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Hyperprolactinemia
Dr Manal Behery
Hypothalamo-Pituitary-Ov-Ut Axis
CNS
Hypothalamus
Pituitary
Ovary
Uterus
Outflow tract
Prolactin
Cell 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 de
ficiency.
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 lesions
Craniopharyngioma
Glioma
Granuloma
Stalk transection
Irradiation damage
Pseudocysts
• Pituitary tumors
Cushing disease
Acromegaly
Prolactinoma
• Reflex causes
Chest wall injury
herpes zoster neuritis
Upper abdominal op
• Hypothyroidism
• Renal failure
• Ectopic pdoduction
Bronchogenic carcinoma
Hypernephroma
(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-pituitary
ovary-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.
Hyperprolactinema for undergraduate

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Hyperprolactinema for undergraduate

  • 3. Prolactin Cell of Origin PRL is 199 polypeptide hormone made by the pituitary lactotrophs.
  • 4. Synthesis and metabolism • Normal serum level= 10- 25 ng/ml, • half life =20 minutes • Metabolized in liver and kidney
  • 5. Types(isoforms) • Little PRL: • 80-90%, MW 23000K, • non glycosylated • high receptor binding bioactivity • full immuno-activity
  • 6. Isoforms • Big PRL: • 8-20%, MW 50000K, mixture of dimeric and trimeric forms of G-PRL • Big-big PRL: • 1-5%, MW 100000K, • polymeric
  • 7. Control of prolactin release: • 1- Prolactin inhibiting factor (dopamine) → ↓ prolactin release. • 2- Estrogen → ↑ prolactin release. • 3- TRH “thyrotropin releasing hormone” → ↑ prolactin release.
  • 8. – 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
  • 9. 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
  • 11. Pathological condition • 1. Pituitary: • * Pituitary adenoma "Prolactinoma". • * Growth H. secreting tumor.
  • 12. 2. Hypothalamic: • * inhibits PIF (dopamine) secretion or access to pituitary. • * Functional "idiopathic“ *Organic lesion: trauma, infection, tumors. • * Psychological disturbance.
  • 13. •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 de ficiency.
  • 14. 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
  • 15. 3. Primary hypothyroidism • ↑ TRH → stimulates lactotrophs to ↑ prolactin secretion.
  • 16. 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
  • 17. Pathologic conditions • Hypothalamic lesions Craniopharyngioma Glioma Granuloma Stalk transection Irradiation damage Pseudocysts • Pituitary tumors Cushing disease Acromegaly Prolactinoma • Reflex causes Chest wall injury herpes zoster neuritis Upper abdominal op • Hypothyroidism • Renal failure • Ectopic pdoduction Bronchogenic carcinoma Hypernephroma
  • 20. 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.
  • 21. CNS-hypothalamus-pituitary ovary-uterus interaction Neural control Chemical control Dopamine (-) Norepinephrine (+) Endorphins (-) Hypothalamus GnRH Ant. pituitary FS, LHH Ovaries Uterus ProgesteroneEstrogen Menses –± ?
  • 22. B. Interference with gonadotrophin action in ovary 2-Decreased ovarian sensitivity to pituitary gonadotropin
  • 23. C-Inhibition of FSH-directed ovarian aromatase • 3-impaired follicular development
  • 24. D- Inhibition of progesterone synthesis 4-Impaired ovarian strediogensis
  • 25. 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
  • 27. 1- History: • of a cause( Drug intake,thyroid,renal...) • of a symptom (galactorrhea,menstrual problem, ...).
  • 28. 2- Examination • - Visual field defect → pituitary adenoma. • - Thyroid → goiter. • - Breast → examined for galactorrhea. • - Chest wall → burn, scar.
  • 29. 1- Prolactin level: • > 100 ng / ml → suggestive of adenoma. • > 300 ng/ ml → diagnostic of adenoma. • > 2000 ng/ ml→cavernous sinus invasion.
  • 30. 2- MRI brain: • - Detect all macroadenoma (> 1cm). • - Detect 70% of microadenoma(<1cm).
  • 31. • 3- Thyroid function tests. • 4- Others : - Liver function test. - Kidney function test.
  • 32. Treatment of the cause • - Treatment of hypothyroidism (thyroxine). • -stop drugs causing hyperprolactinemia. • -PCO,Liver,renal,.....
  • 33. 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.
  • 34. . Lisuride (dopergine): • More potent. - Less side effects.
  • 35. 3. Cabergoline (dostinex): • Selective D2 Agonist tablet 0.5 mg • - Long acting. • - More potent. • - Less side effects
  • 36. . Quinagolid (norprolac): • non-ergot preparation (D2 receptors), • less side effects
  • 37. 3- Trans-sphenoid surgery: • For Pituitary adenoma only if : • - No response to medical ttt. • - Causing visual field defect. • - TTT is not tolerable.