Hyperprolactinemia

Dr Manal Behery

Hypothalamo-Pituitary-Ov-Ut Axis

CNSHypothalamus

Pituitary

Ovary

UterusOutflow tract

ProlactinCell of Origin

PRL is 199 polypeptide hormone

made by the pituitary lactotrophs.

Synthesis and metabolism

• Normal serum level= 10-25 ng/ml,

• half life =20 minutes• Metabolized in liver and

kidney

Types(isoforms)

• Little PRL:• 80-90%, MW 23000K,• non glycosylated • high receptor binding

bioactivity • full immuno-activity

Isoforms• Big PRL:• 8-20%, MW 50000K,

mixture of dimeric and trimeric forms of G-PRL

• Big-big PRL:• 1-5%, MW 100000K,• polymeric

Control of prolactin release:

• 1- Prolactin inhibiting factor (dopamine) → ↓ prolactin release.

• 2- Estrogen → ↑ prolactin release.

• 3- TRH “thyrotropin releasing hormone” → ↑ prolactin release.

– Sleep– Satiety – Stress&Exercise– Sex– Second half Menstrual cycle(luteal phase)– Suckling

If a woman's prolactin level is elevated the first time it is tested, a second sample should be checked when she is fasting and non-stressed.

Physiologic conditions

Pharmacological conditions :

• -Estrogen containing drugs/ pills.

• -Antidopaminergic drugs:

• - Tricyclic antidepressant (TCA)

• -Anti emetics → meteclopromide.

• Antihypertensives: α methyl dopa &reserpine

• Histamine H2-receptor antagonists• Stimulation of serotoninergic system Amphetamines Hallucinogens

Pathological condition

Pathological condition • 1. Pituitary:

• * Pituitary adenoma "Prolactinoma".

• * Growth H. secreting tumor.

2. Hypothalamic:

• * inhibits PIF (dopamine) secretion or access to pituitary.

• * Functional "idiopathic“

*Organic lesion: trauma, infection, tumors.

• * Psychological disturbance.

•A craniopharyngioma is a benign tumor that develops near the pituitary gland .

• most commonly in childhood and adolescence and •in later adult life.compresses the pituitary stalk or gland, the tumor can cause partial or complete pituitary hormone deficiency.

Diagrammatic representation of empty sella syndrome. A, Normal anatomic relationship. B, C, and D, Progression in development of empty sella syndrome.

Note thinning of floor and symmetric enlargement of sella turcica.

Empty sella sydrome

3. Primary hypothyroidism

• ↑ TRH → stimulates lactotrophs to ↑ prolactin secretion.

Other causes

Liver cell failure- Chronic renal failure.Chest wall disease: burn- scar- Herpes

Zoster.Ectopic secretion:Hypernephroma of

kidney. * Oat cell carcinoma of lung hyperestrogenic states e.g PCO

Pathologic conditions

• Hypothalamic lesionsCraniopharyngiomaGliomaGranulomaStalk transectionIrradiation damagePseudocysts• Pituitary tumorsCushing diseaseAcromegalyProlactinoma

• Reflex causesChest wall injuryherpes zoster neuritisUpper abdominal op• Hypothyroidism• Renal failure• Ectopic pdoductionBronchogenic carcinomaHypernephroma

(endocannabinoids)

How prolactin act?

A- Inhibition of pulsatile GnRH secretion

1- Hyperprolactinemia inhibit GnRH activity by interacting with hypothalamic DA and opioid system via the short-loop feedback mechanism.

CNS-hypothalamus-pituitaryovary-uterus interaction

Neural control Chemical control

Dopamine (-)

Norepinephrine (+)

Endorphins (-)

Hypothalamus

GnRH

Ant. pituitary

FS, LHH

Ovaries

Uterus

ProgesteroneEstrogen

Menses

–± ?

B. Interference with gonadotrophin action in ovary

2-Decreased ovarian sensitivity to pituitary gonadotropin

C-Inhibition of FSH-directed ovarian aromatase

• 3-impaired follicular development

D- Inhibition of progesterone synthesis

4-Impaired ovarian strediogensis

Clinical Manifestation

• 1- Galactorrhea: Only in 30- 60 % of cases of hyperprolactinemia due to :

• 2- Infertility: due to:- Anovulation luteal phase defect

• 3- Oligohypomenorrhea , even amenorrhea

• 4- Hirsutism due to decreased SHBG.

• 5 -Decreased libido &osteoporosis

Diagnosis

1- History:

• of a cause( Drug intake,thyroid,renal...)

• of a symptom (galactorrhea,menstrual problem, ...).

2- Examination

• - Visual field defect → pituitary adenoma.

• - Thyroid → goiter.

• - Breast → examined for galactorrhea.

• - Chest wall → burn, scar.

1- Prolactin level:

• > 100 ng / ml → suggestive of adenoma.

• > 300 ng/ ml → diagnostic of adenoma.

• > 2000 ng/ ml→cavernous sinus invasion.

2- MRI brain:

• - Detect all macroadenoma (> 1cm).

• - Detect 70% of microadenoma(<1cm).

• 3- Thyroid function tests.

• 4- Others : - Liver function test. - Kidney function test.

Treatment of the cause

• - Treatment of hypothyroidism (thyroxine).

• -stop drugs causing hyperprolactinemia.

• -PCO,Liver,renal,.....

2- Dopamine agonists:

• Acts on D2 receptors but also D1,Alpha adrenergic.

• 1. Bromocreptine (parlodel): tablet = 2.5 mg oral or even vaginal.- start with ½ tablet → ↑ gradually ,better during meals.

• - Side effects1- Nausea & vomiting.

• 2- Postural hypotension.3- Headache.

• 4- Abdominal cramps.

. Lisuride (dopergine):

• More potent. - Less side effects.

3. Cabergoline (dostinex):

• Selective D2 Agonist tablet 0.5 mg

• - Long acting.

• - More potent.

• - Less side effects

. Quinagolid (norprolac):

• non-ergot preparation (D2 receptors),

• less side effects

3- Trans-sphenoid surgery:

• For Pituitary adenoma only if :

• - No response to medical ttt.

• - Causing visual field defect.

• - TTT is not tolerable.