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.

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.

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.

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.

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.

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.

A comparison of bromocriptine & cabergoline on fertility outcome of hyperprolactinemic infertile women undergoing intrauterine insemination.

Background & objectives: The aim of this study was to compare the effects of bromocriptine versus cabergoline on pregnancy in hyperprolactinaemic infertile women. Methods: A total of 183 infertile women with hyperprolactinemia undergoing intrauterine insemination (IUI) were randomly divided into two groups. Group A: 94 with bromocriptine and group B:89 with cabergoline. The efficacy and safety was evaluated on the basis of normalization of prolactin levels, normalization of menstrual cycle, disappearance of galactorrhea, occurrence of pregnancy and adverse effects with each of these medications. Results: The presence of galactorrhea and irregular menstruation were significantly lower in patients of group B than group A (P<0.001 and P=0.011, respectively) with a significant lower prevalence of side effects in cabergoline group. Pregnancy was significantly more achieved among the women with the treatment of cabergoline (82%) as compared to bromocriptine (56.4%) (P<0.001). Interpretation & conclusions: Our results suggest that cabergoline treatment in infertile women with prolactinemia is more effective. It lowers prolactin with better tolerability and much more effective in the achievement of pregnancy.

Efficacy of cabergoline on rapid escalation of dose in men with macroprolactinomas.

Background & objectives: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas. Materials: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol. Results: The mean age of patients at presentation was 31.7 ± 3.3 yr and duration of symptoms was 25.0 ± 3.6 months. Serum prolactin at baseline was 6249.3 ± 3259.2 μg/l with a tumour volume of 28.9 ± 8.3 cm3. Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 ± 3259.2 to 46.9 ± 14.9 μg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy. Interpretation & conclusions: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.

Utilidad de la cabergolina en pacientes portadores de prolactinoma resistentes o intolerantes a bromocriptina / Usefulness of cabergoline in patients with prolactinemia and resistant or intolerant to bromocriptine

Introducción: La terapia de elección de los prolactinomas son los agonistas dopaminérgicos, cuyo principal exponente es la bromocriptina, sin embargo, hay pacientes que no responden o presentan severos efectos secundarios (resistentes o intolerantes a bromocriptina, respectivamente). El objetivo en este estudio fue valorar la respuesta al uso de cabergolina en pacientes con prolactinomas, intolerantes o resistentes a bromocriptina Material y métodos: Se estudiaron 27 pacientes (25 mujeres y dos varones) en quienes se realizó determinación basal de prolactina y cada mes hasta completar tres meses, registrando los datos asociados a hiperprolactinemia y los efectos secundarios. La dosis inicial fue de 0.25 mg los lunes y jueves durante la primera semana, y 0.5 mg a partir de la segunda. El análisis estadístico incluyó la prueba de Shapiro-Wilk, Kruskal-Wallis y Anova. Resultados: 22 pacientes presentaron microadenomas y cinco macroadenomas. En los intolerantes (n = 11) el valor inicial de prolactina de 61.45 ± 19.82 disminuyó al tercer mes a 4.94 ± 1.79 (p < 0.024). En los resistentes (n = 16), el valor basal fue 119.53 ± 11.52; 15 pacientes redujeron significativamente a 12.95 ± 3.66 (p < 0.005) al tercer mes de tratamiento. En ambos, los signos atribuibles a la hiperprolactinemia mejoraron significativamente, con poca incidencia de efectos secundarios. Conclusiones: La cabergolina es útil en la mayoría de los pacientes considerados intolerantes o resistentes a la bromocriptina.

BACKGROUND: Dopaminergic agonists are the treatment of choice for prolactinomas with bromocriptine (BCE) being the primary agent used. There is a group of patients who are not responders to such therapy or have severe side effects (resistant or intolerant to BCE, respectively). We undertook this study to evaluate the response to the administration of cabergoline (CBG) in patients intolerant or resistant to BCE. METHODS: Twenty seven patients (25 females and 2 males) were recruited with prolactin-pituitary tumors, obtaining basal serum prolactin (PRL) samples and again each month up to 3 months. We recorded signs associated with hyperprolactinemia and secondary effects of CBG. The initial dose was 0.25 mg twice weekly during the first week, with an increase to 0.5 mg twice weekly from the second week until the conclusion of the study. Statistical analysis included Shapiro-Wilk, Kruskal-Wallis and ANOVA tests. RESULTS: Twenty two patients had microadenomas and five had macroadenomas. In the intolerant group (n= 11), the initial PRL value (61.45 +/- 19.82) decreased by the third month to 4.94 +/- 1.79 (p<0.024). In the resistant group (n= 16), basal PRL values were 119.53 +/- 11.52. In 15 of these patients, the PRL value significantly decreased to 12.95 +/- 3.66 ng/ml (p<0.005) by the third month of treatment. In both groups the signs related to hyperprolactinemia significantly improved, with a low incidence of secondary effects due to CBG. CONCLUSIONS: CBG is useful in most patients considered as intolerant or resistant to BCE.

McCune-albright syndrome and acromegaly: hormonal control with use of cabergoline and long-acting somatostatin - case report / Síndrome de McCune-albright associada à acromegalia: controle hormonal com cabergolina e somatostatina de longa duração - relato de caso

OBJECTIVES: The use of drug therapy based on cabergoline, octreotide and long-acting release (LAR) octreotide has presented varying results in the treatment of GH excessive production in patients with McCune-Albright Syndrome. METHODS: We report the case of a 29 year-old female patient presenting McCune-Albright Syndrome and complaint of excessive bone growth. RESULTS: The patient presented a pituitary adenoma involving the right internal carotid artery and excessive secretion of growth hormone (no GH suppression was observed after the oral glucose tolerance test). Due to the presence of diffuse thickness in skull base bones, surgical approach was not considered effective and the patient was submitted to drug therapy with octreotide LAR and cabergoline. At the one year follow-up, GH and IGF-1 levels were normal and no adverse effects were present. CONCLUSION: The use of drug therapy based on the association of cabergoline and octreotide is safe and able to achieve complete hormonal control in the treatment of acromegaly for McCune-Albright patients.

OBJETIVO: O uso de terapia medicamentosa, como cabergolina, octreotide e octreotide de longa duração, tem apresentado resultados variados no tratamento da produção excessiva de hormônio de crescimento (GH) em pacientes com síndrome de McCune-Albright. MÉTODOS: Foi relatado o caso de uma paciente de 29 anos apresentando síndrome de McCune-Albright com queixas de crescimento ósseo excessivo. RESULTADOS: A paciente apresentava adenoma pituitário com envolvimento da artéria carótida interna direita e produção excessiva de GH (sem supressão de GH após o teste de supressão com glicose). Por causa do aumento importante da espessura dos ossos da base do crânio, a abordagem cirúrgica foi considerada pouco efetiva e a paciente foi submetida à terapia medicamentosa com octreotide de longa duração e cabergolina. No seguimento de um ano, os níveis de GH e IGF-1 estavam normais e os efeitos adversos não eram presentes. CONCLUSÃO: A terapia medicamentosa fundamentada na associação de cabergolina e octreotide é segura e capaz de alcançar controle hormonal completo no tratamento de acromegalia na síndrome de McCune-Albright.

Aspectos clínicos e terapêuticos de prolactinomas em homens / Clinical and therapeutic aspects of prolactinoma in men

Em homens, macroprolactinomas predominam em relação aos microprolactinomas e têm maior invasividade que nas mulheres. O tratamento clínico é a primeira opção tanto em macro como em microadenomas, independente do sexo. Comparamos apresentação clínica, níveis de prolactina, invasividade neurorradiológica e resposta da prolactinemia em 42 homens com prolactinomas, 23 com terapia clínica (grupo 1) e 19 que também utilizaram tratamento cirúrgico e/ou radioterápico (grupo 2). Os dados obtidos foram submetidos a análise estatística utilizando-se os testes de qui-quadrado ou exato de Fisher para comparações de proporções. Para comparar médias foi aplicado o teste t de Student ou, na ausência de distribuição normal ou com número pequeno de eventos, o não paramétrico de Mann-Whitney. O nível de significância adotado foi de 5 por cento (p<0,05). Os grupos foram similares para idade (p=0,23), período entre primeiro sintoma e diagnóstico (p=0,82), níveis de prolactina pré tratamento (p=0,41) e proporção de macroadenomas invasivos (p=0,096). Ocorreu percentual significativamente maior de cefaléia (p=0,009), deficit visual (p=0,025), tempo de terapia (p=0,007) e período de acompanhamento (p=0,0005) no grupo 2. Variações dos níveis de prolactina antes e após terapia não apresentaram diferença significativa nos grupos (p=0,49), nem o percentual de normalização da prolactina após tratamento (p=0,20). Concluímos, enfatizando a importância do diagnóstico precoce do prolactinoma em homens, tendo em vista a morbidade demonstrada, e reforçamos a necessidade do uso do agonista dopaminérgico como opção terapêutica inicial independente do tamanho do adenoma

Cabergolina como alternativa no tratamento clínico de prolactinonas: experiência na intolerância/resistência à bromocriptina / Cabergoline as an alternative in prolactinomas clinical treatment: experience in the bromocriptine intolerance/resistance

Cabergolina (CAB, Pharmacia) é um agonista dopaminérgico derivado do ergot com longa ação após administração oral, que já tem demonstrado ser de utilidade para o tratamento da hiperprolactinemia. Quarenta e cinco pacientes (36 mulheres, 9 homens) com prolactinomas (27 micro, 18 macro), intolerantes e/ou resistentes à bromocriptina (BRC) foram tratados com dose semanal de CAB de 0,25 a 7mg (mediana: 1mg) dividida de 1 a 7 administrações. O tratamento, em compassionate basis, variou de 1 a 38 meses (mediana: 12 meses). Entre os 38 pacientes com intolerância persistente à BRC (sintomas digestivos, n=27; hipotensão postural, n=13; congestão nasal, n=5; manifestações psiquiátricas, n=4; retenção urinária, n=1), somente 5 permaneceram intolerantes à CAB (sintomas digestivos, n=2; hipotensão postural, n=2; congestão nasal, n=1). Todos aqueles que toleraram bem a BRC também o fizeram com CAB. Onze casos alcançaram normalização da prolactina durante o uso de BRC. Estes pacientes e outros 19 também resolveram a hiperprolactinemia com CAB. Entretanto, somente 3 dos 7 pacientes resistentes (dose diária de BRC de 10 a 25mg) tiveram a prolactina sérica normalizada durante o uso de CAB. Redução tumoral foi documentada por ressonância mag-nética ou tomografia computadorizada em 7 macroprolactinomas durante o tratamento com CAB. Assim, devido à sua excelente eficácia, tolerabilidade e comodidade posológica, a CAB apresenta-se como importante alternativa no tratamento clínico dos prolactinomas.

Adenomas hipofisarios en adolescentes / Pituitary adenomas in adolescence

Presentamos una serie de 48 pacientes (de 14 a 20 años) con adenoma hipofisario. De éstos, 46 (96 por ciento) presentaban tumores secretantes, 3 enfermedad de Cushing, 9 somatotrofinomas y 34 (29 mujeres y 5 hombres) prolactinomas. Treinta casos fueron diagnosticados como adenomas intraselares (62 por ciento) mientras los restantes 18 (38 por ciento) presentaron expansión extraselar. De los 9 pacientes acromegálicos, 7 desarrollaron bioquímica y clínica típica de la enfermedad mientras 2 fueron exclusivamente diagnosticadas con niveles de GH basales normales, pero pruebas dinámicas anormales. Los prolactinomas fueron no invasivos en mujeres y de crecimiento rápido y de mayor tamaño en hombres. Cuarenta y siete pacientes fueron sometidos a cirugía. Cinco de ellos requirieron craneotomía y el resto fueron abordados por víatranseptoesfenoidal (TSE). Se consiguió remisión de la enfermedad de Cushing, acromegalia y prolactinoma intraselar femeninos. Los resultados en tumores mayores tales como los adenomas no secretantes y prolactinomas masculinos fueron malos luego de haber sido tratados mediante una resección subtotal y los disturbios endocrinológicos persistieron. Nuestros hallazgos demuestran que estos tumores son más agresivos en los jóvenes que en los adultos. Como hubo una estrecha relación entre el tamaño del tumor, su invasividad y el resultado final del paciente, concluímos que el diagnóstico temprano y el tratamiento son esenciales. Las frecuentes consultas de adolescentes tales como menstruaciones irregulares, retraso puberal y alteraciones de crecimiento deberían ser investigadas cuidadosamente y no simplemente consideradas como hechos transitorios o funcionales

Tratamiento de amenorreas hiperprolactinemicas con cabergolina / Treatment of hyperprolactinemic amenorrheas with cabergoline

La cabergolina (CAB) es un agonista dopaminérgico de acción prolongada. En la primera experiencia nacional con CAB -parte de un trabajo multicéntrico internacional- se evaluaron 39 mujeres adultos y adolescentes, de 16 a 44 años, con amenorreas hiperprolactinémicas (18 microadenomas y 21 idiopáticas). Se administró CAB o bromoergocriptina (BEC) durante 24 semanas: 8 semanas fueron a doble ciego y en las 16 restantes (período abierto) 18 pacientes fueron tratadas con CAB y 21 con BEC según distribución al azar. Dosis máxima: CAB = 1,5 mg en 2 ó 3 tomas semanales 0,2, 4,6,8,12,14, 20 y 24 del tratamiento y reistalada la menstruación se dosó Progesterona. En las 4 adolescentes se continuó el tratameiento con CAB durante 1 año más. La prolactina se evaluó estadísticamente según Man Whitney (población general) o Wilcoxon (adolescentes). No hubo diferenciais significativas entre las prolactinas (ng/ml) basales de las pacientes tratadas con BEC o con CAB: 173, 86 + 28,23 y 152,11 + 14,06 respectivamente (p = NS); a la 4º semana hubo menor descenso con BEC que con CAB: 36,36 + 5,71 y 14,06 + 3,60 (p < 0,05) y a las 24 semanas se igualaron las respuestas: 19,88 + 4,48 y 9,63 + 2,62 respectivamente (p = NS). En las adolescentes se observó un marcado descenso de la PRL sin diferenciais entre BEC y CAB: basales: 168,17 + 75,47 y 213 + 96,99 (p = NS); 4 semanas: 48,00 + 8,72 y 35,00 + 12,58 (p = NS); 24 semanas; 34,33 + 10,17 y 21,75 + 7,23 (p = NS) respectivamente. A las 48 semanas persistieron los valores de la semana 24: 23,25 + 11,23 (p = NS). Algunas pacientes tratadas con BEC presentaron náuseas, vómitos y epigastralgias, síntomas no observados con CAB. Todas as pacientes lograron menstruar excepto una tratada con BEC, 6 pacientes tratadas con CAB se embarazaron y las 5 que continuaron bajo nuestro control dieron a luz niños sanos. Se concluye que la CAB constituye un recurso terapéutico útil, particularmente en la dolescencia (grupo etario de difícil manejo), por su fácil administración y casi total ausencia de efectos adversos.

Utilidad del mesilato de pergolide en la enfermedad de Parkinson / Ytility of pergolide mesylate in Parkinsonïs disease

Estudiamos a quince pacientes con enfermedad de parkinson de más de 5 años de evolución, en un estudio clínico abierto. Todos ellos presentaban efectos indeseables secundarios al uso de levodopa, así como fenómeno de Fin de dosis. Todos tomaban levadopa y se les agregó mesilato de pergolide en una dosis promedio de 3 mg, en 24 horas. El estudio duró 12 semanas y las evaluaciones se realizaron cada dos semanas. Cinco pacientes abandonaron el tratamiento por presentar efectos colaterales, el resto mejoraron en cuando a la clasificación de Hoen y Yarth, la escala breve de la enfermedad de Parkinson y la velocidad de empuñamiento en ambas manos con P-0.005.

The efficacy of lisuride in the treatment of hyperprolactinemic amenorrhea.

Thirteen women with hyperprolactinemic amenorrhea were treated with lisuride (Dopergin, Schering AG, Germany). The dosage of lisuride was started with 0.1 mg per day and increased to 0.2 mg per day after one week of treatment. Further increment of the drug depended on clinical and laboratory responses of the patients. One patient dropped out from the study due to marked nausea and dizziness. In ten out of twelve patients serum prolactin decreased to normal. Most patients received lisuride 0.2-0.4 mg per day. Only one got more than 0.4 mg per day. Two patients whose serum prolactin levels did not decrease to normal range had uterine bleeding, quite regularly. Menstrual cycle resumed within 23 to 141 days. All galactorrhea disappeared during treatment. Two of five patients who desired pregnancy became pregnant during the treatment. The course and outcome of pregnancies were normal. Common side effects of lisuride treatment were nausea and dizziness. In conclusion, this study demonstrated that lisuride is another effective prolactin inhibiting agent even at low dose. This drug provides an alternative treatment to bromocriptine.

Evaluación clínica de los efectos de nicergolina en niños con retardo psicomotriz y disfunción cerebral mínima / Clinic evaluation of nicergolina efects in children

Hemos evaluado en un estudio clínico con grupo control, los efectos de la Nicergolina en 2 grupos de niños, uno con retardo psicomotriz por Hipoxia neonatal y otro con disfunción cerebral mínima. Se evaluaron las variaciones en el EEG, y se efectuaron evaluaciones psicológicas, antes y después del tratamiento. Encontramos que todos los niños que recibieron el tratamiento presentaron una mejoría significativa, aunque durante el estudio, no se realizó estimulación temprana ni fisioterapia. Las pruebas estadísticas revelan una significación importante en los resultados; después de 30-45 días de tratamiento a una dosis de 15-30 mg/24 horas