoma volume are possible during treatment with any of available drugs for acromegaly. Changes in pituitary tumor size may arise from the biological nature of adenoma itself, independently of the administered medications. Therefore, an individual approach is necessary in the treatment of patients with acromegaly, based on repeated insight to their clinical, biochemical, pathological and imaging characteristics. In this review, we summarize and comment how pituitary tumor size is affected by the treatment with all currently available drugs in acromegaly: long-acting somatostatin receptor ligands of the first generation (octreotide LAR and lanreotide autogel) and the second generation (pasireotide-LAR), as well as pegvisomant (PEG) and cabergoline (CAB).

Visual morbidity in macroprolactinoma: A retrospective cohort study.

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

Calcium versus cabergoline for prevention of ovarian hyperstimulation syndrome: A systematic review and meta-analysis.

AIM: To conduct the first-ever systematic review and meta-analysis evaluating calcium infusion versus cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) among high-risk women undergoing assisted reproductive technology. METHODS: Six databases were screened from inception until April 1, 2024. The included randomized and non-randomized controlled studies were assessed for quality. The endpoints included the severity of OHSS and selected pregnancy-related outcomes. Endpoints were summarized as risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. RESULTS: Six studies were analyzed, including 1687 patients (828 in the calcium group and 859 in the cabergoline group). The quality of the studies varied and reflected low risk and high risk of bias in two and four studies, respectively, according to the revised Cochrane risk of bias tool. No significant differences were noted between both groups regarding the rates of overall (n = 5, RR = 0.65, 95 % CI [0.39, 1.07], p = 0.09), mild (n = 4, RR = 1.05, 95 % CI [0.59, 1.89], p = 0.86), moderate (n = 5, RR = 0.41, 95 % CI [0.15, 1.08], p = 0.07), and severe (n = 6, RR = 0.36, 95 % CI [0.11, 1.22], p = 0.1) cases of OHSS. Leave-one-out sensitivity analysis of an outlier study revealed that calcium significantly reduced the occurrence of severe OHSS compared with cabergoline (n = 5, RR = 0.16, 95 % CI [0.09, 0.43], p < 0.001, Higgins I2 = 0 %). No significant differences were observed between both groups regarding the rates of clinical pregnancy (n = 4, RR = 0.97, 95 % CI [0.88, 1.07], p = 0.57), ongoing pregnancy, live birth, and spontaneous abortion (Higgins I2 < 50 % for all). CONCLUSION: Both agents yielded similar pregnancy-related outcomes. However, calcium infusion could potentially be more effective than cabergoline in reducing the rate of severe OHSS. Additional high-quality and well-controlled trials are essential to draw firm conclusions.

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

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

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

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

Revealing New Prospects: Antipsychotic Drugs Exert Anti-Tumor Effects against Gastric Cancer through Inducing Apoptosis.

BACKGROUND AND OBJECTIVE: Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC. METHODS: The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining. RESULTS: Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells. CONCLUSION: Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer.

Targeting HTR2B suppresses non-functioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

Diagnosis and Dental Management of a Patient With Forbes Albright Syndrome: A Report of a Rare Case.

Forbes Albright syndrome is a hyperprolactinemia syndrome linked to a pituitary tumor associated with galactorrhea and amenorrhea. Cabergoline, an ergot derivative, is its drug of choice. Here, we report the oral manifestations and management of a case of a 32-year-old female, diagnosed and treated with the same. The patient had an alarming increase in the incidence and progression of dental caries. Her diagnosis and management have been highlighted. This can have overbearing effects on the psychology and function of the individual, thus making early diagnosis and precise management important.

Cardiometabolic effects of hypoprolactinemia.

The fall of PRL levels below the lower limit of the normal range configures the condition of hypoprolactinemia. Unlike PRL excess, whose clinical features and treatments are well established, hypoprolactinemia has been only recently described as a morbid entity requiring prompt identification and proper therapeutic approach. Particularly, hypoprolactinemia has been reported to be associated with the development of metabolic syndrome and impaired cardiometabolic health, as visceral obesity, insulin-resistance, diabetes mellitus, dyslipidaemia, chronic inflammation, and sexual dysfunction have been found more prevalent in patients with hypoprolactinemia as compared to those with normoprolactinemia. This evidence has been collected mainly in patients on chronic treatment with dopamine agonists for PRL excess due to a PRL-secreting pituitary tumour, and less frequently in those receiving the atypical antipsychotic aripiprazole. Nowadays, hypoprolactinemia appears to represent a novel and unexpected risk factor for cardiovascular diseases, as is the case for hyperprolactinemia. Nevertheless, current knowledge still lacks an accurate biochemical definition of hypoprolactinemia, since no clear PRL threshold has been established to rule in the diagnosis of PRL deficiency enabling early identification of those individual subjects with increased cardiovascular risk directly ascribable to the hormonal imbalance. The current review article focuses on the effects of hypoprolactinemia on the modulation of body weight, gluco-insulinemic and lipid profile, and provides latest knowledge about potential cardiovascular outcomes of hypoprolactinemia.

Dopamine receptor agonist cabergoline promotes immunogenic phenotype in human monocyte-derived dendritic cells.

Dendritic cells (DCs) are known as antigen-presenting cells that are capable of regulating immune responses. DCs and T cells can interact mutually to induce antigen-specific T-cell responses. Cabergoline, which is a dopamine (DA) receptor agonist, seems to implement anti-inflammatory properties in the immune system, and therefore in the present study the impact of a DA receptor agonist cabergoline on the monocyte-derived DCs (moDCs) was assessed. Immature moDCs were treated with lipopolysaccharide to produce mature DCs (mDCs). The expression of DCs' related surface markers namely: CD11c, HLA-DR, and CD86 was measured by utilizing of flow cytometry. Real-time PCR was the technique of choice to determine the levels at which diverse inflammatory and anti-inflammatory factors in cabergoline-treated and control mDC groups were expressed. DCs treated with cabergoline displayed a significant decrease in CD86 and HLA-DR expression, markers linked to maturation and antigen presentation, respectively. In addition, the cabergoline-mDC group showed a considerable decline in terms of the levels at which IL-10, TGF-ß, and IDO genes were expressed, and an increase in the expression of TNF-α and IL-12 in comparison to the mDC control group. Our findings revealed that cabergoline as an immunomodulatory agent can relatively shift DCs into an immunogenic state, and there is a requirement for further investigations to evaluate the effects of cabergoline-treated DCs on the T cell responses in vitro, and also in various diseases including cancer in animal models.

Comparative efficacy of metformin combined with cabergoline versus metformin alone in patients with PCOS and hyperprolactinemia: A systematic review and meta-analysis of randomized controlled trials.

Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive years. Metformin (MET) has been shown to improve ovarian function in PCOS-related conditions, while cabergoline is recognized for its powerful and sustained ability to reduce prolactin levels. This study investigates the potential impact of combining cabergoline with metformin while comparing it with metformin alone in the treatment of PCOS alongside hyperprolactinemia. METHOD: To gather data, we searched PubMed, Google Scholar, ScienceDirect, and Cochrane Central. Eligible studies were randomized controlled trials involving patients with PCOS and hyperprolactinemia. Outcome measures included changes in the levels of prolactin, testosterone, DHEAS, BMI and menstrual irregularities. RevMan version 5.4 was used to analyze outcomes. RESULT: This study incorporated three Randomized Controlled Trials (RCTs) involving 405 participants in total. Patients receiving a combination of metformin and cabergoline experienced significant reductions in prolactin and testosterone levels (p= <0.0001 and p=<0.0001, respectively). Conversely, alterations in DHEAS levels and BMI did not reach statistical significance (p = 0.19 and p = 0.71, respectively). Notably, women solely prescribed metformin exhibited significantly higher rates of menstrual irregularities compared to those receiving both metformin and cabergoline (p=<0.0001). CONCLUSION: Our analysis underscores the synergistic effect achieved by pairing metformin and cabergoline in patients with PCOS and hyperprolactinemia. However, we encountered only a restricted number of studies meeting our criteria. It is imperative to consistently assess the combined effects of metformin and cabergoline to gain deeper insights into their effectiveness in addressing PCOS and hyperprolactinemia.

Identification and structural elucidation of an oxidation product generated during stability studies of Cabergoline drug product.

Cabergoline is a dopamine agonist with applications as anti-Parkinson drug and prolactin inhibitor. The cabergoline drug product Laktostop® 50 µg/mL is used in veterinary medicine for lactation suppression in cats and dogs e.g. during false pregnancy. Recently, during ongoing HPLC stability testing of Laktostop® 50 µg/mL a new oxidation product of Cabergoline was identified. A synthesis starting from Cabergoline was developed, followed by full characterization of the unknown impurity. Preliminary HPLC and LC-MS analyses indicated the unknown impurity as mono-oxygenated product of Cabergoline (Cabergoline N-oxide) that is presumably formed with oxygen by a radical mechanism. Thus, Cabergoline was treated with oxidizing agents such as m-chloroperoxybenzoic acid to afford the desired Cabergoline-N-oxide as a byproduct. After isolation by column chromatography, NMR and LC-MS-MS studies provided evidence that oxidation occurred at the N-allyl nitrogen of Cabergoline to form Cabergoline-N-oxide. © 1905 Elsevier Science. All rights reserved.

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

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

Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE).

PURPOSE: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). METHODS: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018-2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. RESULTS: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. CONCLUSIONS: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.