Efficacy and safety of dopamine agonists in patients treated with antipsychotics and presenting a macroprolactinoma.

CONTEXT: In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge. OBJECTIVE: Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics. DESIGN: This was a multicenter (France and Belgium) retrospective study. PATIENTS: Eighteen patients treated with antipsychotics were included. RESULTS: Under DA, median PRL levels decreased from 1247 (117-81 132) to 42 (4-573) ng/mL (P = 0.008), from 3850 (449-38 000) to 141 (60-6000) ng/mL (P = 0.037) and from 1664 (94-9400) to 1215 (48-5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0-57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions. CONCLUSIONS: Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.

Body self-image disturbances in women with prolactinoma

Objective: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. Methods: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. Results: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. Conclusion: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Body self-image disturbances in women with prolactinoma.

OBJECTIVE: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. METHODS: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. RESULTS: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. CONCLUSION: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Impulse control disorders in patients with prolactinoma receiving dopamine agonist therapy: a prospective study with 1 year follow-up.

OBJECTIVE: To assess prospectively the prevalence of impulse control disorders (ICD), psychiatric symptoms, and their clinical correlates in patients with prolactinoma receiving dopamine agonists (DA) in comparison to those with non-functioning pituitary adenomas (NFA) and healthy controls (HC). METHODS: A total of 25 patients with prolactinoma, 31 with NFA, and 32 HCs were included in the study. All patients and controls were screened for the presence of ICDs and other psychiatric disorders using revised version of Minnesota Impulsive Disorders Interview (MIDI-R), Barratt Impulsiveness Scale (BIS-11), Symptom Check List (SCL-90-R) questionnaire and Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). RESULTS: We detected two new cases (8%) of ICD associated with DAs. Both cases presented with hypersexuality, which reversed totally or decreased upon discontinuation of the drug. The re-challenge of the DA in a smaller dose has led to either no symptoms or weaker symptoms than before. There was an increase in the number of patients who screened positive on obsession, interpersonal sensitivity, paranoid ideation, and additional items subscales of SCL-90-R in comparison to HCs at the end of the study period (p < 0.05 for all). Likewise, cumulative DA dose was positively correlated to obsession, interpersonal sensitivity, paranoid ideation, hostility, phobic anxiety subscales, and GSI scores of SCL-90-R (p < 0.05 for all). CONCLUSIONS: DAs are associated with a small but substantial short-term risk of ICD development and a broad range of psychiatric symptoms in patients with prolactinoma receiving DAs.

Improvement in cognitive abilities following cabergoline treatment in patients with a prolactin-secreting pituitary adenoma.

Hyperprolactinaemia may affect sexual and reproductive functioning. However, recent studies suggest that increased prolactin levels may also have negative effects on cognition. We aimed to study whether the reduction in prolactin levels by cabergoline in patients with hyperprolactinaemia is followed by an improvement in cognitive tasks. We studied seven patients with hyperprolactinaemia caused by a prolactinoma that had an indication to start treatment with cabergoline. All patients were assessed twice (baseline and 6-12 months after cabergoline treatment) with a cognitive battery. Plasma prolactin levels were determined. We found a significant improvement in the speed of processing, working memory, visual learning and reasoning and problem-solving domains after cabergoline treatment. Improvements in speed of processing and reasoning and problem solving were greater in patients with baseline prolactin levels above the median. In summary, a reduction in prolactin levels by cabergoline in patients with hyperprolactinaemia is followed by an improvement in cognitive abilities. This finding suggests that prolactin may be involved in cognitive processes, although cabergoline could also have procognitive effects that are independent of prolactin changes. Further clinical trials are needed to confirm the potential cognitive-enhancement properties of cabergoline in patients with chronic hyperprolactinaemia.

The development and validation of the Leiden Bother and Needs Questionnaire for patients with pituitary disease: the LBNQ-Pituitary.

BACKGROUND: Patients report persisting impairment in quality of life (QoL) after treatment for pituitary disease. At present, there is no questionnaire to assess (a) whether patients with pituitary disease are bothered by these consequences, and (b) their needs for support. OBJECTIVE: To develop and validate a disease-specific questionnaire for patients with pituitary disease which incorporates patient perceived bother related to the consequences of the disease, and their needs for support. METHODS: Items for the Leiden Bother and Needs Questionnaire for patients with pituitary disease (LBNQ-Pituitary) were formulated based on results of a recent focus group study (n = 49 items). 337 patients completed the LBNQ-Pituitary and six validated QoL questionnaires (EuroQoL-5D, SF-36, MFI-20, HADS, AcroQol, CushingQoL). Construct validity was examined by exploratory factor analysis. Reliabilities of the subscales were calculated with Cronbach's alphas, and concurrent validity was assessed by calculating Spearman's correlations between the LBNQ-Pituitary and the other measures. RESULTS: Factor analyses produced five subscales (i.e., mood problems, negative illness perceptions, issues in sexual functioning, physical and cognitive complaints, issues in social functioning) containing a total of 26 items. All factors were found to be reliable (Cronbach's alphas all ≥.765), and the correlations between the dimensions of the LBNQ-Pituitary and other questionnaires (all P ≤ .0001) demonstrated convergent validity. CONCLUSIONS: The LBNQ-Pituitary can be used to assess the degree to which patients are bothered by the consequences of the pituitary disease, as well as their needs for support. It could also facilitate an efficient assessment of patients' needs for support in clinical practice. We postulate that paying attention to needs for support will lead to optimal patient care (e.g., improvement in psychosocial care), and positively affect QoL.

Cognitive functioning of patients with a PRL-secreting pituitary adenoma: A preliminary report.

OBJECTIVE: The aim of this study was to evaluate cognitive functions in patients with prolactin (PRL)-secreting pituitary adenoma. METHODS: We conducted a hospital-based case-control study. The effect of PRL overproduction on cognitive processes was assessed with a comprehensive battery of neuropsychological tests to measure verbal memory, nonverbal memory, attention, visuospatial skills, verbal fluency, and executive functions. The data were gathered from 40 participants matched for age, sex, handedness, and education (20 with pituitary adenoma, 20 healthy controls). The patients were examined on the first day of their hospitalization in the Department of Neurosurgery of Medical University of Warsaw. MRI as well as blood test of pituitary hormone level and perimetry test of the visual field were conducted. RESULTS: The group of patients had significantly lower scores on verbal memory, nonverbal memory, and attention tests compared with healthy volunteers. Their results in memory and visuospatial tests were significantly negatively correlated with the level of PRL but there was no marked relationship between cognitive functioning and the size of tumor. CONCLUSIONS: This study demonstrated a significant relationship between PRL overproduction and worsening of cognitive processes, especially in the domains of memory and attention in hospitalized patients with pituitary adenomas. Greater hyperprolactinemia was associated with a larger decrease in cognitive performance. There was no effect of tumor size.

Reduced sleep quality and depression associate with decreased quality of life in patients with pituitary adenomas.

OBJECTIVES: Several studies reported decreased quality of life (QoL) and sleep as well as increased rates of depression for patients with pituitary adenomas. Our aim was to explore to what extent differences in depression and sleep quality contribute to differences in QoL between patients with pituitary adenomas and controls. DESIGN: A cross-sectional case-control study. SETTING: Endocrine Outpatient Unit of the Max Planck Institute of Psychiatry, Munich, Department of Internal Medicine, Ludwig-Maximilians-University, Munich, and the Institute of Clinical Psychology and Psychotherapy, Technical University, Dresden. PARTICIPANTS: Patients with pituitary adenomas (n=247) and controls (from the DETECT cohort, a large epidemiological study in primary care patients) matched individually by age and gender (n=757). MEASUREMENTS: Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and QoL was measured by the generic EQ-5D and calculated by the time trade-off- and VAS-method. Depression was categorized as 'no depression', 'subclinical depression', and 'clinical depression' according to the Beck Depressions Inventory for patients and the Depression Screening Questionnaire for control subjects. STATISTICAL ANALYSES: General linear and generalized, logistic mixed models as well as proportional odds mixed models were calculated for analyzing differences in baseline characteristics and in different subgroups. RESULTS: Patients with pituitary adenomas showed decreased QoL (VAS index: 0.73±0.19) and sleep (PSQI score: 6.75±4.17) as well as increased rates of depression (subclinical or clinical depression: 41.4%) compared with their matched control subjects (VAS index: 0.79±0.18, PSQI score: 5.66±4.31, subclinical or clinical depression: 25.9%). We have shown that a substantial proportion of the reduced QoL (48% respectively 65%) was due to the incidence of depression and reduced sleep quality. CONCLUSIONS: These findings emphasize the importance of diagnosing depressive symptoms and sleep disturbances in patients with pituitary disease, with the ultimate goal to improve QoL in patients with pituitary adenomas.

Towards a better quality of life (QoL) for patients with pituitary diseases: results from a focus group study exploring QoL.

PURPOSE: Patients treated for pituitary adenomas generally report a reduced quality of life (QoL). At present, the patient's perspective of QoL has not been fully addressed and this, and further insight in potential determinants of QoL in pituitary diseases is required to design strategies to improve QoL. We aimed to define patients' perceived QoL and to identify potential factors they perceive to contribute to QoL. METHODS: We conducted four independent focus groups of six patients each, per specific pituitary disease (Cushing's disease, Non-functioning pituitary macroadenoma, acromegaly, prolactinoma). In two sessions these focus groups discussed aspects of QoL. Verbatim transcripts were analyzed using a grounded theory approach. RESULTS: The issues raised by the patient groups were compatible with statements and items of available QoL questionnaires. In addition, other QoL aspects emerged, such as visual limitations (physical problems); issues with a desire to have children/family planning, fear of collapsing, fear of recurrence, panic, persisting thoughts, problems with an altered personality, anger, jealousy, sadness, frustration (psychological problems); and difficulties communicating about the disease, lack of sympathy and understanding by others, and a reduced social network (social problems). Next, this study uncovered factors which might contribute to a decreased QoL (e.g. less effective coping strategies, negative illness perceptions, negative beliefs about medicines, unmet needs regarding care). CONCLUSIONS: This focus group study demonstrated that important disease-specific aspects of QoL are neglected in current pituitary disease-specific questionnaires and elucidated potential factors that contribute to a decreased QoL. Information provided in this study can (and will) be used for developing additional items for disease-specific QoL questionnaires and for the development of a self-management intervention aiming to improve QoL in patients treated for pituitary diseases.

Distinct dopaminergic personality patterns in patients with prolactinomas: a comparison with nonfunctioning pituitary adenoma patients and age- and gender-matched controls.

INTRODUCTION: Personality patterns such as extraversion and novelty seeking have been associated with an altered dopaminergic activity in healthy subjects. Patients with prolactinomas have been described as exhibiting an altered dopaminergic tone and are often treated with dopamine agonists. Little is known about the personality traits of this patient group. Hence, we aimed at examining whether patients with prolactinomas exhibit modified personality patterns compared to patients with nonfunctioning pituitary adenomas and healthy controls. SUBJECTS/METHODS: In this cross-sectional study, 86 patients with prolactinomas and 58 patients with nonfunctioning pituitary adenomas (NFPA) were compared with 172 mentally healthy age- and gender-matched controls. To assess personality traits, standardized personality questionnaires (Eysenck personality questionnaire-EPQ-RK and Tridimensional Personality Questionnaire devised by Cloninger-TPQ) were administered. RESULTS: Patients with either prolactinomas or NFPA showed a distinct personality profile compared to the normal population, characterized by increased neuroticism and they also answered in a socially desirable mode. On harm-avoidant total and subscales, they presented with a higher fear of uncertainty and also increased fatigability and asthenia. The prolactinoma patients, when contrasted with the 'clinical' control group of patients with NFPA and after post hoc tests for multiple comparisons following the Bonferroni-Holm procedure showed significantly reduced extraversion (p = 0.044) and increased shyness with strangers (p = 0.044), tending to be more neurotic and present lower scores in the novelty seeking subscale impulsiveness. CONCLUSION: This is, to our knowledge, the first study providing new evidence of an altered personality profile of prolactinoma patients which might affect the patient-doctor relationship, treatment and patient's quality of life.

Quality of life is decreased in female patients treated for microprolactinoma.

OBJECTIVE: Most studies on treatment of microprolactinoma have focused on clinical and biochemical outcome rather than on functional and mental well-being. We evaluated this topic in female patients with microprolactinoma, because other pituitary adenomas are associated with decreased quality of life. DESIGN: We conducted a cross-sectional study. PATIENTS AND METHODS: To assess the impact of treatment for microprolactinoma on subjective well-being, quality of life was investigated in 55 female patients (mean age 45 +/- 10 years), treated for microprolactinoma in our center, using four validated, health-related questionnaires: Short-Form-36 (SF-36), Nottingham Health Profile (NHP), Multidimensional Fatigue Inventory (MFI-20), and Hospital Anxiety and Depression Scale (HADS). Patient outcomes were compared with those of 183 female controls with equal age distributions. RESULTS: Anxiety and depression scores were increased when compared with controls for all subscales as measured by HADS, and fatigue for all but one subscale as measured by MFI-20. Patients treated for microprolactinoma had worse scores on social functioning, role limitations due to physical problems (SF-36), energy, emotional reaction, and social isolation (NHP) when compared with control subjects. Important independent predictors of quality of life were reproductive status and anxiety and depression scores according to the HADS. CONCLUSION: Quality of life is impaired in female patients treated for microprolactinoma, especially due to increased anxiety and depression. These increased anxious and depressive feelings might be due to possible effects of hyperprolactinemia on the central nervous system. Failure to recognize this association may adversely affect patient-doctor relationships.

Apathy and pituitary disease: it has nothing to do with depression.

Increasingly, patients with pituitary disease are evaluated and treated at cancer centers. In many ways, these patients resemble patients with other malignant brain tumors. Although the majority of pituitary adenomas are benign, the physical, emotional, and cognitive changes that these patients experience on their well-being is malignant. Pituitary disease causes a variety of physical illnesses resulting from the alterations in the hypothalamic-pituitary-end organ axis. In addition, patients with pituitary diseases may experience many emotional problems, including depression, anxiety, behavioral disturbances, and personality changes, above and beyond the many reactions these patients may have to the myriad of adjustments that they must make in their lives. There is a growing understanding that pituitary patients may experience these emotional problems as a result of long-term effects that the pituitary tumor itself, treatment, and/or hormonal changes have on the hypothalamic-pituitary-end organ axis. The authors present a series of cases, in which patients with pituitary disease were diagnosed and treated for depression and showed little response to the treatment for depression. When the diagnosis of apathy syndrome was considered and treatment implemented, the patients' condition improved. A review of the literature on apathy, hypothalamic-pituitary-end organ axis dysfunction, and treatment for apathy syndrome is included.

Quality of life in patients with a pituitary adenoma.

A validated quality of life (QOL) measure, the SF-36 questionnaire, was used to assess patients' perception of the impact of a pituitary adenoma, prior to treatment, on his or her physical and mental functioning. Of 270 new patients evaluated for pituitary disease at the University of Virginia Pituitary Clinic, 168 met the criteria for inclusion (pituitary hormone hypersecretion and/or pituitary adenoma) into this prospective study. Results of the SF-26 questionnaire in 36 patients with acromegaly, 42 patients with Cushing's disease, 39 patients with a prolactinoma and 51 patients with a non functioning macroadenoma prior to treatment were compared with those of the normal population; a comparison of results among patients with different types of pituitary adenomas was also performed. Patients with a pituitary adenoma had a significantly decreased QOL compared with the normal population in both physical and mental measures (p < 0.05). There were different degrees of perceived impairment depending on the type of pituitary adenoma. Patients with acromegaly had impairment in measures of physical function while patient with Cushing's disease had impairment in all but one measures compared with the normal population and with patients with other types of pituitary adenomas. Patients with a prolactinoma had impairment in mental measures and patients with a non-functioning adenoma had impairment in both physical and mental measures compared with the normal population. Patients with a pituitary adenoma have an impaired quality of life that should be routinely assessed in conjunction with endocrine and anatomic studies before and after treatment.

Prolactinoma in some Ménière's patients--is stress involved?

Dizziness is a common complaint in primary care clinics and can enter the diagnostic profile of different pathologies spanning from psychiatric problems to vestibular dysfunction. Episodes of vertigo in Ménière's patients are often reported to be triggered by stress but no physiological data are available to account for the subjective link. The study involved 42 Ménière's patients hospitalized for neurectomy of the vestibular nerve for relief of incapacitating vertigo. In addition 18 patients with neurinoma of the vestibular nerve and 12 patients with facial spasm, who underwent surgery, served as controls. A blood sample was taken on the day of surgery in order to determine the level of battery of different stress hormones. The most striking observation was the presence of hyperprolactinemia (above 20 microg/l) in 14 Ménière's patients. The presence of prolactinoma was confirmed by MRI in six cases out of six investigated and the others have not yet been followed up in this retrospective study. These observations are clearly indicative for systematic determination of prolactin levels before opting for surgery in Ménière's patients.

Dexamethasone suppression test reversal in rapid transcranial magnetic stimulation-treated depression.

OBJECTIVE: The aim of this paper is to report the effect of rapid transcranial magnetic stimulation (rTMS) on the mood and dexamethasone suppression test (DST) of a patient with major depressive disorder (DSM-IV). CLINICAL PICTURE: A 36-year-old woman with a past history of prolactinoma and recurrent major depressive disorder presented with major depression on three separate occasions over a 3-month period. DST was positive on each occasion. TREATMENT: During each episode, a course of rTMS was given. Courses varied from seven to 13 once-daily treatment sessions depending on clinical response. These treatment sessions were 20 trains of 10 Hz for 5 s at 100% of motor threshold. OUTCOME: Remission was achieved, psychiatric rating scales improved and the DST status converted from positive to negative. There were no side effects. CONCLUSION: DST status in major depressive disorder can be converted from positive to negative by rTMS. This so far unreported observation increases our knowledge of rTMS.