Macroprolactinoma during pregnancy - PowerPoint Presentation

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Macroprolactinoma during pregnancy

Slide2

Clinical questions list:

1-what is the effect

of pregnancy on

prolactinoma

size?

2-What is the

management

of

prolactinoma

in pregnancy

?

3-When does

prolactinoma

be treated during pregnancy

?

4-What are

the safe

drugs used in pregnancy for

prolactinoma

?

5-when dose imaging (MRI) be done?

Evaluation & F/U of the

pationt

Slide3

what

is the effect of pregnancy on

prolactinoma

size?

Basal PRL levels gradually increase throughout the course of pregnancy

. There is a gradual increase in the number of pituitary lactotrophs during pregnancy and by term, PRL levels may be increased ten-fold to levels over 200 ng/ml. These elevated PRL levels found at term prepare the breast for lactation. The lactotroph cell hyperplasia occurring during pregnancy is reflected on MRI scans which show a gradual increase in pituitary volume over the course of gestation, beginning by the second month and peaking the first week postpartum with a final height reaching to almost 12 mm in some cases

Mark E.

Molitch

, MD,

Prolactinoma

in

pregnancyBest

Practice & Research Clinical Endocrinology & Metabolism 25 (2011

)

Slide4

Complications

Mass

effect

The growing pituitary mass may impinge the surrounding structures, depending on the direction and severity of the extension. Organs that might be harmed include the optic

chiasm:

the cranial nerves located in the cavernous sinuses (namely the optic, trochlear, abducens and two branches of the trigeminal nerves) adjacent structures, such as the temporal lobe, the nasal cavity and sinuses, the internal ear and the thalamus. The related symptoms are mainly headaches and neuro-ophthalmological, including visual field alterations and ophthalmoplegia. Visual field defects occur more often in larger adenomas and necessitate the evaluation of visual fields in lesions abutting the optic chiasmaTirosh A,Shimon.Management of macroprolactinomasClinical

Diabetes and Endocrinology

2015

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Hypopituitarism

The

gonadotroph

axis

is most often damaged (

73–86 %), presumably due to the double effect of the macroprolactinoma on this axis: increased pressure on the gonadotroph cells from the expanding mass and suppression of GnRH secretion by PRL effect in the hypothalamus . Normal testosterone levels do not exclude the presence of PRL-secreting adenoma. Central hypothyroidism and hypocortisolism might also be induced by macroprolactinomas, though less often (18–41 % and 12–23 %, respectively)Somatotroph axis evaluation is limited in patients with PRL-secreting tumors, due to the possibility of GH and PRL co-secretion in 10 % of these adenomas.Recovery of the gonadotroph

axis was reported in

most

patients with

(recovery

of

thyrotrophs in 25 % of affected patients but no recovery of ACTH secretion and Sibal et al. )

Tirosh

A,Shimon.Management

of

macroprolactinomas

Clinical

Diabetes and Endocrinology

2015

Slide6

Cerebrospinal fluid leak

A

leak in the CSF is usually

iatrogenic

, due to surgery or aggressive DA treatment, although it might be the presenting symptom in

some macroprolactinomas In a recent report on this complication of various pituitary adenomas, PRL-secreting tumors were reported in 81 % (42/52) of cases, many of these being giant prolactinomas. Meningitis, a complication of CSF exposed to the outer environment, was reported in 15–20 % of casesTirosh A,Shimon.Management of macroprolactinomasClinical Diabetes and Endocrinology2015

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Apoplexy

Pituitary apoplexy is characterized by a rapid enlargement of the pituitary due to hemorrhage or infarct

(prevalence

,

0.08

%)Although this is an uncommon complication, it is potentially life threatening, characterized by severe and abrupt headache, together with nausea, vertigo and meningismus .Other symptoms might include acute hypopituitarism and neurologic compromise, including deteriorated consciousness, ophthalmoplegia and restriction of visual fields. Although the syndrome is usually acute and obvious, it may be subtle or even clinically silent Among pituitary tumors, apoplexy tends to occur in larger lesions, due to increased discrepancy between the rate of neoplastic progression and blood supply Importantly, not only treatment with DAs might cause apoplexy, but also its withdrawal ,possibly due to rapid re-growth of the adenoma The management of pituitary apoplexy depends on the clinical manifestations and their severity.

A

main consequence

of apoplexy is the

adrenal crisis

. Thus, administration of

hydrocortisone is indicated immediately on diagnosis, in addition to appropriate glucocorticoid coverage afterwards. Transsphenoidal

surgery for decompression

of the

sella

is indicated in patients with significant visual compromise or with a diminished level of consciousness

,

whereas conservative management is optional for others.

Tirosh

A,Shimon.Management

of

macroprolactinomas

Clinical

Diabetes and Endocrinology

2015

Slide8

AnaEspinosa

De

Ycaza

a

Alice

Y.ChangApproach to the management of rare clinical presentations of macroprolactinomas in reproductive-aged womenVolume 8, October 2015,

Slide9

Managing

Prolactinomas

during Pregnancy

The

main concern is possible tumor enlargement during pregnancy.

The risk of tumor enlargement during pregnancy is found to depend on tumor size. Data in the literature indicate that although tumor enlargement is only 3% for microprolactinomas, it is as high as 32% for macroprolactinomas that were not previously operated on.

by MH

Almalki.

Managing

Prolactinomas

during

Pregnancy

Front

Endocrinol

(Lausanne)

. 2015; 6: 85.

Slide10

MRI

A magnetic resonance imaging (MRI) should be

done before

conception to document tumor size and to serve as a

baseline

for comparison with MRIs done during pregnancy. Furthermore, MRI is helpful in distinguishing between hemorrhage into a tumor versus simple tumor enlargement during pregnancyby MH Almalki.Managing Prolactinomas during PregnancyFront Endocrinol (Lausanne). 2015; 6: 85.

Slide11

Cont…

The patient should be advised to report for urgent assessment in case of

unusual

symptoms such as severe

headache or visual disturbance

, to rule out the possibility of tumor enlargement. In case of macroprolactinoma, symptomatic tumor enlargement occurs in 20–30% of cases .It has been reported that the risk of clinically significant tumor enlargement falls from over 30 to <5%, if the patient is treated with radiation or surgery before pregnancy Pregnant women with large tumors and those with

extrasellar

extension

who have

stopped

bromocriptine are at risk for tumor growth, and

formal visual field testing should be done in each trimester.

Slide12

Cont…

The patient should be advised about the symptoms and the need for urgent evaluation once they appear

.

.

If the patient reports

headache or a change in vision, an MRI should be performed. If the MRI finding is consistent with tumor enlargement, the women should be retreated with a DA 

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Medical therapy

Medical therapy with DAs represents the primary

therapy for :

microadenomas

that require treatment

macroprolactinomasgiant prolactinomas.Melmed fourth edition

Slide14

Melmed

fourth edition

Slide15

Efficacy of Dopamine Agonists

Several studies have reported the efficacy of bromocriptine in lowering PRL levels in patients with a

prolactinoma

. Bromocriptine normalized serum PRL in

78% and 72% of patients with

microprolactinomas andmacroprolactinomas, respectively results from 21 series examining tumor shrinkage among 302 patients with macroadenomas treated with bromocriptine reported a significant decrease intumor size in about 77% with periods of observation ranging from 6 weeks to over 10 years These rates of tumor shrinkage are lower than those observed with cabergolineMelmed Fourth edition

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Williams 2016

Slide17

Williams 2016

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Safety of DA s:

Although 

dopamine

 agonists are typically discontinued when pregnancy is confirmed, pregnancy has usually progressed at least two weeks before confirmation occurs and the drug discontinued, so the fetus is exposed to the dopamine agonist during that time. Evidence to date does

not

suggest risk to the fetus from this exposure.Data from over 6000 pregnancies suggest that the administration of bromocriptine during the first month of pregnancy does not harm the fetus . In this series, the incidence of spontaneous abortions (9.9 percent), multiple births (1.7 percent), and malformations (1.8 percent) was no higher than in the general population. In addition, in a study of children followed for up to nine years after exposure to bromocriptine in utero, no harmful effects were noted .Rarely, dopamine agonist treatment is resumed during pregnancy if adenoma size increases so much as to impair vision. Continuous use of bromocriptine during pregnancy has been reported in approximately 100 women. Although the rate of congenital malformations did not appear to be higher than non-exposed pregnancies, there was one case of undescended testis and one of talipes deformity . Molitch ME. Prolactinoma in pregnancy. Best Pract Res Clin Endocrinol Metab 2011; 25:885.

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Although the number of pregnancies in women taking 

cabergoline

 at the time of conception is

much smaller

, the evidence suggests that this drug is safe as well. In one review of over 700 cases, the incidence of spontaneous abortions (7.6 percent), multiple births (1.7 percent), and malformations (3.2 percent) was no higher than in the general population

. Molitch ME. Prolactinoma in pregnancy. Best Pract Res Clin Endocrinol Metab 2011; 25:885.

Slide20

Mussa

Hussain

Almalki

Managing

Prolactinomas during PregnancyPublished online 2015,

Slide21

williams2016

Slide22

Guide line 2011

In selected patients with

macroadenomas

who become

pregnant

on dopaminergic therapy and who have not hadprior surgical or radiation therapy, it may be prudent tocontinue dopaminergic therapy throughout the pregnancy, especially if the tumor is invasive or is abutting theoptic chiasm (1QEEE).

Slide23

First response to therapy may be expected as soon as

a week or two

after treatment initiation. However, in some patients

shrinkage

may become noticeable after

only 6 months of therapyby MH Almalki.Managing Prolactinomas during PregnancyFront Endocrinol (Lausanne). 2015; 6: 85.

Slide24

Approach to the management of rare clinical presentations of macroprolactinomas in reproductive-aged women

 

                    

Case Reports in Women's Health

Volume 8

,

 October 2015, Pages 9-12

Patients with

prolactinoma

and apoplexy usually develop apoplexy within 1 week to 12 months after initiation of dopamine agonists. No data are available about the risk of recurrent apoplexy and likely reflects the very low risk of a recurrent event. Without data to guide who would benefit from continuing dopamine agonists during pregnancy, practice varies.

Dopamine agonists might be continued or restarted during pregnancy for

macroprolactinomas

with

suprasellar

extension, especially if the patient has mass effect symptoms 

[

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Slide26

Slide27

Pituitary apoplexy may represent the

first

presentation of a pre-existing, unrecognized adenoma in over 80 % of

cases

precipitating factors :hypertension, major surgery especially coronaryartery bypass grafting, dynamic pituitary testing usinggonadotropin-releasing hormone (GnRH), thyrotropinreleasing hormone (TRH), corticotropin-releasing hormone(CRH), insulin tolerance test, anticoagulation therapy, coagulopathies, estrogen therapy, initiation or withdrawal ofdopaminergic therapy, radiation therapy and head trauma,and pregnancy

Slide28

Pituitary surgery is indicated in patients who:

cannot tolerate

resistant

to therapy with Das

patients that seek fertility and harbor adenomas that impinge on the

optic chiasmpsychiatric patients with contraindication to DA pituitaryapoplexy cerebrospinal fluid (CSF) leakManagement of macroprolactinomasClinical Diabetes andEndocrinology2015

Slide29

Resistance to DAs has several different definitions in the literature, including

:

failure

to achieve normal PRL levels or adenoma shrinkage of >50 

%

failure to reduce PRL by >50 %, or to induce ovulation in womenfailure to reduce symptoms or normalize PRL despite CAB dose ≥2 mg/week The prevalence of CAB resistance according to this criteria is 11 % among patients harboring macroprolactinomas 

Slide30

Summary of recommendations for management of

adenoma

before and during pregnancy

Pre-pregnancy

Complete pituitary hormonal work-up with visual fields assessment on physical examination to establish proper diagnosis of pituitary lesionIf diagnosis of micro or macroprolactinoma is confirmed and desire to become pregnant is expressed, treatment with dopaminergic agonist (bromocriptine or cabergoline) to reduce size of the tumour and controlled prolactin level before pregnancy is recommended. For all macroadenoma, consider treatment for reduction in size to less than 1 cm before pregnancy preferably with effective medication (e.g.dopaminergic therapy for macroprolactinoma) and/or surgery/radiotherapy if indicated, to minimise the risk of apoplexy and pressure on the opticchiasm during pregnancy.

Management of

macroprolactinomas

Clinical

Diabetes andEndocrinology

2015

of

macroprolactinomas

Clinical

Diabetes andEndocrinology

2015

Management of

macroprolactinomas

Clinical

Diabetes andEndocrinology

2015

Slide31

During

pregnancy

In women with

microprolactinoma

, discontinue dopamine agonist therapy when pregnancy is confirmed. In women with macroprolactinoma whobecome pregnant under therapy, it seems reasonable to continue dopamine agonist therapy throughout the pregnancy, especially if the initial tumourwas invasive or close to the optic chiasm given the high risk (31%) of tumour growth or apoplexy during pregnancy. Plan a physical examination and an evaluation of thyroidotroph and corticotroph axis functions at each trimester (with follow-up of T4 level and urinaryfree cortisol, which is more reliable than plasma cortisol during pregnancy) in near-to and confirmed macroadenomas to avoid unrecognised relativepituitary insufficiency. Routine evaluation of prolactin level during pregnancy is not recommended for asymptomatic patient. Visual fields should be checked by an ophthalmologist once during pregnancy for women with near-to or established

macroadenomas

.

Repeat

visual

fields during the

third trimester for macroadenoma only.Tirosh

A,Shimon

Management

of

macroprolactinomas

Clinical

Diabetes andEndocrinology

2015

Slide32

Cont…

Inform all patients with micro or

macroadenomas

about symptoms that could be related to

tumour growth or apoplexy (sudden thunderclap headache, visual disturbance) and advise them to come rapidly to the hospital if they become symptomatic for a hormonal and radiologic work-up. Routine radiologic follow-up of adenomas is not recommended during pregnancy. However, if clinical suspicion of tumour growth or apoplexy(development of neurological or visual symptoms), proceed to urgent pituitary MRI without gadolinium, formal visual fields assessment and hormonal work-up. If significative growth of a prolactinoma is established and the patient experiences some neurological symptoms, reinitiation

or increase of the dose

of dopamine

agonist therapy is recommended. If dopamine agonist therapy does

not decrease

tumour

size and

improved

symptoms, consider

surgical resection

, especially in patient with documented optic chiasm compression and visual fields disturbance. If the fetus is near-term, it may be

reasonable to

induce delivery before neurosurgical intervention.

Tirosh

A,Shimon

Management

of

macroprolactinomas

Clinical

Diabetes andEndocrinology

2015

Slide33

There is

no

definitive answer as to the best therapeutic approach in such a patient and

this has

to be a highly individualized decision that the patient has to make after a clear,

documented discussion of the various therapeutic alternatives. One approach is to perform a prepregnancy transsphenoidal surgical debulking of the tumor. This should greatly reduce the risk of serious tumor enlargement, but cases with massive tumor expansion during pregnancy after such surgery have been reported. M.E. Molitch / Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 885–896

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After

surgical

debulking

, a

dopamine agonist

is required to restore normal PRL levels and allow ovulation. Radiotherapy before pregnancy, followed by a dopamine agonist, reduces the risk of tumor enlargement also, it is rarely curative. Radiotherapy may also result in long-term hypopituitarism,so that this approach seems less acceptable than transsphenoidal surgery plus a dopamine agonist. A third approach, that of giving bromocriptine continuously throughout gestation, has been used but data of effects on the fetus are quite meager and data on the effects of continuous cabergoline on the fetus are even fewer; therefore, such treatment cannot be recommended without reservation. Should pregnancy at an advanced stage be discovered in a woman taking bromocriptine or cabergoline, however, the data that exist are reassuring and would not justify therapeutic abortion. A fourth approach, and the one most commonly employed, is to stop the dopamine agonist after pregnancy is diagnosed, as in the patient with a

microadenoma

.

For

patients with

macroadenomas

treated with a dopamine agonist alone or after surgery or irradiation, careful follow-up with 1–3 monthly formal visual field testing is warranted

M.E.

Molitch

/ Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 885–896

Slide35

Repeat MRI

Repeat

MRI is

reserved for patients with

symptoms of tumor enlargement and/or evidence a developing visual field defect or both. Repeat scanning after delivery to detect asymptomatic tumor enlargement may be useful as well. Should symptomatic tumor enlargement occur with any of these approaches,reinstitution of the dopamine agonist is probably less harmful to the mother and child than surgery. There have been a number of cases reported where such reinstitution of the dopamine agonist has worked quite satisfactorily, causing rapid tumor size reduction with no adverse effects on the infant Any type of surgery during pregnancy results in a 1.5–fold increase in fetal loss in the first trimester and a fivefold increase in fetal loss in the second trimester, although there is no risk of congenital malformations from such surgery. Thus, dopamine agonist reinstitution would appear to be

preferable to

surgical decompression. However, such medical therapy

must be very closely monitored

,

and

transsphenoidal surgery or delivery [if the pregnancy is far enough advanced] should be performed

if there

is

no

response to the dopamine agonist and vision is progressively worsening.

M.E. Molitch / Best Practice & Research Clinical Endocrinology & Metabolism 25 (2011) 885–896

Slide36

Postpartum

Breastfeeding and dopamine agonists

 — Breastfeeding increases serum prolactin concentrations

,but

does not appear to 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. Dopamine agonist therapy, which lowers serum prolactin and inhibits lactation, should be withheld until breastfeeding is completed.In contrast, breastfeeding is contraindicated in women who have visual field impairment after delivery because they should be treated with a dopamine agonist.Bronstein MD, Salgado LR, de Castro Musolino NR. Medical management of pituitary adenomas: the special case of management of the pregnant woman. Pituitary 2002; 5:99.

Slide37

Normalization of prolactin after pregnancy 

A significant percentage of women with

lactotroph

adenomas appear to have a remission after delivery, and no

longer require

 dopamine agonist therapy. To evaluate the need for further dopamine agonist therapy after pregnancy, serum prolactin should be measured about three months after delivery in women who do not breastfeed, and after cessation of breastfeeding in those who do. Serum prolactin normalizes within 6 to 12 weeks postpartum in women who do not breastfeed

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