今日の臨床サポート

下垂体腺腫

著者: 齋藤洋一 篤友会リハビリテーションクリニック

監修: 甲村英二 公立学校共済組合 近畿中央病院

著者校正/監修レビュー済:2022/03/02
参考ガイドライン:
  1. 日本内分泌学会間脳下垂体機能障害の診断と治療の手引き(平成30年度改訂)
  1. Fleserius M,et al: A pituitary society update to acromegaly management guidelines2021
  1. Esposito D, et al:Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management 2019
患者向け説明資料

概要・推奨   

  1. 先端巨大症および下垂体性巨人症:治療の第一選択は経蝶形骨洞手術である。合併症などで手術の危険性が高い場合は、薬物療法、放射線療法を行う。術前のソマトスタチン誘導体投与により腫瘍縮小が期待されることがある(推奨度1 エビデンスC,J,G)
  1. クッシング病:治療の第一選択は経蝶形骨洞手術である。合併症などで手術の危険性が高い場合は、薬物療法、放射線療法を考慮する(推奨度1 エビデンスC,J,G)
  1. PRL産生腺腫:ドパミン作動薬による薬物療法が第一選択である(推奨度1 エビデンスC,J,G)
アカウントをお持ちの方はログイン
  1. 非機能性腺腫:視神経、視交叉を圧迫する視力視野障害ある場合、治療の第一選択は経蝶形骨洞手術である。大型腫瘍の残存、再発に対しては放射線治療も考慮される(推奨度1 エビデンスC)[2]
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
齋藤洋一 : 研究費・助成金など(帝人ファーマ(株))[2022年]
監修:甲村英二 : 特に申告事項無し[2022年]

改訂のポイント:
定期レビューを行い、下記の項を加筆修正した。
  1. 概要・推奨の項をガイドラインに基づき、細分化した。
  1. 2021年8月デスモプレシン点鼻薬の製造販売が中止となった。デスモプレシンスプレーまたはミニリンメルトOD錠へ切り替えとなる。
  1. 2020年12月25日ランレオチド皮下注射がTSH産生腺腫に適応拡大された(エビデンスC)。
  1. 2021年6月30日副腎皮質ホルモン合成阻害剤オシドロスタットリン酸塩が発売された。適応として「クッシング症候群(外科的処置で効果が不十分又は施行が困難な場合)」となっている。
  1. 海外で、先端巨大症治療薬オクトレオチド内服薬が、オクトレオチド、ランレオチド注射が有効な患者に対して、高いエビデンスに基づいて、投与が強く推奨されている(推奨度1 エビデンスRs)[1]

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 下垂体は頭蓋底の中央にあるトルコ鞍と呼ばれる骨のくぼみに存在し、重さ700mg、大きさ1cm足らずの組織である。その小さな組織は前葉と後葉に大きく分けられ、前葉の後葉と接するところに中葉が存在する。前葉からは副腎皮質刺激ホルモン(ACTH)、甲状腺刺激ホルモン(TSH)、ゴナドトロピン(LH、FSH)、成長ホルモン(GH)、プロラクチン(PRL)が産生され、後葉からは抗利尿ホルモン(ADH)、子宮収縮ホルモンが分泌される。
  1. 下垂体腺腫は下垂体に発生する良性腫瘍で、下垂体の前葉細胞が腫瘍化したものである。非常にまれに(約0.1%)、頭蓋内に播種したり、他臓器に転移するものも報告されており、下垂体癌と呼ばれる[3]。一般に下垂体腫瘍は人口10万人つき約2人発生すると言われる。1,000例の剖検では18%に腫瘤性病変が認められた[4]
  1. 下垂体腺腫はホルモンを分泌する機能性腺腫と、分泌しない非機能性腺腫(ゴナドトロピン産生腺腫を含む)に分けられる。機能性腺腫で最も多いのはPRL産生腺腫で20~30歳台女性に特に多い。他にGH産生腺腫(先端巨大症)、ACTH産生腺腫(クッシング病)、TSH産生腺腫がある[5]。これらのホルモン産生腺腫は、内分泌異常を起こして発見される。一方、非機能性腺腫の場合腫瘍が増大して、視神経を圧迫することで、視力視野障害を来す。また海綿静脈洞に進展して、動眼神経、外転神経麻痺を起こすこともある。腺腫が内部で出血を起こして、激しい頭痛、視力視野障害、眼球運動障害を来して発症することもある。頭痛で発見されることも多い。頭痛はトルコ鞍周囲の硬膜を下垂体腺腫が圧排することで生じる。したがって、患者は目の奥が痛いと表現し、片頭痛と誤診されるケースがある。
  1. 腫瘍のサイズが1cm以下のとき、microadenomaと呼び、それより大型のものをmacroadenomaと呼ぶ。海綿静脈洞内、鞍上部、蝶形骨洞内に進展する場合、invasive adenomaと呼ぶ。
  1. 日本においては全国にCT. MRIが広く設置され、脳ドックという先進国でも珍しいシステムもある。そのため頭部外傷、頭痛の精査や、ドックで偶然に発見される偶発腫(incidentaloma)が増えている[6]。多くは無症状であるが、精密検査によって、ホルモン過剰分泌がみつかったり、下垂体機能不全や視力視野障害でみつかることもある。米国から偶発腫の治療指針が出された[7]
 
下垂体冠状断の図

トルコ鞍近傍解剖の模式図。下垂体周辺の構造の関係を簡単に示した。

出典

img1:  著者提供
 
 
 
下垂体より分泌されるホルモン

脳下垂体は前葉と後葉に大きく分けられ、前葉の後葉と接するところに中葉が存在する。前葉からは副腎皮質刺激ホルモン(ACTH)、甲状腺刺激ホルモン(TSH)、ゴナドトロピン(LH、FSH)、成長ホルモン(GH)、プロラクチン(PRL)が産生され、後葉からは抗利尿ホルモン(ADH)、子宮収縮ホルモンが分泌される。

問診・診察のポイント  
  1. 無月経・乳汁漏出、先端巨大症様顔貌、クッシング症候などは、厚生労働科学研究費補助金 難治性疾患等政策研究事業「間脳下垂体機能障害に関する調査研究」班が提唱している「間脳下垂体機能障害の診断と治療の手引き」(平成30年度改訂)に従い診察する。他の内分泌内科医がすでに負荷試験などで診断をほぼ確定して、脳神経外科医に紹介される(する)ケースも多い。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

Maria Fleseriu, Beverly M K Biller, Pamela U Freda, Monica R Gadelha, Andrea Giustina, Laurence Katznelson, Mark E Molitch, Susan L Samson, Christian J Strasburger, A J van der Lely, Shlomo Melmed
A Pituitary Society update to acromegaly management guidelines.
Pituitary. 2021 Feb;24(1):1-13. doi: 10.1007/s11102-020-01091-7. Epub 2020 Oct 20.
Abstract/Text Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize outcomes. Given significant novel recent advances in understanding acromegaly natural history and individualized therapies, the Pituitary Society invited acromegaly experts to critically review the current literature in the context of Endocrine Society guidelines and Acromegaly Consensus Group statements. This update focuses on how recent key advances affect treatment decision-making and outcomes, and also highlights the likely role of recently FDA-approved therapies as well as novel combination therapies within the treatment armamentarium.

PMID 33079318
Daniela Esposito, Daniel S Olsson, Oskar Ragnarsson, Michael Buchfelder, Thomas Skoglund, Gudmundur Johannsson
Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management.
Pituitary. 2019 Aug;22(4):422-434. doi: 10.1007/s11102-019-00960-0.
Abstract/Text PURPOSE: Non-functioning pituitary adenomas (NFPAs) are associated with impaired well-being, increased comorbidities, and reduced long-term survival. Data on optimal management of NFPAs around surgical treatment are scarce, and postoperative treatment and follow-up strategies have not been evaluated in prospective trials. Here, we review the preoperative, perioperative, and early postoperative management of patients with NFPAs.
METHODS: We searched Medline and the Cochrane Library for articles published in English with the following items "Pituitary neoplasms AND Surgery" and "Surgery AND Hypopituitarism". Studies containing detailed analyses of the management of NFPAs in adult patients, including pituitary surgery, endocrine care, imaging, ophthalmologic assessment and long-term outcome were reviewed.
RESULTS: Treatment options for NFPAs include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence.
CONCLUSIONS: In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed.

PMID 31011999
Brian T Ragel, William T Couldwell
Pituitary carcinoma: a review of the literature.
Neurosurg Focus. 2004 Apr 15;16(4):E7. Epub 2004 Apr 15.
Abstract/Text Pituitary carcinomas, defined as distant metastases of a pituitary neoplasm, are rare; fewer than 140 reports exist in the English literature. The initial presenting pituitary tumor is usually a secreting, invasive macroadenoma, with adrenocorticotropic hormone (ACTH)--and prolactin (PRL)--secreting tumors being the most common. The latency period between the diagnosis of a pituitary tumor and the diagnosis of a pituitary carcinoma is 9.5 years for ACTH-producing lesions and 4.7 years for PRL-secreting tumors. Survival after documentation of metastatic disease is poor; 66% of patients die within 1 year. Treatment options include additional surgery, radiotherapy, and chemotherapy, all of which are associated with poor results. Future studies will focus on identifying those invasive pituitary tumors most likely to metastasize and treating them aggressively before they progress to pituitary carcinomas.

PMID 15191336
A Teramoto, K Hirakawa, N Sanno, Y Osamura
Incidental pituitary lesions in 1,000 unselected autopsy specimens.
Radiology. 1994 Oct;193(1):161-4. doi: 10.1148/radiology.193.1.8090885.
Abstract/Text PURPOSE: To elucidate the frequency of false-positive results in imaging diagnoses of a functioning pituitary microadenoma, the authors studied various kinds of incidental lesions greater than 2 mm in diameter from a larger series of pituitary glands.
MATERIALS AND METHODS: One thousand pituitary glands were studied in a nonselected autopsy series. Most causes of death were acute diseases or accidents. Each gland was fixed in 10% formalin and was then cut horizontally into three or four pieces, which were prepared for usual light microscopy.
RESULTS: Of 178 glands found to have incidental lesions, 61 (34%) lesions were larger than 2 mm. Included were adenomas and hyperplasias (n = 20), Rathke cysts (n = 37), infarctions (n = 2), and hemorrhages (n = 2). Seventeen (74%) of 23 laterally localized lesions were adenomas, and 33 (87%) of 38 medially situated lesions were Rathke cleft cysts. These lesions were found in 5.8%-8.3% of subjects in every generation aged 30 years or older.
CONCLUSION: Incidental lesions should be considered a cause of false-positive findings (6.1%) when an imaging diagnosis is made of a functioning pituitary microadenoma.

PMID 8090885
Naoko Sanno, Ken'ichi Oyama, Shigeyuki Tahara, Akira Teramoto, Yuzuru Kato
A survey of pituitary incidentaloma in Japan.
Eur J Endocrinol. 2003 Aug;149(2):123-7.
Abstract/Text OBJECTIVE: The development of computed tomography (CT) and magnetic resonance imaging (MRI) has resulted in the discovery of unsuspected endocrinologically silent pituitary masses (pituitary incidentalomas). The aim of this study was to perform a national survey on pituitary incidentalomas in order to establish an appropriate approach to them.
DESIGN AND METHODS: Five hundred and six patients with pituitary incidentalomas were obtained by questionnaire from March 1999 to May 2000 under the auspices of the Ministry of Health, Labor and Welfare in Japan. Two hundred and fifty-eight patients underwent surgery (surgical group), while 248 patients were followed up conservatively for a mean period of 26.9 Months (range 6-173 Months) (non-surgical group). Clinical and biochemical assessment, CT or MRI of the pituitary, and visual field testing by Goldman perimetry were assessed at baseline and 6 Months and Yearly thereafter.
RESULTS: Thirty-three patients with pituitary incidentalomas (13.3%) developed tumor enlargement during the mean follow-up period of 45.5 Months. Of 115 estimated non-functioning adenomas, 23 tumors (20.0%) increased during a mean follow-up period of 50.7 Months (range 10-173 Months), while 5 of 94 (5.3%) estimated Rathke's cysts increased in size during follow-up. Pituitary apoplexy occurred in one of 248 patients (0.4%).
CONCLUSIONS: Pituitary incidentalomas usually follow a benign course. We recommend transsphenoidal adenectomy for a solid mass attached to the optic chiasma estimated to be a pituitary adenoma by MRI. Other patients should be followed up by MRI every 6 Months for the first 2 Years, and then Yearly.

PMID 12887289
Pamela U Freda, Albert M Beckers, Laurence Katznelson, Mark E Molitch, Victor M Montori, Kalmon D Post, Mary Lee Vance, Endocrine Society
Pituitary incidentaloma: an endocrine society clinical practice guideline.
J Clin Endocrinol Metab. 2011 Apr;96(4):894-904. doi: 10.1210/jc.2010-1048.
Abstract/Text OBJECTIVE: The aim was to formulate practice guidelines for endocrine evaluation and treatment of pituitary incidentalomas.
CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails and one in-person meeting.
CONCLUSIONS: We recommend that patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. We recommend that patients with incidentalomas not meeting criteria for surgical removal be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations. We recommend that patients with a pituitary incidentaloma be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.

PMID 21474686
Maria Fleseriu, Richard Auchus, Irina Bancos, Anat Ben-Shlomo, Jerome Bertherat, Nienke R Biermasz, Cesar L Boguszewski, Marcello D Bronstein, Michael Buchfelder, John D Carmichael, Felipe F Casanueva, Frederic Castinetti, Philippe Chanson, James Findling, Mônica Gadelha, Eliza B Geer, Andrea Giustina, Ashley Grossman, Mark Gurnell, Ken Ho, Adriana G Ioachimescu, Ursula B Kaiser, Niki Karavitaki, Laurence Katznelson, Daniel F Kelly, André Lacroix, Ann McCormack, Shlomo Melmed, Mark Molitch, Pietro Mortini, John Newell-Price, Lynnette Nieman, Alberto M Pereira, Stephan Petersenn, Rosario Pivonello, Hershel Raff, Martin Reincke, Roberto Salvatori, Carla Scaroni, Ilan Shimon, Constantine A Stratakis, Brooke Swearingen, Antoine Tabarin, Yutaka Takahashi, Marily Theodoropoulou, Stylianos Tsagarakis, Elena Valassi, Elena V Varlamov, Greisa Vila, John Wass, Susan M Webb, Maria C Zatelli, Beverly M K Biller
Consensus on diagnosis and management of Cushing's disease: a guideline update.
Lancet Diabetes Endocrinol. 2021 Dec;9(12):847-875. doi: 10.1016/S2213-8587(21)00235-7. Epub 2021 Oct 20.
Abstract/Text Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.

Copyright © 2021 Elsevier Ltd. All rights reserved.
PMID 34687601
E Knosp, E Steiner, K Kitz, C Matula
Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings.
Neurosurgery. 1993 Oct;33(4):610-7; discussion 617-8.
Abstract/Text We present 25 pituitary adenomas that were confirmed surgically to have invaded the cavernous sinus space. The surgical results are compared with the preoperative magnetic resonance imaging findings. For comparable radiological criteria, we classified parasellar growth into five grades. This proposed classification is based on coronal sections of unenhanced and gadolinium diethylene-triamine-pentaacetic acid enhanced magnetic resonance imaging scans, with the readily detectable internal carotid artery serving as the radiological landmark. The anatomical, radiological, and surgical conditions of each grade are considered. Grades 0, 1, 2, and 3 are distinguished from each other by a medial tangent, the intercarotid line--through the cross-sectional centers--and a lateral tangent on the intra- and supracavernous internal carotid arteries. Grade 0 represents the normal condition, and Grade 4 corresponds to the total encasement of the intracavernous carotid artery. According to this classification, surgically proven invasion of the cavernous sinus space was present in all Grade 4 and Grade 3 cases and in all but one of the Grade 2 cases; no invasion was present in Grade 0 and Grade 1 cases. Therefore, the critical area where invasion of the cavernous sinus space becomes very likely and can be proven surgically is located between the intercarotid line and the lateral tangent, which is represented by our Grade 2. We also measured tumor growth rates, using the monoclonal antibody KI-67, which shows a statistically higher proliferation rate (P < 0.001) in adenomas with surgically observed invasion into the cavernous sinus space, as compared with noninvasive adenomas.

PMID 8232800
Felipe F Casanueva, Mark E Molitch, Janet A Schlechte, Roger Abs, Vivien Bonert, Marcello D Bronstein, Thierry Brue, Paolo Cappabianca, Annamaria Colao, Rudolf Fahlbusch, Hugo Fideleff, Moshe Hadani, Paul Kelly, David Kleinberg, Edward Laws, Josef Marek, Maurice Scanlon, Luis G Sobrinho, John A H Wass, Andrea Giustina
Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas.
Clin Endocrinol (Oxf). 2006 Aug;65(2):265-73. doi: 10.1111/j.1365-2265.2006.02562.x.
Abstract/Text In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

PMID 16886971
Abstract/Text OBJECT: As an alternative method to inferior petrosal sinus sampling with administration of corticotropin-releasing hormone (CRH), the authors have developed a method of selective venous sampling directly from the cavernous sinus, which is performed using a superselective catheterization technique. The goal of this study is to assess this method.
METHODS: Catheterization to the cavernous sinus was performed in 44 patients with clinical and biochemical features of Cushing's syndrome. Forty of these patients in whom there was a definite clinical and/or histological diagnosis were evaluated. In 35 patients, a pituitary microadenoma was detected on magnetic resonance imaging and/or during surgery. Ectopic lesions were suspected in five patients, who later developed nonpituitary tumors. The central/peripheral (C/P) ratios of adrenocorticotrophic hormone (ACTH) without CRH administration ranged from 5.2 to 448.1 (mean+/-standard deviation, 66.7+/-91.2) in cavernous sinuses and from 1.1 to 52 (mean+/-standard deviation, 8.5+/-9.9) in the inferior petrosal sinuses. The petrosal sinus sampling contained false negative results in eight patients (23%) based on a cutoff point of 2. On the contrary, patients with ectopic lesions did not show any increase in ACTH levels in either sampling portion. The intercavernous gradients of ACTH, ranging from 1.2 to 506.4, indicated the correct lateralization of microadenoma in the lateral wing in all 30 patients. The interpetrosal gradients, ranging from 1 to 31.4, did not give a sufficient value (> or = 1.4) in four patients (13%) with a lateral lesion. In five cases of midline tumors, the intercavernous and interpetrosal gradients indicated false laterality in three and four cases, respectively. The intracavernous (posterior-anterior) gradients, ranging from 1.04 to 60.7 (mean 14.9), showed a higher concentration of ACTH in the posterior portion of the sinus in all patients.
CONCLUSIONS: These results suggest that 1) cavernous sinus sampling without CRH administration can demonstrate hypersecretion of ACTH from the pituitary gland with a high diagnostic accuracy; 2) intercavernous gradients will indicate the correct lateralization in laterally localized microadenomas; and 3) sampling should be performed from the posterior portion of the cavernous sinus.

PMID 9817414

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから