7.31b farmakologi hormon-2

8/13/2019 7.31b Farmakologi Hormon-2

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1. Prolactin

2. TSH

3. FSH & LH

4. Estrogen

5. Progesterone

6. Androgens (Total testosterone, DHEAS)


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It is secreted by:

Mammotropic cells of the anteriorpituitary.

It is necessary forinitiation &maintenance of lactation

Reference values:

Premenopuasal:


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Clinical significance:-Hyposecretion:rare. Pituitary necrosis

or infarction-Hypersecretion:

Idiopathic, Physiologic, pharmacologic,pathologic


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Causes of Hyperprolactinaemia

Physiologic Pharmacologic Pathologic

Pregnancy Metclorpromide Hypothalamic disorders

Lactation Methyldopa PRL secreting tumor

Excerise Reserpine Hpothyroidism

Eating Cimetidine Addsions disease

Stress Estrogen Chest wall disease

Morphine Chronic renal failure

Alcholoic cirrhosis


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Relation between The level & the cause:> 100 ng/ml:

60% pituitary tumor.

> 300 ng/ml:

100% pituitary tumor

Modest elevation can be associated withpituitary tumor


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Clinical conditions associate withhyperprolactinaemia

1. Galactorrhea

2. Oligomenorhea

3. Hirsutism

4. Anovulation

5. Corpus luteum deficiency

6. Infertility


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Hyperprolactinaemia withoutgalactorrhea:66%

1. Inadequate detection

2. Hypoestrogenic state3. Inadequate estrogenic or

progetational priming of the breast4. High PRL does interact with thebreast receptors


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Diagnostic evaluation

History & Examination: Exclude: Recent pregnancy, breast stimulation

Drugs, Breast or chest lesion

Prolactin

>20 ng/ml


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It is secreted bythe thyrotrophic cellsof the anterior pituitary .

It stimulatesthe growth of the thyroidfollicular cells & every step in thyroidhormone synthesis


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Reference values:

Conventional immunoassay:useful indiagnosis of hypothyroidism.can not ddbetween normal values & subnormalvalues in hyperthyroidism

Sensitive Immunoassay:can dd

Subclinical hypothyroidism:IncreaseTSH & normal free T4


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Sensitive TSH

High Normal Low

Free T4 Normal thyroid Free T4

Low Normal Normal High

Hypothyroidism Free T3

Subclinical hypothyroidism Normal High

Subclinical hyperthyroidism Hyperthyroidism


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They are secreted bythe anterior pituitary

The alpha subunitis identical for allglycoprotein hormones (TSH, HCG, LH &FSH), but the beta subunit differs

The peak ofFSH is coincident with the peakof LH, but it is of lesser magnitude & brieferduration

Following the midcycle surge of LH & FSH,there is drop in both


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Normal values:

FSH LH

Adult 5-10 mIU/ml 5-20 mIU/ml

Mid cycle peak 2 times the basal level 3 times the basal level


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Clinical uses:FSH LH

1. Hypogonadotrophic < 5 mIU/ml < 5 IU/ml

state e.g. prepubertal

& pituitary disorders

2. Hypergonadotropic > 40 mIU/ml >40 mIU/ml

state e.g.postmenopuse

Ovarian failure

3. PCOS normal or decreased high

Follicular phase ratio 1 2


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4. Testing for ovarian function:

a. Day 3 FSH

< 10 IU/L = normal

< 15 IU/L : conception rate is twicewhen FSH 15-25 IU/L

> 25 IU/L ( or age >44) isindependently associated with near

zero chance of pregnancy


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b.Clomiphene citrate challenge test (CCCT)

CC 100 mg /day from D5-9

Check FSH on D3 & 10

Sum of FSH >26 IU/L = poor responder

LH can be used for assessment of ovarian

reserve but FSH is better. FSH rises sooner& more dramatically than LH.


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5. Detection of ovulation

LH surge:

Follicular rupture occurs 36 h after theonset of serum LH surge & 12 H after LH

peak.A positive urine result is often found only 12h after the onset of serum LH. (around thepoint of LH peak).

So ovulation is expected to occur 24 h after

the urine LH surge


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6. Diagnosis of the cause ofprecocious puberty:

(Breast development


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X ray of the lower ends of radius & ulna:bone age

a. Retarded:hypothyroidism

b. Normal:Partial

c. Advanced:

FSH:

2 mIU/ml)---- true: CT or MRI----Normal (idiopathic)

Abnormal(CNS lesion)


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7. Diagnosis of the cause ofamenorrheaPrimary Amenorrhea:

absence of menstruation by the age of16 yr regardless of SSC or by the ageof 14 yr in absence of SSC

Secondary Amenorrhea:Cessation of menstruation > 6 months


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1. Pregnancy test.2. TSH &PRL.

3. Progestin challenge test: (MPA5mgX2X5d)positive:Anovulation


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-ve:E + P :-ve:outflow or uterine failure HSG,

hysteroscopy, IVP & laparoscopy.+ve:Ovarian failureor pituitary-hypothalamic dysfunction.


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3. FSH:

high: Ovarian failure.If 1ry: Karyotyping.If 2ndry: premature menopauseLow or Normal: CT of Pituitary-hypothalamic region.

. Abnormal: pituitary disease. Normal: hypothalamic dysfunction.


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More than 30 estrogens have beenidentified, but only 3 estrogensare

used in clinical practice: estrone (E1),estradiol (E2), estriol (E3).

In contrast to E2 which is secretedalmost entirely by the ovary, most E1 isderived from peripheral conversion ofandrostenedione & from E2

metabolism.


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E2 is the most abundantE inpremenopausal females, while E1 is the

E in highest concentration inpostmenopausal females.

E2 is the most potentE

E1, E2 & E3 are bound toSHBG.

E2 & not total E is used for clinicalpurposes.


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Normal values of E2 (pg/ml)

Follicular phase: 25-27

Midcycle peak: 200-600

Luteal phase: 100-300

Postmenopausal: 5-25

E2 i d i th 2 d h lf f th


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E2 rises during the 2nd half of thefollicular phase & reach a peak 24 h

before LH surge & 36 h beforeovulation.

Following LH surge E2 drops topreovulatory levels, but then risesslightly to 100-300 pg/ml during luteal

phase

Cli i l li i


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Clinical applications:

1. E increases in E secretingtumorse.g. granulosa theca cell

tumors

2. To classify hypogonadism: Eis usually interpreted with

gonadotropin measurements 3 T t f i


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3. Test for ovarian reserve:

Low D3 E2 (


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4. An indication of down regulationin the long

protocol for superovulation in ART. E2: < 50

pg/ml5. Monitoring Superovulation in ART:

The goal is an E2 level of 200 pg/ml per large(>14 mm) follicle

The risk of OHSS is significant if E2 is >4000

pg/ml ( Sperof,2002)

The number of follicles & the type of patient

should be considered.

6 M it i f i d ti f


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6. Monitoring of induction of

ovulation with HMG(Sperof,2002).

E2 1000-1500 pg/ml is optimal

1500-2000 pg/ml: increase risk ofOHSS

>2000 pg/ml: high risk of OHSS,

consider cycle cancellation


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I h


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In the serum:

18% is bound to cortisol

binding globulin

79% is bound to albumin

3% is free Normal values (ng/ml):


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Normal values (ng/ml):

P level is low prior to the mid cycle gonadotrophin surge.

Shortly after that, P begin to rise rapidly reaching peaklevels during the middle of the luteal phase (8 days

after LH peak).

Thereafter, a progressive fall occurs with barelydetectable P levels reached prior to menses.

Follicular phase:


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Clinical applications

1. Diagnosis of ovulation:

in cases of infertility & DUB

a midluteal phase serum level of 5 ng/ml2. Diagnosis of corpus luteal dysfunction:

Midluteal phase level of 10 ng/ml.

Sum of 3 progesterone levels from D11-4

before menses: 15 ng/ml


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Androgen production


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Androgen productionAndrostenedione

Testosterone

Adrenal DHEA Ovary

DHEAS

50% 50%50%

25% 25%

90% 10%

100%


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Androgen in the bloodMale Normal female Hirsute female

Free 3% 1% 2%

Albumin 19% 19% 19%SHBG 78% 80% 79%

N l l ( /dl)


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Normal values (ng/dl):Premenopause Postmenopause

Testosterone 20-80 15-70

Androstenedione 60-300 30-150

Free testosterone


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Free testosterone

Good correlation with total production rate

(= secretion rate + peripheral conversionrate) which correlate well with degree of

virilizationNormal level: 1.5-11.4 pg/ml

Not done routinely in presence of hirsutism

Free androgen index (FAI)=TX 100 / SHBGif > 4.5 : PCOS

D h d i d t l h t


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Dehydoepiandrosterone sulphate

(DHEAS)

The principal contribution of 17

ketosteroids (KS) is from DHES.It correlates with urinary 17 KS. It

is more reliable indicator of adrenalandrogen than 24 h 17 KS.

Cli i l li ti


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Clinical application

In PCOS: DHEAS > 2ug/ml

CC + Corticosteroid (ACOG,2002)

In hirsutism: DHEAS: >2 ug/ml

COCs + CorticosteroidsDHEAS:not essential (Sperof,2002)

7.31b farmakologi hormon-2

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