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Prolactinom
  Dr. Mohmmed AL jaberi
         09/05/2012
Outlines
   Intorductions
   Epidemiology
   Clinical Manifestations
   Diagnosis
   Treatment
   Follow Up
   Summary
Introductions
•    Prolactin (PRL) is a polypeptide protein hormone
    secreted by the lactotroph cells in the anterior pituitary
    gland .


•    Suppressed by hypothalamic dopamine to act on
    Lactotroph D2 receptors .

• Prolactin (PRL) is the hormone act as stimulation &
  maintenance of milk production in the breast .
Prolactin Regulation
Epidemiology
•   Most common functional pituitary adenomas .
•   Prolactinoma account for 40 % of pituitary tumor .
•   Microprolactinomas are more frequent in women .
•   Macroprolactinomas are more frequent in men .
•   Gender : femal more than male 10 :1
•   Age : 20-50 years .
•    Some growth hormone producing tumors also
    cosecrete PRL
Clinical Manifestations
• Hormonal Effect :
 • Women : infertility, oligomenorrhea, amenorrhea or
                     rarely galactorrhea .
•   Men : decreased libido, impotence, infertility,
           gynecomastia, or rarely galactorrhea .
Clinical Manifestations
• Mss Effect :     headache ,CSF rhinorrhea ,
 compression of optic chiasma & cranial nerve .
Diagnosis
• Clinically : by excluded          2o cause of HPRL .

(A) Physiological ( pregnancy ,stress ,nipple suckle )
(B) Hypothalamic - pituitary disease ( tumor, trauma, infiltrative )
(C) Others : hypothyroidism, chest injury, CRF .
(D) Drugs .
Drugs
  Antihypertensive agents                   Antipsychotics agent
Methyldopa (Aldomet)                     Phenothiazine drugs
Reserpine (Hydromox, Serpasil,           Haloperidol (Haldol)
others)
                                         Risperidone (Risperdal)
Verapamil (Calan, Isoptin)

                       Gastrointestinal drugs
           Cimetidine (Antiacid)
           Metoclopramide (Antaemetic)


  Antidepressant agents                             Opiates
  Clomipramine (Anafranil)               Codeine
  Desipramine (Norpramin)                Morphine
• Biochemical : by serum PRL
  concentration
* Normal range for serum prolactin is 5 - 20 ng/mL .
* Serum prolactin values above 200 ng/mL usually
  indicate the presence of a lactotroph adenoma

• Hook effect : can be observed in macroprolactinomas.
 the extremely high PRL levels cause antibody saturation , the
   resulting in an artifactually low reported value .
This can be eliminated by dilution of serum samples.

* Other s: FSH ,LH ,GH ,TSH, FT4 , RFT, LFT .
Ranges of serum prolactin concentrations in
   several causes of hyperprolactinemia
• Imaging : MRI Of Head
* Should be performed in a patient with any degree of
  hyperprolactinemia to look for a mass lesion in the
  hypothalamic-pituitary region .
Treatment
* The indications for treatment :
1) Neurologic symptoms .
2) Hypogonadism or other symptoms .


* The corner stone treatment of prolactinomas are
   medical treatment .
1) DOPAMINE AGONISTS
 Dopamine agonists decrease prolactin secretion and
 reduce the size of the lactotroph adenoma in more than
 90 % of patients.
 Decrease symptoms within days .
 Decrease in serum prolactin within 2-3 weeks .
 Decrease in size within 6 weeks ... ( 6 month ) .
1) DOPAMINE AGONISTS
 Bromocriptine : It was given at least twice a day .
                   1.25 -2.5 mg PO at bedtime or with dinner.
                    ( max. 15 mg / d )
 Cabergoline : administered once or twice a week .
                   0.25 mg twice /wk or 0.5 mg once/wk .

 Adverse effects :      Common                   Less common
                      Nausea                   Nasal stuffiness,
                      Postural                 Depression, Raynaud
                      hypotension              phenomenon, Constipation
                      Mental fogginess
                      valvular heart disease
1) DOPAMINE AGONISTS
In a multicenter, randomized, 24-week trial conducted in
459 hyperprolactinemic women *
                                  Cabergoline                           Bromocriptin
    Normal PRL                       83%                                   59%
    Pregnancies                      72%                                   52%
    (Ovulation)
    Stopped S/E                             3%                                   12%

  *  Webster J, Piscitelli G, Polli A, et al.A comparison of cabergoline and bromocriptine in the treatment of

 hyperprolactinemic amenorrhea. Cabergoline comparative Study Group.N Engl J Med 1994;331(14):904–9          .
Dopamine agonist drugs lower serum prolactin
      concentrations in prolactinoma
2)TRANSSPHENOIDAL SURGERY
* The indications for surgery :
1) Patients who do not respond to medical treatment or
   those who show progression after an initial response to
   medical treatment .
2) Women who have a microadenoma, desire pregnancy,
   and cannot tolerate medical treatment.
3) RADIATION THERAPY
* The indications for radiation :
 radiation is primarily used to prevent regrowth of
  residual tumor in a patient with a very large
  macroadenoma after transsphenoidal debulking .
4) ORAL CONTRACEPTIVE
* The indications for Estrogen- progestin :
 can be considered as therapy in women with
 symptomatic microprolactinomas IF :
   women cannot tolerate or
   do not respond to dopamine agonists or
   do not want to become pregnant.
Follow Up
*    After one month of therapy, the patient should be
    evaluated for side effects and serum prolactin should be
    measured , So :
 If the serum PRL is normal and no S/E So,
 (continued).
 If the serum PRL not decreased to normal but no S/E ,
 the dose should be increased gradually to as much as
 1.5 mg of Cabergoline 2 or 3 times / week or 5 mg of
 Bromocriptine 2 times / day. Whatever dose results in a
 normal serum prolactin value should be continued
 If the prolactin has been normal for two or more years and no
    adenoma is seen on MRI So, discontinuation of the drug .
SUMMRAY
• Most common functional pituitary adenomas
• Most frequently in women with gender ratio of 10:1.
• Diagnosis clinically, biochemically & imaging .
• Macroadenoma with low PRL levels ( hook effect) .
• MRI should be performed to confirm the diagnosis .
• Medical therapy with DA is the treatment of choice .
• Cabergoline is the first-line treatment
• Transsphenoidal surgery remains an option when
  medical therapy is ineffective .
• Radiotherapy represents the last option .
Thank You
Prolactinoma

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Prolactinoma

  • 1. Prolactinom Dr. Mohmmed AL jaberi 09/05/2012
  • 2. Outlines  Intorductions  Epidemiology  Clinical Manifestations  Diagnosis  Treatment  Follow Up  Summary
  • 3. Introductions • Prolactin (PRL) is a polypeptide protein hormone secreted by the lactotroph cells in the anterior pituitary gland . • Suppressed by hypothalamic dopamine to act on Lactotroph D2 receptors . • Prolactin (PRL) is the hormone act as stimulation & maintenance of milk production in the breast .
  • 5. Epidemiology • Most common functional pituitary adenomas . • Prolactinoma account for 40 % of pituitary tumor . • Microprolactinomas are more frequent in women . • Macroprolactinomas are more frequent in men . • Gender : femal more than male 10 :1 • Age : 20-50 years . • Some growth hormone producing tumors also cosecrete PRL
  • 6. Clinical Manifestations • Hormonal Effect : • Women : infertility, oligomenorrhea, amenorrhea or rarely galactorrhea . • Men : decreased libido, impotence, infertility, gynecomastia, or rarely galactorrhea .
  • 7. Clinical Manifestations • Mss Effect : headache ,CSF rhinorrhea , compression of optic chiasma & cranial nerve .
  • 8. Diagnosis • Clinically : by excluded 2o cause of HPRL . (A) Physiological ( pregnancy ,stress ,nipple suckle ) (B) Hypothalamic - pituitary disease ( tumor, trauma, infiltrative ) (C) Others : hypothyroidism, chest injury, CRF . (D) Drugs .
  • 9. Drugs Antihypertensive agents Antipsychotics agent Methyldopa (Aldomet) Phenothiazine drugs Reserpine (Hydromox, Serpasil, Haloperidol (Haldol) others) Risperidone (Risperdal) Verapamil (Calan, Isoptin) Gastrointestinal drugs Cimetidine (Antiacid) Metoclopramide (Antaemetic) Antidepressant agents Opiates Clomipramine (Anafranil) Codeine Desipramine (Norpramin) Morphine
  • 10. • Biochemical : by serum PRL concentration * Normal range for serum prolactin is 5 - 20 ng/mL . * Serum prolactin values above 200 ng/mL usually indicate the presence of a lactotroph adenoma • Hook effect : can be observed in macroprolactinomas. the extremely high PRL levels cause antibody saturation , the resulting in an artifactually low reported value . This can be eliminated by dilution of serum samples. * Other s: FSH ,LH ,GH ,TSH, FT4 , RFT, LFT .
  • 11. Ranges of serum prolactin concentrations in several causes of hyperprolactinemia
  • 12. • Imaging : MRI Of Head * Should be performed in a patient with any degree of hyperprolactinemia to look for a mass lesion in the hypothalamic-pituitary region .
  • 13. Treatment * The indications for treatment : 1) Neurologic symptoms . 2) Hypogonadism or other symptoms . * The corner stone treatment of prolactinomas are medical treatment .
  • 14. 1) DOPAMINE AGONISTS  Dopamine agonists decrease prolactin secretion and reduce the size of the lactotroph adenoma in more than 90 % of patients.  Decrease symptoms within days .  Decrease in serum prolactin within 2-3 weeks .  Decrease in size within 6 weeks ... ( 6 month ) .
  • 15. 1) DOPAMINE AGONISTS  Bromocriptine : It was given at least twice a day . 1.25 -2.5 mg PO at bedtime or with dinner. ( max. 15 mg / d )  Cabergoline : administered once or twice a week . 0.25 mg twice /wk or 0.5 mg once/wk .  Adverse effects : Common Less common Nausea Nasal stuffiness, Postural Depression, Raynaud hypotension phenomenon, Constipation Mental fogginess valvular heart disease
  • 16. 1) DOPAMINE AGONISTS In a multicenter, randomized, 24-week trial conducted in 459 hyperprolactinemic women * Cabergoline Bromocriptin Normal PRL 83% 59% Pregnancies 72% 52% (Ovulation) Stopped S/E 3% 12% * Webster J, Piscitelli G, Polli A, et al.A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline comparative Study Group.N Engl J Med 1994;331(14):904–9 .
  • 17. Dopamine agonist drugs lower serum prolactin concentrations in prolactinoma
  • 18. 2)TRANSSPHENOIDAL SURGERY * The indications for surgery : 1) Patients who do not respond to medical treatment or those who show progression after an initial response to medical treatment . 2) Women who have a microadenoma, desire pregnancy, and cannot tolerate medical treatment.
  • 19. 3) RADIATION THERAPY * The indications for radiation : radiation is primarily used to prevent regrowth of residual tumor in a patient with a very large macroadenoma after transsphenoidal debulking .
  • 20. 4) ORAL CONTRACEPTIVE * The indications for Estrogen- progestin : can be considered as therapy in women with symptomatic microprolactinomas IF :  women cannot tolerate or  do not respond to dopamine agonists or  do not want to become pregnant.
  • 21. Follow Up * After one month of therapy, the patient should be evaluated for side effects and serum prolactin should be measured , So :  If the serum PRL is normal and no S/E So, (continued).  If the serum PRL not decreased to normal but no S/E , the dose should be increased gradually to as much as 1.5 mg of Cabergoline 2 or 3 times / week or 5 mg of Bromocriptine 2 times / day. Whatever dose results in a normal serum prolactin value should be continued  If the prolactin has been normal for two or more years and no adenoma is seen on MRI So, discontinuation of the drug .
  • 22. SUMMRAY • Most common functional pituitary adenomas • Most frequently in women with gender ratio of 10:1. • Diagnosis clinically, biochemically & imaging . • Macroadenoma with low PRL levels ( hook effect) . • MRI should be performed to confirm the diagnosis . • Medical therapy with DA is the treatment of choice . • Cabergoline is the first-line treatment • Transsphenoidal surgery remains an option when medical therapy is ineffective . • Radiotherapy represents the last option .