hyper prolactinemia

HyperprolactinemHyperprolactinemiaia

Dr. Ashraf FoudaDr. Ashraf FoudaF.E.B.O.G.F.E.B.O.G.

Obs./Gyn. ConsultantObs./Gyn. Consultant

Is a polypeptide hormone containing Is a polypeptide hormone containing 198 amino acids198 amino acids and having a molecular and having a molecular weight of weight of 22,000 daltons22,000 daltons. .

It circulates in different molecular sizes— It circulates in different molecular sizes— a a (small)(small) form form (mol wt 22,000),(mol wt 22,000), a a (big)(big) form form (mol wt 50,000),(mol wt 50,000), and an even and an even larger larger (big-big)(big-big) form form (mol wt >100,000).(mol wt >100,000).

The small form is biologically active, and The small form is biologically active, and about about 80%80% of the hormone secreted is in this of the hormone secreted is in this form. form.

PROLACTINPROLACTIN

Discovered by Discovered by Sticker 1928Sticker 1928 (Veterinarian). (Veterinarian).

It is one of the It is one of the stress hormonesstress hormones, ,

It has a It has a short half-lifeshort half-life (20 min) (20 min)

and and

Sleep-related circadian rhythmSleep-related circadian rhythm , ,

highest in the early morning & highest in the early morning &

lower in the afternoon .lower in the afternoon .

PROLACTINPROLACTIN

Secreted in a Secreted in a pulsatile pulsatile fashion.fashion.

Its primary function is to Its primary function is to enhance breast enhance breast

developmentdevelopment during pregnancy and to during pregnancy and to

induce lactationinduce lactation. .

However, prolactin also binds to However, prolactin also binds to

specific receptorsspecific receptors in the in the

gonads, lymphoid cells, and liver.gonads, lymphoid cells, and liver.

PROLACTINPROLACTIN

PROLACTINPROLACTIN Source:Source:

– LactotrophsLactotrophs– Decidual cellsDecidual cells– No storage, no feedbackNo storage, no feedback

Action:Action:– BreastBreast– GonadGonad– SexSex

Features:Features:– Short half-lifeShort half-life– Small , Big and big big prolactinSmall , Big and big big prolactin– Cleared by the liver and kidney Cleared by the liver and kidney

EstrogenEstrogen stimulates the proliferation of stimulates the proliferation of

pituitary lactotroph cells, resulting in an pituitary lactotroph cells, resulting in an

increased quantity of these cells in increased quantity of these cells in

premenopausal women, especially during premenopausal women, especially during

pregnancy. pregnancy.

Normal fasting valuesNormal fasting values generally are less generally are less

than than 30 ng/mL30 ng/mL depending on the individual depending on the individual

laboratory.laboratory.

Hyperprolactinemia Hyperprolactinemia is a condition of is a condition of

elevated serum prolactin. elevated serum prolactin.

PROLACTINPROLACTIN

LactationLactation is inhibited by the high levels is inhibited by the high levels of estrogen and progesterone during of estrogen and progesterone during pregnancy. pregnancy.

The The rapid decline of estrogen and rapid decline of estrogen and progesteroneprogesterone in the postpartum period in the postpartum period allows lactation to occur. allows lactation to occur.

During lactation and breastfeeding, During lactation and breastfeeding, ovulation may be suppressedovulation may be suppressed due to the due to the suppression of gonadotropins by suppression of gonadotropins by prolactin.prolactin.

PathophysiologyPathophysiology

Dopamine (Prolactin Inhibiting Factor Dopamine (Prolactin Inhibiting Factor

PIF)PIF) has the has the dominant influencedominant influence

over prolactin secretion. over prolactin secretion.

Secretion of prolactin is under Secretion of prolactin is under

tonic inhibitory control by tonic inhibitory control by

dopaminedopamine, which acts via , which acts via D2-type D2-type

receptorsreceptors located on lactotrophs. located on lactotrophs.


Prolactin production can be stimulated by Prolactin production can be stimulated by the hypothalamic peptides, the hypothalamic peptides, Thyrotropin-Thyrotropin-Releasing Hormone (TRH)Releasing Hormone (TRH) and and Vasoactive Vasoactive Intestinal Peptide (VIP).Intestinal Peptide (VIP).

Thus, primary hypothyroidism Thus, primary hypothyroidism (a high (a high TRH state)TRH state) can cause hyperprolactinemia. can cause hyperprolactinemia.

VIPVIP increases prolactin in increases prolactin in response to response to sucklingsuckling, probably because of its action , probably because of its action on receptors that increase adenosine on receptors that increase adenosine 3',5'-cyclic phosphate 3',5'-cyclic phosphate (c AMP).(c AMP).


Manifestation of Manifestation of hyperprolactinemiahyperprolactinemia

In Females :In Females : Galactorrhea (Non-puerperal lactation)Galactorrhea (Non-puerperal lactation)

– Unilateral or bilateralUnilateral or bilateral– Free floating or expressiveFree floating or expressive

– Continuous or intermittentContinuous or intermittent Ovulatory dysfunctionOvulatory dysfunction

– Oligo-ovulationOligo-ovulation– LPDLPD– AnovulationAnovulation

Menstrual troublesMenstrual troubles– OligomenorrheaOligomenorrhea– Hypomenorrhea Hypomenorrhea – AmenorrheaAmenorrhea

OsteoporosisOsteoporosis Nervous manifestations ( headache )Nervous manifestations ( headache ) Visual field defects ( Bitemporal Visual field defects ( Bitemporal

Hemianopia )Hemianopia ) HirsutismHirsutism

In men:In men: ImpotenceImpotence OligospermiaOligospermia GynecomastiaGynecomastia Headache Headache OsteoporosisOsteoporosis Visual field defectsVisual field defects

Manifestation of Manifestation of hyperprolactinemiahyperprolactinemia

HyperprolactinaemiaHyperprolactinaemia

is present in : is present in :

15–20%15–20% of cases involving of cases involving secondary secondary

amenorrhea or oligomenorrhea.amenorrhea or oligomenorrhea.

30%30% of cases involving of cases involving galactorrhoea galactorrhoea

or infertilityor infertility..

75%75% of cases involving of cases involving both both

amenorrhea & galactorrhoea.amenorrhea & galactorrhoea.

Causes of Causes of hyperprolactinemiahyperprolactinemia

Physiologic factors−PainPain−Nipple Nipple stimulationstimulation−Pregnancy Pregnancy −Pelvic Pelvic examinationexamination−ExerciseExercise−SleepSleep

Drugs–Dopamine-antagonists−Dopamine-depleting agents Dopamine-depleting agents

–Narcotics

Pathologic factors–Hypothalamus–Pituitary–Thyroid

Idiopathic hyperprolactinemiaIdiopathic hyperprolactinemia

Dopamine-depleting agentsDopamine-depleting agents : :AldometAldometReserpineReserpine

Dopamine receptor antagonist :Dopamine receptor antagonist :ChlorpromazineChlorpromazinePromazinePromazineButyrophenone (haloperidol)Butyrophenone (haloperidol)Metoclopramide (primperan)Metoclopramide (primperan)Domperidone (motilium)Domperidone (motilium)Sulpiride (dogmatyl)Sulpiride (dogmatyl)

Drug-induced Drug-induced hyperprolactinemiahyperprolactinemia

– Lactotroph stimulatorLactotroph stimulator EstrogenEstrogen TRHTRH

– NarcoticsNarcotics MorphineMorphine Codeine Codeine MethadoneMethadone

– AmphetamineAmphetamine– H2-receptor blockerH2-receptor blocker

Cimetidine (Tagamet)Cimetidine (Tagamet) Ranitidine (Zantac)Ranitidine (Zantac)

Drug-induced Drug-induced hyperprolactinemiahyperprolactinemia

Hypothalamic CausesHypothalamic Causes

Craniopharyngioma Craniopharyngioma (Rathke’s pouch tumor)(Rathke’s pouch tumor) being the best example. being the best example.

Grossly they can be cystic, Grossly they can be cystic, solid, or mixed, and solid, or mixed, and calcificationcalcification is usually is usually visible on x-ray visible on x-ray examination. examination.

Pituitary CausesPituitary Causes Various types of Various types of pituitary tumors, pituitary tumors,

lactotroph hyperplasia, and the empty lactotroph hyperplasia, and the empty sella syndromesella syndrome can be associated with can be associated with hyperprolactinemia. hyperprolactinemia.

80%80% of all pituitary adenomas secrete of all pituitary adenomas secrete prolactin. prolactin.

The most common pituitary tumor The most common pituitary tumor associated with hyperprolactinemia is the associated with hyperprolactinemia is the prolactinomaprolactinoma, defined as , defined as

1.1. MicroadenomaMicroadenoma if its diameter is less than if its diameter is less than 1 cm and as 1 cm and as

2.2. MacroadenomaMacroadenoma if it is larger. if it is larger.

An intrasellar extension of the An intrasellar extension of the

subarachnoid space resulting in subarachnoid space resulting in

compression of the pituitary gland compression of the pituitary gland

and an and an enlarged sella turcicaenlarged sella turcica that that

may be associated with galactorrhea may be associated with galactorrhea

and hyperprolactinemia.and hyperprolactinemia.

Empty sella syndromeEmpty sella syndrome

HypothyroidismHypothyroidism

About About 3% to 5%3% to 5% of individuals with of individuals with

hyperprolactinemia have hyperprolactinemia have

hypothyroidism, and thushypothyroidism, and thus TSH TSH, ,

the most sensitive indicator the most sensitive indicator

of hypothyroidism, should of hypothyroidism, should

be measured in all individuals with be measured in all individuals with

hyperprolactinemia. hyperprolactinemia.

Secondary amenorrheaSecondary amenorrhea

GalactorrheaGalactorrhea

Ovulatory dysfunctionOvulatory dysfunction

Unexplained infertilityUnexplained infertility

Oligospermic menOligospermic men

Indications for Indications for ProlactinProlactin assayassay

Not all hyperprolactinemic patients display galactorrhea and galactorrhea can be seen with

normal prolactin level

Indications for sella Indications for sella evaluationevaluation

Prolactin levelProlactin level > 100 ng/ml > 100 ng/ml

Nervous manifestationsNervous manifestations

Amenorrhea galactorrhea:Amenorrhea galactorrhea:

– Resistant to treatmentResistant to treatment

– Associated with negative Associated with negative

Progesterone Withdrawal Test.Progesterone Withdrawal Test.

GalactorrheaGalactorrhea It is important to distinguish secretions

that result from intrinsic breast disease

from true galactorrhea.

Galactorrhea is defined as the

non-pueperal secretion of milk and

can be confirmed if necessary by

visualizing fat droplets in

secretions using low

power microscopy.

Galactorrhea is rarely seen in intrinsic breast diseases,

which are usually associated with purulent, clear, yellow (serous), multicoloured or

sanguinous discharge.


Isolated galactorrhea,

with normal menses and normal

serum prolactin levels,

has been estimated to occur in

up to 20% of women

at some point in

their lives.


Hyperprolactinemia is found

in 30% of women with

amenorrhea, and

in 75% of women who have both

amenorrhea and galactorrhea.

Thus, measurement of serum prolactin

levels is indicated in all cases of

galactorrhea.


If no obvious cause is identified or if a tumor If no obvious cause is identified or if a tumor is suspected, MRI should be performedis suspected, MRI should be performed . .

A A prolactinomaprolactinoma is likely if the prolactin level is likely if the prolactin level is greater than 250 ng/mL and less likely if is greater than 250 ng/mL and less likely if the level is less than 100 ng/mL. the level is less than 100 ng/mL.

Prolactin-secreting adenomas are divided Prolactin-secreting adenomas are divided into 2 groups: into 2 groups:

(1) Microadenomas(1) Microadenomas (more common in (more common in premenopausal women), premenopausal women), which are smaller than 10 mm which are smaller than 10 mm and and

(2) Macroadenomas(2) Macroadenomas (more common in (more common in men and postmenopausal women), men and postmenopausal women), which are 10 mm or larger. which are 10 mm or larger.

If the prolactin level is greater than 100 ng/mL If the prolactin level is greater than 100 ng/mL

MRI imagingMRI imaging is performed to is performed to

rule out a prolactin-producing tumor. rule out a prolactin-producing tumor.

When the underlying cause (physiologic, When the underlying cause (physiologic,

medical, pharmacologic) cannot be medical, pharmacologic) cannot be

determined and an MRI does not identify an determined and an MRI does not identify an

adenoma, adenoma, idiopathic hyperprolactinemiaidiopathic hyperprolactinemia is is

diagnosed. diagnosed.

If no obvious cause is identified or If no obvious cause is identified or if a tumor is suspected, if a tumor is suspected, MRI should be performed MRI should be performed..

MacroprolactinemiaMacroprolactinemia Is the apparent increase in serum prolactin Is the apparent increase in serum prolactin

without symptoms. without symptoms. Serum prolactin molecules can polymerize Serum prolactin molecules can polymerize

and subsequently bind to immunoglobulin G and subsequently bind to immunoglobulin G (IgG). (IgG).

This form of prolactin is unable to bind to This form of prolactin is unable to bind to prolactin receptors and exhibits no systemic prolactin receptors and exhibits no systemic response. response.

In the asymptomatic patient In the asymptomatic patient with hyperprolactinemia, this with hyperprolactinemia, this condition should be considered. condition should be considered.

If this condition is suspected, If this condition is suspected, specific specific

serum immunoassaysserum immunoassays must be must be

performed to detect this form of performed to detect this form of

prolactin. prolactin.

Women with macroprolactinemia are Women with macroprolactinemia are

able to conceive. able to conceive.

This condition generally requires This condition generally requires

no treatment.no treatment.

MacroprolactinemiaMacroprolactinemia

Imaging StudiesImaging Studies

Although modern Although modern high-speed helical high-speed helical

CT scannersCT scanners produce very detailed produce very detailed

images, images,

MRI MRI is the imaging study of choice.is the imaging study of choice.

MRI can detect adenomas that are MRI can detect adenomas that are

as small as as small as 3-5 mm. 3-5 mm.

Remember that there are four main Remember that there are four main known causes of hyperprolactinemiaknown causes of hyperprolactinemia1.1. PregnancyPregnancy

2.2. Drug useDrug use

3.3. HypothyroidismHypothyroidism

4.4. Pituitary tumorsPituitary tumors Remember that it is not essential to Remember that it is not essential to

treat asymptomatic treat asymptomatic hyperprolactinemic women but hyperprolactinemic women but follow-up is a mustfollow-up is a must. .

Remember that the problem is Remember that the problem is never never overover once pregnancy occurs once pregnancy occurs

ManagementManagement

Indications for treatment include the Indications for treatment include the presence of significant symptoms such presence of significant symptoms such

as :as :

1.1. Disabling galactorrhea, Disabling galactorrhea,

2.2. Amenorrhea, and infertility; Amenorrhea, and infertility;

3.3. Presence of visual field defect and Presence of visual field defect and cranial nerve palsy; and cranial nerve palsy; and

4.4. Abnormal test results such as detection Abnormal test results such as detection of a pituitary tumor, of a pituitary tumor,

5.5. Diminished libido, Diminished libido,

6.6. Osteopenia, or osteoporesis.Osteopenia, or osteoporesis.

Medical treatmentMedical treatment

1.1. Suppressing prolactin secretionSuppressing prolactin secretion and its clinical and biochemical and its clinical and biochemical consequences, consequences,

2.2. Reducing the sizeReducing the size of the of the prolactinoma, and prolactinoma, and

3.3. Preventing its progression or Preventing its progression or recurrencerecurrence..

Medical treatment Medical treatment goalsgoals

Dopamine agonistsDopamine agonists Are the preferred treatment for Are the preferred treatment for

most patients with hyperprolactinemic most patients with hyperprolactinemic

disorders. disorders.

These agents are extremely effective in:These agents are extremely effective in:

1.1. Lowering serum prolactin levels, Lowering serum prolactin levels,

2.2. Eliminating galactorrhea, Eliminating galactorrhea,

3.3. Restoring gonadal function, and Restoring gonadal function, and

4.4. Decreasing tumor size. Decreasing tumor size.

Dopamine agonistsDopamine agonistsDopamine agonistsDopamine agonists

AgonistAgonistNature Nature DoseDoseMaintenanMaintenancece

BromocriptiBromocriptinene

(Parlodel)(Parlodel)

ErgotErgot2.5-10 2.5-10 mg/daymg/day

7.5 mg/d7.5 mg/d

LisurideLisuride

(Dopergine)(Dopergine)ErgotErgot0.1-0.2 0.1-0.2

mg/daymg/day0.1 mg/day0.1 mg/day

QuinagolideQuinagolide

(Norprolac)(Norprolac)ErgotErgot25-300 25-300

g/dayg/day75 75 g/dayg/day

CabergolineCabergoline

(Dostinex)(Dostinex)ErgotErgot0.25-1 0.25-1

mg/TWmg/TWWW

1 mg/week1 mg/weekNB: Parlodel GH in healthy and it in acromegalics

BromocriptineBromocriptine Is a semisynthetic ergot derivative of Is a semisynthetic ergot derivative of

ergoline, a ergoline, a dopamine D2-receptordopamine D2-receptor agonist agonist

with agonist and antagonistic properties on with agonist and antagonistic properties on

D1 receptorsD1 receptors..

Because of its Because of its short half-lifeshort half-life (3.3 hours), (3.3 hours),

bromocriptine may require bromocriptine may require multiple dosingmultiple dosing

throughout the day.throughout the day.

Approximately Approximately 12 %12 % of patients are unable of patients are unable

to tolerate this medication at therapeutic to tolerate this medication at therapeutic

dosages.dosages.

The most common adverse effects The most common adverse effects are : are :

Nausea and vomiting; Nausea and vomiting; Dizziness due to postural hypotension, Dizziness due to postural hypotension, Headache, Headache, Nasal stuffiness, Nasal stuffiness, Drowsiness, Drowsiness, Fatigue, Fatigue, Abdominal pain, Abdominal pain, Leg cramps, Leg cramps,

BromocriptineBromocriptine

To minimize these symptoms the initial To minimize these symptoms the initial dose should be taken in bed and with food dose should be taken in bed and with food at nighttime. at nighttime.

Most of these reactions are mild, occur Most of these reactions are mild, occur early in the course of treatment, and are early in the course of treatment, and are transient. transient.

To reduce the adverse symptoms, the dose To reduce the adverse symptoms, the dose should be gradually increased every 1 to 2 should be gradually increased every 1 to 2 weeks until prolactin levels fall to normal. weeks until prolactin levels fall to normal.

The usual therapeutic dose is 2.5 mg twice The usual therapeutic dose is 2.5 mg twice or three times a day, but larger doses are or three times a day, but larger doses are sometimes used when a macroadenoma is sometimes used when a macroadenoma is present. present.


To minimize side effects, To minimize side effects,

bromocriptine usually is started at a bromocriptine usually is started at a

low dosage and increased gradually.low dosage and increased gradually.

Vaginal administrationVaginal administration may decrease may decrease

the incidence of side effects.the incidence of side effects.

Is the Is the preferred agentpreferred agent in patients in patients

with with hyperprolactin -induced hyperprolactin -induced

anovulatory infertilityanovulatory infertility..


The safety of The safety of fetal exposurefetal exposure to has been to has been

evaluated extensively, and this it is evaluated extensively, and this it is

not associatednot associated with increased rates of with increased rates of

spontaneous abortion, fetal malformation, spontaneous abortion, fetal malformation,

multiple pregnanciesmultiple pregnancies, or adverse effects on , or adverse effects on

postnatal development. postnatal development. (Category B ) .(Category B ) .

Bromocriptine treatment should be Bromocriptine treatment should be

discontinueddiscontinued when pregnancy is confirmed when pregnancy is confirmed

to limit fetal exposure to the to limit fetal exposure to the

medication.medication.


Drugs safety in Drugs safety in PregnancyPregnancy

FDA system for classifying drugs FDA system for classifying drugs based on potential to cause birth defects (1996)based on potential to cause birth defects (1996)

AABBCCDDEE

No RiskNo Risk

Animal: No RiskAnimal: No RiskHuman: Not AdequateHuman: Not Adequate

Animal: ToxicityAnimal: ToxicityHuman: Not AdequateHuman: Not Adequate

Human: RiskHuman: Risk

Human: Great RiskHuman: Great Risk


Cabergoline is an ergoline derivative Cabergoline is an ergoline derivative

with a with a high affinity and selectivity for high affinity and selectivity for

D2 receptors.D2 receptors.

Unlike bromocriptine, cabergoline Unlike bromocriptine, cabergoline

has has low affinity for D1 receptorslow affinity for D1 receptors..

It has a It has a half-life half-life of approximately of approximately

65 hours65 hours, allowing once- or , allowing once- or

twice-weekly dosing.twice-weekly dosing.

Cabergoline is significantly Cabergoline is significantly more more

effectiveeffective than bromocriptine in than bromocriptine in

normalizing serum prolactin levels normalizing serum prolactin levels

and restoring gonadal function. and restoring gonadal function.

It also is It also is better toleratedbetter tolerated than than

bromocriptine, particularly with bromocriptine, particularly with

regard to upper gastrointestinal regard to upper gastrointestinal

symptoms and patient compliance symptoms and patient compliance


It is much It is much more expensivemore expensive. .

It is often used in patients who It is often used in patients who

cannot tolerate the adverse effects cannot tolerate the adverse effects

of bromocriptine of bromocriptine or in those who or in those who

do do not respond to bromocriptinenot respond to bromocriptine. .


Although no detrimental effects on fetal Although no detrimental effects on fetal

outcomes have been reported in more outcomes have been reported in more

than 300 pregnant women taking than 300 pregnant women taking

cabergoline, the current cabergoline, the current

recommendation is to discontinue recommendation is to discontinue

cabergoline one month before cabergoline one month before

conception is attempted. conception is attempted. (Category (Category

B ) .B ) .


Surgical CareSurgical Care General indications for pituitary surgery General indications for pituitary surgery

include :include :

1.1. Patient drug intolerance, Patient drug intolerance,

2.2. Tumors resistant to medical therapy, Tumors resistant to medical therapy,

3.3. Persistent visual-field defects in spite of Persistent visual-field defects in spite of medical treatment, and medical treatment, and

4.4. Patients with large cystic or hemorrhagic Patients with large cystic or hemorrhagic tumors.tumors.

Trans-sphenoidal surgeryTrans-sphenoidal surgery is the conventional is the conventional procedure. procedure.

RadiotherapyRadiotherapy

Stereotactic radiosurgeryStereotactic radiosurgery has become has become

more popular because MRI allows more more popular because MRI allows more

accurate resolution and dose planning. accurate resolution and dose planning.

RadiotherapyRadiotherapy should be considered in should be considered in

patients with macroadenomas who are patients with macroadenomas who are

resistant to or intolerantresistant to or intolerant of medical of medical

therapy and in whom therapy and in whom surgery has failedsurgery has failed..

Key clinical Key clinical recommendationrecommendation

Cabergoline Cabergoline is more effective and is more effective and

better tolerated than bromocriptine.better tolerated than bromocriptine.

(Grade B)(Grade B)

Dopamine agonistsDopamine agonists are the are the

treatment of choice in most patients treatment of choice in most patients

with hyperprolactinemic disorders. with hyperprolactinemic disorders.

(Grade B)(Grade B)

Bromocriptine is the drug of choiceBromocriptine is the drug of choice when treatment is aimed at when treatment is aimed at hyperprolactin-induced hyperprolactin-induced anovulatory infertility. anovulatory infertility.

(Grade C)(Grade C) MRI MRI of the pituitary fossa should be of the pituitary fossa should be

performed if the serum prolactin level performed if the serum prolactin level is significantly elevated or if there is is significantly elevated or if there is any suspicion of a pituitary tumor. any suspicion of a pituitary tumor.

(Grade C)(Grade C)

Key clinical Key clinical recommendationrecommendation

KEY POINTSKEY POINTS EstrogenEstrogen stimulates prolactin release but stimulates prolactin release but

blocks its action at the receptor in the breast.blocks its action at the receptor in the breast.

Physiologic stimuliPhysiologic stimuli for prolactin release include for prolactin release include

breast and nipple palpation, exercise, stress, breast and nipple palpation, exercise, stress,

sleep, and the noonday meal.sleep, and the noonday meal.

The main symptoms of hyperprolactinemia are The main symptoms of hyperprolactinemia are

galactorrhea and amenorrheagalactorrhea and amenorrhea, the latter , the latter

caused by alterations in normal gonadotrophin-caused by alterations in normal gonadotrophin-

releasing hormone (GnRH) release.releasing hormone (GnRH) release.

Hyperprolactinemia is present in Hyperprolactinemia is present in

15% 15% of allof all anovulatory women anovulatory women and and

20% 20% of women withof women with

amenorrhea of undetermined causeamenorrhea of undetermined cause..

70% 70% of all women withof all women with galactorrhea have galactorrhea have

hyperprolactinemia, but almost hyperprolactinemia, but almost

90% 90% of women withof women with

galactorrhea, amenorrhea, and low galactorrhea, amenorrhea, and low

estrogen levels estrogen levels have hyperprolactinemia.have hyperprolactinemia.

KEY POINTSKEY POINTS

Pathologic causes of hyperprolactinemia Pathologic causes of hyperprolactinemia include : include :

1.1. Pharmacologic agentsPharmacologic agents (tranquilizers, (tranquilizers, narcotics, and antihypertensive drugs), narcotics, and antihypertensive drugs),

2.2. Hypothyroidism,Hypothyroidism,

3.3. Chronic renal diseaseChronic renal disease, ,

4.4. Chronic neurostimulationChronic neurostimulation of the breast, of the breast,

5.5. Hypothalamic diseaseHypothalamic disease, and , and

6.6. Pituitary tumorsPituitary tumors ( Prolactinoma, ( Prolactinoma, Acromegaly, Cushing's disease ).Acromegaly, Cushing's disease ).


About About 3% to 5%3% to 5% of individuals with of individuals with

hyperprolactinemia have hyperprolactinemia have hypothyroidismhypothyroidism..

About About 80%80% of all of all pituitary tumorspituitary tumors secrete secrete

prolactin.prolactin.

About About 25%25% of individuals with of individuals with AcromegalyAcromegaly

and and 10%10% of those with of those with Cushing's diseaseCushing's disease

have hyperprolactinemia.have hyperprolactinemia.

About About 10%10% of individuals with an enlarged of individuals with an enlarged

sella have the sella have the empty sella syndromeempty sella syndrome..


AutopsyAutopsy studies reveal that prolactinomas studies reveal that prolactinomas

are present in about are present in about 10%10% of the population. of the population.

About About 50% of women with 50% of women with

hyperprolactinemia will have a prolactinomahyperprolactinemia will have a prolactinoma, ,

as will nearly all of those with prolactin as will nearly all of those with prolactin

levels greater than 200 ng/ml.levels greater than 200 ng/ml.

About About 20%20% of women with of women with galactorrheagalactorrhea and and

35%35% of those with of those with amenorrhea and amenorrhea and

galactorrheagalactorrhea have have prolactinomas.prolactinomas.


About About 70%70% of women with of women with hyperprolactinemia, galactorrhea, and hyperprolactinemia, galactorrhea, and amenorrhea with low estrogen levelsamenorrhea with low estrogen levels will have a will have a prolactinomaprolactinoma..

Women with regular menses, Women with regular menses, galactorrhea, and normal prolactin galactorrhea, and normal prolactin levels levels do not have prolactinomasdo not have prolactinomas..

About About 13%13% of women with of women with prolactinomas do not have prolactinomas do not have galactorrhea.galactorrhea.


Most macroadenomas enlarge with Most macroadenomas enlarge with time; nearly all microadenomas do not.time; nearly all microadenomas do not.

The The initial operative cure rateinitial operative cure rate for for microadenomasmicroadenomas is about is about 80%80% and for and for macroadenomas 30%,macroadenomas 30%, but the long-term but the long-term recurrence raterecurrence rate is at least is at least 20%20% for each. for each.

Most frequent side effects of Most frequent side effects of bromocriptine are bromocriptine are orthostatic orthostatic hypotension, nausea, and vomitinghypotension, nausea, and vomiting..


In hyperprolactinemia and no In hyperprolactinemia and no macroadenomamacroadenoma, , bromocriptine bromocriptine treatment treatment returns prolactin levels to normal in returns prolactin levels to normal in 90%,90%, induces ovulatory cycles in induces ovulatory cycles in 80%,80%, and and eradicates galactorrhea in eradicates galactorrhea in 60%.60%.

After After 1 year of bromocriptine1 year of bromocriptine treatment, treatment, prolactin levels remain normal in prolactin levels remain normal in 11%11% of of women with women with microadenomas; microadenomas;

After After 2 years2 years permanent remission reaches permanent remission reaches 22%.22%.

After longer use, remissions of After longer use, remissions of 50%50% have have been reported.been reported.


BromocriptineBromocriptine shrinks 80% to 90%shrinks 80% to 90% of of macroadenomasmacroadenomas..

When pregnancy occurs in women with When pregnancy occurs in women with microadenomas, microadenomas, less than 1%less than 1% have visual have visual field changes, tumor enlargement, or field changes, tumor enlargement, or neurologic signs; about neurologic signs; about 20% of women 20% of women with macroadenomaswith macroadenomas have such adverse have such adverse changes.changes.

Pregnancy increases the likelihood that Pregnancy increases the likelihood that prolactin levels will decrease or become prolactin levels will decrease or become normal over time.normal over time.


Estrogen replacement therapy or Estrogen replacement therapy or

oral contraceptivesoral contraceptives will not will not

stimulate growth of prolactin-stimulate growth of prolactin-

secreting microadenomas and can secreting microadenomas and can

be used for therapy of be used for therapy of

hyperprolactinemia and hyperprolactinemia and

hypoestrogenism.hypoestrogenism.


Bromocriptine induction of pregnancy is Bromocriptine induction of pregnancy is

not associated with an increased risk of not associated with an increased risk of

congenital abnormalities, spontaneous congenital abnormalities, spontaneous

abortion, or multiple gestation.abortion, or multiple gestation.

About About 85%85% of patients with of patients with

prolactinomas have no change in prolactinomas have no change in

prolactin levels or tumor size after prolactin levels or tumor size after

delivery, delivery, 10% improve10% improve, and , and 5% worsen5% worsen..


The most frequent cause of The most frequent cause of mildly mildly

elevated prolactin levels is stress.elevated prolactin levels is stress.

The best modality to diagnose pituitary The best modality to diagnose pituitary

adenomas or empty sella syndrome is adenomas or empty sella syndrome is

magnetic resonance imaging (MRI).magnetic resonance imaging (MRI).

The natural history of nearly all The natural history of nearly all

microprolactinomas is to stay the same microprolactinomas is to stay the same

size, with size, with adverse menstrual problems adverse menstrual problems

resolving spontaneously in about one resolving spontaneously in about one

fourth of patients.fourth of patients.


Surgical treatmentSurgical treatment of prolactinomas is of prolactinomas is

recommended only for patients who fail recommended only for patients who fail

to respond or do not comply with medical to respond or do not comply with medical

management.management.

For women who develop side effects with For women who develop side effects with

oral bromocriptine, oral bromocriptine, vaginal administrationvaginal administration

usually alleviates the problem.usually alleviates the problem.

Cabergoline appears to be more effective Cabergoline appears to be more effective

and better tolerated than bromocriptine.and better tolerated than bromocriptine.


THANK YOUTHANK YOU

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hyper prolactinemia