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PRLuRegulated by the hypothalamus 主要是 tonic inhibitionuHypothalamus 分泌 2 種 hypothalamic factors - PIF (PRL-inhibiting factor) Dopamine - PRF (PRL-releasing factor) TRH, VIPPRLuStimulate breast developmentuInitiate and maintain lactation uPRL receptor - alveolar surface of mammary cell - liver, kidney - ovary, testes, prostateuEstrogen - synergistic in promoting breast development - antagonize in effect of lactationBreast developmentu須要多種 hormone 的 coordinated action包括 major stimuli: estrogenprogesteroneprolactinGH placental mammotropic Hminor stmuli: insulincortisolthyroid hormoneBreast developmentuDuct growth: estrogenuLobuloalveolar development: PRL+progesteroneuLactation: PRL + oxytocinGalactorrhea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 hyperprolactinemiaPRLu1928discovered in extract of bovine pituitaryu1970sensitive bioassayu1971RIA (Friesen, Fournier, Desjardians) secreted by the erythrosinophilic subtypeof chromophobic cells in the adenohypophysisPRLuA stress hormoneuSecreted in a pulsatile fashion highest in the early morning (睡醒之前) lower in the afternoonuphysiologic PRL - pain - nipple stimulation - fondling (women only) - pregnancy (可達 200-500 ng/ml) - pelvic examination - exercise - sleepPRLuDaily secretion rate: 400g/天uMetabolic clearance: 40 ml/m2/minuClearance pathway: 25% kidney 75% liveruPlasma T1/2: 50 minuPlasma level: 300 ng/mlumbilical PRL maternal PRLuPituitary PRL: 100 g per pituitary PRLuPRL value 和 prolactinoma tumor size 成正比uPRL 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 PRLuBlood sampling 須注意事項 -indwelling venous cannula -at least 2 hr resting -20 minutes interval 3-6 次 -sampling time usually not criticalHyperprolactinemiauBasic mechanisms () - Hypothalamic dopamine deficiencylhypothalamic tumorlAV malformationlinflammatory processldrugs: methyldopa (Aldomet)reserpine -Defective transport mechanismslpituitary or stalk tumorlhead injurylsection of pituitary stalkHyperprolactinemiauBasic mechanisms () -Lactotroph insensitivity to dopamineldopamine receptor blocking agents - phenothiazine (chlorpromazine) - butyrophenones (haloperidol) - benzamide: metoclopamidesulpiridedomperidone -Stimulation of lactotrophslHypothyroidismlTRHlEstrogenlChest wall injury: herpes zoster, surgerylPRL-producing tumorPituitary tumoru約佔 brain tumor 的 10% 左右 -Prolactinoma40-50% -Non-functioning adenoma 30% -Gonadotroph cell adenoma10-15% -Acromegaly10% -Cushings disease -TSH-secreting adenomaProlactinomauGeneral population 中可能5-10%有 prolactinoma - 這其中只有 5-10% come to clinical attension2/3 microadenoma 1/3 macroadenomauAutopsy study - 6.5-27% (11%) 有 pituitary adenoma - no antemortem endocrine dysfunction - 40-50% (+) for PRL by immunocytochemical stain - 幾乎全部為 microadenomaProlactinomauGrow slowly over yearsuLarge tumor hypopituitarism(singly or incombination)GH deficiency 最常見uImpaired pulsatile gonadotropin (LH, FSH) (via alteration in hypothalamic LHRH secretion) (increased endogenous opiate tone)uBMD ProlactinomauGrade: microadenoma (s suprasellar extension)uGrade: macroadenoma (c or s suprasellar extension)uGrade: localized boney destructionuGrade: diffuse boney destruction_Pituitary capillaryuCapillary in pituitarynormal62 capillaries/0.1mm2microadenoma51.1macroadenoma 9.3由於 capillary number 減少 less inhibited by PRL-inhibiting factorserum PRL 和 tumor size 成正比ProlactinomauEtiology: unclear? Arise de novo? Estrogen-induced? Abnormality of hypothalamic regulation? Monoclonal in originCauses of hyperprolactinemia ()uHypothalamic disease - Tumor: metastatic cacarniopharyngiomagerminomacyst, hamartomaglioma - Infiltrative diseasesarcoidosistbchistiocytosisgranuloma - Pseudotumor cerebri - Cranial irradiation Causes of hyperprolactinemia ()uPituitary disease - Prolactinoma - Acromegaly - Cushings disease - Pituitary stalk section - Empty sella syndrome - Metastatic ca - Meningioma - Intrasella germinoma - Infiltrative diseaselsarcoidosisltbclgiant cell granulomaCause of hyperprolactinemia () uDrug-induced - Monoamine inhibitor (catecholamine depletor)(在 hypothalamus 抑制 dopamine)lAldometlReserpine - Dopamine receptor antagonist(在 pituitary 抑制 dopamine)lChlorpromazine (wintermin)lFluphenazine (wintermin)lPerphenazinelPromazinelButyrophenone (haloperidol)lMotoclopramide (primperan)lDomperidone (motilium)lSulpiride (dogmatyl)Causes of hyperprolactinemia ()uDrug-induced - Lactotroph stimulatorlEstrogenlTRH - NarcoticslMorphinelEnkephalinlCodei