Adrenal insufficiency (AI)

定義
病因	1° : ACTH高        自體免疫(腎上腺炎/Hashimoto), 感染(TB), 藥 (ketoconazole, RIF, 抗痙攣藥) 2°  :  ACTH低/ low Normal:                類固醇, 1° or 2° hypopituitarism
臨床	虛弱 &厭食(99%), BWL Primary only: (因缺乏aldo & ACTH高)        嚴重姿態性低血壓(因嚴重脫水), 低鈉,高血鉀,         皮膚色素沉著過度(in crease, )  Secondary only:       ± other MF pf hypopituitarism
Lab	早晨[cortisol] <3 ug/dL 篩檢: 標準 single dose ACTH (cortrosin, 0.25ml) stimulation test ( 60min後 ≦18ug/dL) ACTH:  Primary: ↑;   Secondary: ↓ or low normal
影像	Pituitary MRI (detect anatomical abn) Adrenal CT:   small non-calcified adrenals -> Autoimmune dz   enlarged -> mets, 出血, 感染, or deposition (也可能呈現正常外觀)
治療	急性: (校正低血壓,脫水,休克, 低血糖,低血鈉)    -N/S + iv hydrocortisone (100mg q6h)(->taper)  慢性:    -cortisone (1# AM; 0.5# PM)
預後

病因:  mc:  自體免疫腎上腺炎, 感染, 甲狀腺炎
   less com: 出血, 藥物, 浸潤性疾病

 Primary =adrenocortical dz = Addison's dz (cortisol↓, ACTH↑)

  

   自體免疫 (mc) : isolated or in a/w PGA synd.
   感染: TB, CMV, histoplasmosis

   血管性: 出血 (sepsis), thrombosis, HIT (heparin-induced thrombocytopenia), trauma
   癌症轉移: (腎上腺90%遭破壞才會造成insuff) 
    deposition dz: hemochromatosis, amyloidosis, sarcoidosis

   藥物: ketoconazole, etomidate (手術短效性催眠,麻醉藥), RIF, 抗痙攣藥,
  

    Kid: 感染(綠膿桿菌, 腦膜炎球菌*

    Adult: 凝血異常

 Secondary: (pituitary fail 分泌 ACTH)(ACTH↓,cortisol↓) (but aldo intact due to RAA axis)

   -Pan-hypopituitarism (any cause 1° or 2° hypopituitarism)

   -長期服用類固醇後,突然停藥 (mc) (can occur after 2 wks "supressive dose")
       * suppressive effect variable (<10 mg/day prednisolone chronically can be suppressive)
   -megestrol (a progestin w/ some glucocorticoid eff)

*PGA (Polyglandular Autoimmune) syndrome  
    Type I (children) : Adrenal insuff, hypoparathyroidism, mucocutaneous candidiasis,
    Type II (adult): Adrenal insuff, autoimmune thyroid dz (thyroiditis), T1DM



臨床:

  虛弱 &厭食(99%), BWL

  姿態性低血壓 (90%)

  低血鈉

  Primary only: (因缺乏aldo & ACTH高) 
      嚴重姿態性低血壓(因嚴重脫水), 低鈉,高血鉀,  
      皮膚色素沉著過度(in crease, )
  Secondary only:
      ± other MF pf hypopituitarism

診斷: Annals 2003

-early AM serum cortisol
    < 3 ug/dL virtually diagnostic
    ≥ 18 ug/dL rules it out (除非 in severe septic shock

   1) 篩檢: 標準 cosyntropin stimulation test (測試腎上腺對ACTH的反應會否上升)
         注射250 ug 人工合成ACTH (Cosyntropin (Cortrosyn)), 30-60min 後測血中 cortisol, 
         正常: 60-min post ACTH -> cortisol ≥ 18 ug/dL
 若無法上升到 18 ug/dL 以上, 則須懷疑有 Adrenal insufficiency.

   2) 測ACTH
         很高: primary AI, 會合併mineralocorticoid 不足症狀, 造成低鈉,高鉀
         正常/偏低: secondary AI, mineralocorticoid 會由RAA SYSTEM 自行調控, 較不會出現異常

Lab	低血糖, eosinophilia, lymphocytosis, ± neutropenia
Early AM serum cortisol (6:00)	< 3 ug/dL (virtually diagnostic) ≥ 18 ug/dL (排除診斷) (除非 in severe septic shock)
標準 cosyntropin (250 ug) stimulation test	(測試腎上腺對ACTH的反應會否上升) cortisol (60-min post ACTH)  ≥ 18 ug/Dl: 正常腎上腺反應  < 18 ug/dL:    1° AI (因adrenal glands dz, unable to give adequate output    Chronic 2° AI (因adrenals atrophied, and unable to response) * very rare, may be normal in acute secondary AI (因腎上腺仍可反應) * early AM cortisol can be used in these cases (rather than post-stim value)
其他test to evaluate HPA axis
Insulin-induced hypoglycemia	(測serum cortisol response)
Metyrapone stimulation test	Block cortisol合成, 因此刺激ACTH
測 plasma [11-deoxycortisol] ≦ 18 歲: < 344 ng/dL > 18歲 : 10-79 ng/dL after a single-dose overnight metapyrone test 正常: >1700 ng/dL	[判讀]:  -suspected congenital adrenal hyperplasia (CAH), elevated 11-deoxycortisol levels indicate possible 11-beta-hydroxylase deficiency.    Pharmacological blockade of 11-beta-hydroxylase with metyrapone normally stimulates a rise in 11-deoxycortisol. A subnormal rise in 11-deoxycortisol levels after a single-dose overnight metapyrone stimulation test is associated with causes of adrenal insufficiency, including the following:     Primary adrenal insufficiency: Addison dz, adrenal adenoma, CAH     Secondary adrenal insufficiency: Pituitary microadenoma, hypothalamic tumor, pituitary apoplexy, head trauma     Tertiary adrenal insufficiency: Hypothalamic dz with ↓ corticotropin-releasing factor (CRF)
測24h 尿17-OHCS (17-hydroxycorticosteroid)   (正常 M：3-12mg/day  F：2-7 mg/day)	17-Hydroxycorticosteroid, 17-OHCS (24h urine) 一般類固醇在肝中代謝，會與葡萄糖醛酸(glucuroic acid)和硫酸根結合成水溶液物質然後由尿液排出，其中17-Hydroxycorticosteroid(17-OHCS)是重要的代謝物，而17-OHCS有80%是皮質醇(cortisol) 代謝， 測尿中17-OHCS可反映血中cortisol的含量，間接評估腎上腺功能。 臨床意義： 　17-OHCS增加於腎上腺皮質功能亢進(原發或繼發)、Cushing 氏疾病、甲狀腺功能亢進、高血壓。 17-OHCS下降於腎上腺皮質功能低下(原發或繼發)、Addison氏病、飢餓、妊娠、腎功能衰竭、肝硬化。
ACTH	Primary: ↑ Secondary: ↓ or low normal
影像	Pituitary MRI (detect anatomical abn) Adrenal CT:   small non-calcified adrenals -> Autoimmune dz   enlarged -> mets, 出血, 感染, or deposition (也可能呈現正常外觀)

特殊狀況:

Adrenal crisis:
  -當慢性AI病人, 因敗血症/開刀, 造成急性AI, 甚至decompensation, 
  -MF: 嗜睡, 昏迷, 體液不足, 導致低血壓/休克
  -治療: 補水, Hydrocortisone 100mg q6h

Critical ill patient 與 AI
  -發生急症(敗血症,外傷,開刀)時, cortisol 會上升6-10倍, 且會失去日夜變化 (白天高,晚上低), 若cortisol 無法提升到身體需要的量, 以控制發炎反應, 維持血壓, 則稱為 relative AI.

診斷: 
  1-cortisol 無法提升至 15 ug/dL
  2-注射250ug Cosyntropin, 血中cortisol 與基準值相比, 無法上升大於 9 ug/dL


治療:

 急性AI: 
   -先校正低血壓,脫水,休克, 低血糖,低血鈉
   -vol resuscitation (N/S) + hydrocortisone (iv) (100mg q6h)(taper if 改善)
 慢性AI:
   -Hydrocortisone: 20–30 mg PO qd ( 2 ⁄ 3 a.m. 1 ⁄ 3 early p.m.) or prednisone 1# (5 mg) PO qam
   -Fludrocortisone (not needed in 2 ° AI): 0.05–0.1 mg PO qam
   *back-up dexamethasone 4 mg IM prefilled syringe given to Pt for emergency situations

  -cortisone (25mg/#) (20-30mg/day) 1# AM; 0.5# PM (靠臨床判斷調整劑量)


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adrenal insufficiency

21.    Single dose ACTH stimulation test –

-          Check plasma Cortical Level at 0 minute

-          ACTH (Cortrosyn ,1mg/1ml /vial )0.25mg(=0.25ml )im or iv injection at 0 minutes

-          check plasma Cortisol level at 30,60 minutes

28 –DDAVP stimulation test for adrenal insufficiency

    -在注射DDAVP 前30 minutes ,set IV line with 3-way cap

    -注射DDAVP (4ug/amp) 2.5amp (即Desmopressin 10ug) iv 時, 設為0分鐘

    -check ACTH and cortisol level at -15,0,15,45,60&90分鐘 

 (判讀標準:

Desmopressin 尚未確定:

ACTH 上升>30-50% or cortisol 上升>20%, favor Cushing disease ;

ACTH 上升<6 pmol/L 為沒有反應)

    注意:Imipramine 會影響cortisol response