糖皮質(zhì)激素的撤藥方案(英漢對照)

1、糖皮質(zhì)激素的撤藥方案著者：Daniel E Furst, MD Kenneth G Saag, MD, ScM David N Orth, MD 譯者：劉湘源由于糖皮質(zhì)激素有強(qiáng)大的抗炎作用及偶爾因被認(rèn)為有免疫抑制活性，在多種疾病治療中采用糖皮質(zhì)激素 長期治療。常使用皮質(zhì)類固醇的風(fēng)濕病有類風(fēng)濕關(guān)節(jié)炎、大和小血管性血管炎、系統(tǒng)性紅斑狼瘡、風(fēng)濕性 多肌痛及某些合并炎性腸病的關(guān)節(jié)炎病例。盡管皮質(zhì)類固醇激素有強(qiáng)大功效，但它所誘導(dǎo)的副作用一般要求在疾病得到控制后逐漸減量，減量必須仔 細(xì)，要防止?jié)撛诩膊〉膹?fù)發(fā)及因使用類固醇期間導(dǎo)致的下丘腦-垂體-腎上腺（HPA）軸抑制引起的皮質(zhì)醇 缺乏。如何減類固醇量尚無很

2、好的對照研究，本章節(jié)將綜述與激素減量相關(guān)的主要問題、文獻(xiàn)報道的減量方案以 及我們在大多數(shù)患者使用的方案。糖皮質(zhì)激素減量指證一在討論不同的糖皮質(zhì)激素減量方案之前，先簡單綜述一下撤藥的指證是有幫助的， 這些指證包括：已獲得想要得到的最大治療益處時在充分的試驗(yàn)性治療后，已獲得不當(dāng)?shù)闹委熞嫣帟r當(dāng)用藥時出現(xiàn)的副作用，如腰椎骨質(zhì)疏松或高血壓變得嚴(yán)重或不能控制時另外，有兩項(xiàng)并發(fā)癥需要立即停藥，而不能緩慢停藥：類固醇激素誘導(dǎo)的急性精神病，對抗精神病藥物無效皰疹病毒誘發(fā)的角膜潰瘍，快速引起角膜穿孔，并可能出現(xiàn)永久性失明時。皮質(zhì)類固醇制劑一雖然存在有其他皮質(zhì)類固醇制劑，但以強(qiáng)的松為代表進(jìn)行討論（見圖1）（見“合成

3、糖 皮質(zhì)激素的結(jié)構(gòu)-功能關(guān)系”章節(jié)）。有不同效能的制劑（如1, 2, 5, 10, 20mg的強(qiáng)的松）和不同的 劑型（片劑、靜脈制劑、肌肉內(nèi)注射制劑和肛門栓劑）。這些具有不同效能和劑型的制劑的吸收或代謝的 不同可影響類固醇激素減量的能力，慶幸的是，大多數(shù)商業(yè)應(yīng)用的強(qiáng)的松和強(qiáng)的松龍制劑是生物性等效 的，這可通過以下觀察數(shù)據(jù)來說明：應(yīng)用健康男性進(jìn)行的交叉研究的體內(nèi)研究顯示，5種不同的強(qiáng)的松口服制劑的任何藥代動力學(xué)參數(shù)均無 統(tǒng)計(jì)學(xué)差異甲基強(qiáng)的松龍的直腸和口服吸收是等價的，口服對直腸用藥的相對生物利用度為90%強(qiáng)的松的全身性生物利用度等于強(qiáng)的松龍（0.77對0.80）,強(qiáng)的松本身無生物活性，而是快速轉(zhuǎn)

4、換為 活性類型強(qiáng)的松龍。然而，有嚴(yán)重肝病的患者轉(zhuǎn)化強(qiáng)的松為強(qiáng)的松龍困難，對于這樣的患者，很可能從強(qiáng) 的松得到的療效與從強(qiáng)的松龍得到的療效不同。另外，某些藥物相互作用可影響強(qiáng)的松的代謝和生物利用 度。類固醇激素的藥代動力學(xué)一如果強(qiáng)的松不同劑量下的藥物搭配發(fā)生改變，那么減量方案可受到潛在影響。雖 然其動力學(xué)有劑量依賴性趨勢，劑量越大，清除越快，但這種作用相對小，通常無重要的臨床意義。有一項(xiàng)對54例不同年齡患者進(jìn)行的有趣研究，這些患者給予口服和靜脈用甲基強(qiáng)的松龍和強(qiáng)的松龍，其中 11例患者（占20%）顯示有不尋常的動力學(xué)，他們的藥物清除率幾乎是其他人的2倍，其原因尚不清 楚。另外的發(fā)現(xiàn)包括：有4例患

5、者的皮質(zhì)類固醇激素吸收不徹底，強(qiáng)的松龍的清除率與年齡之間呈負(fù)相關(guān)（r = -0.88）,這意味著所給的劑量在較老的人中有較大的作用。這種關(guān)系已被其他研究所證實(shí)。此外， 非洲美國人的強(qiáng)的松龍清除率也慢于高加索人。隨患者在動力學(xué)上相互間變異性的程度不同，可以想象到有些患者可能比另一些患者有較大的撤藥癥 狀，該病癥是可出現(xiàn)的，雖然道在血漿皮質(zhì)類固醇激素動力學(xué)和生物活性之間有不同。Chronic corticosteroid therapy is used in the treatment of a variety of disorders because of its potent antiinfl

6、ammatory effects and occasionally because it is thought to have therapy in the nephrotic syndrome is more similar to regimens used in most rheumatic diseases. As a result, short tapering regimens are not generally recommended in patients with rheumatic or renal disease.SUGGESTED TAPERING REGIMEN- Sh

7、ort-term corticosteroid therapy (up to three weeks), even if at a fairly high dose, can simply be stopped and need not be tapered. HPA suppression of this duration will not persist and is highly unlikely to have any clinical consequence. However, in a frail or dangerously ill patient, the clinician

8、may elect to proceed more cautiously as noted below.In patients who have taken a corticosteroid for a longer time, we suggest the following regimen which is largely based on experience and rests upon certain assumptions:The above factors (age, frailty, concomitant illnesses, dangerousness and likeli

9、hood of flare of underlying illness, psychological factors, and duration of previous use) are taken into account.The rheumatic disease is sufficiently stable so that tapering of the dose is appropriate.The patient has received long-term steroid therapy, not recurrent pulses as might be used in asthm

10、a.The observation that HPA suppression is uncommon at prednisone doses below 5 mg/day means that most patients on a daily dose of 5 mg/day do not have to be tapered 12.Our regimen also assumes that repeated morning cortisol determinations are too expensive for routine use (although this might change

11、 if properly designed studies showed that such an approach is better) and that the appropriate end-points are the patients signs and symptoms.The goal of tapering is to use a rate of change that will prevent both recurrent activity of the underlying disease and symptoms of cortisol deficiency due to

12、 persistent HPA suppression. We generally aim for a relatively stable decrement of 10 to 20 percent, while accommodating convenience and individual patient response. The dose is tapered by:10 mg/day every one to two weeks at an initial dose above 60 mg of prednisone or equivalent per day.5 mg/day ev

13、ery one to two weeks at prednisone doses between 60 and 20 mg/day.2.5 mg/day every one to two weeks at prednisone doses between 19 and 10 mg/day.1 mg/day every one to two weeks at prednisone doses between 9 and 5 mg/day.0.5 mg/day every one to two weeks at prednisone doses below 5 mg/day. This can b

14、e achieved by alternating daily doses, eg, 5 mg on day 1 and 4 mg on day 1.This regimen will generally prevent symptoms of cortisol deficiency. At some point, however, many patients with rheumatic diseases complain of recurrent symptoms of the underlying disease. If the symptoms are not major, we tr

15、y to wait seven to 10 days, and use a nonsteroidal antiinflammatory drug or other analgesic. If the symptoms do not subside within this period, we increase the prednisone dose by 10 to 15 percent (to the next convenient mg tablet regimen) and maintain that dose for two to four weeks. If the symptoms

16、 resolve, the above tapering regimen can be resumed, using two to four weeks between decrements rather than one to two weeks.Should this modest increase in dose not be sufficient to alleviate symptoms, we double the prednisone dose. The disease flare is allowed to subside and the taper is reinstitut

17、ed at a slower rate (eg, once monthly) or at smaller decrements (eg, one-half of the original decrement). There arez to our knowledge, no data supporting one method or another.It should also be appreciated that incremental change is inappropriate if life-threatening flares occur (as in acute recurre

18、nce of lupus nephritis, severe hemolysis, acute polymyositis, or vasculitis). In these settings, a return to the original, highest dose of steroids should be instituted. Tapering which is slowed in rate or decrement can be undertaken after the flare subsides.Alternate-day regimen- We are not aware o

19、f any evidence-based data relating to steroid tapering on an alternate-day regimen. We do, however, use the following alternate-day approach (in which the entire dose is given on the alternate days) in some patients. After the daily regimen has reached 20 to 30 mg of prednisone per day, we decrease

20、the alternate day dose by 5 mg every one to two weeks until the dose is 20 to 30 mg alternating with 10 mg. We then decrease the alternate day dose by 2.5 mg every one to two weeks until the prednisone dose on the alternate day has fallen to zero. At that point we decrease the remaining drug in the

21、same manner as was suggested for the daily dosing regimen. Although this regimen is generally effective in most rheumatic diseases, patients with rheumatoid arthritis often do not tolerate alternate-day dosing.immunosuppressive activity 1. Among the rheumatic diseases in which corticosteroids are of

22、ten used are rheumatoid arthritis, large- and small-vessel vasculitis, systemic lupus erythematosus, polymyalgia rheumatica, and, in some cases, the arthritis associated with inflammatory bowel disease 1.Despite its efficacy, steroid-induced side effects generally require tapering as soon as the dis

23、ease being treated is under control. Tapering must be done carefully to avoid both recurrent activity of the underlying disease and possible cortisol deficiency resulting from hypothalamic-pituitary-adrenal (HPA) axis suppression during the period of steroid therapy.There are no well controlled stud

24、ies examining how best to taper steroids. This card will review the major issues related to tapering, the regimens that have been reported in the literature, and the regimen(s) we use in most patients.INDICATIONS FOR WITHDRAWING GLUCOCORTICOIDS- Before discussing the different glucocorticoid withdra

25、wal regimens, it is helpful to first briefly review the indications for such withdrawal. These include the following:When the maximum desired therapeutic benefit has been obtainedWhen inadequate therapeutic benefit has been obtained after an adequate trialWhen side effects, such as lumbar spine oste

26、oporosis or hypertension, become serious or uncontrollable with medicationIn addition, there are two complications that require immediate cessation of steroid therapy, not tapering:Steroid-induced acute psychosis, which is often unresponsive to antipsychotic medicationsHerpesvirus-induced corneal ul

27、ceration, which can rapidly lead perforation of the cornea and possibly permanent blindnessCORTICOSTEROID PREPARATIONS- Prednisone will be the agent discussed, although other corticosteroid preparations are available (show figure 1). (See card “Structure-function relationships of synthetic glucocort

28、icoids). These preparations are available in various strengths (eg, 1, 2, 5, 10, 20 mg for prednisone) and in various formulations (tablet, intravenous preparations, intramuscular preparations, and rectal suppositories). Differences in the absorption or metabolism of these various strengths and form

29、ulations could affect the ability to taper steroids. Fortunately, most commercially available prednisone and prednisolone preparations appear to be bioequivalent. This can be illustrated by the following observations:In vivo studies using healthy males in a crossover study revealed no statistical di

30、fference in any pharmacokinetic parameter with five different oral prednisone preparations 2.Rectal and oral absorption of methylprednisolone are equivalent, with the relative bioavailability of oral to rectal administration being 90 percent 3.The systemic bioavailability of prednisone is equivalent

31、 to that of prednisolone (0.77 to 0.80) 4. Prednisone itself is biologically inactive, but it is rapidly converted to the active form prednisolone. However, patients with severe liver disease may have difficulty converting prednisone to prednisolone; in such patients, it is possible that one might n

32、ot get the same effect from prednisone as from prednisolone. In addition, certain drug interactions can affect the metabolism and bioavailability of prednisone.Steroid pharmacokinetics- Tapering regimens could potentially be influenced if drug disposition changed at varying prednisone doses. Althoug

33、h there is a trend toward dosedependent kinetics, with larger doses being cleared more rapidly, the effect is relatively small and usually not of great clinical importance 5-7.One interesting study examined 54 patients of varying ages who were given oral and intravenous methylprednisolone and predni

34、solone 8. Eleven patients (20 percent) demonstrated unusual kinetics. Their drug clearance was approximately twice that of the rest of the population without an identifiable cause. Other findings included incomplete absorption of corticosteroids in four patients and an inverse correlation (r = -0.88

35、) between prednisolone clearance and age, which means that a given dose may have a greater effect in older persons. This relation to age has been confirmed in other studies 9. In addition, prednisolone clearance is also slower in African-Americans compared to Caucasians 10.With this degree of interp

36、atient variability in kinetics, it is conceivable that some patients may show greater withdrawal symptoms than others. This may occur despite the known difference between plasma corticosteroid kinetics and biologic activity.下丘腦-垂體-腎上腺軸的抑制一雖然有一種重要變量（在試驗(yàn)前曾治療的療程）總不能清楚地說明，但大 多數(shù)研究已顯示，當(dāng)強(qiáng)的松劑量超過5mg/d時，可出現(xiàn)下丘

37、腦-垂體-腎上腺軸的抑制。40mg/m2/d或 該劑量以上的強(qiáng)的松治療5天（尤其是分次給予時）即可開始出現(xiàn)下丘腦-垂體-腎上腺軸的抑制。即使甲 基強(qiáng)的松龍單次進(jìn)行關(guān)節(jié)內(nèi)注射時，也可引起短暫的抑制。另一方面，在強(qiáng)的松撤藥時，劑量在5mg/d 或5mg/d以下（每天早上一次）通常不引起下丘腦-垂體-腎上腺軸的抑制。另外，許多研究顯示，隔日治 療方案（如隔2天用2次）比每日療法對下丘腦-垂體-腎上腺軸的抑制和對白細(xì)胞反響的損害小。然而，對這種治療劑量和療程下的具體患者并不能準(zhǔn)確預(yù)測到下丘腦-垂體-腎上腺軸受抑制的可能性及程 度。例如有一項(xiàng)對279例患者應(yīng)用5-30mg/d強(qiáng)的松或其等效物治療1周至1

38、5年的評價，通過最后一 次應(yīng)用強(qiáng)的松24小時后早上一次性注射促皮質(zhì)激素釋放激素100mg來測定下丘腦-垂體-腎上腺軸功能（見下面），結(jié)果發(fā)現(xiàn)針對促皮質(zhì)激素釋放激素產(chǎn)生血漿ACTH和皮質(zhì)醇的反響缺乏者有43例患者 （15%）,遲鈍者有133例（占48%）,正常患者有103例（占37%）。這種反響性與激素劑量或療 程的相關(guān)性差，因此下丘腦-垂體-腎上腺軸不同抑制程度的決定因素尚不清楚。生物節(jié)律的喪失 皮質(zhì)醇分泌有晝夜節(jié)律，可被強(qiáng)的松的應(yīng)用所打破。如有一項(xiàng)評價用強(qiáng)的松治療34例 RA患者的研究，采用的是敏感的皮質(zhì)類固醇激素抑制試驗(yàn)（加壓素，美替拉酮，或胰島素誘導(dǎo)性低血糖） 而非測定血漿皮質(zhì)醇，有16

39、例患者出現(xiàn)皮質(zhì)類固醇激素晝夜節(jié)律異常（見“枯興綜合征的原因確定”章 節(jié)），這種異常節(jié)律與激素應(yīng)用時間的長短有關(guān)，而與每天的劑量無關(guān)。另一項(xiàng)研究發(fā)現(xiàn)，低劑量的強(qiáng)的 松龍（平均5.6mg/d）對晝夜節(jié)律無影響，然而，該研究應(yīng)用的腎上腺抑制測定方法（血漿皮質(zhì)醇測定 法）相對不敏感。很可能長期應(yīng)用皮質(zhì)類固醇激素引起了某些內(nèi)源性皮質(zhì)類固醇晝夜節(jié)律的受抑。下丘腦-垂體-腎上腺軸抑制程度一有人可能預(yù)測如應(yīng)用強(qiáng)的松的患者的下丘腦-垂體-腎上腺軸的抑制程度 高，撤藥更為困難。抑制程度可通過測定恢復(fù)正常下丘腦-垂體-腎上腺反響性所需的時間來估計(jì)，對兩項(xiàng) 長期用皮質(zhì)類固醇治療患者的研究已提出了這個問題。一項(xiàng)研究對1

40、2例患者在終止應(yīng)用強(qiáng)的松后一年間內(nèi)進(jìn)行了反復(fù)檢測，發(fā)現(xiàn)劑量超過7.5mg/d時恢復(fù)期延 長，且獲得胰島素誘導(dǎo)性低血糖正常反響的時間需1年，然而，除所有患者1年內(nèi)有恢復(fù)以外，抑制時間 的長短未明確說明。第二項(xiàng)研究綜述了 50例長期應(yīng)用強(qiáng)的松、而劑量已減少到10mg/d以下的患者，患者輸注ACTH進(jìn)行刺 激試驗(yàn)，服用5mg/d以下的23例患者中有3例患者（13%）受到抑制，而劑量超過5mg/d的患者中 這種抑制更為普遍。因此，對日劑量減量到這種低水平并保持至少數(shù)天無病癥出現(xiàn)或無既往疾病復(fù)發(fā)的患 者在激素減量過程中，一般不需轉(zhuǎn)換為隔日療法。短程治療后的恢復(fù)較快。象上面提到的那樣，應(yīng)用短至5天的大劑量

41、強(qiáng)的松后即可見到下丘腦-垂體-腎上 腺軸的受抑。如果強(qiáng)的松的應(yīng)用未超過7-10天，雖然某些患者的腎上腺功能恢復(fù)正常需7天或7天以 上，但大多數(shù)患者僅需2-4天。例如給予數(shù)天大劑量的強(qiáng)的松然后再在數(shù)天內(nèi)快速減量，那么強(qiáng)的松停止治 療1周后下丘腦-垂體-腎上腺軸的功能恢復(fù)正常。HYPOTHALAMIC-PITUITARY-ADRENAL AXIS SUPPRESSION- Most studies have shown that HPA axis suppression occurs at prednisone doses above 5 mg/day, although an important

42、 variable, the underlying duration of treatment prior to testing, was not always clearly delineated 11-15. Suppression can begin after as little as five days with prednisone doses of 40 mg/m2 per day or higher, particularly if given in multiple daily doses 14. Even a single intraarticular injection

43、of methylprednisolone can cause transient suppression 15. On the other hand, doses of 5 mg/day or less given once daily in the morning are generally not associated with pituitary-adrenal suppression when prednisone is withdrawn. In addition, a number of studies have demonstrated that alternate-day t

44、herapy (ie, giving twice the daily dose once every two days) produces less HPA suppression and/or less impairment of the leukocyte response than daily prednisone 16-18.However, the likelihood and degree of HPA suppression cannot be accurately predicted in an individual patient from the dose or durat

45、ion of therapy. One report, for example, evaluated 279 patients who had been treated with 5 to 30 mg/day of prednisone or its equivalent for one week to 15 years 19. HPA axis function was assessed by the administration oflOO fit of CRH (corticotropin releasing hormone) as a bolus morning injection 2

46、4 hours after the last prednisone dose (see below). The plasma ACTH and cortisol responses to CRH were absent in 43 patients (15 percent), blunted in 133 (48 percent), and normal in 103 (37 percent). There was a poor correlation with dose or duration of therapy. The factors determining the variable

47、degree of suppression are not well understood.Loss of circadian rhythm- Cortisol secretion undergoes a diurnal rhythm, which can be disrupted by the use of prednisone 20. One report, for example, evaluated 34 prednisone- treated patients with rheumatoid arthritis. Using sensitive tests of corticoste

48、roid suppression (vasopressin, metyrapone, or insulin-induced hypoglycemia) rather than plasma cortisol, sixteen of the patients were found to have an abnormal circadian corticosteroid rhythm 21. (See card Establishing the cause of Cushings syndrome). The abnormality was related to the duration of u

49、se, not to the daily dose. Another trial found no effect of low doses of prednisolone (mean 5.6 mg/day) on the diurnal rhythm; however, this study used a relatively insensitive measure of adrenal suppression (plasma cortisol measurement) 22. It is probable that some suppression of the endogenous cor

50、ticosteroid diurnal rhythm is caused by long-term corticosteroid usage.Degree of HPA suppression- One might expect more difficulty in withdrawing patients from prednisone if they have profound HPA suppression. The degree of suppression can be estimated by the time required to recover normal HPA resp

51、onsiveness. Two studies have addressed this issue in patients treated with chronic corticosteroid therapy.One report repeatedly examined 12 patients during the year after prednisone was discontinued 13. Doses in excess of 7.5 mg/day delayed recovery; attainment of a normal response to insulin-induce

52、d hypoglycemia required one year. However, the duration of suppression was not clearly defined except that recovery had occurred in all patients by one year.The second study reviewed 50 charts of patients who had been on long-term prednisone therapy but whose dose had been tapered to 10 mg/day or le

53、ss 12. The patients were given a stimulation test using ACTH infusion. Three of 23 patients (13 percent) who had been on 5 mg/day or less were suppressed. Suppression was more common in patients receiving more than 5 mg/day. Thus, patients who can be tapered to this low daily dose and maintained on

54、it for at least a few days without developing symptoms or a flare of the underlying disease do not generally require switching to alternate-day therapy during the tapering process.Recovery is much more rapid after short-term therapy. As noted above, HPA suppression can be seen after as little as fiv

55、e days of high-dose prednisone administration 14. Adrenal function returns to normal in most of these patients within two to four days, although some require seven or more days, provided the prednisone has not been given for more than seven to ten days. As an example, large doses of prednisone given

56、 for a few days and then tapered rapidly over a few more days result in normal HPA function one week after stopping the prednisone 23.下丘腦-垂體-腎上腺軸抑制的估計(jì)一在臨床上要識別下丘腦-垂體-腎上腺軸抑制程度并不簡單，可用許多 的試驗(yàn)，每一項(xiàng)試驗(yàn)對類固醇撤藥患者均有某些限制。血漿或尿中所分泌的游離皮質(zhì)醇不能定量下丘腦-垂體-腎上腺軸功能的儲存情況。然而，如測定到的數(shù)值 在正常范圍的上半?yún)^(qū)，那么下丘腦-垂體-腎上腺軸不太可能有明顯受抑，當(dāng)下丘腦-垂體-腎上腺軸

57、恢復(fù)后， 這些指標(biāo)可最快地恢復(fù)正常，但它們不是腎上腺對應(yīng)急反響的最好測試法（見“尿皮質(zhì)類固醇激素和游離 皮質(zhì)醇分泌的測定”章節(jié)）。對人工合成ACTH （促腎上腺皮質(zhì)激素）的反響是評估腎上腺皮質(zhì)功能最好的方法。然而，這不能提供 有關(guān)下丘腦功能的信息，及下丘腦或垂體功能不全的患者測得的腎上腺皮質(zhì)功能可能正常（見“腎上腺功 能不全對ACTH反響的評價”章節(jié)）。美替拉酮刺激測定整個下丘腦-垂體-腎上腺軸，但測定應(yīng)急反響并不重要（見“美替拉酮刺激試驗(yàn)”）測定應(yīng)急反響的最好方法是在胰島素誘導(dǎo)性低血糖期間測定血漿皮質(zhì)醇水平（如果測定仔細(xì)的話），這 很可能是測定腎上腺抑制最敏感的試驗(yàn)，長期應(yīng)用皮質(zhì)類固醇激素后

58、最常出現(xiàn)長時間的異常（見“胰島素 誘導(dǎo)性低血糖試驗(yàn)”章節(jié)）。然而，胰島素誘導(dǎo)性低血糖難以實(shí)施，如果進(jìn)行不合適，會帶來某些危險， 目前在臨床實(shí)踐中未普遍使用。促皮質(zhì)激素釋放激素試驗(yàn)也可用于評估ACTH和腎上腺的反響，且無胰島素誘導(dǎo)的低血糖相關(guān)的危險。 然而，該試驗(yàn)昂貴，在類固醇激素逐漸減量前不能廣泛使用。因此，臨床上評估下丘腦-垂體-腎上腺軸功能所用的每項(xiàng)試驗(yàn)均有其局限性。目前，類固醇激素撤藥最常 用的方法是經(jīng)驗(yàn)性撤藥，類似于下面所描述的一種方案。類固醇激素依賴性的其它形式一已證實(shí)其他形式的類固醇激素依賴性（并非因下丘腦-垂體-腎上腺軸受 抑引起的病癥和生化改變）可阻礙類固醇激素的逐漸減量，這些

59、因素包括：對類固醇激素精神性依賴疾病的復(fù)燃，需開該藥治療盡管下丘腦-垂體-腎上腺軸功能正常，也無疾病的復(fù)燃，但有明顯的腎上腺功能不全病癥?？偨Y(jié)一在考慮皮質(zhì)類固醇激素治療逐漸減量之前，評估下丘腦-垂體-腎上腺軸功能是否明顯受抑是很重要 的。以下患者無下丘腦-垂體-腎上腺軸的受抑，無需進(jìn)行評價這種可能性的測試：任何劑量的糖皮質(zhì)激素應(yīng)用時間不到3周的患者糖皮質(zhì)激素長期隔日療法罕有下丘腦-垂體-腎上腺軸功能的抑制。相反，應(yīng)考慮進(jìn)行下丘腦-垂體-腎上腺軸功能的抑制功能測試情況包括：強(qiáng)的松口服劑量在20mg/d以上、持續(xù)時間超過3周的任何患者臨床上發(fā)生枯興綜合征的任何患者對于不需進(jìn)行下丘腦-垂體-腎上腺軸

60、功能測試的患者，應(yīng)象對待繼發(fā)性腎上腺功能不全患者一樣處理，包 括讓他們帶上醫(yī)藥緊急救護(hù)手卡或項(xiàng)卡，在其錢包或皮夾內(nèi)放置緊急醫(yī)療信息，最可靠的是，預(yù)先帶上內(nèi) 含4mg磷酸地塞米松的1ml注射器，以防在緊急的時候注射（見“腎上腺功能不全的治療”章節(jié)）。下丘腦-垂體-腎上腺軸受抑居中類型的患者包括服用強(qiáng)的松10-20mg/d超過3周者。這些患者不需檢 測，除非需緊急停藥或急性應(yīng)急反響如手術(shù)。對于后一種情況，可預(yù)防性給予應(yīng)急劑量的糖皮質(zhì)激素，或 者如時間容許，象我們喜歡采用的用低劑量的二十四肽促皮質(zhì)素刺激試驗(yàn)來檢測腎上腺的反響。下丘腦-垂體-腎上腺軸中度受抑類型也包括強(qiáng)的松（或等效物）劑量在10mg/