Management of prolactinoma during pregnancy

Lactotroph adenomas (prolactinomas) usually cause infertility because of: the inhibitory effect of elevated prolactin sometimes because of the mass effect of a macroadenoma on gonadotropin secretion, resulting in anovulation and decreased estradiol and progesterone secretion

However, our ability to treat both of these abnormalities allows most women with this disorder to become pregnant.

Effect of pregnancy on tumor size

The pituitary gland undergoes global hyperplasia during pregnancy The pituitary gland undergoes global hyperplasia during pregnancy. a physiologic doubling occurs in the volume of a normal pituitary gland.

The placental estrogen surge during pregnancy has been shown to induce the mitotic activity of lactotrophic cells as well as synthesis of prolactin. So, prolactin levels increase by 10-fold during this period.

Tumour cells in patients with prolactinoma express estrogen receptors . The risk that the increase in size of a lactotroph adenoma will be clinically important depends upon the size of the adenoma before pregnancy.

The principal risk during pregnancy to a mother with a lactotroph adenoma is an increase in adenoma size sufficient to cause neurologic symptoms, most importantly visual impairment.

For a microadenoma (tumor less than 10 mm in diameter) the risk is small. Tumor progression rates of 1-5% carries a low risk for neurologic complications (1%).

The risk is substantially higher in women with macroadenomas (tumors ≥10 mm in diameter) tumor enlargement (15-35%)

Management

Before pregnancy   Management of women with lactotroph adenomas should begin before conception with advice to the woman and her partner about the potential risks of pregnancy to her and the fetus.

Before pregnancy   The main concern for the mother is adenoma growth, while the potential risk for the fetus is exposure to dopamine agonists.

Awoman who has a microadenoma

  should be told that the risk of clinically important enlargement of her adenoma during pregnancy is very small , and that it should not be a deterrent to becoming pregnant. She should also be told that in the unlikely event that symptoms due to growth of the adenoma do occur during pregnancy

 bromocriptine or cabergoline would likely be effective in reducing adenoma size. If she is willing to take this very low risk, she should be given bromocriptine or cabergoline before pregnancy in whatever dose is necessary to lower her serum prolactin concentration to normal.

When the serum prolactin concentration is normal and menses have occurred regularly for a few months, the woman can attempt to become pregnant.

the patient is advised to use mechanical (barrier) methods of contraception until her menstrual cycles resume and the first few cycles have occurred, so that accurate dating of pregnancy can be performed

When the first menstrual period is missed and a pregnancy test is positive, we recommend the discontinuation of bromocriptine to prevent fetal exposure

Current data suggest that bromocriptine or cabergoline use during the first month of pregnancy (eg, ovulation induction) does not harm the fetus

increased rates of spontaneous abortion, ectopic pregnancy, or teratogenic effects have not been reported with BEC therapy.

However, few data are available about the risk of either drug later in pregnancy.

During the pregnancy

Discontinue dopamine-agonist therapy The woman should be seen every three months and asked about headaches and changes in vision If not previously done, arrange for baseline Goldman visual field perimetry and repeat every 2 months during pregnancy

Monitoring of patients with serial gross visual field examinations and funduscopic examination is recommended If New-onset headaches, or change in visual perimetry result or visual field deficits, or funduscopic changes occur, MRI scanning is advisable.

Most authorities recommend not measuring prolactin because serum prolactin can increase to as high as 400 ng/mL during a normal pregnancy.

If no symptoms occur during pregnancy, serum prolactin can be measured two months after delivery or cessation of nursing

Common presenting complaints are

Macroadenomas 

Larger intrasellar tumour that abuts the optic chiasm Advise against pregnancy until tumour growth is controlled

Small intrasellar or inferiorly extending tumour that does not abut the optic chiasm Treat as microprolactinoma

Refer to endocrinology or neurosurgery Dopamine agonists to decrease size before she attempts to become pregnant& agonist therapy should be maintained throughout pregnancy

Women with macroadenomas should also be seen at least every three months, and more often the larger the adenoma.

If before pregnancy the macroadenoma extends above the sella, visual fields should be done before pregnancy and every three months during the pregnancy, even if the patient has no visual symptoms.

 If bromocriptine is used first, and the adenoma does not respond, cabergoline should then be administered . If cabergoline is not successful in alleviating severely compromised vision after several weeks then we suggest transsphenoidal surgery in the second trimester. In contrast, in the third trimester, surgery for persistent visual symptoms should be deferred until after delivery, if possible.

Ureter— Unilateral ureteral obstruction; hydroureter, hydronephrosis Bowel—constipation/tenesmus. / difficult defecation can caused by large posterior fibroid Vessels: Varicosity or edema of the lower extremities.

Indications for surgery  If the adenoma is : very large elevates the optic chiasm do not experience pituitary tumor shrinkage during dopamine agonist therapy (unresponsive to treatment), even if it is not elevating the optic chiasm cannot tolerate bromocriptine or cabergoline

Postoperative treatment with bromocriptine or cabergoline may also be helpful in reducing adenoma size further and lowering the serum prolactin concentration to normal. Such a regimen reduces the chance that symptomatic expansion will occur during pregnancy , but it may still occur.

The Task Force recommends: formal visual field assessment followed by MRI without gadolinium in pregnant women with prolactinomas who experience severe headaches and/or visual field changes .

In pregnant patients with prolactinomas, the Task Force recommends: against performing serum prolactin measurements during pregnancy against the use of routine pituitary MRI during pregnancy in patients with microadenomas or intrasellar macroadenomas unless there is clinical evidence for tumor growth such as visual field compromise

Breastfeeding does not increase the risk of lactotroph adenoma growth. Therefore, breastfeeding is an option for women with micro- and macroadenomas that remained stable in size during pregnancy. However, dopamine agonist treatment should be withheld until breastfeeding is completed.

Breastfeeding breastfeeding is contraindicated in women who have visual field impairment after delivery because they should be treated with a dopamine agonist.

Dopamine agonists in general should not be used in patients with pregnancy-induced hypertension, for example, preeclampsia, eclampsia, and post partum hypertension, unless the potential benefit is judged to outweigh the possible risk.

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