This slide is about work up of hyperprolactinemia

1. Hyperprolactinemia
충북의대 전현정

2. Regulation of prolactin secretion
Stimulatory signal
Predominant inhibitory signa
Renal clearance

3. Causes of hyperprolactinemia(1)

5. Causes of hyperprolactinemia(2)

6. Causes of hyperprolactinemia(3)

7. Incidence of hyperprolactinemia (1)
 Unselected healthy adult : 0.4 % - 5.0 %
 Among women with Amenorrhea : 9%
 Among women with galactorrhea : 25%
 Among women with amenorrhea and galactorrhea : 70%
 Among men with impotence or infertility : 5%

8. Clinical presentation of hyperprolactinemia (1)
Premenopausal women
31 < PRL < 50 g/L
 Short luteal phase
 Decreased libido
 Infertility
51 < PRL < 75 g/L
 Oligomenorrhea
100 g/L < PRL
 Hypogonadism
 Galactorrhea
 Amenorrhea
 Increased body weight – associated with prolactin-secreting tumor
 Osteopenia – patients with associated hypogonadism
 Degree of bone loss – related to duration and severity of hypogonadism

9. Clinical presentation of hyperprolactinemia (2)
Men
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Decreased libido
Impotence – unresponsive to testosterone treatment
Decreased sperm production
Infertility
Gynecomastia
Rarely galactorrhea
Decreased muscle mass
Body hair
Osteoporosis

10. Female
 Galactorrhea
 Amenorrhea
 Oligomenorrhea
 Infertility
 History of fracture
Male
 Low libido
 Impotence
 Infertility
 Gynecomastia
 Galactorrhea
 History of fracture or osteoporosis
We should check serum Prolactin level.

11. Nipple discharge
Rule out breast pathology
(by history, physical examination, mammography)
Galactorrhea

12. Step 1.
Galactorrhea
Evaluation for breast tumor
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Unilateral
Single duct
Bloody or Serosanguineous
Associated with breast mass

13. Galactorrhea
 Bilateral
Check prolactin
 Multiductal
 Milky (can be yellow, green or brown)
Milk production is in doubt
Sudan IV staining for
Fat droplet

14. Step 2.
Galactorrhea
Elevated prolactin
Check physiologic or secondary cause
1.
2.
3.
4.
5.
Pregnancy history
Medication
Recent breast / nipple manipulation
Kidney / Liver disease
Check
- Thyroid function test
- BUN/Creatinine
- hCG

15. Objectives of treatment of hyperprolactinemia
 Restoration and maintenance of normal gonadal function
 Restoration of normal fertility
 Prevention of osteoporosis

16. Drug induced hyperprolactinemia
1. Discontinuation of the medication for 3 days or
substitution of an alternative drug
followed by recheck of serum prolactin
2. PRL Level : 25 to 100 μg/L
- Metoclopramide, risperidone, phenothizines > 200 μg/L
- associated with variants of the D2 receptor gene
3. If the drug cannot be discontinued and the onset of the hyperprolactinem
does not coincide with therapy initiation
 Check Sellar MRI
4. Start Estrogen or testosterone therapy
- If the drug cannot be discontinued and the patients have hypogondal
symptoms

17. Step 3.
Galactorrhea
Elevated prolactin
1. Exclude physiologic or secondary causes
2. If, negative clinical symptoms
: evaluate macroprolactinemia
Sellar MRI
To evaluate pituitary lesion
Prolactinoma
Hypothalamic stalk interruption

18. Macroprolactinemia
Type of PRL
Size
Monomeric- PRL
23 kDa
Big-PRL
50 – 60 kDa
Big-Big PRL
150 kDa
(Macro-PRL)
Distribution
85- 95%
10%
5%
 Definition of macroprolactinemia : elevated Big-Big PRL, over 60%
 Mechanism of Elevated prolactin
① Difficult to remove due to big size via kidney
② Difficult to absorption or break down in target tissue
③ Difficult to control H-P axis feedback
 Asymptomatic

19. Step 3.
Elevated prolactin
Galactorrhea
Normal
&
Asymptomatic
Follow-up
Measurement of
Prolactin
Once yearly
Normal
&
Symptomatic
Sellar MRI
Microadenoma
&
Symptomatic
Dopamine agonist
therapy
Macroadenoma
Measure other pituitary hormones
to exclude
associated deficiency or excess

20. Objectives of treatment of hyperprolactinemia
 Restoration and maintenance of normal gonadal function
 Restoration of normal fertility
 Prevention of osteoporosis
If a pituitary tumor is present:
 Correction of visual or neurological abnormalities
 Reduction or removal of tumor mass
 Preservation of normal pituitary function
 Prevention of progression of pituitary or hypothalamic disease

21. Macro-adenoma
Measure other pituitary hormones
to exclude
associated deficiency or excess
“Hook effect”
Isolated Prolactin excess
Dopamine agonist therapy
Stalk effect (Prolactin level
not high enough for size of tumor)
Pituitary surgery recommended
Normal
Reduced
No effect on prolactin level
Prolactin level Prolactin level
After 6 months therapy
After 6 months therapy
Asymptomatic
Measure prolactin level
Every 4 – 6 months;
MRI every 1 – 2 yrs
Symptomatic
despite prolactin
reduction
Pituitary surgery

22. Hook phenomenon
 Mildly elevated prolactin level
 A Very large pituitary tumor
To distinguish
1. Large prolactinoma
2. NFPA
Dilution of sample and recheck
prolactin

23. Indications for pituitary surgery in patients with
hyperprolactinemia
 Resistance or intolerance to optimal medical therapy
 Instra-sellar tumor for whom long-term drug therapy is not acceptable
 Tumors pressing on the optic chiasm
 Surgery should be avoided in cases of extrasellar (without optic chiasm compress
because of the low success rate

24. Micro-adenoma
Normal & Symptomati
Micro & Symptomatic
c
Idiopathic hyperprolactinemia
Prolactinoma
Dopamine agonist therap
y
1) Periodic PRL check starting 1 month after therapy
2) Repeat MRI in 1 year
- if new symptoms : galactorrhea, visual disturbance, headache
other hormone disorders

26. Dopamine agonist therapy (Outcomes)
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Reduction in tumor size : 62%
Resolution of visual field defect : 67%
Resolution of amenorrhea : 78%
Resolution of infertility : 53%
Improvement of sexual function : 67%
Resolution of galactorrhea : 86%
Normalization of prolactin level : 68%

27. Micro-adenoma
Normal & Symptomati
Micro & Symptomatic
c
Dopamine agonist therapy
Normal
Prolactin level
Reduced prolactin level
After 6 months therapy
Asymptomatic
atic
Prolactin level still elevated
After 6 months therapy*
Symptom
Consider pituitary surgery
Measure prolactin level
Every 4 – 6 months

28. Dopamine agonist resistance
① A failure to achieve a normal prolactin level on maximum dose
② A failure to achieve a 50 % reduction in tumor size
③ A failure to restore fertility in patients
Bromocriptine : 25 % of patients are resistant
Cabergoline : 10 %
1. Switch to cabergoline
2. TSA
1) cannot tolerate high doses of cabergoline (11mg/week)
2) who are not responsive to dopamine agonist therapy
3. Radiotherapy
1) who fail surgical treatment

29. Dopamine agonist therapy may be tapered
 Undertaken after 2 years
who no longer have elevated serum PRL
who have no visible tumor remnant on MRI
 May be possible to discontinue therapy when menopause occ