Download 부신피질호르몬의 종류

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부신피질 호르몬이란?
부신피질호르몬제제와 올바른 사용
부신피질호르몬제제 사용시 문제점
부신피질 호르몬이란?
부신피질호르몬제제와 올바른 사용
부신피질호르몬제제 사용시 문제점
15%
Zona glomerulosa: Aldosterone
75%
Zona fasciculata: Cortisol
10%
Zona reticularis: Sex steroid
Cell types
Vessels
Compound E
Sep 21, 1948
The first injection of compound E for rheumatoid
arthritis
Cortisone
Nobel
Prize
in 1950
Charles H. Slocumb (left)
Howard F. Polley
Edward c. Kendall
Philip S. Hench
A Famous Sufferer of Addison’s Disease


John Kennedy was sick from
age 13 on.
In 1930, when he was 13, he
developed abdominal pain.
By 1934 he was sent to the
Mayo Clinic where they
diagnosed colitis or it was
called colitis.
By 1940 his back started
hurting him, by 1944 he had
his first back operation, by
1947 he was officially
diagnosed as having
Addison's Disease.
John F. Kennedy
Steroid Biosynthesis

Source: LDL cholesterol

ACTH increase the
number of LDL receptors

Daily secretion of
cortisol
 15 ~ 30 mg
LDL Cholesterol
부신피질호르몬의 종류
1. Glucocorticoid(당류코르티코이드)
 Cortisol: 15 – 30 mg/day
2. Mineralocorticoid(염류코르티코이드)
 Aldosterone: 50 – 250 g/day
3. Adrenal androgen(안드로젠)
 15 – 30 mg/day
 Dehydroepiandrosterone (DHEA)
 DHEAS
일중변동 (Circadian rhythm)
JCEM 94:1548-1554, 2009
Steroid Transport

Unbound form (free cortisol)
 Less than 5% of circulating cortisol
 Hypersecretion of corsitol: urine free cortisol 

Bound form
 Cortisol binding globulin (CBG): high affinity
○ CBG is reduced in inflammation site
○ CBG increased in high-estrogen state (preg., pill)
○ Synthetic steroid bind less to CBG
 Albumin: low affinity

Synthetic glucocorticoid: low affinity to CBG
Mechanism of cellular cortisol action
Liver, Adipose tissue
Kidney
Cortisol
11β-HSD2
Cortisone
Cortisol
Glucocorticoid
receptor
11β-HSD1
Cortisone
Effect
글루코코르티코이드 기능
대사에 관한 작용
- glycogen metabolism
- gluconeogenesis
- peripheral glucose utilization
- lipid metabolism
 면역계에 대한 작용: 항염증작용
 근골격계에 대한 작용
 기타 작용

Immune-adrenal axis
Leukocytosis
- release from BM
- Inhibition of egress
through the capillary wall
Anti-pyretic action
- Inhibition of IL-1
Suppress cell-mediate
immunity
Effects on Skeletal System
- Deplete the protein matrix of the
vertebral column (trabecular bone)
Effects on Liver
- Fatty acid mobilization by activation of
cellular lipase
Effects on Glucose Metabolism
-
Antagonizing action of insulin
Inhibition of insulin secretion
Inhibition of peripheral glucose uptake
Promote gluconeogenesis
합성 글루코코르티코이드를 장기 투여할 때
나타나는 부작용
부신피질 호르몬이란?
부신피질호르몬제제와 올바른 사용
부신피질호르몬제제 사용시 문제점
의인성 쿠싱증후군을 일으키는 요인





Formulation of steroid
Pharmacokinetics
Affinity for the GR
Biologic potency
Duration of action
합성 스테로이드의 특징
Affinity for CBG
Affinity for GR
국소 스테로이드 사용시 주의
Topical Steroid + Disruption of skin integrity
Inhaled steroid + Anti-fungal agent
Issues affecting withdrawal
from steroid therapy
The possibility of suppression of the HPA axis
The possibility of worsening of the underlying
disease
Steroid withdrawal syndrome
Corticosteroid Products
Relative biologic potencies of synthetic
steroids
Steroid
Anti-inflammatory
Action
Hypothalamic-Pituitary
-Adrenal Suppression
Salt Retention
Cortisol
1
1
1
Prednisolone
3
4
0.75
Methylprednisolone
6.2
4
0.5
Fludrocortisone
12
12
125
5
4
0
26
17
0
Triamcinolone
Dexamethasone
PDL vs. methylprednisolone
Prednisolone
Methylprednisolone
Potency
4
5
Mode of
administration
oral
oral, parenteral
Action duration
intermediate
Intermediate or
long
PDL 60 mg/d
for 4 days
PDL 50 mg/d
for 2 days
14 days
PDL 40 mg/d
for 2 days
PDL 30 mg/d
for 2 days
PDL 10 mg/d
for 2 days
PDL 20 mg/d
for 2 days
부신피질 호르몬이란?
부신피질호르몬제제와 올바른 사용
부신피질호르몬제제 사용시 문제점
단기간 스테로이드 사용시 문제점
Hypothalamic-pituitary-adrenal (HPA) axis
suppression
 Hyperglycemia
 Gastrointestinal effects
 Psychiatric effects

HPA axis 억제
2차성 부신기능저하증

장기간 스테로이드 치료를 받는
 일반 인구의 1%가 해당
 70세 이상 인구에서는 2.5%가 해당

원인 약제
 스테로이드 (가장 흔함)
 항진균제: ketoconazole > itraconazole, fluconazole
 수면제: etomidate
 항암제: sunitinib
스테로이드제제 치료전 고려사항

얼마나 사용할 것인가?
 1~3주: 안전
 장기간 사용할 것이라면 alternative day therapy 고려

약제의 형태
 Topical > Systemic

전신 스테로이드 제제일 경우
mineralocorticoid activity가 있으면 안된다.
사용전 동반질관의 고려 사항






당뇨병
골다공증
소화성 궤양: gastritis, esophagitis
결핵 또는 만성 감염증
고혈압, 심혈관질환
심리학적 문제점
스테로이드에 의한 부신기능 억제

기전
 Negative feedback control of the HPA axis

관여하는 요인
 기간: 3 주 이내 사용에서는 대부분 안전
 용량: PDL 50 mg 이면 HPA axis 억제

고용량 스테로이드를 단기간 자주 사용하는 경우
 안전하지 않다.

저용량 스테로이드를 장기간 사용하는 경우
 HPA axis 억제는 사례별로 다름.
부신억제에서 회복되는 기간?
일반적으로 6~9 개월
 돌아오는 순서

 CRH 분비: 수주내 회복
 ACTH 분비
 Cortisol 분비
부신기능저하의 증상

일차성 부신기능저하증 (Addison’s syndrome)
과 유사
 Anorexia
 Nausea
 Weight loss
 Arthralgia
 Lethargy
 Skin desquamation
 Postural dizziness
부신 기능을 평가하기 위한 방법
CRH stimulation test
 Insulin induced hypoglycemic stimulation test
 Rapid ACTH stimulation test

 1 μg ACTH (corticotropin) IV
 정상반응
○ 주사 30 분 뒤 혈청 코르티솔 25 μg/dL 이상 증가.
○ 기저치로부터 9 μg/dL 이상 상승
 250 μg ACTH (corticotropin) IV
스테로이드 중지시 요령
수주에 걸쳐 생리적 요구량에 해당되는
용량으로 감량 (PDL 7.5 mg/day)
2-4 주 간격으로 환자의 상태를
보면서 1mg 씩 감량 (PDL)
Hydrocortisone 20mg/day로 교체
10mg/day가 될때까지 매주
2.5mg/day씩 감량
2-3 개월 뒤 HPAaxis 평가를 위한
신속 ACTH 자극검사
Normal
스테로이드 완전 중지
Duration of Glucocorticoid Treatment
Dose
(mg PDL
/day)
≥ 7.5 mg
≤ 3 wks
Can
stop
Reduce rapidly
(2.5 mg every 3-4 d
ays)
Then
5-7.5 mg
Can
stop
Reduce by 1 mg ev
ery 2-4 wks
< 5 mg
Can
stop
>3
wks
or
Convert 5 mg pred to HC
20 mg and
Then
↓ by 2.5 mg/wk to 10 mg
for 2-3 mo
Reduce by 1 mg ev
ery 2-4 wks
Rapid ACTH test
 If pass, withdraw
 If fail, continue
Alternative-day steroid therapy

How to minimize the Cushingoid effects
 Single dose of intermediate-acting steroid in
the morning, every other day

3 Consideration
 Transition schedules that allow the patient to
adjust gradually.
 Supplementary NSAID: minimize the patient’s Sx
 Many Sx may occur during the off day
○ May represent relative adrenal insufficiency
Withdrawal of steroid following long-term use
The dosage is gradually reduced
 Finally discontinued after a replacement
dosage has been reached (5 to 7.5 mg PDL)
 Check the pituitary-adrenal axis before
discontinuing steroid

 Especially, long term use
생리적 스테로이드 보충
Drug-Induced Hyperglycemia
Textbook of Diabetes 4th Edition
GLUCOCORTICOIDS:
Insulin antagonistic hormones

Liver
 promote gluconeogenesis

Muscle & adipose tissue
 antagonize uptake and utilization of insulin

Pancreas
 inhibitory effect on insulin release and stimulation of
glucagon secretion
Typical Pattern of Steroid Diabetes

Elevated glucose after meals

Decrease to normal glucose overnight
Hyperglycemia Management
Decision Making
Short term drug use?
 Long term drug use?
 Is this new hyperglycemia/diabetes?
 Do they have pre existing diabetes?

 What is their current control?
 What is their current therapy?
○ Orals- non sulfonylurea vs. sulfonylurea
○ Insulin- premix vs. basal/bolus insulin
Treatment Algorithm for Steroid-induced
Hyperglycemia
<216 mg/dL
216-306mg/dL
>306mg/dL
<144 mg/dL
Textbook of Diabetes 4th Edition
Oral Diabetes Medications



In general minimal benefits
Long acting agents like glyburide and glimiperide will
have minimal effect on post prandial hyperglycemia
and increase risk of fasting hypoglycemia.
The use of rapid-acting drugs such as repaglinide,
nateglinide, and acarbose all make physiological
sense but in clinical practice often are ineffective.
INSULIN
Most effective
 Peak action of the insulin needs to correspond
to the post absorptive state - the primary
affect of steroids is on glucose disposal
following the meal.

 Rapid acting analog insulin before the meals

Cautious use of long acting insulin
 Ratio prandial:basal 70:30
요약





스테로이드 치료 전 당뇨병, 위궤양, 감염증 등
의 동반질환 유무 점검
스테로이드 제제의 종류, 용량, 사용기간을 고려
해야 한다.
사용 기간은 1~3 주 이내의 경우 안전하다.
선택한 제제가 염류코르티코이드 활성도가 높
지 않아야 한다.
장기간 사용 또는 부신기능저하 증세가 있을 경
우 신속 ACTH 자극 검사가 필요하다.