Utility of Colour Flow Doppler Ultrasonography to Differentiate Gestational Transient Thyrotoxicosis and Graves Disease in Pregnancy.

Introduction: Accurate diagnosis of the etiology of thyrotoxicosis in pregnancy is important to guide appropriate treatment. The role of thyroid blood flow velocities by color Doppler to differentiate between Graves' disease (GD) in pregnancy and gestational transient thyrotoxicosis (GTT) is not well explored. This study evaluated inferior thyroid artery (ITA)-peak systolic velocity (PSV) as a marker for differential diagnosis of thyrotoxicosis in pregnancy. Methods: Fifty-six pregnant patients with thyrotoxicosis (30 with GTT and 26 with GD) along with 30 age-matched healthy euthyroid pregnant subjects were enrolled. Thyroid ultrasound examinations and color Doppler was performed by an ultrasound scanner. The studies of the right and left ITAs were performed with Doppler, and the PSV and End diastolic velocity (EDV) values were obtained from the right and left ITA. Results: The mean total T4 value in GD and GTT were almost similar (25.04 ± 2.43 vs 23.25 ± 2.81, P value = 0.14). Beta HCG levels were significantly higher in cases of GTT as compared to GD (152946 ± 26694 vs 120608 ± 21244 mIU/ml, P < 0.0001). The ITA-PSV and EDV in patients with GTT were significantly lower than those of pregnant patients with GD (right: 22.5 ± 6.8 and 8.3 ± 2.3; left: 22.97 ± 6.3 and 8.13 ± 2.01; P < 0.001). receiver-operating-characteristic (ROC) curve demonstrated an optimal cutoff value of mean right ITA-PSV of 35 cm/sec to differentiate GTT from GD during pregnancy, with 84.6% and 93.3% sensitivity and specificity. Conclusion: Thyroid artery velocities can help to differentiate between GD and GTT. The cutoff point of mean ITA-PSV at 35 cm/s had an excellent value in differentiating between the two, with good sensitivity and specificity.

Preconceptional Counseling in Women with Hyperthyroidism.

Preconception evaluation of couples wishing to conceive is an important step toward a healthy pregnancy and it is especially important in people with a chronic condition or at genetic risk. The most common endocrine disorders in women at reproductive age are those involving the thyroid gland and it is well recognized that hyperthyroidism (HT), over-function of the thyroid gland, is associated with risks of maternal, fetal, and neonatal complications. The aim of this paper is to review the latest evidence regarding the components of preconception counseling in women with HT that contemplate a pregnancy. We also want to raise awareness among healthcare professionals about the importance of periconceptional counseling in improving pregnancy outcomes and avoid maternal and fetal complications related to thyroid dysfunction. In women with Graves' disease seeking pregnancy, it is essential to discuss all the treatment options along with the associated risks and benefits. Extensive prospective studies are still needed to understand the implications of current recommended strategies for the management of HT in preconception and during pregnancy.

Gestational Transient Thyrotoxicosis Complicated by Thyroid Storm in a Patient With Hyperemesis Gravidarum.

We describe a patient with gestational transient thyrotoxicosis (GTT) associated with hyperemesis gravidarum (HG) in a twin gestation complicated by thyroid storm resulting in intrauterine fetal demise. GTT is a well-documented complication of the first trimester of pregnancy that may affect up to 60% of pregnancies with HG. Typically, GTT is not associated with unfavorable maternal or fetal outcomes and has a spontaneous resolution. Aside from supportive care, the use of antithyroid drugs (ATD) in GTT is not regularly recommended. Although to our knowledge one similar case has been reported in the literature, the incidence of thyroid storm in GTT has not yet been established. Our case highlights that, although rare, GTT may be complicated by thyroid storm resulting in adverse maternal and fetal outcomes. Our case further suggests that consideration of ATD use in GTT should be given in pregnancies with higher serum human chorionic gonadotropin (hCG) concentration as occurs in HG and multiple pregnancies.

Immune checkpoint inhibitor-induced hypothyroidism predicts treatment response in Japanese subjects.

Background: Immune checkpoint inhibitors (ICIs) cause a variety of immune-related adverse events (irAEs). Among them, thyroid dysfunction is most frequently observed. Patients with irAEs have higher survival rates than those without irAEs, but there is no certainty as to whether the degree of thyroid dysfunction is associated with treatment response or survival with ICIs. Method: This is a single-center, retrospective, observational study. The study included 466 patients who received ICI at Kawasaki Medical School Hospital from September 1, 2014, to May 31, 2022 and evaluated the degree of abnormal thyroid function and survival and remission rates after treatment with ICIs. Primary hypothyroidism of less than 10 µIU/mL TSH was classified as grade 1, and primary hypothyroidism requiring more than 10 µIU/mL TSH or levothyroxine as grade 2-4. Result: The mean age of the study participants was 68.2 ± 10.3 years, and the percentage of male participants was 72.6%. The frequency of ICI-induced thyroid dysfunction in the study participants was 28.2%. TSH levels were significantly higher in Grade 1 and Grades 2-4 when treated with ICI compared to NTF (p<0.0001). The survival rate at 1 year after ICI administration was significantly higher with 64.9% for grade 1 and 88.9% for grades 2-4 compared to 52.1% for NTF (p<0.0001). Cancer stage at the time of ICI administration did not differ among the groups (p=0.68). Nevertheless, the remission rate assessed by RECIST criteria was significantly higher in grades 2-4 compared to NTF (p<0.0001). Conclusion: ICI-induced thyroid dysfunction was significantly correlated with survival, mean observation time, and treatment remission rate. It is important to monitor thyroid hormone levels regularly in patients receiving ICIs.

Gestational and Postpartum Complications in Patients with First Trimester Thyrotoxicosis: A Prospective Multicenter Cohort Study from Northeast China.

Objective: Gestational transient thyrotoxicosis (GTT) and Graves' disease (GD) are the most common causes of hyperthyroidism during pregnancy. However, few studies have compared pregnancy outcomes of patients who had GTT with those who had GD in the first trimester of pregnancy. Methods: We conducted a prospective multicenter cohort study in China. Participants received questionnaires, physical examinations, and underwent measurements of thyrotropin (TSH), free thyroxine (fT4), thyroid peroxidase antibody (TPOAb), TSH receptor antibody (TRAb), and urinary iodine in the first trimester. The patients diagnosed with either GTT or GD and normal thyroid function (NTF) group were followed until delivery. The thyroid function and pregnancy outcomes were reported. Results: A total of 125 pregnant women with thyrotoxicosis and 246 age-matched pregnant women with NTF were included. (1) The thyroid function of the GTT group returned to normal range in the third trimester, but was consistently abnormal in the GD group. (2) The incidence of gestational diabetes mellitus (GDM) in the GTT group (11.5%, 9/78) was significantly higher than that in NTF group (4.9%, 12/246) (p = 0.037). The incidence of premature delivery in the GD untreated (30.8%, 8/26, p = 0.002) and treated groups (28.6%, 6/21, p = 0.008) was both, respectively, higher than that in the NTF group (7.7%, 19/246). Miscarriage (15.4%, 4/26 vs. 3.7%, 9/246, p = 0.026) and gestational hypertension (19.2%, 5/26 vs. 3.3%, 8/246, p = 0.004) were more prevalent in the GD untreated group than in the NTF group. (3) The presence of positive TRAb and positive TPOAb in the first trimester were independent risk factors for miscarriage (odds ratio [OR] = 5.23, confidence interval [CI] = 1.11-24.78, p = 0.037) and low birth weight infants (OR = 7.76, CI = 1.23-48.86, p = 0.029), respectively. Conclusion: In conclusion, pregnancy outcomes appear variable, according to the etiology of first trimester thyrotoxicosis. GTT appears to be associated with GDM. GD appears to be associated with an increased risk of premature delivery, gestational hypertension, and miscarriage. The diagnosis of GTT and GD patients during early pregnancy and appropriate treatment of GD patients may be associated with improved pregnancy outcomes.

Thyroid Storm Caused by Hyperemesis Gravidarum.

Background: Transient thyrotoxicosis has been documented in the setting of hyperemesis gravidarum (HG) with elevated human chorionic gonadotropin (hCG) levels. Thyroid storm in pregnancy is rarer and typically associated with autoimmune hyperthyroidism. We described thyroid storm in a primigravid 18-year-old patient due to hCG level elevation secondary to HG, which resolved in the second trimester of pregnancy. Case Report: Our patient presented with vomiting, hyperthyroidism, and cardiac and renal dysfunction at 16 weeks' gestation. She was clinically found to have a thyroid storm, with undetectable thyroid-stimulating hormone (TSH) and a free thyroxine level of >6.99 ng/dL. The hCG level was elevated at 246 030 mIU/L (9040-56 451 mIU/L). She was treated with methimazole, saturated solution potassium iodide, and propranolol. Because thyroid autoantibodies were absent, thyroid ultrasound yielded normal results, and thyroid function testing results rapidly improved as the hCG level decreased, the medications were tapered and ultimately discontinued by day 10 of hospitalization. The thyroid function remained normal after discharge. Discussion: Because hCG and TSH have identical alfa subunits and similar beta subunits, hCG can bind to the TSH receptor and stimulate thyroxine production. The hCG level peaks at around 8-14 weeks of gestation, correlating with decreased TSH levels in this same time frame. This case emphasizes the relevant physiology and importance of timely and thorough evaluation to determine the appropriate management, prognosis, and follow-up for patients with thyroid storm in the setting of HG. Conclusion: Although transient thyrotoxicosis is documented in patients with HG, thyroid storm is rare, and our case illustrates a severe example of these comorbidities.

Perinatal effects of maternal FT3/FT4 ratio on gestational transient thyrotoxicosis

ABSTRACT Objective: The effects of maternal thyroid hormone levels on the course of pregnancy and birth weight have attracted interest. The aim of the present study was to consider FT3 and FT3/FT4 ratio in the evaluation of the effects of maternal thyroid functions in gestational transient thyrotoxicosis (GTT). Materials and methods: This case-control study included 45 patients with GTT and 45 healthy pregnant women. Maternal history before pregnancy, thyroid function tests, thyroid autoantibodies, and thyroid ultrasonography results in 6th to 10th weeks of pregnancy were used in the differential diagnosis of GTT. In both groups, the effects of FT3, FT4 and FT3/FT4 ratios on gestational age and birth weight were evaluated. Results: There was no significant difference in the gestational age between the GTT and control groups (39,3±1,0 weeks and 39,2±1,2 weeks, respectively). Birth weights were similar in both groups (3205,2±4899 g and 3196,6±309,3 g, respectively). When maternal weight was adjusted, a positive correlation was observed between maternal FT3/FT4 ratio and birth weight (r=0,317, p=0,017). Additionally there was a positive correlation between the gestational age and the birth weight in the control group (ρ=0,726, p=0,001). Conclusion: GTT had no significant effect on the gestational age and the birth weight. On the other hand an increase in the maternal FT3/FT4 ratio had a positive effect on the birth weight in the patient with GTT. Maternal characteristics (age, weight, BMI) and FT3/FT4 ratio should be taken into consideration in future impact assessment studies on this issue.

Perinatal effects of maternal FT3/FT4 ratio on gestational transient thyrotoxicosis.

OBJECTIVE: The effects of maternal thyroid hormone levels on the course of pregnancy and birth weight have attracted interest. The aim of the present study was to consider FT3 and FT3/FT4 ratio in the evaluation of the effects of maternal thyroid functions in gestational transient thyrotoxicosis (GTT). METHODS: This case-control study included 45 patients with GTT and 45 healthy pregnant women. Maternal history before pregnancy, thyroid function tests, thyroid autoantibodies, and thyroid ultrasonography results in 6th to 10th weeks of pregnancy were used in the differential diagnosis of GTT. In both groups, the effects of FT3, FT4 and FT3/FT4 ratios on gestational age and birth weight were evaluated. RESULTS: There was no significant difference in the gestational age between the GTT and control groups (39,3±1,0 weeks and 39,2±1,2 weeks, respectively). Birth weights were similar in both groups (3205,2±4899 g and 3196,6±309,3 g, respectively). When maternal weight was adjusted, a positive correlation was observed between maternal FT3/FT4 ratio and birth weight (r=0,317, p=0,017). Additionally there was a positive correlation between the gestational age and the birth weight in the control group (ρ=0,726, p=0,001). CONCLUSION: GTT had no significant effect on the gestational age and the birth weight. On the other hand an increase in the maternal FT3/FT4 ratio had a positive effect on the birth weight in the patient with GTT. Maternal characteristics (age, weight, BMI) and FT3/FT4 ratio should be taken into consideration in future impact assessment studies on this issue.

Lessons of the month: Not just morning sickness.

A 34-year-old woman (gravida 4; para 3) at 17 weeks of pregnancy presented with abnormal behaviour for 3 weeks associated with difficulties in walking. She had been admitted 2 months prior with hyperemesis gravidarum and was also diagnosed with thyrotoxicosis. Vomiting and poor oral intake persisted after discharge. She was euthyroid otherwise. Clinical examination revealed a dehydrated and confused patient. She had nystagmus and ataxic gate. Magnetic resonance imaging of the brain showed symmetrical signal changes of posteromedial part of thalamus. A diagnosis of Wernicke's encephalopathy (WE) was made and intravenous thiamine was given leading to gradual improvement of symptoms. Her thyroid function test normalised without any treatment. WE can occur in severe hyperemesis gravidarum. Prompt recognition of WE and replacement with thiamine is important to prevent neurological sequelae and mortality. Gestational transient thyrotoxicosis, which is self-limiting, is more prominent in patients with hyperemesis gravidarum and requires only symptomatic treatment.

Pitfalls in the assessment of gestational transient thyrotoxicosis.

Gestational transient thyrotoxicosis (GTT) is associated with direct stimulation of the maternal thyroid gland by human chorionic gonadotropin (hCG). It is characterized by slightly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels in early pregnancy and mild or no symptoms. While GTT must be distinguished from Graves' disease (GD), which is associated with maternal and fetal complications, treated GD and new-onset GD in pregnancy are occasionally challenging to distinguish. Evaluating serum hCG levels and TSH receptor antibody (TRAb) titers can help, but the results are not irrefutable due to pregnancy-related immunosuppression. Moreover, GTT can follow unusual clinical courses in relation to some pregnancy complications. Excessive hCG production can cause severe GTT symptoms in patients with hyperemesis gravidarum, trophoblastic disease, or multiple pregnancies. Thyrotoxicosis can emerge beyond the second trimester in patients with gestational diabetes mellitus and mirror syndrome, because of delayed elevations in the hCG levels. Detailed knowledge about GTT is necessary for correct diagnoses and its appropriate management. This review focuses on the diagnosis of GTT, and, particularly, its differentiation from GD, and unusual clinical conditions associated with GTT that require comprehensive management.

Hyperthyroidism in the pregnant woman: Maternal and fetal aspects.

Hyperthyroidism during pregnancy is uncommon. Nonetheless, prompt identification and adequate management of hyperthyroidism in a pregnant woman is essential, because uncontrolled thyrotoxicosis significantly increases the risk of maternal and fetal complications. Also, fetal prognosis may be affected by the transplacental passage of maternal thyroid stimulating antibodies or thyrostatic agents, both of which may disrupt fetal thyroid function. Birth defects have been reported in association with the use of antithyroid drugs during early pregnancy. Although rarely, offspring of mothers with Graves' disease may develop fetal/neonatal hyperthyroidism, the management of which requires a close collaboration between endocrinologists, obstetricians, and neonatologists. Because of the above considerations, the management of pregnant and lactating women with hyperthyroidism requires special care, bearing in mind that both maternal thyroid excess per se and related treatments may adversely affect the newborn's health. In this review we discuss the diagnosis and management of hyperthyroidism in pregnancy, along with the impact of thyrotoxicosis and medications on fetal outcome.

Relationship between gestational transient thyrotoxicosis and vitamin D.

BACKGROUND/AIM: Gestational transient thyrotoxicosis (GTT) is a transient, mild hyperthyroidism that occurs early in pregnancy and is due to human chorionic gonadotropin. There is no clear information about why only some pregnant women develop GTT. Previous papers stated that vitamin D plays a role in thyroid functions. We aimed to evaluate the relationship between vitamin D and GTT. MATERIALS AND METHODS: Fifty-three patients diagnosed with GTT at the 6th to 10th weeks of gestation were included in the study (GTT group). Thirty-five pregnant women with normal thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) levels served as a control group. Vitamin D, TSH, fT3, and fT4 levels were followed during entire the pregnancy. RESULTS: TSH levels had been normalized at the 20th week of gestation in all patients with GTT (mean TSH: 0.56 ± 0.2 µIU/mL). Vitamin D levels were significantly lower in the GTT group than the controls (11.1 ± 7.7 and 16.5 ± 0.5 ng/mL, respectively; P = 0.008). CONCLUSION: Pregnant women who are diagnosed with GTT should be evaluated for possible vitamin D deficiency.

Clinical analysis of 65 cases of hyperemesis gravidarum with gestational transient thyrotoxicosis.

AIM: We investigated thyroid function and the impact of gestational transient thyrotoxicosis (GTT) on pregnancy outcome in patients with hyperemesis gravidarum (HG; n = 143) who were hospitalized for rehydration. METHODS: Serum thyroid-stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), thyroid globulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and hCG were measured after admission. RESULTS: The total prevalence of thyrotoxicosis in HG was 48.3%; GTT was the main form (45.5%). The total incidence of GTT increased significantly if serum hCG was more than 80,000 IU/L, subclinical GTT if serum hCG was 80,000-140,000 IU/L and clinical GTT if serum hCG was more than 180,000 IU/L. GTT did not require antithyroid therapy. The course of TSH, FT3 and FT4 were followed in 34 cases of GTT; thyroid function normalized by the second trimester. Of 65 patients with GTT, two underwent abortions due to unplanned pregnancies, two delivered prematurely and two infants had macrosomia. There were no other complications. All newborns (n = 63) of mothers with GTT had normal TSH levels. CONCLUSION: GTT is common in HG. The severity of GTT is related to serum hCG levels. In patients with HG and GTT, thyroid function normalized by the second trimester without antithyroid treatment. GTT did not affect pregnancy outcomes.

Hyperthyroidism and pregnancy.

Association of hyperthyroidism and pregnancy is not an unusual event, and has an impact on both the mother and fetus. After delivery, it may also affect the newborn and the nursing mother. Clinical management of this situation is quite different from that required by non-pregnant hyperthyroid women and poses significant diagnostic and therapeutic challenges. This review addresses aspects related to the unique characteristics of biochemical assessment of thyroid function in pregnancy, the potential causes of hyperthyroidism in pregnancy, and the clinical and therapeutic approach in each case. Special attention is paid to pregnancy complicated with Graves' disease and its different the maternal, fetal, neonatal, and postnatal consequences.

Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study

OBJECTIVE: To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy. METHODS: The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 ageand sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography. RESULTS: The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease. CONCLUSIONS: This study suggests that the measurement of inferior thyroid artery-blood flow velocities with colorflow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.