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Thyroid in pregnancy

Thyroid in pregnancy. DR. PREKSHA JAIN DR. BHAVNA KUMARE. CONTENTS. Introduction & incidence Physiological changes in pregnancy Normal values in pregnancy Events in fetus Interpretation of tests Hypothyroidism Hashimoto thyroiditis Subacute thyroiditis Subclinical hypothyroidism.

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Thyroid in pregnancy

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  1. Thyroid in pregnancy DR. PREKSHA JAIN DR. BHAVNA KUMARE

  2. CONTENTS • Introduction & incidence • Physiological changes in pregnancy • Normal values in pregnancy • Events in fetus • Interpretation of tests • Hypothyroidism • Hashimoto thyroiditis • Subacute thyroiditis • Subclinical hypothyroidism • Neonatal hypothyroidism • Autoimmune diseases • Hyperthyroidism • Grave’s disease • Thyrotoxicosis • Thyroid cancer • Postpartum management & postpartum thyroiditis • Thyroid nodule in pregnancy REFERENCE: de Swiet’s, Fogsi, William’s

  3. INTRODUCTION • Highly vascular organ • 15-20 gm • Isthmus cross 2nd to 4th cartilage • Follicle, C cells/parafollicular cells • Produce T4 & T3 • Synthesis- Iodide trapping, Oxidation & iodination, Coupling, Release • Transport (TBG, TTR, Albumin) • Free hormone levels- T4 (0.03%) < T3 (0.3%)

  4. INCIDENCE • M/c endocrine disorder in pregnancy • 1-2% pregnant women • Overt Hypothyroidism- 0.05% • Subclinical hypothyroidism- 2% • Hyperthyroidism- 0.05-0.2% (Grave’s – 90%) • Postpartum thyroiditis- 5-10%

  5. NORMAL CHANGES IN PREGNANCY

  6. NORMAL VALUES IN PREGNANCY

  7. EVENTS IN FETUS • Maternal thyroxine in coelomic fluid @ 6 weeks • T3 is present in fetal brain @ 7 weeks • THR gene expression in brain @ 8 weeks • Fetal iodine uptake @ 10-14 weeks • Fetal thyroxine secretion @ 18 weeks • 30% Maternal thyroxine in fetal serum at birth

  8. INTERPRETATION OF TESTS

  9. HYPOTHYROIDISM • Nonspecific insidious clinical findings like weight gain, fatigue, cold intolerance & muscle cramps • 1-3 per 1000 pregnancies • Types- • PRIMARY • SECONDARY/CENTRAL • SUBCLINICAL • OVERT

  10. CAUSES OF HYPOTHYROIDISM PRIMARY HYPOTHYROIDISM SECONDARY HYPOTHYROIDISM • Endemic iodine deficiency • Hashimoto thyroiditis • Subacute thyroiditis • Suppurative thyroiditis • Previous thyroidectomy • Previous radioablation • Medication exposure • Hth/ pituitary tumor • Surgery • Radiation • Sheehan’s • Lymphocytic hypophysitis Subclinical hypothyroidism Isolated hypothyroxinemia

  11. IODINE DEFICIENCY GOITER • Leading cause of preventable Mental retardation (developing countries) • Mean IQ loss 13.5points • Median Urinary Iodine Excretion determine iodine sufficiency • Iodine requirement • Non pregnant 150µg • Pregnancy 175µg • Lactation 200µg

  12. SPECTRUM OF IDD • FETUS • Stillbirth • Perinatal & infant mortality • Neurological Cretinism • Myxedematous cretinism • Mental deficiency • Mutism, spastic diplegia • Squint • Dwarfism, psychomotor defects • Hypothyroidism • NEONATE • Neonatal hypothyroidism • CHILD & ADOLESCENT • Mental & physical development • ADULT • Goiter & its complications • Iodine induced hypothyroidism • ALL AGES • Goiter • Susceptibility to nuclear radiation

  13. HASHIMOTO THYROIDITIS • M/c cause of hypothyroidism in pregnancy (developed countries) • Lymphadenoid thyroiditis; chronic lymphocytic thyroiditis • Autoimmune destruction of thyroid cells • Transient hyperthyroidism hypothyroidism (90% destroyed)

  14. SUBACUTE THYROIDITIS SUBACUTE GRANULOMATOUS THYROIDITIS SUBACUTE LYMPHOCYTIC THYROIDITIS • Painful • Viral infection • Sudden onset • Fever, myalgia, neck pain • Painfully enlarged thyroid • Painless • Postpartum thyroiditis • Painlessly enlarged gland

  15. Transient hyperthyroidism Subacute thyroiditis • 4-6weeks • Symptomatic treatment Transient hypothyroidism 90% 10% Recover Persistent goiter

  16. LYMPHOCYTIC HYPOPHYSITIS • Secondary hypothyroidism • Peripartum period • Autoimmune • Ant pituitary destruction • Panhypopituitarism to single hormone deficiency • Mass effects (headache & visual changes) • Imaging: enhancing sellaturcica mass

  17. SUBCLINICAL HYPOTHYROIDISM • TSH & Normal FT4 & FT3 • 2-5% in pregnancy • 31% positive for TPO Ab • Associated with Gest HTN, preterm deliveries, stillbirths, abruption. • Fetal psychomotor development may be impaired • Routine screening not recommended

  18. ISOLATED HYPOTHYROXINEMIA • Normal TSH FT4 • 1-2% pregnancies • No adverse effects in pregnancy • No benefit of levothyroxine t/t

  19. SYMPTOMS & SIGNS OF HYPOTHYROIDISM • Fatigue • Constipation • Cold intolerance • Weight gain • Carpel tunnel syndrome • Hair loss • Voice changes • Slow thinking • Dry skin • Goiter • Insomnia • Periorbital edema • Myxedema • Prolonged relaxation of DTRs • PR slow

  20. EFFECTS OF HYPOTHYROIDISM • ON PREGNANCY • Prolonged infertility t/t • Recurrent abortions • Preeclampsia 5-10% • Placental abruption 1% • Preterm delivery 10-15% • Anemia • Myxedema coma • Malpresentation • LBW • PPH • Stillbirth • ON FETUS • Neurodevelopmental delay • Deafness • Stunted growth • Peripartum hypoxia • Neonatal mortality

  21. LAB TESTS & SCREENING • TSH • FT4 • Antithyroidab (Anti TPO & antithyroglobulin) • Case finding approach rather than universal screening • TSH should be done ideally before pregnancy • If not done, high risk women should be screened – • Strong family history • Autoimune disorder • Presence of goiter • Personal history of thyroid disease • Therapeutic neck irradiation • Medications

  22. MANAGEMENT • Prepregnancy: 1.7µg/kg levothyroxine started • During pregnancy: • If TSH > 5µU/ml start t/t • If TSH 2.5-5µU/ml & AMA positive start t/t • If TSH 2.5-5µU/ml & AMA negative monitor closely 4-6wks TSH normalized Pregnancy

  23. PREGNANCY BLOOD VOLUME & TBG INCREASED FREE T4 DECREASED EUTHYROID HYPOTHYROID COMPENSATE THYROXINE DOSE INCREASED 25-40% 4-6 WEEKS REPEAT TSH (GOAL 0.5-2.5mIU/L) ADJUST DOSE REPEAT TSH EVERY 8WEEKS

  24. LEVOTHYROXINE SODIUM • Most widely prescribed t/t • Category A • 25-300 mcg • If newly diagnosed in pregnancy started @ 1-2µg/kg/d or approx 100-150µg/d • If previously hypothyroid dose increased by 25-40% • Taken empty stomach • Separated from multivitamins, calcium, iron, soy products by 4hrs • Postpartum: • Decrease dose by 30% (if newly diagnosed) • Prepregnancy dose (known case) • Reassess after 6 weeks

  25. Adverse effect On mother – Hyperthyroidism Transient hair loss BMD Myocardial effects On Fetus – LBW Smaller HC • LABOR & DELIVERY- • Should be euthyroidclincally & biochemically • Stillbirth, preterm, preeclampsia, abruption • POSTPARTUM- • Return to prepregnant dose • Breast feeding is not contraindicated

  26. NEONATAL HYPOTHYROIDISM • M/c endocrinopathies • Causes: Primary, secondary, tertiary. • Cord blood at birth OR heel prick on 3rd day • Symptoms & Signs • Goal – To normalize TSH(<5mU/l) & T4 (10-16µg/dl) as quickly as possible. • 3rd trim fetal T4 req : 6µg/kg/d • M/m- • In utero: Intraamniotic 250-500µg thyroxine 7-10d interval • In term infants: 10-15µg/kg/d

  27. AUTOIMMUNE THYROID DISEASE • Thyroid antibodies- • TPOab (TMA, 10-15% normal population) • TgAb • TSHRAb (types- stimulating, inhibiting, blocking) • Increased miscarriage, postpartum thyroid dysfunction • Causes : • Increased maternal age • Autoimmune imbalance • Fetal to maternal cell trafficking

  28. TSH RECEPTOR ANTIBODIES • IgG type • Cross placenta • 2 types: • Stimulating – TSI in Grave’s disease • Blocking – TBII in Hashimoto thyroiditis

  29. Trophoblast secrete immunosuppressant factors Antibody titres Grave’s disease improvement Ab increase post partum Postpartum flare up POSTPARTUM THYROIDITIS

  30. HYPERTHYROIDISM • 0.05-0.2% pregnancies • Types : • Subclinical- TSH normal FT3, FT4 • Overt- TSH FT4, FT3 • Gestational- detected in pregnancy • Symptoms: Palmar erythema, emotional lability, vomiting, goiter, heat intolerance, exophthalmos, fail to gain weight.

  31. CAUSES OF THYROTOXICOSIS • INTRINSIC THYROID DISEASE • Grave’s • Toxic nodule • Subacute thyroiditis • EXOGENOUS THYROID HORMONE • Factitious • Therapeutic • GESTATIONAL THYROTOXICOSIS • Hyperemesis • GTD • Hydatidiform mole • Multiple gestations • Hydrops • RARE • Tsh producing pituitary tumour • Iodine deficiency • Struma ovarii

  32. GESTATIONAL TRANSIENT THYROTOXICOSIS • Cross reactivity between HCG & TSH at receptor • TSHR ab negative, rarely symptomatic • Nausea & vomiting, dehydration, electrolyte imbalance & weight loss. • Spontaneous resolution by 18 weeks. • Antithyroid medications avoided.

  33. GRAVE’S DISEASE • Autoimmune. Incidence 0.5% • M/c cause hyperthyroidism in pregnancy • Triad – hyperthyroidism, exophthalmos, pretibial myxedema • Others- Clubbing, thyroid bruit, chemosis, • Physiology • Ab: TPO, Tg, TSHR

  34. MATERNAL RISKS • Heart failure • Thyroid storm • Preeclampsia(11%) • Anemia • Infection • Fever • Psychosis, seizure, coma • Diarrhea, pain, vomiting • Atrial fibrillation • Preterm • Spontaneus loss • FETAL RISKS • Fetal tachycardia • IUGR • Fetal goiter • IUFD • Stillbirth • Non immune hydrops • Craniosynostosis • Mental deficiency • Poor wt gain, feeding, jaundice, hepatospleenomegaly

  35. PRESENTATION OF HYPERTHYROIDISM • Nervousness, agitation • Tachy, palpitation • Wt loss, increased appetite • Change in bowel habits • Skin moist & soft • Onycholysis • Hair soft, thin, fine • Eyes signs (lid retraction, lag, proptosis)

  36. TREATMENT OF THYROTOXICOSIS • MATERNAL • DOC Propylthiouracil 50-100mg TDS • Carbimazole 5-20mg BD • Thyroid studies 4weekly • Dose adjusted based on T4 • FETAL/NEONATAL • 50% mortality of thyrotoxicosis • Carbimazole10mg/kg • Lugol’s iodine • Propanolol 2mg/kg/d • Digoxine & diuretics

  37. DIAGNOSIS • Clinical presentation • Thyroid examination – • Grave’s- diffuse, symmetric, soft • Nodular • Subacute thyroiditis- Generalised tenderness • TFT • Thyroid Ab test

  38. ANTENATAL MANAGEMENT • Detected in 1st trim- observe • Persists in 2nd trim- t/t • THIONAMIDES: 1. Propylthiouracil • Less readily crosses placenta • 50-150mg TDS • Category D • Side effects- m/c rash Fetal hypothyroidism Transient leukopenia (10%) Agranulocytosis (0.3-0.4%) discontinue t/t Hepatotoxicity (0.1-0.2%) Vasculitis

  39. 2. Methimazole: • 5-20mg BD • Crosses placenta readily • Category D • Methimazoleembryopathy- Esophageal atresia, choanal atresia, cutis aplasia • FETAL MONITORING: • 10% hypothyroidism • Clinical exam • USG • Cordocentesis • Selective Fetal blood sampling • Subtotal thyroidectomy rarely • Radioactive iodine ablation is contraindicated

  40. LABOR & DELIVERY • Antithyroid drugs • Beta blockers • Supportive care • Fetal thyrotoxicosis T/t of maternal thyrotoxicosis • Fetal goiter consider mode of delivery • EXIT procedure: • Ex utero intrapartum treatment • Fetus with large neck masses causing airway obstruction

  41. POSTPARTUM MANAGEMENT • Immunosupression disappears • Relapse in 70 % • TSH & freeT4 done 6weeks post partum • Lactating mother- • PTU & methimazole excreted in breast milk • PTU protein bound. Safer • Methimazole only at low doses (10-20mg/d)

  42. THYROID STORM • Acute exacerbation of hyperthyroidism, life threatening, hypermetabolic state • Rare in pregnancy • Pregnant women with thyrotoxicosis has minimal cardiac reserve • Decompensation precipitated by sepsis, preeclampsia & anemia • Features • Lab tests- increased T4 & T3, TLC, Transaminases, calcium • Management..

  43. START THIONAMIDES & CONTROL HEART RATE(<90bpm) PTU 1g PO or NGT 100mg 6hrly PROPRANOLOL 1-2mg IV over 5min to total 6-10mg 60-80mg 4hrly PO/NGT CORTICOSTEROIDS Dexa 1-2mg PO/IV/IM 6hrly Or Hydrocort 100mg IV 8hrly Or Prednisone 60mg/d PO IODINE (after 1-2hrs of thionamide) Sodium iodide 500-1000mg IV 8hrly Or SSKI 5drops PO 8hrly Or Lugol’s solution 10 drops PO 8hrly Or Lithium carbonate 300mg PO 6hrly Or iodinated radiocontrast agents iopodate 0.5-1g PO per day

  44. THYROID CANCER IN PREGNANCY • Types: Papilllary (m/c in pregnancy), follicular, medullary, Hurthle cell, anaplastic • Excellent long term prognosis • Surgery delayed postpartum • Sr. thyroglobulin- tumor marker • Postsurgical whole body scintigraphy & radioiodine remnant ablation – contraindicated in pregnancy & lactation

  45. PRECONCEPTIONAL COUNSELLING • Clinical situations • Hyperthyroidism under t/t- • Side effects of antithyroid drugs on fetus • Wait 6mth after radioablation (4mth at least) • Euthyroid at time of conception • Previous ablation for Grave’s disease- • The dose needs to be increased soon after conception • High maternal titers of TSI may be present in spite of euthyroid ; fetus at risk • Previous t/t for thyroid carcinoma • Wait 1 yr after completion of radioactive t/t for conception. • Inadequate t/t • Central congenital hypothyroidism in infant

  46. POSTPARTUM THYROIDITIS • Rebound autoimmunity lymphocytic infilteration of gland • High chances(40-50%) if high titers of ab in early pregnancy • Anti- TPO 90% with PPT • Type 1 diabetics- 18-25% chances • 20-50% will develop permanent hypothyroidism within 2-10yrs • Phases- • Hyperthyroid • Hypothyroid

  47. HYPERTHYROID PHASE • Release of stored hormone • 1-4mth postpartum • Self limiting • Abrupt onset • Fatigue,palpitation, insomnia,nervousness • Small painless goiter • HYPOTHYROID PHASE • Loss of functioning thyrocytes • 3-8mth • Lasts longer • Fatigue, wt gain, depression, loss of conc.

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