Hormone Action & Endocrine Dynamic Test
Sung-Woon Kim
Endocrinology & Metabolism,
College of Medicine
T
YPE
N
AME
Site of R
ECEPTOR
P
EPTIDE
I
NSULIN
, G
LUCAGON
, ACTH…
M
EMBRANE
S
TEROID
E
2
, P
ROGESTERONE,
T…
N
UCLEUS
V
ITAMIN
D
A
MINE
T
HYROID
H
ORMONE
M
EMBRANE
TYPES OF HORMONES
1 Gene 1 Enzyme theory
DNA
RNA
Protein;Polypeptide
T
RANSCRIPTIONT
RANSLATIONHormone Secretion
Nucleus
Cytoplasm
호르몬 생성의 유전자적 조절
1. Transcription
5. Protein assembly
4. Translation
3. Transport
2. RNA splicing
+ 1
Transcription initiation5’
ATGGGAAAA … Met Gly Translation initiation …. Lys3’
TATA BOX SPECIFIER -25 ~ -35
CAAT BOX QUANTIFIER -70 ~ -80
Direction of Transcription
“upstream”
“downstream”
A single base mutation in the 5’ untranslated region of the factor IX gene.
This A to G mutation affects the level of factor IX gene expression, leading to hemophilia
Human GH
191개의 아미노산
GHRH
SMS
+
-IGF-I
(insulin-like growth factor-I)
+
IL-6?
- (?!)
GH [m.w. = 22,000]
N-terminal C-terminal 70 44 [41, 29] 14, 28 191, 192 1998.5 FAMILYMEDICINEAbreviation
Function
Site of Synthesis
mRNA
Transfer genetic information
Nucleoplasm
from nucleus to cytoplasm
tRNA
Transfer aminoacids to
Nucleoplasm
mRNA ribosome complex
rRNA
Structural framework for
Nucleus
ribosomes
snRNA
Structural and regulatory
Nucleoplasm
role in chromatin
scRNA
Selection of proteins for
Cytosol and ER
export
GLUCOSE ACETYLCHOLINE ATP cAMP
PLC
AC
Gs
GK ATP Ca++ INFLUX IP3 DAG PKC Ca++INSULIN SECRETION
PKA ? GLUCAGON GLUT 298 BLOCK LECTURE, SOPHOMORE
Action of TRH on the thyrotroph
(TSH producing cell in pituitary).
98 BLOCK LECTURE, SOPHOMORE
I
I
I
I
H
C
H
2
C
O
NH
2
COONa
TETRAIODOTHYRONINE
T
3
[TRIIODOTHYRONINE]
98 BLOCK LECTURE, SOPHOMORE
Tumour
Sequence of hormone loss as the tumour grows
LH FSH TSH ACTH PRL GH
Triple Stimulation Test
0
5
10
15
20
25
30
35
40
-30
0
30
60
90 120
Insulin stimulation [GH, ACTH, Cort]
TRH stimulation [TSH, PRL]
LHRH stimulation [LH, FSH] other hypothalamic stimulation
GHRH stimulation [GH]
CRH stimulation [ACTH, cort]
quadraple stimulation test
hyper-response
normal
hypo-response
delayed response
Interpretation of Hormone levels
TRO P HIC HORMO N E LEVELS Low normal h ighLow Normal High
TARGET HORMONE LEVELS
primary failure of Target Tissues ectopy or target hormone resistance Normal Pituitary Failure primary target organ hyperfunction
Insulin stimulation
dose 0.1 unit / kg in Acromegaly 0.15 u / kg in Sheehan syndrome, 0.05 u / kg i.v.closed watching for severe hypoglycemia
0
20
40
60
80
100
120
140
160
-30 0
30 60 90 120
Glucose (mg/dl)
min
insulin1. GH
30 - 60 min 에 10 ng 이상의 peak 만약 peak 가 7-10 ng 이면
partial GH deficiency
2. ACTH
plasma (EDTA tube) 로 sampling 얼음에 채워서 degradation 방지 대개 30분에 기저치의 2배이상 자극
3. Cortisol
30분에 15 ug / dl 이상 자극되면 정상
Insulin stimulation test [ GH ]
0 5 10 15 20 25 30 -30 0 30 60 90 120 17세 남자 short stature, BA=14세 -30 0 30 60 90 120 sugar - 85 43 65 68 71 GH (ng/ml) 1.3 0.01 1.5 7.3 4.3 1.2 1.0 이 환자의 진단은?partial GH deficiency due to craniopharyngioma
GH (ng/ml)
min
26세 남자 protruding jaws for 1 yr.
-30 0 30 60 90 120
sugar - 109 71 74 88 95
GH (ng/ml) 51.8 49.2 48.2 40.4 38.2 36.4
이 환자의 진단은?
GH producing pituitary adenoma ( acromegaly ) 0 10 20 30 40 50 -30 0 30 60 90 120
GH (ng/ml)
min
insulin26세 남자 protruding jaws for 1 yr. -30 0 30 60 90 120 sugar 109 71 74 88 95 GH (ng/ml) 51.8 49.2 48.2 40.4 38.2 36.4 paradoxical response of GH to TRH -30 0 30 60 90 120 GH (ng/ml) 31.2 26.2 34.6 33.1 31.4 36.6 TSH(uU/ml) - 0.34 6.42 4.79 3.18 2.14 T3 : 135 ng/dl T4 : 8.6 ug/dl 0 5 10 15 20 25 30 35 40 45 50 55 -30 0 30 60 90 120
min
GH (ng/ml)
TRH 200 ug insulinGH and TSH responses
Insulin stimulation [ACTH]
17세 남자 Nausea, Vomiting for 1 yr.
-30
0
30
60
90
120
sugar
-
88
33
65
76
72
ACTH 59.3
35.4
23.8
26.4
27.6
28.7
Cortisol 66.6
43.2
17.5
40.3
28.6
30.1
이 환자의 진단은?
Cushing뭩 disease
( pituitary tumor, TSA was done
with both adrenal hyperplasia)
0 40 80 120 160 200 240 280 -30 0 30 60 90 120
min
ACTH (pg/ml)
insulin47세 여자 Moon face
Weight gain (11 kg/ 3 mo.) for 1 yr. -30 0 30 60 90 120 sugar - 165 152 123 147 151 ACTH 5.8 10.1 19.4 12.6 15.8 20.2 Cortisol 42.6 34.2 38.6 40.8 39.7 35.5 이 환자의 진단은? Cushing뭩 syndrome
( adrenal single adenoma, 3x4 cm, right) 0 40 80 120 160 200 240 280 -30 0 30 60 90 120
ACTH (pg/ml)
Insulin stimulation [ACTH]
정상 기저치 1.0 - 5.0 uU / ml 기저치가 6 uU / ml 이상 hypothyroidism을 의심 Primary hyperthyroidism에서는 대개 TSH 0.1 uU / ml 이하 Hypothalamic hypothyroidism delayed response 60분 이후에 peak
0
5
10
15
20
25
30
35
40
-30
0
30
60
90 120
Normal Primary Hypothyroidism Primary hyperthyroidism TRH 200ugTRH stimulation test [ TSH ]
TRH stimulation test [ TSH ]
33세 여자 weight loss (9 kg/1 mo),heat intolerence for 2 mo.
T3 : 352 ng/dl T4 : 13.2 ug/dl
0 30 60 90 120
TSH(uU/ml) 0.1 0.1 0.1 0.3 0.2
이 환자의 진단은?
Primary hyperthyroidism with Graves’ disease
TSH (uU/ml)
min
0 5 10 15 20 25 30 35 40 45 -30 0 30 60 90 120 TRH 200ug45세 여자 generalized weakness for 5 yrs weight gain (4 kg / 3 months)
T3 : 65 ng / dl T4 : 2.6 ug / dL
0 30 60 90 120
TSH 4.3 40.5 37.5 30.3 20.2
이 환자의 진단은?
primary hypothyroidism due to thyroiditis
TRH stimulation test [ TSH ]
min
TSH (uU/ml)
0 5 10 15 20 25 30 35 40 45 -30 0 30 60 90 120 TRH 200ug23세 여자 Malaise for 3 mos. T3 : 134 ng / dl T4 : 7.4 ug / dl 0 30 60 90 120 TSH 1.8 35.6 27.9 20.4 15.6 이 환자의 진단은? subclinical hypothyroidism 0 5 10 15 20 25 30 35 40 45 -30 0 30 60 90 120
TRH stimulation test [ TSH ]
min
TSH (uU/ml)
TRH 200ug0 10 20 30 40 50 60 70 80 90 -30 0 30 60 90 120
21세 남자
Anosmia, Lt for 1 yr.
0
30
60
90
120
LH (uU/ml) 5.2
6.3
10.2
9.6
7.7
FSH (uU/ml)
2.1
3.4
4.1
4.2
3.2
After 5 days of GnRH administration
0
30
60
90
120
LH (uU/ml)
8.6
40.5
33.1
20.9
13.3
이 환자의 진단은?
Hypothalamic GnRH deficiency
due to Kalman’s syndrome
due to Kalman’s syndrome
min
LH (uU/ml)
LHRH
0 10 20 30 40 50 60 70 80 90 -30 0 30 60 90 120
67세 여자 Low back pain with osteoporosis
for 10 yrs. 0 30 60 90 120 LH (uU/ml) 65.3 87.4 88.6 79.6 70.3 FSH (uU/ml) >145 >145 >145 >145 >145 E2 : 2.3 pg/ml 이 환자의 진단은?
postmenopausal ovarian failure
LH (uU/ml)
LHRH
