Dose Of Cabergoline Research Articles

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma.

Background:Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear.Objective:The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used.Design:A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma.Results:Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves.Conclusion:Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure.

Cabergoline for Cushing’s disease: a large retrospective multicenter study

The efficacy of cabergoline in Cushing's disease (CD) is controversial. The aim of this study was to assess the efficacy and tolerability of cabergoline in a large contemporary cohort of patients with CD. We conducted a retrospective multicenter study from thirteen French and Belgian university hospitals. Sixty-two patients with CD received cabergoline monotherapy or add-on therapy. Symptom score, biological markers of hypercortisolism and adverse effects were recorded. Twenty-one (40%) of 53 patients who received cabergoline monotherapy had normal urinary free cortisol (UFC) values within 12 months (complete responders), and five of these patients developed corticotropic insufficiency. The fall in UFC was associated with significant reductions in midnight cortisol and plasma ACTH, and with clinical improvement. Compared to other patients, complete responders had similar median baseline UFC (2.0 vs 2.5xULN) and plasma prolactin concentrations but received lower doses of cabergoline (1.5 vs 3.5 mg/week, P < 0.05). During long-term treatment (>12 months), cabergoline was withdrawn in 28% of complete responders because of treatment escape or intolerance. Overall, sustained control of hypercortisolism was obtained in 23% of patients for 32.5 months (19-105). Nine patients on steroidogenesis inhibitors received cabergoline add-on therapy for 19 months (1-240). Hypercortisolism was controlled in 56% of these patients during the first year of treatment with cabergoline at 1.0 mg/week (0.5-3.5). About 20-25% of CD patients are good responders to cabergoline therapy allowing long-term control of hypercortisolism at relatively low dosages and with acceptable tolerability. No single parameter, including the baseline UFC and prolactin levels, predicted the response to cabergoline.

Erratum to: Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia.

Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as it permits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology.

Prospective, long-term study of the effect of cabergoline on valvular status in patients with prolactinoma and idiopathic hyperprolactinemia.

Since the 1990's cabergoline has been the treatment of choice in prolactinoma, as itpermits rapid and effective hormonal and tumor control in most cases. Evidence of cardiac valvulopathy was demonstrated in Parkinson's disease patients treated with dopamine agonists. Retrospective studies in prolactinoma patients treated with cabergoline at lower doses did not show such an effect. However, few prospective data with long-term follow-up are available. The aim of this study was to assess the safety of cabergoline regarding cardiac valvular status during prospective follow-up in patients treated for prolactinoma or idiopathic hyperprolactinemia. We report here a series of 100 patients (71F; median age at diagnosis: 41.5 years) treated with cabergoline for endocrine diseases (prolactinoma n = 89, idiopathic hyperprolactinemia n = 11). All patients underwent complete transthoracic echocardiographic studies at baseline and during long-term prospective surveillance using the same equipment and performed by the same technicians. The median interval between baseline and last follow-up echocardiographic studies while on cabergoline was 62.5 months (interquartile range: 34.75-77.0). The median total duration of cabergoline treatment was 124.5 months (interquartile range: 80.75-188.75) and the median cumulative total dose of cabergoline was 277.8 mg (interquartile range : 121.4-437.8 mg) at last follow-up. We found no clinically relevant alterations in cardiac valve function or valvular calcifications with cabergoline treatment. Our data suggest that findings from retrospective analyses are correct and that cabergoline is a safe chronic treatment at the doses used typically in endocrinology.

National consensus on the management of patients with hyperprolactinemia (2016)

Hyperprolactinemia is a steady rise prolactin in serum. Hyperprolactinemia can be physiological, pathological and pharmacological. Pathologic causes include the specific state of the anterior hypophyseal lobe, disorders of the hypothalamic-pituitary system and systemic disorders. If there is a diagnosis of hyperprolactinemia it is recommended to exclude its secondary causes: pregnancy, kidney or liver failure, hypothyroidism, parasellar tumors.For diagnosis a single evaluation prolactin serum levels (≥ 25 ng/ml in females and ≥ 20 ng/ml in males) is enough. Laboratory tests should be evaluated in conjunction with clinical data and additional methods: evaluation of stress, breast ultrasound and/or mammography, assessment of the gonadotropins, estradiol and progesterone levels. In patients with hyperprolactinemia without clinical manifestations it should be macroprolactinemia excluded. There is pharmacological hyperprolactinemia if prolactin level ≈ 200 ng/ml, microprolactinoma if 250 ng/ml, macroprolactinoma if 500 ng/ml and above. Neuroimaging study should be performed in patients with any degree of hyperprolactinemia to exclude hypothalamic-pituitary area pathology.Treatment goal is normalize the prolactin level, to restore gonadal function and galactorrhea termination and, in the case of prolactinoma to reduce the tumor mass and local compression effects. Treatment often includes administration of dopamine agonists such as bromocriptine or cabergoline, or the use of herbal medicines with dopaminergic action, containing standardized extracts of Vitex agnus castus. Cabergoline is the drug of first line as the most effective against the normalization of prolactin levels and reduce the size of the pituitary tumor.Surgical treatment (transsphenoidal surgery) is recommended for patients with intolerance to high doses of cabergoline and resistance to other drugs in this group. Radiation therapyshould be used when radical surgery is impossible, in cases of intolerance or resistance to dopamine agonists, while aggressive prolactinoma or carcinomas.

A Follow-Up Study of the Prevalence of Valvular Heart Abnormalities in Hyperprolactinemic Patients Treated With Cabergoline.

Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate. Our objective was to provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used. Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalized estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group. Thirteen centers of secondary/tertiary endocrine care across the United Kingdom were included. There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97 mg (20-377) and 232 mg (91-551), respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.

Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas.

The optimal duration of cabergoline (CAB) treatment of prolactinomas that minimizes recurrences is not well established. 2011 Endocrine Society Guidelines suggested that withdrawal may be safely undertaken after 2years in patients achieving normoprolactinemia and tumor reduction. We analyzed 74 patients (mean age=46.9±14.4, M/F=19/55, macro/micro=18/56) bearing a prolactinoma divided in 3 groups: group A (23) treated for 3years, group B (23) for a period between 3 and 5years, and group C (28) for a period >5years. CAB therapy was interrupted according to Endocrine Society Guidelines. Prolactin (PRL) levels were measured 3, 6, 12 and 24months after withdrawal. Recurrence was defined with PRL levels ≥30ng/ml. Groups did not differ in pretreatment PRL levels (123.2±112.1, 120.9±123.8, 176.6±154.0), pituitary deficit (4, 17, 17%), mean CAB weekly dose (0.7±0.4, 0.6±0.3, 0.7±0.4) and PRL levels before withdrawal (17.1±19.6, 11.4±8.8, 13.8±13.5). Recurrence occurred within 12months in 34 patients (45.9%), without significant differences among groups. Neuroradiological evaluation showed a significantly higher presence of macroadenoma in group C (13, 17 and 39%, respectively). Recurrence rate of hyperprolactinemia did not depend on sex, tumor size or CAB dose but it was significantly correlated with PRL levels at diagnosis and before withdrawal (p=0.03). Finally, patients with pituitary deficit at diagnosis showed a significantly higher recurrence rate (p=0.03). The study provides additional evidence that prolonging therapy for more than 3years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis.

Autoimmune Fibrotic Adverse Reactions in One-Year Treatment with Cabergoline for Women with Prolactinoma.

Cabergoline is related to an elevated risk of fibrotic adverse reactions including cardiac valvular and pleuropulmonary fibrosis. We investigated pulmonary and cardiac valve fibrosis and immunological markers before and after 3 and 12 months of treatment with cabergoline in women with prolactinoma. The study included thirty-two women with newly diagnosed prolactinoma and 28 healthy women. CAB cumulative dose was 7.8±5.5 mg after 3-month therapy, and 31±22 mg after 12-month follow-up. The risk of autoimmune adverse fibrotic reactions related to CAB treatment including cardiac valvulopathy and pulmonary fibrosis were assessed by a transthoracic echocardiography and pulmonary function tests, respectively. Immunological markers including Antistreptolysin O, Rheumatoid factor, Immunglobuline E, Antinuchlear antibody were also evaluated. Before the start of CAB therapy, the total prevalence of trace grade of mitral, aortic, pulmonic, and tricuspid valve regurgitations were found as 34%, 3%, 6.3%, and 39 % respectively in women with prolactinoma. After improving of prolactin levels with CAB treatment, no change was found in the prevalence of the all valve regurgitations. There was no deterioration in pulmonary function tests. Rheumatoid factor was found higher in newly diagnosed women with prolactinoma than in healthy women (p=0.01), and this was improved by CAB therapy (p=0.005). The prospective study indicated that sufficient cabergoline doses for a period of one year treatment of prolactinoma were not found to be related to fibrotic adverse reactions including cardiac valvular and pulmonary fibrosis or increased levels of immunological marker, apart from rheumatoid factor. For the first time Rf was found higher in newly diagnosed women with prolactinoma and was improved after cabergoline therapy.

Efficacy and safety of long-term cabergoline treatment of antipsychotic-induced hyperprolactinemia (naturalistic study)

IntroductionAntipsychotic-induced hyperpolactinemia (AIH) is associated with disturbing clinical symptoms, such as sexual dysfunctions, menstrual disorders and galactorrhea. Long-term studies of dopamine agonists in AIH are scarce.ObjectivesTo assess efficacy and safety of cabergoline use in psychiatric patients with AIH, including impact on sexual function and quality of life(QoL).MethodsIt was an open-labeled non-randomized naturalistic prospective comparison of cabergoline vs nо treatment in 84 chronic psychiatric patients (F/M = 77/7) with AIH. Cabergoline treatment was started in 44 patients, the сontrol group included 40 patients who rejected the treatment with cabergoline. For assessment of QoL, sexual dysfunction and other hyperprolactinemia symptoms, UKU side effects rating scale (UKU) and SF-36 were used.ResultsThe main and control groups were comparable on all main clinical and psychiatric characteristics. The effective cabergoline dose was 0,25-3 (median-0,5) mg weekly; total cabergoline exposure–534 patient-weeks. Normal prolactin levels were achieved after 4-44 (median-14) weeks in 95% of patients. At 3 months after cabergoline discontinuation, prolactin remained normal in 71%, and AIH recurred in 29% of patients. Prolactin normalization was associated with significant reduction of menstrual disorders, galactorrhea, improvement of UKU scores on sexual desire, orgastic dysfunction, total UKU score and SF-36 scores on subscales of social functioning (P = 0,006), role-emotional (P = 0,042), and mental health (P = 0,049). The rate of psychosis exacerbation in control group was higher than in the treatment group (37,5% vs 0%; P &lt; 0,001).ConclusionsCabergoline is effective and safe in majority of AIH patients. Long-term cabergoline treatment is not associated with psychosis exacerbation. Beyond reversal of typical AIH symptoms, treatment with cabergolin improves sexual function and QoL.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effect of Repeated Cabergoline Treatment on the Vernal Transition and Hair Shedding of Mares (Year 1) and a Subsequent Comparison of the Effect of Starting Date on Prolactin Suppression (Year 2)

Two studies were conducted to determine efficacy of cabergoline for suppressing prolactin (PRL) and the possible effects on vernal transition in mares. In experiment 1, six mares each received either vehicle or cabergoline (5 mg, intramuscularly) every 10 days for 12 treatments beginning February 4, 2013. Blood samples were drawn regularly, and mares were challenged with sulpiride periodically to assess PRL suppression. Weekly hair samples were obtained to determine shedding. Prolactin was suppressed (P < .05) by cabergoline, but suppression waned in spring. There was no effect (P > .05) of treatment on day of first ovulation, luteinizing hormone, or follicle stimulating hormone. Hair shedding was generally suppressed (P = .05). In 2014 (experiment 2), eight of the same 12 mares were used in a similar experiment to determine if the rise in PRL observed in experiment 1 was due to refractoriness to cabergoline or perhaps another factor. Treatment began on April 6, 2014, corresponding to the increase in PRL in treated mares in experiment 1. Mares were treated with cabergoline or vehicle until June 5. Prolactin was suppressed (P < .05) by cabergoline, and the pattern of apparent escape from suppression was similar to year 1. We conclude that (1) cabergoline at this dose alters hair shedding but does not alter the time of first ovulation in mares and (2) relative to our previous reports of cabergoline treatment in the fall, there is a seasonal effect on the ability of this dose of cabergoline to suppress unstimulated PRL secretion.

Anti-proliferative effects of high doses cabergoline in patients with organic hyperprolactinemia

The aim of the study – to inestigate the antiproliferative effect of cabergoline (CAB) which was used in different regimes of suppressive therapy during 12 months in patients with prolactinomas.Materials and methods. It was examined and underwent a 12 month course of treatment by selective dopamine agonist (AgDof) CAB 61 patients with prolactinoma (PROL) (52 women and 9 men) aged 16–66 years. The total duration of the disease ranged from 1 to 60 months, average (12,3±10,1) months. Among the women, treated with CAB, it was mikroPROL 40, macro&amp;giant PROL-12. Among men it 2 was microadenoma, 7 macroadenoma. PROL was verified using magnetic resonance imaging (MRI). Pituitary volume was calculated by the formula Di Chiro-Nelson using the correction coefficient. Were estimated total and partial secretory activity (PSA) in PROL for VS Pronin. PRL blood levels (ng/mL) were determined by commercial reagent kit ELISA (DRG Diagnostics, USA) on automated analyzer Stat Fax 2100 (Awareness Technology, USA). Applied two modes of therapy: 1 – the mode of gradual increase of a CAB dose, since 0,5 mg a week with the subsequent control of the PRL blood level in each 4 weeks and titration CAB dose if necessary (increase in a week dose by 0,25–0,5 mg); 2 – the mode of high starting doses from calculation: the quantity of tablets CAB (0,5 mg) corresponded to frequency rate of increase of the PRL blood level in relation to the upper limit of age norm, but no more than 4 mg (8 tablets) a week. The statistical data analysis was carried out with the certified program package Statgraphics Plus for Windows 3.0 (Manugistic Inc. USA).Results and discussion. At purpose of high starting doses of CAB after 1 month of treatment PRL level in 58.1% of patients decreased to the reference values, including in patients with macroPROL after 1 month at 26.3% of patients had achieved target levels, after 3 months – at 84.2%, and by 6 months of treatment – at 100% patients. In all patients it was a statistically significant decreasing the pituitary volum after 12 months of treatment (p&lt;0,001), but only in patients who were treated high starting high dose CAB recorded decrease in the size of adenoma by 50% or more of the basal volume: at 9 microPROL and 4 macroPROL. It was a positive correlation between the total and the average cumulative therapeutic CAB dose during the treatment period with the volume of the pituitary gland and PSA indicates whether the use of high starting doses in patients with both micro- and macro&amp;giant PROL.Conclusions. The most expressed anti-proliferative effect is noted at application of high starting doses of CAB. Optimum therapeutic average and cumulative doses of CAB for achievement of the maximum therapeutic effect at patients with microPROL are doses of 0,8 mg/week and 33,8 mg/year, respectively; for patients with macro&amp;giant PROL – 1,3 mg/week and 67,6 mg/year, respectively. At patients with microPROL the positive therapeutic effect is reached on a smaller cumulative CAB dose which is associated with a lower risk of complications in the long term period.

Valvular Heart Disease in Patients with Prolactinomas on Cabergoline Treatment

Dopamine agonists are the first line treatment of prolactinomas and Parkinson’s disease. Ergot dopamine agonists have been associated with the development of (moderate to severe) clinically significant valvular thickening and retraction in patients with Parkinson’s disease heart valve insufficiency. In patients receiving dopamine agonists for hyperprolactinemia, most studies show no increased risk of valvulopathy. Objective: The objective was to document any possible association between the use of cabergoline (CB) in patients with prolactinomas treated at the clinic of Endocrinology and Metabolism Clinics Hospital and echocardiographic findings of valvular heart disease. Furthermore, to assess the presence of alterations in the structure and function related to heart valve dose and duration of treatment with cabergoline. Methods: We performed an analytical, observational and retrospective study of such cases-matched controls. Data from 22 patients with prolactinomas treated with cabergoline for a minimum of six months, treated between 2010 and 2012. They were matched with a control group consisting of 22 healthy subjects’ staff members and patients attending this clinic, adjusted analyzed for age and sex. We performed transthoracic echocardiography with color Doppler on the same team, by a cardiologist experienced in echocardiography. Heart valve regurgitation was quantified according to the guidelines of the American Society of Echocardiography. Abnormal mitral or its peak as one greater than 5 mm valve thickening was defined. Results: There were no cases of moderate-severe valvular regurgitation in either group. The prevalence of mild regurgitation was similar between patients and controls. There were no cases of pulmonary valve insufficiency. Only three patients and three subclinical valvular fibrosis controls (p=0.66) was evidenced. There were no cases of abnormal mitral valve thickening and no significant differences between the average thickness of the mitral valve between the two groups (p=0.65). There was no thickening of the other leaflets. We not observe a correlation between the cumulative dose of cabergoline or duration of treatment and valvular regurgitation. We found a significant correlation between the cumulative dose of cabergoline and mitral valve thickness (p=0.002,r 2=0.37). If we exclude from the analysis the patient presented mitral valve thicker (3.8mm), who received the highest doses of cabergoline (1962), this correlation is not observed (p=0.753). We also found a correlation between the maximum dose of cabergoline and mitral valve thickness (p=0.0008). Again, excluding the single patient who received the maximum dose this correlation is not observed (p=0.116). We found no relationship between the mitral valve thickness and length of treatment (p=0.084). There was no increase in the mitral tenting area. Patients treated with cabergoline had an ejection fraction (LVEF) significantly lower (60.9%±1.97) than controls (64.8%±4.9) (p=0.004). Those with overweight-obesity had significantly lower LVEF (60%) compared to those with normal weight (65%) (p=0.045). No relationship between LVEF and sex, high blood pressure (hypertension), smoking, diabetes (DM), impaired fasting glucose (IFG), oral glucose (IOG) or dyslipidemia in either group met intolerance. Nor association between cumulative dose of cabergoline (p=0.64) or duration of treatment (p=0.93) with LVEF. Conclusion: Cabergoline at doses commonly used in patients with prolactinomas not associated with higher prevalence of clinically significant valvular regurgitation, but with greater thickness mitral valvular (though without being abnormal thickening) associated with the cumulative dose

Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients.

The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. Twenty patients (19 naïve and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

Comparative efficacy and safety of generic (Bergolak) vs. brand cabergoline in the treatment of patients with prolactin-secreting tumors

Objective: To evaluate the effectiveness and safety of cabergoline drug Bergolak («Veropharm», Russia) in the treatment of patients with prolactin-secreting tumors.Materials and methods: The study included 14 patients (14 women, mean age 46±12) diagnosed with prolactinoma. The patients were switched to Bergolak after 1 month of treatment by original cabergoline. Dose of cabergoline varied from 0,125 mg to 3,25 mg per week. Prolactin level, symptoms of hyperprolactinemic hypogonadism, side-effects were evaluated at the baseline, after 1 month of original cabergoline treatment and 1 and 2 months of Bergolak therapy.Results: Statistical differences in the level of prolactin (p 0.05), and the incidence of side-effects (p 0.43) during Bergolak therapy in comparison with the original drug was not registered.Conclusions: Bergolak showed to be effective drug for treatment of patients with prolactin-secreting tumors. The incidence of side-effects during Bergolak therapy is equal to the original cabergoline treatment.

Second Attempt of Cabergoline Withdrawal in Patients with Prolactinomas after a Failed First Attempt: Is it Worthwhile?

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31–75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24–30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24–26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3–15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.

Cushing’s Disease and High Dose Cabergoline Monotherapy: Rapid and Sustained Clinical and Biochemical Improvement, with Reversal of Diabetes, Hypertension and Infertility

Aims: To assess the effects of high dose long term cabergoline monotherapy in a patient with Cushing's disease refusing any form of surgical intervention. Presentation of the Case: A 32-year-old Omani female with hypertension, diabetes mellitus and secondary infertility of 10 years and amenorrhoea of 2 years duration, was referred with recurrent thigh abscesses. She was on 100 units of mixed insulin in two divided doses, metformin 1 gm bd, lisinopril 20 mg od, amlodipine 10 mg od and indapamide 1.5 mg od .She had all the features of Cushing’s syndrome, with a blood pressure (BP) of 180/110 mmHg, plethoric facies, central obesity and striae. Investigations revealed diabetes, HBA1c 10.7% and ACTH-dependant Cushing’s syndrome, Case Study Elshafie et al.; BJMMR, 9(1): 1-5, 2015; Article no.BJMMR.18691 2 720 nmol/L (normal <624) and ACTH 14.9 pmol/L. (normal 1.6-13.8). The pituitary MRI and computerised tomographic ( CT) scans from neck to pelvis “ were normal” A neuroendocrine tumour (NET) was deemed unlikely as serum cortisol levels did not “suppress during by a 72 hours trial” of octreotide 100 mcg 8 hourly and her serum chromograninA level (CgA) was normal. A diagnosis of Cushing’s disease was made. She refused inferior petrosal sinus sampling (IPSS) and any form of surgery. A trial of cabergoline was agreed upon. Her response was dramatic: On 1 mg daily initially, the serum cortisol was normal after one week, and by 4 months her blood sugar and blood pressure were normal off all other medications. The HBA1c had fallen from 10.7% to 5.4%. Shortly afterwards she became pregnant and on a reduced dose of cabergoline (1.5 mg/week), she delivered a healthy full term baby, echocardiography was normal in both mother and baby. She has now been in complete remission for more than 4 years on cabergoline 0.5 mg 3 times a week without any side effects. Conclusion: This case provides an example of successful acute and sustained primary “monotherpy” with initially high dose cabergoline in Cushing’s disease. The additional positive metabolic effects and the lack of significant side effects makes high dose cabergoline monotherapy an attractive first or second line treatment for patients with Cushing's disease.

Effects of combination therapy: somatostatin analogues and dopamine agonists on GH and IGF1 levels in acromegaly.

Background and aimsAcromegaly is a complex endocrine disorder caused by excessive secretion of GH, secondary to a GH secreting pituitary adenoma or a mixed pituitary adenoma secreting GH and PRL.MethodsThe aim of this study was to evaluate the effects of combination therapy: dopamine agonist and somatostatin analogue on GH and IGF1 levels in a group of 30 patients with acromegaly. Cabergoline in a dose of 2 mg/week and 4 mg/week respectively was associated with Sandostatin LAR in a dose of 20 mg/month and 30 mg/months respectively. Eight patients were treated with Lanreotide 30 mg/week and Cabergoline 2 mg/week and 3 patients were treated with Bromocriptine 10 mg/day and Sandostatin LAR 30 mg/month.ResultsCombination therapy: Cabergoline and Sandostatin achieved normal levels of IGF1 in 32% of the patients, better results being obtained after 12 months of treatment in the group treated with 4 mg Cabergoline/week. In 37% of cases the levels of IGF1 decreased by 50% after 12 months of treatment. In the group treated with Cabergoline and Somatuline a normal level of IGF1 was achieved in 25% of patients after 12 months of treatment. The outcome for the group treated with Sandostatin and Bromocriptine was similar to that obtained under Cabergoline 2 mg/week. There was no significant correlation between the level of GH and the type or dose of dopamine agonist used.ConclusionsIn conclusion, combination therapy consisting of dopamine agonist and somatostatin analogue achieves a significant reduction of IGF1 levels in patients with mixed adenomas secreting GH and PRL. A decrease in IGF1 levels is directly correlated with the dose of Cabergoline used.

Surgical treatment of prolactinomas: cons.

Prolactinomas account for approximately 40 % of all pituitary adenomas. Over 95 % of prolactinomas are microadenomas (< 10 mm diameter). Treatment is indicated to correct hypogonadism, restore other hormonal deficits, and alleviate local mass effects. Dopamine agonists (DA) are highly effective in achieving these goals and are well-tolerated. The vast majority of prolactinomas will respond to conventional doses of cabergoline (≤2 mg/week) that do not carry an increased risk of cardiac valvular abnormalities. DA therapy may be successful withdrawn in a subset of patients and thus is not necessarily a lifelong commitment. Although transsphenoidal surgery (TSS) is an option for prolactinoma treatment, it is less effective than medical management, carries considerably more risk, and is more expensive. The benefit/risk ratio for DA therapy compared to TSS actually becomes increasingly more favorable as tumor size increases. Therefore DA should remain the clear treatment of choice for essentially all patients with prolactinomas, reserving TSS as a second-line option for the very small number of patients that do not tolerate or are completely resistant to DA therapy.

Evaluation of the valvular and biventricular functions in Parkinson patients using ergotamine-derived dopamine agonist: an observational study

In this study, we aimed to evaluate the impact of cabergoline use in patients with Parkinson's disease on valvular and biventricular functions. In this observational cohort study, patients with Parkinson disease were divided into 2 groups as 34 patients (41.2% female, age; 57.4±15.3 years) using cabergoline (Group 1) and 42 patients (61.9% female, age; 53.7±7.1 years) not using cabergoline (Group 2). In addition to conventional echocardiography and diastolic functions, tissue Doppler imaging was used to evaluate both global and regional systolic - diastolic functions. Correlations were assessed using Pearson correlation coefficient for normally distributed variables. In group 1 patients cabergoline was used for 7.7±5.1 years and mean and cumulative cabergoline dose were 3.3±1.1 mg and 9.8±7.0 g respectively. Left ventricular systolic functions and tissue Doppler measurements of septal and lateral mitral annulus and right ventricular systolic and diastolic velocities were similar between groups. Mitral valve tenting area was significantly higher in patients using cabergoline (p=0.007). The association between cumulative cabergoline dose and diastolic functions was also evaluated which revealed that among diastolic function parameters, Epeak (r=0.253, p=0.042), E/A (r=0.256, p=0.026) and DT (r=-0.382, p=0.001) were correlated with cumulative cabergoline dose. There was a positive correlation between cumulative cabergoline dose and duration of cabergoline therapy with composite regurgitation score (r=0.435, p<0.001; r=0.485, p<0.001, respectively). Our findings indicated that despite the well known effects of cabergoline on valvular functions, we did not observe any alteration in systolic functions, but diastolic functions which was associated with cumulative cabergoline dose in patients with Parkinson's disease.

Early prediction of long-term response to cabergoline in patients with macroprolactinomas.

BackgroundCabergoline is typically effective for treating prolactinomas; however, some patients display cabergoline resistance, and the early characteristics of these patients remain unclear. We analyzed early indicators predicting long-term response to cabergoline.MethodsWe retrospectively reviewed the cases of 44 patients with macroprolactinomas who received cabergoline as first-line treatment; the patients were followed for a median of 16 months. The influence of various clinical parameters on outcomes was evaluated.ResultsForty patients (90.9%) were treated medically and displayed tumor volume reduction (TVR) of 74.7%, a prolactin normalization (NP) rate of 81.8%, and a complete response (CR; TVR >50% with NP, without surgery) rate of 70.5%. Most patients (93.1%) with TVR ≥25% and NP at 3 months eventually achieved CR, whereas only 50% of patients with TVR ≥25% without NP and no patients with TVR <25% achieved CR. TVR at 3 months was strongly correlated with final TVR (R=0.785). Patients with large macroadenomas exhibited a low NP rate at 3 months, but eventually achieved TVR and NP rates similar to those of patients with smaller tumors. Surgery independently reduced the final dose of cabergoline (β=-1.181 mg/week), and two of four patients who underwent surgery were able to discontinue cabergoline.ConclusionDetermining cabergoline response using TVR and NP 3 months after treatment is useful for predicting later outcomes. However, further cabergoline administration should be considered for patients with TVR >25% at 3 months without NP, particularly those with huge prolactinomas, because a delayed response may be achieved. As surgery can reduce the cabergoline dose necessary for successful disease control, it should be considered for cabergoline-resistant patients.