THYROID DISEASE IN PREGNANCY

Transcription

1 THYROID DISEASE IN PREGNANCY Grand Rounds December 5, 2018 Maria Kolojeski, DO (PGY3)

2 REVIEW OF THYROID HORMONES Hypothalmus Thyroid Releasing Hormone (TRH) Anterior Pituitary Thyroid-Stimulating Hormone (TSH) Thyroid Triiodothyronine (T3) Thyroxine (T4) Iodine

3 THYROID CHANGES IN PREGNANCY Thyroid Volume: 30% larger in 3 rd vs 1 st trimester Increased thyroid binding globulin Increased in total T3 & T4 levels Free T3 & T4 typically remain stable Weak stimulation of TSH receptors by hcg (first 12 weeks) Increases serum free T4 Thyrotropin (AKA: Thyroid Stimulating Hormone [TSH]) Decreases in early pregnancy Transient subclinical hyperthyroidism, Gestational transient hyperthyroidism Returns to baseline in second trimester Increased in third trimester due to placental deiodinase

4 THYROID LABORATORY WORKUP First Trimester miu/l Second Trimester miu/l Third Trimester miu/l If TSH abnormal order free T4 Rarely T3 toxicosis is the cause Consider antibody testing if euthyroid but clinical signs present Williams Obstetrics 24ed. Ch. 58 Fig.1. Universal screening not recommended

5 THYROID HORMONES & THE FETUS Maternal T4 crosses the placenta Fetal brain development Provides thyroid hormone before 12 weeks Fetal thyroid begins to produce own thyroid hormone & concentrate iodine 30% of T4 at term is estimated to be of maternal production

6 IODINE REQUREMENTS Iodine deficiency in Pregnancy Causes Increased thyroid hormone production Increased renal iodine loss Fetal iodine requirement Mild mental impairment to cretinism Iodine Intake in Pregnancy Reproductive age: 150mcg daily Pregnant: 220mcg daily Lactating: 290mcg daily About 50% of PNV don t contain iodine Not to excess 500mcg daily

7 HYPERTHYROIDISM Prevalence: % pregnancies (US); studies in UK ( %), China (1%) Causes: Graves disease (95%), trophoblastic disease, toxic multinodular goiter, toxic adenoma, thyroiditis, exogenous thyroid hormone Diagnosis: low TSH and high free T4 Symptoms: fatigue, nervousness, frequent stools, sweating, tachycardia, tremors, weight loss, heat intolerance, insomnia, palpitations, HTN, insomnia, +/- goiter Additional symptoms associated with Grave s Disease: ophthalmopathy, dermopathy Complications: SAB, preeclampsia, heart failure, preterm birth, low birth weight, fetal thyroid disease, infection, anemia, hearing loss SUBCLINICAL HYPERTHYROIDISM Prevalence in pregnancy: 1.7% No associations with adverse pregnancy outcomes Antithyroid medications have can have adverse effects on the fetus

8 THYROID STIMULATING ANTIBODIES Risk of immune-mediated fetal hypothyroidism and hyperthyroidism Thyroid stimulating immunoglobulins (TSI) stimulate fetal thyroid 1-5% of neonates have hyperthyroidism or neonatal Grave s disease TSH-binding inhibitory immunoglobulins inhibit fetal thyroid Decreased occurrence with maternal treatment during pregnancy However increased risk if previous maternal treatment via surgery or radioiodine ablation Consider fetal thyrotoxicosis in all women with a history of Grave s American Thyroid Association and American Associate of Clinical Endocrinologists recommend antibody testing between 22-26wga in women with a history of Grave s disease. ACOG does not, due to no change in management.

9 HYPERTHYROIDISM MANAGEMENT Thioamides decrease production of T3 & T4; cross the placenta Proplthiouracil (PTU) first trimester Inhibits iodination of tyrosine and conversion of T4 to T3 in peripheral tissues Hepatotoxicity ( %), ANCA (20%; rare for serious vasculitis) Methimazole (MMI) second & third trimesters Inhibits iodination of tyrosine Associated with esophageal and choanal atresia, fascial dysmorphism, aplasia cutis, omphalocele Side effects: transient leukopenia (10%), agranulocytosis ( %) Dosage: PTU mg PO TID; MMI 10-40mg PO divided into BID or TID dosing Beta blockers Surveillance: measure T4 level q2-4 weeks Used for management of tachycardia and tremors Avoid longer than 2-6 weeks due to increased risk of IUGR, bradycardia & hypoglycemia Dosing Metoprolol 25-50mg daily Propranolol 20mg q6-8hr

10 HYPERTHYROIDISM MANAGEMENT Thyroidectomy rarely performed during pregnancy Reserved for individuals with allergy to thioamides or agranulocytosis Pretreatment with a beta-blocker and potassium iodine Fetal Monitoring Postpartum Fetal heart rate monitoring, growth ultrasounds; Consider fetal thyroid ultrasound if mother with Grave s or TRAb 2-3x normal Methimazole preferred due to PTU side effects If dose >20mg daily, then infants should have thyroid function testing at 1 and 3 months of age TSH and free T4 at 6 weeks Not recommended Routine thyroid antibody testing Some recommend if require treatment with thioamides to test initially, at and wga Routine fetal thyroid evaluation: fetal US, cord blood sampling Consider in cases of IUGR, fetal tachycardia, fetal hydrops, goiter

11 HYPERTHYROID EMERGENCIES Thyroid Storm Incidence: 1-2% of pregnant patients with hyperthyroidism High risk of maternal heart failure Abrupt onset Diagnosis: fever, tachycardia, cardiac dysrhythmia, CNS dysfunction If suspect, order TSH & free T4, CBC, LFTs, Ca2+ Treat underlying cause Avoid delivery Thyrotoxic Heart Failure & Pulmonary Hypertension Incidence: 8% pregnant patients with uncontrolled hyperthyroidism Excess T4 -> high-output cardiomyopathy that can develop into dilated cardiomyopathy Precipitating conditions: preeclampsia, anemia, sepsis Frequently these conditions are reversible

12 MANAGEMENT of THYROID STORM or THYROTOXIC HEART FAILURE in PREGNANCY Inhibit release of T3 & T4 PTU 1,000mg PO load, then 200mg PO q6hr Iodine (1-2hr after PTU) Sodium iodine 500-1,000mg IV q8hr OR Potassium iodide, 5 drops PO q8hr OR Lugol solution, 10 drops PO q8hr OR Lithium carbonate, 300mg PO q6hr (iodine allergy) Block peripheral T4 -> T3 Dexamethasone, 2mg IV q6hr x 4 Hydrocortisone, 100mg IV q8hr x 3 OR Consider beta-blocker for tachycardia Caution in those with heart failure Propranolol, 10-40mg PO q4-6hr; (labetalol, esmolol) Don t forget supportive care! O2, IVF, telemetry, NG tube, cooling measure, avoid salicylates

13 HYPOTHYROIDISM Complicates 2 10 per1,000 pregnancies Causes: Iodine deficiency, chronic autoimmune thyroiditis (Hashimoto s), prior radioiodine ablation/surgery, pituitary/hypothalamic disorders Diagnosis: high TSH and low free T4 Consider measurement of TPO antibodies if TSH 2.5 Symptoms: fatigue, constipation, cold intolerance, muscle cramps, dry skin, hair loss, prolonged relaxation of DTRs, weight gain, edema, +/- goiter Paresthesias: early symptom present in 75% of hypothyroid patients Other: large tongue, myxedema, hoarse voice Complications: SAB, preeclampsia, preterm birth, low birth weigh, impaired neuropsychologic development, placental abruption, fetal death

14 HYPOTHYROIDISM SUBCLINICAL HYPOTHYROIDISM Prevalence in pregnancy: 2-5% Approximately 1/3 have TPO antibodies Possible increased risk of NICU admission, RDS, abruption, preterm birth, GDM No evidence that treatment improves outcomes ISOLATED MATERNAL HYPOTHYROXINEMIA Prevalence in pregnancy: 1.3% No increased rates of TPO antibodies Inconsistent data on adverse pregnancy outcomes (neurodevelopment, macrosomia) No evidence that treatment improves outcomes

15 ANTITHYROID ANTIBODIES Hashimoto s thyroiditis glandular destruction via thyroid peroxidase (TPO) Ab & antithyroglobulin Ab (TG) Euthyroid Autoimmune Thyroid Disease TPO & TG antibodies are present in 6-20% of reproductive-aged women Women with these antibodies are at an increased risk for Early pregnancy loss (2-5 fold) Placental abruption (3 fold) Postpartum thyroid complications Permanent thyroid failure 1 in 180,000 neonates will experience fetal hypothyroidism as a result of maternal TPO antibodies attacking the fetal thyroid

16 HYPOTHYROIDISM MANAGEMENT T4 replacement recommended Levothyroxine 1-2mcg/kg daily Surveillance: measure TSH levels q4-6 weeks If preexisting hypothyroidism, need for T4 increase in 1/3 of patients Increased T4 needs can occur as early as week 5 of gestation Anticipatory increase in dose by 25% at pregnancy confirmation (in those with no reserve) Adjust dosages in 25-50mcg increments Postpartum Return to prepregnancy dose if preexisting condition Measure TSH at 4-6 weeks after delivery Safe to use in breastfeeding; can improve milk production Not recommended Routine thyroid antibody testing

17 MYXEDEMA COMA Extreme/severe hypothyroidism Mortality rate: 20% Rare in pregnancy Diagnosis: think low Hypoventilation, hypothermia, hypotension, hyponatremia, and bradycardia Treatment Levothyroxine (IV/NG) mcg bolus IV, mcg IV daily NG doses 30-50% higher than IV; PO mcg daily once stable Liothyronine (T3 replacement) 10mcg q8hr Hydroxycortison 100mg q8hr until cortisol level known, then titrate Supportive: IVF, electrolyte replacement, telemetry, intubation, warming Cardiac enzymes and cultures to further evaluate

18 FETAL & NEONATAL EFFECTS Goitrous Thyrotoxicosis Transfer of TSI across the placenta; increased risk if 3x normal limit Nonimmune hydrops, heart failure, accelerated bone maturation, tachycardia, IUGR Treatment: increase thioamide (regardless of maternal levels) May need antithyroid drug during neonatal period Fetal Thyrotoxicosis Placental transfer of TSI s/p ablation or thyroidectomy Goitrous Hypothyroidism Due to maternal intake of thioamides Delayed bone maturation, hydramnios, hyperextension Treatment: decrease maternal thioamide dosage Possible intramniotic thyroxine injection Nongoitrous Hypothyroidism Transfer of TSH receptor blocking antibodies Williams Obstetrics 24ed. Ch. 58 Fig.3.

19 FETAL & NEONATAL MANAGEMENT Method of diagnosis: amniotic fluid or fetal cord blood sampling Goiter complications Compression of trachea and/or esophagus hydramnios and/or airway compromise Fetal neck hyperextension labor dystocia Fetal Thyrotoxicosis Maternal thioamides; treat mother with levothyroxine supplementation if needed Fetal Hypothyroidism Discontinuation of maternal thioamide (if applicable and able) Intraamniotic levothyroxine injections mg q1-4 weeks (no established protocol)

20 CONGENITAL HYPOTHYROIDISM Prevalence: 1 in births; female:male = 2:1 Causes Iodine deficiency most common Developmental disorders agenesis and hypoplasia Hereditary defects in thyroid hormone production (dyshormonogenesis) Failure of stimulation from pituitary Complications: mental deficiencies/cognitive defects, limb length Most treatable cause of mental deficiency One study found that 8% of 1420 infants had other major congenital malformations Universal newborn screening: TSH & free T4; required in US Management: Thyroxine replacement (early & aggressive)

21 THYROID NODULES Present in 1-2% of reproductive aged women Workup 15% of Chinese women at nodules >2mm 50% multiple; mostly nodular hyperplasia Some studies have shown 40% malignancy rate of solitary nodules TSH Neck ultrasound (adequate for detecting nodules >0.5cm) Malignant characteristics: irregular margins, microcalcifications, hypoechogenic pattern FNA Surgery: second trimester is optimal timing Reserved for fast going masses, compression symptoms (recurrent laryngeal nerve) Radioiodine scanning contraindicated in pregnancy Recommend waiting 6 months after ablation Recommend waiting 3 months after delivery to undergo ablation due to storage of iodide in the breast tissue

22 THYROID CANCER Requires multidisciplinary approach Typically well differentiated and slow growing Monitor with ultrasound every trimester If discovered in 1 st - 2 nd trimesters, possible thyroidectomy in 3 rd trimester otherwise delay surgery until after delivery. Injury or inadvertent removal of parathyroid glands Injury to recurrent laryngeal nerve Persistent disease s/p radioiodine treatment Pregnancy has does not lead to recurrence, however progression can occur Follow with US and thyroglobulin levels Continue levothyroxine

23 POSTPARTUM THYROIDITIS Thyroid dysfunction within 12 months of delivery Transient autoimmune thyroiditis account for 5-10% of cases Approximately 50% of women with TPO antibodies in first trimester developed postpartum thyroiditis Thyrotoxicosis Release of excess thyroid hormone Abrupt onset Small, painless goiter Lasts a few months Fatigue, irritability, weight loss, palpitations, heat intolerance Thioamides ineffective Consider beta-blocker if severe Hypothyroidism Thyromegaly more common Typically 4-8 months postpartum Fatigue, cold intolerance, weight gain, constipation, depression T4 replacement for 6-12 months Most cases will resolve spontaneously One third develop overt hypothyroidism

24 REFERENCES 1. American College of Obstetrics and Gynecology. Practice Bulletin No. 148: Thyroid Disease in Pregnancy. Obstetrics and Gynecology. 2015;125: Cunningham, F. Gary,, et al. Williams Obstetrics. 24 th edition. New York: McGraw-Hill Education, Foley, F. Michael,, et al. Obstetric Intensive Care Manual. 5 th edition. New York: McGraw-Hill Education, Lafranchi, Stephen and Maynika Rastogi. Familial Thyroid Dyshormonogenesis. Orphanet Encyclopedia, August, 2010, Accessed 2 December National Library of Medicine (US). Genetics Reference [Internet]. Bethesda, MD: The Library; 27 November Congenital Hypothyroidism; [reviewed 2015 September]. Available from: Accessed 2 December Newborn screening for congenital hypothyroidism. Journal of Clinical Research in Pediatrtic Endocrinology vol. 5 Suppl 1,Suppl 1 (2013): Ross, S. Douglas. (2018). Hyperthyroidism during pregnancy: treatment. In J. E. Mulder (Ed.), UpToDate. ay_rank=1#h17. Accessed 4 December Ross, S. Douglas. (2018). Hypothyroidism during pregnancy: clinical manifestation, diagnosis, and treatment. In J. E. Mulder (Ed.), UpToDate. rank=1. Accessed 4 December Ross, S. Douglas. (2018). Overview of Thyroid Disease in Pregnancy. In J. E. Mulder (Ed.), UpToDate. &display_rank=1. Accessed 11 November 2018.

25 THYROID DISEASE IN PREGNANCY QUESTIONS?