Thread by @TimKorevaar

A tweetorial on hyperthyroidism during pregnancy.

Following yesterday's @ObsMedEd webinar on thyroid disease in pregnancy:

#MedTwitter #FirstTweetorial
Feedback and discussion more than welcome!

[Picture: neonatal Graves' disease] nejm.org/doi/full/10.10…

Hyperthyroidism occurs in 1%-2.2% of pregnancies, depending on the reference range you use.

Probably 95% of hyperthyroidism in pregnancy is physiological due to thyroid stimulation by hCG.

liebertpub.com/doi/abs/10.108…
academic.oup.com/clinchem/artic…
Figure from rdcu.be/uKOO

hCG --> high structural similarity with TSH --> weak binding affinity for TSH receptor (TSHr)
--> ~50% increase thyroid hormone production/secretion in pregnancy
--> negative feedback --> lower TSH --> (subclinical) hyperthyroidism

Physiological or hCG-mediated hyperthyroidism should be distinguished from pathophysiological hyperthyroidism.

Physiological: similar risk or even protective of adverse pregnancy outcomes

Pathophysiological: higher risk of adverse pregnancy outcomes.

Let's look at the differential diagnosis.

First thing to distinguish is Graves' disease.
Risk factors: clinical signs, FT4 >1.5x ULN, persisting hyperthyroidism after week 18.

Graves' disease complicates 0.5% of pregnancies.

--> 90% have pre-existing disease - newly diagnosed is very rare!

Higher risk of various pregnancy complications, especially if biochemically uncontrolled.

Thus, preconception counselling is pivotal!

pubmed.ncbi.nlm.nih.gov/24481256/

In any woman <45 yrs diagnosed with Graves' disease, discuss:

Antconception
Pregnancy planning
Contacting you upon a positive pregnancy test
Treatment options [see very basic info below]

Besides the hard contraindication for conception within 6 months after radioactive iodine due to radioactivity, there is also a relative contraindication for ~18 months due to a flare in TSHr antibodies.

To measure = to know, though.

eje.bioscientifica.com/view/journals/…

So, why not treat all women with antithyroid drugs (ATD) before or during pregnancy?

Recent data indicates a higher risk of fetal birth defects.

Absolute risk increase is 3% [PTU] to 5% [MMI].
i.e. 1:20 - 1:33

academic.oup.com/jcem/article/9…
pubmed.ncbi.nlm.nih.gov/29357398/

Mind that any choice has pros & cons.

If ATD required, PTU is preferred
-Lower overall risk
-Less severe fetal birth defects
-No dose-dependent risks [see 2nd link above)
rdcu.be/LS6f

In addition, be aware of fetal hypothyroidism [placental passage, see below]

For any ATD, reducing the exposure around pregnancy will reduce the potential risks.

- Never use block & replace, always titrate
- Consider to stop ATD upon conception --> median time to relapse ~3 months, longer if mild disease

liebertpub.com/doi/full/10.10…
academic.oup.com/jcem/article/1…

Monitor disease activity/treatment:

-Check TSH/FT4 every 4-6 weeks
-> maternal tft=fetal tft
-> Immunetolerance -> lower TRAb in 2nd & 3rd trimester -> often ATD dose reduction required

- Fetal ultrasound every 4 weeks after week 18 (=time of fetal thyroid functional maturity)

Risk assessment of neonatal Graves':
TRAb in early pregnancy
- Negligible risk if <3x ULN, no need to repeat
- If >3x ULN recheck at 25 and 36 weeks
+ intensify ultrasound monitoring

Recheck TRAb if biochemical/ultrasound deterioration.
pubmed.ncbi.nlm.nih.gov/29325496/
Next: some pearls!

Combined stimulating/blocking TRAb can occur, fetal hypOthyroidism in TRAb+ women is possible.

If maternal TFTs/TRAb do not fit with fetal (hyperthyroidism) state, seek expert consultation (amniocentesis?).

Also, TRAb can persist after thyroidectomy!
acpjournals.org/doi/10.7326/L1…

How about the rest of the differential?

Autonomous nodules/multinodular goiter
-> treatment depends on severity and persistence of hyperthyroidism -> mostly mild [below]

Be aware: prior risk of nodule on ultrasound ~25%
Gestational pertechnate scanning possible if necessary.

Subactue thyroiditis is very rare during pregnancy.
Similar to nodular disease, treatment depends on severity and persistence of hyperthyroidism.

Finally: biotine use (vitamin B7)

Found in hair & nail growth vitamin supplements, used in pregnancy also.

Interference in thyroid assays occurs at dosages >2-3mg per day -> biochemically mimics Graves' hyperthyroidism

nejm.org/doi/full/10.10…
jamanetwork.com/journals/jamai…

Summary:
Hyperthyroidism in pregnancy

-Mostly hCG-mediated and benign.
-Think Graves' (clinical signs, FT4>1.5x ULN, persisting hyperthyroidism).
-Balance treatment pros and cons.
-PTU is preferred ATD.
-Monitor TFTs and fetus.
-Nodules/subactue thyroiditis, think severity.

Was this helpful and would you appreciate a tweetorial on subclinical hypothyroidism in pregnancy as a follow-up?

[Any other suggestions or comments more than welcome]
[Join our research efforts consortiumthyroidpregnancy.org]

@threadreaderapp please unroll.