今日の臨床サポート

クッシング症候群

著者: 田辺晶代 国立国際医療研究センター病院 糖尿病内分泌代謝科

監修: 平田結喜緒 公益財団法人 兵庫県予防医学協会 健康ライフプラザ

著者校正/監修レビュー済:2021/04/21
患者向け説明資料

概要・推奨   

  1. クッシング症候群はまれな疾患である。身体所見やホルモン基礎値からクッシング症候群が疑われても、診断を確定するためには各種内分泌機能検査が必要である(推奨度2)
  1. クッシング症候群を疑った際には皮下出血斑、打撲痕、四肢近位筋力低下、赤色皮膚線条の有無を確認する(推奨度1)
  1. 副腎偶発腫瘍に対して副腎性クッシング症候群のスクリーニング検査を施行することが推奨される(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
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。
※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、実際の保険適用の査定において保険適用及び保険適用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用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:
田辺晶代 : 特に申告事項無し[2021年]
監修:平田結喜緒 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 副腎性サブクリニカルクッシング症候群 新診断基準(2017)に基づき副腎性サブクリニカルクッシング症候群の診断基準について改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
ポイント:
  1. クッシング症候群とは、コルチゾール過剰産生により、満月様(円形)顔貌、野牛肩、中心性(腹部)肥満と四肢近位筋萎縮、皮膚菲薄化、赤色皮膚線条、皮下出血斑などの特徴的な身体所見(クッシング徴候)を呈する疾患群である。クッシング病、コルチゾール産生副腎皮質腫瘍や異所性ACTH産生腫瘍などが含まれる。
  1. クッシング症候群はまれな疾患であり、クッシング症候群の年間頻度は下垂体性が1.2~1.7人/100万人、副腎腺腫が0.6人/100万人であった。また、クッシング症候群を疑い検査を施行された症例の9.2%(794/8,631例)が最終的にクッシング症候群と確定診断された。
 
  1. クッシング症候群を疑った際には皮下出血斑、打撲痕、四肢近位筋力低下、赤色皮膚線条の有無を確認する(推奨度1O)(参考文献:[1]
  1. 研究背景:クッシング徴候の頻度と識別指数が提示されている。
  1. 研究事例の説明:クッシング症候群の症例で頻度が高い臨床症状、身体所見は体重増加、肥満、皮下出血斑、満月様顔貌、月経異常、多毛、高血圧である。一方、特異度が高いのは皮下出血斑、打撲痕、四肢近位筋力低下、赤色皮膚線条である。
  1. 結論:特徴的といわれるクッシング徴候の中でも特異度が高いのは皮下出血斑、打撲痕、四肢近位筋力低下、赤色皮膚線条である。
 
ACTH依存性とACTH非依存性:
  1. クッシング症候群はACTH依存性とACTH非依存性に大別される。
  1. ACTH依存性クッシング症候群の病因は、ACTH産生下垂体腺腫(クッシング病)と異所性ACTH症候群である。
  1. ACTH依存性クッシング症候群ではACTH、血中コルチゾールともに正常~上昇している。
  1. ACTH非依存性クッシング症候群の病因には副腎コルチゾール産生腺腫、副腎癌、両側大結節性副腎過形成(BMAH)などがある。
  1. ACTH非依存性クッシング症候群ではACTHが低値、血中コルチゾールが正常~上昇している。
病歴・診察のポイント  
  1. クッシング症候群の特徴的身体所見である満月様顔貌、野牛肩、中心性肥満と四肢近位筋萎縮、皮膚菲薄化、赤色皮膚線条、皮下出血斑などを確認する。クッシング症候群の症例で頻度が高い臨床症状、身体所見は体重増加、肥満、皮下出血斑、満月様顔貌、月経異常、高血圧である。一方、特異度が高いのは皮下出血斑、打撲痕、四肢近位筋力低下、赤色皮膚線条である。ACTH依存性クッシング症候群および副腎皮質腫瘍が副腎男性ホルモンを同時産生している場合は多毛、髭などの男性化徴候がみられる。

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文献 

著者: E J Ross, D C Linch
雑誌名: Lancet. 1982 Sep 18;2(8299):646-9.
Abstract/Text
PMID 6125785  Lancet. 1982 Sep 18;2(8299):646-9.
著者: Massimo Terzolo, Giuseppe Reimondo, Silvia Bovio, Alberto Angeli
雑誌名: Pituitary. 2004;7(4):217-23. doi: 10.1007/s11102-005-4024-6.
Abstract/Text Clinically inapparent adrenal masses, or adrenal incidentalomas, are discovered inadvertently in the course of workup or treatment of unrelated disorders. Cortical adenoma is the most frequent type of adrenal incidentaloma accounting for approximately 50% of cases in surgical series and even greater shares in medical series. Incidentally discovered adrenal adenomas may secrete cortisol in an autonomous manner, that is not fully restrained by pituitary feed-back, in 5 to 20% of cases depending on study protocols and diagnostic criteria. A number of different alterations in the endocrine tests aimed to assess the function of the hypothalamic-pituitary-adrenal axis has been demonstrated in such patients. This heterogeneous condition has been termed as subclinical Cushing's syndrome, a definition that is more accurate than preclinical Cushing's syndrome since the evolution towards clinically overt hypercortisolism does occur rarely, if ever. The criteria for qualifying subclinical cortisol excess are controversial and we presently do not have sufficient evidence to define a gold standard for the diagnosis of subclinical Cushing's syndrome. An increased frequency of hypertension, central obesity, impaired glucose tolerance, diabetes and hyperlipoproteinemia has been described in patients with subclinical Cushing's syndrome; however, there is not evidence-based demonstration of its long-term complications and, consequently, the management of this condition is largely empirical. Either adrenalectomy or careful observation associated with treatment of metabolic syndrome has been suggested as treatment options because data are insufficient to indicate the superiority of a surgical or nonsurgical approach to manage patients with subclinical hyperfunctioning adrenal cortical adenomas.

PMID 16132200  Pituitary. 2004;7(4):217-23. doi: 10.1007/s11102-005-40・・・
著者: Rossella Libè, Chiara Dall'Asta, Laura Barbetta, Andrea Baccarelli, Paolo Beck-Peccoz, Bruno Ambrosi
雑誌名: Eur J Endocrinol. 2002 Oct;147(4):489-94.
Abstract/Text BACKGROUND: The incidence of adrenal incidentalomas has sharply increased in recent decades and concurrent subtle endocrine abnormalities, or even subclinical conditions, have been identified. Nonetheless, data concerning possible changes in adrenal size and/or hormonal pattern during follow-up are still inadequate.
OBJECTIVE: To evaluate long-term morphological and functional evolution of adrenal incidentalomas after initial diagnosis and to identify possible risk factors for hormonal hyperactivity and mass enlargement.
PATIENTS: Sixty-four patients (34-79 years) were followed-up for 12-120 months (median 25.5 months). Initial computerized tomography scan showed a unilateral mass in 51 patients and bilateral lesions in 13 patients. Average mass diameter at diagnosis was 2.5+/-0.1 cm (range 1.0-4.0). Twelve patients had subclinical Cushing's syndrome, 41 had mild hormonal alterations, and 11 had normal adrenal function at baseline. All patients were investigated by morphological and functional evaluation 6 and 12 months after diagnosis, and then at 1-year intervals.
RESULTS: During follow-up, a mass size increase >/=1 cm was observed in 13 patients, and 18 developed further subtle endocrine alterations. Cumulative risk of developing endocrine abnormalities was 17% at 1 year, 29% at 2 years, and 47% at 5 years. The risk was higher in the first 2 years of follow-up if the initial tumor diameter was >or=3 cm. Overall, cumulative risk of mass enlargement was 6% at 1 year, 14% at 2 years, and 29% at 5 years, and it was greater in patients with normal adrenal function than in those with subtle hormonal abnormalities (P<0.05). One female subject showed a mass enlargement after 6 months of follow-up and was eventually diagnosed with non-Hodgkin's lymphoma.
CONCLUSIONS: Patients with an adrenal incidentaloma are at risk for tumor growth and development of hormonal alterations. The risk of adrenal malignancy, although not elevated, also indicates the need for long-term follow-up.

PMID 12370111  Eur J Endocrinol. 2002 Oct;147(4):489-94.
著者: Bogdan Catargi, Vincent Rigalleau, Agathe Poussin, Nathalie Ronci-Chaix, Veronique Bex, Vincent Vergnot, Henri Gin, Patrick Roger, Antoine Tabarin
雑誌名: J Clin Endocrinol Metab. 2003 Dec;88(12):5808-13. doi: 10.1210/jc.2003-030254.
Abstract/Text Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.

PMID 14671173  J Clin Endocrinol Metab. 2003 Dec;88(12):5808-13. doi: ・・・
著者: Iacopo Chiodini, Maria Lucia Mascia, Silvana Muscarella, Claudia Battista, Salvatore Minisola, Maura Arosio, Stefano Angelo Santini, Giuseppe Guglielmi, Vincenzo Carnevale, Alfredo Scillitani
雑誌名: Ann Intern Med. 2007 Oct 16;147(8):541-8.
Abstract/Text BACKGROUND: Hypercortisolism is known to cause osteoporosis.
OBJECTIVE: To evaluate the prevalence of subclinical hypercortisolism in participants referred for evaluation of osteoporosis.
DESIGN: Cross-sectional study.
SETTING: Two community hospitals and research institutes in Italy.
PATIENTS: 219 patients without clinically overt hypercortisolism or other secondary causes of osteoporosis who were referred for evaluation of osteoporosis between January 2005 and December 2005.
MEASUREMENTS: Bone mineral density was measured by using dual-energy x-ray absorptiometry, and hypercortisolism was assessed with serum cortisol levels after a dexamethasone suppression test. Also measured were 24-hour urinary free cortisol levels and midnight plasma cortisol levels.
RESULTS: Seven of 65 patients with T-scores of 2.5 or less and vertebral fractures had subclinical hypercortisolism (prevalence, 10.8% [95% CI, 3.23% to 18.31%]). This prevalence was 4.8% (CI, 1.32% to 8.20%) among patients with osteoporosis. In multivariable analyses adjusted for age, sex, and body mass index, a positive dexamethasone suppression test result was associated with the presence of osteoporosis (odds ratio, 3.37 [CI, 1.78 to 6.43]; P < 0.001) and vertebral fractures (odds ratio, 1.70 [CI, 1.04 to 2.79]; P = 0.035).
LIMITATIONS: The study was conducted in a referral setting; its findings may not apply to the general population.
CONCLUSIONS: Subclinical hypercortisolism may be more common than is generally recognized in patients with osteoporosis in whom secondary causes of osteoporosis have been excluded.

PMID 17938392  Ann Intern Med. 2007 Oct 16;147(8):541-8.
著者: J Lindholm, S Juul, J O Jørgensen, J Astrup, P Bjerre, U Feldt-Rasmussen, C Hagen, J Jørgensen, M Kosteljanetz, L Kristensen, P Laurberg, K Schmidt, J Weeke
雑誌名: J Clin Endocrinol Metab. 2001 Jan;86(1):117-23.
Abstract/Text The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.

PMID 11231987  J Clin Endocrinol Metab. 2001 Jan;86(1):117-23.
著者: Mohamed B Elamin, M Hassan Murad, Rebecca Mullan, Dana Erickson, Katherine Harris, Sarah Nadeem, Robert Ennis, Patricia J Erwin, Victor M Montori
雑誌名: J Clin Endocrinol Metab. 2008 May;93(5):1553-62. doi: 10.1210/jc.2008-0139. Epub 2008 Mar 11.
Abstract/Text CONTEXT: The diagnosis of Cushing's syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy.
OBJECTIVE: Our objective was to summarize evidence on the accuracy of common tests for diagnosing CS.
DATA SOURCES: We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts.
STUDY SELECTION: Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays vs. reference standard in patients suspected of CS.
DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95% confidence interval (CI) for each result.
DATA SYNTHESIS: We found 27 eligible studies, with a high prevalence [794 (9.2%) of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI 5.5-20.5; LR- 0.16, CI 0.08-0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI 3.5-21.8; LR- 0.07, CI 0-1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI 9.3-28.8; LR- 0.06, CI 0.03-0.14). Combined testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7-358; LR- 0.11, CI 0.007-1.57).
CONCLUSIONS: Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.

PMID 18334594  J Clin Endocrinol Metab. 2008 May;93(5):1553-62. doi: 1・・・
著者: Katherine Samaras, Sarah Pett, Andrew Gowers, Marilyn McMurchie, David A Cooper
雑誌名: J Clin Endocrinol Metab. 2005 Jul;90(7):4394-8. doi: 10.1210/jc.2005-0036. Epub 2005 Mar 8.
Abstract/Text Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (
PMID 15755851  J Clin Endocrinol Metab. 2005 Jul;90(7):4394-8. doi: 10・・・
著者: Smita K Baid, Ninet Sinaii, Matt Wade, Domenica Rubino, Lynnette K Nieman
雑誌名: J Clin Endocrinol Metab. 2007 Aug;92(8):3102-7. doi: 10.1210/jc.2006-2861. Epub 2007 Jun 5.
Abstract/Text CONTEXT: Although bedtime salivary cortisol measurement has been proposed as the optimal screening test for the diagnosis of Cushing's syndrome, its performance using commercially available assays has not been widely evaluated.
OBJECTIVE: Our objective was to compare RIA and tandem mass spectrometry (LC-MS/MS) measurement of salivary cortisol in obese subjects and healthy volunteers.
DESIGN AND SETTING: We conducted a cross-sectional prospective study of outpatients.
SUBJECTS AND METHODS: We studied 261 obese subjects (186 female) with at least two additional features of Cushing's syndrome and 60 healthy volunteers (30 female). Subjects provided split bedtime salivary samples for cortisol measurement by commercially available RIA and LC-MS/MS. Results were considered normal or abnormal based on the laboratory reference range. Subjects with abnormal results underwent evaluation for Cushing's syndrome.
RESULTS: In paired samples, RIA gave a lower specificity than LC-MS/MS in obese subjects (86 vs. 94%, P = 0.008) but not healthy volunteers (86 vs. 82%, P = 0.71). Among subjects with at least one abnormal result, both values were abnormal in 44% (confidence interval 26-62%) of obese and 75% (confidence interval 33-96%) of healthy volunteers. In obese subjects, salivary cortisol concentrations were less than 4.0 to 643 ng/dl (<0.11-17.7 nmol/liter; normal, < or =100 ng/dl, 2.80 nmol/liter) by LC-MS/MS and less than 50 to 2800 ng/dl (1.4-77.3 nmol/liter; normal, < or =170 ng/dl, 4.7 nmol/liter) by RIA. Cushing's syndrome was not diagnosed in any subject.
CONCLUSION: Salivary cortisol levels should not be used as the sole test to diagnose Cushing's syndrome if laboratory-provided reference ranges are used for diagnostic interpretation.

PMID 17550962  J Clin Endocrinol Metab. 2007 Aug;92(8):3102-7. doi: 10・・・
著者: Giorgio Arnaldi, Tatiana Mancini, Barbara Polenta, Marco Boscaro
雑誌名: Pituitary. 2004;7(4):253-6. doi: 10.1007/s11102-005-1172-7.
Abstract/Text Chronic cortisol hypersecretion causes central obesity, hypertension, insulin resistance, dyslipidemia, protrombotic state, manifestations which form a metabolic syndrome in all patients with Cushing's syndrome. These associated abnormalities determine an increased cardiovascular risk not only during the active phase of the disease but also long after the "biomedical remission". Clinical management of these patients should be particularly careful in identifying global cardiovascular risk. Considering that remission from hypercortisolism is often difficult to achieve care and control of all cardiovascular risk factors should be one of the primary goals during the follow up of these patients. Extending the indications of the recent consensus on Cushing's syndrome, we suggest to carry out an OGTT to avoid underestimation of diabetes mellitus, an echocardiography and Doppler ultrasonography of the epiaortic vessels in all patients at diagnosis and during follow-up.

PMID 16416038  Pituitary. 2004;7(4):253-6. doi: 10.1007/s11102-005-117・・・
著者: B Swearingen, B M Biller, F G Barker, L Katznelson, S Grinspoon, A Klibanski, N T Zervas
雑誌名: Ann Intern Med. 1999 May 18;130(10):821-4.
Abstract/Text BACKGROUND: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported.
OBJECTIVE: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques.
DESIGN: Retrospective case series.
SETTING: Tertiary care center.
PATIENTS: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996.
INTERVENTION: Transsphenoidal adenomectomy and as-needed adjunctive therapy.
MEASUREMENT: Record review with follow-up interview.
RESULTS: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2).
CONCLUSION: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.

PMID 10366371  Ann Intern Med. 1999 May 18;130(10):821-4.
著者: A Colao, R Pivonello, S Spiezia, A Faggiano, D Ferone, M Filippella, P Marzullo, G Cerbone, M Siciliani, G Lombardi
雑誌名: J Clin Endocrinol Metab. 1999 Aug;84(8):2664-72. doi: 10.1210/jcem.84.8.5896.
Abstract/Text Patients with Cushing's disease (CD) mainly die because of cardiovascular accidents. The aim of this study was to evaluate whether patients with CD still have increased cardiovascular risk and suffer from premature atherosclerosis once cured. Fifteen patients cured from CD for a long term period (5 yr), 30 sex-and age-matched controls, and 30 body mass index (BMI)-matched controls were included in this study. BMI; waist to hip ratio (WHR); systolic (SBP) and diastolic (DBP) blood pressures; serum total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol; serum triglycerides, fibrinogen, and lipoprotein(a) levels; prothrombin time; activated partial thromboplastine time; and basal and glucose load-stimulated insulin and glucose levels were measured in patients and controls. By echo-Doppler ultrasonography, the intima media thickness (IMT), systolic and diastolic media-media distances, blood systolic (SPV) and diastolic (DPV) peak velocity, systolic (SLD) and diastolic (DLD) lumen diameter, and distensibility coefficient (DC) were measured at both common carotid arteries where the presence, size, and location of atherosclerotic plaques were also evaluated. Compared with a sex- and age-matched control population, CD patients had BMI (P < 0.001), WHR (P < 0.001), SBP (P < 0.005), DBP (P < 0.05), fasting glucose (P < 0.001) and insulin (P < 0.05), glucose load-stimulated glucose and insulin levels (P < 0.05), total cholesterol (P < 0.05), LDL cholesterol (P < 0.01), fibrinogen (P < 0.01), and lipoprotein(a) (P < 0.05) levels higher and HDL cholesterol levels (P < 0.05) lower than controls. At ultrasonography, in the patients, IMT (P < 0.05), SPV (P < 0.05) and DPV (P < 0.001) were significantly increased whereas SLD (P < 0.001), DLD (P < 0.001), and DC (P < 0.05) were significantly decreased compared to controls. In addition, CD patients had higher WHR (P < 0.05), DBP (P < 0.05), glucose load-stimulated glucose and insulin levels (P < 0.05), and fibrinogen levels (P < 0.01) and lower HDL cholesterol (P < 0.05) levels than BMI-matched controls. At ultrasonography, increased common carotid arteries IMT (P < 0.05) and DPV (P < 0.05) and decreased DLD (P < 0.05) and DC (P < 0.05) were measured in patients compared to those in BMI-matched controls. Atherosclerotic plaques were found in 26.7% of patients, in none of the sex- and age-matched controls, and in 3.3% of the BMI-matched controls. In CD patients, a significant correlation was found between both WHR and fasting serum insulin levels and DBP (r = 0.52 and r = 0.55; P < 0.05), triglycerides levels (r = 0.56 and r = 0.77; P < 0.05), and IMT (r = 0.64 and r = 0.56; P < 0.05). Right (r = -0.70; P < 0.005) and left (r = -0.65; P < 0.01) DC were inversely correlated to the duration of CD in the patient group. At the multiple regression analysis, WHR was the best predictor of fasting insulin levels (beta = 0.77; P < 0.05), and vice versa, fasting insulin level was the best predictor of WHR (beta = 1.20; P < 0.05). In conclusion, patients cured from CD for a long term period have a high prevalence of atherosclerosis and maintain increased several cardiovascular risk factors of the active disease, probably due to a residual abdominal obesity and/or insulin resistance syndrome.

PMID 10443657  J Clin Endocrinol Metab. 1999 Aug;84(8):2664-72. doi: 1・・・

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