Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

Changes in Regional Cerebral Perfusion after Nicergoline Treatment in Early Alzheimer's Disease: A Pilot Study

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.

Mean platelet volume in patients with prolactinoma

ABSTRACT Objective 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. Subjects and methods 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). Results 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). Conclusion Our results showed that MPV, a marker of platelet function, was unchanged in patients with prolactinoma.

Prolactinomas may have unusual presentations resulting from massive extrasellar tumor extension / Prolactinomas podem ter apresentações incomuns resultantes de maciça extensão tumoral extrasselar

ABSTRACT The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18–54 years); median serum prolactin level was 4,562 ng/ml (1,543–18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41–60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7–84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.

RESUMO O objetivo desta série de casos é relatar oito pacientes com prolactinomas gigantes enfatizando as formas de apresentação e uma complicação do tratamento. O estudo incluiu seis homens e duas mulheres. A mediana de idade foi 29 anos (18–54); e dos níveis de prolactina foi 4.562 ng/ml (1.543–18.690); três pacientes (37,5%) apresentaram pan-hipopituitarismo; a mediana do máximo diâmetro tumoral foi 50 mm (41–60 mm). Cinco pacientes (62,5%) apresentaram alterações no campo visual e três tiveram melhora durante o tratamento; seis pacientes (75%) alcançaram normalização da prolactina em 10,5 meses (7–84) com dose mediana de cabergolina de 2,0 mg / semana (1,0 a 3,0). Um paciente se apresentou como um verdadeiro incidentaloma. Um paciente apresentou uma fistula liquórica durante o tratamento medicamentoso e recusou correção cirúrgica. No entanto a fistula foi resolvida com medidas conservadoras. Esta série de casos ilustra um subtipo raro de macroprolactinomas, a importância de considerar apresentações incomuns no diagnóstico, a eficácia do tratamento farmacológico e suas possíveis complicações.

Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome / Tratamento da miocardiopatia periparto com agonista dopaminérgico e subsequente gestação com resultado satisfatório

Abstract Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases.

Resumo Os mecanismos fisiopatológicos da miocardiopatia periparto ainda não são totalmente definidos, apesar de haver forte associação com vários fatores já conhecidos, incluindo a pré-eclâmpsia. O tratamento segue as mesmas recomendações para a insuficiência cardíaca com disfunção sistólica. Estudos clínicos e experimentais recentes sugerem que os produtos de degradação da prolactina podem induzir a miocardiopatia. A supressão farmacológica da produção de prolactina por agonista do receptor D2 da dopamina, bromocriptina ou cabergolina, vem demonstrando resultados satisfatórios na resposta terapêutica do tratamento. Apresentamos o relato de uma primigesta, adolescente, com miocardiopatia periparto que evoluiu para a normalização da função ventricular esquerda após a administração da cabergolina, utilizada como adjuvante na terapêutica da disfunção cardíaca. Subsequentemente, apesar do intervalo entre as gestações ser considerado curto, apresentou evolução satisfatória em uma nova gestação sem qualquer alteração cardíaca durante todo o período gestacional ou puerpério. Os agonistas dopaminérgicos, drogas de uso oral e de preço acessível para a maioria dos centros terciários, em particular em países subdesenvolvidos, não podem ser esquecidos frente a casos de miocardiopatia periparto.

Análisis de costo-efectividad de pramipexol comparado con levodopa y cabergolina para pacientes con síndrome de piernas inquietas en Colombia / Análise de custo-eficácia do pramipexol e cabergolina comparação com levodopa para pacientes com síndrome das pernas inquietas na Colômbia

Problema de investigación: Describir los costos y la efectividad del pramipexol comparado con levodopa y cabergolina para el tratamiento de pacientes con síndrome de piernas inquietas.Tipo de evaluación económica\r\nAnálisis de costo-utilidad. Población objetivo: Población adulta con diagnóstico de síndrome de piernas inquietas. Intervención y comparadores: Intervención: Pramipexol, Comparadores: Levodopa y cabergolina. Horizonte temporal: 16 semanas. Perspectiva Sistema: General de Seguridad Social en Salud (SGSSS). Tasa de descuento: No aplica. Estructura del modelo: Modelo de Markov. Fuentes de datos de efectividad y \r\nseguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: Años de vida ajustados por calidad (AVAC). Costos incluidos: Costos de medicamentos, Costos de procedimientos. Fuentes de datos de costos:SISMED, Manual tarifario ISS 2001. Resultados del caso base: En el escenario del caso base, pramipexol es una estrategia costo-efectiva con respecto a levodopa. El costo por AVAC ganado con pramipexol es de $7.480 comparado con levodopa. Análisis de sensibilidad: El análisis de sensibilidad determinístico y el diagrama de tornado mostraron que la variable con mayor impacto sobre las estimaciones de costo-efectividad es el precio de levodopa. No se realizó análisis de sensibilidad probabilístico. Conclusiones y discusión: Pramipexol ofrece una mejor relación entre costos y efectividad respecto a levodopa y cabergolina. De acuerdo con el criterio de los expertos clínicos la cabergolina no hace parte de la práctica clínica habitual para este trastorno y la \r\nlevodopa tiene un uso que requiere de supervisión por el efecto que agudiza las manifestaciones clínicas. La principal limitación de este estudio está relacionada con la poca información proveniente de estudios de investigación clínica y evaluaciones económicas.(AU)

Análisis de impacto presupuestal de octreótide, lanreotide para pacientes con acromegalia en Colombia / Budget impact analysis of octreotide, lanreotide for patients with acromegaly in Colombia

Tecnologías evaluadas: Octreótide, lanreótide. Población: Pacientes con acromegalia. Perspectiva: Tercer pagador que corresponde al Sistema General de Seguridad Social en Salud. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Se incluyen los costos de los tratamiento por año de las tecnologías evaluadas. Fuente de costos: SISMED. Escenarios: Se construye un primer escenario en donde se otorga a octreótide 60% y a lanreótide 40%. Un segundo escenario en donde se propone una distribución del 50% para cada uno, estas\r\ndistribuciones se mantienen en los tres años. Para cabergolina se realiza un análisis complementario en dónde se estima la población particular que usaría esta tecnología para esta indicación. Resultados: Para la financiación de octreótide y lanreótide para acromegalia se estima la necesidad de incorporar en el resupuesto un valor de 26,3 mil millones en el escenario 1 y 25,9 mil millones en el escenario 2, en el primer año. Para la población específica que usaría cabergolina se estima un presupuesto adicional de 44 millones.(AU)

Prolactinomas: evolution after menopause

ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.

Galactorreia: como abordar essa complicação incomum após mamoplastia de aumento / Galactorrhea: how to address this unusual complication after augmentation mammoplasty

INTRODUÇÃO: Galactorreia e formação de galactocele após mamoplastia de aumento é uma complicação descrita na literatura, porém a causa permanece desconhecida. MÉTODOS: Apresentamos um caso de uma paciente de 28 anos que foi submetida à cirurgia de mamoplastia de aumento via sulco inframamário, com implante colocado no plano subfascial, que evoluiu, no 7º dia pós-operatório, com galactorreia exteriorizada pela incisão, e propomos um algoritmo para diagnóstico e tratamento de galactorreia após mamoplastias. RESULTADOS: A complicação foi tratada com o uso de agente supressor da lactação, a cabergolina, apresentando boa evolução. CONCLUSÃO: Galactorreia é uma complicação incomum após mamoplastias de aumento, que deve ser sempre lembrada em casos de drenagem de secreção pela incisão por tratar-se de um diagnóstico diferencial com infecção.

INTRODUCTION: Galactorrhea and galactocele formation after breast augmentation are complications reported in the literature, but the cause remains unknown. METHODS: We present a case of a 28-year-old patient who underwent breast augmentation surgery via the inframammary fold with an implant placed in the subfascial plane, which developed galactorrhea from the incision on the seventh postoperative day, and we propose an algorithm for the diagnosis and treatment of galactorrhea after mammoplasties. RESULTS: The complication was treated with the use of a lactation suppressor, cabergoline, presenting good outcomes. CONCLUSION: Galactorrhea is an uncommon complication after augmentation mammoplasties, which should always be considered in cases of secretions from an incision because it is a differential diagnosis for infections.

Cabergoline plus metformin therapy effects on menstrual irregularity and androgen system in polycystic ovary syndrome women with hyperprolactinemia

30% of patients with polycystic ovary syndrome [PCOS] show mild, transient hyperprolactinemia. It is suggested that a reduction of the dopamine inhibitory effect might raise both prolactin and luteinizing hormone. To investigate the adjuvant cabergoline therapy effects on menstrual irregularity and androgen system in PCOS women with hyperprolactinemia. This randomized clinical trial was done on 110 polycystic ovary syndrome women with increased serum prolactin concentration [1.5 fold more than normal level [>37.5 ng/ml]]. Participants were divided into two groups: Case group [n=55] treated with metformin 1gr/day and cabergoline 0.5 mg/week for 4 months and control group [n=55] treated with metformin 1g/day and placebo weekly. Testosterone, prolactin, and dehydroepiandrosterone sulfate level were measured before and four months after intervention in two groups. Also, situation of menstrual cycles asked and recorded before and after intervention. We found decrease in the mean of dehydroepiandrosterone sulfate, weight and total testosterone level in the two groups after intervention but their changes were not significant. Patients in case group showed a significant decrease in serum prolactin level before and after intervention [p<0.001], but no difference was found in control group. All patients in both studied groups had irregular menstrual cycles, which regulate after intervention and the difference was significant [p=0.02]. The results showed that cabergoline can be used as a safe administration in PCOS patients with hyperprolactinemia to improve the menstrual cycles. Considering that the administration of cabergoline plus metformin may reduce the required duration and dose of metformin, patient acceptability of this approach is higher

Does twice-weekly cabergoline improve anthropometrical and biochemical profiles in prediabetes? a randomized double-blind clinical trial pilot study

Dopaminergic signaling is one of the regulatory pathways being investigated for its implication in glucose metabolism. The aim of this study was to determine the effect of cabergoline on biochemical and anthropometric parameters in prediabetes stage [impaired fasting glucose and impaired glucose tolerance]. In this double blind, placebo-controlled, pilot study, 27 prediabetic adults were randomized to receive 0.25-mg cabergoline twice weekly for two weeks, followed by 0.5 mg twice weekly for next 14 weeks [n = 13] or placebo [n = 14]. All subjects were advised to follow a 500 kcal-deficit energy diet. Fasting plasma glucose [FPG], oral glucose tolerance, glycated hemoglobin [A1c], fasting, and 2-h insulin were measured at baseline and at 16-week follow-up. Homeostasis model assessment [HOMA] 2 was calculated to estimate steady-state beta-cell function, insulin sensitivity, and insulin resistance. Our results showed significant reductions in fasting [P = 0.004] and 2-h plasma glucose [P = 0.01] after treatment, and significant improvements in beta-cell function [P = 0.03] and insulin resistance [P = 0.04] in the cabergoline group. The trend of non-significant A1c changes was decreasing in the cabergoline group versus an increasing trend in the placebo group. All anthropometric parameters were similar between the two groups. Our results revealed that twice-weekly cabergoline could improve glucose metabolism in prediabetes stage. Larger studies of longer duration are warranted to investigate the effect of cabergoline in preventing progression of prediabetes to type 2 diabetes mellitus

Efectividad y seguridad de Pramipexol comparado con Levodopa, Pergolida, Cabergolina, Ropinirole para el tratamiento del Síndrome de Piernas Inquietas / Effectiveness and safety of Pramipexole compared to Levodopa, Pergolide, Cabergoline, Ropinirole for the treatment of Restless Legs Syndrome

IIntroducción: el Síndrome de Piernas Inquietas (SPI) se define como un trastorno neurológico que afecta de un 5 % a un 15% de la población general, de causa desconocida, incurable y de evolución crónica, con afectación del sueño y la calidad de vida en alerta. Se cuenta con tratamientos para aliviar los síntomas que afectan la calidad de vida, una primera línea de tratamiento son los agonistas dopaminérgicos entre ellos la Levodopa, el Pramipexol y la Pergolida (8), (9), (10). Objetivo: evaluar la efectividad y seguridad del pramipexol, comparado con otros agonistas dopaminergicos para el tratamiento del Síndrome de Piernas Inquietas (RSL). Metodología: la evaluación fue realizada de acuerdo al protocolo definido previamente por el grupo desarrollador el cual incluye una revisión sistemática de la literatura en MEDLINE, EMBASE, LILACS, COCHRANE y Google para dar respuesta a la pregunta de investigación desarrollada bajo la estrategia PICOT en compañía de expertos técnicos y metodológicos. En el estudio de Scholz con el uso del pramipexol se observó una diferencia de medias de -5.16 [IC95% -6.87 a -3.45] comparado con placebo en la escala de síntomas IRLS (I²= 76%). Los agonistas dopaminérgicos comparados con el placebo produjeron una diferencia de medias en la reducción del PLMSI de −22.38 (IC95% −27.82 a −16.94) por hora de sueño (I² = 73%). El Pramipexol produjo contra placebo una diferencia de medias de -30.47 [IC9% -51.58 a -9.35] (I² = 85%) en el Cambio en el PLMSI (calidad del sueño, a favor de pramipexol. Los agonistas dopaminérgicos comparados con placebo reportaron una diferencia de medias de 0.4 [IC95% 0.33 a 0.47] a favor de los agonistas dopaminergicos respecto a la calidad del sueño autoreportada. En un análisis de subgrupos por medicamentos, el pramipexol produjo contra placebo un cambio en la calidad del sueño autoreportada con una diferencia de medias de 0.44 [IC: 0.33, 0.54], a favor de pramipexol. Los agonistas dopaminérgicos produjeron mejoría en la calidad de vida comparado contra placebo con una diferencia de medias de 0.34 [IC95% 0.23 a 0.44] (I²= 61%). En un análisis de subgrupos por medicamento, el pramipexol produjo mejoría en la calidad de vida comparado contra placebo con una diferencia estandarizada de medias de 0.30 [IC95% 0.13 a 0.47]. Los agonistas dopaminérgicos (cabergolina o pramipexol) comparados con levodopa produjeron un cambio en la línea de base del IRLS con una diferencia de medias de -5.25 [IC95% -8.40 a -2.10] (I²= 55%). En comparaciones indirectas dentro del estudio Ying Sun el pramipexol versus el ropirinole mostró una diferencia de medias en la escala de síntomas IRLS de -1.48 (IC95% -4.47 a 0.45) sin embargo esta diferencia no fue estadísticamente significativa. Respecto a la seguridad, los eventos adversos fueron más frecuentes en el grupo de pacientes que recibió agonistas dopaminérgicos comparado con los pacientes que recibieron placebo con un OR de 1.82 [IC95% 1.59 a 2.08]. Los retiros por eventos adversos fue superior en el grupo de agonistas dopaminergicos versus placebo, con un OR 1.82, (IC95% 1.35 a 2.45), diferencia estadísticamente significativa y mostró una heterogeneidad moderada (I² = 41%). Los retiros por eventos adversos fue superior en el grupo de agonistas dopaminergicos versus placebo, con un OR 1.82, (IC95% 1.35 a 2.45), diferencia estadísticamente significativa y mostró una heterogeneidad moderada (I² = 41%). En un análisis de subgrupos por medicamentos, se reportaron más retiros con pramipexol que con placebo con un OR de 1.11 [IC95% 0.66 a 1.87], esta diferencia no fue estadísticamente significativa con una heterogeneidad moderada (I²= 44%). Conclusiones: Efectividad: Los agonistas dopaminergicos, dentro de los cuales está incluido el pramipexol, son más efectivos que el placebo en el tratamiento de las personas con RLS para los desenlaces de escala de síntomas IRLS, la reducción del PLMSI , la calidad de sueño autoreportada y calidad de vida. En un análisis por subgrupos dentro de la comparación entre agonistas dopaminergicos y el placebo, el pramipexol se mostró más efectivo que el placebo en los desenlaces del cambio del PLMSI, calidad del sueño y en la calidad de vida. Los agonistas dopaminergicos, dentro de los cuales está incluido el pramipexol, son más efectivos que la levodopa para los desenlaces de escala de síntomas IRLS. Al comparar el pramipexol de forma indirecta con el ropirinole (agonista dopaminergico) no se observaron diferencias estadísticamente significativas. Seguridad: Los eventos adversos son más frecuentes en el de grupo tratamiento con agonistas dopaminergicos (dentro de los cuales se encuentra el pramipexol) comparado con placebo. No se encontraron diferencias en seguridad entre el pramipexol y el placebo.(AU)

Treatment results of high dose cabergoline as an adjuvant therapy in six patients with established severe ovarian hyper stimulation syndrome

The beneficial role of cabergoline as a prophylactic agent to prevent ovarian hyper stimulation syndrome [OHSS] among high-risk patients has been demonstrated in previous studies. But data for its role as a treatment for established severe OHSS is still limited. We represent the treatment results of high dose oral cabergoline in management of six patients after the syndrome is established. High-dose oral cabergoline [1 mg daily for eight days] was prescribed as an adjuvant to symptomatic treatment for six hospitalized patients with established severe OHSS following infertility treatment cycles. In two cases OHSS resolved rapidly despite the occurrence of ongoing pregnancy. Considering the treatment outcomes of our patients, high dose cabergoline did not eliminate the need for traditional treatments, but it was a relatively effective and safe therapy in management of established severe OHSS, and prevented the increase in its severity following the occurrence of pregnancy

Resultados visuales en pacientes con macroprolactinoma tratados con agonistas de dopamina / Visual outcome in patients with macroprolactinoma treated with dopamine agonists

Background: Dopamine agonists (DA) effectively reduce tumor size of macroprolactinomas, with the consequent improvement of eventual visual impairment. Aim: To study the visual outcomes in patients with macroprolactinoma treated with DA. Material and Methods: Retrospective cohort study which included patients with macroprolactinoma controlled at a Neuro-endocrinology and Neuro-ophthalmology Department between 1997'and2011, and treated exclusively with DA (bromocriptine or cabergoline). Patients who were operated or had previous radiotherapy and those with an incomplete follow up, were excluded. We analyzed and compared the visual status before and after the beginning of DA treatment. Results: Thirty one patients aged 8 to 59years, were included. Eighteen patients (58%) had visual impairment at the moment of diagnosis (group 1) and 13 had no alterations (group 2). Mean follow up was 36.5 months. Fifteen patients from group 1 (83%) had visual improvement, two remained stable (11 %) and one had a visual deterioration (6%). In group 2, only one non-compliant patient had a visual deterioration. Conclusions: DAs are effective in the management of neuro-ophthalmic complications associated to macroprolactinomas and should be considered asfirst choice therapy in these tumors.

Effects of cabergoline administration on uterine perfusion in women with polycystic ovary syndrome

The aim of this study was to determine the effects of Cabergoline administration on uterine blood flow in women suffering from polycystic ovary syndrome [PCOS]. This study is a randomized, controlled, triple-blind trial which is tested on 40 women who were randomly divided into two groups of 20 people and using a randomized block design during which the subjects were assessed and included. They were suffering from polycystic ovarian syndrome. Inclusion criteria were classically defined PCOS criteria including: oligomenorrhea or amenorrhea, clinical or Laboratory findings based on increase in blood level androgen [testosterone] and ultrasound confirmation of PCOS. Exclusion criteria were Pregnancy, lactation, Dopamine Agonist Therapy. After selection of intervention and placebo groups, primary control Doppler ultrasound was done for both groups. Then a weekly dose of Cabergoline 0.5 mg was administered to intervention group for duration of 12 weeks. Placebo group were administered placebo in the same fashion. At the end of 12 weeks, Doppler ultrasound was performed and the results were recorded in the check lists. No significant difference was noticed in both groups with respect to their age, employment, level of education, type of infertility, duration of marriage, and results of RI and PI before intervention. Later PCOS patients under the treatment of Cabergoline showed a significant increase in uterine blood flow Pulsatility Index [PI] before 2.65 +/- 0.52 and after 1.98 +/- 0.52 and RI before 0.85 and after intervention 0.77], yet no significant difference were found in PCOS patient under the treatment of placebo. PCOS patients were shown to have more resistance in uterine blood flow than healthy people; however, Cabergoline administration proved to increase uterine blood perfusion and regulate menstruation cycle

Comparison of albumin and cabergoline in the prevention of ovarian hyperstimulation syndrome: a clinical trial study

Ovarian hyperstimulation syndrome [OHSS] is the most serious and potentially life-threatening iatrogenic complication associated with ovarian stimulation during Assisted Reproductive Technology [ART] protocols. OHSS typically is a result of ovarian expression of vascular endothelial growth factor [VEGF] which increases vascular permeability. Comparison of albumin and cabergoline in the prevention of OHSS.95 high risk infertile women for OHSS [more than 20 follicles in both ovaries at day of Human Chorionic Gonadotropin [HCG] injection] were randomly divided into two groups. First group including 48 women received 10 unit intravenous albumin at starting oocyte retrieval, and second group including 47 women received 0.5 mg/day dopamine agonist [Cabergolin] at day of HCG injection till 8 days. The dosage of human Menopausal Gonadotropin [HMG] used, total number of follicles developed, number of oocytes retrieved, serum E2 concentrations during the luteal phase, development of ascites, number of embryos generated, clinical pregnancy rate, results of the in vitro fertilization-embryo transfer [IVF-ET] cycles and incidence and severity of any OHSS were evaluated. There was evidence of a statistically significant reduction in the incidence of OHSS in the cabergolin group [53.7%] versus albumin group [46.3%] [p=0.04]. But there was no significant difference of a reduction in severe OHSS [p=0.62]. There was no difference in clinical pregnancy rate too. Administration of cabergolin can prevent incidence of OHSS and does not appear to effect on its severity

Glucocorticoid hypersensitivity syndrome: a case report / Síndrome de la hipersensibilidad glucocorticoidea reporte de caso

Glucocorticoid hypersensitivity syndrome has been reported to date only in several patients. This article describes a unique case of this syndrome in a 24-year old female admitted to hospital because of arterial hypertension and obesity. Although her clinical picture suggested Cushing's syndrome, she had low adrenocorticotropic hormone (ACTH) and cortisol levels with a poor response to corticotrophin-releasing hormone and Synacthen. In turn, an overnight dexamethasone suppression test with 0.25 mg of dexamethasone led to a dramatic decrease in morning cortisol. A diagnosis of glucocorticoid hypersensitivity was made and the patient started treatment with ketoconazole and cabergoline, which resulted in some clinical improvement. This case illustrates the need for clinical awareness of glucocorticoid hypersensitivity in patients suspected of Cushing's syndrome.

El síndrome de la hipersensibilidad glucocorticoidea ha sido reportado hasta la fecha en varios pacientes. Este artículo describe un caso único de este síndrome en una mujer de 24 años, ingresada en el hospital debido a hipertensión arterial y obesidad. Aunque su cuadro clínico hizo pensar en el síndrome de Cushing, presentaba un bajo nivel tanto de hormona adrenocorticotropa (ACTH) como de cortisol, acompañado de una respuesta pobre a la hormona liberadora de corticotropina y al synacthen. A su vez, una prueba de supresión de la dexametasona realizada durante la noche con 0.25 mg de dexametasona, condujo a una disminución dramática del cortisol en la mañana. Se hizo un diagnóstico de hipersensibilidad glucocorticoide, y la paciente empezó el tratamiento con ketoconazol y cabergolina, lo cual trajo como consecuencia cierta mejoría clínica. Este caso ilustra la necesidad de una mayor conciencia clínica en torno a la hipersensibilidad glucocorticoidea en pacientes sospechosos de padecer el síndrome de Cushing.

Cushing's disease. Sustained remission in five cases induced by medical therapy with the dopamine agonist cabergoline

We report five cases of Cushing's disease where the patients were given a therapeutic trial of cabergoline. Morning serum cortisol, adrenocorticotrophic hormone [ACTH], and sleeping cortisol concentrations were significantly raised. Magnetic resonance imaging [MRI] scans revealed pituitary microadenomas in 3 patients but were normal in the others. Ectopic ACTH production was excluded in the 2 patients with normal MRI scans. All were given a therapeutic trial of cabergoline [1 mg daily]. Four patients responded with a prompt fall in serum cortisol levels and had a sustained clinical and biochemical remission for 378, 44, 28 and 14 days, respectively. One patient failed to respond. In conclusion, we suggest that all patients with Cushing's disease should undergo a therapeutic trial of cabergoline. Responders can then be prepared for surgery or, if needed, treated medically in the long term

Update in Prolactinomas / 한양의대학술지

Prolactinomas are frequent causes of gonadal dysfunction and infertility. Dopamine agonists are the main treatment of prolactinoma and the excellent efficacy of the dopamine agonist is well known. Current challenges related to the treatment of prolactinomas include the relationship of long term use of cabergoline and cardiac valvulopathy, the remission after discontinuation of dopamine agonists, the management of pregnant women with prolactinoma, and the role for surgery on long-term management of prolactioma. Herein, these current issues and questions in the management of prolactinomas, including safety of cabergoline, recurrence after discontinuance of dopamine agonist, pregnancy, and role of surgical resection are addressed.

Recovery pattern of hypothalamo-pituitary-testicular axis in patients with macroprolactinomas after treatment with cabergoline.

Background & objectives: Hyperprolactinaemia affects testicular functions by influencing hypothalamo-pituitary-testicular (HPT) axis at various levels. Available literature on the level of defect, time course of improvement of gonadal functions and its relation with decline in prolactin levels is scanty. We carried out this study to evaluate the HPT axis in patients with macroprolactinomas, before and six months after cabergoline therapy. Methods: Fifteen men with macroprolactinomas underwent gonadotropin and testosterone response to their respective stimuli before and after six months of cabergoline therapy. Results: Serum prolactin levels decreased after six months of therapy. Pretreatment, mean lutenizing and follicle stimulating hormones (LH and FSH) levels were 2.0 ± 0.4 and 1.4 ± 0.2 IU/l, respectively. However, LH and FSH responses to GnRH were preserved in majority of the patients and LH peaked to 12.1 ± 2.3 IU/l (P<0.01), while FSH to 2.9 ± 0.4 IU/l suggesting the influence of hyperprolactinaemia at the level of hypothalamus with preserved gonadotrope reserve. After cabergoline therapy, there was an increase in basal as well as stimulated LH and FSH levels, though these were not statistically significant when compared to respective pretherapy levels. Basal testosterone (T) levels significantly improved after therapy, but peak T response to hCG was similar at both pre- and post treatment. A significant correlation was observed between peak LH and peak T at baseline (r=0.53, P<0.01) and it further strengthened after therapy (r=0.70, P<0.01). After cabergoline therapy, there was significant improvement in seminal volume, sperm count and motility and sperm count correlated with peak FSH response (r=0.53, P<0.05). Interpretation & conclusions: Hyperprolactinaemia affects testicular functions probably by influencing at the level of hypothalamus resulting in subnormal basal secretion of gonadotropins required for optimal testicular functions.