경희대학교 의과대학·의학전문대학원

전체 글

(1)

Hormone Action & Endocrine Dynamic Test

Sung-Woon Kim

Endocrinology & Metabolism,

College of Medicine

(2)
(3)

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

(4)



1 Gene 1 Enzyme theory

DNA

RNA

Protein;Polypeptide

T

RANSCRIPTION

T

RANSLATION

Hormone Secretion

Nucleus

Cytoplasm

호르몬 생성의 유전자적 조절

(5)

1. Transcription

5. Protein assembly

4. Translation

3. Transport

2. RNA splicing

(6)

+ 1

Transcription initiation

5’

ATGGGAAAA … Met Gly Translation initiation …. Lys

3’

TATA BOX SPECIFIER -25 ~ -35

CAAT BOX QUANTIFIER -70 ~ -80

(7)

Direction of Transcription

“upstream”

“downstream”

(8)

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

(9)

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 FAMILYMEDICINE

(10)

Abreviation

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

(11)
(12)

GLUCOSE ACETYLCHOLINE ATP cAMP

PLC

AC

Gs

GK ATP Ca++ INFLUX IP3 DAG PKC Ca++

INSULIN SECRETION

PKA ? GLUCAGON GLUT 2

(13)
(14)

98 BLOCK LECTURE, SOPHOMORE

(15)

Action of TRH on the thyrotroph

(TSH producing cell in pituitary).

98 BLOCK LECTURE, SOPHOMORE

(16)

I

I

I

I

H

C

H

2

C

O

NH

2

COONa

TETRAIODOTHYRONINE

T

3

[TRIIODOTHYRONINE]

98 BLOCK LECTURE, SOPHOMORE

(17)

Tumour

Sequence of hormone loss as the tumour grows

LH FSH TSH ACTH PRL GH

(18)

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

(19)

Interpretation of Hormone levels

TRO P HIC HORMO N E LEVELS Low normal h igh

Low Normal High

TARGET HORMONE LEVELS

primary failure of Target Tissues ectopy or target hormone resistance Normal Pituitary Failure primary target organ hyperfunction

(20)

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

insulin

(21)

1. 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

(22)

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

(23)

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

insulin

(24)

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 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 insulin

GH and TSH responses

(25)

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)

insulin

(26)

47세 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]

(27)

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 200ug

TRH stimulation test [ TSH ]

(28)

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 200ug

(29)

45세 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 200ug

(30)

23세 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 200ug

(31)

0 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

(32)

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

(33)

Hormone

Peak time

normal response

GH

30 - 60 min

> 10 ng/mL

ACTH

30 - 60 min

> 2 times than basal

TSH

15 - 30 min

3 - 5 times than basal

> 15 uU /ml

PRL

15 - 30 min

2 - 8 times than basal

LH

15 - 20 min

4 - 6 times than basal

FSH

120 min

> 2times than basal

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