This document discusses hyperprolactinemia, including its causes, clinical manifestations, diagnosis, and treatment. Prolactin is a hormone produced by the pituitary gland that regulates lactation. Hyperprolactinemia can be caused by physiological conditions like pregnancy or pathological conditions like pituitary adenomas. Common symptoms include galactorrhea, infertility, and menstrual irregularities. Diagnosis involves measuring prolactin levels and imaging tests. Treatment focuses on addressing the underlying cause, such as using dopamine agonists to reduce prolactin levels or surgery to remove pituitary tumors.

1. Hyperprolactinemia
Dr Manal Behery
Professor OB&GYNE ZAGAZIG University
2014

2. Hypothalamo-Pituitary-Ov-Ut Axis
CNS
Hypothalamus
Pituitary
Ovary
Uterus
Outflow tract

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. Prolactin bioactivity and immunoreactivity

8. 1- Prolactin inhibiting factor (dopamine) → ↓ prolactin
release.
2- Estrogen → ↑ prolactin release.
3- TRH “thyrotropin releasing hormone” → ↑ prolactin
release.
Estrogen
Dopamine
TRH
Control of prolactin release:

9. How does prolactin act?

10. 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.

11. CNS-hypothalamus-pituitary
ovary-uterus interaction
Neural control Chemical control
Dopamine
(-)
Norepinephrine
(+)
Endorphins
(-)
Hypothalamus
GnRH
Ant. pituitary
FS, LHH
Ovaries
Uterus
ProgesteroneEstrogen
Menses
–± ?

12. B. Interference with gonadotrophin action in ovary
2-Decreased ovarian sensitivity to pituitary
gonadotropin

13. C-Inhibition of FSH-directed ovarian
aromatase
• 3-impaired follicular development

14. D- Inhibition of progesterone synthesis
4-Impaired ovarian strediogensis

15. Causes of hyperprolactinemia

16. – 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

17. 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

18. Pathological condition

19. 1. Pituitary:
• * Pituitary adenoma
"Prolactinoma".
• * Growth H. secreting
tumor.

20. 2. Hypothalamic:
• * A craniopharyngioma is a benign tumor that
develops near the pituitary gland inhibits PIF
(dopamine) secretion or access to pituitary.
• Emty sella syndrome
*Organic lesion: trauma, infection, tumors
.
• * Psychological disturbance.

21. 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

22. 3. Primary hypothyroidism
• ↑ TRH → stimulates lactotrophs to ↑
prolactin secretion.

23. 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

25. Clinical Manifestation
• 1- Galactorrhea: Only in 30- 60 % of cases
• 2- Infertility: due to:- Anovulation luteal phase
defect
• 3- Oligohypomenorrhea , even amenorrhea
• 4- Hirsutism due to decreased SHBG.
• 5 -Decreased libido &osteoporosis

26. Diagnosis

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.