# 2021/10/08 星期五值日生：Clinical problem solver episode 161- Hypoglycemia
## Case profile
### History
* 19 y/o male
* Underlying: sensory neuron hearing loss since birth
* SSx: 2~3 days of subjective fever, upper respiratory symptoms, AMS (with eyes open but poorly responding)
* Rx: LMD: sudafed (psudoephedrine) and Tamiflu
* Deny similar episode before this visit
* PMH: no DM, sensory neuron hearing loss since birth
* Current medication: nil
* denied insulin use
* Family denied insulin or other hypoglycemic agent at home
* Social history: deny illicit drug, tobacco, or alcohol usage; work in retail; lived with parents
* Family history: no DM history

### Evaluation at ER
* confusion but awake, BP 100/60mmHg, f/s 24
* Rx:
-> give 2 amps D50W + 1L N/S-> mental status improved
-> ER Keep D10W IVD and serum glu normal after D10W IVD D/C at evening, can eat by mouth
-> Recurrent hypoglycemia (f/s 45) next morning

### Physical examination (after sugar administration)
* Afebrile, BP 147/72, SaO2: 99% (RA)
* General appearance: well-appearing, no acute distress, BMI: 21
* HEENT: unremarkable, no lymphadenopathy
* CV: unremarkable, pectus excavatum
* Chest: bilateral clear breath sound
* Abd: normoactive bowel sound, non-tenderness, non-distend
* Limb: no peripheral edema
* Skin: no raches

### Neurological examination
* Consciousness: awake, alert and oriented
* Cranial nerve: intact
* Extremities: freely movable

### Lab
* Initial evaluation
* Lab: Na 128, K 3.5, Cl 98 23, BUN11, Cr 0.65
* AST 23, ALT 13, Bil(T) 1.0, ALK-p 26
* WBC 8700, absolute Eos count 620, Hb 8.9, Plt 139000
* Urine Sulfonylurea Screen (-)(但原則上2週後才會出來XD), U/A: ketone(1+)
* Further test
* Morning cortisol: <5 (low), ACTH (Cortrosyn) stimulation test: Cortisol <5
* TSH: 8.97 (H); free T3: 2.4 (L); free T4: 8 (L); thyroid peroxidase antibody (-); anti-thyroglobulin (H)
* ACTH: undetectable(<5); 21 hydroxylase antibody: undetectable
* FSH(WNL); LH(WNL); prolactin(WNL); testosterone(WNL)
* Hx: 無性腺發育異常 (pubic hair、蛋蛋大小、變聲WNL)、有鬍子(但不太需要刮)、晨勃(+)
* PE: 6尺高(=182cm)(Father 5.6; 哥哥 5.7)

## Case resolution
* Brain MRI: large and partially empty sella tucica (atypical for this age group), no other pituitary lesion
* Diagnosis
1. Secondary adrenal insufficiency, r/o empty sella tucica related, auto-antibodies against ACTH producing cell, underlying genetic disorder (r/o Pendred syndrome: hearing loss and a thyroid condition，但不能解釋adrenal insufficiency)
2. Primary hypothyroidism
* Treatment
1. Hydrocortisone
2. Levothyroxine

## Clinical pearls
### Hypoglycemia
#### 最初要釐清的：
1. 知道病人有沒DM
2. 最常見住院造成hypoglycemia
1. Renal failure
2. Liver failure
3. Further exacerbated by infection
#### True hypoglycemia→ Wipple triad!
1. 血糖低：有人認為定義為65以下，但對低血糖的界定仍需因個人體質而異
2. 低血糖症狀 (AMS,…)
3. 給糖水之後改善
#### Etiology
##### 病史釐清:
* Hx: illicit drug (永遠抱持一顆懷疑的心)
* BMI可作為營養不良的參考
* FHx: 明確釐清有其必要性，細問到底是沒有還是不確定有沒有
#### Thinking process
* Insulin medicated or Non-insulin mediated
* C-peptide, insulin數值在recurrent hypoglycemia後可進一步survey

### Adrenal insufficiency
1. Diagnostic test
* Cortisol
Random cortisol角色在於特別低可以診斷為adrenal insufficiency，但若數值borderline則較不具參考性
* ACTH (Cortrosyn) stimulation test
* 不局限於早晨施作，肇因於給予的劑量遠超過生理劑量(super physiologic dosage)，故在任何時間施作皆有其作用
* ACTH數值可用來鑑別central與primary adrenal insufficiency，但仍舊受限於lab無法很快得到結果。
* 另外若已知ACTH不足，則無須再驗21 hydroxylase antibody (已經證實並非primary adrenal insufficiency
* ACTH test須注意準確度問題，避免lab error造成不必要intervention
2. Central adrenal insufficiency
1. TSH數值可能因此較原先低，但在此病人身上TSH數值borderline
2. 另需釐清其他賀爾蒙有無受到影響，原則上影響順序為growth hormone→生殖 (女: 月經週期、男: 性慾sexual drive、勃起、發育)→thyroid→glucocortical-axis。仍有極少數isolated pituitary loss of function，可能與IgG4相關 (目前仍證據不足)
* 由此可知從簡單的history taking中詢問gonadal function對診斷治療的重要性
3. Mass effect造成的isolated adrenal insufficiency極少見，此情況可能自體免疫造成較合理

### Hypothyroidism
1. Antibody test在安排上面的必要性可被挑戰
* 一來是佐證為Hashimoto’s disease並不會影響處置
* 二來TPO在15% general population中可見
* Thyroglobulin只用於thyroid cancer治療之後續追蹤
2. 治療hypothyroidism之前一定要先治療adrenal insufficiency!!!!
3. Central hypothyroidism時可見正常的TSH數值，肇因於TSH本身為結構複雜的化合物，所以實驗室測到其實是無作用的TSH
4. Subclinical hypothyroidism並非一定要接受治療，可以watchful waiting
5. 此case之中TSH、free T3和T4數值較無法與19歲這個年齡correlation

### Empty sella
* 可能原先為pituitary adenoma (可進一步有mass effect或是根本沒症狀)，後來因特殊原因pituitary gland萎縮而呈現出空空如也，像Sheehan syndrome這類型pituitary apoplexy

### Autoimmune polyendocrine syndrome
* 須以更多peripheral endocrine problem作為佐證，釐清病人有無: 第一型DM、21 hydroxylase antibody

### Hashimoto’s encephalopathy
* 需質疑此診斷是否真的存在，因general population有高TPO盛行率
## Reflexion
1. 低血糖在臨床上並非少見，這集以一個特別的case呈現，讓整體evaluation完整而清楚。
2. 這集討論關於antibody的角色的部份十分有趣，有些檢查一開始被host駁斥(XD)沒有做的必要性，但當survey到後面時卻意外發現可以幫助排除其他可能狀況(如Autoimmune polyendocrine syndrome)。另外也看到國外跟國內對於做檢查的態度差異很大，在國外Host提到在抽血確診Hashimotos' disease不影響處置的狀況下他不太會抽，但在國內甚麼都馬抽抽看
3. 這個case整合性討論如何診斷內分泌疾病的過程讓我學到不少，尤其在臨床practice實用的小細節，以及各種檢體到底 to 抽 or not to 抽 (笑
## Podcast連結
* https://clinicalproblemsolving.com/2021/02/18/episode-161-consult-question-1-hypoglycemia/