Endocrine disease in pregnancy

SpR teaching 6/5/16

(ambitious) Objectives:

• Hypothyroidism: – treatment, monitoring, outcomes

• Hyperthyroidism: – prenatal counselling, treatment options, complications,

monitoring

• Prolactinoma

• Addison's

Case 1

30 yr old woman, 1st pregnancy, 8/40

Diagnosed with Hashimotos 5 yrs ago, on levothyroxine 125 mcg OD

Last TSH 3.4 6/12 ago

GP calls for advice: what do you recommend?

Hypothyroidism discussion points:• What are the risks of under-treated hypothyroidism?

– Both obstetric and to offspring

• What is the “right” TSH target?

• Would you change her T4 dose?

• How often to monitor TFTs?

• (Should we screen for hypothyroidism in pregnancy?)

Hypothyroidism

• TSH Ref range in pregnancy is lower: – ideally use trimester/assay specific range, typically: – TSH <2.5 during 1st trimester– TSH <3 2nd/3rd trimester

• Dose: 1.5-2mcg/kg /day…. or increase daily dose by 30-50% .... or take 2 extra doses per week. Ideally optimise pre-pregnancy.

Risks of under-treated hypothyroidism

• Miscarriage• Abruption• Prematurity• Pre-eclampsia • Adverse neurodevelopmental outcomes in

offspring– Haddow et al, NEJM 1999– Li et al, Clin Endo 2010 …….and lots more

Case 2

22 yr old woman with T1DMUnplanned pregnancy, now 6/40

• TSH 4.1, fT4 13 (and HbA1c 85…)

• Would you start levothyroxine?• What dose?• What about post natal treatment?

Subclinical hypothyroidism

• To screen or not to screen?

• To treat or not?– Does it make a difference if TPO+ve or not?

• Should treatment be continued postnatally?

Case 3

• 36 yr old woman

• 3rd pregnancy, now 11/40

• Seen by OBS with hyperemesis, admitted for treatment

• TSH 0.016, fT4 26

Thyrotoxicosis in pregnancy

• What’s the underlying aetiology?– Goitre, TED, TRAB, fT3?

• Natural history of GTT?

• Treatment?

Case 4

40 yr old woman, 4th pregnancy (unplanned)Referred by community midwife at 14/40.

Previously seen in endocrine clinic with Graves disease. Variable concordance treatment.

No medication at present.

fT4 29, fT3 9, TSH <0.014

Pre-existing hyperthyroidism and pregnancy

• Pre-pregnancy advice

• Medication choices

• Monitoring

Complications of untreated Graves disease in pregnancy

• Foetal:– Miscarriage– IUGR– Prematurity– Placental abruption– Neonatal thyrotoxicosis

• Maternal:– Preeclampsia– Thyroid storm– High output cardiac failure

Treatment options in pregnancy

• ATDs: PTU v CBZ– Both equally effective, & both cross placenta– Carbimazole embryopathy v PTU hepatotoxicity (& ??

Birth defects)– PTU 1st trimester then switch to CBZ– Keep fT4 to upper end of ref range– Do not use block & replace– Short term b blocker use is fine

• Surgery: only in difficult cases; 2nd trimester • RAI: absolutely contraindicated

Graves disease in pregnancy: monitoring

• TFTs 3-4 wkly after each dose change, 6-8 weekly if stable

• Check TRAB at 24-28/40: if +ve, foetal USS monthly for foetal goitre from 28/40

• Aim for lowest possible ATD dose; may be able to stop medication by 3rd trimester.

• Target fT4 towards upper end of ref range• Risk of relapse post partum• low dose ATDs fine if breastfeeding (even though

excreted into and found in breast milk: take in divided doses post feed)

Foetal hyperthyroidism

• High foetal heart rate (>160 beats/minute)• foetal goitre• poor growth• craniosynostosis • Cardiac failure and hydrops may occur with

severe disease.

Case 5• 33 yr old woman• Presented with primary infertility• PRL 1800 – 2500, no medication• MRI: 11mm prolactinoma• Started on cabergoline 500mcg weekly• PRL into normal range; wants to conceive ASAP. • Asks about pregnancy management: what do you tell

her?

Prolactinoma and pregnancy

• Micro v. macro

• Treatment in pregnancy

• Monitoring

• Postnatal management

Case 6

• 28 yr old woman• Seen at 11/40 with presyncope, nausea &

vomiting: treated symptomatically (BP 80/40, Na 129)

• Low BP noted at CMW appointments• Presents at 28/40 with prem labour and IUGR• Profound hypotension post delivery. Na 122• SST: baseline cortisol 34, rises to 44!

Addison’s and pregnancy

• No XS foetal morbidity (if pre-existing Addison’s)• Management no different to non-pregnant state• May need HC dose increase 3rd trimester (or times of

acute stress) > extra 5-10mg daily• Fludrocortisone: no change• In labour: HC 50-100mg IM QDS, or 200mg/24hr via

continuous IVI• Tail off back to normal dose post delivery/for

breastfeeding

Addison’s presenting in pregnancy

• May present as adrenal crisis at time of delivery due to late diagnosis

• Associated with foetal growth restriction• Diagnose in usual way • No pregnancy specific ref range available for

cortisol/ACTH, but cortisol normally rises in pregnancy so use higher cutoffs e.g random am cortisol< 300 in 1st trimester, < 450 in 2nd trimester, <600 in 3rd, should raise suspicion in clinical context

What we haven’t talked about…

• Phaeochromocytoma• Cushings• Hypopituitarism• Primary hyperparathyroidism• CAH

Questions?