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MRCOG PART 1 - CLINICAL MX & DATA

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MRCOG I Single best answers: Endocrinology

Answer Posted by Farrukh G.

1)    C

2)    A

HUMAN CHORIONIC GONADOTROPIN (HCG)

•   Glycoprotein, with carbohydrates making up about one third of its molecular weight. This accounts for the longer half life of HCG (24h) compared to say LH (2h)

•   Alpha chain similar to alpha chain of FSH, LH, TSH - therefore has some intrinsic TSH activity

•   Unique beta chain

•   All human tissues make HCG but the placenta is unique in being able to glycosylate it, increasing the half life and giving biological activity. Sialic acid residues are essential for the longer half life

•   HGC is produced mainly by the syncytiotrophoblast although gene expression also occurs in cytotrophoblasts

HCG is detectable in the 8 cell stage embryo and takes over from LH in supporting the corpus luteum about 8 days after ovulation (1 day after implantation)

 

3)    C

GnRH is a decapeptide synthesized by placental cells (as well as the hypothalamus) nnnnnnnnand the receptors are present in the placenta. In vitro, GnRH stimulates HCG production while endorphins are inhibitors

 

4)    B

5)    C

6)    C

7)    A

 

Maternal HCG ~100IU/L at the time of the first missed period and peaks at ~100,000IU/L at ~10 weeks gestation

Levels fall to about 10,000 - 20,000IU/L at 18-20 weeks and remain at this level till term

Mainly excreted by the kidneys - as a reduced fragment of the beta sub-unit called the beta-core fragment

Maternal, urinary, placental and amniotic fluid HCG levels at term are higher in pregnancies with a female fetus

Useful in the diagnosis and management of trophoblastic disease and ectopic pregnancy

HCG is produced by virtually all tissues - pulsatile release from the pituitary gland together with LH - levels may be within the sensitivity of current assays in post-menopausal women with very high LH levels. Non-glycosylated therefore very short half life

 

8)    D

9)    D

 

OESTROGEN SECRETION

Under fetal control and is a fundamental feto-maternal signalling mechanism

The placenta lacks 17-alpha hydroxylase and 17-20 desmolase activity and cannot convert C21 products (progesterone / pregnenolone) to C19 products (androstendione / DHEA)

In early pregnancy, the placenta utilises maternal androgens for oestrogen production

By 20 weeks gestation, the majority of placental oestrogen production is from fetal DHEA-Sulphate. The fetus rapidly sulphates steroids, preventing biological activity.

The placenta has an active sulphatase to remove sulphate groups

Fetal DHEA-S is converted to oestradiol and oestrone. The placenta cannot produce oestriol from DHEA-S

Fetal DHEA-S is hydroxylated by the fetal liver to 16-alpha-hydroxy-DHEA-S. This is then utilised by the placenta for OESTRIOL production. Oestriol is first detectable at 9 weeks gestation when fetal adrenal gland secretion of precursor begins.

In the absence of a normal fetal adrenal gland, maternal oestrogen concentrations are very low (for instance, anencephaly)

OESTRIOL is the main placental oestrogen. Oestradiol and oestrone are derived equally from maternal and fetal precursors

Maternal oestraDIOL levels are higher than in the fetus

Fetal oesTRIOL levels are higher than maternal levels

Placental aromatisation of maternal androgens is so effective that the fetus is protected from masculinisation. Extremely high androgen levels or non-aromatisable analogues are required for fetal effects

 

10) B

11) A

12) B

13) C

 

PROGESTERONE SECRETION

Produced by the corpus luteum until 10 weeks gestation –exclusively until 7 weeks after which placental production begins

At term, the placenta produces ~250mg/day

Progesterone production by the placenta is independent of the quantity of precursor available, utero-placental perfusion, fetal well-being or even the presence of a live fetus

Produced from maternal cholesterol (LDL); about 3% is derived from maternal pregnenolone. Levels rise with increasing gestation age

Human decidua and fetal membranes also produce progesterone, mainly from pregnenolone sulphate

Amniotic fluid progesterone concentration is maximal at 10-20 weeks gestation and fall gradually

Myometrial progesterone concentrations are about 3x maternal plasma levels in early pregnancy, and equal to plasma levels at term

Levels of 17-alpha hydroxyprogesterone are high in early pregnancy (corpus luteum), return to pre-pregnancy levels at about 10 weeks (placenta has little 17-alpha hydroxylase activity) and increase after 32 weeks due to placental utilization of fetal precursors

Progesterone serves as a substrate for glucocorticoid and mineralocorticoid production by the fetal adrenal gland, although fetal serum LDL cholesterol is also utilized

The fetal adrenal cortex lacks significant 3-beta-hydroxysteroid dehydrogenase and isomerase activity and relies on placental progesterone

Maintains the decidua and stimulates prolactin secretion from the decidua

Inhibits myometrial contractions, prostaglandin production and sensitivity to oxytocin

 

14) D

15) D

16) B

 

LEUTENISING HORMONE (LH)

Glycoprotein produced by the anterior pituitary. Protein hormones are not

significantly protein bound

Acts via a receptor on the cell membrane

Has an alpha and a beta subunit

Concentrations are low in childhood, increase during puberty and are elevated after the menopause

Concentrations begin to rise within a few days of the onset of menstruation but fall during the latter part of the follicular phase (negative feed-back from rising

oestrogen concentrations)

There is a pre-ovulatory LH peak occurring about 18h before ovulation. Without the LH surge, ovulation does not occur

Stimulates the synthesis of androstendione and testosterone by the theca cells which are converted to oestrogen by the granulosa cells

Stimulates progesterone production by the granulosa cells and later the conversion of granulosa into lutein cells

FSH and oestrogen induce the expression of LH receptors by granulosa cells

 

17) E

 

Secretion of LH is regulated by:

1) GnRH from the anterior pituitary

2)Oestrogen from the ovary - initially inhibits LH secretion but induces the pre-ovulatory surge

3) Inhibin - mainly inhibits FSH, but also LH secretion

4) Progesterone - in high concentrations inhibit LH secretion

 

18)B

19) E

 

 

 

FOLLICLE-STIMULATING HORMONE (FSH)

Gonadotropin - produced by the anterior pituitary gland.

Glycoprotein

Has an alpha and a beta sub-unit

Functions via a receptor on the cell membrane

Main function is the stimulation of the growth of 6-12 primary follicles per month

Concentartions are low during childhood, increase during puberty and are elevated after the menopause

Concentrations begin to rise within a few days of the onset of menstruation and then fall as the oestrogen levels rise. There is a pre-ovulatory surge in FSH concentration

Stimulates granulosa cell proliferation and also the ovarian stroma to form the theca interna and externa of the vesicular follicle

 

Production is regulated by:

1) GnRH: from the hypothalamus - stimulates FSH production

2) Oestrogen from the ovary - negative feed-back to inhibit pituitary FSH production

3) Inhibin: from the ovary - inhibits FSH production

4) Activin: from the ovary - stimulates FSH production

5) High levels of progesterone inhibit FSH production

 

 

20)D

21)C

22) D

 

GONADOTROPIN RELEASING HORMONE

Decapeptide produced by the arcuate and preoptic nuclei of the hypothalamus and stored in the median eminence. Synthesised as a preprohormone

Pulsatile release under influence of higher centres: 8-10 pulses per day in the adult male; pulsatility in the female is dependent on the menstrual cycle

Acts via a cell-surfece receptor

Stimulates LH and FSH release from the anterior pituitary

Sustained high levels cause down-regulation of pituitary GnRH receptors and androgen / oestrogen production by the gonad becomes suppressed

 

 

23)E

 

24) B

 

 

MENOPAUSE

Average age 50.8 years

Caused by 'burn-out' of the ovarian follicles - insufficient to produce enough

oestrogen to suppress FSH secretion or to induce LH surge

Oestrogen and progesterone levels fall

FSH & LH concentrations are elevated which suppress GnRH secretion

 

 

25) D

 

PUBERTY

Initiated by maturation in higher centres which result in pulsatile release of GnRH by the hypothalamus

Prior to the onset of puberty, the hypothalamus is capable of secreting GnRH and the pituitary and ovaries are capable of a response

Oestrogen, progesterone, LH & FSH levels are low prior to puberty.