5Clinical presentation - 1 A 19 year old primi with H/o 54 days amenorrhea was referred by obstetrician with C/o palpitations, weight loss of 2-3 months duration (8 kg), Her haemoglobin was 9.8 g/dl, HR 120/mt with prominent eye sign.
6Q1In a background of clinical suspicion of Graves disease, the preferred investigation of choice :TSH, T3, T4TSH, FT4, FT3TSH, FT44. TSH, FT4, Anti-TPO antibodies
7Thyroid Function Tests in Pregnancy-hyperthyroidism TSHLowFT4NormalHighHyperthyroidismFT3SubclinicalHyperthyroidismNormal
8Q2Her TSH was < (n mIU/L)and FT (n ng/dl). Her TPO antibodies were positive. Drug of choice is Propanolol +CarbimazoleMethimazolePTU
13Approach in Pregnant & 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)
14Thyrotoxicosis & Pregnancy: Rx No RAI ever (destroy fetal thyroid)PTUStart 100 mg tid, titrate to lowest possible doseMonitor dose by: FT4, TSHTSH alone is less useful (lags, hCG suppression)Aim for high-normal to slightly elevated hormone levelsFT ng/dl and TSH 0.5 – 2.5mIU/L3rd trimester: titrate PTU down & decrease prior to delivery if TFT’s permitConsider fetal U/S wk to R/O fetal goitreIf allergy/neutropenia on PTU: 2nd trimester thyroidectomyPropranolol
15TO summarize…. Arrive at the diagnosis. Correlate clinically Rule out hyperemesisTreat with PTU and propranolol in hyperthyroidismWatch for neutropenia and infectionsMonitor FT4 to assess control
16Points to ponder……. Target FT4 is 0.85-1.9 ng/dl TSH alone not helpful in monitoring PTU dose.PTU dose adjusted every 3-4 weeks.Symptoms improve in 3-4 wk but full response only after 8 weeks.Block and replace therapy avoided in pregnancy due to risk to fetus.Fetal monitoring is importantSubclinical hyperthyroidism-no intervention.
17Q4 Clinical Presentation - 2 Known hypothyroidism on 150 mcg Eltroxin with H/o 3 months amenorrhea comes with TSH,T3,T4 results. TSH-2.5(n 0.3 – 4.5 mIU/L) T4 – 16.4 (n ug/dl) T3 – 3.2 (n ng/dl).Eltroxin should be stopped.Eltroxin dose should be increased in pregnancyCheck FT4 aloneCheck FT4 ,FT3
18Thyroid Function Tests in Pregnancy-hypothyroidism TSHHighFT4NormalLowSubclinical HypothyroidismPrimary Hypothyroidism
19Thyroid & 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 hypothyroid mothers vs. normal mothers:Average of 7 IQ points less in childrenIncreased risk of IQ < 85 (19% vs. 5%)
20Causes & Diagnosis of Hypothyroidism Hashimoto’s (chronic thyroiditis; most common in developed countries) & iodine deficiency -> both associated with goiterSubacute thyroiditis -> not associated with goiterThyroidectomy, radioactive iodine treatmentIodine deficiency (most common worldwide; rare in US)
22Points to ponder ….. Known hypothyroid, eltroxin is increased by 30-50% in first trimester.First time diagnosed start eltroxin at 1-2 mcg/kg /dayTarget TSH is 0.5 – 2.5mU/LTSH checked initially at 4-6 weeks and later 8 weeksSpace eltroxin and vitamin tablets to avoid interaction.Postpartum-dose is reducedRecommended iodide salt avg 250 mcg/day
23Q5 Clinical Presentation - 3 27 year old female and 3 MA with clinical features suggestive of hypothyroidism has a TSH 6.8 and FT4 1.2 ng. This isOvert HypothyroidismSubclinical HypothyroidismSubacute ThyroiditisOvert Hyperthyroidism
24Recommended approach in this patient Q6Recommended approach in this patientStart eltroxinRepeat TSH every 4 weeks until weeks and atleast once between weeksRepeat TSH & FT4 every 4 weeks until weeks and atleast once between weeksNo Intervention at all.
25Pregnancy: 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
26Takeaways……..Thyroid is second commonest endocrine disorder in pregnancy.Untreated hypothyroidism-fetus more affectedUntreated hyperthyroidism-mother more affectedSubclinical hypothyroidism- treatSubclinical hyperthyroidism-followupRoutine screening- not recommended
28Management…..LT4 1-2 mcg/kg/dayDose adjustments by mcg
29Hyperthyroidism & Pregnancy TPO antibodies are increased in (80–90%) of patients with Graves disease+ Other autoimmune disorders(TRAbs) are increased in >80% of patients with Graves disease
30Endo consult FT3, rT3 MRI, α-SU TSH Low High FT4 & FT3 FT4 Low High Central Hypothyroid1° Thyrotoxicosis1° HypothyroidIfequivocal2° thyrotoxicosisRAIUTRH Stim.Endo consultFT3, rT3MRI, α-SUMRI, etc.
31EFFECTS OF PREGNANCY ON THYROID PHYSIOLOGY Physiologic ChangeThyroid-Related Consequences↑ Serum thyroxine-binding globulin↑ Total T4 and T3; ↑ T4 production↑ Plasma volume↑ T4 and T3 pool size; ↑ T4 production; ↑ cardiac outputD3 expression in placenta and (?) uterus↑ T4 productionFirst trimester ↑ in hCG↑ Free T4; ↓ basal thyrotropin; ↑ T4 production↑ Renal I- clearance↑ Iodine requirements↑ T4 production; fetal T4 synthesis during second and third trimesters↑ Oxygen consumption by fetoplacental unit, gravid uterus, and mother↑ Basal metabolic rate; ↑ cardiac output
33No 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
356. Women with type I diabetes. 7. Women with other autoimmune disorders.8. Women with infertility who should have screening with TSH as part of their infertility work-up.9. Women with previous therapeutic head or neck irradiation.10. Women with a history of miscarriage or preterm delivery.
36Why treat hypothyroidism in preg? To prevent:Premature birthLBWAbruption,PPHImpaired neuropsychological development in child
37Physiologic thyroid adaptations in pregnancy TBGFT4, FT3hCGTSHPlasma iodide
38Thyrotoxicosis & 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?
39Hyperthyroidism & Pregnancy ComplicationsFirst-trimester spontaneous abortions.High rates of still births and neonatal deaths.low birth weight infants : ↑ 2-3 folds.Premature delivery.Fetal or neonatal hyperthyroidism.Intrauterine growth retardation .
40Case Presentation - 2A 19 year old primi with H/o 54 days amenorrhea was referred by obstetrician for C/o palpitations, weight loss of 2-3 months duration (8 kg), Her hemaglobin was 9.8 g/dl, HR 120/mt with prominent eye sign.
41Q1In a background of clinical suspicion of Graves disease, the preferred investigation of choice :TSH, T3, T4TSH, FT4, FT3TSH, FT4TSH, Anti-TPO antibodies
42Q2Her TSH was < and FT Her TPO antibodies were positive. Drug of choice:CarbimazoleMethimazoleBetablockersPTU
43Q3 Restart LT4 in preconception dose Wait for 4 weeks and recheck TSH Known hypothyroidism on 150 kg LT4 lost following and came 2 years later with H/o 3 months amenorrhea. She had stopped LT4 since conception and has checked TSH now which was 2.8Restart LT4 in preconception doseWait for 4 weeks and recheck TSHRestart LT4 in low doseWait till delivery and then restart LT4
44The Fetal Thyroid Begins concentrating iodine at 10-12 weeks Controlled by pituitary TSH by approximately 20 weeks
4510-12 wks of gestation: Fetal thyroid concentrates iodine, synthesize T3 and T4. The fetal pituitary differentiates. Prior to 12 weeks the mother is the sole source of thyroid hormone to the fetus. Fetal thyroid function is at low basal level till wks At birth TSH 70uU/ml. Day 2max. TSH 12uU/ml
46Treatment indicated if FT4>2.0ng/dl PTU mg q12 hours in pt. with minimal symptoms (doses>200 mg of PTU can result in fetal goiter & HypothyroidismPt with large goiters & long disease duration may require larger initial doses mg tidClinical improvement (weight gain & ↓in HR) is noted in the first 2-6 wks, with FT4 improvement in the first 2 wksOnce clinical improvement occurs the dose of PTU is ↓by half. Goal to keep FT4 at the upper limit of normal, with least amt of medicationIn 30% of pt PTU may be D/C’ed in the last 4 - 8wks of pregnancy (Mestman. Best Practice & Research clin endoMetb.,200,vol 18,no. 2,27-88)
47CENTRAL CONGENITAL HYPOTHYROIDISM Uncontrolled maternal hyperthyroidismHigh levels of serum T4 in maternal circulation cross placental barrierFeed back to the fetal pituitary with suppression of fetal pituitary TSHDiagnosis : Neonatal serum FT4 is low & serum TSH is low normal or inappropriate for the level of FT4. In majority of infants there is a return to euthyroidism in a few weeks to months.Rx with LT4 and long term follow up
48Physiologic Changes in Thyroid Function During Pregnancy Maternal StatusTSH**initial screening test**Free T4Free Thyroxine Index (FTI)Total T4Total T3Resin Triiodo-thyronine Uptake (RT3U)PregnancyNo changeIncreaseDecreaseHyperthyroidismIncrease or no changeHypothyroidismDecrease or no change
49Physiologic adaptation during pregnancy increase in thyroid-binding globulinsecondary to an estrogenic stimulation of TBG synthesis and reduced hepatic clearance of TBG ;two to threefoldlevels of bound proteins, total thyroxine, and total triiodothyronine are increased and resin triiodothyronine uptake (RT3U) is decreasedbegins early in the first trimester, plateaus during midgestation, and persists until shortly after deliverydecrease in its hepatic clearance,estrogen-induced sialylationfree T4 and T3 increase slightly during the first trimester in response to elevated hCG. decline to nadir in third trimester
50human chorionic gonadotropin (hCG) intrinsic thyrotropic activitybegins shortly after conception, peaks around gestational week 10,declines to a nadir by about week 20directly activate the TSH receptorpartial inhibition of the pituitary gland (by cross-reactivity of the α subunit)transient decrease in TSH between Weeks 8 and 14mirrors the peak in hCG concentrations20% of normal women, TSH levels decrease to less than the lower limit of normal
51Graves' hyperthyroidism occurs in approximately 0 Graves' hyperthyroidism occurs in approximately 0.2 percent of women, and it occurs in approximately one to five percent of infants born to these mothers [2-4].
52Hyperthyroidism & Pregnancy CausesGraves disease (85–90% of all cases)Sub-acute thyroiditisToxic MNGToxic adenomaTSH-dependent thyrotoxicosisIodine-induced hyperthyroidismExogenous T3 or T4
53Management TSH >2.5 monitor Target TSH 0.5—2.5 Always check FT4 TPO antibodies if TSH is 3-10TSH to be checked every 8 weeksLT4 1-2 mcg/kg/dayDose adjustments by mcg
54Neonatal Grave’sRare, 1 - 5% infants born to Graves’ moms2 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, persistent brain dysfunctionScreen for fetal goiter even in mothers treated previously with RAI or ATD before consumption.
55Pregnancy: screen for thyroid dysfn ? Universal screening not currently recommended:ACOG, AACE, Endo Society, ATAControversial !Definitely screen:Goitre, Family H/o 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
568. SCREENING FOR THYROID DYSFUNCTION DURING PREGNANCY 1. Women with a history of hyperthyroid or hypothyroid disease, PPT, or thyroid lobectomy.2. Women with a family history of thyroid disease.3. Women with a goiter.4. Women with thyroid antibodies (when known).5. Women with symptoms or clinical signs suggestive of thyroid underfunction or overfunction, including anemia,elevated cholesterol, and hyponatremia.
57Hyperthyroidism & Pregnancy TPO antibodies are increased in (80–90%) of patients with Graves disease+ Other autoimmune disorders(TRAbs) are increased in >80% of patients with Graves disease