4thShiftCASEDISCUSSION

C8

CENTRALHYPOTHESIS
pituitary microadenoma (compressedthepituitarystalk= dec FSH,LH)>incprolactin>amenorrhea,
infertility

PROBLEMSGENERATED
1.CauseofamenorrheaGioseppeBobbyNavalesNaceno
The most common type of pituitary tumor is a prolactinoma, a tumor that hypersecretes prolactin.
Hyperprolactinemia (high prolactin secretion) causes infertility because prolactin inhibits GnRH
secretion. GnRH is required to stimulate secretion of the gonadotropins, FSH and LH. WhenGnRH
secretionis low, FSH andLH secretion arelow andsodonot stimulate gameteproductionandgonadal
steroid synthesis. Thus, hyperprolactinemia is an example of infertility due to hypogonadotropic
hypogonadism, low gonadal function that results from low gonadotropin secretion. In females this
causes a lack of ovulation, which is known asanovulation. Typically, femaleswithhyperprolactinemia
will present with amenorrhea (lack of menstruation) and sometimes galactorrhea (abnormal milk
production). Prolactinomas seem to be less common in males, but in males hyperprolactinemia also
causes hypogonadism, which causes infertility and loss of libido. Another concern is that decreased
gonadalsteroidsecretionwillleadtoosteoporosis.

2.CauseofincserumprolactinMikaelaAngelicaNaui

Causeofincserumprolactin:
The patient has pituitary microadenoma, a type of prolactinoma which is less than 10mm in size.
Prolactinomasarebenign,prolactinsecretingtumors.

'Thestalkeffect': the tumorinterfereswiththedeliveryofdopaminetotheprolactinsecretingcellsofthe

pituitary,thusprolactinlevelsareelevated

3.IndicationandmorespecificMOAofBromocriptineAngeloNavarroIselineNavarro

4.SignificanceofTVSresultsCiaraMorales

Transvaginal ultrasound
is an imaging technique used to create a picture of the genital tract in
women. The handheld device that produces the ultrasound waves is inserteddirectlyintothevagina,
close to the pelvic structures, thus often producing a clearer and less distorted image than obtained
through transabdominalultrasoundtechnology, where theprobeis located externallyon the skin ofthe
abdomen.

Transvaginal ultrasound is routinelyusedintheinitialevaluationoftheinfertilepatientand provides

information about diseases such as ovarian cysts, dilated tubes uterine fibroids, large endometrial
polyps, and birth defects oftheuterus.Advantages of TVS are thatit isa well tolerated,radiationfree
methodwhichprovidesinformationonthesizeandpositionoftheuterus,andtuboovariandiseases

During fertilityinvestigation andtreatment, anassessment ofendometrialreceptivity isgenerally based

on endometrial thickness and appearancein conjunctionwithan estimationof uterine arterybloodflow
velocities using Doppler ultrasound (
Friedleret al., 1996
). A typical trilaminar appearance with a
minimumthicknessof7mmand a uterine artery pulsatilityindexof<3.0 areregardedassound markers
ofendometrialreceptivity(
Steeretal.,1992

Zaidietal.,1995
)


5.RelationshipofprolactinandfertilityBeteenaRaeMunoz

Prolactin is a hormonethatplaysa rolein fertility by inhibitingfolliclestimulatinghormone (FSH)and

gonadotropinreleasinghormone (GnRH),thehormones thattriggerovulationandalloweggstodevelop
andmature.Itaffects fertility, because if you have too muchprolactininyourbody,ovulationwill notbe
triggeredandyouwillbeunabletogetpregnant.
Prolactin
is a hormone found in the body, and it plays an important role in fertility and conception.
Prolactin comes from the pituitary gland and it is the hormone that helps prepare a woman
for
breastfeeding
bystimulatingmilkproductionand enlargingher mammary glands.Prolactinisalsoan
important part of conception,since itinhibits FSH andGnRH,bothofwhichareimportanthormonesfor
ovulation. If you have low levels of prolactin in your body, it isusually not abigdeal. If you have too
muchprolactininyourbody,ovulationwillnotbetriggeredandyouwillbeunabletogetpregnant.

LEARNINGISSUES
1.HPOaxisofprolactininrelationtoGnRH,FSH,LHJermineMoniqueMuaripPatriciaMoran
ThehypothalamussecretesGnRH whichtravelsdowntheanteriorportionofthepituitary viathe
hypophyseal portal system and binds to receptors on the secretory cells of the adenohypophysis
. In
responsetoGnRHstimulationthesecellsproduceLHandFSH,whichtravelintothebloodstream.
These two hormones play an importantrole in communicatingtothegonads. Infemales FSH
and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the
menstrual cycleand ovarian cycle
.Estrogenformsanegativefeedbackloop byinhibiting theproduction
of GnRH in the hypothalamus. In males LH stimulates the interstitial cells located in the testes to
producetestosterone,andFSHplaysarolein
spermatogenesis
.

One of the mostimportantfunctionsofthisHPG axis isto regulate reproductionby controlling

the uterineand ovarian cycles.Infemales,thepositivefeedbackloopbetweenestrogenandluteinizing
hormone helptoprepare the follicleintheovaryandtheuterus forovulationand implantation.Whenthe
eggis released, theempty follicle sac beginsto produce progesterone toinhibitthe hypothalamusand
the anterior pituitary thus stopping the estrogenLH positive feedback loop. If conception occurs, the
placenta will take over the secretion of progesterone therefore the mother cannot ovulate again. If
conceptiondoes not occur, decreasing excretionofprogesterone will allow the hypothalamus torestart
secretion of GnRH. These hormone levels also control the uterine (menstrual) cycle causing the
proliferation phase in preparation for ovulation, the secretory phase after ovulation,and menstruation
when conception does not occur. The activation of the HPG axis in both males and females during
pubertyalsocausesindividualstoacquiresecondarysexcharacteristics.
Inmales, the productionofGnRH, LH,and FSH are similar, but the effectsofthesehormones
are different. FSH stimulates sustentacular cells to release androgenbindingprotein
, which promotes
testosterone binding. LH binds to the interstitial cells, causing them to secrete testosterone
.
Testosteroneis requiredfor normalspermatogenesisand inhibitsthehypothalamus.Inhibinisproduced
by the spermatogenic cells, which, also through inactivating activin, inhibits the hypothalamus. After
pubertythesehormoneslevelsremainrelativelyconstant.

Elevated levels of prolactin decrease the levels of sex hormones estrogen in women and
testosterone inmen. Theeffectsofmildlyelevatedlevelsof prolactinaremuchmorevariable,inwomen,
substantiallyincreasingordecreasingestrogenlevels.
Prolactin is sometimes classified as a gonadotropin
although in humans it has only a weak
luteotropic effect while the effect of suppressing classical gonadotropic hormones is more important.
Prolactin within the normal reference ranges can act as a weak gonadotropin
, but at the same time
suppresses
GnRH
secretion.TheexactmechanismbywhichitinhibitsGnRHispoorlyunderstood.


Hyperprolactinemia inhibits the secretion of gonadotropinreleasing hormone (GnRH) from the
hypothalamus (by increasing the releaseofdopaminefromthearcuate nucleus
), which in turninhibits
the release of folliclestimulating hormone (FSH) andluteinizinghormone(LH) from the pituitarygland
andresultsindiminished
gonadal
sexhormone
production(termed
hypogonadism
).

2.MenstrualcyclehormonalchangesFrancesValerieNatividadMichelleMorco

MENSTRUATION toPREOVULATORY PHASE LH andFSHlevels low and are constantestrogen

levelsarerisingwhileprogesteronelevelsareconstantlylow

PROLIFERATIVE PHASELH starting to increaseFSHdecreasing

estrogen levels increasingwhile
progesteroneisstilllow

OVULATIONLHsurgeFSHveryslightincreaseestrogenatitspeakwhileprogesteronestilllow

SECRETORY LHand FSH levelsare verylowestrogendecreasingwhile

progesteroneishighest in
thisphase

3.PhysiologiceffectsofprolactinJohanneMorales

Prolactin,
also called luteotropic hormone (LTH) or luteotropin, a protein hormone produced by the
pituitary gland of mammals that acts with otherhormones to initiate secretionof milkby the mammary
glands
.Ontheevolutionaryscale,prolactin isanancienthormone serving multiplerolesin mediatingthe
care of progeny (sometimes called the parenting hormone). It is a large protein molecule that is
synthesizedinand secreted from lactotrophs, whichconstitute about20percentof theanteriorpituitary
gland
andarelocatedlargelyinthelateralregionsofthe
gland
.

Physiologicalimportanceofprolactin
In women the major action of prolactin is to initiate and sustain lactation
. In breastfeeding
mothers, tactile stimulation of the nipples and the breastby the suckling infant blocks the secretionof
hypothalamic dopamine(which normally inhibitsprolactin) into the hypophysealportal circulationof the
pituitary gland. This results ina sharprise inserumprolactinconcentrations, followedby aprompt fall
when feeding stops. High serum prolactin concentrations inhibit secretion of gonadotropinreleasing
hormone (GnRH) from the hypothalamus
,therebydecreasingthesecretionofgonadotropins(
luteinizing
hormone and folliclestimulating hormone
), and may also inhibit the action of gonadotropins on the
gonads. Thus, high serum prolactin concentrations during lactationreduce fertility,protectinglactating
womenfromapremature
pregnancy
.
Because prolactin acts to maintain the corpus luteumof the ovary
,which is thesourceof the
female sex hormone progesterone
, it helps to sustain pregnancy
. In addition, prolactin secretion
increases progressively during pregnancy. The secretion of prolactin also can be stimulated by high
doses of estrogens
, and it istransiently stimulated by stressand exercise. Thefunction of prolactin in
malesisnotknown.

Regulationofprolactinsecretion
The hypothalamicregulationofprolactinsecretionby theanteriorpituitaryglandisdifferentfrom
the hypothalamic regulation of other pituitary hormones intworespects.First, hypothalamic control of
prolactin secretion is primarily inhibitory, whereas the hypothalamic control of the secretion of other
anterior pituitary hormones isstimulatory.Thus,iftheanteriorpituitaryisseparatedfromtheinfluenceof
the hypothalamus
, the secretion of prolactin increases whereas that of the other anterior pituitary
hormones decreases. The hypothalamic factor that inhibits prolactin secretion is the neurotransmitter

dopamine
, whichis not aneuropeptide, asaretheother hypothalamichormonesthat regulate anterior
pituitary hormone secretion. Drugs that mimic the action of dopamine are therefore useful intreating
patientswithhighserumprolactinconcentrations.
Prolactinstimulating factors also exist, and included among them are GnRH,
thyrotropinreleasing hormone
, and vasoactive intestinal polypeptide
. However, the physiologic
importance of these prolactinstimulating factors is not welldefined. One example of a
prolactinstimulating factor for which a role has been identified isestrogen
,which stimulatesprolactin
synthesisandsecretioninthelatestagesofpregnancytopreparethemammaryglandsforlactation.

4.PathophysiologyofpituitarymicroadenomaClaireMonzonNerissaNeryNatata

Bydefinition,amicroadenomaisatumorlessthan10mmin diameter.Pituitaryadenomasmay
secrete hormones, but most are clinically inactive. Many pituitary lesions are discovered while
investigating other neurologic problems these lesions are calledincidentalomas. With the use of MRI
increasing,thediscoveryofsuchincidentalmicroadenomaswillbecomemoreofaclinicalproblem.

Most pituitary tumors are sporadic. Some are part of genetic syndromes such as multiple endocrine
neoplasiatype1(MEN1),McCuneAlbrightsyndrome,orCarneycomplex.Clonalanalysisshows almost
all are monoclonal in origin from a genetically mutated single cell. The cause of sporadic tumors is
unknown.

Ofthesecretory tumors, themostcommonare prolactinomas. Other secretorytumorsmay secrete(1)

corticotropin, causing Cushing disease (2) growth hormone, causing acromegaly (3) gonadotropins
with clinical presentations reflective of severityand sex(rare)(4)or thyroidstimulatinghormone(TSH),
causing hyperthyroidism (rare). Most clinically nonsecreting adenomas are gonadotropin in origin and
secrete fragments of beta or alpha subunits of gonadotropin peptide. Such clinically inactive
microadenomasareoflittleclinicalconsequence.

5.ConceptMapBeatriceNicoleB.NaidasFerdinandSherwinMorataJuanCarlosMoreno