Months Of Cabergoline Treatment Research Articles

Risk of impulse control disorders in patients with Cushing's disease: do not blame cabergoline but do not give up caution.

To asses risk of new-onset impulse control disorders (ICDs) in patients with Cushing's disease (CD) who initiated cabergoline (CBG) and to determine frequency of ICDs in CBG-treated patients with CD. This naturalistic observational study had prospective and cross-sectional arms which included patients at five referral centers based in Istanbul. Patients who were scheduled for CBG were assigned to prospective arm. These patients underwent neuropsychological tests (Barratt Impulsiveness Scale, Minnesota Impulsive Disorders Interview, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Go/No-Go Task, Iowa Gambling Task, and Short Penn Continuous Performance Test) for assessment of impulsivity and psychiatric evaluations at baseline, 3, 6, and 12months of CBG treatment. Impulsivity and new-onset ICDs were prospectively assessed. Patients with CD with current CBG treatment for ≥ 3months and matched CBG-naïve patients with CD were included in cross-sectional arm. These patients underwent the same neuropsychological and psychiatric assessments. The impulsivity and frequency of ICDs were compared between CBG-treated and CBG-naïve patients with CD. The follow-up duration of prospective cohort (n = 14) was 7.3 ± 2.3months. One patient developed major depressive episode and another patient developed compulsive gambling after CBG. We observed no significant changes in impulsivity scores during follow-up. In cross-sectional arm, CBG-treated (n = 34) and CBG-naïve patients (n = 34) were similar in impulsivity scores and frequency of ICDs [3 patients (8.8%) vs. 2 patients (5.9%) respectively, p = 1.0]. CBG-treated patients with CD appeared to have a low risk of ICDs, suggesting that CBG still holds promise as a safe agent in CD.

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study.

Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline's cardiometabolic effects.

Autoimmune Thyroiditis Attenuates Cardiometabolic Effects of Cabergoline in Young Women With Hyperprolactinemia.

Both prolactin excess and autoimmune (Hashimoto) thyroiditis may predispose to the development of cardiometabolic disorders. The aim of this study was to investigate whether autoimmune thyroiditis determines cardiometabolic effects of cabergoline. The study population consisted of 2 groups of young women: 32 women with euthyroid Hashimoto thyroiditis (group A) and 32 individuals without thyroid disorders (group B). Both groups were matched for age, body mass index, blood pressure, and prolactin levels. Plasma prolactin, thyroid antibodies, glucose homeostasis markers, plasma lipids, circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, and the urinary albumin-to-creatinine ratio were assessed before and after 6months of cabergoline treatment.All women completed the study. Both groups differed in thyroid antibody titers, insulin sensitivity, high-density lipoprotein cholesterol, hsCRP, homocysteine, and the albumin-to-creatinine ratio. Although cabergoline treatment reduced prolactin levels, improved insulin sensitivity, decreased glycated hemoglobin, increased high-density lipoprotein cholesterol, decreased hsCRP, and reduced the albumin-to-creatinine ratio in both treatment groups, these effects (except for glycated hemoglobin) were more pronounced in group B than in group A. Only in group B, the drug decreased triglycerides, uric acid, fibrinogen, and homocysteine. In group A, hsCRP levels correlated with both baseline thyroid antibody titers and with other cardiometabolic risk factors. The impact of cabergoline on cardiometabolic risk factors depended on the degree of reduction in prolactin levels, while in group A additionally correlated with the effect of treatment on hsCRP. The obtained results suggest that coexisting autoimmune thyroiditis attenuates cardiometabolic effects of cabergoline in young women with hyperprolactinemia.

Clinical Outcome of Invasive Pituitary Prolactinomas Treated with Cabergoline

Background: Treatment of invasive prolactinoma, which has several characteristics including invasive growth into cavernous sinuses and formation of giant adenomas compressing adjacent neural structures, resulting in neurological dysfunction, has been very challenging. There are relatively few reports available describing long-term treatment outcome.
 Aims of the study: In this study we evaluate the results of cabergoline administration as initial treatment during 4 years follow up period.
 Methods: We prospectively categorized 36 patients into four groups according to the results of 3 months of cabergoline treatment: group 1, tumor volume reduction (TVR) ˃25% with normalized serum prolactin (NP) (n = 24); group 2, TVR˃25% without NP (n = 4); group 3, TVR ˂25% with NP (n = 5); and group 4, TVR ˂25% without NP (n = 3).
 Results: During follow-up, 22 patients (91.7%) in group 1 achieved TVR˃50% with NP. Three patients (75%) in group 2 achieved TVR˃50% with NP after treatment for 8 months. In group 3, four patients (80.0%) continued medication because of improvement of symptoms and achieved additional TVR(18.8–46.4%). Surgery was performed on five patients (one in group 2, one in group 3, and three in group 4), and complete resection was achieved in four (80.0%). Overall, 25 (69.4%) of the 36 patients treated with cabergoline had complete response and 6 (16.7%) had partial response but did not require surgery. Thus, the overall response rate was 86%,with only five patients (14%) requiring surgical debulking. NP was not achieved by surgery alone in all cases, even after total resection of tumor.
 Conclusion: Patients who achieve TVR˃25%with NP with 3 months of cabergoline administration had a high possibility of showing good long term response (TVR˃50% with NP) to cabergoline. A higher dose of dopamine agonist (DA) should be considered for patients who achieve TVR˃25% without NP.

Restoration of fertility in a woman with giant prolactinoma in response to cabergoline treatment.

A 32-year-old woman presented with primary amenorrhoea, prolactin (PRL) level of 154 150 mIU/L and was diagnosed with a giant pituitary adenoma measuring maximum 6.2 cm. Cabergoline (CAB) treatment at a dose of 0.5 mg/week was prescribed to the patient. The treatment decreased the tumour size after 3 months (MRI scans of the brain) and brought back to normal the level of the PRL (345 mIU/L) after 6 months of CAB treatment. After 7 months of CAB treatment, menarche was achieved, and after 12 months, the patient became pregnant. She discontinued taking CAB at 4-week gestation. The pregnancy resulted in a missed miscarriage at 6-7 weeks; an abortion was conducted by the vacuum aspiration method. The MRI scans of the brain did not show any tumour enlargement. After 18 months from the start of the treatment the patient got pregnant for the second time. At 25-week gestation an MRI scan of the brain was conducted which did not show any increase in the tumour size. At 38 weeks the patient delivered a healthy full-term girl via C-section. The patient chose not to breastfeed and resumed CAB therapy after the delivery. During the treatment, the PRL level returned to the normal range and the menstrual cycle was restored. After 3 years the patient got pregnant for the third time. The patient did not receive CAB during the pregnancies; the examination did not show any tumour enlargement. Further MRI scans did not show any tumour growth. CAB therapy was effective in normalization of the PRL level, tumour shrinkage, menarche and pregnancy-induction which led to the birth of healthy children in a woman with primary amenorrhoea and a giant prolactinoma invading the skull base bones. Giant prolactinomas are very rarely found in women. Cabergoline therapy can be effective in the normalization of the PRL level, tumour shrinkage, menarche induction in a woman with primary amenorrhoea, and giant prolactinoma. Cabergoline therapy can be effective in pregnancy induction which leads to the birth of children in a woman with giant prolactinoma. Cabergoline discontinuation did not trigger tumour enlargement during pregnancy.

SUN-446 Association between Prolactin Level and Tumor Size Reduction at 3 Months after Cabergoline Treatment in Patients with Macroprolactinoma

Objectives: Prolactin (PRL) normalization after 3 months of Cabergoline (CAB) treatment are useful predictors of responsiveness in patients with prolactinoma. However, differences within the PRL normalization cut-off value have not been identified. Methods: We reviewed the medical records of patients with prolactinomas who were treated with CAB as a primary drug at Severance Hospital. We included patients who had a full dataset of pituitary hormone assays and sella MRI at baseline, follow-up PRL assay and sella MRI at 3 months after CAB treatment. Results: Among the 217 patients, 123 patients had macroprolactinoma. After 3 months of CAB treatment, PRL normalization was achieved in 109 (88.6%) of macroprolactinoma patients, the mean size reduction was 22.9%. We divided these patients into two groups according to the PRL level at 3 months. When we classified by 5ng/mL, low normal group (PRL≤5, n=82) and high normal group (5<PRL≤20, n=27) did not differ in baseline PRL, tumor size and size reduction. When we classified by 1ng/mL, low normal group (PRL≤1, n=49) and high normal group (1<PRL≤20, n=60) did not differ in baseline PRL and tumor size. However, size reduction was significantly different between the two groups (27.18±18.31 vs. 19.46±13.87%, P=0.014). Even if we narrow down the high normal group (1<PRL≤10, n=50 and 1<PRL≤5, n=33), similar results came back (27.18±18.31 vs. 19.30±13.66%, P=0.017 and 27.18±18.31 vs. 19.22±14.33%, P=0.039). Conclusion: Prolactin drops to less than 1ng/ml at 3 months after CAB treatment predicts better response of macroprolactinoma.

Giant prolactinoma, germline BRCA1 mutation, and depression: a case report

BackgroundGiant prolactinomas are very rare pituitary tumors that may exhibit an aggressive behavior and present with a life-threatening condition.Case presentationA 25-year-old white woman was admitted to our hospital with a headache, psychomotor retardation, reduced vision, and loss of autonomy in daily activities. Her past medical history was significant for having oligomenorrhea and a depressive syndrome since her mother’s death. She also had a breast cancer gene 1 (BRCA1) mutation and a family history of breast cancer. She had marked hyperprolactinemia (7615 ng/dL), central hypocortisolism, growth hormone deficiency, and a giant pituitary tumor (52 × 30 × 33 mm) which was shown in magnetic resonance imaging with obstructive hydrocephalus, requiring emergency surgery. Treatment with cabergoline led to a 99.8% reduction in serum prolactin levels and significant tumor shrinkage. Her depressive symptoms progressively improved and psychiatric drugs were withdrawn after 3 months of cabergoline treatment. Currently, she is being followed in Endocrinology, Neurosurgery, and Neurophthalmology out-patient clinics and in a breast cancer unit. Careful monitoring, support, and follow-up will be essential throughout this patient’s life.ConclusionsThis case is a rare presentation of a giant prolactinoma in a young woman, who presented a life-threatening event. She also had an unexpected association between diseases or symptoms that may have contributed to the delay in diagnosis. Given the concomitant presence of a giant prolactinoma, a BRCA1 mutation, and depressive symptoms, a possible association was hypothesized. The breast cancer risk in a BRCA1 mutation carrier and the possible interference of hyperprolactinemia and life events were also discussed. However this hypothesis requires further investigation.

A meta-analysis of the prevalence of cardiac valvulopathy in hyperprolactinemic patients treated with Cabergoline.

Cabergoline is first line treatment for most patients with lactotrope pituitary tumors and hyperprolactinemia. Its use at high-dose in Parkinson's disease has largely been abandoned, because of its association with the development of a characteristic restrictive cardiac valvulopathy. Whether similar valvular changes occur in patients receiving lower doses for treatment of hyperprolactinemia is unclear, although stringent regulatory recommendations for echocardiographic screening exist. To conduct a meta-analysis exploring any link between the use of cabergoline for the treatment of hyperprolactinemia and clinically-significant cardiac valvulopathy. Full-text papers published up to and including January 2017 were found via PubMed and selected according to strict inclusion criteria. All case-control studies were included where patients had received ≥6 months cabergoline treatment for hyperprolactinemia. Single case reports, previous meta-analyses, review papers and papers pertaining solely to Parkinson's disease were excluded. 13/76 originally selected studies met inclusion criteria. A list of desired data were compiled and extracted from papers by independent observers. Each also independently graded for paper quality (bias) and met to reach consensus. More tricuspid regurgitation was observed (OR 3.74; 95% CI 1.79-7.8 p<0.001) in the cabergoline treated patients compared to controls. In no patient was tricuspid valve dysfunction diagnosed as a result of clinical symptoms. There was no significant increase in any other valvulopathy. Treatment with low dose cabergoline in hyperprolactinemia appears to be associated with an increased prevalence of tricuspid regurgitation. The clinical significance of this is unclear and requires further investigation. 51.

Cabergoline-induced fibrosis of prolactinomas: a neurosurgical perspective

Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading...

Mean platelet volume in patients with prolactinoma.

Prolactin is a multifunctional pituitary hormone. The effect of prolactin on platelet activation is not well understood. Prolactinomas are the most common type of pituitary adenomas, and they are medically responsive to dopamine agonists. Mean platelet volume (MPV) is a marker of platelet function and activation. The aim of this study was to evaluate MPV values before and 6 months of cabergoline treatment when normoprolactinemia was achieved. A total of 101 newly diagnosed prolactinoma patients and 102 healthy control subjects were included in the study. Patients with hematological disorders that affect MPV and those on medications were excluded. Prolactin, platelet count and MPV levels were recorded before and 6 months after the initiation of cabergoline treatment (0.5 to 1 mg, two times a week). There was no significant difference in platelet count and MPV before and after 6 months of treatment with cabergoline in patients with prolactinoma compared with the control group (p > 0.05). Our results showed that MPV, a marker of platelet function, was unchanged in patients with prolactinoma.

Metabolic abnormalities in patients with prolactinoma: response to treatment with cabergoline.

BackgroundHyperprolactinemia has been associated with changes in body composition and metabolic abnormalities. Normalization of prolactin (PRL) with dopamine agonists has been found to reverse these abnormalities. This study was designed to assess the anthropometric and metabolic alterations associated with prolactinoma and response of these abnormalities to cabergoline treatment.MethodsIn a non-randomised matched prospective design, 19 consecutive patients with prolactinoma (median PRL 118.6 (105.3) μg/L) and 20 controls were studied. The controls were age, gender and body mass index (BMI) matched. Anthropometric data and metabolic variables were studied at baseline, 3 and 6 months after cabergoline treatment.ResultsPatients with prolactinoma had increased level of fasting plasma glucose (P < .001), LDL-cholesterol (P = .001) and triglycerides (TG) (P = .009) as compared to age, gender and BMI matched healthy controls. There was a significant decrease of body weight at 3 months (P = .029), with a further decline at 6 months (P < .001) of cabergoline therapy. In addition, there was a significant decrement of BMI (P < .001), waist circumference (P = .003), waist-hip ratio (P = .03) and total body fat (P = .003) at 6 months of cabergoline treatment. A significant decline in plasma glucose (P < .001), total cholesterol (P = .009), LDL-cholesterol (P < .001) and TG (P < .001) was seen after 6 months of cabergoline treatment.ConclusionsPatients with prolactinoma have adverse metabolic profile compared with matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities.

A case of giant prolactinoma, initially misdiagnosed as sinonasal neuroendocrine carcinoma

Abstract Giant prolactinomas are defined as pituitary tumors greater than 4 cm, often associated with very high prolactin level (> 1000 ng/mL). They are relatively rare tumors and can present differently from typical prolactinomas. They can be highly invasive, resulting in acute neurological complication at the time of presentation. We present a case of a young woman with giant prolactinoma initially misdiagnosed as sinonasal neuroendocrine carcinoma. The acute presentation of headache, ptosis and impending brain herniation, requiring emergent ventriculostomy and intubation, led to the clinical suspicion of a more sinister diagnosis. Transnasal biopsy of the mass was consistent with sinonasal neuroendocrine carcinoma, and chemotherapy was planned. Laboratory testing, however, revealed an elevated prolactin (27,400 ng/mL, after 1:100 dilution). Re-review of pathology with additional immunohistochemical staining was requested and confirmed the diagnosis of prolactinoma. After 5 months of cabergoline treatment, prolactin level has decreased to 118 ng/mL. There has been a marked reduction in tumor size and an almost complete resolution of neurological symptoms. Given their atypical presentation and potential for sharing common immunohistochemical stains with other neuroendocrine neoplasms, giant prolactinomas extending into the nasal cavity can be misdiagnosed as other neuroendocrine neoplasms which may develop at this site. Accurate diagnosis is imperative to prevent unnecessary surgery and/or radiation and to ensure implementation of dopamine agonist therapy.

Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels

Currently available studies that fully analyse the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and CAB dosage. This is a retrospective clinical-based therapy analysis. Forty-three patients with prolactinoma (eight men, 35 women), aged 33·65 ± 11·23 years, were evaluated metabolically at baseline and after 12 months of CAB treatment. Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homoeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment. Twelve months of CAB reduced WC (P < 0·001), total (P = 0·001) and low-density lipoprotein \terol (P < 0·001), triglycerides (P = 0·024), fasting insulin (P < 0·001), AUCINSULIN (P < 0·001), HbA1c (P = 0·022), Homa-IR (P < 0·001) and VAI (P < 0·001), with a concomitant increase in high-density lipoprotein cholesterol (P < 0·001) and in ISI Matsuda (P < 0·001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (>0·50 mg/week) of CAB showed lower BMI (P = 0·009), fasting insulin (P = 0·001), Homa-IR (P < 0·001) and VAI (P = 0·018) and higher ISI Matsuda (P = 0·002) and DIo (P = 0·011), compared with those on lower doses. A significant metabolic improvement was observed in patients with prolactinoma after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses.

Mineral'naya plotnost' kosti i pokazatelikostnogo metabolizma u muzhchin s sindromomgiperprolaktinemii razlichnogo geneza

Hypogonadism is the most popular cause of BMD decreasing not only in women, but also in men. There are several studies showed a correlation between duration of hypogonadism and BMD reducing degree.&#x0D; Despite wide light exposure of osteoporosis problem at women with hyperprolactinemia, there are a few researches devoted to the same question at men.&#x0D; The aim of our study was to assess the biochemical parameters of bone metabolism and the bone mineral density (BMD) in men with tumoral and not tumoral hyperprolactinemia.&#x0D; In 24 men with hyperprolactinemia and 17 healthy controls we evaluated BMD, serum osteocalcin (OK) and C-terminal telopeptide of type I collagen (CTX), as well as calcium total, ionized calcium and alkaline phosphatase. All men with hyperprolactinemia were also studied after 24 months of cabergoline treatment.&#x0D; The results showed significant differences between study groups in BMD of vertebra and femur bone (p = 0,000052 up = 0,002718). We confirm increasing of BMD in vertebra and femur bone after cabergoline treatment (p = 0,003 и p = 0,027).

The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males

Alterations of sperm number and motility are found in hyperprolactinaemic men. Cabergoline treatment reverses alterations in semen. No information is currently available on the quality of seminal tests in hyperprolactinemia in response to cabergoline treatment. To further investigate the effect of hyperprolactinaemia and its treatment with cabergoline on semen quality. Forty-three men with hyperprolactinaemia (32 macro- and 11 micro-prolactinomas); 60 healthy men served as control. Live spermatozoa count, sperm membrane function, kinetic index, nuclear DNA integrity, sperm curvilinear and linear velocity and amplitude of lateral movement of the sperm head were investigated before and after 6 and 24 months of treatment with cabergoline. Open prospective. At study entry, semen functional tests were severely and similarly impaired both in patients with macro- and micro-prolactinomas compared to controls. After 6 and 12 months of treatment there was a significant improvement of semen quality in patients achieving normalization of prolactin levels, although most of the parameters remained lower than in controls. After 24 months of treatment, seminal fluid characteristics were similar to the controls except for live spermatozoa count, sperm membrane function, sperm kinetic index and sperm nuclear DNA integrity, which remained abnormal in 9.3-53% of the patients. Twenty-four months of cabergoline treatment restored gonadal function in 66.7% of men with hyperprolactinaemia.

Outcome of Cabergoline Treatment in Men with Prolactinoma: Effects of a 24-Month Treatment on Prolactin Levels, Tumor Mass, Recovery of Pituitary Function, and Semen Analysis

The outcome of 24 months of cabergoline treatment on prolactin (PRL) normalization, tumor shrinkage, restoration of pituitary function, and semen alterations was prospectively investigated in 41 men with macro- (age 17-70 yr) and 10 with microprolactinoma (age 18-53 yr). Fifty-one age-matched men served as controls for semen analysis. At study entry, of the 41 patients with macroprolactinoma, 17 (41.4%) had visual field defects, 14 (34.1%) had headache, eight (19.5%) had galactorrhea, 22 (53.6%) had hypopituitarism apart from hypogonadism, and 30 (73.2%) had low testosterone levels; of the 10 patients with microprolactinoma, none had visual field defects, galactorrhea, or hypopituitarism apart from hypogonadism, two had headache (20%), and five had low testosterone levels (50%; P = 0.3). After 24 months of therapy, 1) PRL levels normalized in 31 patients with macro- (75.6%) and in eight with microprolactinoma (80%; P = 0.9), and galactorrhea disappeared in all patients; 2) maximal tumor diameter reduced by 73.7 +/- 22.6% in macro- and 72.8 +/- 28.3% in microprolactinomas (P = 0.91), and 15 macro- (30%) and seven microprolactinomas (46.7%; P = 0.37) disappeared; 3) visual field defects disappeared in 15 (75%) patients with macroprolactinoma, and headache disappeared in 15 (83%) patients with macro- and in one with microprolactinoma (50%); 4) GH secretion recovered in 62.5% and ACTH secretion in 60% of patients; 5) testosterone levels normalized in 25 patients with macro- (60.9%) and six with microprolactinoma (60%) after 6 months, and 20 patients required testosterone or gonadotropin replacement (in 14 or six patients, respectively); and 6) sperm volume and count normalized in all patients who normalized testosterone levels, whereas motility normalized in more than 80%. Cabergoline therapy was well tolerated; only 4.5% of patients had side effects at high doses. These data demonstrate that cabergoline treatment is as effective and safe in men as in women with prolactinoma and can be successfully used as primary therapy even in men bearing large macroprolactinomas.

Giant prolactinomas in men: efficacy of cabergoline treatment.

The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas. Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.