Hormones

Question 1

How many different forms of hCGs can be present in a blood sample?

Answer 1

-

Question 2

What is the (1.)source of cell synthesis, (2.)mode of action, and (3.) site of action for hCG?

Answer 2

1. Syncytiotrophoblast
2. Endocrine
3. LH/hCG receptor

Question 3

What is the (1.)source of cell synthesis, (2.)mode of action, and (3.) site of action for sulfated hCG?

Answer 3

1. Gonadotrope
2. Endocrine
3. LH/hCG receptor

Question 4

What is the (1.)source of cell synthesis, (2.)mode of action, and (3.) site of action for sulfated hCG?

Answer 4

1. Cytotrophoblast
2. Autocrine
3. TGF beta antagonism

Question 5

What is the (1.)source of cell synthesis, (2.)mode of action, and (3.) site of action for hCG beta?

Answer 5

1. Advanced malignancies
2. Autocrine
3. TGF beta antagonism

Question 6

What is the (1.)source of cell synthesis, (2.)mode of action, and (3.) site of action for hyperglycosylated hCG beta?

Answer 6

1. Advanced malignancies
2. Autocrine
3. TGF beta antagonism

Question 7

What is the function of hCG (intact)?

Answer 7

Functions to advance uterine angiogenesis and promote progesterone production by corpus luteal cells

Question 8

Where is hCG produced?

Answer 8

Produced by syncytiotrophoblast cells in pregnancy and by hydatidiform moles

Question 9

What are the alpha subunits in hCG similar to?

Answer 9

Alpha subunits are similar to hCG-H, pituitary hCG, LH, FSH, TSH

Question 10

What are the beta subunits of hCG similar to? What are they used for?

Answer 10

Beta subunits similar to LH but differentiates hCG, hCG-H and pituitary hCG from other molecules.

Question 11

What is Hyperglycosylated hCG (hCG-H)?

Answer 11

1. An independent molecule to regular hCG
2. A structural variant of regular hCG
3. It is an autocrine or cytokine that promotes growth, invasion and malignancy. It is not a hormone.

Question 12

Where is Hyperglycosylated hCG (hCG-H) produced?

Answer 12

Produced by cytotrophoblast cells of the placenta

Question 13

What is the function of hyperglycosylated hCG?

Answer 13

1. It is an accurate marker of invasive mole and invasive choriocarcinoma
2. Very useful in the diagnosis and management of gestational trophoblastic disease

Question 14

What is the free beta subunit of hCG?

Answer 14

1. Originates from beta subunit of hCG with triantennary N-linked and O-linked hexosamines.
2. It is autocrine or cytokine

Question 15

Where is the free beta subunit of hCG produced?

Answer 15

1. Produced in most gynecological malignancies, moles, non-trophoblastic malignancies.
2. Produced by 68% of ovarian, 51% endometrial, 46% cervical malignancies.

Question 16

What is the function of the free beta subunit of hCG?

Answer 16

It blocks apoptosis in cancer cells and promotes the growth of the malignancy thereby leading to poor outcomes.

Question 17

How are hCG (intact), hCG-H, and free beta subunits broken down?

Answer 17

Protease degradation (tumor macrophages)

Question 18

What is hCG (intact) broken down into?

Answer 18

1. Nicked
 hCG (Intact)
2a. Nicked
free β subunit
2b. Free alpha subunit
3. Beta-subunit core fragments

Question 19

Why is testing for alpha subunits not a specific way to check for pregnancy?

Answer 19

Alpha subunits are similar to hCG-H, pituitary hCG, LH, FSH, TSH

Question 20

What is the most specific test for pregnancy?

Answer 20

Beta subunit hCG but false positives are still possible due to variant hCGs

Question 21

How is the pituitary hCG similar/different from regular hCG?

Answer 21

Has the same amino acid structure as regular hCG but is a sulfated variant of hCG (instead of sialylated oligosaccharide) produced at low levels during the menstrual cycle.

Question 22

What is the function of pituitary hCG?

Answer 22

Functions similarly to LH

Question 23

What is the FDA approved use of hCG tests?

Answer 23

FDA approved assay for pregnancy diagnosis

Question 24

How is hCG relevant to ectopic pregnancy?

Answer 24

Workup of suspected ectopic pregnancy, serial hCG testing is used (along TVU: transvaginal ultrasound)

Question 25

What are the uses of hCG tests?

Answer 25

1. Pregnancy test 2. Ectopic pregnancy 3. tumor marker 4. Maternal serum screening for fetal aneuploidies

Question 26

What is maternal serum screening for fetal aneuploidies?

Answer 26

1. Maternal serum screening for fetal aneuploidies (e.g., fetal trisomy 21-Down’s syndrome) A. Quad test -Alpha fetoprotein, estriol, inhibin A, hCG

Question 27

What do hCG assays measure?

Answer 27

hCG assays measure the intact (whole) molecule, it does not measure the free alpha-or beta-subunits.

Question 28

What do total beta-hCG assays measure?

Answer 28

Total β-hCG assays measure both the intact hCG and free beta subunits.

Question 29

What hCG assay would be used as a tumor marker?

Answer 29

a total β-hCG assay may be preferred, because cancer patients produce significant amounts of free beta subunit

Question 30

What is the high dose hook effect?

Answer 30

The concentration of hCG is so high that it exceeds the optimum performance of the assay and usually yields a false low result.

Question 31

What diseases are asst. with hCG testing?

Answer 31

1. Gestational trophoblastic disease A. Hydatidiform moles B. Trophoblastic malignancy -Placental site trophoblastic tumors (cytotrophoblast cells arising from the placental implantation site) -Choriocarcinoma (both cytotrophoblastic and syncytiotrophoblastic elements) 2. Non-gestational malignancy 3. Testicular cancer

Question 32

What is important to remember about hCG test ordering?

Answer 32

Assay sensitivity is a key issue when ordering hCG tests.

Question 33

What is the variant hook effect?

Answer 33

1. Occurs in women who are more than five weeks pregnant. 2. If a device was developed to only measure intact hCG, it has problem when there’s too much of the variant hCG from five week’s gestation and later

Question 34

What are examples of detection limits forhCG?

Answer 34

Urine home pregnancy test kits : 50 U/L Urine Qualitative hCG test in lab : 25 – 50 U/L Serum Quantitative hCG test in lab: 1 – 2 U/L Serum Quantitative β-hCG test in many labs: 1 – 3 U/L Serum Quantitative β-hCG test in our lab: 0.1U/L

Question 35

what may hCG assays detect?

Answer 35

``` hCG hCG-beta Nicked hCG Hyperglycosylated hCG (hCG-H) Hyperglycosylated hCG-beta hCG and hCG-Beta missing the C-terminal peptide ```

Question 36

Where is GnRH secreted from?

Answer 36

Hypothalamus

Question 37

Where are LH and FSH secreted from?

Answer 37

Anterior pituitary

Question 38

What triggers the release of LH and FSH from the ant. pit?

Answer 38

GnRH (gonadotropin-releasing hormone)

Question 39

What is the function of LH?

Answer 39

LH binds to the Leydig cell receptors to enhance conversion of cholesterol to testosterone

Question 40

What is the function of FSH?

Answer 40

FSH activates the seminiferous tubules for sperms production.

Question 41

How are the structures of LH and FSH similar/different?

Answer 41

LH and FSH each consists of two subunits; both sharing the same α-subunit but with different β-subunits that confer their functional specificities.

Question 42

What is the relationship between (primary) gonadal steroids and pituitary gonadotropins?

Answer 42

As a rule, in primary states, gonadal steroids and pituitary gonadotropins are inversely correlated.

Question 43

How are levels of pituitary hormones regulated?

Answer 43

The negative feed-back signals from the gonadal steroids cause elevation, if deficient, or depression, if excessive, of the pituitary hormones.

Question 44

How are disorders of the reproductive system hormones classified?

Answer 44

Disorders of reproductive systems may generally be viewed from the stand-point of hormone deficiency or excess, and of primary (gonadal) or secondary (pituitary) origin.

Question 45

What is the relationship between (secondary) gonadal steroids and pituitary gonadotropins?

Answer 45

In the secondary state, gonadal steroids and pituitary gonadotropins are directly correlated since deficient or excessive gonadotropins secretion would act to inhibit or stimulate the target hormone productions accordingly.

Question 46

What is the clinical usefulness of LH and FSH?

Answer 46

1. Evaluate infertility 2. Diagnosis menopause in order to initiate hormone replacement therapy 3. Diagnosis of conditions

Question 47

What conditions are asst. with increased LH and FSH?

Answer 47

Gonadal failure (turner syndrome) Klinefelter syndrome, polycystic ovaries Preconscious puberty Pituitary adenoma

Question 48

What conditions are asst. with decreased LH and FSH?

Answer 48

Pituitary failure Hypothalamic failure Anorexic nervosa Stress

Question 49

What factors may interfere with FSH and LH assays?

Answer 49

hCG and TSH may interfere with various immunoassays due to similarities in the alpha and/or beta subunits. Patients with hCG producing tumors and hypothyroidism may produce falsely elevate LH or FSH levels. Several therapeutic and abused drugs can cause an increase or decrease in blood levels of LH and FSH.

Question 50

Where is prolactin released?

Answer 50

produced by the lactotrophs of the pituitary.

Question 51

What is the function of PRL?

Answer 51

major function of PRL is the initiation and maintenance of milk production.

Question 52

What is the major circulating form of PRL?

Answer 52

nonglycosylated monomer.

Question 53

What is the normal PRL level?Why is it this level?

Answer 53

Normal level is low (<25 F) because of the inhibitory actions of prolactin-inhibiting factor (PIF) a.k.a. dopamine from the hypothalamus.

Question 54

How often should PRL samples be drawn when assessing for hyperprolactinemia? Why?

Answer 54

PRL secretion is pulsatile with a short half-life, more than one sample should be drawn at 30 minute intervals when screening a patient for hyperprolactinemia.

Question 55

When are PRL levels elevated?

Answer 55

Elevated during sleep and peaks in early morning hours.

Question 56

Why is PRL clinically significant?

Answer 56

1. PRL is a sensitive indicator of pituitary dysfunction | 2. Test for prolactinemia

Question 57

What isthe most common pituitary hormone hypersecretion syndrome in both males and females?

Answer 57

Hyperprolactinemia is the most common pituitary hormone hyper secretion syndrome in both males and females

Question 58

What type of tumors can raise the PRL level to >1000 ng/ml?

Answer 58

Pituitary tumors >1000 ng/mL | Tumors arising from lactotrope cells account for about half of all functioning pituitary tumors.

Question 59

What are normla physiologic causes of elevated PRL levels?

Answer 59

pregnancy and lactation are the important physiologic causes of elevated PRL levels. Third trimesters: 95 – 473 ng/mL

Question 60

What occurs with PRL levels in women with amenorrhea and/or galactorrhea?

Answer 60

Hyperprolactinemia i | Three quarters of patients with amenorrhea and/or galactorrhea.

Question 61

What physiologic and pathologic factors (as well as medications) raise PRL levels that rarely exceed 200 ng/mL?

Answer 61

Stress | Phenothiazines, oral contraceptives, opiates and estrogens

Question 62

What conditions cause hypoprolactinemia?

Answer 62

1. Pituitary apoplexy (Sheehan syndrome) | 2. Any condition that results in pituitary destruction

Question 63

What is Pituitary apoplexy (Sheehan syndrome)

Answer 63

Women who develop severe hemorrhage after obstetric delivery and experience circulatory collapse, bleeding into the pituitary gland (apolexy), resulting in an infarcted pituitary.

Question 64

What conditions can cause falsely low PRL levels?

Answer 64

Falsely lowered results may occur because of assay artifacts; sample dilution is required to measure these high values accurately (hook effect).

Question 65

What conditions can cause falsely high PRL levels?

Answer 65

Falsely elevated values may be caused by aggregated forms of circulating PRL, which are biologically inactive as macroprolactinemia.

Question 66

Why is the first response ovulation test unique?

Answer 66

It's the ovulation test that actually detects your own personal LH surge. It detects and tracks your personal daily baseline levels of luteinizing hormone (LH) to detect your personal surge, unlike some other ovulation tests that use a preset "average" level to determine an LH surge.