Birth defects after use of antithyroid drugs in early pregnancy:a Swedish nationwide study

Objective Antithyroid drugs (ATDs) may have teratogenic effects, but more evidence is needed on the risk and types of birth defects after the use of methimazole (MMI) and propylthiouracil (PTU). This study aimed to evaluate the association between the use of ATDs in early pregnancy and birth defects. Design Swedish nationwide register-based cohort study. Methods The study included 684 340 children live-born in Sweden from 2006 to 2012. Exposure groups defined by maternal ATD use in early pregnancy were MMI (n = 162); PTU (n = 218); MMI and PTU (n = 66); ATD before or after, but not in pregnancy (n = 1551) and non-exposed (never ATD (n = 682 343)). Outcome was cumulative incidence of birth defects diagnosed before two years of age. Results The cumulative incidence of birth defects was not significantly different in children exposed to MMI (6.8%, P = 0.6) or PTU (6.4%, P = 0.4) vs non-exposed (8.0%). For subtypes of birth defects, MMI was associated with an increased incidence of septal heart defects (P = 0.02). PTU was associated with ear (P = 0.005) and obstructive urinary system malformations (P = 0.006). A case of choanal atresia was observed after exposure to both MMI and PTU. The incidence of birth defects in children born to mothers who received ATD before or after, but not in pregnancy, was 8.8% and not significantly different from non-exposed (P = 0.3), MMI exposed (P = 0.4) or PTU exposed (P = 0.2). Conclusions MMI and PTU were associated with subtypes of birth defects previously reported, but the frequency of ATD exposure in early pregnancy was low and severe malformations described in the MMI embryopathy were rarely observed. </jats:sec

Adjuvant Treatment of Graves' Disease with Diclofenac : Safety, Effects on Ophthalmopathy and Antibody Concentrations

BACKGROUND: Orbital morphological changes are often present in patients with Graves' disease (GD) already at diagnosis, and cyclooxygenase type 2 (COX-2) is overexpressed in active Graves' ophthalmopathy (GO).OBJECTIVE: To investigate if adjuvant treatment of GD with the COX inhibitor and peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist diclofenac decreases the development of ophthalmopathy and if laboratory parameters are affected.METHODS: This is a multicenter trial where 61 subjects were randomized to methimazole (block and replace with l-thyroxine) either with or without diclofenac 50 mg 1 × 2 for 12 months. The primary end point development of GO after 24 months was evaluated. Smoking habits were registered and the thyroid parameters TSH, free T4, free T3, TSH receptor antibodies (TRAb) and anti-TPO were followed. Safety parameters (kidney, liver and blood) and adverse events were regularly registered.RESULTS: GO developed in 11% (n = 3) of the patients treated with diclofenac and in 21% (n = 6) of the controls (p = 0.273). The adverse event profile was acceptable without any severe events related to diclofenac. Both TRAb and anti-TPO concentrations decreased during treatment with methimazole, but the anti-TPO concentrations were lower in patients treated with diclofenac after 15 months (p = 0.031). The TRAb concentrations were not significantly changed between groups. Smokers had higher concentrations of TRAb than nonsmokers both at diagnosis of GD (p = 0.048) and after 15 months (p = 0.042).CONCLUSIONS: Treatment with diclofenac had no significant influence on development of GO. Diclofenac reduces anti-TPO concentrations and seems to be safe to use in GD patients

Incidence of hyperthyroidism in Stockholm, Sweden, 2003-2005

Objectives: To investigate the incidence of hyperthyroidism in Stockholm County in those patients who were diagnosed with hyperthyroidism for the First time during the years 2003-2005. Design: All new cases of hyperthyroidism >= 18 years of age were prospectively registered to calculate the total incidence of hyperthyroidism, as well as the incidence of the subgroups: Graves' disease (GD), toxic multinodular goitre and solitary toxic adenoma (STA). Eight specialized units/hospitals in Stockholm County participated in the registration. The participating physicians were all specialists in medical endocrinology. oncology, nuclear medicine or surgery. Results: Duringa 3-year period, 1431 new patients of hyperthyroidism were diagnosed in a well-defined adult population (>18 years of age) of in average 1 457 036 inhabitants. This corresponds to a mean annual incidence of hyperthyroidism of 32.7/100 000. The incidence of GD was 24.5/100 000 per year. toxic nodular goitre was 3.3/100 000 per year and STA was 4.9/100 000 per year. Conclusions: The total incidence of hyperthyroidism in Stockholm County was found to be 32.7/100 000 per year. of which 75% had GD. There were a higher percentage of smokers among the patients with hyperthyroidism compared with the overall population in Stockholm, but no difference in the frequency of smoking between patients with GD and toxic nodular goitre

Treatment of patients with Graves' disease in Sweden compared to international surveys of an 'index patient'

Introduction The treatment strategies for a 42-year-old female index patient with moderate Graves' disease (GD) vary according to several international surveys. The important question whether surveys of treatment preferences in theoretical patient cases also match how real patients are treated has not yet been addressed. Materials and Methods From a Swedish cohort of 1186 GD patients (TT-12 cohort), 27 women were identified using the same criteria as from the index patient surveys from the European and American Thyroid Associations. This 'index patient cohort' was age 40-45, otherwise healthy female, with two children and uncomplicated GD. The applied first-line treatment of the patients in the index cohort, together with its variations, was compared with the treatment preferences according to international surveys. A comparison with the TT-12 cohort was also performed. Results In the 'Index cohort', 77.8% were treated with antithyroid drugs (ATD), and 22.2% were treated with radioiodine (I-131). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where I-131 was preferred. The distribution of treatment in the TT-12 cohort did not significantly differ from the index cohort. ATD was the preferred treatment in male and young (age 19-22) patients, as was RAI in old (age 69-73) patients. The age-related, but not the gender-related, cases differed significantly from the entire TT-12 cohort. Conclusion The treatment choice in an index patient in Sweden seems in line with European practice, where ATD is the preferred first choice. This differs compared to US and North African survey intentions, where I-131 is more often used. Age more than gender influences the treatment choice of GD patients. This is, to our best knowledge, the first time an index patient from 'real life' has been presented and compared to treatment preferences of international thyroid association surveys

Long term outcome after toxic nodular goitre

Background: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort. Methods: TNG patients (n = 638) de novo diagnosed between 2003–2005 were invited to engage in a 6–10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines. Results: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population. Conclusion: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG

Impaired Quality of Life after Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves' Hyperthyroidism:A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey

BACKGROUND: Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey. METHODS: The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity. RESULTS: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism. CONCLUSIONS: GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies

Thyroid-Associated Ophthalmopathy after Treatment for Graves' Hyperthyroidism with Antithyroid Drugs or Iodine-131.

Context: Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO). Objectives: The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs. Design: We conducted a randomized trial (TT 96) with a follow-up of 4 yr. Patients, Setting, and Intervention: Patients with a recent diagnosis of Graves' hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T4 was given in both groups. Main Outcome Measure: Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001). Results: The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism. Conclusions: Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality

Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis

Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed (p  >  0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T-score ≤ −2.5 but not in those with a T-score  >  −2.5; in those with a body mass index (BMI)  <  25 kg/m2 but not ≥ 25 kg/m2; and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline