Download - 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)