6TSH Low High FT4 & FT3 FT4 Low High Low High Central Hypothyroid 1° Thyrotoxicosis1° HypothyroidIfequivocal2° thyrotoxicosisRAIUTRH Stim.Endo consultFT3, rT3MRI, α-SUMRI, etc.
7Case 1GH, IGF-1 normalLH, FSH, E2, progesterone, PRL normal for pregnancy8 AM cortisol 345, short ACTH test normalMRI: normal pituitaryTGAB, TPOAB negativeNormal pregnancy, delivery, baby, lactation
8Thyroid & Pregnancy: Normal Physiology Increased estrogen increased TBG (peaks wk 15-20)Higher total T4 & T3:normal FT4 & FT3 if normal thyroid fn. and good assaymany automated FT4 assays underestimate true FT4 level (except Nichols equilibrium dialysis free T4 assay)if suspect your local FT4 assay is underestimating FT4 can check total T4 & T3 instead (normal pregnant range ~ 1.5x nonpregnant)hCG peak end of 1st trimester, hCG has weak TSH agonist effect so may cause:slight goitremild TSH suppression ( mU/L) in 9% of pregmild FT4 rise in 14% of preg
9Thyroid & Pregnancy: Normal Physiology Fetal thyroid starts working at wksT4 & T3 cross placenta but do so minimallyCross placenta well:MTZ > PTUTSH-R Ab (stim or block)ATD (PTU & MTZ):Fetal goitre (can compress trachea after birth)MTZ aplasia cutis scalp defectsOther MTZ reported embryopathy: choanal atresia, esophageal atresia, tracheo-esophageal fistulaTherefore do NOT use MTZ during pregnancy, use PTU instead
11No TSH & FTI at end of 1st trimester as expected from hCG effect Requirement to increase LT4 dose occurred between weeks 4 -20Despite exponential rise in estradiol throughout pregnancy (note y-axis units) TBG levels plateau at 20 wks
12LT4 dose requirement tied to rising TBG levels (THBI inversely proportional to TBG level)By 10 wks need average increase of 29% LT4 doseBy 20 wks need average increase of 48% LT4 doseNo increase of dose beyond 20 wks required
13* Regardless of cause of hypothyroidism (Hashimoto’s, thyroidectomy) initial LT4 dose increase is usually required early (~ week 8), before 1st prenatal visit!
14Thyroid & Pregnancy: Hypothyroidism 85% will need increase in LT4 dose during pregnancy due to increased TBG levels (ave dose increase 48%)Risks:increased spont abort, HTN/preeclampsia, abruption, anemia, postpartum hemorrhage, preterm labour, baby SGAFetal neuropsychological development (NEJM, 341(8): , Aug 31, 2001):Cognitive testing of children age 7-9Untreated hyothyroid mothers vs. normal mothers:Average of 7 IQ points less in childrenIncreased risk of IQ < 85 (19% vs. 5%)Retrospective study, data-dredging?
15LT4 dose adjustment in Pregnancy: - Optimize TSH preconception (0 LT4 dose adjustment in Pregnancy: - Optimize TSH preconception (0.4 – 2.5 mU/L) - TSH at pregnancy diagnosis (~3-4 wk gestation), q1mos during 1st wks and after any LT4 dose change, q2mos 20 wks to term - Instruct women to take 2 extra thyroid pills/wk (q Mon, Thurs) for 29% dose increase once pregnancy suspected (+ commercial preg test) - If starting LT4 during preg: initial dose 2 ug/kg/d and recheck TSH q4wk until euthythyroidTSHDose AdjustmentTSH increased but < 10Increase dose by 50 ug/dTSH 10-20Increase dose by ug/dTSH > 20Increase dose by 100 ug/d
16Pregnancy: screen for thyroid dysfn ? Universal screening not currently recommended:ACOG, AACE, Endo Society, ATAControversial!Definitely screen:Goitre, FHx thyroid dysfn., prior postpartum thyroiditis, T1DMIdeally, check TSH preconception:mU/L: recheck TSH during 1st trimestermU/L: do not need to recheck during pregIf TSH not done preconception do at earliest prenatal visit:mU/L: hCG effect (9% preg), recheck in 5wk< 0.1 mU/L: recheck immediately with FT4, FT3, T4, T3
19Thyrotoxicosis & Pregnancy Diagnosis difficult:hCG effect:Suppressed TSH (9%) +/- FT4 (14%) until 12 wksEnhanced if hyperemesis gravidarum: 50-60% with abnormal TSH & FT4, duration to 20 wksFT4 assays reading falsely lowT4 elevated due to TBG (1.5x normal)NO RADIOIODINEMeasure:TSH, FT4, FT3, T4, T3, thyroid antibodies?Examine: goitre? orbitopathy? pretibial myxedema?
20Pregnant & Suppressed TSH Recheck in 5 wksFT4, FT3, T4, T3Thyroid Ab’sExamineStill suppressedNormalizesHyperemesis GravidarumVery High TFT’s:TSH undetectablevery high free/total T4/T3hyperthyroid symptomsno hyperemesisTSH-R ab +orbitopathygoitre, nodule/TMNGpretibial myxedemaDon’t treat with PTUAbnormal TFT’s past 20 wkTreat Hyperthyroidism (PTU)
21Thyrotoxicosis & Pregnancy: Rx No RAI ever (destroy fetal thyroid)PTUStart 100 mg tid, titrate to lowest possible doseMonitor qmos on Rx: T4, T3, FT4, FT3TSH less useful (lags, hCG suppression)Aim for high-normal to slightly elevated hormone levelsT nM, T nM, FT pM3rd trimester: titrate PTU down & d/c prior to delivery if TFT’s permit to minimize risk of fetal goitreConsider fetal U/S wk to R/O fetal goitreIf allergy/neutropenia on PTU: 2nd trimester thyroidectomy
22Thyrotoxicosis & Lactation ATD generally don’t get into breast milk unless at higher doses:PTU > mg/dMTZ > 20 mg/dGenerally safeI prefer PTU > MTZ for preg lactatingTake ATD dose just after breast-feedingShould provide 3-4h interval before lactates again
23Neonatal Grave’s Rare, 1% infants born to Graves’ moms 2 types: Transplacental trnsfr of TSH-R ab (IgG)Present at birth, self-limitedRx PTU, Lugol’s, propanolol, prednisonePrevention: TSI in mom 2nd trimester, if 5X normal then Rx mom with PTU (crosses placenta to protect fetus) even if mom is euthyroid (can give mom LT4 which won’t cross placenta)Child develops own TSH-R abStrong family hx of Grave’s3-6 mos20% mortality, persistant brain dysfunction
24Postpartum & Thyroid 5% (3-16%) postpartum women (25% T1DM) Up to 1 year postpartum (most 1-4 months)Lymphocytic infiltration (Hashimoto’s)Postpartum Exacerbation of all autoimmune dx25-50% persistant hypothyroidismSmall, diffuse, nontender goitreTransiently thyrotoxic Hypothyroid
26Postpartum & Thyroid Distinguish Thyrotoxic phase from Grave’s: Rx: No Eye disease, pretibial myxedemaLess severe thyrotoxic, transient (repeat thyroid fn 2-3 mos)RAI (if not breast-feeding)Rx:Hyperthyroid symptoms: atenolol mg odHypothyroid symptoms: LT ug/d to startAdjust LT4 dose for symtoms and normalization TSHConsider withdrawal at 6-9 months(25-50% persistent hypothyroid, hi-risk recur future preg)
27Postpartum & Thyroid Postpartum depression When studied, no association between postpartum depression/thyroiditisOverlapping symtoms, R/O thyroid before start antidepressentsScreening for Postpartum ThyroiditisHOW: TSH q3mos from 1 mos to 1 year postpartum?WHO:Symptoms of thyroid dysfn.GoitreT1DMPostpartum thyroiditis with prior pregnancy
29Gestational Diabetes Mellitus (GDM) “Glucose intolerance with onset/discovery during pregnancy”Some T2DM picked up during pregnancyRarely some T1DM may present during pregnancyPrevalence higher than previously thought in Canada:% non-Aboriginal (but multi-ethnic) population% Aboriginal
30Gestational Diabetes Mellitus (GDM) Prior “selective screening” resulted in missed cases:Caucassians < 25 y.o.No personal or FHx of DMNo prior infant with birth weight > 4 kgTreatment of GDM reduces perinatal morbidityDiagnosis GDM maternal anxiety ?Evidence controversial for thisTherefore all women should be screened
35GDM Treatment CBG qid: FBS, 1-2h pc Dietary: 3 small meals, 3 small snacksIf glycemic targets not met: InsulinMultiple Daily Injection (MDI) bestInsulins: regular, lispro, aspart ? (still new)No glargine (stimulates IGF-I receptors)
36GDM Treatment No OHA’s, not standard of care yet. Glyburide Metformin Minimal crossing of placenta, 3rd trimester most organogenesis complete1 RCT: 404 women, mild GDM, glyburide vs. insulin, no difference in outcomesFurther study before safety establishedMetforminRetrospective cohort: preeclampsia & stillbirthBias: DM women older, more obese
37GDM: Labour & Postpartum NPO during Labour:Monitor CBG q1h, target BS 4 – 6.5 mMHypoglycemia (BS < 4 mM): IV D5WHyperglycemia (BS > 6.5 mM): IV D5W & IV insulin gttPostpartum:D/C all insulin (IV and SC)CBG in recovery:> 10 mM CBG qid, may need Rx for T2DM< 10 mM stop CBG monitoringFBS or 2hPG in 75g OGTT within 6 mos postpartum and prior to any future planned pregnanciesEncourage: breast feeding, healthy diet, exercise to prevent future Type 2 DM, GDMScreen for future T2DM (GDM is a risk factor)
42T1DM & T2DM: Labour & Postpartum NPO during Labor:Monitor CBG q1h, target BS 4.0 – 6.5 mMIV D5W & IV insulin gtt (Hamilton Health Sciences Protocol)Postpartum:D/C all IV insulinInsulin resistance/requirements rapidly fall during & after laborT2DM: monitor CBG qidRestart insulin if CBG > 10 mMT1DM: postpartum honeymoonCBG q1h x 4h, then q2h x 4h, then q4hRestart MDI insulin S.C. when CBG > 10 mMNo OHA, ACE-I or ARB during breast feeding!