Seasons but not ethnicity influence urinary iodine concentrations in Belgian adults.

BACKGROUND: Mild iodine deficiency (MID) is endemic in Belgium. Previous surveys, which assessed iodine nutrition in Belgium, focused on children. The iodine status of adults and the influence of ethnicity or seasonality on urinary iodine concentrations (UIC) have not been investigated. Since the nutritional profile of children differs from that of adults, we may anticipate similar differences in iodine status. Seasonal fluctuations in UIC have also been reported from other MID regions. AIM OF THE STUDY: We aimed at assessing iodine status and its association with ethnicity and seasonality in adults. METHODS: A stratified random sample of 401 healthy subjects aged between 40 and 60 years, of Belgian, Moroccan, Turkish and Congolese descent residing in Brussels was obtained. Iodine status and thyroid function were determined. RESULTS: Median UIC was 68 µg/L. The frequency of UIC below 100 µg/L was 73.3%, of which 41.9% fell between 50 and 99 µg/L, and 29.8% between 49 and 20 µg/L. There was no difference in UIC and thyroid function between subjects of different ethnic origins. The frequency of UIC below 50 µg/L was higher in the fall-winter compared to spring-summer periods (P = 0.004). Serum FT3 concentrations, but not FT4 and TSH, were significantly greater in winter than in summer. CONCLUSION: Seasonal fluctuations in UIC suggest that the risk of iodine deficiency among adults living in Brussels is higher in fall-winter than in spring-summer. The prevalence of MID in Brussels is high among adults but ethnicity does not appear to influence iodine status.

Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation.

The human thyroid gland acquires a differentiation program as early as weeks 3-4 of embryonic development. The onset of functional differentiation, which manifests by the appearance of colloid in thyroid follicles, takes place during gestation weeks 10-11. By 12-13 weeks functional differentiation is accomplished and the thyroid is capable of producing thyroid hormones although at a low level. During maturation, thyroid hormones yield increases and physiological mechanisms of thyroid hormone synthesis regulation are established. In the present work we traced the process of thyroid functional differentiation and maturation in the course of human development by performing transcriptomic analysis of human thyroids covering the period of gestation weeks 7-11 and comparing it to adult human thyroid. We obtained specific transcriptomic signatures of embryonic and adult human thyroids by comparing them to non-thyroid tissues from human embryos and adults. We defined a non-TSH (thyroid stimulating hormone) dependent transition from differentiation to maturation of thyroid. The study also sought to shed light on possible factors that could replace TSH, which is absent in this window of gestational age, to trigger transition to the emergence of thyroid function. We propose a list of possible genes that may also be involved in abnormalities in thyroid differentiation and/or maturation, hence leading to congenital hypothyroidism. To our knowledge, this study represent the first transcriptomic analysis of human embryonic thyroid and its comparison to adult thyroid.

Near total thyroidectomy is an optimal treatment for graves' disease.

Surgical management of Graves' disease is still debated. We report our current experience with thyroidectomy for Graves' disease at a tertiary center. A retrospective database of 132 patients who underwent surgery for Graves' disease from January 1985 to December 2008 was collected. During that period, 16 patients underwent subtotal thyroidectomy and 116 patients underwent near total thyroidectomy. Eighty-seven patients (66%) underwent surgery for recurrent disease after medical therapy. Forty-five patients (34%) had surgery as a primary treatment, the indications were large goiter size in 22 (17%), patient preference in 19 (14%), and associated cold nodule in 3 (2%). The incidence of cancer was 4.4%. Permanent hypoparathyroidism was observed in one patient who underwent a second surgery for recurrence. Unilateral transitory vocal cord palsy was observed in nine patients (7%), bilateral transitory vocal cord palsy was observed in one patient, and no definitive vocal cord palsy was observed. Two patients (1.5%) experienced post-operative hemorrhagia requiring surgical revision. Near total thyroidectomy for Graves' disease provides an immediate and definitive treatment with a low complication rate. Near total thyroidectomy offers an appropriate treatment for coexisting malignancy. This procedure can be safely recommended as a primary treatment, in experienced hands.

The role of thyroid autoimmunity in fertility and pregnancy.

The thyroid gland and gonadal axes interact continuously before and during pregnancy. Hypothyroidism influences ovarian function by decreasing levels of sex-hormone-binding globulin and increasing the secretion of prolactin. In women of reproductive age, hypothyroidism can be reversed by thyroxine therapy to improve fertility and avoid the need for use of assisted reproduction technologies. For infertile women, preparation for medically assisted pregnancy comprises controlled ovarian hyperstimulation that substantially increase circulating estrogen concentrations, which in turn can severely impair thyroid function. In women without thyroid autoimmunity these changes are transient, but in those with thyroid autoimmunity estrogen stimulation might lead to abnormal thyroid function throughout the remaining pregnancy period. Prevalence of thyroid autoimmunity is significantly higher among infertile women than among fertile women, especially among those whose infertility is caused by endometriosis or ovarian dysfunction. Presence of thyroid autoimmunity does not interfere with normal embryo implantation, but the risk of early miscarriage is substantially raised. Subclinical and overt forms of hypothyroidism are associated with increased risk of pregnancy-related morbidity, for which thyroxine therapy can be beneficial. Systematic screening for thyroid disorders in pregnant women remains controversial but might be advantageous in women at high risk, particularly infertile women.

Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease.

BACKGROUND: Since the histological expression of galectins is increased in thyroid carcinoma, determination of their serum levels may provide useful preoperative information. The goal of this study was to determine if a difference in galectin serum levels could be detected between benign and malignant nodular thyroid diseases. DESIGN: Using validated ELISAs, the concentrations of several galectins were prospectively measured in serum samples from 30 healthy individuals and preoperatively in 90 patients with thyroid disease. Seventy-one patients had multiple thyroid nodules (MTN), 13 patients had a single thyroid nodule (STN), and 6 patients had Graves' disease. Nine of 71 patients with MTN had fine-needle aspiration biopsy (FNAB) of their nodules and in 7 patients a "benign" diagnosis was made, in 0 patient a "malignant" diagnosis was made, and in 2 patients a "suspicious" diagnosis was made. Six of 13 patients with STN had FNAB of their nodules and in 2 patients a "benign" diagnosis was made, in 3 patients a "malignant" diagnosis was made, and in 1 patient a "suspicious" diagnosis was made. RESULTS: Thyroid disease was associated with higher levels of galectins-1 and -3 compared to normal subjects. Using a threshold value of 3.2 ng/mL as a cut-off point, the measurement of serum galectin-3 separated micro- and macropapillary thyroid carcinoma (PAP_CA) from patients with nonmalignant thyroid disease with 74% specificity, 73% sensitivity, 57% positive predictive value, and 85% negative predictive value. Elevated serum galectin-3 concentrations (>3.2 ng/mL) detected 87% of macropapillary thyroid carcinomas and 67% of micropapillary thyroid carcinomas. CONCLUSIONS: Serum levels of galectins-1 and -3 are relatively high in patients with thyroid malignancy but there is considerable overlap in serum galectin-3 concentrations between those with benign and malignant nodular thyroid disease and, to a lesser extent, between those with and without nodular thyroid disease.

Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline.

OBJECTIVE: The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum. PARTICIPANTS: The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration. EVIDENCE: Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system. CONSENSUS PROCESS: Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society's CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines. CONCLUSIONS: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported.

Clinical and biological consequences of iodine deficiency during pregnancy.

The main change in thyroid function associated with the pregnant state is the requirement of an increased production of thyroid hormone that depends directly upon the adequate availability of dietary iodine and integrity of the glandular machinery. In healthy pregnant women, physiological adaptation takes place when the iodine intake is adequate, while this is replaced by pathological alterations when there is a deficient iodine intake. Pregnancy acts typically, therefore, as a revelator of underlying iodine restriction. Iodine deficiency has important repercussions for both the mother and the fetus, leading to hypothyroxinemia, sustained glandular stimulation and finally goitrogenesis. Furthermore, because severe iodine deficiency may be associated with an impairment in the psychoneurointellectual outcome in the progeny, because both mother and offspring are exposed to iodine deficiency during gestation (and the postnatal period), and because iodine deficiency is still prevalent today in several large regions of the world, iodine supplements should be given systematically to pregnant and breastfeeding mothers. Particular attention is required to ensure that pregnant women receive an adequate iodine supply, in order to reach the ideal recommended nutrient intake of 250 microg iodine/day.

Thyroid function inside and outside of pregnancy: what do we know and what don't we know?

A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports on the session that examined the prevalence of thyroid dysfunction in reproductive-age women and the factors associated with abnormal function. For this session the following papers were presented: "Thyroidal Economy in the Pregnant State: An Overview," "The Prevalence of Thyroid Dysfunction in Reproductive-Age Women- United States," and "Risk Factors for Thyroid Disease: Autoimmunity and Other Conditions." These presentations were formally discussed by invited respondents and by others in attendance. Salient points from this session about which there was agreement include the following: physiologic changes associated with pregnancy require an increased availability of thyroid hormones by 40% to 100% in order to meet the needs of mother and fetus during pregnancy. In the first trimester of gestation the fetus is wholly dependent on thyroxine from the mother for normal neurologic development. For the maternal thyroid gland to meet the demands of pregnancy it must be present, disease-free, and capable of responding with adequate stores of iodine. Thyroid autoimmunity is common and may contribute to miscarriages, as well as to hypothyroidism. With sufficient iodine nutrition, autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism. As of 1994, iodine nutrition in the United States appeared to be adequate, but its continued monitoring is essential.

Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated with Antithyroid Drug Therapy: How Significant Is the Clinical Problem?

BACKGROUND: The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis. SUMMARY: The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis. CONCLUSIONS: ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

Assisted reproduction and thyroid autoimmunity: an unfortunate combination?

The association between positive thyroid antibodies and an increased miscarriage rate in pregnancies after assisted reproduction technology (ART) remains controversial. We wanted to clarify this issue by performing a prospective cohort study in 234 women by systematically screening for thyroid peroxidase antibodies (TPO-Ab), serum TSH, and free T(4)(FT(4)) before the first ART cycle. Women with overt thyroid dysfunction were excluded. Fourteen percent of the cohort had positive TPO-Ab. Baseline characteristics [age, 33 +/- 5 yr; TSH, 1.6 (0.02-4.1) mU/liter; and FT(4), 12.2 (9.1-18) ng/liter] were comparable to those of the 86% of women without antibodies [age, 32 +/- 5 yr; TSH, 1.3 (0.05-3.6) mU/liter; and FT(4), 11.7 (9.5-16.5) ng/liter]. In the antibody-positive group, the pregnancy rate was 53% vs. 43% in the antibody-negative group, with an odds ratio of 0.67 [95% confidence interval (CI) (0.32-1.41); P = not significant]; however within the group that was pregnant, the miscarriage rate was 53% and 23%, respectively, with an odds ratio of 3.77 [95% CI (1.29-11.05); P = 0.016]. The age of the women was an independent risk factor for miscarriage, odds ratio 1.08 [95% CI (1.03-1.15); P = 0.005]. We conclude that women with positive TPO-Ab before the first ART cycle have a significantly increased risk for miscarriage.

Impact of ovarian hyperstimulation on thyroid function in women with and without thyroid autoimmunity.

Pregnancy is accompanied by changes in thyroid function, but limited data are available on these changes in the very first weeks of pregnancy. Yet, T(4) plays a major role in implantation and early fetal development. We sought to determine thyroid function during this period and during the first trimester, in pregnancies achieved by assisted reproductive technology. Furthermore, the thyroid hormone profile was compared between euthyroid women with (TAI+) and without (TAI-) thyroid autoimmunity. We prospectively analyzed data from 35 women who received ovarian hyperstimulation (OH) and presented clinical pregnancies. The mean age of the women was 32 +/- 5 yr. Thyroid function tests [serum TSH and free T(4) (FT(4))] and thyroid antibody status were determined before OH (baseline values) and every 20 d after ovulation induction during the first trimester of pregnancy. Serum TSH and FT(4) increased significantly at d 20, compared with baseline values (3.3 +/- 2.4 vs. 1.8 +/- 0.9 mU/liter; P < 0.0001 and 13.2 +/- 1.7 vs. 12.4 +/- 1.9 ng/liter; P = 0.005). During the first trimester of pregnancy, there was a significant change over time for TSH and FT(4) (P < 0.001 and P = 0.005, respectively). Nine women (27%) were TAI+. The TSH curve among these TAI+ women was significantly higher compared with TAI- women (P = 0.010). The opposite was observed for the FT(4) curve (P = 0.020). In conclusion, the present study showed a significant increase of serum TSH and FT(4) levels after OH in the very first period of pregnancy compared with pre-OH levels and a significant impact of TAI on the thyroid hormone profile during the first trimester. This provides evidence for an altered thyroid function in euthyroid TAI+ patients.

The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status.

The main change in thyroid function associated with the pregnant state is the requirement of an increased production of thyroid hormone that depends directly upon the adequate availability of dietary iodine and integrity of the glandular machinery. Physiologic adaptation takes place when the iodine intake is adequate, while this is replaced by pathologic alterations when there is a deficient iodine intake. Pregnancy acts typically, therefore, as a revelator of underlying iodine restriction. Iodine deficiency (ID) has important repercussions for both the mother and the fetus, leading to sustained glandular stimulation, hypothyroxinemia and goitrogenesis. Furthermore, because severe ID may be associated with an impairment in the psycho-neuro-intellectual outcome in the progeny-because both mother and offspring are exposed to ID during gestation (and the postnatal period), and because ID is still prevalent today in several European countries-it has been proposed already in the early 1990s that iodine supplements be given systematically to pregnant and breast-feeding women. Particular attention is required to ensure that pregnant women receive an adequate iodine supply, by administering multivitamin tablets containing iodine supplements, in order to achieve the ideal recommended dietary allowance of 200-250 microg iodine/day.

Thyroid autoimmunity and the risk of miscarriage.

Approximately one-third of all pregnancies end in miscarriage. The etiology of recurrent abortion remains unknown in approximately 50% of all women. In the early 1990s it was discovered that unselected euthyroid women who present with thyroid antibodies (thyroid peroxidase and thyroglobulin) in the first trimester of pregnancy have a two-four-fold increase in their miscarriage rates. The majority of studies investigating women with recurrent abortion have also found a significant increase in thyroid antibody positivity compared with controls. Although the etiology of miscarriage in thyroid antibody women remains unknown, recent data have revealed a potential direct effect of thyroglobulin antibodies on pregnancy loss in a murine model. Uncontrolled studies assessing the effect of levothyroxine on decreasing the miscarriage rate in euthyroid antibody positive women, have demonstrated a decreased miscarriage rate.

Management of hypo- and hyperthyroidism during pregnancy.

Pregnancy has profound effects on the regulation of thyroid function, and on thyroidal functional disorders, that need to be recognized, carefully assessed and correctly managed. Relative hypothyroxinemia and goitrogenesis may occur in healthy women who reside in areas with restricted iodine intake, strongly suggesting that pregnancy constitutes a stimulatory challenge for the thyroid. Overt thyroid dysfunction occurs in 1-2% of pregnant women, but mild forms of dysfunction (both hyper- and hypothyroidism) are probably more prevalent and frequently remain unrecognized. Alterations of maternal thyroid function have important implications for fetal and neonatal development. In recent years, particular attention has been drawn to the potential risks for the developing fetus due to maternal hypothyroxinemia during early gestation. Concerning hyperthyroidism, the two main causes of thyrotoxicosis in the pregnant state are Graves' disease and gestational transient thyrotoxicosis (GTT). The natural history of Graves' disease is altered during pregnancy, with a tendency for exacerbation during the first trimester, and amelioration during the second and third trimesters. The natural history of the disorder must be considered when treating patients, since antithyroid drugs cross the placenta and can directly affect fetal thyroid function. Algorithms to routinely screen pregnant women for thyroid dysfunction have been proposed in recent years, but these have not yet been implemented systematically, nor have they been the subject of cost-effectiveness analyses.

Acute increase in goiter size during a normal pregnancy: an exceptional case report.

This case report illustrates an exceptional clinical situation in which a pregnant woman abruptly presented, at 5 months' gestation, with major swelling of the thyroid gland that led to respiratory symptoms and emergency hospitalization. The medical condition was shown to be caused by acute intrathyroidal hemorrhage within a preexisting-albeit until then unnoticed-multinodular goiter. The cause of the intrathyroidal hemorrhage could not be firmly delineated, although it remains possible that an unusual extraneous cause constituted a "trauma" that triggered this rare medical condition.

Thyroid dysfunction and autoimmunity in infertile women.

A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup.

High prevalence of thyroid disorders in pregnant women in a mildly iodine-deficient country: a population-based study.

CONTEXT: Many countries in Europe remain mildly iodine deficient but relatively few country-level data exist on mild iodine deficiency (MID) and its impact on thyroid function in pregnant women. OBJECTIVE: To determine the prevalence of thyroid disorders in pregnant women in Belgium and to assess the association between iodine status and serum thyroglobulin (Tg). DESIGN AND SETTING: We conducted a national survey of pregnant women in 55 obstetric clinics. Urinary iodine concentration corrected for creatinine (UIC/Cr) and thyroid function were measured. RESULTS: The frequency of elevated serum TSH was 7.2%, indicating either subclinical hypothyroidism (6.8%) or overt hypothyroidism (0.4%). Among those women, 13.8% were thyroid peroxidase antibodies (TPO-Ab) positive. The frequency of low serum TSH was 4.1%, indicating either subclinical hyperthyroidism (3.6%) or overt hyperthyroidism (0.5%). In the entire population, the frequency of positive TPO-Ab and/or Tg antibodies positive women was 4%. Globally, the prevalence of thyroid disorders (abnormally high or low TSH) or thyroid autoimmunity features was 15.3% and 18.6% in first-trimester pregnant women. Women with an adequate iodine status (UIC/Cr = 150-249 µg/g) had a significantly lower median Tg concentration compared to moderately iodine deficient women (UIC/Cr ≤ 49 µg/g), 19 µg/L and 25 µg/L, respectively. CONCLUSIONS: The prevalence of thyroid disorders was high, affecting one in six pregnant women in Belgium. Therefore, the iodine status in women needs to be improved and screening for thyroid disease should be performed early in pregnancy. In addition, our data suggest that a median Tg of <20 µg/L may indicate iodine sufficiency in pregnant women.

The propylthiouracil dilemma.

PURPOSE OF REVIEW: To bring to the attention of healthcare professionals the additional information on propylthiouracil (PTU)-related hepatotoxicity, based on a reanalysis of medical files reported to the Food and Drug Administration (1982-2008) for acute liver failure in PTU-treated hyperthyroid patients, and propose recommendations for the clinical use of PTU. Thirteen files of PTU-related severe liver adverse effects were analyzed for the pediatric population, seventeen for nonpregnant adults and two for pregnant women. RECENT FINDINGS: The recent findings showed that the daily PTU dose administered was high in the children, with a mean of 300 mg/day for an average 10-year-old individual. With regard to treatment duration, PTU administration lasted for at least 4 months in 75% of pediatric cases. Similarly, in a majority of adult cases (64%), PTU-induced liver injury occurred after a relatively long treatment period (4 months to >1 year). SUMMARY: PTU should not be used in children, in whom methimazole (MMI) represents the logical alternative. In adults, PTU should be restricted to those rare patients with Graves' disease for whom no better alternative can be offered and in patients with thyroid storm. For the special circumstance of pregnancy, PTU is the preferred choice during early gestation; switching back to MMI during later gestational stages remains a matter of clinical judgment. It is unknown whether liver function tests monitoring is worthwhile to prevent life-threatening, PTU-related hepatotoxicity.