今日の臨床サポート

体重増加

著者: 山口征啓 健和会大手町病院 感染症内科

監修: 徳田安春 一般社団法人 群星沖縄臨床研修センター

著者校正/監修レビュー済:2021/04/28
患者向け説明資料

概要・推奨   

  1. 急性の場合は浮腫(水分貯留)、慢性の場合慢性浮腫もしくは肥満によるものが多い
  1. 二次性肥満としては、糖尿病、視床下部性肥満、クッシング症候群、甲状腺機能低下症、多嚢胞性卵巣(polycystic ovary、PCO)、副腎性器症候群、成長ホルモン欠損症などを鑑別する。
  1. クッシング症候群を疑う患者には、尿中遊離コルチゾール(感度85%、特異度92)、深夜の唾液中コルチゾール(感度94%、特異度89%)、1mgデキサメタゾン抑制試験(感度94%、特異度94)がスクリーニング検査として推奨される(推奨度2)
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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:
山口征啓 : 未申告[2021年]
監修:徳田安春 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った。国民健康・栄養調査のデータを更新した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 体重増加とは、体内の脂肪組織が過剰に増加した状態である。一般的に肥満度=(実測体重-標準体重)/標準体重が20%以上の場合、またはBMI=実測体重/(身長×身長)が25以上の場合をいう。多くは体質やエネルギー過剰摂取がその原因であるが、副腎や甲状腺などの内分泌腺の機能異常や薬剤の副作用などが原因になる場合もある。
  1. 急性の体重増加のほとんどは浮腫(水分貯留)によるものである。
  1. 慢性の体重増加は慢性浮腫もしくは肥満によるものである。
  1. 「令和元年国民健康・栄養調査」の結果によると、BMI≧25の割合は男性31.8%、女性21.6%である。男女とも30代から増加し始めるが、男性では40歳代が39.7%とピークで以後減少し、70歳以上で28.5%となるが、女性では30代の15.0%から徐々に増加し60代の28.1%がピークである[1]
 
BMIの状況 -年齢階級、肥満度(BMI)別、人数、割合- 総数・男性・女性、15歳以上(妊婦除外)

  1. BMI≧25の割合は男性31.8%、女性21.6%である。
  1. 男女とも30歳代から増加し始める。
  1. 男性では40歳代が39.7%とピークで以後減少し、70歳以上で28.5%となる。
  1. 女性では30歳代の15.0%から徐々に増加し、60代の28.1%がピークである。

 
  1. 肥満は死亡率の増加と関連があり、糖尿病、高血圧、脂質異常症、心疾患、脳卒中など多くの疾患のリスクファクターであるため、スクリーニングを行って診断し、介入する必要がある。
問診・診察のポイント  
 
  1. 浮腫を除くと、体重増加のほとんどはカロリー摂取と消費のアンバランスによる一次性肥満である。

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文献 

平成24年国民健康・栄養調査結果の概要厚生労働省健康局総務課生活習慣病対策室:平成24年国民健康・栄養調査結果の概要 2013年..
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: Lynnette K Nieman, Beverly M K Biller, James W Findling, John Newell-Price, Martin O Savage, Paul M Stewart, Victor M Montori
雑誌名: J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 10.1210/jc.2008-0125. Epub 2008 Mar 11.
Abstract/Text OBJECTIVE: The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome.
PARTICIPANTS: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.
CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments.
CONCLUSIONS: After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.

PMID 18334580  J Clin Endocrinol Metab. 2008 May;93(5):1526-40. doi: 1・・・
著者: C K Welt, G Arason, J A Gudmundsson, J Adams, H Palsdóttir, G Gudlaugsdóttir, G Ingadóttir, W F Crowley
雑誌名: J Clin Endocrinol Metab. 2006 Nov;91(11):4361-8. doi: 10.1210/jc.2006-1191. Epub 2006 Aug 29.
Abstract/Text CONTEXT: The phenotype of women with polycystic ovary syndrome (PCOS) is variable, depending on the ethnic background.
OBJECTIVE: The phenotypes of women with PCOS in Iceland and Boston were compared.
DESIGN: The study was observational with a parallel design.
SETTING: Subjects were studied in an outpatient setting.
PATIENTS: Women, aged 18-45 yr, with PCOS defined by hyperandrogenism and fewer than nine menses per year, were examined in Iceland (n = 105) and Boston (n = 262).
INTERVENTION: PCOS subjects underwent a physical exam, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound.
MAIN OUTCOME MEASURES: The phenotype of women with PCOS was compared between Caucasian women in Iceland and Boston and among Caucasian, African-American, Hispanic, and Asian women in Boston.
RESULTS: Androstenedione (4.0 +/- 1.3 vs. 3.5 +/- 1.2 ng/ml; P < 0.01) was higher and testosterone (54.0 +/- 25.7 vs. 66.2 +/- 35.6 ng/dl; P < 0.01), LH (23.1 +/- 15.8 vs. 27.6 +/- 16.2 IU/liter; P < 0.05), and Ferriman Gallwey score were lower (7.1 +/- 6.0 vs. 15.4 +/- 8.5; P < 0.001) in Caucasian Icelandic compared with Boston women with PCOS. There were no differences in fasting blood glucose, insulin, or homeostasis model assessment in body mass index-matched Caucasian subjects from Iceland or Boston or in different ethnic groups in Boston. Polycystic ovary morphology was demonstrated in 93-100% of women with PCOS in all ethnic groups.
CONCLUSIONS: The data demonstrate differences in the reproductive features of PCOS without differences in glucose and insulin in body mass index-matched populations. These studies also suggest that measuring androstenedione is important for the documentation of hyperandrogenism in Icelandic women. Finally, polycystic ovary morphology by ultrasound is an almost universal finding in women with PCOS as defined by hyperandrogenism and irregular menses.

PMID 16940441  J Clin Endocrinol Metab. 2006 Nov;91(11):4361-8. doi: 1・・・
著者: D W Polson, J Adams, J Wadsworth, S Franks
雑誌名: Lancet. 1988 Apr 16;1(8590):870-2.
Abstract/Text The prevalence of polycystic ovaries (PCO) in normal women of reproductive age was determined by pelvic ultrasound scanning of 257 volunteers who considered themselves to be normal and who had not sought treatment for menstrual disturbances, infertility, or hirsutism. All women had completed a menstrual history questionnaire. 99 women were on oral contraceptives at the time of the study. Of the 158 subjects who were not on oral contraceptives 18% had irregular cycles. 116 (73%) women had normal ovaries and 36 (23%) had PCO. 5 women had multifollicular ovaries and 1 had small, unstimulated ovaries. Only 1 woman with normal ovaries had an irregular menstrual cycle. Of the women with PCO, 76% had irregular cycles, and 6 of the 8 with regular cycles were hirsute. Women with and those without PCO differed in distribution of serum LH concentrations although the median values were similar. 25% of women with PCO had LH concentrations which exceeded the upper limit of the normal range. Thus PCO are common in normal women. Some of these women may have clinical and biochemical markers of PCO, which suggest that PCO in women who consider themselves to be normal is part of the same clinical spectrum as the classic Stein-Leventhal syndrome.

PMID 2895373  Lancet. 1988 Apr 16;1(8590):870-2.
著者: A Tabarin, F Laurent, B Catargi, F Olivier-Puel, R Lescene, J Berge, F S Galli, J Drouillard, P Roger, J Guerin
雑誌名: Clin Endocrinol (Oxf). 1998 Sep;49(3):293-300.
Abstract/Text OBJECTIVES: The ability of MRI to detect pituitary ACTH-secreting adenomas in patients with Cushing's disease is limited. Owing to different dynamics of contrast enhancement between adenomas and normal pituitary tissue, it has been suggested that obtaining images within seconds after gadolinium (Gad) injection using dynamic procedures increases the sensitivity of MRI in the detection of pituitary microadenomas. The objective of this study was to compare the ability of conventional magnetic resonance imaging (CMRI) and dynamic MRI (DMRI) to detect ACTH-secreting pituitary adenomas.
DESIGN: Twenty-six consecutive patients with ACTH-dependent Cushing's syndrome and 10 normal subjects were investigated. According to the results of inferior petrosal sinus sampling, 21 patients had Cushing's disease and five had ectopic ACTH syndrome. Patients with Cushing's disease were operated regardless of the results of imaging studies. All underwent identical MRI and DMRI procedures using a 1.0 T magnet. Image sampling time during DMRI was 19 sec. Scans were randomly mixed and analysed blind, retrospectively and independently by two experienced radiologists. The clarity of the images was assessed by the analysis of agreement among radiologists. MRI findings were compared to surgical and histopathological findings.
RESULTS: Surgical exploration identified three macrodenomas and 14 microadenomas. One microadenoma was found at pathological examination after subtotal hypophysectomy and no tumour was found in three cases. According to the combined opinion of radiologists, the three macroadenomas were identified equally well with CMRI and DMRI. Eight ACTH-secreting microadenomas were detected with CMRI and 11 with DMRI. The three microadenomas detected with DMRI only were visualized within 60 sec following Gad injection. No false positives occurred with CMRI. Three false positives were obtained with DMRI: one in a patient with ectopic ACTH syndrome while a silent microprolactinoma and normal tissue were found at the site of the radiological abnormality in two patients with Cushing's disease. In our study, the sensitivity of DMRI is greater than that of CMRI (0.67 vs. 0.52) but is associated with a loss in specificity (0.80 vs. 1.00). False positives may result from the increased sensitivity of DMRI which detects incidental pituitary lesions, technical artefacts or lowest clarity of images, as suggested by a lower observer agreement of DMRI (Kappa statistic 0.66 vs. 0.83). Overall, the two MR procedures had equivalent diagnostic power (0.72).
CONCLUSIONS: In our hands, dynamic procedures did not improve the usefulness of MRI in Cushing's syndrome.

PMID 9861318  Clin Endocrinol (Oxf). 1998 Sep;49(3):293-300.
著者: Nicholas Patronas, Nail Bulakbasi, Constantine A Stratakis, Antony Lafferty, Edward H Oldfield, John Doppman, Lynnette K Nieman
雑誌名: J Clin Endocrinol Metab. 2003 Apr;88(4):1565-9. doi: 10.1210/jc.2002-021438.
Abstract/Text Recent studies show that the standard T1-weighted spin echo (SE) technique for magnetic resonance imaging (MRI) fails to identify 40% of corticotrope adenomas. We hypothesized that the superior soft tissue contrast and thinner sections obtained with spoiled gradient recalled acquisition in the steady state (SPGR) would improve tumor detection. We compared the performance of SE and SPGR MRI in 50 patients (age, 7-67 yr) with surgically confirmed corticotrope adenoma. Coronal SE and SPGR MR images were obtained before and after administration of gadolinium contrast, using a 1.5 T scanner. SE scans were obtained over 5.1 min (12-cm field of view; interleaved sections, 3 mm). SPGR scans were obtained over 3.45 min (12- or 18-cm field of view, contiguous 1- or 2-mm slices). The MRI interpretations of two radiologists were compared with findings at surgical resection. Compared with SE for detection of tumor, SPGR had superior sensitivity (80%; confidence interval, 68-91; vs. 49%; confidence interval, 34-63%), but a higher false positive rate (2% vs. 4%). We recommend the addition of SPGR to SE sequences using pituitary-specific technical parameters to improve the MRI detection of ACTH-secreting pituitary tumors.

PMID 12679440  J Clin Endocrinol Metab. 2003 Apr;88(4):1565-9. doi: 10・・・
著者: Michael A Blake, Mannudeep K Kalra, Ann T Sweeney, Brian C Lucey, Michael M Maher, Dushyant V Sahani, Elkan F Halpern, Peter R Mueller, Peter F Hahn, Giles W Boland
雑誌名: Radiology. 2006 Feb;238(2):578-85. doi: 10.1148/radiol.2382041514. Epub 2005 Dec 21.
Abstract/Text PURPOSE: To retrospectively evaluate the accuracy of precontrast attenuation, relative percentage washout (RPW), and absolute percentage washout (APW) in distinguishing benign from malignant adrenal masses at multi-detector row computed tomography (CT).
MATERIALS AND METHODS: This HIPAA-compliant retrospective study had institutional review board approval; the need for informed consent was waived. One hundred twenty-two adrenal masses were evaluated in 99 patients (51 men, 48 women; age range, 37-86 years) who had undergone CT performed according to the study protocol and who either were given a pathologic diagnosis or underwent follow-up imaging. Unenhanced images were obtained before administration of 120 mL of an intravenous contrast agent with a 75-second scan delay. Delayed images were obtained after 10 minutes. RPW and APW were computed. Receiver operating characteristic (ROC) analysis was performed to compare mean attenuation and both RPW and APW. Analysis was first performed with the exclusion of pheochromocytomas, myelolipomas, and cysts. Precontrast attenuation criteria specific for benignity or malignancy were determined, and ROC analysis of results for the entire nonpheochromocytoma group was then performed.
RESULTS: By using an RPW of 37.5% and excluding cysts and myelolipomas, all malignant lesions were detected with a sensitivity of 100% (17 of 17 lesions) and a specificity of 95% (90 of 95 lesions). Area under the binomial ROC curve (A(z)) values were 0.912, 0.985, and 0.892 for precontrast attenuation, RPW, and APW, respectively. Precontrast attenuation of less than 0 or more than 43 HU indicated benign and malignant entities, respectively. Incorporation of these criteria into the APW analysis yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (93 of 95 lesions) for a threshold washout value of 52.0%. This attenuation-corrected APW generated the greatest A(z) value (ie, 0.988). Combining all the information available from the protocol yielded a sensitivity of 100% (17 of 17 lesions) and a specificity of 98% (98 of 100 lesions) for differentiating benign from malignant masses.
CONCLUSION: Precontrast attenuation of less than 0 HU supercedes the washout profile in the evaluation of an individual adrenal mass. Noncalcified, nonhemorrhagic adrenal lesions with precontrast attenuation of more than 43 HU should be considered suspicious for malignancy.

(c) RSNA, 2005
PMID 16371582  Radiology. 2006 Feb;238(2):578-85. doi: 10.1148/radiol.・・・
著者: Ioannis Ilias, Anju Sahdev, Rodney H Reznek, Ashley B Grossman, Karel Pacak
雑誌名: Endocr Relat Cancer. 2007 Sep;14(3):587-99. doi: 10.1677/ERC-07-0045.
Abstract/Text Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1- and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [(131)I]-6-iodomethyl norcholesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [(123)I]- and [(131)I]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours.

PMID 17914090  Endocr Relat Cancer. 2007 Sep;14(3):587-99. doi: 10.167・・・
著者: G A Bray, T F Gallagher
雑誌名: Medicine (Baltimore). 1975 Jul;54(4):301-30.
Abstract/Text Eight patients are presented in whom obesity developed in association with documented hypothalamic lesions. These lesions included trauma, inflammatory disease, an aneurysm of the internal carotid artery, and five cases of tumor. Detailed metabolic studies were performed in four patients with hypothalamic obesity and in five age- and weight-matched patients with essential obesity(i.e., obesity with no definable etiology). Fasting insulin concentrations were significantly higher in the patients with hypothalamic obesity. During a seven-day fast the insulin levels in patients with essential obesity decreased by 24 to 48 hours, whereas patients with hypothalamic obesity showed a variety of changes; In three out of four of these patients with hypothalamic obesity there was no evidence for hyperplasia of the fat cells. Basal oxygen consumption, body composition, and metabolism of adipose tissue did not differ between the patients with essential obesity and those with hypothalamic obesity. There was no difference in activity of the enzymes in the glycerophosphate cycle. Our data on eight patients with hypothalamic obesity were compared with data on patients in literature. Most cases of hypothalamic obesity occur with space-occupying tumors arising at the base of the hypothalamus. However, trauma, inflammatory diseases, and leukemia are also associated with hypothalamic obesity. Patients with hypothalamic obesity rarely weigh more than 140 kg.

PMID 1152672  Medicine (Baltimore). 1975 Jul;54(4):301-30.

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