Thyroid Disorders in Pregnancy PDF

THYROID DISORDERS IN PREGNANCY Dr. CH. Karuna Kumari MS Associate Professor OBG Department Rangaraya Medical College CONTENTS 1 Introduction 2 Thyroid disorde...

THYROID DISORDERS IN PREGNANCY Dr. CH. Karuna Kumari MS Associate Professor OBG Department Rangaraya Medical College CONTENTS 1 Introduction 2 Thyroid disorders during pregnancy 3 RCOG GTGuidelines 4 A Case Scenario  INTRODUCTION Pregnancy is a Natural Stress Test for Thyroid Gland ↑plasma volume ↑ Demand of ↑peripheral metabolism of TH ↓T3 & T4 T3/T4 (30-50%) Non-functioning fetal thyroid until 10-12wks ↑ oestrogen in 2-3 ↑T4, ↑T3 Total T4 folds↑TBG 1.5x non preg range pregnancy ↑Similar structure Transient hCG stimulates of TSH↓in 8- hCG and TSH release of T3/T4 14wks  TRIMESTER SPECIFIC RECOMMENDED GUIDELINES COUNTRY TSH REF RANGE 1st : 2.5 mIU/L ITS 2nd : 3.0mIU/L Guidelines India 3rd : 3.0 mIU/L 2012 1st : 2.5 mIU/L ETA 2nd : 3.0mIU/L 3rd : 3.0 mIU/L Guidelines European 2014 Use locally derived Reference ranges from a ATA specified Pregnant population Guidelines American If the above is not available use and 2017 upper TSH reference limit of 4.0 mIU/L COMMON THYORID FUNCTION DISORDERS IN PREGNANCY TSH fT4 REPORTED PREVALENCE CONDITION CONCENTRATION CONCENTRATION IN PREGNANCY Overt hypothyroidism Increased Decreased 0.2-1% Subclinical hypothyroidism Increased Normal 2.2-10% Isolated hypothyroxinaemia Normal Decreased 1.3-8% Thyrotoxicosis( including gestational transient Decreased Increased 0.05-1.3% thyrotoxicosis) Subclinical hyperthyroidism Decreased Normal 1.5-2% Latest updates in the management of Thyroid disorders  The Cochrane Library Cochrane database of systemic reviews The Database of Abstracts of Reviews of Effects(DARE) Cochrane Central Register of Controlled Trials(CENTRAL) EMBASE MEDLINE Trip National Guideline Clearing House National Institute for Health and Care Excellence(NICE)  CLASSIFICATION OF EVIDENCE LEVELS 1++ High-quality meta-analyses, systematic reviews of RCT or RCT trials with a very low risk of bias 1+ Well-conducted meta-analyses, systematic reviews of RCTor RCT with a low risk of bias 1– Meta-analyses, systematic reviews of RCT or RCT with a high risk of bias 2++ High-quality systematic reviews of case–control or cohort studies or high-qualitycase–control or cohort studies with a very low risk of confounding bias. 2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias. 2– Case–control or cohort studies with a high risk of confounding, bias or chance and asignificant risk that the relationship is not causal 3 Non-analytical studies, e.g. case reports, case series 4 Expert opinion  GRADES OF RECOMMENDATION A : At least one meta-analysis, systematic reviews or RCT rated as 1++, and directly applicable to the target population; or a systematic review of RCTs or a body of evidence consisting principally of studies rated as 1+. B : A body of evidence including studies rated as 2++ directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+ C : A body of evidence including studies rated as 2+ directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 2++ D : Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+ GPP : (Good Practice Points) Recommended best practice based on the clinical experience of the guideline devolpment group  WHAT ARE THE REFERENCE RANGES FOR THYROID FUNCTION TESTS IN EACH TRIMESTER? 1) To diagnose thyroid dysfunction in a pregnant woman, trimester, population, and manufacturer specific reference ranges for serum TSH and fT4 are recommended for correct interpretation of thyroid function tests. (Grade - B) 2) For pregnant women who are on any thyroid-related medication,more specific treatment targets for TSH and fT4 are recommended (Grade - C) 3) In the absence of appropriate information it is reasonable to set an upper limit for TSH of 4.0 mIU/L in pregnancy. (Grade - C)  THE RECOMMENDED TOTAL DAILY IODINE INTAKE IN WOMEN WHO ARE PLANNING PREGNANCY, WHO ARE PREGNANT AND WHO ARE BREASTFEEDING? 1.All pregnant and breastfeeding women should have a total daily intake of approximately 200-250 microgram iodine. (Grade - B) 2.To achieve the recommended daily iodine intake when planning pregnancy, consideration should be given to increasing dietary intake of iodine-rich foods or consuming daily oral supplementation of 150 microgram iodine in the form of potassium iodide (as present in common prenatal supplements). (Grade - C) 3) Supplementation should ideally be started three months in advance of pregnancy or as soon as possible in pregnancy.(Grade - GPP) 4) Women should take a single rather than multiple iodine-containing supplements at the same time.(Grade - GPP) 5) Sustained iodine intake from diet and dietary supplements exceeding 500 microgram daily should be avoided during pregnancy.(Grade - C) 6) Individual assessment of iodine status in pregnancy and in women planning pregnancy is not recommended.(Grade - B) SHOULD ALL PREGNANT WOMEN BE TESTED FOR THYROID DYSFUNCTION AT PREGNANCY BOOKING? Universal testing for thyroid dysfunction during pregnancy is not recommended (Grade - C) SHOULD THYROID FUNCTION TESTING BE CARRIED OUT IN A TARGET POPULATION OF PREGNANT WOMEN WHO ARE AT RISK OF THYROID DYSFUNCTION? 1) Subpopulations with specific risk factors who are known to have a higher prevalence of overt thyroid disorders should be tested for thyroid dysfunction as soon as possible in pregnancy (preferably in the first trimester). (Grade - D) 2) Risk-based testing in pregnancy should be for TSH and fT4 simultaneously.(Grade - GPP) HYPOTHYROIDISM IN PREGNANCY  EFFECTS OF HYPOTHYROIDISM IN PREGNANCY Materna Foetal Neonata Anaemial l Pre-eclampsia Cognitive Hyperbilirubinemia Placental impairment abnormalities Neurological Respiratory distress Low Birth Weight abnormalities infants Developmental Post partum hemorrhage abnormalities Myopathy Congenital Hypothyroidism Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption. Preterm birth was almost 2- fold higher in women with subclinical hypothyroidism.  How should newly diagnosed hypothyroidism, SCH and IH be treated in pregnancy? 1) In women with overt hypothyroidism and severe SCH (TSH >10 mIU/L), newly diagnosed at any time in pregnancy, commence levothyroxine treatment as soon as possible at a suggested dose of 1.6 micrograms/kg/day with repeat thyroid function tests in 4 weeks. (Grade B) 2) In women with SCH (TSH between the upper limit of the reference range and10 mIU/L), newly diagnosed at any time in pregnancy, levothyroxine should be considered, at a suggested dose of 1.0–1.2 micrograms /kg/day. Otherwise perform thyroid function tests at 4–6 week intervals up to 20 weeks’ gestation and at 28 weeks’ gestation. (Grade - C) 3) In women with IH, routine levothyroxine therapy is not recommended. Thyroid function tests should be rechecked 4– 6 weeks later to ensure it remains stable. (Grade C) How should women with hypothyroidism and SCH be cared for before pregnancy? 1) In women with OH and severe SCH (TSH >10 mIU/L), titration of levothyroxine to achieve a preconception target TSH ≤2.5 mIU/l is recommended. (Grade B) 2) In women with SCH, particularly those already known to be TPOAb positive, treatment with levothyroxine should be considered starting preconception,with titration to achieve a preconception target TSH ≤2.5 mIU/l (Grade C) 3) Women on levothyroxine therapy should be counselled to empirically increase their dose of levothyroxine by approximately 25–30% in the event of a positive pregnancy test. This may be achieved by either: Doubling the dose of Levothyroxine on two days of each week or Implementing a dose increment of: 25mcg/day for women taking 100mcg or less levothyroxine daily 50 micrograms per day for women taking greater than 100mcg levothyroxine daily. (Grade - A)  How should levothyroxine be titrated in pregnancy and adjusted after birth? 1) Following birth, for those who were already adequately replaced on levothyroxine preconception, revert to the preconception dose of levothyroxine two weeks postpartum. (Grade D) 2) In women not taking levothyroxine preconception, stop levothyroxine following birth, and check thyroid function six weeks postpartum. (Grade D)  Should women without thyroid disease be offered a thyroid peroxidase antibody (TPOAb) test in pregnancy? 1) Routine testing for TPOAb in euthyroid women is not recommended in pregnancy. (Grade B) 2) If a woman is already known to be positive for TPOAb but euthyroid, they should be offered thyroid function test measurements in the first trimester (preferably at first contact with a healthcare professional, including primary care booking) and at 20 weeks of pregnancy to detect development of hypothyroidism (Grade C) 3) Levothyroxine treatment is not recommended for women with TPOAb in the absence of thyroid dysfunction during pregnancy. (Grade A) HYPERTHYROIDISM IN PREGNANCY  CAUSES SIGNS & SYMPTOMS FETAL EFFECTS 1.THYROTOXICOSIS Graves SYMPTOMS : Thyroid Nodules Low birth weight Sweating , palpitations, heat Subacute thyroidits intolerance, weight loss or failure to Prematurity gain weight , nausea. 2. PREGNANCY INDUCED Hyperemesis Congenital malformations SIGNS : Hydatidiform mole Tremors , warm extremities, Drug induced tachycardia, proptosis, goitre, atrial fibrillation. 3. MISCELLANEOUS  ALGORITHM FOR THYROID TESTING: TSH Levels Increased Norm Decrease al d No testing Free T4 Hypothyroidis needed levels m Norm Increased al Free T3 Hyperthyroidis levels m Norm Increased al Subclinical- hyperthyroidism HYPerTHYROIDIS  HOW SHOULD WOMEN WITH GRAVES’ DISEASE BE COUNSELLED BEFORE PREGNANCY? 1) Pre-pregnancy counselling is recommended in women with hyperthyroidism to minimise maternal and fetal adverse outcomes. (Grade GPP) 2) The option of definitive treatment with radioactive iodine or thyroidectomy should be discussed, especially in women with more severe disease. Following definitive treatment, women should wait at least six months before attempting to conceive. They should also have had serum fT4 within the reference range on two measurements three months apart. (Grade C) 3) A persistently increased TSH-receptor antibody (TRAb) level (usually taken as greater than 3 times the threshold for positivity) assessed around six months post-treatment is associated with increased risk of fetal Grave’s disease and consideration may be given to further delay conception. (Grade D) 4) Women choosing to continue with antithyroid drugs while trying to conceive should be on propylthiouracil (PTU) in preference to carbimazole, at the lowest effective dose to maintain fT4 concentrations in the upper half of the reference range (Grade B)  WHAT IS THE OPTIMAL CARE OF WOMEN WITH GRAVES’ HYPERTHYROIDISM IN PREGNANCY? 1) When pregnant, where the woman has been euthyroid (TSH in the reference range) for 6 months or more on a low dose of an antithyroid drug (