高泌乳激素血症 (Hyperprolactinemia),白永河 內分泌暨新陳代謝科 彰化基督教醫院,PRL,Regulated by the hypothalamus主要是 tonic inhibition Hypothalamus 分泌 2 種 hypothalamic factors PIF (PRL-inhibiting factor)Dopamine PRF (PRL-releasing factor)TRH, VIP,PRL,Stimulate breast development Initiate and maintain lactation PRL receptor alveolar surface of mammary cell liver, kidney ovary, testes, prostate Estrogen synergistic in promoting breast development antagonize in effect of lactation,Breast development,須要多種 hormone 的 coordinated action包括 major stimuli: estrogenprogesteroneprolactinGHplacental mammotropic Hminor stmuli: insulincortisolthyroid hormone,Breast development,Duct growth: estrogen Lobuloalveolar development: PRL+progesterone Lactation: PRL + oxytocin,Galactorrhea,需要 PRL + Gonadal steroid 才會出現 not necessarily seen in all prolactinomas 和 serum PRL level 無關 Galactorrhea 的 incidence 差異很大女性 30-80%男性常 no galactorrhea 即使有 galactorrhea, 其中50%病人的 PRL 可能正常 反之，即使 PRL 100ng/ml, 也可能 no galactorrhea Galactorrhea 為 poor marker of hyperprolactinemia,PRL,1928 discovered in extract of bovine pituitary 1970 sensitive bioassay 1971 RIA (Friesen, Fournier, Desjardians) secreted by the erythrosinophilic subtypeof chromophobic cells in the adenohypophysis,PRL,A stress hormone Secreted in a pulsatile fashionhighest in the early morning (睡醒之前)lower in the afternoon physiologic PRL pain nipple stimulation fondling (women only) pregnancy (可達 200-500 ng/ml) pelvic examination exercise sleep,PRL,Daily secretion rate: 400g/天 Metabolic clearance: 40 ml/m2/min Clearance pathway: 25% kidney 75% liver Plasma T1/2: 50 min Plasma level: 300 ng/mlumbilical PRL maternal PRL Pituitary PRL: 100 g per pituitary,PRL,PRL value 和 prolactinoma tumor size 成正比 PRL 1000 ng/ml tumor extension into cavernous sinus 150 ng/ml 幾乎一定就是 prolactinoma100-150 ng/ml: (1) prolactinoma(2) pseudoprolactinoma(3) drug-induced20-100 ng/ml: 須 repeat 檢查 ( pulsatile secretion)(1) stress of vein puncture (pain)(2) stress or physical examination(3) breast examination(4) pelvic examination,PRL,Blood sampling 須注意事項 indwelling venous cannula at least 2 hr resting 20 minutes interval 3-6 次 sampling time usually not critical,Hyperprolactinemia,Basic mechanisms ()Hypothalamic dopamine deficiency hypothalamic tumor AV malformation inflammatory process drugs: methyldopa (Aldomet)reserpine Defective transport mechanisms pituitary or stalk tumor head injury section of pituitary stalk,Hyperprolactinemia,Basic mechanisms () Lactotroph insensitivity to dopamine dopamine receptor blocking agents phenothiazine (chlorpromazine) butyrophenones (haloperidol) benzamide: metoclopamidesulpiridedomperidone Stimulation of lactotrophs Hypothyroidism TRH Estrogen Chest wall injury: herpes zoster, surgery PRL-producing tumor,Pituitary tumor,約佔 brain tumor 的 10% 左右 Prolactinoma 40-50% Non-functioning adenoma 30% Gonadotroph cell adenoma 10-15% Acromegaly 10% Cushings disease TSH-secreting adenoma,Prolactinoma,General population 中可能5-10%有 prolactinoma 這其中只有 5-10% come to clinical attension2/3 microadenoma1/3 macroadenoma Autopsy study 6.5-27% (11%) 有 pituitary adenoma no antemortem endocrine dysfunction 40-50% (+) for PRL by immunocytochemical stain 幾乎全部為 microadenoma,Prolactinoma,Grow slowly over years Large tumor hypopituitarism(singly or incombination) GH deficiency 最常見 Impaired pulsatile gonadotropin (LH, FSH)(via alteration in hypothalamic LHRH secretion) (increased endogenous opiate tone) BMD ,Prolactinoma,Grade: microadenoma (s suprasellar extension) Grade: macroadenoma (c or s suprasellar extension) Grade: localized boney destruction Grade: diffuse boney destruction,_,_,_,Pituitary capillary,Capillary in pituitarynormal 62 capillaries/0.1mm2microadenoma 51.1macroadenoma 9.3 由於 capillary number 減少 less inhibited by PRL-inhibiting factor serum PRL 和 tumor size 成正比,Prolactinoma,Etiology: unclear? Arise de novo? Estrogen-induced? Abnormality of hypothalamic regulation? Monoclonal in origin,Causes of hyperprolactinemia (),Hypothalamic disease Tumor: metastatic cacarniopharyngiomagerminomacyst, hamartomaglioma Infiltrative diseasesarcoidosistbchistiocytosisgranuloma Pseudotumor cerebri Cranial irradiation,Causes of hyperprolactinemia (),Pituitary disease Prolactinoma Acromegaly Cushings disease Pituitary stalk section Empty sella syndrome Metastatic ca Meningioma Intrasella germinoma Infiltrative disease sarcoidosis tbc giant cell granuloma,Cause of hyperprolactinemia (),Drug-induced Monoamine inhibitor (catecholamine depletor)(在 hypothalamus 抑制 dopamine) Aldomet Reserpine Dopamine receptor antagonist(在 pituitary 抑制 dopamine) Chlorpromazine (wintermin) Fluphenazine (wintermin) Perphenazine Promazine Butyrophenone (haloperidol) Motoclopramide (primperan) Domperidone (motilium) Sulpiride (dogmatyl),Causes of hyperprolactinemia (),Drug-induced Lactotroph stimulator Estrogen TRH Narcotics Morphine Enkephalin Codeine Methadone Amphetamine H2-receptor blocker Cimetidine (Tagamet) Ranitidine (Zantac),