Sheila F. Perillo, MD

Thyroid Disease and Pregnancy

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

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.

Thyrotoxicosis (thyroid storm)

Pregnant women with hyperthyroidism are at increased risk for:spontaneous pregnancy losscongestive heart failurethyroid stormpreterm birthPreeclampsiafetal growth restriction, and increased perinatal morbidity and mortality 

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

Grave's disease

Hyperthyroidism- thyrotoxicosis resulting from an abnormally functioning thyroid gland.

Thyroid storm- acute, severe exacerbation of hyperthyroidism

associated with hyperemesis gravidarumcan be due to high levels of human chorionic

gonadotropin (hCG) resulting from molar pregnancyhigh hCG levels TSH receptor stimulation and

temporary hypothyroidismrarely symptomatic treatment with antithyroxine drugs- not beneficial expectant managementnot associated with poor pregnancy outcomes

gestational transient thyrotoxicosis

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

TSHT4 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 

Impact of Pregnancy on Thyroid:

20 weeks' gestationreduced hepatic clearanceestrogen-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

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

Increase in volumeEcho 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 glandenlargement usually resolves after delivery not associated with abnormal thyroid function tests

Ultrasound evaluation of the thyroid gland during pregnancy

Diagnostic Approach:

Mild hyperthyroidism:Fatigue increased appetiteVomitingPalpitationsTachycardiaheat intolerance, Increased urinary

frequency InsomniaEmotional instability

The suspicion increases if patient has TremorNervousnessfrequent stoolsexcessive sweatingbrisk reflexesmuscle weaknessgoiterHypertensionweight loss. Grave's ophthalmopathy (stare, lid

lag and retraction, exophthalmos) dermopathy (localized or pretibial

myxedema)

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

Characteristics of Thyroid Storm:

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

Other signs of thyrotoxicosis in any patient with postpartum congestive heart failure: tachycardiasevere 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

Patients without classic symptoms

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

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

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

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 hormoneRemove thyroid hormone from the circulation and

increase the concentration of TBGBlock the peripheral conversion of T4 to T3Block the peripheral actions of thyroid hormoneTreat the complications of thyroid storm and provide

supportIdentify and treat potential precipitating conditions

Management of Thyroid Storm:

Supportive adjunctive care for the patient in thyroid storm are:IV fluids and electrolytesCardiac monitoringConsideration 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

Management of Thyroid Storm

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%

Medications:

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

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

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

Dosage/ Management:

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

Medications to control maternal tachycardia

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.

Dosages:

Heart failure due to cardiomyopathy from excessive thyroxine in women with uncontrolled hyperthyroidism is more common in pregnant womenSame treatment as that of thyroid stormMedical emergencyGive 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

therapySubtotal thyroidectomy (during second-trimester

pregnancy) or radioactive iodine (postpartum)for unsuccessful conventional therapy

Most asymptomatic women should have a TSH and free T4 performed approximately 6 weeks postpartum

PTU and methimazole are excreted in breast milkPTU 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 dysfunctionat low doses (10-20 mg/d) it does not seem to pose a major risk

to the nursing infant

Postpartum Care:

PTUfirst-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 functiondoes not readily crosses membranes milk concentrations are quite low

Teratogenic effects of Antithyroid Medications:

Methimazole (Thiamazole, Mercazole, Tapazole): Second-line treatment of Grave's diseasecrosses the human placenta and can induce fetal goiter

and even cretinism in a dose-dependent fashioncommonly associated with fetal anomalies such as

aplasia cutis, esophageal atresia, and choanal atresiaLong-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

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

Radioactive iodine (iodine-131; I-131): contraindicated in pregnant womencost-effective, safe, and reliable treatment for

hyperthyroidism in non-pregnant women ACOG recommendation: women should avoid pregnancy

for 4-6 months following treatmentDetrimental effects on the thyroid of the developing

fetus as 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

Thyroid storma 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.

Summary

Thyroid Storm: Critical Care In ObstetricsWHEC Practice Bulletin and Clinical Management

Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

Published: 2 June 2010