1.

Prolactin
2. TSH

3. FSH & LH
4. Estrogen

5. Progesterone
6. Androgens (Total testosterone, DHEAS)

It is secreted by: Mammotropic cells of the anterior pituitary. It is necessary for initiation & maintenance of lactation Reference values:

Premenopuasal: <20 ng/ml

Postmenopausal: <12 ng/ml

Conditions for detection of PRL Late morning, fasting, After 60 min rest, Not in late follicular phase, 2nd blood sample if the first is raised

Clinical significance:

-Hyposecretion: rare. Pituitary necrosis or infarction -Hypersecretion:

Idiopathic, Physiologic, pharmacologic, pathologic

Causes of Hyperprolactinaemia Physiologic Pregnancy Lactation Excerise Pharmacologic Metclorpromide Methyldopa Reserpine Pathologic Hypothalamic disorders PRL secreting tumor Hpothyroidism

Eating
Stress

Cimetidine
Estrogen Morphine

Addsions disease
Chest wall disease Chronic renal failure Alcholoic cirrhosis

Relation between The level & the cause: > 100 ng/ml: 60% pituitary tumor. > 300 ng/ml: 100% pituitary tumor Modest elevation can be associated with pituitary tumor

Clinical conditions associate with hyperprolactinaemia

1. Galactorrhea 2. Oligomenorhea 3. Hirsutism 4. Anovulation

5. Corpus luteum deficiency

6. Infertility

Hyperprolactinaemia without galactorrhea: 66% 1. Inadequate detection 2. Hypoestrogenic state

3. Inadequate estrogenic or progetational priming of the breast 4. High PRL does interact with the breast receptors

Diagnostic evaluation
History & Examination: Exclude: Recent pregnancy, breast stimulation Drugs, Breast or chest lesion <20 ng/ml

Prolactin
>20 ng/ml TSH

Normal

High (hypothyroidism)

MRI or CT( Normal or hyperplasia, Microadenoma or Macroadenoma)

It is secreted by the thyrotrophic cells of the anterior pituitary . It stimulates the growth of the thyroid follicular cells & every step in thyroid hormone synthesis

Reference values:
Conventional immunoassay: useful in diagnosis of hypothyroidism.can not dd between normal values & subnormal values in hyperthyroidism Sensitive Immunoassay: can dd

Subclinical hypothyroidism: Increase TSH & normal free T4

Clinical conditions associated with thyroid dysfunction: 1. Oligomenorhea 2. Amenorrhea 3. Menorrhagia 4. Anovulation

5. Inadequate corpus luteum

4. Subfertility

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

They are secreted by the anterior pituitary The alpha subunit is identical for all glycoprotein hormones (TSH, HCG, LH & FSH), but the beta subunit differs The peak of FSH is coincident with the peak of LH, but it is of lesser magnitude & briefer duration

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

Normal values:

FSH
Adult Mid cycle peak 5-10 mIU/ml 2 times the basal level

LH
5-20 mIU/ml 3 times the basal level

Clinical uses:
FSH 1. Hypogonadotrophic < 5 mIU/ml LH < 5 IU/ml

state e.g. prepubertal

& pituitary disorders

2. Hypergonadotropic
state e.g.postmenopuse Ovarian failure 3. PCOS Follicular phase ratio

> 40 mIU/ml

>40 mIU/ml

normal or decreased 1

high 2

4. Testing for ovarian function:

a. Day 3 FSH

< 10 IU/L = normal

< 15 IU/L : conception rate is twice when FSH 15-25 IU/L > 25 IU/L ( or age >44) is independently associated with near zero chance of pregnancy

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.

5. Detection of ovulation

LH surge:
Follicular rupture occurs 36 h after the onset of serum LH surge & 12 H after LH peak.

A positive urine result is often found only 12 h after the onset of serum LH. (around the point of LH peak).
So ovulation is expected to occur 24 h after the urine LH surge

LH surge in urine:
Quick, sensitive, relatively inexpensive,

pinpoint the day of ovulation &

has reduced the uncertainty in interpretation of progesterone levels by better-identifying the time of peak progestrone secretion at which to obtain serum

6. Diagnosis of the cause of precocious puberty: (Breast development <8 y or

menstruation <9 y.)

X ray of the lower ends of radius & ulna:bone age a. Retarded: hypothyroidism b. Normal: Partial c. Advanced: FSH:

<2 mIU/ml) ---- pseudo

>2 mIU/ml) ---- true: CT or MRI----Normal (idiopathic) Abnormal (CNS lesion)

7. Diagnosis of the cause of amenorrhea Primary Amenorrhea: absence of menstruation by the age of 16 yr regardless of SSC or by the age of 14 yr in absence of SSC Secondary Amenorrhea: Cessation of menstruation > 6 months

1. Pregnancy test. 2. TSH &PRL. 3. Progestin challenge test: (MPA 5mgX2X5d) positive: Anovulation

-ve: E + P : -ve: outflow or uterine failure HSG, hysteroscopy, IVP & laparoscopy. +ve: Ovarian failure or pituitaryhypothalamic dysfunction.

3. FSH: high: Ovarian failure. If 1ry: Karyotyping. If 2ndry: premature menopause Low or Normal: CT of Pituitaryhypothalamic region. . Abnormal: pituitary disease . Normal: hypothalamic dysfunction.

More than 30 estrogens have been identified, but only 3 estrogens are used in clinical practice: estrone (E1), estradiol (E2), estriol (E3). In contrast to E2 which is secreted almost entirely by the ovary, most E1 is derived from peripheral conversion of androstenedione & from E2 metabolism.

E2 is the most abundant E in premenopausal females, while E1 is the E in highest concentration in postmenopausal females. E2 is the most potent E

E1, E2 & E3 are bound to SHBG.

E2 & not total E is used for clinical purposes.

Normal values of E2 (pg/ml)

Follicular phase: 25-27 Midcycle peak: 200-600 Luteal phase: 100-300 Postmenopausal: 5-25

E2 rises during the 2nd half of the follicular phase & reach a peak 24 h before LH surge & 36 h before ovulation. Following LH surge E2 drops to preovulatory levels, but then rises slightly to 100-300 pg/ml during luteal phase

Clinical applications:
1. E increases in E secreting tumors e.g. granulosa theca cell tumors 2. To classify hypogonadism: E is usually interpreted with gonadotropin measurements

3. Test for ovarian reserve: Low D3 E2 (<75 pg/ml) combined with normal FSH: good ovarian reserve

Evaluation of both E2 & FSH is better predictor of ovarian reserve than using either measurement alone.

4. An indication of down regulation in the long protocol for superovulation in ART. E2: < 50 pg/ml

5. 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. Monitoring of induction of ovulation with HMG (Sperof,2002). E2 1000-1500 pg/ml is optimal 1500-2000 pg/ml: increase risk of OHSS >2000 pg/ml: high risk of OHSS, consider cycle cancellation

In the serum:
18% is bound to cortisol binding globulin

79% is bound to albumin

3% is free

Normal values (ng/ml):

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

Shortly after that, P begin to rise rapidly reaching peak levels during the middle of the luteal phase (8 days after LH peak). Thereafter, a progressive fall occurs with barely detectable P levels reached prior to menses. Follicular phase: <1

Luteal phase: 5-20

Post menopause: <1

Clinical applications

1. Diagnosis of ovulation:
in cases of infertility & DUB a midluteal phase serum level of 5 ng/ml

2. 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

Androgen production
Androstenedione
50% 25% 50%

Testosterone
25%

50%

Adrenal
90%
100%

DHEA
10%

Ovary

DHEAS

Androgen in the blood

Male Normal female Hirsute female

Free 3% 1% Albumin 19% 19% SHBG 78% 80%

2% 19% 79%

Normal values (ng/dl):

Premenopause Testosterone Androstenedione 20-80 60-300 Postmenopause 15-70 30-150

Free testosterone Good correlation with total production rate (= secretion rate + peripheral conversion rate) which correlate well with degree of virilization Normal level: 1.5-11.4 pg/ml Not done routinely in presence of hirsutism Free androgen index (FAI)= TX 100 / SHBG if > 4.5 : PCOS

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 adrenal androgen than 24 h 17 KS.

Clinical application In PCOS: DHEAS > 2ug/ml

CC + Corticosteroid (ACOG,2002) In hirsutism: DHEAS: >2 ug/ml

COCs + Corticosteroids
DHEAS: not essential (Sperof,2002)