Hyperprolactinemia

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Hyperprolactinemia

  1. 1. 高泌乳激素血症 (Hyperprolactinemia) <ul><li>白永河 </li></ul><ul><li>內分泌暨新陳代謝科 </li></ul><ul><li>彰化基督教醫院 </li></ul>
  2. 2. PRL <ul><li>Regulated by the hypothalamus </li></ul><ul><li>主要是 tonic inhibition </li></ul><ul><li>Hypothalamus 分泌 2 種 hypothalamic factors </li></ul><ul><ul><li>PIF (PRL-inhibiting factor) </li></ul></ul><ul><ul><li>Dopamine </li></ul></ul><ul><ul><li>PRF (PRL-releasing factor) </li></ul></ul><ul><ul><li>TRH, VIP </li></ul></ul>
  3. 3. PRL <ul><li>Stimulate breast development </li></ul><ul><li>Initiate and maintain lactation </li></ul><ul><li>PRL receptor </li></ul><ul><ul><li>alveolar surface of mammary cell </li></ul></ul><ul><ul><li>liver, kidney </li></ul></ul><ul><ul><li>ovary, testes, prostate </li></ul></ul><ul><li>Estrogen </li></ul><ul><ul><li>synergistic in promoting breast development </li></ul></ul><ul><ul><li>antagonize in effect of lactation </li></ul></ul>
  4. 4. Breast development <ul><li>須要多種 hormone 的 coordinated action </li></ul><ul><li>包括 major stimuli: estrogen </li></ul><ul><li> progesterone </li></ul><ul><li> prolactin </li></ul><ul><li> GH </li></ul><ul><li>placental mammotropic H </li></ul><ul><li>minor stmuli: insulin </li></ul><ul><li> cortisol </li></ul><ul><li> thyroid hormone </li></ul>
  5. 5. Breast development <ul><li>Duct growth: estrogen </li></ul><ul><li>Lobuloalveolar development: PRL+progesterone </li></ul><ul><li>Lactation: PRL + oxytocin </li></ul>
  6. 6. Galactorrhea <ul><li>需要 PRL + Gonadal steroid 才會出現 </li></ul><ul><li>∴ not necessarily seen in all prolactinomas </li></ul><ul><li>和 serum PRL level 無關 </li></ul><ul><li>Galactorrhea 的 incidence 差異很大 </li></ul><ul><li>女性 30 ~ -80% </li></ul><ul><li>男性常 no galactorrhea </li></ul><ul><li>即使有 galactorrhea, 其中 50% 病人的 PRL 可能正常 </li></ul><ul><li>反之,即使 PRL> 100ng/ml, 也可能 no galactorrhea </li></ul><ul><li>∴ Galactorrhea 為 poor marker of hyperprolactinemia </li></ul>
  7. 7. PRL <ul><li>1928 discovered in extract of bovine pituitary </li></ul><ul><li>1970 sensitive bioassay </li></ul><ul><li>1971 RIA (Friesen, Fournier, Desjardians) </li></ul><ul><li>secreted by the erythrosinophilic subtype </li></ul><ul><li>of chromophobic cells in the adenohypophysis </li></ul>
  8. 8. PRL <ul><li>A stress hormone </li></ul><ul><li>Secreted in a pulsatile fashion </li></ul><ul><li>highest in the early morning ( 睡醒之前 ) </li></ul><ul><li>lower in the afternoon </li></ul><ul><li>physiologic PRL ↑ </li></ul><ul><ul><li>pain </li></ul></ul><ul><ul><li>nipple stimulation </li></ul></ul><ul><ul><li>fondling (women only) </li></ul></ul><ul><ul><li>pregnancy ( 可達 200-500 ng/ml) </li></ul></ul><ul><ul><li>pelvic examination </li></ul></ul><ul><ul><li>exercise </li></ul></ul><ul><ul><li>sleep </li></ul></ul>
  9. 9. PRL <ul><li>Daily secretion rate: 400 μ g/ 天 </li></ul><ul><li>Metabolic clearance: 40 ml/m 2 /min </li></ul><ul><li>Clearance pathway: 25% kidney </li></ul><ul><li> 75% liver </li></ul><ul><li>Plasma T 1/2 : 50 min </li></ul><ul><li>Plasma level: < 15 ng/ml </li></ul><ul><li>♂ :5 ng/ml (3-10) </li></ul><ul><li>♀ :8 ng/ml (5-15) </li></ul><ul><li> fetal PRL > 300 ng/ml </li></ul><ul><li> umbilical PRL > maternal PRL </li></ul><ul><li>Pituitary PRL: 100 μ g per pituitary </li></ul>
  10. 10. PRL <ul><li>PRL value 和 prolactinoma tumor size 成正比 </li></ul><ul><li>PRL > 1000 ng/ml -> tumor extension into cavernous sinus </li></ul><ul><li>> 150 ng/ml -> 幾乎一定就是 prolactinoma </li></ul><ul><li> 100-150 ng/ml: (1) prolactinoma </li></ul><ul><li> (2) pseudoprolactinoma </li></ul><ul><li> (3) drug-induced </li></ul><ul><li> 20-100 ng/ml: 須 repeat 檢查 ( ∵ pulsatile secretion) </li></ul><ul><li>(1) stress of vein puncture (pain) </li></ul><ul><li>(2) stress or physical examination </li></ul><ul><li>(3) breast examination </li></ul><ul><li>(4) pelvic examination </li></ul>
  11. 11. PRL <ul><li>Blood sampling 須注意事項 </li></ul><ul><ul><li>indwelling venous cannula </li></ul></ul><ul><ul><li>at least 2 hr resting </li></ul></ul><ul><ul><li>20 minutes interval × 3-6 次 </li></ul></ul><ul><ul><li>sampling time usually not critical </li></ul></ul>
  12. 12. Hyperprolactinemia <ul><li>Basic mechanisms ( Ⅰ ) </li></ul><ul><ul><li>Hypothalamic dopamine deficiency </li></ul></ul><ul><ul><ul><li>hypothalamic tumor </li></ul></ul></ul><ul><ul><ul><li>AV malformation </li></ul></ul></ul><ul><ul><ul><li>inflammatory process </li></ul></ul></ul><ul><ul><ul><li>drugs: methyldopa (Aldomet) </li></ul></ul></ul><ul><ul><ul><li> reserpine </li></ul></ul></ul><ul><ul><li>Defective transport mechanisms </li></ul></ul><ul><ul><ul><li>pituitary or stalk tumor </li></ul></ul></ul><ul><ul><ul><li>head injury </li></ul></ul></ul><ul><ul><ul><li>section of pituitary stalk </li></ul></ul></ul>
  13. 13. Hyperprolactinemia <ul><li>Basic mechanisms ( Ⅱ ) </li></ul><ul><ul><li>Lactotroph insensitivity to dopamine </li></ul></ul><ul><ul><ul><li>dopamine receptor blocking agents </li></ul></ul></ul><ul><ul><ul><ul><li>phenothiazine (chlorpromazine) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>butyrophenones (haloperidol) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>benzamide: metoclopamide </li></ul></ul></ul></ul><ul><ul><ul><ul><li> sulpiride </li></ul></ul></ul></ul><ul><ul><ul><ul><li> domperidone </li></ul></ul></ul></ul><ul><ul><li>Stimulation of lactotrophs </li></ul></ul><ul><ul><ul><li>Hypothyroidism </li></ul></ul></ul><ul><ul><ul><li>TRH </li></ul></ul></ul><ul><ul><ul><li>Estrogen </li></ul></ul></ul><ul><ul><ul><li>Chest wall injury: herpes zoster, surgery </li></ul></ul></ul><ul><ul><ul><li>PRL-producing tumor </li></ul></ul></ul>
  14. 14. Pituitary tumor <ul><li>約佔 brain tumor 的 10% 左右 </li></ul><ul><ul><li>Prolactinoma 40-50% </li></ul></ul><ul><ul><li>Non-functioning adenoma 30% </li></ul></ul><ul><ul><li>Gonadotroph cell adenoma 10-15% </li></ul></ul><ul><ul><li>Acromegaly 10% </li></ul></ul><ul><ul><li>Cushing's disease </li></ul></ul><ul><ul><li>TSH-secreting adenoma </li></ul></ul>
  15. 15. Prolactinoma <ul><li>General population 中可能 5-10% 有 prolactinoma </li></ul><ul><ul><li>這其中只有 5-10% come to clinical attension </li></ul></ul><ul><li>2/3 microadenoma </li></ul><ul><li>1/3 macroadenoma </li></ul><ul><li>Autopsy study </li></ul><ul><ul><li>6.5-27% (11%) 有 pituitary adenoma </li></ul></ul><ul><ul><li>no antemortem endocrine dysfunction </li></ul></ul><ul><ul><li>40-50% (+) for PRL by immunocytochemical stain </li></ul></ul><ul><ul><li>幾乎全部為 microadenoma </li></ul></ul>
  16. 16. Prolactinoma <ul><li>Grow slowly over years </li></ul><ul><li>Large tumor -> hypopituitarism </li></ul><ul><li> (singly or incombination) GH deficiency 最常見 </li></ul><ul><li>Impaired pulsatile gonadotropin (LH, FSH) </li></ul><ul><li>(via alteration in hypothalamic LHRH secretion) (increased endogenous opiate tone) </li></ul><ul><li>BMD ↓ </li></ul>
  17. 17. Prolactinoma <ul><li>Grade Ⅰ : microadenoma (s suprasellar extension) </li></ul><ul><li>Grade Ⅱ : macroadenoma (c or s suprasellar extension) </li></ul><ul><li>Grade Ⅲ : localized boney destruction </li></ul><ul><li>Grade Ⅳ : diffuse boney destruction </li></ul>_ _ _
  18. 18. Pituitary capillary <ul><li>Capillary in pituitary </li></ul><ul><li>normal 62 capillaries/0.1mm2 </li></ul><ul><li>microadenoma 51.1 </li></ul><ul><li>macroadenoma 9.3 </li></ul><ul><li>由於 capillary number 減少 </li></ul><ul><li>∴ less inhibited by PRL-inhibiting factor </li></ul><ul><li>serum PRL 和 tumor size 成正比 </li></ul>
  19. 19. Prolactinoma <ul><li>Etiology: unclear </li></ul><ul><li>? Arise de novo </li></ul><ul><li>? Estrogen-induced </li></ul><ul><li>? Abnormality of hypothalamic regulation </li></ul><ul><li>? Monoclonal in origin </li></ul>
  20. 20. Causes of hyperprolactinemia ( Ⅰ ) <ul><li>Hypothalamic disease </li></ul><ul><ul><li>Tumor: metastatic ca </li></ul></ul><ul><ul><li> carniopharyngioma </li></ul></ul><ul><ul><li> germinoma </li></ul></ul><ul><ul><li> cyst, hamartoma </li></ul></ul><ul><ul><li> glioma </li></ul></ul><ul><ul><li>Infiltrative disease </li></ul></ul><ul><ul><li> sarcoidosis </li></ul></ul><ul><ul><li> tbc </li></ul></ul><ul><ul><li> histiocytosis </li></ul></ul><ul><ul><li> granuloma </li></ul></ul><ul><ul><li>Pseudotumor cerebri </li></ul></ul><ul><ul><li>Cranial irradiation </li></ul></ul>
  21. 21. Causes of hyperprolactinemia ( Ⅱ ) <ul><li>Pituitary disease </li></ul><ul><ul><li>Prolactinoma </li></ul></ul><ul><ul><li>Acromegaly </li></ul></ul><ul><ul><li>Cushing's disease </li></ul></ul><ul><ul><li>Pituitary stalk section </li></ul></ul><ul><ul><li>Empty sella syndrome </li></ul></ul><ul><ul><li>Metastatic ca </li></ul></ul><ul><ul><li>Meningioma </li></ul></ul><ul><ul><li>Intrasella germinoma </li></ul></ul><ul><ul><li>Infiltrative disease </li></ul></ul><ul><ul><ul><li>sarcoidosis </li></ul></ul></ul><ul><ul><ul><li>tbc </li></ul></ul></ul><ul><ul><ul><li>giant cell granuloma </li></ul></ul></ul>
  22. 22. Cause of hyperprolactinemia ( Ⅲ ) <ul><li>Drug-induced </li></ul><ul><ul><li>Monoamine inhibitor (catecholamine depletor) </li></ul></ul><ul><ul><li>( 在 hypothalamus 抑制 dopamine) </li></ul></ul><ul><ul><ul><li>Aldomet </li></ul></ul></ul><ul><ul><ul><li>Reserpine </li></ul></ul></ul><ul><ul><li>Dopamine receptor antagonist </li></ul></ul><ul><ul><li>( 在 pituitary 抑制 dopamine) </li></ul></ul><ul><ul><ul><li>Chlorpromazine (wintermin) </li></ul></ul></ul><ul><ul><ul><li>Fluphenazine (wintermin) </li></ul></ul></ul><ul><ul><ul><li>Perphenazine </li></ul></ul></ul><ul><ul><ul><li>Promazine </li></ul></ul></ul><ul><ul><ul><li>Butyrophenone (haloperidol) </li></ul></ul></ul><ul><ul><ul><li>Motoclopramide (primperan) </li></ul></ul></ul><ul><ul><ul><li>Domperidone (motilium) </li></ul></ul></ul><ul><ul><ul><li>Sulpiride (dogmatyl) </li></ul></ul></ul>
  23. 23. Causes of hyperprolactinemia ( Ⅳ ) <ul><li>Drug-induced </li></ul><ul><ul><li>Lactotroph stimulator </li></ul></ul><ul><ul><ul><li>Estrogen </li></ul></ul></ul><ul><ul><ul><li>TRH </li></ul></ul></ul><ul><ul><li>Narcotics </li></ul></ul><ul><ul><ul><li>Morphine </li></ul></ul></ul><ul><ul><ul><li>Enkephalin </li></ul></ul></ul><ul><ul><ul><li>Codeine </li></ul></ul></ul><ul><ul><ul><li>Methadone </li></ul></ul></ul><ul><ul><li>Amphetamine </li></ul></ul><ul><ul><li>H2-receptor blocker </li></ul></ul><ul><ul><ul><li>Cimetidine (Tagamet) </li></ul></ul></ul><ul><ul><ul><li>Ranitidine (Zantac) </li></ul></ul></ul>
  24. 24. Causes of hyperprolactinemia ( Ⅴ ) <ul><li>Major systemic disease </li></ul><ul><ul><li>1 ° hypothyroidism </li></ul></ul><ul><ul><li>CRF </li></ul></ul><ul><ul><li>Liver cirrhosis </li></ul></ul><ul><ul><li>Seizure </li></ul></ul><ul><li>Neurogenic </li></ul><ul><ul><li>breast manipulation </li></ul></ul><ul><ul><li>chest wall lesion </li></ul></ul><ul><ul><ul><li>burn </li></ul></ul></ul><ul><ul><ul><li>herpes zoster </li></ul></ul></ul><ul><ul><ul><li>mastectomy </li></ul></ul></ul><ul><li>Stress: ‧ physical (pain) </li></ul><ul><ul><li>‧ psychologic </li></ul></ul><ul><li>PCO </li></ul><ul><li>Idiopathic </li></ul>
  25. 25. Symptoms and Signs (Female) <ul><li>Delayed menarche </li></ul><ul><li>Disturbance of menstrual function (60-90%) </li></ul><ul><li>amenorrhea </li></ul><ul><li>oligomenorrhea </li></ul><ul><li>regular mens c infertility </li></ul><ul><li>Galactorrhea (30-80%) </li></ul><ul><li>和 duration of gonadal dysfunction 有關 </li></ul><ul><li>amenorrhea 愈久,較不會有 galactorrhea </li></ul><ul><li>Estrogen deficiency </li></ul><ul><ul><li>libido ↓ hirsutism </li></ul></ul><ul><ul><li> vaginal dryness (DHEA by adrenal ↑ ) </li></ul></ul><ul><ul><li>dyspareunia (free testosterone ↑ ) </li></ul></ul>_
  26. 26. Symptoms and Signs (male) <ul><li>男性和 postmenopausal 女性較常以 mass effect 表現 </li></ul><ul><li>Headache (63%) </li></ul><ul><li>Visual abnormality </li></ul><ul><ul><li>visual acuity ↓ </li></ul></ul><ul><ul><li>ophthalmoplegia </li></ul></ul><ul><ul><li>visual field defect </li></ul></ul><ul><ul><li>( 先 bitemporal upper quadrant anopia) </li></ul></ul><ul><ul><li>( 再 bitemporal hemianopia) </li></ul></ul><ul><li>Hypogonadism </li></ul><ul><ul><li>libido ↓ (83%) adiposity (70%) </li></ul></ul><ul><ul><li>impotence galactorrhea (14-33%) </li></ul></ul><ul><ul><li>infertility gynecomastia ( 少見 ) </li></ul></ul>
  27. 27. Mass effect <ul><li>Suprasellar extension: bitemporal hemianopia </li></ul><ul><li>Extends posteriorly </li></ul><ul><ul><li>homonymous visual field defect </li></ul></ul><ul><li>Lateral extension (into the cavernous sinus) </li></ul><ul><ul><li>compress cranial nerve 3, 4, 5, 6 </li></ul></ul><ul><li>Extend into the temporal lobe : seizure </li></ul>
  28. 28. Hyperprolactinemia <ul><li>干擾 hypothalamic-pituitary-ovarian axis </li></ul><ul><li>at 3 locations </li></ul><ul><ul><li>hypothalamic level </li></ul></ul><ul><ul><ul><li>interfer tonic or cyclic release of GnRH (LHRH) </li></ul></ul></ul><ul><ul><li>pituitary level </li></ul></ul><ul><ul><ul><li>desensitize gonadotropin response to GnRH </li></ul></ul></ul><ul><ul><li>ovarian level </li></ul></ul><ul><ul><ul><li>impaires progesterone production </li></ul></ul></ul><ul><ul><ul><li>(by ovarian granulosa cell) </li></ul></ul></ul>
  29. 29. PRL <ul><li>PRL function in male: unclear </li></ul><ul><ul><li>sperm production </li></ul></ul><ul><ul><li>prostate citrate production </li></ul></ul><ul><li>PRL ↑-> 5 α -reductase ↓ </li></ul>Spermatogenesis testosterone dihydrotestosterone (biologically active) 5 α -reductase
  30. 30. Pseudoprolactinoma <ul><li>任何 intrasellar or parasellar tumor </li></ul><ul><li> (non-PRL-secreting pituitary adenoma) </li></ul><ul><li>-> pituitary stalk compression </li></ul><ul><li>-> interfer with PIF delivery (Dopamine) </li></ul><ul><li>-> PRL ↑ ( 很少 > 150 ng/ml) </li></ul><ul><li>例如 : </li></ul><ul><li>non-functioning pituitary adenoma </li></ul><ul><li>craniopharyngioma </li></ul><ul><li>tuberculum sella meningioma </li></ul><ul><li>aneurysm </li></ul>
  31. 31. Normoprolactinemic galactorrhea <ul><li>enhanced sensitivity of breast to PRL </li></ul><ul><li>常見於 persistence of postpartum galactorrhea </li></ul><ul><li> after discontinuation of oral pills </li></ul>
  32. 32. Pregnancy with prolactinoma <ul><li>Microadenoma </li></ul><ul><li>5% progress to macroadenoma </li></ul><ul><li>Macroadenoma </li></ul><ul><li>25% expand and produce symptoms </li></ul><ul><li>(15-35%) </li></ul>
  33. 33. Primary hypothyroidism <ul><li>常有 breast tenderness, 偶而 galactorrhea </li></ul><ul><li>PRL 大部份正常 </li></ul><ul><li>但也可能上昇,通常 < 100 ng /ml </li></ul><ul><li>long-standing hypothyroidism 時 </li></ul><ul><li>可能出現 sellar enlargement </li></ul><ul><li>如果又加上 PRL ↑ ,易誤為 prolactinoma </li></ul><ul><li>PRL response to TRH ↑ </li></ul>
  34. 34. CRF <ul><li>PRL ↑ in 60-70% ( < 150ng/ml) </li></ul><ul><li>PRL response to TRH ↓ </li></ul><ul><li>receptor or postreceptor defect in the lactotroph </li></ul><ul><li>not altered by HD </li></ul><ul><li>reversed by renal transplantation </li></ul>
  35. 35. D.D. of hyperprolactinemia <ul><li>Prolactinoma </li></ul><ul><li>Primary hypothyroidism (TSH) </li></ul><ul><li>CRF (BUN/Cr) </li></ul><ul><li>Liver cirrhosis (GOT/GPT, A/G) </li></ul><ul><li>Cushing's syndrome (cortisol) </li></ul><ul><li>Acromegaly (GH) </li></ul><ul><li>Drug-induced (history taking) </li></ul><ul><li>Pregnancy ( β -HCG) </li></ul><ul><li>Pseudoprolactinoma </li></ul><ul><li>Physiologic hyperprolactinemia </li></ul>
  36. 36. Treatment of microadenoma <ul><li>Disadvantage of untreated microadenoma </li></ul><ul><ul><li>loss of libido </li></ul></ul><ul><ul><li>dyspareunia, hypogonadism </li></ul></ul><ul><ul><li>BMD ↓ </li></ul></ul><ul><ul><li>premature CAD </li></ul></ul><ul><ul><li>enlargement of tumor mass </li></ul></ul>
  37. 37. Microadenoma <ul><li>Indication of treatment </li></ul><ul><ul><li>desire of becoming pregnant </li></ul></ul><ul><ul><li>須 eliminate galactorrhea </li></ul></ul><ul><ul><li>須 relieve symptoms of hypogonadism </li></ul></ul><ul><li>如果上述 concern 不存在 </li></ul><ul><ul><li>periodically follow up 即可 </li></ul></ul>
  38. 38. Prolactinoma <ul><li>Therapeutic decision making </li></ul><ul><ul><li>Microadenoma </li></ul></ul><ul><ul><ul><li>desire for pregnancy (-) -> periodically follow up </li></ul></ul></ul><ul><ul><ul><li>desire for pregnancy (+) -> surgery </li></ul></ul></ul><ul><ul><ul><li>recurrent after surgery -> pharmacotherapy </li></ul></ul></ul><ul><ul><li>Macroadenoma </li></ul></ul><ul><ul><ul><li>Ⅰ : PRL 200-500 ng/ml, invasiveness (-): surgery </li></ul></ul></ul><ul><ul><ul><li>Ⅱ : PRL 500-1000 ng/ml, 或 invasiveness (+) </li></ul></ul></ul><ul><ul><ul><li> pharmacotherapy or surgery </li></ul></ul></ul><ul><ul><ul><li>Ⅲ : PRL > 1000 ng/ml, invasiveness (+) </li></ul></ul></ul><ul><ul><ul><li>pharmacotherapy </li></ul></ul></ul>
  39. 39. Pharmacotherapy of prolactinoma <ul><li>Ergot preparation </li></ul><ul><ul><li>Bromocriptin (approved by FDA) </li></ul></ul><ul><ul><li>Lisuride </li></ul></ul><ul><ul><li>Pergolide </li></ul></ul><ul><ul><li>Metergoline </li></ul></ul><ul><ul><li>Terguride (greater pituitary selectivity) </li></ul></ul><ul><ul><li>Cabergoline (longer duration of action) </li></ul></ul><ul><li>non-Ergot preparation </li></ul><ul><ul><li>CV 205-502 (Octahydrobenzquinolone) </li></ul></ul>
  40. 40. Bromocriptine <ul><li>Dopamine agonist, 1971 </li></ul><ul><li>semisynthetic ergot alkaloid </li></ul><ul><li>binds to the dopamine receptor </li></ul><ul><li>affinity 為 dopamine 的 5-10X </li></ul><ul><li>使 PRL 恢復至 normal, in 64-100% </li></ul><ul><li>改善 galactorrhea, 57-100% </li></ul><ul><li>恢復 mens and ovulation, 57-100% </li></ul><ul><li>改善 visual field defect, 60-80% </li></ul><ul><li>使 tumor size reduction, 60-80% </li></ul><ul><li>但無法改善 loss of sleep-related PRL pulsatile secretion </li></ul>
  41. 41. Bromocriptine therapy <ul><li>the only FDA approved drug in the USA </li></ul><ul><li>initial dose : 1.25 mg H.S. </li></ul><ul><li>dose adjustment: 改換成 1.25 mg QD ( c meal) </li></ul><ul><li> 每隔 3 天增加 1.25 mg </li></ul><ul><li>standard dose: 2.5 mg tid </li></ul><ul><li>maintain dose: 2.5 mg bid </li></ul>_
  42. 42. Bromocriptine therapy <ul><li>Drug efficacy in reducing PRL doesn't necessarily predict tumor size reduction </li></ul><ul><ul><li>即使 PRL 沒有下降到正常,也可能有 tumor shrinkage </li></ul></ul><ul><ul><li>即使 PRL 下降到正常,也不一定就有相等程度的 tumor size reduction </li></ul></ul><ul><li>Short treatment period -> w ithdrawl </li></ul><ul><li> -> rapid reexpansion of tumor size </li></ul><ul><ul><li>therapeutic course 須持續幾年 </li></ul></ul><ul><ul><li>long-term therapy 後才停藥,可能不會有 tumor reexpansion, </li></ul></ul><ul><ul><li>但是 PRL 會再度上昇 </li></ul></ul>
  43. 43. Bromocriptine therapy <ul><li>Intolerate to oral therapy 時,可改用 vaginal administration (the same dosage) </li></ul><ul><li>Patient 必須被告知可能 restore fertility </li></ul><ul><li>∴ 須事先使用 mechanical contraception </li></ul><ul><li> ( 否則會在服藥治療期間 conception 而不自知 ) </li></ul><ul><li> 直到 regular menstrual flow × 3 cycles </li></ul><ul><li>Not teratogenic in human </li></ul><ul><li>fetal loss </li></ul><ul><li>congenital malformation </li></ul><ul><li>Injectable form available in Europe </li></ul><ul><li>effective for 4-6 wk </li></ul>: not increased ]
  44. 44. Bromocriptine therapy <ul><li>對於 large pituitary tumor </li></ul><ul><li> 如果 PRL > 200 ng/ml ,大部份是 prolactinoma </li></ul><ul><li> 如果 PRL < 200 ng/ml ,可能是 2 ° hyperprolactinemia </li></ul><ul><li> (pseudoprolactinoma) </li></ul><ul><li>Bromocriptine Rx Prolactinoma Pseudoprolactinoma </li></ul><ul><li>PRL ↓ ↓ </li></ul><ul><li>tumor size ↓ ( -) </li></ul>
  45. 45. Bromocriptine therapy <ul><li>Tumor most likely to response </li></ul><ul><ul><li>highest PRL </li></ul></ul><ul><ul><li>not combined PRL + GH secreting tumor </li></ul></ul><ul><li>Visual field defect 的改善,往往在 pituitary MRI 看到 tumor size reduction 之前 </li></ul><ul><li>( 表示仔細的 monitorning of visual acuity 和 visual field 為 more sensitive indicator of tumor response than image study) </li></ul>
  46. 46. Bromocriptine therapy <ul><li>Side effect </li></ul><ul><ul><li>GI upset : nausea, vomiting </li></ul></ul><ul><ul><li> abdominal fullness </li></ul></ul><ul><ul><li> abdominal cramping </li></ul></ul><ul><ul><li> constipation </li></ul></ul><ul><ul><li>Dizziness (orthostatic hypotension) </li></ul></ul><ul><ul><li>Headache </li></ul></ul><ul><ul><li>Fatigue </li></ul></ul><ul><ul><li>Nasal stuff </li></ul></ul><ul><ul><li>CSF rhinorrhea </li></ul></ul><ul><ul><li>Hallucination and psychosis (1.3%) </li></ul></ul>
  47. 47. Transsphenoid hypophysectomy <ul><li>Indication of surgical therapy </li></ul><ul><ul><li>intolerate to pharmacologic agent </li></ul></ul><ul><ul><li>inadequate to pharmacologic agent </li></ul></ul><ul><ul><ul><li>poor compliance </li></ul></ul></ul><ul><ul><ul><li>irregular follow up </li></ul></ul></ul><ul><ul><li>desire of becoming pregnant </li></ul></ul><ul><ul><li>cystic tumor </li></ul></ul><ul><ul><li>tumor apoplexy </li></ul></ul>
  48. 48. Surgical therapy <ul><li>cure rate recurrent rate </li></ul><ul><li>Microadenoma 70-90% 15-50% </li></ul><ul><li>Macroadenoma 20-30% 70-80% </li></ul>Varies with p't selection and surgical technique OP 後若 PRL > 9 ng/ml 可能表示會 recurrent Recurrent 時,再 reoperation 的效果並不好
  49. 49. Transsphenoid hypophysectomy <ul><li>Criteria of cure </li></ul><ul><ul><li>total removal of tumor mass </li></ul></ul><ul><ul><li>normalization of PRL </li></ul></ul><ul><ul><li>resumption of ovulatory menstruation </li></ul></ul><ul><ul><li>restore infertility </li></ul></ul><ul><ul><li>no evidence of recurrence over 5 years </li></ul></ul><ul><li>Criteria of recurrence </li></ul><ul><ul><li>reappearance of hyper PRL over 5-yr period </li></ul></ul>
  50. 50. Surgical therapy <ul><li>Surgical success rate </li></ul><ul><li>Microadenoma ↓ </li></ul><ul><li>Macroadenoma ↑ </li></ul>Preoperation bromocriptine therapy:
  51. 51. Surgical therapy <ul><li>Surgical success rate </li></ul><ul><li>bromocriptine-treated 44% </li></ul><ul><li>no bromocriptine 78% </li></ul><ul><li>fibrosis induced by bromocriptine </li></ul><ul><li>shrinkage of tumor cell </li></ul><ul><ul><li>enlargement of the extracellar & perivascular space </li></ul></ul><ul><ul><li>filled by the collagen deposition </li></ul></ul><ul><ul><li>more dense consistency of the adenoma </li></ul></ul><ul><li>shrunken tumor adhere to adjacent normal pituitary tissue </li></ul>Preoperation bromocriptine in microadenoma (Landolt, 1982)
  52. 52. Radiotherapy <ul><li>some effectiveness in reducing PRL </li></ul><ul><li>more slowly </li></ul><ul><li>less completely </li></ul><ul><li>alternative therapy (generally not recomnend as primary therapy) </li></ul><ul><li>indication: postoperation recurrence </li></ul>
  53. 53. When to check PRL <ul><li>Amenorrhea, oligomenorrhea </li></ul><ul><li>Galactorrhea </li></ul><ul><li>Sexual dysfunction </li></ul><ul><ul><li>loss of libido </li></ul></ul><ul><ul><li>dyspareunia ( ♀ ) </li></ul></ul><ul><ul><li>impotence ( ♂ ) </li></ul></ul><ul><li>Infertility </li></ul><ul><li>Visual field defect </li></ul><ul><li>Headache </li></ul>

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