As an endcorinogist I observe an increase number of consultasion for abnormal thyroid function test in pregnant women Pregnancy has a considerable effect on maternal thyroid function. And turkey is in iodine deficient area During the first trimester of pregnancy, maternal serum TSH levels are significantly lower than prepregnancy levels as a result of cross-reactivity of human chorionic gonadotropin (hCG), which is secreted by the placenta, to the TSH receptor on the thyroid gland.The pattern of changes in serum concentrations ofthyroid function studies and hCG according to gestationalage. The shaded area represents the normal range ofthyroid-binding globulin, total thyroxine, thyroid-stimulatinghormone or free T4 in the nonpregnant woman.TBG,thyroid-binding globulin; T4, thyroxine; TSH, thyroid-stimulatinghormone. Modified from Brent GA. Maternal thyroidfunction: interpretation of thyroid function
Significant but reversible changes thyrıid hormone metabolism aims to meet the increased metabolilic needs during pregnancy.
Consequently thyroid function test results of healthy pregnant women differ than those of healthy non pregnant women.thyroid function tests should be interpreted usingpregnancy spesific or trimester-specific TSH and T4 reference ranges for pregnant women. Reference range of TSH lower throughout the pregnancy. upper limit of normal for TSH in the first trimester of pregnancy is approximately 2.5 otal T4 and T3 levels during pregnancy are 1.5-fold higher than in nonpregnant women. Reference ranges for free T4 are method-specific, and trimester-specific reference ranges should be provided with the assay kit
subclinical hypothyroidism represents early, mild thyroid failureSubclinical hypothyroidism is more common in iodinesufficient countriesWomen with TSH levels of 10 or above irrespective of their ft4 levels ara also considered to have OH.SCH is defined as a serum TSH between 2.5-10 with normal t4 concentration
İt wouldbe anticipated that the such percenteges would be higher in areas of iodine insufficiency
The symptoms of hypothyroidism are neither sensitivenor specifi c.Work up any woman with symptoms or personal history of thyroid disease
Subclinical hypothyroidism is more common in iodinesufficient countriesSubclinical hypothyroidism is more common in iodinesufficient countries, and iodine supplementation mightincrease the incidence
Hypothyroidism has been shown to be associated with an increased risk of adverse maternal and fetal outcomes.he risk of these complications is greater in women with overt, rather than subclinical, hypothyroidism.NBS: 1/4000 w/ congenital cretinism. First few days usually mom’s hormones are still present.gHTN – strong associated b/t inadequately treated hypothyroidism and pre-eclampsia;that it is an acceptable cause of reversible HTN in the non-pregnant population as wellControversial whether subclinical hypothyroidism carries this risk…
the risk of these complications is greater in women with overt, rather than subclinical, hypothyroidism.Overt hypothyroidism is associated with an increased risk of miscarriage and preterm delivery, as well as decreased IQ and low birthweight in offspringThe risk of complications during pregnancy is lower in women with subclinical, rather than overt hypothyroidism. However, in some studies, women with subclinical hypothyroidism were also reported to be at increased risk for severe preeclampsia, preterm delivery, and/or pregnancy loss It is uncertain if the children of women with subclinical hypothyroidism are at risk for neuropsychological impairment.subbclinical hypothyroidism is associated with an increased risk of pregnancy complicationsHypothyroidism can have adverse effects on pregnancy outcomes, depending upon the severity of the biochemical abnormalities.
of miscarriage and preterm delivery, as well as decreased IQ and low birthweight in offspring.14,16 Treatment of overt hypothyroidism during pregnancy is, therefore, mandatory and consists of levothyroxine therapy adjusted to achieve a normal trimester-specific serum TSH level. whereas treatment for subclinical hypothyroidism in pregnancy remains controversial
vigorous debate is ongoing on the pros and cons of trating subclinical hypothyroidism during pregnancy
Subclinical hypothyroidism is also associated with an increased risk of miscarriage and preterm delivery, and decreased IQ in offspring.7,15,18,19 However, treatment of subclinical hypothyroidism is not universally advocated, as only one study has shown that such treatment decreases the occurrence of adverse events in the mother and fetusSCH may be associated with an adverse outcomefor both the mother and offspring. In retrospective studies,and in prospective studies on women with SCH and TPOAb, T4 treatment improved obstetrical outcome, but ithas not been proved to modify long-term neurological development in the offspring
TSH monitor required in pregnancy.In women being treated with levothyroxine before becoming pregnant, TSH levels need to be evaluated every 4 weeks during the first 20 weeks of gestation and should be measured at least once during the second half of pregnancy,26 and more frequently if euthyroidism has not been achieved.
Subclinical hypothyroidism in pregnancy
Contemporary Management ofSubclinical Hypothyroidism During Pre-conception and Pregnancy Dilek Gogas Yavuz MD Marmara University School of Medicine Section of Endocrinology and Metabolism
Physiologic Changes in PregnancyEstrogen-mediated increase in circulating levels of TBGhCG stimulation of TSH- Receptors •Increase in total serum T4 and Total T3 but no/minimal change in free T3 or T4 •serum TSH concentrations are appropriately reduced
Effects Of Pregnancy On Thyroid PhysiologyPhysiologic Change Thyroid-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 ↑ T4 productionFirst trimester ↑ in hCG ↑ Free T4; ↓ basal thyrotropin; ↑ T4 production↑ Renal I- clearance ↑ Iodine requirements↑ T4 production; fetal T4 synthesisduring second and third trimesters↑ Oxygen consumption by ↑ Basal metabolic rate; ↑ cardiac outputfetoplacental unit, gravid uterus, andmother
Trimester-spesific reference ranges for Thyroid hormones• The upper limit for total T3 and T4 levels in pregnancy may TSH level as 1.5 times the be estimated upper limit of thebe considered the should nonpregnant reference range for a given most accurate indicator assay . of gestational thyroid status• Reference ranges for free T4 are method- specific, and trimester-specific reference ranges should be provided with the assay kitThe measurement of free T3 and T4 levels in pregnancy is difficult, owing to a highcirculating level of TBG and a decreased level of circulating albumin, which mightdecrease the reliability of immunoassays.
Definitions: Hypothyroidism: An eleveted TSH in conjuction with a decreased fT4 concentration Subclinical hypothyroidism: Serum TSH concentration above the upper limit of the trimester-spesific reference range with normal T4 (TSH:2.5-10 mIU/L and normal T4)
Signs & Symptoms of Hypothyroidism Similar to symptoms of pregnancy; Vague and nonspecific Fatigue Hair loss, Constipation Voice changes Cold intolerance Intellectual slowness Muscle cramps +/- goiter Insomnia Periorbital edema Weight gain Dry skin Carpal tunnel syndrome Prolonged DTR relaxation phase
Causes of Subclinical Hypothyroidism PRIMARY SECONDARY(thyroid dysfunction) (pituitary dysfunction) • Hashimoto thyroiditis • Sheehan’s syndrome • Endemic iodine deficiency • Lymphocytic hypophysitis• History of ablative radioiodine therapy or • history of a thyroidectomy. hypophysectomy.
Untreated Hypothyroidism Associated with Increased Risk of:Maternal Fetal Preeclampsia Preterm birth Low birth weight gestational Perinatal morbidity and hypertension mortality Placental abruption Increased NICU admission Preterm delivery, very Neuropsychological and preterm delivery (<32 cognitive impairment: weeks) Congenital cretinism – Increased rate of growth restriction, deafness, neuropsych caesarean section impairment from severe Postpartum hemorrhage Iodine deficiency or untreated congenital hypothyroidism
The risk is greatest in overt hypothyroidism compared to subclinical hypothyroidism Subclinical Overt Hypothyroidism Spontaneous abortion 10-70% 60% Preeclampsia 0-17% 0-44% Abruption 0% 0-19% Stillbirth/fetal loss 0-3% 0-12% Anemia 0-2% 0-31% Postpartum hemorrhage 0-17% 0-19% Preterm birth 0-9% 20-31%1Montoro et al, Ann Intern Med 1981; 2Davis et al, Obstet Gynecol 1988; 3Leung et al,Obstet Gynecol 1993; 4Wasserstrum et al, ClinEndocrinol 1993; 5Glinoer, Thyroid Today, 1995,6Allan et al, J Med Screen 2002; 7Abalovich et al, Thyroid 2002; 8Stagnaro-Green etal, Thyroid, 2005; 9Sahu et al, Arch Gynecol Obstet 2009L,aFranchi, Thyroid 2005
Should hypothyroidism be treated in pregnancy?Treatment of overt hypothyroidism during pregnancy is mandatory TSH ↑ and T4 ↓ TSH >10 mIU/L irrespective level of T4 no prospective randomised controlled trials of LT4 intervention Overt hypothyroidism is associated with an increased risk of miscarriage and preterm delivery, as well as decreased IQ and low birth weight in offspring NATURE REVIEWS | ENDOCRINOLOGY, Nov 2012
vigorous debate is ongoing on the pros and cons oftrating subclinical hypothyroidism during pregnancy MATERNAL HEALTH Negro R et al, Universal Screening vs Case Finding for Detection and Treatment of Thyroid Dysfunction During Pregnancy, J Clin Endocrinol Metabolism 2010 95:1699 FETAL HEALTH Lazarus J et al. Controlled Antenatal Thyroid Screening (CATS) Study.
Universal Screening vs Case Finding for Detection and Treatment of Thyroid Dysfunction During Pregnancy NO BENEFIT to pregnancy outcome 2Aim: the potentialreduction in pregnancy complications/patient 1.5associated adverse effectsafter LT4 treatment in 1 0.7 0.7hypothyroid women vs 0.5case finding hypothyroidwomen not receiving 0LT4Rx Universal Screen Case Finding Negro R et alJ Clin Endocrinol Metabolism 2010 95:1699
Maternal Hypothyroidism and Cognitivedevelopment NO difference in IQ scores• Controlled antenatal thyroid screening study 120• 22,000 women: ½ screened 100 (TSH, FT4) at mean 12.5 weeks 80 100 99 IQ score gestation, ½ not screened 60• Intervention: LT4 0.15mg/day 40 if TSH >2.5mIU/L 20• Outcome: IQ testing at 3 years 0 Universal Screen Control John Lazarus ITC 2010
Subclinical hypothyroidism was associated with increased fetaldistress, preterm delivery,Poor vision development and neurodevelopmental delay. OH SCH J Clin Endocrinol Metab, October 2011, 96(10):3234–3241
Should subclinical hypothyroidismbe treated in pregnancy? 2010- NO 2011 – YES but ...... 2012 – YES for all pregnant SCH 2012 – YES for all pregnant SCH
Optimal treatmentOral Levothytoxin (LT4)Goal:normalise maternal serum TSH vlaues within thetrimester spesific pregnancy reference range First Trimester : 0.1-2.5 mIU/L Second trimester : 0.2-3 .0 mIU/L Third trimester: 0.3- 3.0 mIU/L Levothyroxine ingestion should be separated from prenatal vitamins containing iron, iron and calcium supplements and soy products by at least 4 hours to ensure adequate absorption.
Hypotiroidism diagnosed duringpregancy Overt hypothyroid: if treatment naive, begin LT4 at 100-125mU/L or 1-2mcg/kg/day If TSH concentration is 2.5-10 mIU/L a starting levothyroxine dose of 50 /d is recommended
Hypothyroid women : pre conception Pre conception education of hypothyroid women and optimization of LT4 dosage Check thyroid function tests as soon as pregnancy confirmed Increased LT4 dosage required in majority of woman Average dose increase about 30%
Levothyroxine titration for women withknown hypothyroidism during preganancyOne option: take two additional LT4 pills/week• Adjust levothyroxine in 25-50mcg increments with goal TSH 0.5- 2.5-3.0 mU/L• TIMING for increase as early at 7-8 weeks gestation
pregnant hypothyroid women who taking LT4:monitorising TSH levels need to be evaluated every 4 weeks during the first 20 weeks of gestation measured at least once during the second half of pregnancy more frequently if euthyroidism has not been achieved. Check TSH 4-6 weeks after each dose adjustment Yassa J Clin Endocrinol Metab 2010 95:3234
Levothyroxine Drug Facts Pregnancy: Category A Breastfeeding: Safe Not contraindicated. Levothyroxine is excreted into breastmilk in small quantities Drug interactions: Interfere w/absorption: Iron salts, Antacids, Calcium salts Separate ingestion by >4 hours.
Isolated maternal hypothyroxinemia normal TSH free T4 below 0.86 ng/dl. In the first half of pregnancy, prevalence 1.3%. not associated with adverse perinatal outcome
Universal screening did notresult a decrease in adverse outcomes. Insufficient evidence to recommend universalscreening for thyroid disease in pregnant women
Serum TSH values should be obtained early in pregnancy inthe following women at high risk of hypothyroidism: • Age >30 years • Family history of thyroid disease • Symptoms of thyroid dysfunction or the presence of goitre • History of thyroid dysfunction or prior thyroid surgery • Prior therapeutic head or neck irradiation • Positive results of TPO autoantibody testing • T1DM or other autoimmune disorders • Infertility • History of miscarriage or preterm delivery • Morbid obesity (BMI ≥40 kg/m2) • Residence in an area of known moderate-to-severe iodine deficiency • Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast American Thyroid Association 2011
Thyroid autoimmunity Anti TPO ab (+) or Anti TG Ab (+)• Who are euthyroid in the early stages of pregancy are at risk of developing Subclinical /overt hypothyroidism.• Should be monitored every 4-6 week for elevation of TSH above the normal range of pregnancy
Overt/subclinical hypothyroidismBefore pregnancyAdjustment of LT4 dose During pregnacyGoal: TSH level <2.5 mIU/l Thyroid function tests should be normalised as rapidly as possible TSH :2.5-3.0 mIU/L
Universal screening of heathy women for thyroiddysfunction is not recommendedhigh risk individuals for thyroid illnessshould be screened with prenatal TSHUniversal screening for the presence of anti TPOanibodies is not recommended
Thank youInstitute of Medicine Report, November 2010