Hyperthyroidism in Pregnancy

Authors: Amanda Ammentorp, DO (Flight Surgeon, USAF) and Nicolas Ferry, MD (Flight Surgeon, USAF) // Reviewed by: George Willis, MD (@DocWillisMD); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Cases

#1: A 32-year-old female presents to the emergency department with increased anxiety, tachycardia, and heat intolerance.

#2: A 42-year-old female presents to the emergency department with concern for neck mass after years of infertility and recent positive pregnancy test.

These are two classic cases of how hyperthyroidism may present in the emergency department; however, if the patient is also pregnant the situation becomes much more concerning.

Even though there is an overall low incidence, hyperthyroidism has many pregnancy complications to include maternal heart failure, premature delivery and pre-eclampsia (1). Although rare, thyroid storm can also develop. Emergency physicians should have a high clinical index of suspicion as the prognosis for the mother and fetus is good with appropriate treatment and can prevent further pregnancy complications. We will discuss how these patients may present to the emergency department, the appropriate evaluation for this condition and finally emergency department management of these patients.


Normal Thyroid Physiology in Pregnancy

In order to understand the physiology surrounding this condition, it is important to remember the normal changes the thyroid undergoes in response to pregnancy. Something important to remember in order to understand the physiology surrounding this condition is how the thyroid function normally changes in response to pregnancy. Due to the increased metabolic demand during pregnancy and increased estrogen production, the amount of thyroxine-binding globulin (TBG) is elevated. Overall, this leads to an increase of total T4 and T3 by about 50% in the first half of pregnancy. Once 20 weeks are reached, the body has achieved a new steady state of higher thyroid hormone, and the production rate returns to pre-pregnancy rate of production (2). Another factor is hCG, which also has minimal thyroid-stimulating activity and can bind to the TSH receptor; when hCG peaks around 10-12 weeks, total T4 and T3 can increase, causing a minority of women to have transient hyperthyroidism (usually subclinical) and is a normal physiologic finding (3). This increase in thyroid hormone production through hCG stimulation will decrease TSH production; once hCG has peaked and starts to decrease, thyroid hormone production decreases and TSH production will return to normal once it is no longer inhibited. T4 and T3 concentrations will also return to normal range (4).


ED Presentations

There are two main causes of hyperthyroidism in pregnant women: Grave’s disease (0.1-1% of pregnancies) and hCG-mediated hyperthyroidism from gestational transient thyrotoxicosis (1-3% of pregnancies). Other less common pathologies include presentations due to molar pregnancy or autonomous thyroid hormone production from a thyroid nodule, as well as subacute/silent thyroiditis, although less common (5).

Nonspecific symptoms of hyperthyroidism include tachycardia, heat intolerance, weight loss, increased perspiration, anxiety and hand tremor. Ophthalmopathy and a goiter may also be present and are more suggestive of Graves’ disease than hCG-mediated hyperthyroidism. A pregnant patient concerned about lack of pregnancy-related weight gain can also alert the emergency physician in addition to the symptoms mentioned above.

Other potential symptoms may be from complications of hyperthyroidism in pregnancy, especially if they have not yet seen an OB/GYN or have poor access to prenatal care/OB care during their pregnancy. Pregnancy complications can include spontaneous abortion, premature labor, intrauterine growth restriction (IUGR), pre-eclampsia, stillbirth and heart failure in the mother (6). Due to the overall high prevalence of hypertension, it can be easily missed (or often overlooked) even though it may be the first sign of hyperthyroidism. Symptoms to look for with these complications include shortness of breath, edema, and hypertension. An OB ultrasound would also be prudent and will be discussed further below.

Lastly, pregnancy can be a precipitating factor for thyroid storm. Although very rare (1% of pregnancies with hyperthyroidism), the classic triad of symptoms is extreme fever (>104℉), tachycardia, and altered mental status (7). More on thyroid storm can be found at this emDocs article: http://www.emdocs.net/thyroid-storm-management/.


Evaluation

A reasonable ED evaluation for patients with the symptoms described above and specific to these conditions includes a TSH and pregnancy test. If the pregnancy test is positive, and the patient has no previous OB ultrasounds available, an OB ultrasound would be appropriate to attempt to date the pregnancy.

Because of the fluctuations in the levels of thyroid hormone, the American Thyroid Association (ATA) published guidelines based on the trimester of pregnancy for reference ranges of TSH and serum free T4 (8). In weeks 7-12, they recommended broadening the TSH reference range to 0.1-4 mU/L, and then in the 2nd and 3rd trimester there will be a gradual return to the normal lab reference ranges. For total T4, an increase about 5% per week starting at week 7 is considered within normal, and then at 16 weeks, total T4 and T3 levels will be 1.5x higher than in non-pregnant women (due to TBG excess from increased metabolic demand and estrogen production).

If the TSH is low, a free or total T4 should be considered for further evaluation. A patient with overt hyperthyroidism in pregnancy will have an undetectable or low TSH as well as elevated free/total T4 within the lab limits listed above. Once this is determined, it is important to establish whether the patient has Graves’ disease which can be done through measuring TSH receptor antibody concentrations with a TSI (8). This is not necessarily something that needs to be performed in the emergency department and can be completed in the outpatient setting with OB/GYN or the primary care physician. This is an important test, as delay in results could affect overall care of the patient and fetus.


Management

Management will differ depending on if the patient has hCG-mediated hyperthyroidism or another cause. hCG-mediated is usually transient and doesn’t require treatment. For other causes, the best outcome for mother and fetus depends on appropriately controlling the hyperthyroidism.

The overall goal is to maintain the mother in a slight hyperthyroid state to avoid fetal hypothyroidism, as the fetus is more sensitive to anti-thyroid drugs and fluctuations in thyroid hormone levels (9). To do this, the mother’s free T4 should be at or just above the trimester-specific upper level of normal and total T4 should be 1.5 times the non-pregnant reference range. TSH should be below reference range for pregnancy (0.1-0.3), with the goal of utilizing the lowest possible dose of medication to achieve these levels (10).

Most mothers are started on a thionamide medication due to teratogenic risks associated with many alternative therapies. If they are diagnosed in the first trimester, oral propylthiouracil (PTU) is started, 50 mg 2-3 times daily. After the first trimester, they should be started on oral methimazole, 5-10 mg daily. PTU is preferred in the first trimester as it is less potent than methimazole, which is especially important during organogenesis stage of fetal development. Both of these medications have some teratogenic effects and can cause hepatotoxicity (<0.1%) so appropriate counseling is encouraged (8). If a patient is started on these medications, they should have at least monthly thyroid function tests and close OB follow-up and care.

For symptomatic control, the American Thyroid Association recommends starting a beta-blocker, a first-line agent being metoprolol orally 25-50 mg daily. Propranolol 20 mg orally every 6-8 hours is an alternative option if metoprolol is contraindicated or poorly tolerated. It is recommended to wean the patient off beta-blockers as soon as her thionamide has taken effect and reached appropriate levels in order to decrease side effects, as beta-blockers can cause intrauterine growth retardation, hypoglycemia, respiratory depression and bradycardia if used for more than 2-6 weeks (11).

Managing thyroid storm in pregnancy is very similar to treatment plans in non-pregnant patients (5). Supportive therapy with oxygen is encouraged. Beta-blocking drugs are first line to control tachyarrhythmias. PTU is preferred in thyroid storm as it blocks the conversion of T4 to T3. One hour after starting PTU, it is appropriate to start oral potassium iodide to block additional thyroid hormone release. This is summarized in table 3.

Disposition of these patients is dependent on the institution and follow up availability. In a facility with easy access to consultations, reaching out to OB and/or endocrine to guide close outpatient follow-up and dosing guidelines for these medications is helpful. In a smaller community setting, discharging a patient on a beta-blocker as above with close follow-up with OB and endocrine to start a thionamide medication is also reasonable with good return precautions.


Must-Knows/Summary:

-Untreated hyperthyroidism in a pregnant patient can have serious health consequences in the mother and the fetus.

-The lab reference ranges change for pregnant patients (TSH threshold is lowered to 0.1-4, total T4 threshold increases by 1.5x).

-Use beta-blockers for symptomatic control; first line for hyperthyroidism in pregnancy is metoprolol 25-50 mg daily. For thyroid storm, use propranolol or esmolol as discussed above.

Use PTU for anti-thyroid drug treatment starting in first trimester and methimazole in the second trimester (PTU is less potent).

-Make sure your pregnant patients, and especially those with a new diagnosis of hyperthyroidism, have close OB follow-up on discharge to facilitate medication dose changes and monitoring the pregnancy.


References

  1. Miller LK, Wing DA, Leung AS, Koonings PP, Montoro MN, Mestman JH. Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. International Journal of Gynecology & Obstetrics. 1994;84:946-949.
  2. Ain KB, Mori Y, Refetoff S. Reduced clearance rate of thyroxine-binding globulin (TBG) with increased sialylation: a mechanism for estrogen-induced elevation of serum TBG concentration. J Clin Endocrinol Metab 1987; 65:689.
  3. Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid. Best Pract Res Clin Endocrinol Metab.2004; 18: 249-265.
  4. Ballabio M, Poshychinda M, Ekins RP. Pregnancy-induced changes in thyroid function: role of human chorionic gonadotropin as putative regulator of maternal thyroid. J Clin Endocrinol Metab 1991; 73:824.
  5. Cooper DS, Laurberg P 2013 Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol 1:238–249.
  6. Luewan S, Chakkabut P, Tongsong T. Outcomes of pregnancy complicated with hyperthyroidism: a cohort study. Arch Gynecol Obstet 2011; 283:243.
  7. ACOG Practice Bulletin No. 37: Thyroid Disease in Pregnancy. Obstetrics & Gynecology. 2002;100(2):387-396.
  8. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017; 27:315.
  9. Momotani N, Noh J, Oyanagi H, et al. Antithyroid drug therapy for Graves’ disease during pregnancy. Optimal regimen for fetal thyroid status. N Engl J Med 1986; 315:24.
  10. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid 2016; 26:1343.
  11. Lydakis C, Lip GY, Beevers M, Beevers DG. Atenolol and fetal growth in pregnancies complicated by hypertension. Am J Hypertens 1999; 12:541.

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