HyperprolactinaemiaHyperprolactinaemiaHyperprolactinaemia.Hyperprolactinaemia.

IntroductionIntroductionIntroduction.Introduction.Prolactine (PRL) is secreted from the Prolactine (PRL) is secreted from the Anterior HypophisisAnterior HypophisisAnterior Hypophisis.Anterior Hypophisis.Normal blood level of PRL: 150Normal blood level of PRL: 150--500 IU/L500 IU/Lor 12.5 or 12.5 –– 25 ng/ml.25 ng/ml.During pregnancy,During pregnancy,→→a tenfold increase in a tenfold increase in g p g y,g p g y,serum PRL level.serum PRL level.

∗ There are at least 4 basic molecular types of PRL∗ There are at least 4 basic molecular types of PRL

hormone circulating in the normal women’s blood :

~ Little Prolactin (native PRL), MW 23 kDa.

~ Big Prolactin, MW ± 50 kDa.

~ Big-big Prolactin, MW ± 150 kDa.

~ Glycosilated Prolactin, MW 25 kDa.

DefinitionDefinitionDefinition.Definition.Hyperprolactinaemia is inapropriately Hyperprolactinaemia is inapropriately i d PRL l l i h thi d PRL l l i h thincreased PRL level occuring when the increased PRL level occuring when the woman is nonwoman is non--pregnant, and may cause pregnant, and may cause

hh l t hl t h b thb thamenorrhoeaamenorrhoea or or galactorrhoeagalactorrhoea or both.or both.

AetiologyAetiologyAetiologyAetiologyPituitary(Pituitary(Hypophisis) tumor; Hypophisis) tumor; y(y( yp p )yp p )1.Microadenoma :1.Microadenoma :<10mm diameter<10mm diameter2.Macroadenoma:>10mm diameter.2.Macroadenoma:>10mm diameter.

H th idiH th idiHypothyroidism.Hypothyroidism.Primary hypothyroidismPrimary hypothyroidism→→TRHTRH↑↑ →→ ↑↑PRL production.PRL production.

Drugs :Drugs :Drugs :Drugs :Dopamine agonist: Dopamine agonist: Phenothiazines,Butyrephenones,Phenothiazines,Butyrephenones,Benzamides,Cimetidine,MethyldopaBenzamides,Cimetidine,MethyldopaOther drugs: antidepressants,opiates,cocaine etcOther drugs: antidepressants,opiates,cocaine etc

IdiopathicIdiopathicIdiopathicIdiopathic

DiagnosisDiagnosisDiagnosisDiagnosis

The diagnosis of hyperprolactinaemia can The diagnosis of hyperprolactinaemia can be made on a single serum measurementbe made on a single serum measurementbe made on a single serum measurement.be made on a single serum measurement.A serum PRL of A serum PRL of ≥≥800 IU/L in the presence 800 IU/L in the presence f lif li hh th l i lth l i lof oligoof oligo--or amenorrhoea, or amenorrhoea, →→ pathological pathological

significance.significance.CTCT--scanning or MRI should be done to scanning or MRI should be done to exclude a hypophysis tumor.exclude a hypophysis tumor.

Mechanism of amenorrhoeaMechanism of amenorrhoeaMechanism of amenorrhoea.Mechanism of amenorrhoea.

Raised PRLRaised PRL →→ Disturbance of normalDisturbance of normalRaised PRL Raised PRL →→ Disturbance of normal Disturbance of normal hypothalamic GnRH releasehypothalamic GnRH release→→LHpulsatility LHpulsatility suppressed suppressed →→ Anovulation/Amenorrhoea.Anovulation/Amenorrhoea.Control of PRL release:Control of PRL release:

11..↑↑TRHTRH→↑→↑HypothalamusHypothalamus→→hypophysishypophysis→↑→↑PRL PRL ypyp yp p yyp p y22..↓↓DopamineDopamine→→hypophysishypophysis→↑→↑PRLPRL33..↑↑EstrogenEstrogen→→hypophysishypophysis→↑→↑PRLPRL33 ↑↑ st ogest oge →→ ypop ys sypop ys s→↑→↑44. Breast suckling. Breast suckling→↑→↑TRH….TRH….→↑→↑PRLPRL

TreatmentTreatmentTreatment.Treatment.

11 MedicamentMedicament1.1. Medicament.Medicament.a. a. BromocriptineBromocriptine;;2,5mg orally2,5mg orally 22--3 X daily 3 X daily with meals Or by vaginal administrationwith meals Or by vaginal administrationwith meals.Or by vaginal administration.with meals.Or by vaginal administration.b. b. QuinagolideQuinagolide.(A new dopamine .(A new dopamine

i t) d t l t d b tti t) d t l t d b ttagonist),once a day,tolerated better.agonist),once a day,tolerated better.c.c. CabergolineCabergoline ( a new dopamine ( a new dopamine agonist, long halfagonist, long half--life.Administered life.Administered weekly.weekly.

22 Surgical treatmentSurgical treatment22. Surgical treatment.. Surgical treatment.* Trans* Trans--sphenoidal surgery is usually sphenoidal surgery is usually done to resect both microdone to resect both micro and orand ordone to resect both microdone to resect both micro--and or and or macroadenomas.macroadenomas.

* Th lt f t t t tl* Th lt f t t t tl* The results of treatment vary greatly * The results of treatment vary greatly between centres,between centres,±±50%50%

33. Radiotherapy (very rare). Radiotherapy (very rare)

IS THERE ANY QUESTION?IS THERE ANY QUESTION?

Pituitary AdenomaPituitary AdenomaPituitary AdenomaPituitary AdenomaPituitary adenomas secreting hormones other Pituitary adenomas secreting hormones other y gy gthan prolactin may also affect menstrual than prolactin may also affect menstrual function.function.* ACTH i* ACTH i ↑↑ i li l C hi ’C hi ’* ACTH secreting tumor* ACTH secreting tumor→↑→↑cortisol cortisol →→Cushing’s Cushing’s disease.disease.* Adenoma or adenocarcinoma of the adrenal* Adenoma or adenocarcinoma of the adrenal Adenoma or adenocarcinoma of the adrenal Adenoma or adenocarcinoma of the adrenal cortex maycortex may→↑→↑cortisol.cortisol.* Ectopic production of ACTH by other tumors * Ectopic production of ACTH by other tumors ctop c p oduct o o C by ot e tu o sctop c p oduct o o C by ot e tu o ssuch as Bronchial carcinoma or carcinoid tumorssuch as Bronchial carcinoma or carcinoid tumors→↑→↑cortisol.cortisol.

CUSHING’S SYNDROMECUSHING’S SYNDROMECUSHING S SYNDROMECUSHING S SYNDROMECortisol excessCortisol excess→↑→↑protein catabolismprotein catabolism→→↑↑

pp↑↑gluconeogenesisgluconeogenesis→→conversion to fatconversion to fat→→deposition to face,neck and trunk.deposition to face,neck and trunk.Cortisol excessCortisol excess→→depression of immunedepression of immuneCortisol excessCortisol excess→→depression of immune depression of immune reaction.reaction.Cortisol excessCortisol excess→↑→↑protein catabolismprotein catabolism→→wasting of limbs.wasting of limbs.

Excess of other steroids:Excess of other steroids:Excess of other steroids:Excess of other steroids:Estrogen Estrogen →→ amenorrhoeaamenorrhoeaAndrogenAndrogen →→ mild virilismmild virilismAndrogen Androgen →→ mild virilismmild virilism

NOWNOW

PAUSEPAUSE

HYPERANDROGENEMIAHYPERANDROGENEMIAHYPERANDROGENEMIAHYPERANDROGENEMIA

Hyperandrogenemia is a condition that theHyperandrogenemia is a condition that theHyperandrogenemia is a condition that the Hyperandrogenemia is a condition that the circulating level of testosterone, dehydrocirculating level of testosterone, dehydro--testosterone and adrostenedion is hightestosterone and adrostenedion is hightestosterone and adrostenedion, is high, testosterone and adrostenedion, is high, and may stimulate the derangement of and may stimulate the derangement of physical conditionphysical conditionphysical condition.physical condition.Normal Androgen level: depends on the Normal Androgen level: depends on the phase of the menstrual cyclephase of the menstrual cyclephase of the menstrual cycle.phase of the menstrual cycle.Increase LH level Increase LH level →→ ↑↑androgen.androgen.

CLINICAL APPEARANCESCLINICAL APPEARANCESCLINICAL APPEARANCESCLINICAL APPEARANCES

PCOSPCOS isis →→ Functional derangaement ofFunctional derangaement ofPCOSPCOS is is →→ Functional derangaement of Functional derangaement of the Hypothalamothe Hypothalamo--pituitarypituitary--ovarian axis ovarian axis associated with anovulationassociated with anovulationassociated with anovulation.associated with anovulation.

→→ LH levels relatively high,FSH LH levels relatively high,FSH l l l ti l ll l l ti l llevels are relatively low.levels are relatively low.

→→ LH:FSH ratio elevated.LH:FSH ratio elevated.↑↑LH LH →↑→↑levels of Testosterone,Androstenelevels of Testosterone,Androstene

dione and DHA from Ovariumdione and DHA from Ovariumdione and DHA from Ovarium dione and DHA from Ovarium

Some of these androgensSome of these androgens→→estrone inestrone inSome of these androgensSome of these androgens→→estrone in estrone in peripheral tissuesperipheral tissuesHigh androgen levelsHigh androgen levels →→ ↓↓SHBG by 50%SHBG by 50%High androgen levels High androgen levels →→ ↓↓SHBG by 50% SHBG by 50% →↑→↑unbound,active androgensunbound,active androgens

The pathophysiology of PCOS is unknownThe pathophysiology of PCOS is unknown(Genetic element?)(Genetic element?)

Clinical features of PCOSClinical features of PCOSClinical features of PCOSClinical features of PCOS

VariableVariableVariableVariableThe classic ‘Stein Leventhal’ syndrome,:The classic ‘Stein Leventhal’ syndrome,:

* li h* li h* oligomenorrhea* oligomenorrhea* hirsutism* hirsutism* obesity* obesity* infertility* infertility infertility. infertility.

Diagnosis of PCOSDiagnosis of PCOSDiagnosis of PCOSDiagnosis of PCOS

No specific features of PCOS areNo specific features of PCOS areNo specific features of PCOS are No specific features of PCOS are diagnostic of the condition.diagnostic of the condition.→→ on clinical on clinical grounds supported by :grounds supported by :grounds supported by :grounds supported by :1.Ultrasound 1.Ultrasound →→ **follicular cysts(follicular cysts(Ø:6Ø:6--8mm)8mm)

**↑↑ i li l**↑↑ovarian volumeovarian volume( 25% of normal women)( 25% of normal women)

Eleveted LH:FSH ratio.Eleveted LH:FSH ratio.Eleveted free testosterone levelsEleveted free testosterone levelsEleveted free testosterone levels.Eleveted free testosterone levels.

2 Infertility2 Infertility→→ovulation disordersovulation disorders2. Infertility2. Infertility→→ovulation disorders.ovulation disorders.3. Amenorrhea,3. Amenorrhea,4 Ob it4 Ob it4. Obesity4. Obesity5. Hirsutism5. Hirsutism

LongLong-- term effects of PCOSterm effects of PCOSLongLong term effects of PCOSterm effects of PCOS

Increased risk of endometrial cancer(3X)Increased risk of endometrial cancer(3X)Increased risk of endometrial cancer(3X)Increased risk of endometrial cancer(3X)Increased risk of Diabetes Mellitus Increased risk of Diabetes Mellitus ((Hyperinsulinemia due to insulineHyperinsulinemia due to insuline((Hyperinsulinemia due to insuline Hyperinsulinemia due to insuline resistance)resistance)I d i k f h t i dI d i k f h t i dIncreased risk of hypertension and Increased risk of hypertension and cardiovascular disease.cardiovascular disease.

Treatment of PCOSTreatment of PCOSTreatment of PCOSTreatment of PCOSAimed at relieving symptoms and preventing Aimed at relieving symptoms and preventing g y p p gg y p p glong term effects.:long term effects.:* Infertility* Infertility →→:1. Treat cause if known eg.:1. Treat cause if known eg.↑↑PRL.PRL.

2 O l ti i d ti2 O l ti i d ti2. Ovulation induction.2. Ovulation induction.

* Amenorrhea* Amenorrhea →→:1 need contraception:1 need contraception→→ Amenorrhea Amenorrhea →→:1. need contraception:1. need contraception→→combined OC Pillscombined OC Pills

2. need no contraception2. need no contraceptionpp→→ cyclical gestogenscyclical gestogens

* Hirsutism* Hirsutism →→ 1.Local treatment1.Local treatment Hirsutism Hirsutism →→ 1.Local treatment1.Local treatment2.Medicament treatment.:2.Medicament treatment.:

* Low dose oral contraceptivwes* Low dose oral contraceptivwes Low dose oral contraceptivwes Low dose oral contraceptivwes* Medroxyprogesterone acetate* Medroxyprogesterone acetate* C t t t* C t t t* Cyproterone acetate* Cyproterone acetate* Dexamethasone* Dexamethasone* GnRH analoque (addback HRT)* GnRH analoque (addback HRT)* Etc.* Etc.

THANK YOU.THANK YOU.

OOTHANK YOUTHANK YOU