RESUMEN
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.
Asunto(s)
Hiperprolactinemia/diagnóstico , Hiperprolactinemia/terapia , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/terapia , Guías de Práctica Clínica como Asunto , Prolactinoma/diagnóstico , Prolactinoma/terapia , Antineoplásicos/uso terapéutico , Brasil , Bromocriptina/uso terapéutico , Cabergolina , Agonistas de Dopamina/uso terapéutico , Ergolinas/uso terapéutico , Femenino , Humanos , Masculino , Prolactina/sangreRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/terapia , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/terapia , Prolactinoma/diagnóstico , Guías de Práctica Clínica como Asunto , Prolactina/sangre , Brasil , Prolactinoma/terapia , Bromocriptina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Ergolinas/uso terapéutico , Cabergolina , Antineoplásicos/uso terapéuticoRESUMEN
Prolactinomas são os tumores hipofisários funcionantes mais freqüentes, sendo as drogas agonistas dopaminérgicas (AD) a principal opção para seu tratamento. Resistência à bromocriptina (BRC), primeiro AD a ser utilizado, definida como ausência de normalização da prolactina (PRL) ou de redução tumoral durante o tratamento, é relatada em 5 a 18 por cento dos pacientes tratados. Novos AD, como a cabergolina (CBG), são alternativa eficaz já que podem normalizar a PRL e reduzir tumores em até 86 por cento e 92 por cento dos casos, respectivamente. Mesmo assim, uma porcentagem dos pacientes pode ser chamada de resistente aos AD. Os mecanismos para a resistência ainda não são completamente elucidados e, embora pouco freqüentes, os prolactinomas resistentes aos AD representam um desafio para o tratamento. As alternativas como cirurgia e radioterapia podem não alcançar a normalização da PRL e, portanto, não resolver os sintomas ligados à hiperprolactinemia. Tratamento do hipogonadismo com reposição de esteróides sexuais, assim como estimulação ovulatória quando o desejo for a gravidez, podem ser alternativas para casos com crescimento tumoral controlado. Novas drogas como anti-estrógenos, novos AD, análogos específicos de subtipos do receptor da somatostatina, drogas quiméricas com ação no receptor da somatostatina e da dopamina e antagonistas da PRL estão sendo estudados e podem representar alternativas futuras ao tratamento deste grupo de pacientes.
Asunto(s)
Humanos , Agonistas de Dopamina/uso terapéutico , Neoplasias Hipofisarias/terapia , Prolactinoma/terapia , Resistencia a Antineoplásicos , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológicoRESUMEN
OBJECTIVE: Somatostatin analogues have become the mainstay of the medical treatment of acromegaly. The aim of our study was to evaluate the efficacy and tolerability of octreotide-LAR (OCT-LAR) treatment in acromegalic patients. DESIGN: Prospective open trial. PATIENTS AND METHODS: Eighty acromegalic patients (46 women; 18-80 years) were treated with OCT-LAR. Mean +/- SD duration of follow-up was 16.6 +/- 6.6 months (6-24 months). Twenty-eight patients received OCT-LAR as primary treatment. The target was to achieve normal IGF-I levels. Clinical activity was evaluated by symptom score and fasting samples for GH and IGF-I serum concentrations, obtained under basal conditions as well as during treatment. Pituitary tumour volume was assessed by magnetic resonance imaging of the sella. A tumour volume reduction of at least 25% was considered significant. RESULTS: Clinical improvement was attained in most patients. Fifty-nine (74%) of them attained mean GH < 2.5 ng/ml and 33 (41%) achieved normal IGF-I by the 24th month of treatment. GH and IGF-I control increased throughout treatment. Regarding the 46 patients treated for at least 12 months there was a significant decrease of GH and IGF-I levels by the third month compared to basal levels, persisting with no subsequently variation. In the patient group that achieved normal serum IGF-1 during treatment (controlled group: n = 43) 20 patients maintained normal levels up to the latest follow-up, whereas 23 of them once again showed altered serum IGF-1-values of some measurements during follow-up, despite dose maintenance or elevation. Baseline percentage of the upper limit of IGF-I normal range, GH levels by the third month and length of treatment were predictive factors of IGF-I normalization. Tumour shrinkage occurred in 76% of primary patients. Among 21 diabetic patients, four worsened and five improved glycaemic control, based on glycated haemoglobin. One previously intolerant patient progressed to overt diabetes. Nine patients developed gall bladder sludge, other nine patients acquired microlithiasis and one patient developed gallstone pancreatitis. CONCLUSION: OCT-LAR is an effective agent in alleviating symptoms, suppressing GH, normalizing IGF-I and inducing tumour shrinkage in many acromegalic patients. Overall, OCT-LAR is well tolerated and should be recommended for nonsurgically cured acromegalics, and also be considered as primary therapy for selected cases, mainly for those with a low probability of surgical cure.
Asunto(s)
Acromegalia/tratamiento farmacológico , Antineoplásicos Hormonales/administración & dosificación , Octreótido/administración & dosificación , Acromegalia/sangre , Acromegalia/complicaciones , Adenoma/sangre , Adenoma/complicaciones , Adenoma/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/efectos adversos , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Octreótido/efectos adversos , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/tratamiento farmacológico , Factores Sexuales , Resultado del TratamientoRESUMEN
Prolactinomas are the more prevalent functioning pituitary tumors, and dopamine agonist drugs (DA) are the main therapeutic option for patients harboring such tumors. Bromocriptine (BRC) resistance, defined as failure to normalize prolactin (PRL) and/or to shrink the tumor is reported in 5 to 18% of the patients treated with this drug, the first DA widely used. Cabergoline (CBG) can bring PRL to normalization and reduce tumor size in up to 86% and 92% of the patients, respectively. Even with this newer DA, a subset of patients does not respond to therapy and are truly resistant. The mechanisms for resistance are not yet fully clarified, so the treatment for the resistant prolactinoma is still a challenge. Transsphenoidal surgery associated or not to radiotherapy is an important tool, but PRL may not normalize, mainly in macroprolactinomas. Treatment with sex steroids or ovulation induction can solve the hypogonadism or infertility, when the tumor growth is under control. New drugs as anti-estrogens, new DA, specific analogs for somatostatin receptor subtypes, chimeric molecules associating dopamine and somatostatin effect, and PRL antagonists are under investigation and can be future alternatives for DA resistance.
Asunto(s)
Agonistas de Dopamina/uso terapéutico , Neoplasias Hipofisarias/terapia , Prolactinoma/terapia , Resistencia a Antineoplásicos , Humanos , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológicoRESUMEN
Bromocriptine (BRC) and other dopamine agonist drugs are the first-choice treatment for prolactinomas. However, the major disadvantage is the need for prolonged therapy. We retrospectively studied 131 patients [62 microprolactinoma (MIC), 69 macroprolactinoma (MAC)], who achieved serum prolactin (PRL) normalization during BRC use. Twenty-seven percent of them (31% MIC and 69% MAC) underwent previous surgery. Twenty-seven patients (20.6%: 25.8% MIC and 15.9% MAC) persisted with normoprolactinemia after a median time of 44 months of BRC withdrawal. The median time of BRC use was 47 months. There were no statistically significant differences regarding age, gender, BRC initial dose, length of BRC use, tumor size, pregnancy during treatment, previous surgery, or radiotherapy among patients who persisted with normoprolactinemia and those who did not, using both univariate and multivariate analysis. BRC-induced prolactinoma cell alterations are highly controversial; and so, whether the mechanism of PRL normalization after BRC withdrawal is related to BRC use or whether it is attributable to natural history is a matter for debate. A periodic assessment of PRL levels during BRC (and other dopamine-agonist drugs) withdrawal is recommended to avoid the unnecessary maintenance of therapy in a subset of patients with prolactinomas.
Asunto(s)
Bromocriptina/administración & dosificación , Antagonistas de Hormonas/administración & dosificación , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactina/sangre , Prolactinoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/patología , Embarazo , Prolactinoma/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Bromocriptina/uso terapéutico , Ergolinas/uso terapéutico , Prolactinoma/tratamiento farmacológico , Antagonistas de Dopamina/uso terapéutico , Tolerancia a Medicamentos/fisiología , Resistencia a Medicamentos/fisiologíaRESUMEN
Serum prolactin level is very important to discriminate prolactiomas from other causes of hyperprolactinemia, specially pseudoprolactinomas. We describe two hyperprolactinemic men: case 1 is 28y old with headache, left eye visual loss and ptosis associated with a huge mass of the sellar region who was operated on elsewhere by transcranial route. These was no visual amelioration. Two months after surgery the patient was admitted to our Unit with impairment of right eye vision. Galactorrhea was found and imaging evaluation showed persistence of a large tumor. After blood sampling for hormonal assessment, oral bromocriptine (10 mg/day) was started and a dramatic right visual improvement was noticed. However, basal prolactin by immunoradiometric assay (IRMA) was 97mug/L. Due to the clinical signs and response suggesting prolactinoma, prolactin level was reassessed. A two-incubation and serial dilution of the same sample up to 1:1,200 disclosed a prolactin value of 25,572 mug/L. Case 2 is 20y old with headache, bitemporal hemianopsia, seizures and hypogonadism secondary to a giant tumor arising from the sellas region. Initial serum prolactin level measured by IRMA was 104 mug/L, which after two-incubations and dilutions up to 1:200 disclosed a value of 17,736 mug/L; clinical treatment was instituted with good results. In order to avoid unnecessary surgeries, we recommend a two-incubation procedure in routine prolactin determinations when IRMA is used.