Endocrine disorders in obstructive sleep apnoea syndrome: A bidirectional relationship.

Obstructive sleep apnoea (OSA) is a common disorder characterized by recurrent episodes of apnoea or hypopnea due to total or partial pharyngeal collapse and temporary upper airway obstruction during sleep. The prevalence of OSA is increasing and currently affects about 30% of men and 13% of women in Europe. Intermittent hypoxia, oxidative stress, systemic inflammation, and sleep fragmentation resulting from OSA can provoke subsequent cardiometabolic disorders. The relationships between endocrine disorders and OSA are complex and bidirectional. Indeed, several endocrine disorders are risk factors for OSA. Compared with the general population, the prevalence of OSA is increased in patients with obesity, hypothyroidism, acromegaly, Cushing syndrome, and type 1 and 2 diabetes. In some cases, treatment of the underlying endocrine disorder can improve, and occasionally cure, OSA. On the other hand, OSA can also induce endocrine disorders, particularly glucose metabolism abnormalities. Whether continuous positive airway pressure (CPAP) treatment for OSA can improve these endocrine disturbances remains unclear due to the presence of several confounding factors. In this review, we discuss the current state-of-the-art based on the review of the current medical literature for key articles focusing on the bidirectional relationship between endocrine disorders and OSA and the effects of treatment. Screening of OSA in endocrine patients is also discussed, as it remains a subject of debate.

Obstructive sleep apnea is not associated with diabetic retinopathy in diabetes: a prospective case-control study.

PURPOSE: Diabetic retinopathy (DR) is the most common ocular complication of type 2 diabetes mellitus (T2D) and is associated with diabetes duration, glycemic control, and hypertension (HTN). Obstructive sleep apnea (OSA) is frequent in T2D and is associated with poor glycemic control. However, it is unclear if there is an association between OSA and DR. This study aimed to assess whether or not the presence of OSA in patients with T2D was associated with DR. METHODS: In this prospective case-control study, consecutive patients with DM attending the ophthalmology clinics were recruited to include patients with DR (cases) and without DR (controls). OSA was diagnosed by attended polysomnography (PSG). Blood pressure and a fasting morning blood sample, including glycosylated hemoglobin (HbA1c), were recorded. Patients were matched for age, body mass index (BMI), gender, and T2D duration. RESULTS: Thirty diabetic patients with DR were matched with 30 controls. In all patients, the prevalence of moderate-to-severe OSA was 57%. In the logistic regression analysis, DR was associated with increased HbA1c (OR 2.63, 95% CI 1.35-5.16, p = 0.004) but not with any PSG parameter. In the DR group, PSG parameters were not associated with the severity of ocular disease (non-proliferative, proliferative, presence/absence of macular edema). The proliferative aspect of DR was correlated with age (p = 0.017). DR occurred more frequently in uncontrolled diabetes compared to well-controlled diabetes (80% vs 38%, p = 0.029). CONCLUSIONS: In patients with T2D, the presence of DR is not associated with OSA, but with poorly controlled T2D.

Prevalence of undiagnosed glucose intolerance and type 2 diabetes in patients with moderate-to-severe obstructive sleep apnea syndrome.

PURPOSE: Overweight and obesity are major causal factors for obstructive sleep apnea syndrome (OSAS), providing insight into why one third of patients with OSAS suffer from diabetes mellitus and another third from glucose intolerance. However, a significant proportion of the general population remains undiagnosed for glucose metabolism disorders. The primary aim of this study was to establish the prevalence of known and newly diagnosed glucose metabolism disorders in patients with moderate and severe OSAS referred to the sleep lab for continuous positive airway pressure (CPAP) therapy. METHODS: We prospectively included consecutive patients with moderate or severe OSAS referred for CPAP therapy. A fasting blood sample was collected to determine glycosylated hemoglobin (HbA1c), glucose, and homeostatic model assessment (HOMA) index. Baseline demographic data and medication intake were recorded. RESULTS: Of 280 consecutive patients (70% men, mean ± SD body mass index 33 ± 7 kg/m2, apnea-hypopnea index 49 ± 25), 22% exhibited diabetes and 44% glucose intolerance. Undiagnosed diabetes and glucose intolerance was found in 79 of 280 patients (28%). Insulin resistance was associated with OSAS severity in multivariate linear regression analysis (regression coefficient 2.40 [95% CI 0.07-4.72]; p = 0.04). CONCLUSION: In this population of overweight and obese patients with moderate and severe OSAS, 66% of patients had diabetes or glucose intolerance and 28% were newly diagnosed. Diabetes and glucose intolerance were not related to OSAS severity, contrary to insulin resistance. These data suggest that there is value in systematic screening for glucose metabolism disorders in all patients with moderate and severe OSAS.

Prevalence of newly established thyroid disorders in patients with moderate-to-severe obstructive sleep apnea syndrome.

BACKGROUND: Hypothyroidism can directly cause obstructive sleep apnea (OSA) but may also contribute to it through its impact on the metabolic syndrome. The purpose of this study was to establish the prevalence of known and newly diagnosed overt and subclinical hypothyroidism (SCH) among patients with OSA. METHODS: We prospectively included all consecutive moderate or severe OSA patients referred for CPAP therapy. A fasting blood sample was collected to determine thyroid-stimulating hormone (TSH) and free T4 (FT4) levels. RESULTS: A total of 280 patients were included (70% male). Mean ± SD body mass index (BMI) and apnea-hypopnea index (AHI) were 33 ± 7 kg/m2 and 49 ± 25, respectively. Median (range) serum TSH levels and mean ± SD FT4 levels were comparable between severe and moderate OSA (1.7 (1.3-2.6) vs 2.1 (1.2-2.8); p = 0.378 and 15.3 ± 2.3 vs 15.3 ± 2.3; p = 0.981). TSH and FT4 levels were not correlated with AHI (p = 0.297 and p = 0.370, respectively), but TSH was correlated with BMI (p = 0.049).Of all patients, 8.9% had increased serum TSH levels (severe and moderate OSA patients had similar levels (p = 0.711)) and 8.2% were newly diagnosed patients (no differences were observed between severe and moderate OSA (p = 0.450)). A total of 16.4% of patients had some type of thyroid disorder. Thyroid function parameters were associated with BMI but not with the severity of OSA. CONCLUSION: In our population of moderate or severe OSA, 16% of patients had a thyroid problem and 8% of these were newly diagnosed with SCH.

Maternal thyroid parameters in pregnant women with different ethnic backgrounds: Do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?

OBJECTIVE: Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a thyroid-stimulating hormone (TSH) upper reference limit (cut-off) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cut-offs (institutional, ethnicity-specific, 2.5 mIU/L [Endocrine Society] and 4.0 mIU/L [American Thyroid Association]). DESIGN: Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women. METHOD: The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-abs), TSH and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with sub-Saharan (SaBg; 28.6%), 754 North African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded. RESULTS: The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; P<.001, respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; P=.006 and .014, respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cut-off, but when 4.0 mIU/L or the institutional cut-off (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1% vs 3.3%, P=.008 and .013, respectively). The use of ethnicity-specific cut-offs did not change the prevalence of SCH as compared to the use of institutional cut-offs. However, when these cut-offs were used, the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; P<.001) relative to the 2.5 mIU/L cut-off. CONCLUSIONS: Pregnant women with a sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cut-offs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cut-off.

Thyroid autoimmunity, hypothyroidism and ovarian reserve: a cross-sectional study of 5000 women based on age-specific AMH values.

STUDY QUESTION: Is there any association between thyroid autoimmunity (TAI) and diminished ovarian reserve (DOR)? SUMMARY ANSWER: TAI and hypothyroidism are not associated with low ovarian reserve. WHAT IS KNOWN ALREADY: TAI is a common co-existent endocrinopathy in women with primary ovarian insufficiency. Several studies support a potential link between TAI and the reduction in ovarian reserve. However, robust evidence regarding its prevalence in women with DOR is lacking. STUDY DESIGN, SIZE, DURATION: This study is a large cross-sectional analysis of retrospective data from the Centre for Reproductive Medicine/University Hospital of Brussels. Serum measurements were taken for anti-Mullerian hormone (AMH), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroperoxidase (anti-TPO). PARTICIPANTS/MATERIALS, SETTING, METHODS: Among 5076 consecutive women, 4894 women had their AMH, FT4, TSH and anti-TPO levels measured on the same day. AMH levels were plotted in relation to age for the whole patients' cohort and age-specific AMH values (per year) were considered in order to categorize women according to the AMH levels of ovarian reserve. There were 3929 women who demonstrated normal reserve, 487 women who had low ovarian reserve and 478 women who demonstrated high ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: Serum FT4 and TSH levels were comparable between different ovarian reserve categories (P = 0.611 and 0.811, respectively). No significant differences were observed in the prevalence of positive anti-TPO antibodies among women with low (12.1%), normal (10.3%) and high (9.8%) ovarian reserve (P = 0.423). Finally, the prevalence of overt or subclinical hypothyroidism was comparable between the groups (4.1% in low, 4.6% in normal and 3.8% in high ovarian reserve women, P = 0.645).Analysis according to the exact cause of low ovarian reserve demonstrated that women with a genetic cause of low ovarian reserve had a significantly higher prevalence of overt hypothyroidism and subclinical hypothyroidism compared with women with unexplained low ovarian reserve for their age (25 versus 3.2%, P = 0.002 and 18.8 versus 1.6%, P = 0.004, respectively). On the contrary, no significant differences were observed in the prevalence of hypothyroidism between genetic causes and iatrogenic causes (P = 0.316) and between iatrogenic and unexplained causes (P = 0.219) of low ovarian reserve. LIMITATIONS, REASONS FOR CAUTION: This is a cross-sectional analysis based on retrospective data collection. Due to the retrospective design of this study, the presence of biases related to such a study design cannot be excluded. Furthermore, this study assessed only the association of TAI, and not autoimmunity in general, with ovarian reserve. WIDER IMPLICATIONS OF THE FINDINGS: TAI and hypothyroidism are not associated with low ovarian reserve. Future research should focus on examining underlying mechanisms, other than TAI, which may have an effect on ovarian reserve. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared.

Screening and management of hypothyroidism in pregnancy: results of an Asian survey.

Maternal hypothyroidism in pregnancy is associated with several adverse outcomes. The American Thyroid Association and the Endocrine Society Guidelines for the management of thyroid diseases in pregnancy were published in 2011 and 2012, respectively; however, impact of the guidelines in routine clinical practice is unknown. We therefore carried out a survey to study current practices in the screening and management of hypothyroidism in pregnancy. We collected completed questionnaire survey based on clinical case scenarios from 321 members of the Asia-Oceania Thyrpid Association (AOTA). Responses from 310 clinician members (from 21 Asian countries) were analyzed. For a woman with hypothyroidism planning pregnancy, 54% favored testing thyroid function before adjusting the dose, whilst 32% recommended increasing the dose of L-thyroxine (L-T4) as soon as pregnancy is confirmed. For a pregnant woman with newly diagnosed overt hypothyroidism, most responders initiated a full dose of L-T4. One half of responders used serum TSH and free T4 to monitor the dose of L-T4. Although the target of thyroid function tests that responders aimed to achieve with L-T4 was inconsistent, but a majority aim to keep TSH within recommended trimester specific range. Twenty-one % responders or their institutions screened all pregnant women for thyroid dysfunction, 66% performed targeted screening of only the high-risk group, whilst 13% did not carry out systemic screening. Majority of responders practices within recommendations of major professional societies; however, there is wide variation in the clinical practice in the treatment and screening of hypothyroidism during pregnancy in Asia.

Management of hyperthyroidism during pregnancy in Asia.

Maternal hyperthyroidism in pregnancy is associated with adverse impacts on both mother and fetus. Recently, the American Thyroid Association and the Endocrine Society have published guidelines for the management of thyroid diseases in pregnancy. We aimed to disclose the impact of these guidelines in current practices of Asian members of the Asia-Oceania Thyroid Association (AOTA) regarding the management of hyperthyroidism in pregnancy. Completed questionnaire survey, based on clinical case scenarios, was collected from 321 Asian physician members of AOTA from 21 Asian countries in 2013. For a woman with Graves' disease planning pregnancy, 92% of clinicians favored antithyroid treatment, 52% with propylthiouracil (PTU) while 40% preferred methimazole (MMI). For a pregnant woman with newly diagnosed overt hyperthyroidism, nearly all responders initiated PTU treatment. To monitor dosage of antithyroid drugs, approximately 73% of responders used TSH and free T4 (FT4) levels without free T3 (FT3) (53%) or with FT3 (20%). Majority of responders targeted achieving low serum TSH with FT4 (or total T4) in the upper end of the normal range. For management of gestational thyrotoxicosis, 40% chose to follow up and 52% treated patients with PTU. Although timing of TSH receptor antibodies measurement in pregnant hyperthyroid patients was variable, 53% of responders would check it at least once during pregnancy. Nearly 80% of responders do not treat subclinical hyperthyroidism in pregnancy. Therefore, despite wide variations in the management of hyperthyroidism during pregnancy in Asia, majority of Asian physicians practice within the recommendations of major professional societies.

Update on therapeutic use of levothyroxine for the management of hypothyroidism during pregnancy.

Hypothyroidism is a relatively common finding during pregnancy. This may be due either to the presence of existing thyroid disease and/or to the increased demands that pregnancy places the thyroid gland to provide thyroid hormones for the mother and the developing fetus. There is no doubt that overt hypothyroidism is associated strongly with adverse pregnancy outcomes, including miscarriage. Meta-analyses show that thyroid hormone replacement with levothyroxine (LT4) reduces the risk of adverse pregnancy outcomes in the setting of overt hypothyroidism. Accordingly, management guidelines in this area are unanimous in recommending intervention with to control the level of thyrotropin (TSH) to below 2.5 µIU/mL. The evidence for an adverse impact of subclinical hypothyroidism (SCH) on pregnancy outcomes is less clear, although meta-analyses suggest that SCH reduces the chance of a successful pregnancy outcome. Guidelines also support intervention for some patients with SCH, particularly where TSH is high (>10 µIU/mL), or where TSH is above its trimester-specific reference range in a woman with thyroid autoimmunity (giving LT4 to euthyroid women with thyroid autoimmunity is not supported). Real-world evidence suggests that hypothyroidism in pregnancy is often overlooked or that LT4 is not given appropriately to gain tight control of TSH. More research is needed to identify the barriers to optimal thyroid care with LT4 at this crucial time.

Thyroid function monitoring during pregnancy in euthyroid women with thyroid autoimmunity.

BACKGROUND: Thyroid autoimmunity (TAI) may be present in 1-17% of pregnant women. Monitoring of thyroid function in euthyroid pregnant women positive for anti thyroperoxidase antibodies (TPOAb +) is recommended. OBJECTIVE: To determine the prevalence and possible clinical and biological risk factors of biochemical progression (rise in serum TSH> 2.5 mU/L) at second blood sampling during pregnancy, in euthyroid women (TSH ≤ 2.5 mU/L) according to their TPOAb status. METHODS: This study included demographic and biological data from two previously published cohorts (n=274 women from August 1996 to May 1997 Copenhagen cohort, and n=66 women from January 2013 to December 2014 Brussels cohort) having at least two measurements of TSH and free thyroxine (FT4) and at least one of TPOAb during spontaneously achieved singleton pregnancies. RESULTS: The majority of women studied did not show biochemical progression. Only 4.2% progressed, significantly more frequently among TPOAb + women, as compared to TPOAb - group (9.4% vs 2.7%, p=0.015). No rise in serum TSH > 4 mU/L at 2nd sampling was observed. Higher baseline TSH levels were associated with biochemical progression in both TPOAb+ (p=0.05) and TPOAb - women (p<0.001), whereas maternal age, BMI, multiparity, smoking, FT4 and TPOAb concentrations were not significantly different between women with and without progression. CONCLUSIONS: Only a minority of euthyroid women with thyroid autoimmunity presented biochemical progression and none with a TSH > 4mU/L. Larger studies are needed to better target the subset of women that would benefit most from repeated thyroid function monitoring during pregnancy.

Long-term hypothyroidism in patients started on levothyroxine during pregnancy.

Background: Current guidelines recommend different postpartum approaches for patients started on levothyroxine (LT4) during pregnancy. Objective: We studied the postpartum management of these patients and determined factors associated with long-term hypothyroidism. Methods: A retrospective study was conducted at a tertiary center between 2014 and 2020, with LT4 initiation according to 2014 ETA recommendations. We performed multivariate logistic regression (MVR) and a receiver operating characteristic curve analysis to determine variables associated with long-term hypothyroidism and their optimal cutoffs. Results: LT4 was initiated in 177 pregnant women, and 106/177 (60%) were followed at long-term (at least 6 months post partum) (28.5 (9.0-81.9) months). LT4 could have been stopped in 45% of patients who continued it immediately after delivery. Thirty-six out of 106 (34%) patients were long-term hypothyroid. In them, LT4 was initiated earlier during pregnancy than in euthyroid women (11.7 ± 4.7 vs 13.7 ± 6.5 weeks, P = 0.077), at a higher thyroid-stimulating hormone (TSH) level (4.1 (2.2-10.1) vs 3.5 (0.9-6.9) mU/L, P = 0.005), and reached a higher dose during pregnancy (62.8 ± 22.2 vs 50.7 ± 13.9 µg/day, P = 0.005). In the MVR, only the maximal LT4 dose during pregnancy was associated with long-term hypothyroidism (odds ratio (OR) = 1.03, 95% CI: 1.00-1.05, P = 0.003). The optimal cutoffs for predicting long-term hypothyroidism were an LT4 dose of 68.75 µg/day (87% specificity, 42% sensitivity; P = 0.013) and a TSH level ≥ 3.8 mU/L (68.5% specificity, 77% sensitivity; P = 0.019). Conclusion: One-third of the patients who started on LT4 during pregnancy had long-term hypothyroidism. The TSH level at treatment initiation and the LT4 dose during pregnancy could guide the decision for continuing long-term LT4.

EMAS position statement: Thyroid disease and menopause.

INTRODUCTION: Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS: This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Thyroid autoimmunity and pregnancy in euthyroid women.

Women with thyroid autoimmunity (TAI), predominately characterized by increased levels of thyroid peroxidase antibody (TPOAb), are at risk for developing pregnancy related complications. In this review, we discuss the importance of TAI during natal and perinatal stages. Before pregnancy, TAI is associated with higher mean serum TSH levels and certain causes of subfertility. During pregnancy, TAI increases the risk of an insufficient response of the thyroid to an increasing strain induced by pregnancy, and consequently (subclinical) hypothyroidism might develop. Euthyroid women with TAI have a higher rate of maternal and foetal complications, but it seems that causality cannot be pinned down to thyroid dysfunction alone. Almost half of the women known with TAI prior to pregnancy will also develop post-partum thyroiditis (PPT). However, any relation between PPT and post-partum depression remains uncertain. More research is required to explain possible associations between TAI and pregnancy morbidities, and studies should focus on a better understanding of TAI as such. Given the many unanswered questions, at present, it is not recommended to screen all (potentially) pregnant women for the presence of TAI.

Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis.

Hyperthyroidism is a common condition with a global prevalence of 0·2-1·3%. When clinical suspicion of hyperthyroidism arises, it should be confirmed by biochemical tests (eg, low TSH, high free thyroxine [FT4], or high free tri-iodothyonine [FT3]). If hyperthyroidism is confirmed by biochemical tests, a nosological diagnosis should be done to find out which disease is causing the hyperthyroidism. Helpful tools are TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy. Hyperthyroidism is mostly caused by Graves' hyperthyroidism (70%) or toxic nodular goitre (16%). Hyperthyroidism can also be caused by subacute granulomatous thyroiditis (3%) and drugs (9%) such as amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors. Disease-specific recommendations are given. Currently, Graves' hyperthyroidism is preferably treated with antithyroid drugs. However, recurrence of hyperthyroidism after a 12-18 month course of antithyroid drugs occurs in approximately 50% of patients. Being younger than 40 years, having FT4 concentrations that are 40 pmol/L or higher, having TSH-binding inhibitory immunoglobulins that are higher than 6 U/L, and having a goitre size that is equivalent to or larger than WHO grade 2 before the start of treatment with antithyroid drugs increase risk of recurrence. Long-term treatment with antithyroid drugs (ie, 5-10 years of treatment) is feasible and associated with fewer recurrences (15%) than short-term treatment (ie, 12-18 months of treatment). Toxic nodular goitre is mostly treated with radioiodine (131I) or thyroidectomy and is rarely treated with radiofrequency ablation. Destructive thyrotoxicosis is usually mild and transient, requiring steroids only in severe cases. Specific attention is given to patients with hyperthyroidism who are pregnant, have COVID-19, or have other complications (eg, atrial fibrillation, thyrotoxic periodic paralysis, and thyroid storm). Hyperthyroidism is associated with increased mortality. Prognosis might be improved by rapid and sustained control of hyperthyroidism. Innovative new treatments are expected for Graves' disease, by targeting B cells or TSH receptors.

An Exceptional Cause of Increased 18F-Fluorodeoxyglucose Uptake on PET/CT in a Thyroid Nodule.

A 41-year-old female underwent a cervical spine CT for the workup of posterior neck pain irradiating to the shoulders for several months. An incidental thyroid nodule was found and classified as Bethesda III on the Fine-needle aspiration cytology (FNAC) results. Three months later, the patient developed mild shortness of breath, dry cough, and fever. Chest X-ray revealed a mild enlargement in the bilateral hilar regions. CT showed mediastinal and bilateral hilar enlarged lymph nodes and pulmonary micronodules. The workup was further completed with a 18F-FDG PET/CT, showing intense FDG uptake in the mediastinal and bilateral hilar lymph nodes and increased uptake in the thyroid nodule. Endobronchial Ultrasound-guided Transbronchial needle aspiration (EBUS-TBNA) of a left hilar lymph node showed epithelioid non-necrotizing granulomas. Because of the FNAC results, size of the nodule and tracheal shift, thyroid lobectomy was performed one month later. Histopathological results also revealed multiple non-necrotizing epithelioid granulomas, suggesting systemic sarcoidosis with involvement of the thyroid. To our knowledge, this is the first report of thyroid sarcoidosis detected on 18F-FDG PET/CT. Although an increased FDG uptake in a thyroid nodule is usually suggestive of thyroid malignancy, toxic nodule, or follicular hyperplasia, our case report shows that it could also suggest thyroid sarcoidosis.

Ovarian stimulation does not induce thyrotropin receptor autoantibodies in women with thyroid autoimmunity.

Women of subfertile couples with thyroid autoimmunity (TAI) have an increased risk of miscarriage when pregnant after an assisted reproductive technology (ART) treatment. This might amongst others be due to the presence of thyrotropin receptor antibodies (TSH-R-Ab) that can impede the development of the corpus luteum. TSH-R-Ab can be present in women with TAI and/or be induced by the ovarian stimulation procedure (OS) that is performed to initiate the ART. In this prospective pilot study, we determined the presence of both binding and functional TSH-R-Ab (stimulating or blocking) with five different assays before and after OS in ten women (eleven cycles) with TAI of subfertile couples and in one woman without TAI. Mean (SD) age was 38.8 (±3.2) years, median (range) cumulative OS dose 1413 (613-2925) IU/L. Median baseline serum levels of thyrotropin, free thyroxine, and thyro-peroxidase antibodies were 2.33 (2.23-2.61) mIU/L, 16.8 (14.4-18.5) pmol/L and 152 (86-326) kIU/L, respectively. Oestradiol levels increased during OS from 40 (26-56) ng/L to 963 (383-5095) ng/L; P < .01. TSH-R-Ab measurements in all subject samples were below the cut-off of the corresponding immunoassay and four bioassays before or after OS.

Gestation-suppressed serum TSH levels during early pregnancy are not associated with altered maternal and neonatal outcomes.

Objective: The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes. Methods: In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.4 weeks of pregnancy for TSH, free T4 (FT4) and TPOAb. Exclusion criteria were twin- and assisted- reproduction pregnancies, women with TSH levels >3.74 mIU/L, severe hyperthyroidism, treated for thyroid dysfunction before or after screening and gestational blood sampling <6 or >16 weeks of pregnancy. The prevalence of adverse pregnancy outcomes was compared between the study group sTSH (TSH: < 0.06 mIU/L; n = 36) and euthyroid controls (TSH: 0.06-3.74 mIU/L; n = 1045), and the impact of sTSH on pregnancy outcomes verified in logistic regression analyses. Results: Median (IQR) serum TSH level in women with sTSH was 0.03 (0.03-0.03) vs 1.25 (0.81-1.82) mIU/L in controls and FT4 levels 18.0 (14.4-20.3) vs 14.2 (12.9-15.4) pmol/L; both P < 0.001. None of the women with sTSH had thyrotropin receptor antibodies. Compared with controls, the prevalence of TPOAb positivity (TAI) was comparable between groups (5.6% vs 6.6%; P = 0.803). The prevalence of maternal and neonatal pregnancy outcomes was comparable between the study and control group. The logistic regression analyses with corrections for TAI, FT4 and demographic parameters confirmed the absence of an association between sTSH, and the following outcomes: iron deficient anaemia (aORs (95% CI)): 1.41 (0.64-2.99); P = 0.385, gestational diabetes: 1.19 (0.44-2.88); P = 0.713, preterm birth: 1.57 (0.23-6.22);P = 0.574 and low Apgar-1' score: 0.71 (0.11-2.67); P = 0.657. Conclusions: Suppressed serum TSH levels during the first to early second trimester of pregnancy were not associated with altered maternal or neonatal outcomes.

Impact of thyroid hormone treatment on maternal pregnancy outcomes in women with subclinical hypothyroidism without TPOAb: a retrospective cross-sectional study.

BACKGROUND: Evidence on the impact of thyroid hormone treatment (LT4) on maternal pregnancy outcomes in women with subclinical hypothyroidism (SCH) without thyroid peroxidase antibodies (TPOAb) positivity is scarce. METHODS: Single centre, cross-sectional study in 1460 women screened for TSH, free T4 and TPOAb at median 13 (11-17) weeks of gestation during the period 2013-2014. Exclusion criteria were twin- and assisted reproduction pregnancies, TPO positivity, overt thyroid dysfunction, and treatment with LT4 before screening. The impact of LT4 on maternal pregnancy outcomes was investigated in a group of 53 women with SCH (TSH > 3.74 mIU/L) in which LT4 was initiated at median 13 (10-22) weeks (treated group). The control group included 18 women with SCH (TSH > 3.74 mIU/L). The prevalence of pregnancy complications in these two groups was compared with that in a euthyroid reference (REF) group of 1389 women (TSH ≤ 3.74 mIU/L). RESULTS: The prevalence of pre-eclampsia and gestational diabetes (GDM) was higher in the control group vs the REF group (16.7% vs 5.0% and 27.8% vs 18.9%; p = 0.017 and p = 0.016, respectively), but comparable in the treated group vs the REF group (7.6% vs 5.0% and 22.6% vs 18.9%; p = 0.918 and 0.676, respectively). The prevalence of iron-deficiency anaemia was lower in the treated vs the REF group (17.0% vs 32.5%; p = 0.017). CONCLUSION: Pregnant women with untreated SCH and without TPOAb positivity had a higher prevalence of pre-eclampsia and GDM compared with euthyroid women, while this was not the case in women with treated SCH, even when it was initiated after the first trimester.