ํ˜„๋‚ด - HAC (06.19 13).jpg

์•„๋ž˜๋Š” ํ•„๊ธฐ


  • ์ฟ ์‹ฑ = ๊ณ ์ฝ”๋ฅดํ‹ฐ์†”ํ˜ˆ์ฆ, ๋ถ€์‹ ํ”ผ์งˆ๊ธฐ๋Šฅํ•ญ์ง„์ฆ
  • ๊ฐ•์•„์ง€์—์„œ๋Š” ํ”ํ•˜์ง€๋งŒ
  • ๊ณ ์–‘์ด์—์„œ๋Š” iatrogenic์ด ๋” ๋งŽ์Œ.

Cortisol : ์ฒด๋‚ด ํ•ญ์ƒ์„ฑ์„ ์กฐ์ ˆํ•˜๋Š” steroid hormone

  • xksekswl whwjf
  • ํ˜ˆ์•• ์กฐ์ ˆ, ๊ทผ์œก/ํž˜์ค„, โ‡’ ๋ฆผํ”„์ ˆ, ์œ„์ถ• ๋“ฑ์ด ๋‚˜ํƒ€๋‚  ์ˆ˜ ์žˆ์Œ.

1. Classification

Hyperadrenocorticism (HAC)

  • Pituitary-dependant HAC (PDH) : ๊ฐ€์žฅ ๋งŽ์Œ. (80-85%)
  • Functional adrenal tumor-dependent HAC (ATH)
  • Occult HAC : ์ฝ”ํ‹ฐ์†” ์ˆ˜์น˜๊ฐ€ ๋†’์œผ๋‚˜ ์ฆ์ƒ์ด ์—†์Œ. โ‡’ Early stage cushing ํ˜น์€ ๊ณ„์† ์ด๋ ‡๊ฒŒ ์œ ์ง€.^[์Šค์ฝ”ํ‹ฐ์‹œ ํ…Œ๋ฆฌ์–ด=ํ‰์ƒ ์ด๋ ‡๊ฒŒ๋งŒ ๊ฐ–๊ณ  ์žˆ๋Š” ์• ๋“ค ๋งŽ์Œ]
  • Atypical HAC : ๋ถ€์‹ ์—์„œ ๋ถ„๋น„ํ•˜๋Š” ์„ฑํ˜ธ๋ฅด๋ชฌ ์ˆ˜์น˜๊ฐ€ ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚จ.
  • Meal/food-induced HAC : ์Œ์‹ ๋“ฑ์— ์ž๊ทน๋˜์–ด ์ƒ๊น€, ์ง„์งœ ๋“œ๋ฌธ ์ผ€์ด์Šค.
  • Iatrogenic HAC : ์Šคํ…Œ๋กœ์ด๋“œ ์ œํ˜•์— ์˜ํ•ด ๋ฐœ์ƒ

Pituitary-dependent HAC

  • HPA Axis์˜ ์˜ํ–ฅ์„ ๋ฐ›์Œ.

  • ์„ ์ข…(์–‘์„ฑ) ๋•Œ๋ฌธ์— ํ˜ธ๋ฅด๋ชฌ ์งˆํ™˜์ด ๋ฐœ์ƒํ•˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ์Œ.

  • Functional ACTH-secreting pituitary adenoma (85% of PDH)

  • Hyperplasia

  • Carcinoma

  • ganglion cell tumor

  • Pituitary macrotumor syndrome : ๋„ˆ๋ฌด ์ปค์ง€๋ฉด ์ฃผ๋ณ€ ์กฐ์ง๋„..

    • ๋ณดํ†ต 3mm๋„ ์•ˆ ๋˜๋Š” ์ž‘์€ ์ข…๊ดด์— ์˜ํ•ด ๋‚˜ํƒ€๋‚˜๋Š”๋ฐ,
    • ์ด ์ผ€์ด์Šค๋Š” 1cm ์ด์ƒ ์ปค์งˆ ๋•Œ.
    • ์–‘์„ฑ ์ข…์–‘์ธ ๊ฒฝ์šฐ๊ฐ€ ๋งŽ์Œ.

Adrenal gland

  • ๋ถ€์‹  ์ข…์–‘์ด ๋ฐœ์ƒํ•˜๋Š” ๊ฒฝ์šฐ
  • medulla ์ชฝ origin
  • ์ˆ˜์ˆ  ์‹œ ์šฐ์ธก ์‹ ์žฅ์ด ์กฐ๊ธˆ ๋” ๋‚œ์ด๋„ ๋†’์€

Adrenal tumors

  • Functional = ๊ณผ๋„ํ•œ ํ˜ธ๋ฅด๋ชฌ ๋ถ„๋น„์— ์˜ํ•ด
    • ๋ถ€์‹ ์—์„œ ์ฝ”ํ‹ฐ์†”์„ ๋ถ„๋น„ํ•˜๋Š” ์ข…์–‘ ์ž์ฒด๊ฐ€ ์›์ธ..
    • ์„ฑํ˜ธ๋ฅด๋ชฌ ๋ฐœ์ƒ
  • Non-functional =

2. Clinical features

Predisposition

  • Age : > 6y old
  • Breed : Dachshunds, Poodles, Boxers, Boston Terriers, Terrier breeds, German Shepherd dogs, Beagles, Labrador Retrievers, and Australian Shepherds
  • Sex : No / functional adrenal tumor๋Š” ์•”์ปท์—์„œ ์กฐ๊ธˆ ๋” ํ˜ธ๋ฐœ

Common features

(5P signs)

  • Polyuria : ์ˆ˜๋ถ„์ด๋‡จ ๋ฐœ์ƒ
    • in cats, ์ง€์†๋˜๋ฉด ์š”๋‹น์ด ๋ฐœ์ƒํ•˜๋ฉด์„œ ๋‹น์ด ๊ฐ™์ด ๋น ์ ธ๋‚˜๊ฐ (์šฉ์งˆ์ด๋‡จ)
  • Polydipsia : secondary to PU
  • Panting
  • Polyphagia : ์ŠคํŠธ๋ ˆ์Šค ๋ฐ›์•„๋„ ์ฝ”ํ‹ฐ์†” ์˜ฌ๋ผ๊ฐ.
  • Pot-belly (abdominal enlargement) = pendulous abdomen
    • ๊ฐ„๋น„๋Œ€(hepatopathy), ํ”ผ๋ถ€ ์ž์ฒด๊ฐ€ ์–‡์•„์ ธ ๊ธด์žฅ๋„ ์ €ํ•˜, ๋ฐฐ๊ฐ€ ์ถ• ์ณ์ ธ ๋‚ด๋ ค์˜ด.
  • Skin changes
  • Musculoskeletal abnormalities
Skin changes
  • Dystrophic calcinosis cutis : ์นผ์Š˜์ด ์ด์ƒํ•˜๊ฒŒ,, / ํ”ผ๋ถ€์— ์ž˜ ์นจ์ฐฉ๋จ
  • Increased susceptibility to cutaneous infections : ์„ธ๊ท  ๊ฐ์—ผ์— ์ทจ์•ฝํ•ด์ง - ํŠนํžˆ ๋น„๋‡จ๊ธฐ, ํ”ผ๋ถ€
  • ์–ผ๊ตด, ๋‹ค๋ฆฌ ์ชฝ์€ ๋น„๊ต์  ์ž˜ ์•ˆ ๋‚˜ํƒ€๋‚จ. ์ฟ ์‹ฑ์Šค๋Ÿฌ์šด๋ฐ ์–ผ๊ตด/๋‹ค๋ฆฌ ์ชฝ์—๋„? - ๋‹ค๋ฅธ ํ”ผ๋ถ€ ์งˆํ™˜์˜ ๋ณ‘๋ฐœ ์˜์‹ฌ.
    • ์•Œ๋Ÿฌ์ง€๋Š” ์Šคํ…Œ๋กœ์ด๋“œ ์“ฐ๋ฉด ์ข‹์•„์ง€๋Š”๋ฐ, ๊ทธ๋ž˜์„œ ์ฟ ์‹ฑ ์žˆ์„ ๋• ์ฝ”ํ‹ฐ์†” โ†‘, ํ”ผ๋ถ€ ์ข‹์•„์กŒ๋‹ค๊ฐ€, ์ฟ ์‹ฑ ์ข‹์•„์ง€๋ฉด ํ”ผ๋ถ€ ์•ˆ ์ข‹์•„์กŒ๋‹ค๊ฐ€..
Distribution of skin changes

Classical cutaneous signs
- Bilaterally symmetrical alopecia (head&limb๋Š” ๋‚จ์•„์žˆ์Œ)
- Dry and lusterless haircoat (Curlyํ•œ hair๊ฐ€ ์ง๋ชจ์ฒ˜๋Ÿผ ํŽด์ง)
- Variable hyperpigmentation
- Hypotonic
- Phlebectasias
- Comedones (๋ธ”๋ž™ํ—ค๋“œ์ฒ˜๋Ÿผ ๋ณด์ž„) & milia
- Calcinosis cutis (mineralization โ†’ ๋งŒ์กŒ์„ ๋•Œ ๋” ๋”ฑ๋”ฑํ•˜๊ณ , ์‚ฌ๊ฐ์‚ฌ๊ฐํ•œ ๋А๋‚Œ)
- Cutaneous ossification (์นผ์Š˜ํ™”๋ฅผ ์˜ค๋ž˜ ๋ฐฉ์น˜ํ•˜๋ฉด ๊ณจํ™”์ฒ˜๋Ÿผ ์ง„ํ–‰, ์ž˜๋ผ๋‚ด์ง€ ์•Š์œผ๋ฉด ์–ด๋–ป๊ฒŒ ๋ชปํ•จ..)
(cats)
- Skin atrophy
- Skin fragillity
Cardiorespiratory chage
  • Systemic hypertension ์ „์‹ ๊ณ ํ˜ˆ์•• ์œ ๋ฐœ (80% ์ด์ƒ / ์‹ฌํ•œ ๊ฒฝ์šฐ๋„ 50% ์ด์ƒ)
  • ํ˜ˆ์ „ ๋งŽ์ด ์ƒ๊น€ (ํ˜ˆ์•ก์ด ๋ˆ์ ํ•ด์ง) : ํํ˜ˆ๊ด€์ด ๊ฐ€์žฅ ๋งŽ์ด ๋ง‰ํž˜.
  • ํ˜ˆ์•• ์ƒ์Šน ๊ฐ€๋Šฅ์„ฑ์ด ๋†’๋‹ค. โ‡’ CHF, ์‹ฌ๊ทผ๋น„๋Œ€
  • ๊ฐ์—ผ ์ทจ์•ฝ, ํ๋ ด ๋ฐœ์ƒ
Urogenital
  • Glomerulonephropathy
  • UTI โ‡’ ์ด๊ฒƒ๋„ ์‹ฌ์žฅ ๋ฐ๋ฏธ์ง€ ์œ ๋ฐœ
  • Urolithiasis (์š”๊ฒฐ์„) : Calcium oxalate ํ”ํ•จ
  • Peresistent anestrus
Others
  • Insulin-resistant ์œ ๋ฐœ
  • ํ˜ˆ์••์ด ๋†’์•„์„œ ์•ˆ๊ตฌ ์ชฝ ๋ฌธ์ œ

3. Diagnosis

Baseline Diagnostics
Signalment
History taking
Physical examination
- Systolic
- Diastolic
Routine laboratory tests
CBC
-
Serum biochemical profile
-
- isoenzyme โ‡’ ์„ธ์„ธํ•œ ๋ถ„๋ฅ˜
TEG ๊ฒ€์‚ฌ
- ๊ณผ์‘๊ณ  ์ƒํƒœ, ํ˜ˆ์ „ ๊ด€๋ จ ๊ฒ€์‚ฌ๋„ ์ง„ํ–‰
- R, K ๊ฐ’ ๊ฐ์†Œ / ฮฑ, MA ๊ฐ’ ์ฆ๊ฐ€

- ์น˜๋ฃŒ ํ›„ ์ •์ƒํ™”๋จ.
Urinalysis
Urine culture
Endocrine
Endocrine Diagnostics
Initial endocrine screening
- LDDS
- Corticotropin
- UCCR
Differentiation between PDH & ATH
- LDDST
- High-Dose Dexamethasone Suppression (HDDS) test
  • ๋‚ด์ธ์„ฑ cortisol ์ฆ๊ฐ€ โ†’ ACTH ๋ถ„๋น„ ๊ฐ์†Œํ•จ.
  • ํ™˜์ž : ์—ฌ์ „ํžˆ ์ฝ”ํ‹ฐ์†” ๋†’๊ฒŒ ๋‚˜์˜ด.
  • Adrenal tumor vs. cushing
  • ์ฝ”ํ‹ฐ์†”์ด
  • ์‚ด์ง ์–ต์••๋˜์—ˆ๋‹ค๊ฐ€ ์˜ฌ๋ผ๊ฐ€๋ฉด : PDH ๊ฐ€๋Šฅ์„ฑ
  • 8์‹œ๊ฐ„..

ACTH (Cprtocptrpin stimulation test)

  • Iatrogenic lseks

HDDS (High-Dose Dexamethasone Suppression) test

  • PDH์™€ ATH ๊ฐ๋ณ„ : ์š”์ฆ˜์€ ๋ณต๋ถ€์ดˆ์ŒํŒŒ๋ฅผ ๋” ๋งŽ์ด ํ™œ์šฉ
Imaging
  • ๋ณต๊ฐ• ์žฅ๊ธฐ๊ฐ€ ์ปค์ ธ ๋ณต๊ฐ• ์„ ์˜ˆ๋„ ์ฆ๊ฐ€
Radiography (Abd.)

- Excellent abdominal detail
- Hepatomegaly
- Distention of urinary bladder
- Cystic calculi
- Adrenal mass
- Calcified adrenal gland
- Dystrophic calcification of soft tissues, calcinosis cutis
- Osteoporosis of vertebrae
ใ…
- ํŽธ์ธก ๋น„๋Œ€
- ์ข…์–‘ํ™”๋œ ์กฐ์ง์€ ์˜ํ–ฅ์„ ์•ˆ ๋ฐ›๊ณ 
- ๋ฐ˜๋Œ€์ชฝ ์กฐ์ง์€ ์œ„์ถ• (์ด๋ฏธ ๊ณผ๋„ํ•œ ๋ถ„๋น„)
- ๊ฐ‘์ž๊ธฐ ์ ˆ์ œํ•ด๋ฒ„๋ฆฌ๋ฉด ์ ์‘ ๋ถˆ๊ฐ€
- ํšŒ๋ณต ๋•Œ๊นŒ์ง€ ์Šคํ…Œ๋กœ์ด๋“œ ํˆฌ์•ฝ ํ•„์š”
U/S
- ๋น„๋Œ€ (Cr/Cd ํ•œ์ชฝ๋งŒ ๋น„๋Œ€๋ผ๋„ O)
MRI : ์ฟ ์‹ฑ๋งŒ ์žˆ๋Š” ํ™˜์ž์—์„œ ์ž˜ ์ฐ์ง„ X
- ์„ ์ข… โ†’ ๋‡Œํ•˜์ˆ˜์ฒด ๋น„๋Œ€ (P:B ratio < 0.31)
- ๋‡Œํ•˜์ˆ˜์ฒด ํฌ๊ธฐ๊ฐ€ 1cm ์ด์ƒ์ด๋ฉด ์‹ ๊ฒฝ์ฆ์ƒ ๊ฐ€๋Šฅ

4. Treatment

  • ์ž„์ƒ ์ฆ์ƒ ์กฐ์ ˆ์ด ๋ชฉํ‘œ
Adrenal-directedPituitary-directed
- Trilostane : ์„ฑํ˜ธ๋ฅด๋ชฌ ๋ถ„๋น„ ์ด์ƒ ์‹œ์—๋„ ์‚ฌ์šฉ
- Mitotane
- ketoconazole
- Adrenalectomy
Adrenal-directed Tx.
Drugs
Trilostane
[Vetoryl]
โœ”๏ธ ๋ฐฅ์ด๋ž‘ ๊ฐ™์ด ๋จน์ด๋„๋ก
๐Ÿ“ˆ ๋ชจ๋‹ˆํ„ฐ๋ง 1 :
- 1-7 ์šฉ๋Ÿ‰์œผ๋กœ ๋‚˜์˜ค๋ฉด ์ ์ ˆ ์šฉ๋Ÿ‰์œผ๋กœ ๋ณด๊ณ  ์œ ์ง€
- ์ตœ์†Œ 2-3์ผ ์ œ๋Œ€๋กœ ๋จน์ธ ๋‹ค์Œ ํ‰๊ฐ€.
๐Ÿ“ˆ ๋ชจ๋‹ˆํ„ฐ๋ง 2
base
๐Ÿฉท Mean survival time- ๋…ธ๋ น์— ์ง„๋‹จ๋œ ๊ฒฝ์šฐ ๋ถ€์ •์ 
โ—๋ถ€์ž‘์šฉ๋ถ€์‹ ํ”ผ์งˆ๊ธฐ๋Šฅ์ €ํ•˜์ฆ
Mitotane
[Lysodren]
- ๋‹ค๋ฅธ ์กฐ์ง ๊ดด์‚ฌ ์œ„ํ—˜

Induction phase
- PDH : 15-25mg/kg PO BID
- ADH :

Maintenance phase
- PDH :
- ADH :
Ketoconazole- ๊ณฐํŒก์ด๋ฅผ ์ฃฝ์ด๋Š” ์•ฝ (ํ•ญ์ง„๊ท ์ œ; -onazole)
- ํ˜ธ๋ฅด๋ชฌ์•ฝ ๋น„์‹ธ์„œ ๋ชป ์“ธ ๋•Œ๋„ ์‚ฌ์šฉ
- ๊ณฐํŒก์ด์— ๋Œ€ํ•ด์„œ๋Š”
- ํ˜ธ๋ฅด๋ชฌ์€ ๋” ๊ณ ์šฉ๋Ÿ‰์œผ๋กœ

Adrenalectomy

  • ์ˆ ํ›„ ๋ถ€์ž‘์šฉ
  • ๋ฐ˜๋Œ€์ชฝ ๋ถ€์‹ ์ด ์œ„์ถ•๋œ ์ƒํƒœ : hypocortisol ๋‚˜ํƒ€๋‚œใ„น ์ˆ˜ ์žˆ์œผ๋ฏ€๋กœ, ์ผ์‹œ์ ์œผ๋กœ steroid ํˆฌ์•ฝ ํ•„์š”.
  • ์˜ˆํ›„ ์ธ์ž : ์•…์„ฑ ๊ฐ„์œผ์„ฑ์ด ์žˆ์„ ๋•Œ..
Pituitary-directed Tx.
Hypophysectomy
๋ถ€์ž‘์šฉ
- ์š”๋ถ•์ฆ, ๊ฐ‘์ƒ์„ ๊ธฐ๋Šฅ์ €ํ•˜์ฆ, ๋ถ€์‹ ํ”ผ์งˆ๊ธฐ๋Šฅ์ €ํ•˜์ฆ,
์ˆ˜์ˆ  ๋‚œ์ด๋„๋ฅผ ๊ณ ๋ คํ•ด RT๋ฅผ ๋” ํ™œ์šฉ.
RT ํ›„ ๋‡Œํ•˜์ˆ˜์ฒด ํฌ๊ธฐ๊ฐ€ ํ›จ์”ฌ ์ž‘์•„์ง„ ์–‘์ƒ.
8๋งˆ๋ฆฌ ์ค‘ ์ ˆ๋ฐ˜๋งŒ ์‹ ๊ฒฝ์ฆ์ƒ ๊ฐœ์„ ๋œ ๋…ผ๋ฌธ.
Iatrogenic HAC
  • ์Šคํ…Œ๋กœ์ด๋“œ๋ฅผ ๋งŽ์ด ์ค˜์„œ ๋ฐœ์ƒ
  • ์Šคํ…Œ๋กœ์ด๋“œ๋ฅผ ๋Š๋Š” ๊ฒŒ ์šฐ์„ .
  • ๊ธฐ์กด ๋ถ€์‹ ?์ด ์ œ๋Œ€๋กœ ๊ธฐ๋Šฅ์„ ๋ชป ํ•˜๊ณ  ์žˆ๋Š”๋ฐ ์Šคํ…Œ๋กœ์ด๋“œ๋ฅผ ๊ฐ‘์ž๊ธฐ ๋Š์œผ๋ฉด ๋ถ€์‹ ํ”ผ์งˆ๊ธฐ๋Šฅ์ €ํ•˜์ฆ,

Complication management

  • ๊ฐ€์žฅ ๋Œ€ํ‘œ์ ์ธ 3๊ฐ€์ง€

    • Secondary bacterial pyoderma, Demodicosis, Calcinosis cutis/Cutaneous ossification
  • ์ €ํ˜ˆ๋‹น shock์ด ์˜ฌ ์ˆ˜ ์žˆ์Œ