Thyroid Disease and Pregnancy

1. Thyroid Disease and Pregnancy Sheila F. Perillo, MD

2. Thyroid disease is the second most common endocrine disease affecting women of reproductive age

3. Thyrotoxicosis (thyroid storm) • a generic term referring to a clinical and biochemical state resulting in over-production of and exposure to thyroid hormone • Overt hyperthyroidism complicates approximately 2 in 1,000 pregnancies.

4. Pregnant women with hyperthyroidism are at increased risk for: • spontaneous pregnancy loss • congestive heart failure • thyroid storm • preterm birth • Preeclampsia • fetal growth restriction, and • increased perinatal morbidity and mortality 

5. Grave's disease • the most common cause of thyrotoxicosis in pregnancy • An autoimmune condition characterized by production of thyroid-stimulating immunoglobulin (TSI) and thyroid-stimulating hormone binding inhibitory immunoglobulin (TBII) facilitate the thyroid-stimulating hormone (TSH) receptor in the mediation of thyroid stimulation and inhibition

6. Hyperthyroidism- thyrotoxicosisresulting from an abnormally functioning thyroid gland. • Thyroid storm- acute, severe exacerbation of hyperthyroidism

7. gestational transient thyrotoxicosis • associated with hyperemesisgravidarum • can be due to high levels of human chorionic gonadotropin (hCG) resulting from molar pregnancy • high hCG levels  TSH receptor stimulation and temporary hypothyroidism • rarely symptomatic • treatment with antithyroxine drugs- not beneficial • expectant management • not associated with poor pregnancy outcomes

8. Impact of Pregnancy on Thyroid: • Thyroxine (T4), the major secretory product of the thyroid gland, is converted in peripheral tissues to triiodothyronine (T3) • T3- biologically active form • T4- secretion is under the direct control of pituitary TSH • T4 and T3 are transported in the peripheral circulation bound to thyroxine-binding globulin (TBG), transthyretin(formerly called "prealbumin") and albumin. • Less than 0.05% of plasma T4, and less than 0.5% of plasma T3, are unbound and able to interact with target tissues 

9. 20 weeks' gestation • reduced hepatic clearance • estrogen-induced change in the structure of TBG that prolongs serum half-life  plasma TBG increases 2.5 folds   25% to 45% increase in serum total T4 (TT4) from a pregravid level of 5 to 12 mg to 9 to 16 mg ** Total T3 (TT3) increases by about 30% in the first trimester and by 50% to 65% later

10. Pregnancy  increase in available protein transient change in free T4 (FT4) and free thyroxine index (FTI) in the first trimester (possibly related to an increase in hCG) • Increased concentrations of TSH  stimulate restoration of the free serum T4 level, such that FT4 and FTI levels are generally maintained within the normal non-pregnant range

11. Ultrasound evaluation of the thyroid gland during pregnancy • Increase in volume • Echo structure remains unchanged (Plasma iodide levels decrease in pregnancy due to fetal use of iodide and increased maternal renal clearance) • 15% to 18% increase in size of the thyroid gland • enlargement usually resolves after delivery • not associated with abnormal thyroid function tests

12. Diagnostic Approach: • Mild hyperthyroidism: • Fatigue • increased appetite • Vomiting • Palpitations • Tachycardia • heat intolerance, • Increased urinary frequency • Insomnia • Emotional instability • The suspicion increases if patient has • Tremor • Nervousness • frequent stools • excessive sweating • brisk reflexes • muscle weakness • goiter • Hypertension • weight loss. • Grave's ophthalmopathy (stare, lid lag and retraction, exophthalmos) • dermopathy (localized or pretibialmyxedema)

13. Untreated hyperthyroidism poses considerable maternal and fetal risks, including preterm delivery, severe preeclampsia, heart failure, and thyroid storm

15. Characteristics of Thyroid Storm: • - a hypermetabolic complication of hyperthyroidism: • hyperpyrexia (temperature >41ºC) • cardiovascular compromise (tachycardia out of proportion to the fever, dysrhythmia, cardiac failure) • gastrointestinal upset (diarrhea) • central nervous system changes (restlessness, nervousness, changed mental status, confusion, and seizures).

16. Thyroid storm is a clinical diagnosis, and treatment should be initiated before confirmatory test results are available.

17. Patients without classic symptoms • Other signs of thyrotoxicosis in any patient with postpartum congestive heart failure: • tachycardia • severe hypertension  • central nervous system (CNS) features, such as coma after cesarean section or seizures suggestive of eclampsia • Delay in diagnosis increase the risk of maternal mortality

18. Thyroid storm is usually seen in patients with poorly controlled hyperthyroidism complicated by additional physiologic stressors, such as infection, surgery, thromboembolism, preeclampsia, and parturition

19. Laboratory Tests: • CBC (Leukocytosis) • Thyroid function test results are consistent with hyperthyroidism (elevated FT4/FT3 and depressed TSH) but they may not always correlate with the severity of the thyroid storm • Baseline electrolyte (occasionally hypercalcemia) • Glucose • Renal • Liver function testing (elevated hepatic enzymes) • Coagulation studies • CT or MRI of the brain (unconscious patients, signs of focal CNS signs) • blood, uterine and wound cultures (as appropriate) • chest x-ray • 12-lead electrocardiogram (ECG) and continuous cardiac monitoring • Pulse oximetry • blood gas analysis

20. Management of thyroid Storm • Thyroid storm is a clinical diagnosis based on severe signs of thyrotoxicosis: • significant hyperpyrexia (>103ºF or >41ºC) neuropsychiatric symptoms • Tachycardia with a pulse rate exceeding 140 beats/min • congestive heart failure • Gastrointestinal symptoms (nausea and vomiting) accompanied by liver compromise

21. Management of Thyroid Storm: • Obstetric intensive care unit (ICU)/ ICU that has continuous fetal monitoring and can handle an emergent delivery • Therapy is designed to: • Reduce the synthesis and release of thyroid hormone • Remove thyroid hormone from the circulation and increase the concentration of TBG • Block the peripheral conversion of T4 to T3 • Block the peripheral actions of thyroid hormone • Treat the complications of thyroid storm and provide support • Identify and treat potential precipitating conditions

22. Management of Thyroid Storm • Supportive adjunctive care for the patient in thyroid storm are: • IV fluids and electrolytes • Cardiac monitoring • Consideration of pulmonary artery catheterization (central hemodynamic monitoring to guide beta-blocker therapy during hyperdynamic cardiac failure) • Cooling measures: blanket, sponge bath, acetaminophen, avoid salicylates (risk of increased T4). Acetaminophen is the drug of choice • Oxygen therapy (consider arterial line to follow serial blood gases) • Nasogastric tube

23. Medications: • Reduce synthesis of thyroid hormones: • Thionamides : propylthiouracil (PTU) • Methimazole) inhibit iodination of tyrosine -- leading to reduce synthesis of thyroid hormones and block peripheral conversion of T4 to T3  • can reduce the T3 concentration by 75%

24. Iodide (Lugol's iodine, SSKI (Strong Solution of Potassium Iodide), sodium iodide, orografin, or lithium carbonate) inhibit proteolysis of thyroglobulin block the release of stored hormone **Because one of the side effects is an initial increase in production of thyroid hormone, it is therefore very important to start PTU before you give iodides

25. Glucocorticoids  block release of stored hormone (as do iodides), and peripheral conversion of T4 to T3 (as do thionamides) They may also bolster adrenal function, and prevent adrenal insufficiency

26. Dosage/ Management: • PTU orally or via nasogastric tube, 300-800 mg loading dose followed by 150-300 mg every 6 hours • One hour after instituting PTU give: Sodium iodide, 500 mg every 8-12 hours or oral Lugol's solution, 30-60 drops daily in divided doses. • Iodides may be discontinued after initial improvement • Give adrenal glucocorticoids (Hydrocortisone, 100 mg IV every 8 hour, or Prednisone, 60 mg PO every day, or • Dexamethasone, 8 mg PO every day) • Glucocorticoids may be discontinued after initial improvement

27. Medications to control maternal tachycardia • Beta-blocker agents -- • Propranolol can be used to control autonomic symptoms (especially tachycardia) • Some effect on inhibition of peripheral conversion of T4 to T3, but will not alter thyroid hormone release nor prevent thyroid storm. • Use with caution: it has a tendency to increase pulmonary diastolic pressure, and cardiac failure is a frequent presentation of thyroid storm • Reserved for heart rates of 120 beats per minute or higher • Propranolol, labetalol, and esmolol

28. Dosages: • Propranolol,1-2 mg/min IV or dose sufficient to slow heart rate to 90 bpm; or 20-80 mg PO or via nasogastric tube every 4-6 hourly • Esmolol, a short-acting beta-acting antagonist given IV with a loading dose of 250 to 500 µg/kg of body weight followed by a continuous infusion at 50 to 100 µg/kg/min • Echocardiogram and/or pulmonary artery catheter to help guide management, especially in cardiac failure • If patient has severe bronchospasm -- give 1-5 mg reserpine every 4-6 hours or 1 mg/kg orally of guanethidine every 12 hours.

29. Heart failure due to cardiomyopathy from excessive thyroxine in women with uncontrolled hyperthyroidism is more common in pregnant women • Same treatment as that of thyroid storm • Medical emergency • Give phenobarbital to control restlessness • Phenobarbital: 30 to 60 mg orally every 6-8 hours as needed • Plasmapheresis or peritoneal dialysis • to remove circulating thyroid hormone • reserved for patients who do not respond to conventional therapy • Subtotal thyroidectomy (during second-trimester pregnancy) or radioactive iodine (postpartum) • for unsuccessful conventional therapy

30. Postpartum Care: • Most asymptomatic women should have a TSH and free T4 performed approximately 6 weeks postpartum • PTU and methimazole are excreted in breast milk • PTU is largely protein bound and does not seem to pose a significant risk to the breastfed infant • Methimazole has been found in breastfed infants of treated women in amounts sufficient to cause thyroid dysfunction • at low doses (10-20 mg/d) it does not seem to pose a major risk to the nursing infant

31. Teratogenic effects of Antithyroid Medications: • PTU • first-line treatment for Grave's disease in pregnancy due to lower risks of teratogenicity than methimazole. • It crosses the human placenta and associated with fetal hypothyroidism • Cordocentesis is sometimes recommended to test fetal thyroid function • does not readily crosses membranes • milk concentrations are quite low

32. Methimazole (Thiamazole, Mercazole, Tapazole): • Second-line treatment of Grave's disease • crosses the human placenta and can induce fetalgoiter and even cretinism in a dose-dependent fashion • commonly associated with fetal anomalies such as aplasia cutis, esophagealatresia, and choanalatresia • Long-term follow-up studies of exposed children: • no deleterious effects on their thyroid function or physical and intellectual development with doses up to 20 mg/d  • excreted in breast milk

33. The American College of Obstetricians and Gynecologists (ACOG) recommends treatment for women with a systolic blood pressure higher than 170 mmHg and/or diastolic blood pressure above 109 mmHg There is no consensus whether lesser degrees of hypertension require treatment during pregnancy because antihypertensive therapy improves only the maternal, not the fetal, outcome in women with mild to moderate chronic hypertension

34. Radioactive iodine (iodine-131; I-131): • contraindicated in pregnant women • cost-effective, safe, and reliable treatment for hyperthyroidism in non-pregnant women  • ACOG recommendation: women should avoid pregnancy for 4-6 months following treatment • Detrimental effects on the thyroid of the developing fetusas a result of I-131 treatment for thyrotoxicosis of the mother in the first trimester of pregnancy are reported. • Breast-feeding should be avoided for at least 120 days after treatment

35. Summary • Thyroid storm • a life-threatening condition, requiring early recognition and aggressive therapy in an intensive care unit setting. • During gestation, women with hyperthyroidism should have their thyroid function checked every 3-4 weeks. • Grave's disease represents the most common cause of maternal hyperthyroidism during pregnancy • Only 0.2% of gestations are complicated by thyroid storm and more than 90% of cases are caused by Grave's disease • Increased production of thyroid hormone occurs when autoantibodies (thyroid-stimulating antibody [TSAb] -- formerly known as LATS [long-acting thyroid stimulator]) against TSH receptors -- acts as TSH agonists.

38. Thyroid Storm: Critical Care In Obstetrics • WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC). • Published: 2 June 2010