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Table of Contents
REVIEW ARTICLE
Year : 2015  |  Volume : 3  |  Issue : 1  |  Page : 3-7

Management of prolactinoma during pregnancy and postpartum


1 Department of Endocrinology, Sir Ganga Ram Hospital, New Delhi, India
2 Consultant Gynecologist, Race Course Medical Centre, Vadodara, India

Date of Web Publication3-Aug-2018

Correspondence Address:
J Lakhani Om
Department of Endocrinology, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2347-6486.238517

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  Abstract 


Prolactinoma is classified as microprolactinoma when it measures <10 mm and macroprolactinoma when it measures ≥10 mm. Prolactinoma is an important cause of amenorrhea and infertility in premenopausal female. With early diagnosis and treatment with dopamine agonist, many patients have restoration of fertility within few months of treatment. In presence of estrogenic environment of pregnancy there is a tendency for prolactinoma to increase in size during pregnancy. This may be associated with visual field compromise and rarely pituitary apoplexy. This review discusses some key points in management of prolactinoma during pregnancy and postpartum.
In case of microprolactinoma, the risk of complications are low hence it is recommended to keep a close follow up of patient without any need for intervention. In case of macroprolactinoma it is recommended to use barrier contraception to prevent pregnancy for at least 6-12 months after detection and starting treatment to allow proper shrinkage of the tumor with dopamine agonist. Once pregnancy is confirmed -In those with low risk features, dopamine agonist is stopped and a close follow up is advised. In those with high risk features, it is recommended to continue the dopamine agonist therapy with a close follow up. Postpartum period generally doesn’t pose much threat to prolactinoma and treatment may be discontinued if patient wishes to breast feed her infant.

Keywords: Hyperprolactinemia and Pregnancy, Prolactinoma and Pregnancy, Prolactinoma and Postpartum


How to cite this article:
Om J L, Rishma L, Desai M, Tripathi S. Management of prolactinoma during pregnancy and postpartum. J Integr Health Sci 2015;3:3-7

How to cite this URL:
Om J L, Rishma L, Desai M, Tripathi S. Management of prolactinoma during pregnancy and postpartum. J Integr Health Sci [serial online] 2015 [cited 2019 Jun 19];3:3-7. Available from: http://www.jihs.in/text.asp?2015/3/1/3/238517




  Introduction Top


Prolactin secreting pituitary adenoma (prolactinoma) is the commonest pituitary tumor. They are usually benign tumors and are classified as microprolactinoma, when they are less than 10 mm in diameter and macroprolactinoma, when size is more than 10 mm diameter. It is often a cause of anovulatory infertility. Female patients with prolactinoma typically present with amenorrhea and galactorrhea, occasionally associated with headache and visual disturbances. It is also a differential diagnosis of polycystic ovarian syndrome. First line of treatment of prolactinoma is with dopamine agonist therapy. Cabergoline is generally preferred over other agents because of ease of administration and fewer side effects. Bromocriptine and quinagolide are alternative drugs.[1] When patients with prolactinomas become pregnant, clinicians are confronted with two major issues:

Possible growth of the prolactinoma during pregnancy

  1. Use of dopamine agonist during pregnancy and their impact on the fetus.


Because of increase estrogen during pregnancy, there is a possible risk of growth of prolactin secreting tumors during pregnancy.[2] In this review we have elaborated on the management of prolactinoma during pregnancy and postpartum period.


  Methodology Top


A search for literature in Pubmed index was done using search strings ‘Hyperprolactinemia’, ‘Macroprolactinoma’, ‘Prolactinoma’, ‘Hyperprolactinemia and pregnancy’ and ‘Prolactinoma and Pregnancy’ . Guidelines, review articles and studies published in high impact journals between years 2000 to 2015 were included in the review.


  Discussion Top


Size of the prolactinoma before pregnancy is an important factor that will help predict the potential problems during pregnancy. To understand the management of prolactinoma in pregnancy, we classified prolactinomas in three groups 1) Microprolactinoma 2) Macroprolactinoma with low risk features 3) Macroprolactinoma with high risk features [Figure 1].
Figure 1: Management of prolactinoma in pregnancy

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Management of microprolactinoma during pregnancy

Microprolactinoma generally do not pose a threat during pregnancy. According to a compiled data of 5 large studies 2.6% of patient with microprolactinoma have a symptomatic enlargement during pregnancy and no cases of microprolactinoma have required any form of surgical intervention during pregnancy.[3] It is recommended to stop dopamine agonist once pregnancy is confirmed. A close follow up of case of microprolactinoma during pregnancy with regular clinical assessment is generally advised. Visual field assessment must be done in each trimester.[4] Measurement of prolactin levels or MRI is not required in case of microprolactinoma, though a close clinical follow up for symptoms of tumour expansion like headache or visual disturbances is recommended.

Management of macroprolactinoma during pregnancy

Management of macroprolactinoma is more complicated. As per a study in females with macroprolactinoma who have not undergone surgery or radiation before pregnancy, the risk of growth is around 31% with 8.5% needing surgical intervention during pregnancy to halt the growth of tumor.[3] The potential problems of undertreated macroprolactinomas include visual compromise and pituitary apoplexy. Untreated (or ‘undertreated’) hyperprolactinemia can also lead to ectopic pregnancy.[5] Hence management of macroprolactinoma should begin with good planning before pregnancy.

It is essential to counsel all patients with macroprolactinoma to use barrier contraceptive for at least 6 months to 1 year after starting treatment with Dopamine agonist.[6],[7] With appropriate medical treatment ovulatory menses is restored in 90% of women with macroprolactinoma and pregnancy can potentially occur within few months of starting therapy.[7] If the prolactinoma has not been properly treated before pregnancy, it can cause a threat during pregnancy. It is important to understand that treatment with dopamine agonist not only reduces the prolactin level but also reduces the size of the tumor. 80% of prolactinomas treated with dopamine agonist reduce to 25% of their original size.[7] Hence a good duration of treatment with dopamine agonist before pregnancy can cause sufficient shrinkage of tumor and avoid unnecessary problems antepartum.

Some endocrinologists recommend that patients with macroprolactinoma desirous of pregnancy should undergo neurosurgical tumor debulking before pregnancy is planned. Growth of tumor has been reported in only 7% of cases during pregnancy in those who have undergone surgery.[3] However surgical resection of tumor can cause other anterior pituitary defects including gonadotropin deficiency which can further affect the fertility. Hence a routine surgical resection is generally not recommended these days.[2]

It is not recommended to measure prolactin level during pregnancy. Prolactin levels are bound to increase in pregnancy and do not reflect the tumor growth. Measurement of prolactin level in pregnancy therefore is not useful. Levels in pregnancy may go up to 150-300 ug/l.[2]

The other problem with prolactinoma during pregnancy is the potential effects of dopamine agonist on the fetus. Bromocriptine is known to cross the placenta. However, when follow up studies of patients taking bromocriptine or cabergoline during pregnancy were done, it was found that neither bromocriptine nor cabergoline was found to cause any adverse effects to the fetus. Another dopamine agonist quinagolide is harmful to the fetus and must be avoided.[2] The choice between bromocriptine and cabergoline is difficult to make. On one hand there are more studies showing safety of bromocriptine during pregnancy compared to cabergoline. Bromocriptine is also endorsed by Endocrine society for use in pregnancy.[2] On the other hand, bromocriptine has more side effects than cabergoline and efficacy is also less compared to cabergoline.[1] Hence the choice should be based on clinical judgement and patient and clinician preference.

It is very important to understand that the goals of treating prolactinoma before pregnancy and during pregnancy are very different. The aim of treating before pregnancy is to restore ovulatory menses and fertility in most premenopausal women with prolactinoma apart from reduction in size of tumor. The aim of treating during pregnancy is solely to avoid the growth of the tumor during pregnancy and prevent any compromise on visual function.[4]

The decision whether to continue dopamine agonist during pregnancy is unclear. Endocrine society guidelines clearly state that once patient becomes pregnant , the dopamine agonist must be stopped.[2] However, we often see patients who become pregnant and have not taken dopamine agonist therapy for sufficient time prior to pregnancy. In such a scenario it may be advisable to continue dopamine agonist therapy. Hence we have divided macroprolactinoma into two subgroups – macroprolactinoma with low risk features and macroprolactinoma with high risk features.

Macroprolactinoma with low risk features include those who full fill all of the following criteria- a) Taken dopamine agonist therapy for at least 6 month before pregnancy b) Recent MRI (<3 month) before pregnancy showing tumor not compressing upon the optic chiasma or invading the surrounding structures c) Patient likely to come for regular antenatal follow up. Additionally patients who have undergone surgical resection or radiotherapy for prolactinoma before pregnancy should be considered as low risk for tumor growth during pregnancy. For such a group of patient it is recommended that Dopamine agonist can be stopped and the patient followed up carefully during pregnancy.[8],[9]

Macroprolactinoma with high risk features include those with any of the following a) Taken dopamine agonist therapy for <6 months or irregularly with evidence of little or no tumor shrinkage on recent MRI b) MRI before pregnancy showing tumor abutting the optic chiasma or invading the surrounding structures. For such a group of patients we advise to continue dopamine agonist therapy with close follow up throughout pregnancy.[2],[10]

All patients with macroprolactinoma (whether treated or not) must undergo visual perimetry testing every two months during pregnancy. They should also be questioned for any new onset of headache or visual disturbances.[4] Headache in cases of Pituitary adenoma is often described as unilateral, orbital or frontal in location, throbbing, or of severe intensity and associated with nausea. It is often exacerbated by light and movement and often lasts for median duration of 6 hours.[11] Any such headache in patients with prolactinoma during pregnancy must be taken seriously. Any evidence of visual field defects on perimetry, and/or headache of nature as described above mandates a MRI of the sella (without Gadolinium contrast). Such patients would also require to be restarted on dopamine agonist therapy if not already on treatment.[2] If patient is already on treatment with dopamine agonist, the dose must be increased with close monitoring of response. If there is blunted response to dopamine agonist, then surgery may be required. Transsphenoidal surgery is the preferred mode of surgery and it is preferably in the second trimester. If close to term then delivery may be considered. Surgery carries a risk of abortion and this must be explained to the patient.[7]

Management of prolactinoma during pregnancy is summarized in [Figure 1]. The key recommendations of Endocrine society guidelines are summarized in [Table 1].
Table 1: Key recommendations from endocrine society guidelines on hyperprolactinemia

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Management of prolactinoma post-partum

Management of prolactinoma postpartum depends on whether patient wants to continue breastfeeding. If patient is not going to breast feed the baby, the dopamine agonist may be restarted. If patient plans to breast feed the dopamine agonist would interfere with lactation and hence it is not given. Growth of prolactinoma during lactation is not reported and presence of prolactinoma should not be considered as contraindication for lactation.[4] However, just like during pregnancy, prolactin levels may fluctuate postpartum and hence it is not recommended to monitor patient with prolactin level. Rather clinical and visual field assessment must be done during the postpartum period.

It is heartening to note that prolactinoma tend to become docile postpartum. Amongst the patients who were found harbouring the tumor antepartum, 27 % had complete resolution or cure of the tumor postpartum.[1] It is recommended to measure serum PRL after 2 months of delivery and repeat a MRI Sella with contrast 2 months after stopping lactation.[4]


  Conclusion Top


Management of prolactinoma during pregnancy requires good team work between endocrinologist and obstetrician. In case of a microprolactinoma, a regular follow up with visual field assessment every trimester be enough. A macroprolactinoma with low risk features requires discontinuation of dopamine agonist and a close follow up, while that with high risk features requires continuation of dopamine agonist. In case of new onset headache or visual field abnormalities, a MRI Sella without contrast is recommended with possible need for restarting medical therapy with dopamine agonist.[12]



 
  References Top

1.
Bronstein MD. Disorders of Prolactin secreation and Prolactinomas. In: Jameson JL, Groot LD, editors. Endocrinology Adult and Pediatric: Saunders Elsevier; 2010. p. 333-58.  Back to cited text no. 1
    
2.
Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, Wass JA. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society  Back to cited text no. 2
    
3.
Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocrine reviews. 2006 Aug;27(5):485-534.  Back to cited text no. 3
    
4.
Karaca Z, Tanriverdi F, Unluhizarci K, Kelestimur F. Pregnancy and pituitary disorders. European Journal of Endocrinology. 2010 Mar 1;162(3):453-75.  Back to cited text no. 4
    
5.
Rossi AM, Vilska S, Heinonen PK. Outcome of pregnancies in women with treated or untreated hyperprolactinemia. European Journal of Obstetrics & Gynecology and Reproductive Biology. 1995 Dec 31;63(2):143-6.  Back to cited text no. 5
    
6.
Bevan JS. Prolactinomas and hyperprolactinaemia (including macroprolactinaemia). In: Wass JAH, Stewart PM, Amiel SA, Davies MC, editors. Oxford Textbook of Endocrinology and Diabetes. 2nd Edition ed. Oxford: Oxford Univeristy Press; 2011.  Back to cited text no. 6
    
7.
Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism. 2011 Feb;96(2):273-88.  Back to cited text no. 7
    
8.
Cappabianca P, Colao A, Fahlbusch R, Fideleff H. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clinical endocrinology. 2006 Aug 1;65(2):265- 73.  Back to cited text no. 8
    
9.
Laway BA, Mir SA. Pregnancy and pituitary disorders: Challenges in diagnosis and management. Indian journal of endocrinology and metabolism. 2013 Nov 1;17(6):996.  Back to cited text no. 9
    
10.
Imran SA, Ur E, Clarke DB. Managing prolactin- secreting adenomas during pregnancy. Canadian family physician. 2007 Apr 1;53(4):653-8.  Back to cited text no. 10
    
11.
Rabinovich IH, Gómez RC, Mouriz MG, García- Agulló DO. Clinical guidelines for diagnosis and treatment of prolactinoma and hyperprolactinemia. Endocrinología y Nutrición (English Edition). 2013 Jul 31;60(6):308-19.  Back to cited text no. 11
    
12.
Levy MJ, Matharu MS, Meeran K, Powell M, Goadsby PJ. The clinical characteristics of headache in patients with pituitary tumours. Brain. 2005 Aug 1;128(8):1921-30.  Back to cited text no. 12
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]


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