Dopamine Agonist Treatment Research Articles

Medically induced CSF rhinorrhea following treatment of macroprolactinoma: case series and literature review.

Although several reports have addressed cerebrospinal fluid (CSF) rhinorrhea following dopamine agonist (DA) therapy of macroprolactinomas, further study is warranted for this relatively uncommon entity. Toward this aim, our retrospective series and review of literature further clarifies recommendations in treatment of this rare problem. We retrospectively reviewed all macroprolactinoma cases in our hospital for a 15-year period. Our systematic search of PubMed identified original articles and reviews of all macroprolactinoma cases with an associated medication-induced CSF leak. Five patients with drug-induced CSF leak were identified; four of these patients received cabergoline therapy an average of 6 weeks before the onset of rhinorrhea and then underwent surgical repair of the CSF leak. Of 35 published studies included, we identified 60 patients with medication-induced CSF leak. Medical therapy included bromocriptine in 34 patients, cabergoline in 21 patients, and use of both DAs in two patients. Three cases did include complete diagnostic and treatment data. Median time from initiation of the DA treatment to occurrence of rhinorrhea was 6weeks. For CSF rhinorrhea, 49 patients underwent surgical repair (38 by the transnasal approach) and seven patients were treated nonoperatively. Baseline skull base erosion in macroprolactinomas in combination with subsequent tumor shrinkage induced by DA therapy may result in spontaneous CSF rhinorrhea. Therefore, such patients should be advised about and monitored for this potential setback. Once CSF leak is diagnosed, prompt treatment must be carried out to avoid infectious complications. Transnasal surgery appears the most effective therapeutic approach.

Pharmaceutical interventions for weight-loss maintenance: no effect from cabergoline.

Weight regain is a major limitation to successful weight maintenance following weight loss. Observational studies suggest that stimulation of dopamine receptors in the central nervous system is associated with weight loss and inhibition of weight gain. Our objective was to test the hypothesis that dopamine agonist treatment would prevent weight regain following acute weight loss in individuals with obesity. We conducted a 2-year double blind randomised controlled trial comparing the effect of a dopamine agonist, cabergoline, with placebo on weight regain in obese individuals who had lost at least 5% of their body weight using an 800 kcal/day commercial meal replacement programme. The primary outcome measure was the difference in mean weight between the treatment and control groups over the 2-year period following randomisation. At 24 months, there was no difference in body weight between cabergoline and placebo treatment after adjustment for age, gender and baseline values (0.6 kg (95% CI: -1.5, 2.6), p = 0.58). The mean (±SD) baseline body weight of the randomised participants was 101.8 kg, the mean (±SD) weight loss with the 800 kcal/day diet was 7.1 ± 1.8 kg and the mean (±SD) weight regain at 24 months was 5.1 ± 7.5 kg. There were no significant differences in BMI, percent weight loss, waist circumference, resting energy expenditure, blood pressure or metabolic parameters at 24 months between the two groups. Treatment with the dopamine agonist cabergoline does not prevent weight regain in obese individuals following weight loss.

Impact of menopause on outcomes in prolactinomas after dopamine agonist treatment withdrawal.

Discontinuation of dopamine agonist (DA) treatment in women with prolactinoma after menopause is a potential approach; studies systematically assessing long-term outcomes are lacking. Our aim was to investigate the natural history of prolactinoma in this group. Retrospective cohort study of women with prolactinoma diagnosed before menopause and who after menopause were not on DA. Thirty women were included. Twenty-eight received DA (median duration 18years, median age at DA withdrawal 52years). At last assessment (median follow-up 3years) and compared with values 6-12months after stopping DA, Prolactin (PRL) increased in 15%, decreased but not normalized in 33% and was normal in 52%; PRL levels or visible adenoma on imaging before DA withdrawal, treatment duration and presence of macro-/microadenoma at diagnosis were not predictors of normoprolactinaemia at last review, whereas PRL values 6-12months after stopping DA were. Adenoma regrowth was detected in 2/27 patients (7%), who showed gradual increase in PRL. Comparison with 28 women who had DA withdrawal before their menopause revealed lower risk of hyperprolactinaemia recurrence in the postmenopausal group (HR:0.316, 95% CI: 0.101-0.985, P<.05). Two women with microprolactinoma diagnosed in perimenopausal period had not been offered DA; PRL decreased (but not normalized) during observation of 1 and 8years. Prolactin normalized over time in nearly half of the women and serum PRL 6-12months after DA withdrawal is useful predictor. Nonetheless, 7% of the patients demonstrated adenoma regrowth which, given the life expectancy postmenopause, necessitate regular monitoring of the cases with persistent hyperprolactinaemia.

Longitudinal analysis of impulse control disorders in Parkinson disease.

To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD). We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists. Generalized estimating equations and Poisson models with robust variance were used to study the association between several time-dependent definitions of dopamine agonist (DA) use, taking dose and duration of treatment into account, and ICDs at each visit. Other antiparkinsonian drugs were also examined. Among 411 patients (40.6% women, mean age 62.3 years, average follow-up 3.3 years, SD 1.7 years), 356 (86.6%) took a DA at least once since disease onset. In 306 patients without ICDs at baseline, the 5-year cumulative incidence of ICDs was 46.1% (95% confidence interval [CI] 37.4-55.7, DA ever users 51.5% [95% CI 41.8-62.1], DA never users 12.4% [95% CI 4.8-30.0]). ICD prevalence increased from 19.7% at baseline to 32.8% after 5 years. ICDs were associated with ever DA use (prevalence ratio 4.23, 95% CI 1.78-10.09). Lifetime average daily dose and duration of treatment were independently associated with ICDs with significant dose-effect relationships. Similar analyses for levodopa were not in favor of a strong association. ICDs progressively resolved after DA discontinuation. In this longitudinal study of patients with PD characterized by a high prevalence of DA treatment, the 5-year cumulative incidence of ICDs was ≈46%. ICDs were strongly associated with DA use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation. NCT01564992.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14years). Mean adenoma size was 23.8 ± 16.2mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics

To present the histological and immunohistochemical characteristics of pituitary lactotroph adenomas (PLAs) resistant to dopamine agonist treatment. The investigators examined paraffin-embedded blocks and histological sections obtained from 19 patients (13 women, 6 men), whose median age was 29 (19, 38) years, after surgical treatment (adenomectomy) for PLAs resistant to dopamine agonist treatment. Immunohistological examination was performed using antibodies against prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), type 2 dopamine receptors (DR2), estrogen receptors-α (ERα), the proliferation marker Ki-67, and the endothelial cell marker CD34. The expression of PRL by adenoma cells was revealed in all the patients. The coexpression of PRL and GH without clinical and laboratory signs of acromegaly was established in 3 cases. No expression of TSH, ACTH, LH, or FSH was revealed in any cases. Positive immunoreaction using antibodies against DR2 and ERα was detected in 8 and 6 cases, respectively. No expression of any of the studied receptors was found in 6 patients. Ki-67 was more than 3% in 3 patients and higher in patients with supra- or retrosellar growth. There was a positive correlation between the serum level of Ki-67 and that of PRL at the onset of the disease. There were 37 (25, 85) adenoma vessels, as measured by CD34 immunoexpression. It was ascertained that the patients with parasellar adenoma had more tumor vessels than those without parasellar growth of adenoma and that with the latter invading the cavernous vessels, the number of vessels was statistically significantly more. PLAs resistant to dopamine agonists in addition to PRL (100%) can express GH in 16% of cases are characterized by the immunoexpression of DR2 (42%) and ERα (32%), a low proliferative activity, increased angiogenesis in the adenomas with parasellar growth and invasion into the cavernous sinus.

Prolactinomas: how to handle prior to and during pregnancy?

Prolactinomas are the most common cause of pathological hyperprolactinemia, leading to central hypogonadism and, therefore, a frequent etiology of infertility. Treatment, usually with dopamine agonist (DA), can reverse hyperprolactinemia and hypogonadism, allowing pregnancy in the majority of cases. Bromocriptine is still the DA of choice for such purpose. Important issues in DA-induced pregnancies include fetal exposition, both malformations and neuropsychological development and tumor size increase. Regarding microprolactinomas and intrasellar macroprolactinomas, DA should be withdrawn as soon as pregnancy is confirmed. In expansive/invasive macroprolactinomas, DA maintenance should be individualized. Patient follow-up includes periodically clinical evaluation, sellar imaging only indicated in the presence of tumor mass effects related symptoms. Neurosurgery, both before and during gestation, is indicated in cases in which DA treatment failed. Breastfeeding is usually allowed. As tumor volume decrease and remission of hyperprolactinemia may occur after pregnancy, serum prolactin levels and tumor status should be reevaluated.

Pediatric prolactinoma: initial presentation, treatment, and long-term prognosis.

In pediatric prolactinoma, diagnosis is based on hyperprolactinemia and imaging. Dopamine agonist treatment is effective and safe. Overall survival and functional capacity as a measure of quality of survival were not impaired, indicating an optimistic prognosis. Surgery should be considered only in emergency situations of threatened visual function, not presenting a fast response to dopamine agonist treatment. Severe side effects of medication and lack of efficacy should be considered as contraindications. What is Known: • In pediatric prolactinoma-a very rare pediatric neuroendocrinological disease-gender-related differences in terms of clinical presentation at initial diagnosis are known. • Due to the rareness of the disease, reports on long-term outcome and prognosis after childhood-onset prolactinoma based on prospective follow-up are not published. What is New: • Dopamine agonist treatment is efficient and safe for tumor volume reduction in pediatric prolactinoma and surgical interventions are recommended only for decompression of the optic chiasm in case of threat to vision. In case of inefficient response to medication, side effects or parental refuse, alternative therapeutic options should be considered. • Quality of life in terms of survival and functional capacity was not impaired in pediatric prolactinoma patients when compared with 235 long-term survivors of different sellar masses.

Males with prolactinoma are at increased risk of incident cardiovascular disease.

To investigate whether the risk of incident cardiovascular disease (CVD) is increased in patients with prolactinoma. Population-based, retrospective, open-cohort study using The Health Improvement Network (THIN) database. A total of 2233 patients with prolactinoma and 10355 matched controls (1:5 ratio) from UK General Practices contributing to THIN were included. Sex, age, body mass index and smoking status were used as matching parameters. The primary outcome was any incident CVD, defined by Read codes suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were calculated with Poisson regression, using clinically relevant parameters as model covariates. Sensitivity analyses were performed to check whether a change in the initial assumptions could have an impact on the findings. During the 6-year observation period, the composite CVD outcome was recorded in 54 patients with prolactinoma and 180 "nonexposed" individuals. The incidence rate was 1.8 and 14.8 per 1000 person-years for the females and males with prolactinoma, respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval (CI): 0.61-1.61, P=.968)] in female patients and 1.94 (95% CI: 1.29-2.91, P=.001) in male patients. These findings remained robust in sensitivity analyses restricting to patients with documented record of dopamine agonist treatment and those with newly diagnosed prolactinoma. In contrast to females, men with prolactinoma have increased risk for incident CVD; the aetiology of this gender-specific finding remains to be elucidated.

Pulmonary Artery Occlusion and Mediastinal Fibrosis in a Patient on Dopamine Agonist Treatment for Hyperprolactinemia.

Unusual forms of pulmonary hypertension include pulmonary hypertension related to mediastinal fibrosis and the use of serotonergic drugs. Here, we describe a patient with diffuse mediastinal fibrosis and pulmonary hypertension while she was on dopamine agonist therapy. A young woman, who was treated with cabergoline and bromocriptine for hyperprolactinemia, presented with progressive dyspnea over several months. Based on the clinical investigation results, in particular, elevated pulmonary arterial pressures and significant perfusion defects on computed tomography (CT) pulmonary angiography and ventilation/perfusion (V/Q) scintigraphy, chronic thromboembolic pulmonary hypertension (CTEPH) was initially considered the most plausible diagnosis. However, during an attempted pulmonary endarterectomy, loose fibrous tissues were observed in the mediastinum and cryosection of the right pulmonary artery showed fibrosis and chronic inflammation. Subsequent investigations revealed that diffuse mediastinal fibrosis with concurrent pulmonary hypertension, and not CTEPH, was the most likely diagnosis and cabergoline and bromocriptine may have triggered the fibrotic changes. Both drugs are ergot-derived dopamine agonists, which are known to cause cardiac valve fibrosis and less frequently, non-cardiac fibrotic changes. The underlying mechanism is attributed to their interactions with serotonin receptors. There is much evidence that serotonin, a potent vasoconstrictor and mitogen, is involved in the pathogenesis of pulmonary hypertension. In conclusion, as CT and V/Q scintigraphy findings can occasionally be deceptive, physicians should be particularly aware of differential diagnoses in patients without obvious history of venous thromboembolism that are suspected of having chronic thromboembolic pulmonary hypertension.

Electronic survey of management of hyperprolactinemia in Brazil: Endocrinologists versus gynecologists

Hyperprolactinemia is a frequent condition in clinical practice, responsible for 20–25% of secondary amenorrhea cases. We performed an electronic survey among members of the Brazilian Society of Metabolism and Endocrinology (SBEM) and the Brazilian Federation of Association of Gynecology and Obstetrics (FEBRASGO) to assess diagnostic and therapeutic preferences for management of hyperprolactinemia. Electronic addresses of SBEM and FEBRASGO members were obtained from the directories of these societies, and these members were invited, through electronic messages (e-mail), to answer an online questionnaire that included 10 questions about the treatment of micro and macroprolactinomas, maximum dose of dopamine agonist, how to exclude primary hypothyroidism and macroprolactinemia, hyperprolactinemia and pregnancy. We received responses to the questionnaire by e-mail from 521 SBEM members and 233 FEBRASGO members. The results of this survey demonstrate that there are many area of agreement between SBEM and FEBRASGO members and most of their responses follow the latest Endocrine Society Guideline. Relative to a survey performed several years ago, our findings show that SBEM members have incorporated some of latest recommendations in this field. The principal issues of concern for both groups are duration of dopamine agonist treatment for patients with microprolactinoma and dopamine agonist withdrawal during pregnancy.

Fertility, pregnancy, and prolactinoma: A survey of pituitary surgeons’ view and review of the literature

ObjectivePituitary surgeons frequently encounter female prolactinoma patients seeking treatment to restore fertility. Current medical guidelines recommend using dopamine agonist (DA) for this, but for fetal safety, DA should stop upon pregnancy confirmation. The probability that prolactinoma may grow during pregnancy makes this last recommendation imperfect. With the advances in endoscopic surgery, we queried the potential role for surgery in these infertile patients, who may be ambivalent about both stopping and continuing DA while pregnant. MethodsAn anonymous survey was sent to pituitary surgeons to investigate how they would advise prolactinoma patients on treatment of infertility, and counsel them about pregnancy. Directories from various US-based neurosurgical societies were culled. Surgeons who designated themselves as “skull base”/“pituitary” were surveyed. ResultsSeventy-six surgeons responded (41%). The majority (67%) adhered to medical guidelines for microprolactinoma, but 26% recommended surgery. However, for a macroprolactinoma at diagnosis, the number of surgeons who recommended DA treatment vs. surgical treatment were almost evenly split (χ2p=0.06). The practice setting of a multidisciplinary clinic with endocrinologists did not significantly influence our respondents’ choice. For a patient who presented after becoming pregnant on DA, our respondents were against surgery to prevent tumor growth (96%). ConclusionA review of the current literature shows that both medical and surgical therapy have flaws. Significant numbers of surgeons considered surgery a legitimate option for prolactinoma patients seeking to be pregnant. The divergence between these surgeons’ opinion and current medical guidelines warrants further investigation and discussion.

Expression of Stem Cell Markers and Dopamine D2 Receptors in Human and Rat Prolactinomas.

BackgroundDopamine agonists (DAs) are the first-line treatment for prolactinomas. DAs primarily target the dopamine D2 receptor (D2R). Tumor stem-like cells (TSLCs) are associated with the tolerance to radiotherapy and chemotherapy. TSLCs have also been identified in pituitary adenomas. We aimed to characterize the expression pattern of stem cell markers and D2R in human and rat prolactinomas.Material/MethodsHuman prolactinoma specimens (n=14) were obtained from patients with surgical resection. The xenograft model of rat prolactinomas was generated by endermically injecting MMQ cells, HE and PRL were confirmed by immunohistochemical staining of tumor sections, and the expression of serum PRL was measured by ELISA. The expression of stem cell markers (CD133, Nestin, Oct4, and Sox2) and D2R in prolactinomas was detected by immunofluorescence. The proportion of CD133-expressing cells after DA treatment was evaluated by flow cytometry in vitro.ResultsWe found that a small subpopulation of cells expressing stem cell markers existed both in human and rat prolactinomas. Furthermore, the CD133-expressing cells showed negative D2R expression. Conversely, the D2R-expressing cells showed negative CD133 expression. The proportion of CD133-expressing cells in surviving tumor cells was significantly increased after DA treatment.ConclusionsOur results confirmed the existence of cells expressing stem cell markers in human and rat prolactinomas. Additionally, the CD133-expressing cells might resist DA therapy due to the lack of D2R expression.

Pituitary Macroadenoma Treated with Cabergoline: the Role of Neuro-Ophthalmic Examination in Diagnosis and Follow Up Management

Background: To describe the importance of neuro-ophthalmic examination on pituitary macroadenomapatient with bitemporal hemianopia and treated with cabergoline.Case Illustration: A 50-year-old female came with blurry vision on both eyes. She had 20/40 and 20/30vision right eye and left eye respectively, no RAPD, no limitation of gaze, anterior and posterior segmentswere unremarkable. She had superior bitemporal defect expanding to inferior quadrant of visual fieldby Humphrey. MRI scan showed suggestive pituitary macroadenoma with bleeding and supression tosuperior chiasm. The prolactin level was elevated and she was then referred to endocrinologist andgiven dopamine agonist (cabergoline) treatment. Six months after cabergoline therapy, patient’s visualacuity had improved to 20/25 on both eyes, no progression on Humphrey visual field defect and alterationin size of the macroadenoma from MRI.Conclusion: A characteristic visual field defect can be a first sign for pituitary macroadenoma. Surgicalare not always necessary. Medicine therapy can be beneficial for secreting pituitary macroadenoma.Ophthalmology examination can help assessing the prognosis of the disease.Keywords: bitemporal hemianopia, pituitary macroadenoma, prolacin, cabergoline

MRI follow-up is unnecessary in patients with macroprolactinomas and long-term normal prolactin levels on dopamine agonist treatment.

Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first-line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once prolactin is controlled. The aim of our study was to determine whether a regular MRI follow-up was necessary in patients with long-term normal prolactin levels under DA. We conducted a retrospective multicenter study (Marseille, Paris La Pitie Salpetriere and Nancy, France; Liege, Belgium) including patients with macroprolactinomas (largest diameter: >10 mm and baseline prolactin level: >100 ng/mL) treated by dopamine agonists, and regularly followed (pituitary MRI and prolactin levels) during at least 48 months once normal prolactin level was obtained. In total, 115 patients were included (63 men and 52 women; mean age at diagnosis: 36.3 years). Mean baseline prolactin level was 2224 ± 6839 ng/mL. No significant increase of tumor volume was observed during the follow-up. Of the 21 patients (18%) who presented asymptomatic hemorrhagic changes of the macroprolactinoma on MRI, 2 had a tumor increase (2 and 7 mm in the largest size). Both were treated by cabergoline (1 mg/week) with normal prolactin levels obtained for 6 and 24 months. For both patients, no further growth was observed on MRI during follow-up at the same dose of cabergoline. No significant increase of tumor size was observed in our patients with controlled prolactin levels on DA. MRI follow-up thus appears unnecessary in patients with biologically controlled macroprolactinomas.

Abnormal Sleep Delta Rhythm and Interregional Phase Synchrony in Patients with Restless Legs Syndrome and Their Reversal by Dopamine Agonist Treatment.

Background and PurposeThe purpose of this study was to characterize abnormal cortical activity during sleep in restless legs syndrome (RLS) patients and to determine the effects of treatment with a dopamine agonist. Based on whole-brain electroencephalograms, we attempted to verify alterations in the functional network as well as the spectral power of neural activities during sleep in RLS patients and to determine whether the changes are reversed by treatment with pramipexole.MethodsTwelve drug-naïve RLS patients participated in the study. Overnight polysomnography was performed before and after treatment: the first recording was made immediately prior to administering the first dose of pramipexole, and the second recording was made 12–16 weeks after commencing pramipexole administration. Sixteen age-matched healthy participants served as a control group. The spectral power and interregional phase synchrony were analyzed in 30-s epochs. The functional characteristics of the cortical network were quantified using graph-theory measures.ResultsThe delta-band power was significantly increased and the small-world network characteristics in the delta band were disrupted in RLS patients compared to the healthy controls. These abnormalities were successfully treated by dopaminergic medication. The delta-band power was significantly correlated with the RLS severity score in the RLS patients prior to treatment.ConclusionsOur findings suggest that the spectral and functional network characteristics of neural activities during sleep become abnormal in RLS patients, and these abnormalities can be successfully treated by a dopamine agonist.

CSF Rhinorrhea: An Early Complication of Dopamine-Sensitive Macroprolactinoma

Objective: Cerebral spinal fluid (CSF) leak is a known surgical complication of invasive macroprolactinomas. Case reports suggest this complication can occur with dopamine agonist treatment alone.Methods: We present clinical features, imaging, and biochemical characteristics of one such case of an invasive macroprolactinoma complicated with early CSF leak.Results: A 35-year-old obese male presented with weight gain of over 100 pounds within the last year and absent morning tumescence. Laboratory evaluation was notable for elevated total prolactin (PRL) (4,655 ng/mL) and low total testosterone (24 ng/dL). Magnetic resonance imaging (MRI) revealed a large pituitary adenoma (4.2 × 2.5 × 3.5 cm) extending into the cavernous and sphenoid sinuses, partially eroding the sphenoid bone. Dopamine agonist, cabergoline 250 μg twice/week was started. After two doses, the patient developed CSF rhinorrhea and was hospitalized. Adenoma was smaller in size (4.1 × 1.9 × 3.3 cm), and total PRL declined to 824 ng/mL. An endoscopic subtotal resection of adenoma with CSF leak repair was performed. Treatment with cabergoline was continued, resulting in complete resolution of CSF leak within a few days. Two months later, cabergoline dose was increased to 500 μg twice a week as adenoma size remained unchanged. One month later, MRI showed regression of the pituitary tumor with cystic changes. Serum PRL level substantially declined (total PRL, 102 ng/mL).Conclusion: Clinicians should be highly observant of and educate patients about CSF rhinorrhea as potential early consequence of medical therapy of macroprolactinoma to avoid misdiagnosis and fatal sequelae of this complication.Abbreviations: CSF cerebral spinal fluid; DA dopamine agonist; MRI magnetic resonance imaging; PRL prolactin

Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients.

We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

Cataplexy in a patient treated for prolactinoma: Case report

Introduction. Isolated cataplexy, without the presence of narcolepsy, is a relatively rare condition, and can be regarded as attacks of motor inhibition with loss of muscle tone and areflexia. The diagnosis of cataplexy relies on the clinical presentation and medical history and it is rarely confirmed by video-polygraph. We here described a female patient treated for prolactinoma who developed isolated cataplexy. Case report. A 53-year-old female treated with bromocriptine for a macroprolactinoma presented with sudden episodes of weakness and toneless legs leading to falls and injuries on several occasions. Cardiovascular evaluation was completely normal. Psychiatric evaluation showed no psychotic phenomenology or suicidal ideas. Pituitary imaging showed empty sella with a remnant sellar mass with infra- and parasellar extension. Neurological examination revealed mild obstructive sleep hypopnea/apnea. Electroencephalographic monitoring during sleep and awakening did not show appearance of epi potentials. HLA haplotyping was positive for HLADR3,16; DR51;DQ1 allele, confirming a diagnosis of isolated cataplexy. Treatment included tricyclic antidepressants and reduction of bromocriptine dosage with resolution of cataplexy. Conclusion. We reported the first case of isolated cataplexy most probably associated with dopamine agonist treatment for prolactinoma.

Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment.

About 80% of prolactinomas respond to dopamine agonists (DA) with hormonal normalization and tumor shrinkage. Mechanisms of DA resistance include reduction of dopamine receptor subtype 2 (DRD2) expression, short and long isoform ratio and post-receptor mechanisms. It was suggested that polymorphisms in the gene encoding dopamine receptor subtype 2 gene (DRD2) could be associated with variable effectiveness of cabergoline (CAB). To assess the influence of DRD2 polymorphisms in responsiveness of CAB treatment in patients with prolactinoma. Cross-sectional retrospective case-control study analyzing the frequency of five DRD2 polymorphisms in 148 patients with prolactinoma and 349 healthy subjects. The association of genetic variants and clinical characteristics with CAB responsiveness was performed in 118 patients (mean age at diagnosis 29years; range 11-61years) with hormonal evaluation. Patients with prolactin (PRL) normalization were considered as responders. No association in genotypes and allele proportions was found comparing patients and controls. On pharmacogenetic study, 118 patients on CAB were included and 20% were non-responders. No association was found between clinical characteristics (gender, age, PRL level and tumor size at diagnosis) and polymorphisms of DRD2 with CAB responsiveness. Otherwise, there was association between polymorphisms rs1076560 (allele A) and rs1800497 (allele T) and the presence of macroadenomas. No correlation was found between DRD2 polymorphisms and CAB responsiveness in patients with prolactinoma. More data are necessary in order to assess the influence of DRD2 genotyping on DA treatment response.