Pregnancy in patients with pheochromocytoma and paraganglioma - PowerPoint Presentation

Slide1

Pregnancy in patients with pheochromocytoma and paraganglioma

Irina Bancos

Associate Professor

Endocrinology

Mayo Clinic, Rochester, Minnesota

Slide2

Disclosure

Nothing to disclose in relation to current presentation

Other disclosures: advisory board, consulting, data safety board for

Adrenas

, HRA

Phrma

,

Strongbridge

, Sparrow pharmaceutics (fee to institution)

Some recommendations are based on “expert opinion”/unpublished data based on the Mayo Clinic clinical practice

Slide3

Outline

Review the take home message from a recent international multicenter study on PPGL in pregnancy

Provide several recommendations/suggestions for women with or at risk for PPGL and pregnancy

Q/A

Slide4

Pheochromocytoma and

paraganglioma

(PPGL)

Rare neuroendocrine tumors that usually secrete catecholamines

Catecholamine excess

 potentially severe

clinical consequences of hypertensive crisis, stroke, and death

Genetic association – in 40%

Young women (of reproductive age) with PPGL are more likely to have a genetic association

Pregnancy in PPGL



extremely rare

Slide5

PPGL in pregnancy: literature review

Systematic review of literature

: included studies 2005-2015, reporting on at least 5 pregnancies

Author, year

Country

Period of enrollment

Women

(n)

Pregnancies (n)

Oliva, 2010

USA

1984-200967Huddle, 2011 South Africa1980-200999Song , 2013China1983-201155Salazar-Vega, 2014ArgentinaNot reported1516Wing 2015 New Zealand2006-2013  49van der Weerd , 2017Netherlands1999-2015 66Donatini, 2018 France1997-20151010Quartermaine, 2018 United Kingdom2011-20151010

Outcomes:

Maternal death (3%) and complications (7%)Fetal death (13%) and complications (3%)

Patients:

65 women with PPGL during 72 pregnancies

PPGL diagnosis:

before(11%), during (64%), and after pregnancy (25%)

Delivery:

C-section (74%), vaginal delivery (16%), other (7%)

PPGL surgery:

during pregnancy in ¼ of women

Slide6

PPGL in pregnancy: literature review

Outcomes:

Maternal death

(3%)

and complications

(7%)

Fetal death

(13%)

and complications

(3%)

Limitations

:Small sample sizeUnclear relationship to time of PPGL diagnosisRecommended type of delivery?Timing of surgery?Effectiveness of alpha-blockade?Predictors of unfavorable pregnancy outcomes?Systematic review of literature: included studies 2005-2015, reporting on at least 5 pregnanciesPatients: 65 women with PPGL during 72 pregnanciesPPGL diagnosis: before(11%), during (64%), and after pregnancy (25%)Delivery: C-section (74%), vaginal delivery (16%), other (7%)PPGL surgery: during pregnancy in ¼ of women

Slide7

Objectives

To describe the characteristics, clinical course, and outcomes of women with PPGL during pregnancy

To determine predictors of maternal and fetal outcomes in women with PPGL

To determine the best approach to management of PPGL during (and hopefully before) pregnancy

Slide8

Methods

I

nternational retrospective multi-center study - 28 countries across the world

Inclusion criteria: patients with PPGL and pregnancy occurring between

1980 and 2019

meeting one of the following:

PPGL discovered before or at any time during pregnancy

PPGL discovered within 12 months postpartum

Slide9

 Country

of

Origin

Multi-center

collaboration

 Systematic

review

Total

USA71778Germany13 13Argentina 1616Netherlands9515China10515Italy11 11Russia11 11Asia (India, Singapore, Thailand)14 14Eastern and Southeastern Europe (Belarus, Ukraine, Poland, Czech republic, Turkey, Serbia)15 15Brazil8 

8

France11

11

Denmark

8

 

8

New

Zealand

 

10

10

South

Africa

 

9

9

United

Kingdom

6

6

Other (Israel, Ireland, Portugal,

Sweden)

6

 

6

Chile

2

 

2

Australia

2

 

2

Total

197

52

249

Slide10

Patients

232

patients with PPGL during

249 pregnancies

(10 patients - 2 pregnancies, 1 patient - 3 pregnancies, 1 patient – 6 pregnancies)

TUMOR SIZE:

5.3 (1.3-31) cm

FUNCTION:

95% - functioning

GENETICS:

only 62% tested

Slide11

PPGL discovery in relation to pregnancy

Before pregnancy

N=37 (15%)

During pregnancy

N=134 (54%)

After pregnancy

N=78 (31%)

249

Functioning PPGL

N=77, 33%

Functioning PPGL

N=119, 52% Functioning PPGL N=35, 15%231Alpha-blockade during pregnancy: N=98, 63%Antepartum PPGL surgery: N=39, 25%Median gest. week of 24 (2-38 weeks)Median of 6 (0-52) weeks post-delivery

Slide12

PPGL discovery in relation to pregnancy

Before pregnancy

N=37 (15%)

During pregnancy

N=134 (54%)

After pregnancy

N=78 (31%)

249

Functioning PPGL

N=77, 33%

Functioning PPGL

N=119, 52% Functioning PPGL N=35, 15%231Alpha-blockade during pregnancy: N=98, 63%Antepartum PPGL surgery: N=39, 25%Median gest. week of 24 (2-38 weeks)Median of 6 (0-52) weeks post-delivery0, 0%0, 0%10, 8%3, 3%10, 13%15, 19%30, 9%18, 8%Combined: 33 (14%)

Slide13

What are the important factors to assure a safe and healthy pregnancy in a woman with a

functioning

PPGL?

Timeline

for diagnosis of PPGL (before or during pregnancy)

Degree

of catecholamine excess

Location

of PPGL

Metastatic

PPGLPresent genetic predispositionTherapy during pregnancy:Alpha-adrenergic blockade

SurgeryType of delivery

Slide14

Timeline of PPGL discovery in relation to pregnancy

Before pregnancy

N=37 (15%)

During pregnancy

N=134 (54%)

After pregnancy

N=78 (31%)

249

Functioning PPGL

N=77, 33%

Functioning PPGL

N=119, 52% Functioning PPGL N=35, 15%231Alpha-blockade during pregnancy: N=98, 63%Antepartum PPGL surgery: N=39, 25%Median gest. week of 24 (2-38 weeks)Median of 6 (0-52) weeks post-delivery0, 0%0, 0%10, 8%3, 3%10, 13%15, 19%30, 9%18, 8%Combined: 33 (14%)

Slide15

Timeline of PPGL discovery in relation to pregnancy

Before pregnancy

N=37 (15%)

Functioning PPGL

N=35, 15%

0, 0%

0, 0%

Appropriate planning for therapeutic procedures

before

pregnancy

Early initiation of alpha-adrenergic blockade before or during pregnancy

Reflect a higher level of expertise/monitoring (medical provider) and self-care (patient)

Slide16

Timeline of PPGL discovery in relation to pregnancy

Before pregnancy

N=37 (15%)

During pregnancy

N=134 (54%)

After pregnancy

N=78 (31%)

249

Functioning PPGL

N=77, 33%

Functioning PPGL

N=119, 52% Functioning PPGL N=35, 15%231Alpha-blockade during pregnancy: N=98, 63%Antepartum PPGL surgery: N=39, 25%Median gest. week of 24 (2-38 weeks)Median of 6 (0-52) weeks post-delivery0, 0%0, 0%10, 8%3, 3%10, 13%15, 19%30, 9%18, 8%Combined: 33 (14%)

Slide17

Timeline of PPGL discovery in relation to pregnancy

Before pregnancy

N=37 (15%)

During pregnancy

N=134 (54%)

Functioning PPGL

N=119, 52%

Functioning PPGL

N=35, 15%

Alpha-blockade during pregnancy:

N=98,

63%Antepartum PPGL surgery: N=39, 25%Median gest. week of 24 (2-38 weeks)0, 0%0, 0%10, 8%3, 3%When compared to the “before” pregnancy group  8.3 times higher risk of complicationsLate diagnosis during pregnancy  later or inadequate, or absent therapy

Slide18

What are the important factors to assure a safe and healthy pregnancy in a woman with a

functioning

PPGL?

Timeline

for diagnosis of PPGL (

before

or during pregnancy)

Degree

of catecholamine excess

(↑ levels)

Location of PPGL (abdominal/pelvic)Metastatic PPGL

(↓ complications)Present genetic predisposition(↓ complications)Therapy during pregnancy:Alpha-adrenergic blockade(↓ ↓ complications)Surgery (↔ no effect on complications)Type of delivery (C-section vs vaginal) (↔ no effect on complications)Not when diagnosed before delivery!!Planning!!If optimal (dose and duration)Decision needs to be individualized based on above factors

Slide19

Delivery: C section or vaginal?

C-section

70%

Higher degree of catecholamine excess

More likely abdominal or pelvic PPGL – 82%

Vaginal

30%

Lower degree of catecholamine excess

Slightly more likely abdominal or pelvic PPGL – 64%

Same maternal age, same tumor size, same rate of metastatic disease

Same rate of complications

Slide20

Conclusions

Recognizing PPGL before delivery

is key!

Patients with

metastatic

PPGL can have a safe pregnancy if under close monitoring

Surgery during pregnancy can be safe, but may not be necessary, especially if extra-abdominal PPGL



individualized to specific situation

(and only with optimal alpha-blockade!)

Alpha-blockade prevents adverse outcomes (especially if optimal as far as duration and dose)Choice of C-section vs vaginal delivery is individualized

Slide21

Recommendations for pre-conception planning in women at risk for PPGL

Known germline variant associated with PPGL

(e.g. RET, neurofibromatosis type 1, Von Hippel-Lindau)

Biochemical testing

Cross-sectional imaging (preferably MRI)

Personal history of PPGL

Biochemical testing

Cross-sectional imaging (preferably MRI)

Genetic testing for germline variants

Family history of PPGL

(first or second degree relative)

Biochemical testingGenetic testing for germline variants

Slide22

Medication timing and treatment goals for PPGL in pregnancy

Alpha-adrenergic blocker

Start at time of PPGL diagnosis

Titrate to low-normal systolic blood pressure (90-110 mmHg)

Balance dosing with side effects to find a maintenance dose

Emphasize increasing fluid and sodium intake

Intensify therapy at 36 weeks to prepare for delivery, if needed

Beta-adrenergic blocker

Start after at least 1 week of alpha-adrenergic blockade

Add only if needed to control heart rate

Titrate to heart rate 80-90 beats per minute

Calcium channel blockerStart after titration of alpha-adrenergic blockade for 2-3 weeksAdd only if persistent hypertension despite adequate alpha- and beta-adrenergic blockade

Slide23

Q/A

High blood pressure during pregnancy

 decreased blood flow to the placenta

 less oxygen to baby --> growth restriction, prematurity

Long term effects on baby: unclear in PPGL, but some data from patients with preeclampsia

Maternal catecholamines are reported to be broken down by the placental enzymes (Catechol) methyltransferase)



< 10% reach the baby

Evidence of pregnancy triggering PPGL formation?

No evidence of fertility treatments/estrogen/progesterone/pregnancy triggering tumor formation

Risk to pregnancy if PPGL was removed prior to conception?

Not unless another unrecognized functioning PPGLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972176/

Slide24

Thank you

Questions:

bancos.irina@mayo.edu

Twitter: @IrinaBancos

Acknowledgements:

International multicenter PPGL in Pregnancy workgroup (https://pubmed.ncbi.nlm.nih.gov/33248478/ )

William Young and Lucinda Gruber (recommendations from the upcoming review: “

Pheochromocytoma and Paraganglioma in Pregnancy: A New Era” (in press)