Management of Thyroid Disorders during Pregnancy: A Survey of Physicians from the Middle East and North Africa

Abstract

Objectives We explored the clinical practice of screening and managing hyperthyroidism and hypothyroidism during pregnancy in the Middle East and North Africa.

Methods We used an online questionnaire based on clinical case scenarios to a regional physician database and invited those managing pregnant women with thyroid disease to respond.

Results We analyzed 136 eligible responses. For a woman with newly diagnosed Graves' disease (GD) and wishing to conceive, 77.5% of the respondents would initiate antithyroid drugs (ATDs), while 20.3% would recommend definitive treatment with radioiodine or surgery. In the case of a relapsed GD before pregnancy, 84.3% preferred definitive treatment. For a woman with newly diagnosed GD during pregnancy, 39.4% will start propylthiouracil (PTU), 8.5% with methimazole/carbimazole, while 50.0% will start with PTU and then switch to methimazole after the first trimester. Respondents used several combinations of tests to monitor the dose of ATDs, and the thyroid test results they targeted were inconsistent, though nearly half of the respondents targeted achieving low serum thyroid-stimulating hormone (TSH) with free thyroxine (or total T4) in the upper end of the normal range. For a lactating woman with GD, 80.3% would give ATDs without stopping lactation. For the management of gestational thyrotoxicosis, 45.1% chose to follow-up, and 40.8% treated patients with PTU. Although the timing of TSH receptor antibody measurement in pregnant hyperthyroid patients was variable, 53% of respondents would check it at least once during pregnancy. The starting dose of L-thyroxine for a woman diagnosed with overt hypothyroidism in pregnancy, preconception management of euthyroid women with known thyroid autoimmunity, and approach related to ovarian hyperstimulation in women with thyroid peroxidase antibodies were widely variable. For women with known hypothyroidism, 34.6% of respondents would increase the L-thyroxine dose by 30 to 50% as soon as pregnancy is confirmed. Concerning screening, 42.7% of respondents perform universal evaluation and 70% recommend TSH < 2.5 mUI/L in the first trimester and TSH < 3 mUI/L in the second and third trimester as target results in known hypothyroid women.

Conclusion Physicians' clinical practices regarding thyroid disorders in pregnant women vary. This highlights the need for focused training and quality assurance to achieve more consistent care.

Keywords

screening - management - pregnancy - thyroid - hypothyroidism in pregnancy - hyperthyroidism in pregnancy

Introduction

Both overt and subclinical maternal thyroid hormone disorders are common in pregnancy and may be associated with several adverse outcomes.[1] [2] While it is generally accepted that optimal treatment of maternal hyperthyroidism and hypothyroidism is vital to achieving a successful pregnancy outcome, the screening and treatment of these disorders is still a matter of controversy.[3] [4] [5] [6]

Hyperthyroidism in pregnancy affects between 0.1 and 1% of women·[7] Graves' disease (GD) is the most common cause of hyperthyroidism in pregnancy. Gestational transient thyrotoxicosis (GTT) is also fairly common and accounts for 10% of cases. GTT most often presents as a subclinical hyperthyroidism and is not associated with an adverse pregnancy outcome.[7] [8] [9] GD and GTT must be distinguished because their clinical courses, associated risks for the mother and the fetus, and management approaches are different. Prolonged inadequately controlled maternal overt thyrotoxicosis is associated with maternal and fetal/neonatal complications. Early and optimal treatment with antithyroid drugs (ATDs) can prevent such complications.[10] [11] However, there have been several reports of severe congenital malformations associated with methimazole-carbimazole (MMI/CMZ) use in early pregnancy. In contrast, propylthiouracil (PTU) is associated with rare but severe liver failure.

On the other hand, hypothyroidism complicates 2 to 3% of pregnancies and up to 6.3% if the trimester-specific reference range is used.[1] The most common cause in the Western world is Hashimoto's thyroiditis and iodine deficiency in iodine-deficient regions. Overt hypothyroid pregnant women suffer increased rates of early pregnancy loss, preeclampsia, placental abruption, growth restriction, prematurity, and stillbirths, and their fetuses are at risk for impaired neurologic development.[1] [2] Although it is well known that overt hypothyroidism has a deleterious impact on obstetrical outcomes, data regarding several questions is critically needed.[3] [5]

International professional organizations published several guidelines for managing thyroid disorders during pregnancy over the past two decades.[12] [13] [14] [15] [16] [17] There is an overall consensus regarding diagnosing overt and subclinical hyperthyroidism and hypothyroidism in pregnancy using the pregnancy-specific reference ranges for thyroid-stimulating hormone (TSH) and the assay trimester-specific ranges for free thyroxine (FT4). However, there is controversy on managing subclinical thyroid disease, thyroid function surveillance protocols, and iodine nutrition recommendations.[18] [19] [20] Despite the abundance of these guidelines, the degree of acceptance and applicability by the health community has been variable in concordance with these guidelines. It has been the subject of several surveys from Europe, Asia, and the Americas for hyperthyroidism and hypothyroidism.[21] [22] [23] [24] [25] Physicians in the Middle East and North Africa (MENA) have not been well represented in these surveys. In the present study, we surveyed a sample of relevant MENA physicians to explore their perceptions and practices regarding screening and managing thyroid disorders during pregnancy.

Materials and Methods

We aimed to explore the perceptions and patterns of clinical practice in managing thyroid disease during pregnancy. We used a Web-based commercial survey management service (Survey Monkey, Palo Alto, California, United States) to formulate, disseminate, and analyze the survey.

In the absence of a single MENA regional endocrine society with a membership list that can define a study population, a few questions were added to define the professional profiles of the respondents and their practices. The target population was identified from pooled electronic mail lists of various groups or forums in various parts of the MENA region, similar to previously published studies.[26] [27] They all received an initial email that explained the rationale and what is required from the respondents and four subsequent reminder emails over 12 weeks, including a unique email-specific electronic link to the questionnaire. At the end of the study, survey responses were collected anonymously, stored electronically, and analyzed. Only independent doctors (consultants and specialists) who confirmed that they managed thyroid disease during pregnancy and provided substantial responses were included. No data are available on nonrespondents.

The survey questionnaire was analogous to that used by previous international studies.[21] [22] [23] [24] [25] The questionnaire was served in its original English language ([Supplementary Material S1], available in the online version). The survey questionnaire consisted of clinical case scenarios with questions related to clinical practice about the screening and management of hyper- and hypothyroidism in pregnancy. Respondents were asked to select one or multiple answers or respond to a grid. However, they could also provide their answer for most questions if it was not included in the questionnaire. Descriptive statistics and frequencies were adjusted on a 100% basis, excluding the nonrespondents. Comparisons were made using the chi-square test.

Results

Respondents' and Service Profiles

One hundred and twenty-five responses fulfilled the entry criteria and provided substantial responses. Most responses came from the United Arab Emirates, Saudi Arabia, and Qatar, with smaller numbers from Oman, Libya, Lebanon, Iraq, Iran, Tunisia, Algeria, Syria, Egypt, Bahrain, Kuwait, Jordan, and Yemen. Endocrinologists represented 60.8%, followed by 12.8% internists with practice in endocrinology, 12.8% were obstetricians, 7.2% were internists, 6.5% were primary care physicians, and 1 obstetric physician. Most (75.2%) were senior doctors (consultant/attending physician); the rest were subconsultant specialists. Respondents reported that the management of thyroid disorders during pregnancy in their institutions was performed by endocrinologists (71.0%), followed by internists with practice in endocrinology (22.6%), and obstetric physicians (6.5%). Just under a quarter (22%) of respondents reported the existence of joint multidisciplinary clinics.

Management of Hyperthyroidism during Pregnancy

The responses to the key issues addressed in the survey regarding management of hyperthyroidism during pregnancy are summarized in [Table 1] and illustrated in [Fig. 1].

Fig. 1 Respondents' management of hyperthyroidism during pregnancy. (A) Initial treatment of choice for a 26-year-old woman with newly diagnosed Graves' disease (GD) (n = 102) and a 34-year-old woman with a third relapse of GD (n = 103), both wishing to become pregnant soon. (B) Choice of treatment for newly diagnosed GD in a 24-year-old woman (n = 102) and for a 24-year-old woman with gestational transient thyrotoxicosis (GTT), both at 8 weeks gestation (n = 103). (C) The measurement of thyrotropin receptor antibodies (TRAb) during pregnancy in a woman with Graves' disease on antithyroid drugs (responses = 102) and in a euthyroid pregnant woman previously treated with radioactive iodine or total thyroidectomy (responses = 103).

Table 1 Physicians' practices in screening and management for hyperthyroidism during pregnancy represented by responses to seven key questions

Variables: Seven key survey questions and determined answers	Responders (%)
1. Prepregnancy approach for a newly diagnosed Graves' disease
PTU	57.8
MMI/CMZ	22.6
Surgery	3.9
Radioiodine	8.8
2. Treatment for Graves' hyperthyroidism in the first trimester
PTU	46.1
PTU in the first trimester, then MMI/CMZ	48.0
MMI/CMZ	2.0
3. Tests to monitor antithyroid drug dosage in pregnancy
TSH and FT4	33.7
TSH, FT4, and FT3	28.7
FT4 alone	4.0
TSH, TT4, TT3	8.9
4. Target thyroid function in treated hyperthyroidism
Low TSH and FT4 (or TT4) in the upper end of the normal range	51.5
TSH and FT4 (or TT4) in the normal range	26.2
Low TSH and FT4 (or TT4) in the normal range	14.6
Low TSH, independent of FT4 (TT4) levels	3.9
Others	3.9
5. Treatment for gestational thyrotoxicosis
Follow-up, no treatment	61.2
PTU, in the first trimester, then MMI/CMZ	13.6
PTU	13.6
MMI/CMZ	1.0
6. Checking TRAb in hyperthyroid pregnant
No	23.5
Yes, in the first trimester, and if positive in the third trimester	43.1
Yes, in each trimester	23.5
Yes, in the first and third trimesters	5.9
7. Postpartum lactating woman with Graves' hyperthyroidism
MMI/CMZ but continue lactation	49.5
PTU but continue lactation	25.7
MMI/CMZ and stop lactation	17.8
PTU and stop lactation	55.0

Abbreviations: FT3, free triiodothyronine; FT4, free thyroxine; MMI/CMZ, methimazole/carbimazole; PTU, propylthiouracil; TRAb, thyrotropin receptor antibody; TSH, thyroid-stimulating hormone; TT3, total triiodothyronine; TT4, total thyroxine.

Treatment of GD

When respondents were asked how they would treat a woman with newly diagnosed GD wishing to become pregnant soon, most respondents (80.4%) reported that they would treat the woman with ATDs, with a preference for PTU (57.8%). For a woman with a third relapse of GD and wishing to become pregnant, most respondents preferred a definitive treatment (83.5%) with surgery or radioiodine rather than another course of ATDs (10/7%) as compared to respondents' preferred treatment for a patient with newly diagnosed GD ([Fig. 1A]). For newly discovered GD in an 8-week pregnant woman, nearly half (48.0%) of the respondents would treat her with PTU in the first trimester and then switch to MMI/CMZ. In contrast, slightly fewer (46.1%) would be treated with PTU throughout the pregnancy, and only a minority would use MMI/CMZ ([Fig. 1B]).

Respondents used several different combinations of tests to monitor the dose of ATDs during pregnancy. Most respondents (83.2%) would measure serum TSH and FT4. They aimed to achieve variable target thyroid function test (TFT) results. However, just over half (51.5%) of the respondents targeted low serum TSH with FT4 (or total T4) in the upper end of the reference range.

Over three-quarters (76.4%) of the respondents would measure the thyrotropin receptor antibodies (TRAb) at least on one occasion in a pregnant woman being treated with ATDs for GD; however, the timings for the test were variable, 43.1% would do it in the first trimester and if positive in the third trimester ([Fig. 1C]). In a euthyroid pregnant woman previously treated with radioiodine or total thyroidectomy for GD, 42.7% of the respondents would never measure TRAb ([Fig. 1C]). In a pregnant woman with GD treated with ATDs, 47/103 (45.6%) of the respondents routinely monitored the fetus with an ultrasound scan. In comparison, 14.7% carried out fetal ultrasound monitoring if the mother had TRAb, and 3.9% did not carry out fetal ultrasound monitoring. However, 35.9% stated that this did not apply to their practice.

Treatment of Gestational Hyperthyroidism

For an 8-week pregnant woman with GTT, 61.2% of the respondents would follow-up without specific treatment; however, 28.2% would treat the woman with ATDs ([Fig. 1B]).

Treatment of GD during Lactation

For a lactating woman who has a relapsed GD, the majority (75.2%) of respondents recommended treatment with ATDs without stopping lactation. However, 22.8% of the respondents would treat the woman with ATDs and advise her to stop lactation. More respondents preferred MMI/CMZ over PTU (67.3% vs. 30.9%).

Screening and Management of Hypothyroidism in Pregnancy

The responses to the key issues addressed in the survey regarding management of hyperthyroidism during pregnancy are summarized in [Tables 2] and [3] and illustrated in [Fig. 2]. More specific questions are addressed in [Tables 4] [5] [6].

Table 2 The screening and management practices for hypothyroidism during pregnancy represented by six key questions

The six key survey questions and some of the predetermined answers	Respondents (%)
1. Screening for thyroid function in pregnancy
All	45.2
Targeted screening	39.3
2. Choice of treatment of overt hypothyroidism
Start on a full dose	40.0
Double dose first	28.9
3. Prepregnancy recommendation for hypothyroid women with TSH > 2.4 mIU/L
Check thyroid function when pregnant	48.4
Increase L-T4 by 30–50%	31.9
Increase L-T4 by 2 tablets/weekly	25.3
4. Tests to monitor L-T4 dose
TSH, FT4	49.5
TSH alone	21.8
TSH, FT4, FT3	11.9
5. Target thyroid function in treated hypothyroidism
TSH < 2.5 mIU/L in the first trimester and < 3.0 mIU/L thereafter	65.6
TSH and FT4 within the trimester-specific range	28.9
6. Levothyroxine treatment in pregnancy
Isolated hypothyroxinemia	14.6
TPO-Ab positive, TSH < 2.5 mIU/L	6.2
TPO-Ab positive, TSH 2.5–5 mIU/L	65.4
TPO-Ab negative, TSH 2.5–5 mIU/L	19.8

Abbreviations: FT4, free thyroxine; FT3, free triiodothyronine; L-T4, levothyroxine; TSH, thyroid-stimulating hormone, TPO-Ab, thyroid peroxidase antibodies.

Table 3 Management of hypothyroidism during pregnancy represented by three clinical case scenarios

Case scenarios and questions:	Responses (%)
Case 1. A 26-year-old woman has autoimmune hypothyroidism and is euthyroid (prepregnancy TSH 2.4 mUI/L) on L-thyroxine replacement. She expresses her wish to become pregnant soon. What advice would you give?
Increase the dose of L-T4 by 30–50% as soon as pregnancy is confirmed	31.9
Increase the dose of L-T4 by two tablets per week as soon as pregnancy is confirmed	25.3
Check thyroid function tests as soon as pregnancy is confirmed and increase the dose of L-T4 if necessary	48.4
Increase L-T4 dose before pregnancy to obtain a low normal TSH level	6.6
Case 2. A 26-year-old woman has autoimmune hypothyroidism and is euthyroid (TSH 1.8 mUI/L) on L-T4 replacement. She is infertile and should undergo an ovarian hyperstimulation before an IVF procedure. What advice would you give?
Increase the dose of L-T4 by 30–50% as soon as pregnancy is confirmed	24.4
Immediately increase the dose of L-T4 before the hyperstimulation to obtain a low normal TSH level	11.1
Check thyroid function tests after hyperstimulation and increase the dose of L-T4 if necessary	68.9
Case 3. A 24-year-old woman is 12 weeks pregnant and has just been diagnosed with overt primary hypothyroidism (TSH 86 mUI/L). What dose of L-T4 would you initially start?
Start on a small dose (e.g., 25–50 mcg daily)	10.0
Start on a full dose (e.g., 100–125 mcg daily)	40.0
Start on a dose based on pregnancy-adapted body weight	22.2
Start on a double dose (e.g., 200 mcg daily) for a few days, then a dose based on pregnancy-adapted body weight	28.9
Start on a dose based on pretreatment TSH level	5.6
Other	2.2

Abbreviations: IVF, in vitro fertilization; L-T4, L-thyroxine; TSH, thyroid-stimulating hormone.

Note: [Supplementary Material S1] of the supplementary material gives the full case scenarios.

Fig. 2 Some aspects of screening and management of hypothyroidism during pregnancy. (A) Risk factors used by respondents for screening pregnant women for thyroid dysfunction and stratification and (B) target thyroid function test results in hypothyroid pregnant women on L-thyroxine replacement.

Table 4 Starting dose of L-thyroxine in a 24-year-old pregnant woman diagnosed with overt hypothyroidism (TSH 86 mIU/L) at 12 weeks gestation (N = 90)

Starting dose of L-T4	Respondents [n (%)]
Start on a full dose (e.g., 100–125 mcg daily)	36 (40.0%)
Start for a few days on a double dose (e.g., 200 mg daily), then a dose based on pregnancy-adapted body weight	26 (28.9%)
Start on a dose based on pregnancy-adopted body weight	20 (22.2%)
Start on a small dose (e.g., 25–50 mcg daily)	9 (10.0%)
Start on a dose based on pretreatment TSH level	5 (5.6%)
Other (specify)	2 (2.2%)

Abbreviations: L-T4, L-thyroxine; TSH, thyroid-stimulating hormone.

Table 5 Responders' recommendations to a hypothyroid woman treated with L-T4 (TSH 2.4 mU/L) who is planning a pregnancy or in the process of undergoing ovarian hyperstimulation before the IVF procedure

Recommendations	Responders, n (%)		p-Value (chi-square)
	Planning pregnancy	Ovarian hyperstimulation
a1. Increase L-T4 dose by 30–50% as soon as pregnancy is confirmed	29 (31.9)	22 (24.4)	< 0.0004
a.2 Increase L-T4 dose by two tablets per week as soon as pregnancy is confirmed	23 (25.3)	_
b. Check thyroid function as soon as pregnancy is confirmed/hyperstimulation, and increase L-T4 dose if necessary	44 (48.4)	62 (68.9)
c. Increase the L-T4 dose before pregnancy/hyperstimulation to obtain a low normal TSH level	6 (6.6)	10 (11.1)

Abbreviations: IVF, in vitro fertilization; L-T4, L-thyroxine; TSH, thyroid-stimulating hormone.

Table 6 Different tests are used by responders to monitor the L-T4 dose and to screen thyroid dysfunction in pregnancy

Tests	Responders, n (%)
	Monitoring L-T4 dose (N = 103)	Screening thyroid dysfunction (N = 83)
TSH	84 (83.2)	83 (100.0)
Free T4	84 (83.2)	44 (53.0)
Free T3	37 (36.6)	14 (16.9)
Total T4	25 (24.8)	9 (10.8)
Total T3	13 (12.9)	3 (3.6)
TPO-Ab	−	29 (34.9)
Urinary Iodine	−	0 (0.0)
Other	4 (4.0)[a]	1 (1.2)[b]

Abbreviations: FT4, free thyroxine; FT3, free triiodothyronine; TPO-Ab, thyroid peroxidase antibodies; TRAb, thyrotropin receptor antibody; TSH, thyroid-stimulating hormone; TSI, thyroid-stimulating immunoglobulin; TT3, total triiodothyronine.

Note: The choices shown are not mutually exclusive. Seven combinations were reported, along with some additional isolated choices.

^a TSI, TRAb, improvement in symptoms, FT4, and TSH.

^b Antithyroglobulin antibodies.

Screening for Thyroid Dysfunction

While 45.2% of respondents or their institutions screened all pregnant women for thyroid dysfunction, 39.3% performed targeted screening of only the high-risk group, and 15.5% did not carry out systemic screening. Diverse risk factors to classify a “high-risk” group may be used in the targeted screening strategy ([Fig. 2A]). Respondents' timing of screening thyroid function in pregnancy was variable; 61.0% screened in a prepregnancy visit, 30.5% in the first antenatal visit, and 8.5% did not have specific timing. Likewise, tests used for screening were also highly inconsistent. Respondents were asked whether they would routinely repeat TFTs during the pregnancy if the initial screening was normal; of 82 respondents, 20.7% would routinely repeat the tests in later pregnancy, 37.8% would repeat them only in the presence of thyroid peroxidase antibodies (TPO-Ab) or specific features on thyroid ultrasonography, and 40.2% would not repeat.

Respondents used varied criteria to start L-thyroxine (L-T4) replacement following the screening, for instance, TSH above the trimester-specific reference range (by 54.3%), TSH above 2.5 mIU/L (33.3%), TSH above 5 mIU/L (22.2%), FT4 below the trimester-specific reference range (17.3%), and TSH above the population reference range (9.9%). There was also inconsistency in respondents' approach to the outcomes of screening thyroid function in pregnancy. For example, 14.6% of the respondents would treat isolated hypothyroxinemia, while 69.5% would follow-up without treatment. Furthermore, respondents' definition of isolated hypothyroxinemia was not consistent: 57.1% defined it as normal TSH with FT4/total thyroxine (TT4) below the trimester-specific reference range, 28.7% as normal TSH with FT4/TT4 below the population reference range, 3.9% as normal TSH with FT4/TT4 below the 2.5th centile, and 10.4% as normal TSH with FT4/TT4 below the fifth centile.

Treatment of Hypothyroidism

Respondents were asked what dose of L-T4 they would start for a 24-year-old woman who is 12 weeks pregnant and has just been diagnosed with overt primary hypothyroidism. Respondents suggested variable regimes to initiate L-T4 replacement for the woman, although most recommended starting on a full replacement dose, empirically (100–125 mcg, 40.0%) or based on pregnancy-adopted body weight ([Table 4]). However, 10.0% of respondents recommended a small starting dose of L-T4 (25–50 mcg/daily). Many respondents perceived that overt hypothyroidism diagnosed in the late first trimester, despite adequate L-T4 replacement, would result in subtle (50.0%) or clinically significant (26.7%) neuropsychological impairment of the offspring. However, 20.0% of respondents felt that there would be no consequences to the offspring. Although a majority of respondents (84.1%) would not endorse abortion in such a situation, 12.5% would recommend abortion.

Monitoring of Hypothyroidism

Physicians' recommendations for adjusting the dose of L-T4 in a hypothyroid woman who is planning pregnancy were inconsistent ([Table 5]). Although many (57.1%) of the respondents would recommend the woman increase the dose of L-T4 as soon as pregnancy is confirmed, 48.4% would check TFTs before adjusting the dose. Likewise, respondents' recommendations to a hypothyroid woman who is in the process of undergoing ovarian hyperstimulation before in vitro fertilization were also variable ([Table 5]). Respondents also used various combinations of tests to monitor the dose of L-T4 in pregnancy ([Table 6]). Likewise, the target TFT results that respondents aim to achieve with L-T4 in pregnancy were also inconsistent. However, two-thirds of respondents (65.6%) aim to keep TSH < 2.5 mIU/L during the first trimester and < 3 mIU/L beyond it ([Fig. 2B]).

Discussion

This present study describes self-reported clinical practices relating to the management of hyperthyroidism and treatment and screening of maternal hypothyroidism in pregnancy by physicians from the MENA region. Our previous thyroid survey studies included questions on managing thyroid disorders during pregnancy.[26] [27] Only physicians who declared they routinely manage thyroid disorders in pregnant women were included in the present study. The primary target population was those who identified themselves as endocrinologists. Internists with a special interest in endocrinology are a loosely defined group in the MENA region. Again, the main inclusion criterion was the self-declaration that the respondents treated thyroid disease during pregnancy. Subgroup analysis was not possible.

The present study survey has revealed a wide blend of variations in the clinical practice relating to the management of maternal hyperthyroidism and hypothyroidism during pregnancy in the MENA region, despite the existence of good clinical practice guidelines for many years.[12] [13] [14] [15] [16] [17] [18] [19] [20] Some of these predate our survey studies; the survey showed inconsistencies in several aspects of managing women with GD planning pregnancy. In our survey, almost half of the respondents adopted the use of PTU in the first trimester and switched to MMI/CMZ after the first trimester despite the risk of liver failure with PTU. In addition, respondents to this survey used various combinations of tests for monitoring the dose of ATDs during pregnancy.

There was a high degree of inconsistency between the guidelines and some aspects of the respondents' clinical practice, such as the target thyroid function for pregnant hypothyroid women on L-T4 treatment and targeted screening for thyroid dysfunction. The role of universal screening for thyroid dysfunction in pregnant women has been hotly debated over the years[5] [6]; the American Thyroid Association (ATA) and some members of the Endocrine Society (ES) have recommended targeted case-finding, although some of the latter society members recommended universal screening in pregnancy,[2] [3] although some studies have shown that the targeted case-finding approach misses a proportion of women with thyroid dysfunction.[5] [6] In the present survey, slightly more MENA physicians chose universal rather than targeted screening at variance with the other surveys. Generally, there was a reasonable degree of consistency between the clinical practices of MENA physicians and guidelines, such as the initiation of antithyroid treatment in the first trimester, tests to monitor drug therapy, and thyroid function for a pregnant hyperthyroid woman. Maternal hyperthyroidism diagnosed during pregnancy should be corrected because hyperthyroidism has detrimental effects on both mother and fetal health.[7] [28] Based on current data, MMI and PTU have equal efficacy in treating pregnant women, and both could cause differential teratogenic effects.[29] However, PTU hepatotoxicity that may occur anytime during treatment has caused concern regarding its use as the first-line drug for the treatment of hyperthyroidism, limiting its use to the first trimester of pregnancy.[30] The ES guidelines state that MMI may be administered if the patient has an adverse response or cannot tolerate PTU or if this drug is not available. In addition, recommendations for changing PTU to MMI after the first trimester have caused concerns for some thyroidologists; therefore, the ES recommends that practitioners use their clinical judgment in switching patients from one drug to another.[12] [14]

In the present survey, 96% of respondents begin treatment of hyperthyroid pregnant women with PTU, and almost half (48%) will switch to MMI after the first trimester. For preconception counseling of a Graves' patient, 80% of the MENA clinicians advised ATDs (58% PTU and 22% MMI), and only 12% will ablate the thyroid (radiation or surgery) before allowing the patient to consider pregnancy; this is in agreement with ATA, which recommends the use of MMI/CMZ and change to PTU once the pregnancy is confirmed.[13] It is noteworthy that following treatment of hyperthyroidism with ATDs or surgery, serum TRAb will decrease to normal values in most patients. TRAb titers will increase during the first year after radioiodine therapy, followed by a subsequent gradual fall.[31] [32] However, even 4 to 6 years after radioiodine therapy, many patients are still TRAb positive, an issue which is of utmost importance, as a high titer of TRAb is a risk factor for fetal and neonatal hyperthyroidism.[33] Over one-third of the clinicians monitor ATD treatment by TSH and FT4 levels, and another 29% with TSH, FT4, and free triiodothyronine (FT3). Determination of serum total triiodothyronine (TT3) levels used by 9% of physicians is not recommended as it has been reported that normalization of maternal TT3 leads to elevated serum TSH in infants; in addition, two-thirds of respondents target achieving low TSH and FT4 (or TT4) in the normal range during such therapy. This is also considered good practice since guidelines recommend TSH and FT4 assessment as the main tests for such monitoring and advise aiming for FT4 within the upper end of the normal range or just above the upper limit of normal while utilizing the smallest possible dose of ATDs during pregnancy.[13] [14] It was disappointing and of concern that 26% of MENA respondents target the normal range for serum TSH and FT4 concentrations. This approach could increase the chance of fetal goiter and hypothyroidism.[34] Inconsistency in test combinations used by the respondents for monitoring ATD doses during pregnancy may, to some extent, be due to the availability of tests in different settings. On the other hand, many physicians use FT4 alone or in combination with other tests, perhaps due to the controversy over the accuracy of FT4 assays during pregnancy.[35] In GTT, observation was selected by 60% of respondents, while too many (28.2%) preferred treatment with antithyroid medications, reflecting a lack of understanding of the differences.

Routine measurement of TRAb in a hyperthyroid pregnant woman under ATD therapy is recommended by major endocrine organizations. The prevalence of fetal and neonatal hyperthyroidism ranges between 1 and 5% in women with a current or past history of GD, and lack of treatment will increase morbidity and mortality in the fetus and infants.[36] Serum TRAb titers increase following radioiodine therapy and may remain high for many years thereafter. Measuring TRAb by 24 to 28 weeks of gestation is recommended to detect at-risk pregnancies. A titer over three times that of upper normal limit warrants close follow-up of the fetus, and joint management with fetal medicine is necessary. It is concerning that nearly half (43%) of clinicians surveyed indicated that they do not routinely check TRAb. Although there is not enough evidence to recommend or advise against the use of thyroid ultrasound in differentiating the cause of hyperthyroidism in pregnancy, it has been recommended to use an ultrasound scan for monitoring the fetus in women with GD under ATD therapy; ultrasonography should be performed in those with uncontrolled hyperthyroidism or with high TRAb titers, both of which can compromise fetal well-being. Almost 40% of MENA respondents did not adhere to this recommendation.

In this survey, for the management of hyperthyroidism in a postpartum lactating woman, 75% of the respondents chose antithyroid therapy and continuing lactation; however, 31% of them preferred treatment with PTU. The ATA and ES both recommended treating lactating hyperthyroid women with MMI because treatment with PTU may cause liver damage.[30] It has been shown that MMI therapy up to 20 mg daily does not cause any alterations in thyroid function and mental or physical development of children aged 48 to 86 months breastfed by lactating hyperthyroid mothers.[37] Checking the thyroid functions of breastfeeding infants and mothers taking ATDs is recommended. Prescribing the treatment in divided doses immediately after breastfeeding was also suggested. It is unfortunate, however, that 23% of the surveyed physicians recommended stopping lactation while treating the lactating mother with antithyroid medications. Compared to the European surveys,[21] the results of this study did not differ greatly in various aspects of management of hyperthyroidism during pregnancy except for TRAb monitoring noted above in addition to slightly more checking of FT3 in combination with TSH and FT4 for monitoring the dose of ATDs by the European physicians.

Regarding the management of hypothyroidism, there was a mixed pattern of concordance and variance between the guidelines and some aspects of the respondents' clinical practice, such as the target thyroid function for pregnant hypothyroid women on L-T4 treatment and targeted screening of pregnant women for hypothyroidism.[38] [39] Similar to other surveys from Europe, Asia, and Latin America,[22] [23] [24] the current study has several uncertainties surrounding screening thyroid function in pregnancy. Some use targeted high-risk pregnancy screening, while others use universal screening. In the present survey, 39% of the respondents or their institutions use a targeted strategy recommended by the ATA and some members of the ES. Unfortunately, 15.5% of respondents do not carry out systematic screening. In the same token, 61% of the respondents reported that they screened thyroid function during prepregnancy visits, but 30.5% would do so in the first antenatal visit. Identifying and treating hypothyroidism in the first antenatal visit may arguably be too late to prevent the associated adverse effects; however, implementing systemic screening of thyroid function in all women contemplating pregnancy would be an enormous challenge, especially for developing countries of the MENA region.

Furthermore, it has been suggested that if screening is limited to the first trimester, over 40% of pregnant women with hypothyroidism could be missed,[40] and 58% of our respondents agreed that TFTs should be repeated in later stages of pregnancy if the initial screening was normal, 21% routinely, and 37.8% in the presence of thyroid antibodies. Maternal hypothyroidism diagnosed in pregnancy should be corrected as promptly as possible because maternal thyroid hormones play an important role in early fetal neurological development.[41] [42] In this survey, 40% of respondents initiated a full replacement dose of L-T4 for pregnant women newly diagnosed with overt hypothyroidism. However, a small minority (10%) still started on a small dose of L-T4. Despite the absence of evidence to support such a practice, unfortunately, 12.5% of respondents may discuss abortion in overt hypothyroid pregnant patients in the first trimester. Indeed, the intelligence quotients (IQs) of the children whose mothers had been hypothyroid during early pregnancy were reported to be normal and similar to those of their siblings who were not exposed to maternal hypothyroidism in utero.[41] On the other hand, treatment of maternal hypothyroidism has not improved IQ or impaired cognitive function in another study.[42]

The dose of L-T4 needs to be increased from very early pregnancy in most women.[43] About a quarter of women on L-T4 replacement have biochemical evidence of underreplacement at their first antenatal visit, which may be prevented by optimizing the L-T4 dose before pregnancy.[44] In the present study, 32% of respondents would advise the woman to increase the dose of L-T4 once pregnancy is confirmed, according to previous recommendations and evidence.[13] [14] [15] [16] However, the survey has highlighted inconsistency in clinicians' approach to optimizing L-T4 replacement in hypothyroid women planning pregnancy, with almost half of the respondents choosing to check thyroid function as soon as pregnancy is confirmed. Regarding the target thyroid function for pregnant hypothyroid women, most respondents (95%) aimed to achieve TSH and FT4 within the trimester-specific reference range or TSH < 2.5 mIU/L in the first trimester and < 3 mIU/L later on as recommended by the guidelines.[13] [14] An increased risk of miscarriage in TPO-Ab-negative women with TSH 2.5 to 5 mIU/L has been reported, but there is no randomized controlled trial evidence to show the benefit of L-T4 in these women.[45] In contrast, there is some evidence that thyroid autoimmunity is associated with adverse obstetric outcomes. A randomized controlled trial has shown that L-T4 treatment may reduce miscarriage and preterm delivery in euthyroid TPO-Ab-positive pregnant women.[46] In another prospective trial, L-T4 treatment reduced the risk of preterm delivery in euthyroid TPO-Ab-positive women undergoing assisted reproduction technologies.[47] In this survey, only a very low minority of respondents (15%) would treat euthyroid pregnant women with isolated TPO-Ab positivity. This practice agrees with guidelines, which do not recommend L-T4 for these pregnant women, underlining the need for further studies.

Although maternal hypothyroxinemia is associated with impaired neuropsychological development of offspring, there is no consensus on the definition and implications of isolated maternal hypothyroxinemia.[48] Eighty-five percent of the MENA respondents do not treat maternal hypothyroxinemia in pregnancy. This is the highest rate compared to the other three surveys from Europe, Latin America, and Asia.[21] [22] [23] [24] [25]

The present study provides a snapshot of current practices in managing thyroid disorders during pregnancy in the MENA region during the study period. It complements the previous surveys from other parts of the world.[21] [22] [23] [24] [25] It is somewhat surprising that up to 40% of respondents would not check anti-TSH-R antibodies in pregnant women treated with thyroidectomy or radioactive iodine ablation ([Fig. 1C]); similarly, more than 15% of respondents would not give full-dose levothyroxine to a first-trimester pregnant woman with overt hypothyroidism ([Table 4]). Such gaps in the basic understanding of thyroid disease in pregnancy suggest that a good number of respondents were not up to date on this condition and may not be at the forefront of clinical practice regarding thyroid disease in pregnancy, calling for more intensive education.

A few limitations are noteworthy. First, this was a self-reported survey rather than an audit of clinical practice outcomes. Second, most of the respondents to the survey are endocrinologists, and their approach to managing thyroid disorders in pregnancy may differ from that of other health care professionals, including obstetricians. However, some of them do manage these patients in multidisciplinary settings. Third, a selection bias could have influenced the results, with more keen physicians responding to the request using convenience sampling methods. Fourth, some respondents had a smaller patient population, and they should have been analyzed separately. Finally, the inhomogeneous distribution with overrepresentation of some countries and the variations in resources between countries could limit the generalizability of the survey's results.

Conclusion

This is the first dedicated survey on managing thyroid disorders in pregnant women in the MENA region. It showed that management is far from uniform in the region. Clinical practices regarding the screening for and managing thyroid disorders in pregnant women vary widely. Similarities and differences with practices in other regions were observed. This disparity in clinical practice could reflect the limited evidence in this field and the need for further studies to promote evidence-based clinical practice and reduce variability in care.

The survey also highlights the need for focused training and quality assurance to achieve more consistent care for pregnant women with thyroid disease in the MENA region. To reach optimal impact in the medical community, guidelines for treating thyroid disorders in pregnancy could be written by and for endocrinologists, obstetricians, internists, and family practitioners. Management of thyroid disorders during pregnancy should be adequately covered in continuous professional development events of all related specialties.

Conflict of Interest

None declared.

Acknowledgment

We are grateful to all respondents who shared their expertise and opinions by participating in the survey.

Authors' Contributions

S.A.B. adapted the questionnaire and managed the survey process. All authors examined the data and contributed to revising and finalizing the manuscript. All authors approved the final manuscript version.

Compliance with Ethical Standards

The Sheikh Khalifa Medical City (Abu Dhabi, UAE) IRB approved the study. Before accessing the survey questions, all participants provided electronic informed consent.

Data Availability

Deidentified raw data are available at a reasonable request from the corresponding author.

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Publication History

Article published online:
11 March 2025