高泌乳激素血症.ppt
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1、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 al
2、veolar 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: estrogen progesterone prolactin GH placental mammotropic H minor stmuli:
3、insulin cortisol thyroid 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 ga
4、lactorrhea 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 subtype of ch
5、romophobic cells in the adenohypophysis,PRL,A stress hormone Secreted in a pulsatile fashion highest 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 rat
6、e: 400g/天 Metabolic clearance: 40 ml/m2/min Clearance pathway: 25% kidney 75% liver Plasma T1/2: 50 min Plasma level: 300 ng/ml umbilical 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
7、就是 prolactinoma 100-150 ng/ml: (1) prolactinoma (2) pseudoprolactinoma (3) drug-induced 20-100 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 cann
8、ula 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 sta
9、lk tumor head injury section of pituitary stalk,Hyperprolactinemia,Basic mechanisms () Lactotroph insensitivity to dopamine dopamine receptor blocking agents phenothiazine (chlorpromazine) butyrophenones (haloperidol) benzamide: metoclopamide sulpiride domperidone Stimulation of lactotrophs Hypothyr
10、oidism 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 pr
11、olactinoma 這其中只有 5-10% come to clinical attension 2/3 microadenoma 1/3 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 (s
12、ingly 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 b
13、oney destruction Grade: diffuse boney destruction,_,_,_,Pituitary capillary,Capillary in pituitary normal 62 capillaries/0.1mm2 microadenoma 51.1 macroadenoma 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
14、? Estrogen-induced ? Abnormality of hypothalamic regulation ? Monoclonal in origin,Causes of hyperprolactinemia (),Hypothalamic disease Tumor: metastatic ca carniopharyngioma germinoma cyst, hamartoma glioma Infiltrative disease sarcoidosis tbc histiocytosis granuloma Pseudotumor cerebri Cranial irr
15、adiation,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 Monoami
16、ne 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) Sulpiri
17、de (dogmatyl),Causes of hyperprolactinemia (),Drug-induced Lactotroph stimulator Estrogen TRH Narcotics Morphine Enkephalin Codeine Methadone Amphetamine H2-receptor blocker Cimetidine (Tagamet) Ranitidine (Zantac),Causes of hyperprolactinemia (),Major systemic disease 1hypothyroidism CRF Liver cirr
18、hosis Seizure Neurogenic breast manipulation chest wall lesion burn herpes zoster mastectomy Stress: physical (pain) psychologic PCO Idiopathic,Symptoms and Signs (Female),Delayed menarche Disturbance of menstrual function (60-90%) amenorrhea oligomenorrhea regular mens c infertility Galactorrhea (3
19、0-80%) 和 duration of gonadal dysfunction 有關 amenorrhea 愈久,較不會有 galactorrhea Estrogen deficiency libido hirsutism vaginal dryness (DHEA by adrenal ) dyspareunia (free testosterone ),_,Symptoms and Signs (male),男性和 postmenopausal 女性較常以mass effect 表現 Headache (63%) Visual abnormality visual acuity opht
20、halmoplegia visual field defect (先 bitemporal upper quadrant anopia) (再 bitemporal hemianopia) Hypogonadism libido (83%) adiposity (70%) impotence galactorrhea (14-33%) infertility gynecomastia (少見),Mass effect,Suprasellar extension: bitemporal hemianopia Extends posteriorly homonymous visual field
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