Spontaneous coronary artery dissection in association with cabergoline therapy.

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognised cause of acute coronary syndrome. While numerous risk factors are associated with SCAD, one potential cause is coronary artery vasospasm. The use of cabergoline-an ergot derivative and dopamine agonist that may induce vasospasm-has been associated with SCAD in one other case report worldwide. Here, we describe SCAD in a 37-year-old woman on long-term cabergoline therapy with no other cardiac risk factors. Cabergoline-induced SCAD should be considered in patients presenting with an acute coronary syndrome who are treated with this medication.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study.

INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Incidence of Cabergoline-Associated Valvulopathy in Primary Care Patients With Prolactinoma Using Hard Cardiac Endpoints.

BACKGROUND: Controversy exists as to whether low-dose cabergoline is associated with clinically significant valvulopathy. Few studies examine hard cardiac endpoint data, most relying on echocardiographic findings. OBJECTIVES: To determine the prevalence of valve surgery or heart failure in patients taking cabergoline for prolactinoma against a matched nonexposed population. DESIGN: Population-based cohort study based on North East London primary care records. METHODS: Data were drawn from ~1.5 million patients' primary care records. We identified 646 patients taking cabergoline for >6 months for prolactinoma. These were matched to up to 5 control individuals matched for age, gender, ethnicity, location, diabetes, hypertension, ischemic heart disease, and smoking status. Cumulative doses/durations of treatment were calculated. Cardiac endpoints were defined as cardiac valve surgery or heart failure diagnosis (either diagnostic code or prescription code for associated medications). RESULTS: A total of 18 (2.8%) cabergoline-treated patients and 62 (2.33%) controls reached a cardiac endpoint. Median cumulative cabergoline dose was 56 mg (interquartile range [IQR] 27-123). Median treatment duration was 27 months (IQR 15-46). Median weekly dose was 2.1 mg. Neither univariate nor multivariate analysis demonstrated a significant association between cabergoline treatment at any cumulative dosage/duration and an increased incidence of cardiac endpoints. In a matched analysis, the relative risk for cardiac complications in the cabergoline-treated group was 0.78 (95% CI, 0.41-1.48; P = 0.446). Reanalysis of echocardiograms for 6/18 affected cabergoline-treated patients showed no evidence of ergot-derived drug valvulopathy. CONCLUSIONS: The data did not support an association between clinically significant valvulopathy and low-dose cabergoline treatment and provide further evidence for a reduction in frequency of surveillance echocardiography.

Cardiac valvular abnormalities associated with use and cumulative exposure of cabergoline for hyperprolactinemia: the CATCH study.

BACKGROUND: Whether lower dose cabergoline therapy for hyperprolactinemia increases risk of valvular dysfunction remains controversial. We examined valvular abnormalities among asymptomatic adults with hyperprolactinemia treated with dopamine agonists. METHODS: This cross-sectional study was conducted among adults receiving cabergoline or bromocriptine for > 12 months for hyperprolactinemia and had no cardiac-related symptoms. Cardiac valve morphology and function were assessed from transthoracic echocardiograms at the study visit (except for two participants) with evaluation performed blinded to type and duration of dopamine agonist received. RESULTS: Among 174 participants (mean age 49 ± 13 years, 63% women) without known structural heart disease before starting therapy, 62 received only cabergoline, 63 received only bromocriptine, and 49 received both. Median cabergoline use was 2.8 years in cabergoline only users and 3.2 years for those exposed to both cabergoline and bromocriptine; median bromocriptine use was 5.5 years in bromocriptine only users and 1.1 years for those exposed to both cabergoline and bromocriptine. Compared with bromocriptine only users (17.5%), regurgitation of ≥1 valve was more common for cabergoline only (37.1%, P = 0.02) but not for combined exposure (26.5%, P = 0.26). Compared with bromocriptine only exposure (1.6%), regurgitation of ≥2 valves was more common for cabergoline only (11.3%, P = 0.03) and combined exposure (12.2%, P = 0.04). Cabergoline only users had higher age-sex-adjusted odds for ≥1 valve with grade 2+ regurgitation compared to bromocriptine only users (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI]:1.3-7.5, P = 0.008), but the association for combined exposure to cabergoline and bromocriptine was not significant (aOR 1.7, 95%CI:0.7-4.3, P = 0.26). Compared to bromocriptine only, age-sex-adjusted odds of ≥2 valves with grade 2+ regurgitation were higher for both cabergoline only (aOR 8.4, 95% CI:1.0-72.2, P = 0.05) and combined exposure (aOR 8.8, 95% CI:1.0-75.8, P = 0.05). Cumulative cabergoline exposure > 115 mg was associated with a higher age-sex adjusted odds of ≥2 valves with grade 2+ regurgitation (aOR 9.6, 95%CI:1.1-81.3, P = 0.04) compared to bromocriptine only. CONCLUSIONS: Among community-based adults treated for hyperprolactinemia, cabergoline use and greater cumulative cabergoline exposure were associated with a higher prevalence of primarily mild valvular regurgitation compared with bromocriptine. Research is needed to clarify which patients treated with dopamine agonists may benefit from echocardiographic screening and surveillance.

Safety of Cabergoline for Postpartum Lactation Inhibition or Suppression: A Systematic Review.

This study sought to perform a systematic review of adverse events reported with the use of cabergoline for postpartum lactation inhibition or suppression in women aged 15 to 50. Following registration with PROSPERO (CRD42017049894), a comprehensive search of the Ovid databases Medline, Embase, and CENTRAL, along with PubMed, was conducted from January 1, 1985 to January 25, 2018. All study designs investigating cabergoline use for postpartum lactation inhibition or suppression in women aged 15 to 50 were included. A total of 695 articles were retrieved, and 25 articles were eligible for inclusion. Adverse events were then reported in terms of frequency, with percentages calculated according to the total number of women exposed to the intervention. A bias assessment of the articles was also performed. Among a total of 757 women, 108 adverse events were observed in 96 women (14.2%). The most common adverse events were dizziness (35 of 757), headache (30 of 757), and nausea or vomiting (19 of 757). These events were described as short-lived, self-resolving, and dose dependent. One pharmacovigilance study reported 29 "serious" events from a total of 175 events in 72 case reports, which included thromboembolic and neurologic events. Four case studies specifically addressed the psychiatric population, with one half reporting psychiatric symptoms following administration of cabergoline. In conclusion, this systematic review demonstrates that adverse events were generally benign and tolerable following the administration of cabergoline. However, pharmacovigilance data reveal that vigilance is still needed given the occurrence of rare but serious events.

Case of fertility treatment-induced Stevens-Johnson syndrome with a severe ocular complication.

Pharmacological regimens with multiple medications are being used in fertility treatments. Herein, we report a case of a 40-year-old Japanese woman who developed Stevens-Johnson syndrome (SJS) with a severe ocular complication during fertility treatment. Despite early multimodal interventions, including methylprednisolone pulse therapy and plasma exchange, her ocular complications persisted for more than a year. The four drugs administered in this case (cabergoline, medroxyprogesterone acetate, clomiphene, and intravenous human chorionic gonadotropin) have never been reported to induce SJS. Based on this case, we suggest that obstetricians, gynecologists, and dermatologists should be aware of fertility treatment-induced severe drug eruptions.

Start low, go slowly - mental abnormalities in young prolactinoma patients under cabergoline therapy.

Background Prolactin-secreting pituitary adenomas in childhood and adolescence are rare. First-line therapy consists of dopamine agonists (DAs) like cabergoline. Experience in treating prolactinomas in paediatric and adolescent patients is limited. Methods This study was a retrospective analysis of clinical data, laboratory data, radiological findings and medical treatment of paediatric and adolescent patients with prolactinomas between 2009 and 2018. Results Our cohort of nine patients had a median age at diagnosis of 13 years (range 5-17). Main presenting symptoms were weight gain, disorders of the pituitary-gonadal axis and headache. Treatment with cabergoline resulted in a marked reduction in prolactin concentration in all nine patients. Tumour mass reduction was confirmed by magnetic resonance imaging (MRI) scan in seven patients. Noteworthy is that cabergoline therapy triggered frequent adverse effects in a total of eight patients - seven of whom suffered from mental disorders, five of whom had neurological symptoms and five of whom had gastrointestinal problems. The adverse effects occurred at a median dose of only 0.5 mg/week (range 0.25-2.0). Most symptoms were alleviated after the cabergoline dose was lowered. Therapy discontinuation was not necessary in any patient. Conclusions Cabergoline effectively lowers prolactin levels and may reduce tumour mass in paediatric and adolescent patients with prolactinomas. Potential adverse effects may include mental disorders and behavioural problems even at low cabergoline doses. Low starting doses and careful individual dose adjustments are required to enable therapy adherence.

Giant cabergoline-resistant prolactinoma in a man who presented with a psychotic episode during treatment: a case report.

BACKGROUND: Prolactinomas are tumors of the pituitary gland that usually respond very well to treatment with cabergoline. Resistance to cabergoline is very rare, but when it occurs, it is a difficult problem to resolve if the tumor is inoperable. CASE PRESENTATION: A 62-year-old white man was treated for a giant macroprolactinoma detected during investigation of a subacute subdural hematoma of the left frontal lobe. The patient was treated with cabergoline for 17 years with a dose ranging from 1.0 mg to 3.5 mg per week. We were not able to normalize his prolactin level, which initially was 14,992 ng/ml and ultimately 1754 ng/ml. The tumor significantly shrank during the follow-up period but persisted. The patient had cardiac valvulopathies that did not worsen. He had an ischemic stroke and developed a psychotic condition that was successfully treated by lowering the cabergoline and administering quetiapine and mirtazapine together. This regimen led to a small increase in the patient's prolactin that returned to previous levels and remained as such until the last medical evaluation. The tumor continued to shrink and had a cystic degeneration in the last evaluation. CONCLUSIONS: Combined use of cabergoline with quetiapine and mirtazapine to treat a psychotic crisis may have contributed to shrinking the tumor in our patient because these antipsychotics have action mediated by growth factors that interfere with growth of pituitary tumors.

Status epilepticus induced by treatment with dopamine agonist therapy for giant prolactinoma: a case report.

BACKGROUND: Dopamine agonists are the standard first-line medical therapy for prolactinoma. We report a rare case of giant prolactinoma with a first epileptic seizure due to rapid reduction of the tumor as a complication of dopamine agonist therapy. CASE PRESENTATION: A 27-year-old Japanese man presented to our institution with a history of visual disturbance for 1 year and general fatigue for 3 months. Magnetic resonance imaging showed a tumor that arose from the pituitary and extended to the bilateral anterior skull base, the clivus, and the cavernous sinus, with compression of the optic chiasm and the bilateral frontal and temporal lobes. On the basis of the patient's serum concentration of prolactin, we diagnosed a prolactinoma and started dopamine agonist therapy with cabergoline. The patient had a general seizure immediately after starting dopamine agonist therapy and required general anesthetic treatment following the rapid reduction of the tumor. We speculated that the rapid reduction of the tumor resulted in the retraction of the surrounding brain structure, and the epileptic seizure was then induced by dopamine agonist therapy. CONCLUSIONS: We report a rare case of giant prolactinoma with a first epileptic seizure immediately after the initiation of dopamine agonist therapy. Clinicians need to be aware that the rapid reduction of a giant prolactinoma by dopamine agonist therapy may cause an epileptic seizure.

Endonasal Chiasmapexy Using Autologous Cartilage/Bone for Empty Sella Syndrome After Cabergoline Therapy for Prolactinoma.

BACKGROUND: Visual field deterioration caused by secondary empty sella after cabergoline therapy for prolactinoma is a rare event. Chiasmapexy is performed to treat empty sella syndrome. Although various materials have been used for the elevation of the optic chasm, the most appropriate material remains to be established. Here, we describe the efficiency of chiasmapexy for empty sella syndrome following dopamine agonist treatment and the utility of septal cartilage and sphenoidal sinus bone as materials for chiasmapexy. CASE DESCRIPTION: A 35-year-old male with a history of cabergoline therapy for prolactinoma presented with visual deterioration. His magnetic resonance imaging revealed optic chiasm herniation into the empty sella. Endoscopic endonasal transsphenoidal chiasmapexy was performed using septal cartilage and sphenoidal sinus bone as materials for elevating the chiasm. Visual function improved immediately after operation. CONCLUSIONS: Chiasmapexy is an effective surgical method for treating visual deterioration caused by empty sella after cabergoline treatment. Endoscopic endonasal chiasmapexy with septal cartilage and sphenoidal sinus bone is a considerable option because it is minimally invasive and involves decreased risk of infection.

Pituitary Apoplexy in Long-Term Cabergoline User During Thrombocytopenia Due to Chemotherapy for Chronic Myelocytic Leukemia.

BACKGROUND: Pituitary apoplexy (PA) is a life-threatening syndrome. The usage of a dopamine agonist, such as bromocriptine or cabergoline, is considered a predisposing factor for PA, which commonly occurs 1.5 years within commencement. CASE DESCRIPTION: A 64-year-old female with a >15-year history of cabergoline therapy for pituitary prolactinoma was referred to our department of neurosurgery after complaining of headache, blurred vision, diplopia, and ptosis for 3 days during hospital admission for chemotherapy of chronic myelocytic leukemia. Computed tomography and magnetic resonance imaging revealed findings indicative of PA. As the patient was experiencing thrombocytopenia related to chemotherapy, blood transfusion was preceded, and after a platelet count of 15.0 × 104/µL was confirmed, transnasal neuroendoscopic surgery was performed 5 days from the onset of symptoms. The majority of the prolactinoma was removed, and the prolactinoma in the cavernous sinus was intentionally left. The postoperative course was generally good. The ptosis and diplopia improved, and the blurred vision resolved. CONCLUSIONS: PA related to dopamine agonist therapy can occur in cases of elevated bleeding tendency, even in long-term users, suggesting that attention should be paid in the administration of a dopamine agonist in the patient experiencing thrombocytopenia. Surgical intervention should be performed after the preoperative platelet number and adequate response to transfusion are confirmed, and the aggressive removal of prolactinoma in the cavernous sinus should be avoided to reduce the risk of hemorrhagic complications.

[Drug-induced valve heart disease]. / Valvulopathies médicamenteuses.

Drug-induced valve heart disease. Numerous reports have shown an unquestionable association between fibrotic valve heart disease (VHD) and the following drugs: ergot alkaloids (methysergide and ergotamine), ergot-derived dopaminergic agonists (pergolide and cabergoline) and drugs metabolized into norfenfluramine (fenfluramine, dexfenfluramine and benfluorex). These drugs have a common pharmacological action on a specific serotonin receptor - the 5HT2B receptor leading to VHD. All four valves can be affected, but the mitral and aortic valves are predominantly involved. Echocardiography is the method of choice to detect these VHD and evaluate its severity. The most characteristic feature is restriction of valve motion, mainly responsible for regurgitation. Histological examination is typical, but rarely available. Drug-induced VHD may be severe, requiring cardiac surgery. The subsequent course is not well documented, varies from one patient to another, with the possibility of regression, stabilisation or deterioration.

Valvulopathies médicamenteuses. Les valvulopathies médicamenteuses sont dues à un effet agoniste de certains médicaments sur les récepteurs cardiaques sérotoninergiques 5-HT2B. Les substances associées à leur survenue sont le méthysergide, l'ergotamine, la fenfluramine, la dexfenfluramine, le pergolide, la cabergoline, le benfluorex et l'ecstasy. Les valvulopathies médicamenteuses sont caractérisées par la présence d'une fibrose engainant les valves cardiaques. Elles sont à l'origine de fuites valvulaires essentiellement du coeur gauche, parfois associées à des sténoses valvulaires. Les atteintes polyvalvulaires sont fréquentes. L'échographie Doppler cardiaque est l'examen diagnostique clé car la clinique est peu sensible et peu spécifique. Les signes échographiques sont un épaississement valvulaire, une rétraction valvulaire et un mouvement valvulaire restrictif systolo-diastolique. Les formes frustes sont fréquentes. L'aspect anatomopathologique est caractéristique, mais rarement disponible. Les formes graves sont rares et peuvent nécessiter un remplacement valvulaire. L'évolution des valvulopathies médicamenteuses est mal connue, variable d'un patient à l'autre, avec possibilité de diminution, de stabilisation ou d'aggravation.