先端巨大症の治療戦略
先端巨大症の治療の第一選択は手術である. 治癒率向上のためには手術成績を向上させることが最も大切である. しかし, 海綿静脈洞浸潤を伴う腺腫では手術のみで根治は困難である. 手術で治癒できない場合には薬物療法が必要である. 手術療法は経鼻的下垂体手術が基本的治療法であり, 内視鏡下手術も顕微鏡下併用, 内視鏡単独含めて一般的になりつつある. 一般に先端巨大症の手術治癒率はおよそ70%前後である. 手術により治癒できない症例では, 薬物療法が行われる. 薬物療法はsomatostatin analogが主流で, わが国では現在2剤が使われておりIGF-I正常化率はおよそ50～70%とされる....
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| Published in | 脳神経外科ジャーナル Vol. 24; no. 8; pp. 521 - 527 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本脳神経外科コングレス
2015
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0917-950X 2187-3100 |
| DOI | 10.7887/jcns.24.521 |
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| Abstract | 先端巨大症の治療の第一選択は手術である. 治癒率向上のためには手術成績を向上させることが最も大切である. しかし, 海綿静脈洞浸潤を伴う腺腫では手術のみで根治は困難である. 手術で治癒できない場合には薬物療法が必要である. 手術療法は経鼻的下垂体手術が基本的治療法であり, 内視鏡下手術も顕微鏡下併用, 内視鏡単独含めて一般的になりつつある. 一般に先端巨大症の手術治癒率はおよそ70%前後である. 手術により治癒できない症例では, 薬物療法が行われる. 薬物療法はsomatostatin analogが主流で, わが国では現在2剤が使われておりIGF-I正常化率はおよそ50～70%とされる. そのほかにdopamine agonistやGH receptor antagonistが用いられる. Dopamine agonistは内服薬であるが有効率は低い. GH receptor antagonistは, 有効率は70～90%と高いが副作用も多い. これらの薬物を併用することにより, IGF-I正常化率を高めることができる. 放射線治療は主に定位的放射線治療が行われるが, IGF-I正常化率は60～70%とされ, 正常化まで数年かかる. 今回は手術療法のトピックス, 薬物併用療法を中心に述べる. |
|---|---|
| AbstractList | 先端巨大症の治療の第一選択は手術である. 治癒率向上のためには手術成績を向上させることが最も大切である. しかし, 海綿静脈洞浸潤を伴う腺腫では手術のみで根治は困難である. 手術で治癒できない場合には薬物療法が必要である. 手術療法は経鼻的下垂体手術が基本的治療法であり, 内視鏡下手術も顕微鏡下併用, 内視鏡単独含めて一般的になりつつある. 一般に先端巨大症の手術治癒率はおよそ70%前後である. 手術により治癒できない症例では, 薬物療法が行われる. 薬物療法はsomatostatin analogが主流で, わが国では現在2剤が使われておりIGF-I正常化率はおよそ50～70%とされる. そのほかにdopamine agonistやGH receptor antagonistが用いられる. Dopamine agonistは内服薬であるが有効率は低い. GH receptor antagonistは, 有効率は70～90%と高いが副作用も多い. これらの薬物を併用することにより, IGF-I正常化率を高めることができる. 放射線治療は主に定位的放射線治療が行われるが, IGF-I正常化率は60～70%とされ, 正常化まで数年かかる. 今回は手術療法のトピックス, 薬物併用療法を中心に述べる. |
| Author | 富永, 篤 木下, 康之 栗栖, 薫 |
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| Copyright | 2015 日本脳神経外科コングレス |
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| References | 13) Feenstra J, de Herder WW, ten Have SM, van den Beld AW, Feelders RA, Janssen JA, van der Lely AJ : Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet 365 : 1644-1646, 2005. 17) Friedrich N, Alte D, Völzke H, Spilcke-Liss E, Lüdemann J, Lerch M. M, Kohlmann T, Nauck M, Wallaschofski H : Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population : results of the Study of Health in Pomerania (SHIP). Growth Horm IGF Res 18 : 228-237, 2008. 38) Yano S, Kawano T, Kudo M, Makino K, Nakamura H, Kai Y, Morioka M, Kuratsu J : Endoscopic endonasal transsphenoidal approach through the bilateral nostrils for pituitary adenomas. Neurol Med Chir (Tokyo) 49 : 1-7, 2009. 28) Mattar P, Alves Martins MR, Abucham J : Short-and long-term efficacy of combined cabergoline and octreotide treatment in controlling igf-I levels in acromegaly. Neuroendocrinology 92 : 120-127, 2010. 18) Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S : Criteria for cure of acromegaly : a consensus statement. J Clin Endocrinol Metab 85 : 526-529, 2000. 5) Carlsen SM, Svartberg J, Schreiner T, Aanderud S, Johannesen O, Skeie S, Lund-Johansen M, Fougner SL, Bollerslev J ; POTA study group : Six-month preoperative octreotide treatment in unselected, de novo patients with acromegaly : effect on biochemistry, tumour volume, and postoperative cure. Clin Endocrinol (Oxf) 74 : 736-743, 2011. 15) Freda PU, Wardlaw SL, Post KD : Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 89 : 353-358, 1998. 26) Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G : Octreotide may act as a radioprotective agent in acromegaly. J Clin Endocrinol Metab 85 : 1287-1289, 2000. 25) Lancranjan I, Atkinson AB : Results of a European multicentre study with Sandostatin LAR in acromegalic patients. Sandostatin LAR Group. Pituitary 1 : 105-114, 1999. 30) Nomikos P, Buchfelder M, Fahlbusch R : The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol 152 : 379-387, 2005. 33) Shimatsu A, Teramoto A, Hizuka N, Kitai K, Ramis J, Chihara K : Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism. Endocr J 60 : 651-663, 2013. 8) Cozzi R, Attanasio R, Barausse M, Dallabonzana D, Orlandi P, Da Re N, Branca V, Oppizzi G, Gelli D : Cabergoline in acromegaly : a renewed role for dopamine agonist treatment? Eur J Endocrinol 139 : 516-521, 1998. 14) Frank G, Pasquini E : Endoscopic endonasal cavernous sinus surgery, with special reference to pituitary adenomas. Front Horm Res 34 : 64-82, 2006. 31) Petersenn S, Farrall AJ, De Block C, Melmed S, Schopohl J, Caron P, Cuneo R, Kleinberg D, Colao A, Ruffin M, Hermosillo Reséndiz K, Hughes G, Hu K, Barkan A : Long-term efficacy and safety of subcutaneous pasireotide in acromegaly : results from an open-ended, multicenter, Phase Ⅱ extension study. Pituitary 17 : 132-140, 2014. 2) Abs R, Verhelst J, Maiter D, Van Acker K, Nobels F, Coolens JL, Mahler C, Beckers A : Cabergoline in the treatment of acromegaly : a study in 64 patients. J Clin Endocrinol Metab 83 : 374-378, 1998. 21) Jackson SN, Fowler J, Howlett TA : Cabergoline treatment of acromegaly : a preliminary dose finding study. Clin Endocrinol (Oxf) 46 : 745-749, 1997. 19) Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S ; Acromegaly Consensus Group : A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95 : 3141-3148, 2010. 9) Cozzi R, Attanasio R, Montini M, Pagani G, Lasio G, Lodrini S, Barausse M, Albizzi M, Dallabonzana D, Pedroncelli AM : Four-year treatment with octreotide-long-acting repeatable in 110 acromegalic patients : predictive value of short-term results? J Clin Endocrinol Metab 88 : 3090-3098, 2003. 11) De P, Rees DA, Davies N, John R, Neal J, Mills RG, Vafidis J, Davies JS, Scanlon MF : Transsphenoidal surgery for acromegaly in wales : results based on stringent criteria of remission. J Clin Endocrinol Metab 88 : 3567-3572, 2003. 27) Lee CC, Vance ML, Xu Z, Yen CP, Schlesinger D, Dodson B, Sheehan J : Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab 99 : 1273-1281, 2014. 24) Knosp E, Steiner E, Kitz K, Matula C : Pituitary Adenomas with invasion of the cavernous sinus space : a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33 : 610-618, 1993. 32) Sherlock M, Fernandez-Rodriguez E, Alonso AA, Reulen RC, Ayuk J, Clayton RN, Holder G, Sheppard MC, Bates A, Stewart PM : Medical therapy in patients with acromegaly : predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab 94 : 1255-1263, 2009. 23) Jane JA Jr, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO, Marshall JC, Laws ER Jr, Vance ML : Endoscopic transsphenoidal surgery for acromegaly : remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 96 : 2732-2740, 2011. 29) Moyes VJ, Metcalfe KA, DrakeWM : Clinical use of cabergoline as primary and adjunctive treatment for acromegaly. Eur J Endocrinol 159 : 541-545, 2008. 10) Cozzi R, Attanasio R, Lodrini S, Lasio G : Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients : efficacy and lack of predictive value of prolactin status. Clin Endocrinol (Oxf) 61 : 209-215, 2004. 22) Jallad RS, Bronstein MD : Optimizing medical therapy of acromegaly : beneficial effects of cabergoline in patients uncontrolled with long-acting release octreotide. Neuroendocrinology 90 : 82-92, 2009. 35) Trainer PJ : ACROSTUDY : the first 5 years. Eur J Endocrinol 161 : S19-24, 2009. 6) Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prévost G, Maisonobe P, Clermont A : Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly : results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 99 : 1282-1290, 2014. 20) Gondim JA, Almeida JP, de Albuquerque LA, Gomes E, Schops M, Ferraz T : Pure endoscopic transsphenoidal surgery for treatment of acromegaly : results of 67 cases treated in a pituitary center. Neurosurg Focus 29 : E7, 2010. 4) Campbell PG, Kenning E, Andrews DW, Yadla S, Rosen M, Evans JJ : Outcomes after a purely endoscopic transsphenoidal resection of growth hormone-secreting pituitary adenomas. Neurosurg Focus 29 : E5, 2010. 34) Shimon I, Cohen ZR, Ram Z, Hadani M : Transsphenoidal surgery for acromegaly : endocrinological follow-up of 98 patients. Neurosurgery 48 : 1239-1243, 2001. 37) Yamada S, Fukuhara N, Oyama K, Takeshita A, Takeuchi Y : Repeat transsphenoidal surgery for the treatment of remaining or recurring pituitary tumors in acromegaly. Neurosurgery 67 : 949-956, 2010. 3) Annamalai AK, Webb A, Kandasamy N, Elkhawad M, Moir S, Khan F, Maki-Petaja K, Gayton EL, Strey CH, O'Toole S, Ariyaratnam S, Halsall DJ, Chaudhry AN, Berman L, Scoffings DJ, Antoun NM, Dutka DP, Wilkinson IB, Shneerson JM, Pickard JD, Simpson HL, Gurnell M : A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy. J Clin Endocrinol Metab 98 : 1040-1050, 2013. 1) Abe T, Lüdecke DK : Recent results of secondary transnasal surgery for residual or recurring acromegaly. Neurosurgery 42 : 1013-1022, 1998. 12) Dehdashti AR, Ganna A, Karabatsou K, Gentili F : Pure endoscopic endonasal approach for pituitary adenomas : early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 62 : 1006-1015, 2008. 16) Freda PU, Reyes CM, Nuruzzaman AT, Sundeen RE, Khandji AG, Post KD : Cabergoline therapy of growth hormone & growth hormone/prolactin secreting pituitary tumors. Pituitary 7 : 21-30, 2004. 36) Vilar L, Azevedo MF, Naves LA, Casulari LA, Albuquerque JL, Montenegro RM, Montenegro RM Jr, Figueiredo P, Nascimento GC, Faria MS : Role of the addition of cabergoline to the management of acromegalic patients resistant to longterm treatment with octreotide LAR. Pituitary 14 : 148-156, 2011. 7) Colao A, Ferone D, Marzullo P, Di Sarno A, Cerbone G, Sarnacchiaro F, Cirillo S, Merola B, Lombardi G : Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab 82 : 518-523, 1997. |
| References_xml | – reference: 16) Freda PU, Reyes CM, Nuruzzaman AT, Sundeen RE, Khandji AG, Post KD : Cabergoline therapy of growth hormone & growth hormone/prolactin secreting pituitary tumors. Pituitary 7 : 21-30, 2004. – reference: 36) Vilar L, Azevedo MF, Naves LA, Casulari LA, Albuquerque JL, Montenegro RM, Montenegro RM Jr, Figueiredo P, Nascimento GC, Faria MS : Role of the addition of cabergoline to the management of acromegalic patients resistant to longterm treatment with octreotide LAR. Pituitary 14 : 148-156, 2011. – reference: 3) Annamalai AK, Webb A, Kandasamy N, Elkhawad M, Moir S, Khan F, Maki-Petaja K, Gayton EL, Strey CH, O'Toole S, Ariyaratnam S, Halsall DJ, Chaudhry AN, Berman L, Scoffings DJ, Antoun NM, Dutka DP, Wilkinson IB, Shneerson JM, Pickard JD, Simpson HL, Gurnell M : A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy. J Clin Endocrinol Metab 98 : 1040-1050, 2013. – reference: 1) Abe T, Lüdecke DK : Recent results of secondary transnasal surgery for residual or recurring acromegaly. Neurosurgery 42 : 1013-1022, 1998. – reference: 8) Cozzi R, Attanasio R, Barausse M, Dallabonzana D, Orlandi P, Da Re N, Branca V, Oppizzi G, Gelli D : Cabergoline in acromegaly : a renewed role for dopamine agonist treatment? Eur J Endocrinol 139 : 516-521, 1998. – reference: 2) Abs R, Verhelst J, Maiter D, Van Acker K, Nobels F, Coolens JL, Mahler C, Beckers A : Cabergoline in the treatment of acromegaly : a study in 64 patients. J Clin Endocrinol Metab 83 : 374-378, 1998. – reference: 4) Campbell PG, Kenning E, Andrews DW, Yadla S, Rosen M, Evans JJ : Outcomes after a purely endoscopic transsphenoidal resection of growth hormone-secreting pituitary adenomas. Neurosurg Focus 29 : E5, 2010. – reference: 10) Cozzi R, Attanasio R, Lodrini S, Lasio G : Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients : efficacy and lack of predictive value of prolactin status. Clin Endocrinol (Oxf) 61 : 209-215, 2004. – reference: 17) Friedrich N, Alte D, Völzke H, Spilcke-Liss E, Lüdemann J, Lerch M. M, Kohlmann T, Nauck M, Wallaschofski H : Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population : results of the Study of Health in Pomerania (SHIP). Growth Horm IGF Res 18 : 228-237, 2008. – reference: 15) Freda PU, Wardlaw SL, Post KD : Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 89 : 353-358, 1998. – reference: 20) Gondim JA, Almeida JP, de Albuquerque LA, Gomes E, Schops M, Ferraz T : Pure endoscopic transsphenoidal surgery for treatment of acromegaly : results of 67 cases treated in a pituitary center. Neurosurg Focus 29 : E7, 2010. – reference: 30) Nomikos P, Buchfelder M, Fahlbusch R : The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol 152 : 379-387, 2005. – reference: 18) Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S : Criteria for cure of acromegaly : a consensus statement. J Clin Endocrinol Metab 85 : 526-529, 2000. – reference: 23) Jane JA Jr, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO, Marshall JC, Laws ER Jr, Vance ML : Endoscopic transsphenoidal surgery for acromegaly : remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 96 : 2732-2740, 2011. – reference: 7) Colao A, Ferone D, Marzullo P, Di Sarno A, Cerbone G, Sarnacchiaro F, Cirillo S, Merola B, Lombardi G : Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab 82 : 518-523, 1997. – reference: 28) Mattar P, Alves Martins MR, Abucham J : Short-and long-term efficacy of combined cabergoline and octreotide treatment in controlling igf-I levels in acromegaly. Neuroendocrinology 92 : 120-127, 2010. – reference: 32) Sherlock M, Fernandez-Rodriguez E, Alonso AA, Reulen RC, Ayuk J, Clayton RN, Holder G, Sheppard MC, Bates A, Stewart PM : Medical therapy in patients with acromegaly : predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab 94 : 1255-1263, 2009. – reference: 38) Yano S, Kawano T, Kudo M, Makino K, Nakamura H, Kai Y, Morioka M, Kuratsu J : Endoscopic endonasal transsphenoidal approach through the bilateral nostrils for pituitary adenomas. Neurol Med Chir (Tokyo) 49 : 1-7, 2009. – reference: 5) Carlsen SM, Svartberg J, Schreiner T, Aanderud S, Johannesen O, Skeie S, Lund-Johansen M, Fougner SL, Bollerslev J ; POTA study group : Six-month preoperative octreotide treatment in unselected, de novo patients with acromegaly : effect on biochemistry, tumour volume, and postoperative cure. Clin Endocrinol (Oxf) 74 : 736-743, 2011. – reference: 26) Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G : Octreotide may act as a radioprotective agent in acromegaly. J Clin Endocrinol Metab 85 : 1287-1289, 2000. – reference: 29) Moyes VJ, Metcalfe KA, DrakeWM : Clinical use of cabergoline as primary and adjunctive treatment for acromegaly. Eur J Endocrinol 159 : 541-545, 2008. – reference: 37) Yamada S, Fukuhara N, Oyama K, Takeshita A, Takeuchi Y : Repeat transsphenoidal surgery for the treatment of remaining or recurring pituitary tumors in acromegaly. Neurosurgery 67 : 949-956, 2010. – reference: 19) Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S ; Acromegaly Consensus Group : A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab 95 : 3141-3148, 2010. – reference: 6) Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prévost G, Maisonobe P, Clermont A : Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly : results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 99 : 1282-1290, 2014. – reference: 9) Cozzi R, Attanasio R, Montini M, Pagani G, Lasio G, Lodrini S, Barausse M, Albizzi M, Dallabonzana D, Pedroncelli AM : Four-year treatment with octreotide-long-acting repeatable in 110 acromegalic patients : predictive value of short-term results? J Clin Endocrinol Metab 88 : 3090-3098, 2003. – reference: 13) Feenstra J, de Herder WW, ten Have SM, van den Beld AW, Feelders RA, Janssen JA, van der Lely AJ : Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet 365 : 1644-1646, 2005. – reference: 22) Jallad RS, Bronstein MD : Optimizing medical therapy of acromegaly : beneficial effects of cabergoline in patients uncontrolled with long-acting release octreotide. Neuroendocrinology 90 : 82-92, 2009. – reference: 34) Shimon I, Cohen ZR, Ram Z, Hadani M : Transsphenoidal surgery for acromegaly : endocrinological follow-up of 98 patients. Neurosurgery 48 : 1239-1243, 2001. – reference: 25) Lancranjan I, Atkinson AB : Results of a European multicentre study with Sandostatin LAR in acromegalic patients. Sandostatin LAR Group. Pituitary 1 : 105-114, 1999. – reference: 33) Shimatsu A, Teramoto A, Hizuka N, Kitai K, Ramis J, Chihara K : Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism. Endocr J 60 : 651-663, 2013. – reference: 35) Trainer PJ : ACROSTUDY : the first 5 years. Eur J Endocrinol 161 : S19-24, 2009. – reference: 14) Frank G, Pasquini E : Endoscopic endonasal cavernous sinus surgery, with special reference to pituitary adenomas. Front Horm Res 34 : 64-82, 2006. – reference: 12) Dehdashti AR, Ganna A, Karabatsou K, Gentili F : Pure endoscopic endonasal approach for pituitary adenomas : early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery 62 : 1006-1015, 2008. – reference: 11) De P, Rees DA, Davies N, John R, Neal J, Mills RG, Vafidis J, Davies JS, Scanlon MF : Transsphenoidal surgery for acromegaly in wales : results based on stringent criteria of remission. J Clin Endocrinol Metab 88 : 3567-3572, 2003. – reference: 27) Lee CC, Vance ML, Xu Z, Yen CP, Schlesinger D, Dodson B, Sheehan J : Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab 99 : 1273-1281, 2014. – reference: 21) Jackson SN, Fowler J, Howlett TA : Cabergoline treatment of acromegaly : a preliminary dose finding study. 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| Snippet | 先端巨大症の治療の第一選択は手術である. 治癒率向上のためには手術成績を向上させることが最も大切である. しかし, 海綿静脈洞浸潤を伴う腺腫では手術のみで根治は困... |
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| SubjectTerms | acromegaly medication surgery |
| Title | 先端巨大症の治療戦略 |
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