When evaluating the role of guidelines in clinical care, the Endocrine Society's “Guidelines on the Management of Thyroid Dysfunction During Pregnancy and Postpartum” were ideal guidelines to evaluate for several reasons: (i) hypothyroidism and pregnancy are common events, (ii) there are adverse outcomes related to untreated hypothyroidism during pregnancy, (iii) certain guideline recommendations were strongly advocated based on U.S. Preventive Service Task Force System and GRADE, and (iv) the guidelines were created by subspecialists but have large implications for medical providers across a variety of disciplines.
The first relevant question was, “Do these guidelines reach their target population?” Based on this study, the guidelines reach a minority of the target population. Obstetricians and family physicians provide the majority of antenatal care, but only 11.5% of these providers read the guidelines. Although the role of maternal thyroid function in pregnancy outcome has been well published over the past 10 years, a larger volume of work has been published in subspecialty journals than in high-impact general journals such as New England Journal of Medicine. Many of these subspecialty journals may not be accessible by primary care physicians. Although guidelines provide opportunity for subspecialty information to reach a broader population, the publication of these guidelines also occurred in a subspecialty journal, thus limiting the ability of generalists to access relevant information. Since this study shows that a small percent of these patients are ultimately referred to endocrinologists, publishing solely in an endocrine journal may not be adequate.
The second relevant question on the role of guidelines in provider education centers on the ability of guidelines to influence patient care. Although previous work has found a link between degree of subspecialization, number of years in practice, and provider knowledge on thyroid disease in pregnancy (25
), no previous study has evaluated factors involved in providing patient education. Importantly, this study found that reading the Endocrine Society's guidelines was associated with increased prepregnancy counseling on changes in thyroid hormone replacement during pregnancy, even when controlling for other variables such as provider sex, practice setting, number of years in practice, and membership to ACOG versus AAFP. This prepregnancy counseling is critical since this empowers a patient to be her own advocate once conception occurs.
Despite improvements in care with exposure to the guidelines, there were other areas of care that were not influenced. If the guidelines do not influence care, the next important questions are the following: (i) Are the guidelines practically applicable? (ii) What obstacles limit implementation?
In this study, reading the guidelines did not impact the time of first prenatal visit. The initial antenatal visit is typically 8–10 weeks of gestation, with the majority of our responders seeing patients between 7 and 12 weeks of gestation. Based on good evidence, the Endocrine Society guidelines strongly recommend providers know that there is a high likelihood that the LT4 dose needs to be increased by 4–6 weeks of gestation and may require a 30%–50% increase (18
). However, the initial antenatal visit is typically scheduled at 8–10 weeks of gestation for two reasons: first, many women do not know they are pregnant soon after conception; second, depending on method of detection, between 30% and 73% of conceptions end in miscarriage, most prior to 6 weeks of gestation (26
). Thus, first antenatal visits are typically scheduled when the fetal heart rate can be assessed.
If the first antenatal visit is after the dose change should have occurred, it may be better to check thyroid function tests at time of positive home pregnancy test. However, only 19% of physicians surveyed addressed LT4 dose at time of positive home pregnancy test, while 70% addressed LT4 dose at the first prenatal visit. There were care providers who added commentary and reported addressing the dose at time of conception if medication history was known, but in many cases, the patient's history is unknown until the initial visit. This lag time between when a dose increase is needed and when it occurs is one explanation for 49% of women on LT4 having a TSH level outside goal range during the first trimester (14
). Since the fetal thyroid does not develop until 13 weeks of gestation, and since the initial antenatal visit may occur after initial dose adjustment is warranted, a second option is to empirically increase the LT4 dose by 30% once conception is confirmed (13
). Although the method of addressing the necessary dose change was not explicitly stated in the guidelines, reading the guidelines was associated with a significantly higher likelihood of empirically increasing the dose. This may be the most practical option given the lag time between change in dose requirement and initial visit. However, not all physicians will be comfortable with this empiric dose increase (14
) since the effects of hyperthyroidism, a potential risk of empiric treatment, on pregnancy are debated (9
). Despite hesitancy of some providers in accepting empiric dose increase, the 2007 Endocrine Society's guidelines suggest that in pregnant women, there are likely no adverse effects of subclinical hyperthyroidism, a more likely outcome of empiric dose increase than overt hyperthyroidism.
This brings to point the issue of the appropriate audience for guidelines. An audience of endocrinologists is clearly too narrow for the topic of thyroid hormone replacement in women of reproductive age. Given that most patients are not under obstetric care before 7–12 weeks of gestation, perhaps an audience of obstetric care providers is also too narrow. It is possible that the audience for these guidelines would be all medical providers who start women of reproductive age on LT4 as most of the patients will not see their obstetric provider until after an initial dose adjustment is warranted. Patient education at the time of initial LT4 prescription is necessary so that the patient can then inform the obstetric team at the time of known conception instead of at the scheduled antenatal visit. If the burden of responsibility falls on all LT4-prescribing providers and the patient, this warrants distribution of the guidelines to an even larger audience.
In regard to women not already on LT4, the current guidelines do not recommend checking a TSH on all pregnant patients but instead recommend TSH screening in patients with risk factors for thyroid disease (18
). There are multiple risk factors for thyroid disease, including a family history of thyroid disease, personal history of thyroid surgery, history of head or neck radiation, goiter, type 1 diabetes or other autoimmune disorder, positive thyroid antibodies, symptoms or signs of thyroid dysfunction, iodine deficiency, history of previous thyroid disorder, infertility, miscarriage, or previous preterm delivery (18
). In this study, only 36% of providers routinely screen pregnant patients for thyroid disease risk factors, whereas close to 50% selectively screen patients with symptoms of hypothyroidism or hyperthyroidism, and another 9% do not routinely screen any patients. Although it is not clear why only a little over one-third of providers routinely screen for thyroid disease risk factors in pregnant patients, given the lengthy list of risk factors and the variety of other patient care issues being addressed at an initial antenatal visit, time constraints may be a limiting factor. Although the likelihood of screening for these risk factors increased if the guidelines were read, on multivariable analysis this association was only a trend.
In our study, only 15% of care providers routinely check TSH on all pregnant patients independent of known risk factors. Previous studies found that 19% of mid-Atlantic ACOG members and 48% of Maine physicians routinely check TSH on all pregnant patients (31
). Despite the Endocrine Society's guidelines reporting inadequate evidence for routine TSH testing in all patients, there are some practical issues that may support this option. First, a recent study found that targeting high-risk patients alone misses one-third of women with overt and subclinical hypothyroidism (33
). Second, if there is an increased likelihood of adverse pregnancy outcome with hypothyroidism, routine TSH testing is cost efficient (34
). Third, the list of relevant risk factors is lengthy, and in our study, only 36% of providers routinely screen for thyroid disease risk factors, thus increasing the likelihood of undiagnosed hypothyroidism during pregnancy. Given the potential risks of not checking TSH, the time constraints of clinical practice limiting screening for all thyroid disease risk factors (19
), and the cost–benefit ratio (34
), checking a TSH on all pregnant patients may be practical despite inconclusive long-term data.
Despite several important findings, there are limitations of this study. First, only members of Wisconsin ACOG and Wisconsin AAFP were surveyed. It is possible that this cohort is not representative of all ACOG and AAFP members. Although no previous survey study has evaluated the current management of thyroid hormone replacement in pregnancy, previous studies have looked at routine testing of TSH in pregnant patients not previously found to have hypothyroidism (31
). TSH screening practices vary widely based on geographic region, and one may extrapolate that the management of thyroid hormone replacement may also vary by geographic region. A second limitation of this study is that practice patterns were based on self-report and thus subject to respondent recall. There was an attempt to decrease recall bias by eliminating subjects who did not see a pregnant patient in 2008 and by surveying subjects February–March of 2009, just 2–3 months after the specified time period to recall. Finally, although all survey studies are at risk for bias by nonresponse, the comparison between the completed survey subjects to the total surveyed population found that they were nearly identical in regard to membership affiliation and urban versus rural practice setting.
In summary, despite their limitations (21
), clinical guidelines do serve a purpose: provider education and standardization of care. In this study, reading the Endocrine Society's “Guidelines on the Management of Thyroid Dysfunction During Pregnancy and Postpartum” was associated with positive changes in clinical practice. Yet, the guidelines reached a minority of obstetric care providers, likely secondary to their publication in a subspecialty journal. In many instances, clinical guidelines are only applicable to a subset of providers, and thus it is appropriate to limit dissemination to scientific journals within relevant societies. However, in the case of thyroid hormone replacement in women of reproductive age, the burden of awareness falls upon multiple care providers and the patient herself. Therefore, these guidelines may have been more effective if they were disseminated to a wider audience.
This study clearly shows that clinical guidelines can influence patient care. However, it also highlights how selective dissemination and lack of clear options for practical implementation can limit the true potential of guidelines. Endocrinologists previously advocated for a multidisciplinary approach to the creation of guidelines on pregnancy and thyroid function (36
). This solution would improve both dissemination and practical applicability. Because of the potential impact on practice patterns and the variety of physicians involved in the care of women of reproductive age, creating and publishing applicable guidelines for this topic should include representatives of relevant physician groups, including experts in endocrinology, obstetrics, and health service research. The role of guidelines in physician education and ultimately in the standardization of care can be optimized with a multidisciplinary approach.