Thyroid and pregnancy Control of Thyroid Function - PowerPoint Presentation

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Thyroid and pregnancy

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Control of Thyroid Function

Hypothalamus releases TRH

Act on the pituitary gland to release TSH

TSH causes the thyroid gland to release the thyroid hormones (T

3 and T4)TRH and TSH concentrations are inversely related to T3 and T4 concentrations. 99% circulating T3 and T4 is bound to TBG. 1%

free form Biologically Active

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Physiologic Changes in Pregnancy

Pregnancy is a state of relative iodine deficiency, because:

- Active transport to fetoplacental unit

- Increase iodine excretion in urine, 2 fold (increased GFT & decreased renal tubular reabsorption) - Thyroid gland increases its uptake from the blood

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TBG

- Increase (hepatic synthesis is increased)

TT4 & TT3

- Increase to compensate for this rise

FT4 & FT3 (crosses the placenta in the 1st half of pregnancy) - Decrease. FT4 are altered less by pregnancy, but do fall little in the 2nd & 3rd trimesters. TSH (does not cross placenta) - decreases in 1st trimester, between 8 to 14 wks HCG, HCG has thyrotropin-like activity - Increase in 2nd & 3rd trimester (Increased TBG)

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Changes of Hormones in Pregnancy

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Thyroid hormones in pregnancy

Maternal

Thyroid volume increases by 10–20% with increased vascularity and a rise in thyroglobulin during pregnancy.

Hepatic synthesis of thyroid-binding globulin (TBG) is increased with increase in total T4 and T3 concentrations

Levels of free T4 and free T3 may rise in the first trimester, due to a hCG thyrotropic effect, but then remain in the normal rangeTSH is usually within normal limits in pregnancy but can be suppressed particularly in the first trimester because there is a negative correlation that exists between TSH and hCG levels in the first half of pregnancyTSH receptor antibodies may cross the placenta when present in high concentrations but the titre decreases with the progression of pregnancy.

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Fetal

TRH & TSH synthesis by 8–10 weeks

Thyroid hormone synthesis by 10–12 weeks

TSH, TBG, free T4 and T3 increase throughout gestation

Maternal TSH does not cross the placentaMaternal T4 and T3 does cross the placenta in small quantities for early fetal growth.

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Hyperthyroidism

Causes of maternal hyperthyroidism:

Graves disease (90% of cases)

toxic noduletoxic multinodular goitre

hydatiform molehyperemesis gravidarum.

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Maternal & fetal outcomes are worse in cases of uncontrolled hyperthyroidism, with higher rates of:

pre-eclampsia

thyroid storm and

thyrotoxic

heart failurefetal growth restrictionprematuritystillbirthsfetal or neonatal thyrotoxicosis neonatal hypothyroidism

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Treatment

Medications

:

carbimazole (CBZ), methiamazole

(MMI) or propylthiouracil (PTU), cross the placenta, but PTU less so than CBZ and MMI.Surgery is rarely performed in pregnancy, possibly if drug resistance or serious side effects with antithyroid drugs, e.g. agranulocytosis. Radioactive iodine treatment is contraindicated during pregnancy and should be avoided for at least 6 months after treatment.

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Hypothyroidism

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Clinical / Subclinical Hypothyroidism

Clinical

Hypothyroidism

Subclinical

HypothyroidismTSHHigh (>10) High (>3 - <10) Free T4 LowNormal Free T3 Normal or lowNormal Serum TSH level > 3.0 mIU/l Subclinical hypothyroidism  elevated TSH with normal FT4, FT3.

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Epidermiology

Overt hypothyroidism complicates up to 3 of 1,000 pregnancies

Subclinical hypothyroidism is estimated to be 2-5 % (

Canaris GH, 2000)

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Symptoms of Hypothyroidism

Slowing of metabolic processes:

Lethargy/fatigue weight gain cognitive dysfunction

cold intolerance constipation bradycardia

delayed relaxation of tendon reflexesslow movement and slow speechDeposition of matrix substances:Dry skin hoarseness edemapuffy face and eyebrow loss peri-orbital edemaenlargement of the tongueOthersDecreased hearing myalgia and paresthesia depressionmenorrhagia arthralgia pubertal delaygalactorrhea

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Overlapping Complaints

Symptoms

Hypothyroidism

Pregnancy

FatigueConstipationHair LossDry SkinBrittle NailWeight GainFluid RetentionBradycardiaCarpel Tunnel Syndrome

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Subclinical Hypothyroidism

Elevated TSH (

> 3.0

mIU/l)

with normal FT4, FT3.31 % with anti-TPO antibodyMore common on women with autoimmune diseases50 %  hypothyroidism in 8 yearsMay cause childhood IQ decreaseIncrease in preterm 4% vs 2.5% in euthyroid mother (Casey BM, 2007)

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Types of Hypothyroidism

Primary hypothyroidism

Secondary/tertiary hypothyroidism

IatrogenicEnvironmental

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Primary Hypothyroidism

Developed Countries

Hashimoto’s thyroiditis – Chronic thyroiditis

prone to develop postpartum thyroiditis

WorldwideIodine deficiencyOther Causes:Subacute thyroiditisThyroidectomy, radioactive iodine treatment

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Hashimoto’s Thyroiditis

An inflammatory disorder of thyroid gland

More common on those with other autoimmune diseases

Almost 100% associated with anti-TPO antibody. (Fitzpatrick & Russell)

May cause transient hyperthyroidismPE: Goiter, rubbery consistency, moderate in size, mostly bilateral, painless.

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Hashimoto’s Thyroiditis

T cells recognize the patient’s own thyroid antigens as foreign



cytotoxic to thyroid epithelial cells

 stimulate B cells to make anti-thyroid antibodies, anti-peroxidase antibody, anti-thyroglobulin antibody, and anti-TSH-receptor antibody  block the action of TSH, leading to hypothyroidism!!

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Hashimoto’s Thyroiditis

Lymphoid infiltrate, often with germinal centers

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Iodine Deficiency

Affect 38% of worldwide population (Pearce EN, 2008)

Sources: Iodized salt and seafood. Others: cow milk, egg, beans…

Perinatal

mortalityCongenital cretinism (growth failure, mental retardation, other neuropsychological deficits) ACOG

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Subacute Thyroiditis

Subacute granulomatous thyroiditis

- Painful - Fever, myalgia

- Viral infection

Subacute lymphocytic thyroiditis - includes postpartum thyroiditis (Prevalent: 5% ) - PainlessSymptomatic Tx for initial hyperthyroidism

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Secondary and Tertiary Hypothyroidism

<1% hypothyroidism cases

Low or normal serum TSH concentrations + low serum T4 and T3

2

nd (TSH deficiency) hypothyroidism: - pituitary tumor - postpartum pituitary necrosis (Sheehan's syndrome) - trauma, infiltrative diseases.3rd (TRH deficiency) hypothyroidism can be caused by - Damages the hypothalamus or - Interferes with hypothalamic-pituitary portal blood flow

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Medication Cause

Inhibit

GIT Absorption of thyroid hormone.

Separated by 4 hours

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Screening and Its Importance

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Overt hypothyroidism in pregnancy is rare

In continuing pregnancies hypothyroidism is associated with increased risk of:

Pre-

eclampsia

Placenta Abruptionincreased c-section ratesFetal death (especially if increased TSH occurs in 2nd trimester) Motherisk April 2007

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More for the Baby!!

Maternal thyroid hormones are important in embryogenesis

No production until 12 weeks, therefore

needs mom’s T4 for fetal brain development

Maternal hypothyroidism can cause negative effect on fetal intellectual development. Higher incidence of LBW (due to medically indicated preterm delivery, pre-eclampsia, abruption)Iodine deficient hypothyroidism -> congenital cretinism (growth failure, mental retardation, other neuropsychological deficits) Motherisk April 2007, CMAJ Apr 2007 176(8)Treatment before 10 weeks’ gestation  No adverse effect

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Indications for Screening

universal

screening is

not recommended (ACOG)

Family Hx of autoimmune thyroid diseaseWomen on thyroid therapyPresence of goiter or thyroid nodulesHx of thyroid surgeryInfertilityUnexplained anemia or hyponatremia or high cholesterol levelPrevious Hx of - neck radiation - postpartum thyroid dysfunction - previous birth of infant with thyroid problemOther autoimmune chronic conditions: Type 1 DM

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Laboratory Workup

Overt hypothyroidism:

symptomatic patient

elevated TSH level low levels of FT4 and FT3Subclinical hypothyroidism: asymptomatic patient elevated TSH normal FT4 and FT3

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Treatment

Replacement with external thyroid hormone --

levothyroxine

(

Levothyroid, Levoxyl, Synthroid, and Unithroid). Levothyroxine (Synthroid) pregnancy category A A sterioisomer of physiologic thyroxine1.6 mcg/kg, usually about 50 to 100 mcg/day for women30-60 minutes before eating breakfast.

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Treatment and Goals

The American Association of Clinical Endocrinologists recommends keeping the thyroid-stimulating hormone (TSH) level between

0.3 and 3.0 mIU/L.

After readjustment of levothyroxine, observe 6-8 weeks

Check TSH every trimester

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Side Effects of L-Thyroxine :

Rapid or irregular heartbeat

Chest pain or shortness of breath

Muscle weakness Nervousness Irritability Sleeplessness

Tremors Change in appetite Weight loss

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Pearls

Safe in pregnancy and lactation

Very little thyroxin crosses the placenta NO risk of thyrotoxicosis of fetusPatients who were on thyroxine therapy before pregnancy should increase the dose by 30% once pregnancy is confirmed (Bombrys et al, 2008) Keep TSH level between 0.3 and 3.0 mU/L.TSH should be monitored every trimester until delivery.

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Overt hypothyroidism (OH) 

OH complicates 2–10 per 1000 pregnancies and is commonly due to:

Hashimoto's thyroiditis

previous radioiodine therapy/thyroid surgeryprevious postpartum thyroiditishypopituitarism

iodine deficiency.

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Maternal and fetal outcomes are worse with OH

higher risks of spontaneous miscarriage, PET,PIH, PPH & low birth weight.

There is a risk of a slight reduction in IQ in the fetus but no increased risk of congenital malformations.

Pregnancy itself probably has no effect on hypothyroidism although approximately 25% of women will require an increase in their thyroxine dose in pregnancy

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Congenital cretinism

is a well-documented syndrome of growth restriction, deafness and neuropsychological impairment, resulting from severe iodine deficiency or untreated congenital hypothyroidism.

woman should be

euthryoid

at conception, on a stable dose of thyroxine and the importance of compliance during the first trimester should be emphasised.

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THANK YOU