Thyroid Disease in Pregnancy


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A normal pregnancy results in a number of important reversible physiological and hormonal changes that alter thyroid structure and more importantly function.

Understanding these change are important to interpreting, identifying and managing of thyroid disease in pregnancy.

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Thyroid Disease in Pregnancy

  1. 1. By La Lura White MDMaternal Fetal Medicine
  2. 2.  A normal pregnancy results in a number of important reversible physiological and hormonal changes that alter thyroid structure and more importantly function. Understanding these change are important to interpreting, identifying and managing of thyroid disease in pregnancy.
  3. 3.  The thyroid gland is located in the anterior neck below the hyoid bone. Consist of two lobes connected by an isthmus. Each lobe is divided into lobules that contain 20-40 follicles each. Follicles consist of follicular cells which surround a glycoprotein material (colloid). Thyroid hormone is produced by the follicular cells.
  4. 4.  The production of thyroid hormone functions on a negative feedback loop. The hypothalamus releases thyrotropin-releasing hormone (TRH) from paraventricular nucleus. Stimulates the anterior pituitary gland to secrete thyroid-stimulating hormone (TSH). This in turn causes the thyroid gland to produce and release thyroid hormone. The thyroid gland produces thyroxine (T4), deiodinated primarily by the liver to its active form, triiodothyronine (T3). The thyroid gland also produces a small amount of T3 directly.
  5. 5.  Increase in dietary iodine from 80-100 mcg/d to 200 mcg./day. Dietary iodine uptake by thyroid gland is reduced to iodide. This is the rate limiting step for hormone synthesis. Iodide binds to thyroglobulin catalyzed by thyroid peroxidase to produce monoidotyrosine (MIT) or di-iodotyrosine (DIT). T4: coupling 2 DIT. T3: coupling DIT+MIT. Stored bound to thyroglobulin as a colloid.
  6. 6.  Under TSH control, thyroglobulin is digested and T3 30 mcg/d) and T4 (90 mcg./d) released into capillary circulation. T4(thyroid origin) and T3(T4 deiodinated by liver and kidneys to T3, only 20% thyroid production) 99% hormone bound mostly to thyroxine-binding globulin (TBG). Other binding proteins include thyroxine-binding pre-albumin and albumin.
  7. 7. Physiological Changes in ThyroidStructure 20% increase in thyroid gland size due to hyperplasia and increased vascularity. T4 production increases approximately 50% starting in early pregnancy. Rarely thyroid gland enlargement causes goiter unless iodine-deficient. Plasma iodide levels decrease as a result of fetal iodide use, placental losses and increased maternal renal clearance resulting in a deficit.
  8. 8.  Physiological Changes in Thyroid Function: Influenced by two hormones: hCG and estrogen. hCG: Shares some structural homology with thyrotropin (TSH). Binds to thyroid gland TSH receptors, exhibit weak thyrotropic stimulation with subsequent hormone production, especially first trimester.
  9. 9.  Week from the Last Menstrual Period Amount of HCG in mIU/ml 3 5 -50 4 3 - 426 5 19 - 7,340 6 1,080 - 56,500 7-8 7,650 - 229,000 9 - 12 25,700 - 288,000 13 - 16 13,300 - 254,000 17 - 24 4,060 - 165,400 25 - 40 3,640 - 117,000 Peaks end first trimester and then declines.
  10. 10.  Increased hCG will stimulate thyroid hormone production and produce a negative feedback, suppress and decrease levels of thyroid stimulating hormone (TSH) in the first trimester. Serum TSH drops to undetectable levels in up to 15% of normal pregnancies. Mistakenly diagnose hyperthyroidism with physiologic decrease in TSH and increase in thyroid hormone. By the second trimester, serum TSH levels return to normal
  11. 11.  Estrogen Stimulates the liver to produce thyroid binding proteins, especially (TBG), major transport protein for thyroid hormone and extend its half-life. Significant increase in secretion TBG (levels ~200 %). Results in lower free thyroid hormone and stimulate positive feedback H-P-T axis. Reduced peripheral TBG degradation rate. 80% TBG (greater affinity) 15% TBPA (greater binding). Increase in total but not free thyroid hormone which remains within normal limits.
  12. 12.  Gestational Transient Thyrotoxicosis) Seen in 10% to 15% of pregnant women during early pregnancy. Mildly increased free T4 and suppressed TSH early in pregnancy not due to intrinsic thyroid pathology. Characterized by mild or no symptoms, and resolves spontaneously by the second half of pregnancy. No evidence of thyroid autoimmunity, when evaluating thyroid antibodies (thyroid peroxidase antibodies ) or immunoglobulins (thyroid- stimulating immunoglobulins). Associated with hyperemesis gravidarum. Also with hydatidiform mole, secondary to high levels of hCG that lead to TSH receptor stimulation. Rarely symptomatic, no treatment with anti-thyroxine medications.
  13. 13.  Fetal thyroid: Form as a midline outpouching of the anterior pharyngeal floor, migrates and reaches its final position by 7 weeks. Lateral contributions from the 4th and 5th pharyngeal pouches give its bilateral shape by week 8-9.
  14. 14.  Fetal Thyroid The fetal thyroid begins concentrating iodine by 10 to 12 weeks and produces thyroid hormones (T4 and T3) between 15 and 18 weeks of gestation, with the fetal pituitary also producing TSH beginning around this time. Although fetal thyroid is functional, it still depends on adequate amounts of iodide from mother. Placental transfer of maternal T4,T3 is believed to occur prior to fetal thyroid hormone synthesis and continue thereafter. May be the only source of thyroid hormone during early fetal life, and it is important to maintain normal maternal thyroid status for brain maturation of the developing child.
  15. 15.  Hypothyroidism Normal Complicates 1-3/1000 pregnancies. Most common cause of primary hypothyroidism in women of child-bearing age is chronic autoimmune thyroiditis (Hashimoto’s thyroiditis). Hashimoto’s thyroiditis Painless inflammation with progressive enlargement of the thyroid gland (diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, eosinpohilic changes).
  16. 16.  Other causes primary hypothyroidism (thyroid gland) Endemic iodine deficiency Ablative radioiodine therapy Thyroidectomy Secondary hypothyroidism (pituitary) Lymphocytic hypophysitis HypophysectomyTertiary hypothyroidism (hypothalamus) Rare
  17. 17. Hypothyroid Symptoms: (similar to pregnancy complaints) Fatigue  Insomnia Constipation  Weight gain Cold intolerance  Hair loss Muscle cramps  Carpel tunnel  Voice changes  Intellectual slowness
  18. 18.  Signs of hypothyroiddism: Peri-orbital edema Dry skin Goiter Prolonged relaxation phase of DTR’s
  19. 19.  Maternal/Fetal Risk Infertility Spontaneous abortion Pre-eclampsia Placental abruption Low birth weight Prematurity Stillbirth
  20. 20.  Fetal Risk: Impaired neurodevelopment Initial phase of the fetal brain (neuronal multiplication, migration, and organization) during the second trimester, the supply of thyroid hormones to the growing fetus is almost exclusively of maternal origin. During the next phase of fetal brain development (glial cell multiplication, migration and myelinisation), from the third trimester up to 2-3 years postnatally, the supply of thyroid hormones to the fetus is essentially of fetal origin. While severe maternal hypothyroidism during the second trimester will result in irreversible neurologic deficits, maternal hypothyroxinemia occurring at later stages will result in less severe, and also partially reversible, fetal brain damage.
  21. 21.  Diagnosis TSH (most sensitive): Non-pregnant normal range for TSH (.45-4.5 mIU/ml). 95% have levels <2.5 mIU/ml., and those with levels 2.5-4.5 mIU/ml are at greater risk for overt disease. T4: (nl 0.7-1.8 ng/dl) For diagnosis of hypothyroidism, elevated TSH and decreased T4.
  22. 22.  Management: Levothyroxine sodium (Synthyroid) 1-2 mcg/kg/d (100 mcg/d). Measure TSH every 6-8 weeks (.5-2.5 mIU/L). T4 can be helpful to determine response to treatment. Adjust medication dose on 25-50 mcg increments.
  23. 23.  Newly diagnosed hypothyroid patient, a full replacement dose of levothyroxine should be instituted immediately, assuming there are no abnormalities in cardiac function. To normalize the T4 pool more rapidly (when clinically required), therapy may be initiated by giving for two-three days a levothyroxine dose which is two-three times the estimated final replacement daily dose. This will allow more rapid normalization of the circulating T4 levels and a more rapid return to the euthyroid state.
  24. 24.  Thyroxine requirements of women with preexisting hypothyroidism increase during pregnancy and about 30-50% will need adjustment of their medication: estrogen-induced increased TBG concentrations increased volume of distribution increased placental T4 degradation and transport Check TSH levels on first prenatal visit Adjustment of levothyroxine dosage should be implemented as early as possible during gestation and certainly within the first trimester.
  25. 25.  Those well-controlled can have TSH levels checked each trimester. Drugs that interfere with levothyroxine: absorption: (cholestyramine, ferrous sulfate, aluminum hydroxide antacids) metabolism: (phenytoin, carbamazepine, rifampin) After delivery: Levothyroxine dose should progressively be reduced to its pregestational level. TSH concentration rechecked at the 6th-8th week postpartum visit. Patient can breastfeed.
  26. 26.  Subclinical hypothyroidism:(elevated TSH/normal T4) Some suggest treat to restore TSH to normal range due to possible increase in fetal wastage or impaired neurodevelopment but no consensus or ACOG recommended. Isolated hypothyroxinemia: (normal TSH/lowT4) May suggest central hypothyroidism (pituitary macroadenoma, pituitary surgery or radiation). Associated with iodine insuffiency causes autoregulatorty response that leads to low T4. Possible treatment for impaired fetal neurodevelopment with central hypothydoidism conditions otherwise no treatment.
  27. 27.  New guidelines of the American Thyroid Association (ATA) reported online July 25, 2010 Women who are already receiving thyroid replacement therapy should increase their dose by 25% to 30% when they become pregnant. Women with subclinical hypothyroidism in pregnancy who are not initially treated should be monitored for progression to overt hypothyroidism. Serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels should be measured approximately every 4 weeks until 16 to 20 weeks gestation and at least once between 26 and 32 weeks gestation.
  28. 28.  In the first trimester, normal range for TSH level is 0.1 to 2.5 mIU/L; this level increases to 0.2 to 3.0 mIU/L in the second trimester and 0.3 to 3.0 mIU/L in the third trimester. During pregnancy and lactation, the minimal suggested daily recommended allowance for iodine is 250 μg. The risk for fetal hypothyroidism may increase when total daily iodine intake from diet and/or supplements is or exceeds 500 μg.
  29. 29.  Congenital hypothyroidism Cretinism: "Jonny druitt syndrome" Dull look Puffy face Thick tongue that sticks out Choking episodes Constipation Dry, brittle hair Jaundice Lack of muscle tone Low hairline Poor feeding Short height Sleepiness Sluggishness
  30. 30.  Other caues congenital hypothyroidim: Thyroid agenesis, inborn errors of metabolism, maternal blocking antibodies, congenital pituitary and hypothalamic hypothyroidism. Neurological impairment if not treated before 3 months postnatal. Neonatal Hypothyroidism
  31. 31.  Hyperthyroidism Hyperthyroidism affects 2/1000 pregnancies Graves disease (diffuse toxic goiter) is the most common form of overt hyperthyroidism. Organ-specific autoimmune process where thyroid stimulating autoantibodies attach to and activate TSH receptors. In some with history of Graves disease, thyroid stimulating autoantibodies activity may decrease with chemical remission. Other etiologies: Functional adenoma or toxic nodular goiter, thyroiditis or excess thyroid intake.
  32. 32.  Symptoms Nausea/Vomiting Weight loss Nervousness Heat intolerance Insomnia Breathlessness Diaphoresis Fatigue Anxiety
  33. 33. Signs: Thyromegaly Diffuse goiter Exophthalmos Pretibial myxedema Increased cardiac output Systolic flow murmur Resting pulse >100 (tachycardia)
  34. 34.  Maternal Risk: Congestive heart failure Thyroid storm Pre-eclampsia
  35. 35.  Fetal Risk Early pregnancy loss (increased risk congenital anomalies untreated) IUGR LBW PTB
  36. 36.  Neonatal hyperthyroidism 1-2% Thyrotropin receptor-stimulating antibodies (TSHR-SAb), can cross the placenta, and cause an overactive thyroid in the fetus. small head circumference, prominent forehead Enlarged thyroid (goiter) Difficulty breathing High blood pressure Tachycardia Arrythmia Emesis Diarrhea
  37. 37.  Hyperthyroidism: Diagnosis Depressed serum TSH (< .45mIU/L) Elevated T4 (>1.8 ng/dl) Rare T3 thyrotoxicosis (check for if depressed TSH but normal T4) Check TSH receptor antibodies, may be increased risk neonatal hypothyroidism)
  38. 38.  Antithyroid drugs: inhibit iodination of thyroglobulin and thyroglobulin synthesis: Propylthiouracil(PTU): Also some blocking T4 to T3 conversion Crosses the placenta less readily Initial daily dose 100-600 mg, suggest start 300 mg/d 100-150 mg q 8 hr. 50 mg. qid 150 mg/d Maintain 50mg bid
  39. 39.  Methimazole :10-40 mg daily dose Management: Maintain T4 in upper normal range using lowest possible dose. May be able to discontinue 32-34 weeks. Improvement in T4 in 4 weeks Normalization TSH 6-8 weeks
  40. 40.  Methamizole: ? Aplasia cutis, esophageal and choanal atresia PTU: severe liver toxicity Thiomide Risk: Rash, hepatitis,drug fever 10% transient leukopenia .1-0.2% agranulocytosis (acute onset, not dose related but others feel related to higher doses and increased maternal age)
  41. 41.  Other treatments: (unable to take medication) Surgery: subtotal thyroidectomy after 1st trimester hypothyroidism recurrent laryngeal nerve paralysis Radioactive iodine ablation is contraindicated and women should avoid pregnancy for at least 6 months
  42. 42.  Monitor closely after delivery. Can get recurrence or aggravation of symptoms first few months. Check TSH and T4 6 weeks postpartum. Can breast feed, most medication protein bound.
  43. 43.  Acute, life-threatening exacerbation of thyrotoxicosis 1-2% of patients with hyperthyroidism progress to thyroid storm Precipitated by a physiologically stressful event, labor, delivery, C/Section, infections If untreated, thyroid storm may be fatal is as high as 20%
  44. 44.  Fever  Nausea Tachycardia  Vomiting Tremor  Diarrhea Delirium  Dehydration Coma
  45. 45.  Tachycardia (out of proportion to the fever)  Diaphoresis (often profuse)  Widened pulse pressure  Congestive heart failure (may be a high output failure)  Atrial fibrillation (may be refractory to attempted rate control with digitalis; converts after antithyroid therapy in 20-50% of patients  ShockUp to one half of patients presenting to the ED in thyroid storm report a dramatic weight loss of more than 40 lb.
  46. 46.  1 gm PTU p.o. or crushed in NG tube the continued 200 mg. q. 6 hours or 600 mg. b.i.d. One hour later give Sodium iodide 500-1000mg IV q. 8 (block release T3 and T4) oral 5gtts KI or 10 gtts Lugol’s solution q. 8 hrs.If hx iodide anaphylaxis, give lithium carbonate 300 mg. q. 6 hrs. Propranolol: 40 mg.p.o q 6 hr. (1-2 mg IV) for tachycardia >120 bpm. Dexamethasone 2 mg q. 6 hrs. X 4 doses (block peripheral conversion T4 to T3) Fluid and nutritional support Treat hyperthermia
  47. 47.  Post-partum Thyroditis 3-6 months postpartum. Up to 10% women first year after childbirth. Secondary to thyroid autoantibodies. Depression, memory impairment, carelessness. Risk: Family hx of thyroid or other autoimmune diseases, 25% +IDDM will develop disease Transient hypo or hyper thyroidism
  48. 48.  Two Phases: 1) 1-4 months post delivery: glandular disruption leads to hormone release (4% transient thyrotoxicosis) abrupt; develop small, painless goiter, fatigue, palpitations antithyroid meds ineffective, can give b- blockers 2) 4-8 months postpartum (2-5% develop hypothyroidism) treat with thyroxine 6-12 months Most recover within 12 months 30% permanent hypothyroidism
  49. 49.  Subclinical Hyperthyroidism Depressed TSH with normal T4 1.7% of pregnancies More common in iodine deficient areas Long-term sequale: Osteoporosis, cardiovascular morbidity, overt thyrotoxicosis, thyroid failure. No adverse pregnancy affects
  50. 50. Obstetrix Professor