Pituitary tumor in Pituitary tumor in pregnancy pregnancy

報告者：報告者： R1 R1 張嘉珮張嘉珮指導教師：楊明智 醫師指導教師：楊明智 醫師日期：日期： 980227980227

In pregnancy the normal pituitary In pregnancy the normal pituitary

gland gland enlargesenlarges. This is mainly due to . This is mainly due to

an increase in the number and size of an increase in the number and size of

the the lactotrophic cells.lactotrophic cells.

This increase in pituitary size does This increase in pituitary size does not not

result in visual field changesresult in visual field changes

Several distinct typesSeveral distinct types of tumors of tumors can occur in the pituitary gland. can occur in the pituitary gland.

Pituitary adenomasPituitary adenomas derived from derived from adenohypophyseal cells are the adenohypophyseal cells are the most commonmost common in pregnancy. in pregnancy.

Lactotroph adenoma Lactotroph adenoma (Pituitary adenoma) (Pituitary adenoma) during pregnancy during pregnancy

Pituitary adenomas are often Pituitary adenomas are often classified on the basis of classified on the basis of sizesize – Microadenomas < 10mm in diameterMicroadenomas < 10mm in diameter– Macroadenomas > 10mm in Macroadenomas > 10mm in

diameter diameter The risks to the motherThe risks to the mother

– adenoma adenoma sizesize The potential risks to the fetusThe potential risks to the fetus

– treatmenttreatmentGonzalez, JG, Elizondo, G, Saldivar, D, Nanez, H. Pituitary gland growth during normal pregnancy: an in vivo study using magnetic resonance imaging. Am J Med 1988; 85:217.

Risks to the mother Risks to the mother

Increase in adenoma size cause Increase in adenoma size cause

neurologic symptoms, most importantly neurologic symptoms, most importantly

visual impairmentvisual impairment

Theoretical basis -- Theoretical basis -- hyper-estrogenemiahyper-estrogenemia

causes lactotroph hyperplasiacauses lactotroph hyperplasia

Microadenomas Microadenomas

The risk of a clinically important The risk of a clinically important increase in the size of a increase in the size of a lactotroph microadenoma during lactotroph microadenoma during pregnancy is pregnancy is smallsmall

Macroadenomas Macroadenomas

The outcome is substantially The outcome is substantially worseworse in in women with macroadenomas women with macroadenomas

In a 1979 survey, 46 women with In a 1979 survey, 46 women with lactotroph macroadenomas were lactotroph macroadenomas were followed during 56 pregnancies. followed during 56 pregnancies. Symptoms occurred in 20 (36 percent): Symptoms occurred in 20 (36 percent): – headacheheadache : 5 : 5– headache and visual impairment :headache and visual impairment : 1414– diabetes insipidusdiabetes insipidus : 1: 1

Gemzell, C, Wang, CF. Outcome of pregnancy in women with pituitary adenoma. Fertil Steril 1979; 31:363.

Potential risks to the Potential risks to the fetus fetus

One potential risk to the fetus results One potential risk to the fetus results

from from dopamine agonistdopamine agonist treatment of treatment of

hyperprolactinemia in order to permit hyperprolactinemia in order to permit

ovulation and thereby conception ovulation and thereby conception

spontaneous abortions spontaneous abortions , , extrauterine extrauterine

pregnanciespregnancies, and , and minor or major minor or major

malformations malformations

Ricci, E, Parazzini, F, Motta, T, et al. Pregnancy outcome after cabergoline treatment in early weeks of gestation. Reprod Toxicol 2002; 16:791.

TREATMENT DURING TREATMENT DURING PREGNANCY PREGNANCY

When a dopamine agonist is needed to When a dopamine agonist is needed to

lower the serum prolactin lower the serum prolactin

concentration to permit ovulation, we concentration to permit ovulation, we

recommend recommend bromocriptinebromocriptine rather than rather than

cabergolinecabergoline, because of the greater , because of the greater

certainty that it does not cause birth certainty that it does not cause birth

defects defects Casanueva, FF, Molitch, ME, Schlechte, JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf) 2006; 65:265.

Early administration Early administration does not harmdoes not harm Bromocriptine during the Bromocriptine during the first monthfirst month of of

pregnancy does not harm -- sufficient data pregnancy does not harm -- sufficient data

are available are available

however, however, insufficient datainsufficient data are available about are available about

the use of bromocriptine the use of bromocriptine laterlater in pregnancy in pregnancy

Schade, R, Andersohn, F, Suissa, S, et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007; 356:29.

Microadenomas (1) Microadenomas (1)

Risk is very Risk is very smallsmall

Should not be a deterrent to becoming pregnant Should not be a deterrent to becoming pregnant

Bromocriptine or cabergoline will likely be Bromocriptine or cabergoline will likely be

effective effective

Should be given bromocriptine or cabergoline Should be given bromocriptine or cabergoline

before pregnancy in before pregnancy in whatever dosagewhatever dosage is is

necessary necessary

Bromocriptine should be discontinued as soon as Bromocriptine should be discontinued as soon as

pregnancy has been confirmed pregnancy has been confirmed

Turkalj, I, Braun, P, Krupp, P. Surveillance of bromocriptine in pregnancy. JAMA 1982; 247: 1589

Microadenomas (2)Microadenomas (2)

During the pregnancy, the woman should be During the pregnancy, the woman should be

seen seen every three monthsevery three months and asked about and asked about

headaches and changes in vision. headaches and changes in vision.

If no symptoms occur, serum prolactin can If no symptoms occur, serum prolactin can

be measured be measured two months after delivery or two months after delivery or

cessation of nursingcessation of nursing, and if it is similar to the , and if it is similar to the

pretreatment value, the drug can be pretreatment value, the drug can be

resumed. resumed.

Macroadenomas (1)Macroadenomas (1)

Relatively Relatively higherhigher risk of clinically important risk of clinically important

tumor enlargement during pregnancy tumor enlargement during pregnancy

If the adenoma If the adenoma does not elevate the optic does not elevate the optic

chiasmchiasm, treatment with bromocriptine or , treatment with bromocriptine or

cabergoline should reduce the chance of cabergoline should reduce the chance of

enlargement during pregnancy enlargement during pregnancy

Ahmed, M, Al-Dossary, E, Woodhouse, NJY. Macroprolactinomas with suprasellar extension: effect of bromocriptine withdrawal during one or more pregnancies. Fertil Steril 1992; 58:492.

Macroadenomas (2)Macroadenomas (2)

Once adenoma has shrinkedOnce adenoma has shrinked, the woman can , the woman can

attempt to become pregnant; the dopamine attempt to become pregnant; the dopamine

agonist should be discontinued when agonist should be discontinued when

pregnancy has been confirmed. pregnancy has been confirmed.

Monitoring during pregnancyMonitoring during pregnancy should be should be

similar to that described above for women similar to that described above for women

with microadenomas with microadenomas

If the adenoma has If the adenoma has enlarged enlarged to a degree that to a degree that

could account for the symptoms, the woman could account for the symptoms, the woman

should be treated with bromocriptine should be treated with bromocriptine

throughout the remainder of the pregnancy.throughout the remainder of the pregnancy.

Konopka, P, Raymond, JP, Merceron, RE, Seneze, J. Continuous administration of bromocriptine in the prevention of neurological complications in pregnant women with prolactinomas. Am J Obstet Gynecol 1983; 146:935.

If the adenoma does not respond to If the adenoma does not respond to

bromocriptinebromocriptine, cabergoline may be , cabergoline may be

successful successful

If If cabergolinecabergoline is not successful, is not successful,

transsphenoidaltranssphenoidal surgerysurgery could be considered could be considered

Liu, C, Tyrrell, JB. Successful treatment of a large macroprolactinoma with cabergoline during pregnancy. Pituitary 2001; 4:179.

Surgery for persistent visual symptoms in the Surgery for persistent visual symptoms in the

third trimesterthird trimester should be should be deferreddeferred until until

delivery if possible delivery if possible

If the adenoma is very large or elevates the If the adenoma is very large or elevates the

optic chiasm, optic chiasm, pregnancy should be strongly pregnancy should be strongly

discourageddiscouraged until the adenoma has been until the adenoma has been

treated by transsphenoidal surgery treated by transsphenoidal surgery

ssummaryummary

A perceived a change in visionA perceived a change in vision should be should be

assessed by a neuroophthalmologist assessed by a neuroophthalmologist

MRI MRI should be performed if an abnormality should be performed if an abnormality

consistent with a pituitary adenoma is consistent with a pituitary adenoma is

confirmed. confirmed.

Pregnancy should also be discouraged in a Pregnancy should also be discouraged in a

woman whose woman whose macroadenoma is macroadenoma is

unresponsiveunresponsive to bromocriptine and to bromocriptine and

cabergoline, even if it is not elevating the cabergoline, even if it is not elevating the

optic chiasm, until the size has been greatly optic chiasm, until the size has been greatly

reduced by transsphenoidal surgery, because reduced by transsphenoidal surgery, because

medical treatment would not likely be medical treatment would not likely be

effective if the adenoma enlarges during effective if the adenoma enlarges during

pregnancypregnancy..

Breast feedingBreast feeding

NotNot increase the risk of lactotroph adenoma increase the risk of lactotroph adenoma

growth growth

Dopamine agonist treatment should be Dopamine agonist treatment should be

withheldwithheld until breastfeeding is completed. until breastfeeding is completed.

Breastfeeding is contraindicated in women Breastfeeding is contraindicated in women

who have neurologic symptomswho have neurologic symptoms at the time of at the time of

delivery (suggesting tumor growth), because delivery (suggesting tumor growth), because

they should be treated with a dopamine they should be treated with a dopamine

agonist.agonist.

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