Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations.

BACKGROUND: Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. OBJECTIVES: We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. METHODS: We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). RESULTS: Median (IQR) micronutrient concentrations were 112 µg/L (80-156 µg/L) for UIC, 67 µg/L (58-76 µg/L) for plasma selenium, and 973 µg/L (842-1127 µg/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 µg/L and 70 µg/L, respectively). Mean ± SD TSH concentration was 1.7 ± 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 µg/L also with fT4 and fT3. Selenium was inversely associated with fT3, and <85 µg/L with tT3. CONCLUSIONS: Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.

Pre- and postoperative 68 Ga-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours.

OBJECTIVES: Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with 68 Ga-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, 68 Ga-DOTATOC, in patients with hormone-producing PitNETs before and after surgery. DESIGN/METHODS: This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre- and postoperatively with 68 Ga-DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax ) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression. RESULTS: Thyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4-60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6-9.3) than normal pituitary gland (SUVmax 13.8; 12.1-15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6-19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P < .01)). In the postoperative evaluation, PET was able to correlate tracer uptake with biochemical cure and noncure in patients with an abnormal postoperative magnetic resonance image and a preoperative tumour uptake SUVmax  > 13.8. CONCLUSIONS: 68 Ga-DOTATOC PET can be used to detect thyrotroph tumours in the pre- and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited.

A randomized, double-blind study of iodine supplementation during pregnancy in Sweden: pilot evaluation of maternal iodine status and thyroid function.

PURPOSE: Pregnant women in Sweden are mildly iodine deficient. We investigated the effect of daily iodine supplementation on the iodine and thyroid status of pregnant women. METHODS: In this pilot, randomized, double-blind trial, 200 thyroid-healthy pregnant women were recruited at mean (standard deviation) pregnancy week 8.85 (1.62) and assigned (1:1) to daily intake of a multivitamin tablet with or without 150 µg of iodine. Urine and serum samples were collected at baseline and once during the second and third trimesters. Urinary iodine concentration (UIC), serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOabs) were analyzed. Neonatal TSH data were collected. UIC and Tg were also analyzed in a group of 89 thyroid-healthy non-pregnant women of reproductive age (WRA). RESULTS: At baseline, the intervention and the control groups had similar median UIC (interquartile range (IQR)): 110 µg/L (74-119) and 111 µg/L (66-168), respectively. The intervention group reached iodine sufficiency with median UIC (IQR) 139 µg/L (89-234) and 136 µg/L (91-211) in the second and third trimester, respectively, without significant difference from the lower limit of the recommended range, i.e. 150-250 µg/L (p = 0.42 and p = 0.87, respectively). The intervention group had higher median UIC and lower median Tg compared to the control group during the second (p < 0.001 and p = 0.019, respectively) and third trimester (p < 0.001 and p = 0.003, respectively), whereas thyroid hormones, serum TPOabs, and neonatal TSH were similar. The WRA group presented median UIC (IQR) 65 µg/L (30-98) and median Tg (IQR) 18 µg/L (13-27). CONCLUSION: A daily supplement containing 150 µg of iodine to a group of pregnant women with mild iodine deficiency improved the iodine status from mild ID to iodine sufficiency. This improvement seems to have had a positive impact on maternal thyroglobulin. This study is now under extension to investigate the children's neuropsychological development. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02378246, May 3, 2015, retrospectively registered.

Inadequate iodine intake in lactating women in Sweden: A pilot 1-year, prospective, observational study.

INTRODUCTION: Breastfed infants depend on breast-milk iodine for growth and brain development, as iodine is a trace element important for thyroid hormone production. Iodine need is higher during lactation; hence, mothers and children are at risk of iodine deficiency. We aimed to explore maternal iodine and thyroidal status during lactation. MATERIAL AND METHODS: Pregnant women were recruited in Gothenburg, southwest Sweden. Maternal urine and serum were collected at pregnancy week 35-37 (n = 84) and 0.5, 4, and 12 months postpartum. Seventy mothers provided breast milk at 0.5 months. RESULTS: Median (interquartile range) breast-milk iodine concentration was 90 (66-116) µg/L. About 58% had breast-milk iodine concentration <100 µg/L. Iodine supplement users (n = 13) had higher breast-milk iodine concentration than non-users (n = 49) (140 µg/L vs 71 µg/L, P = .001). Exclusively breastfeeding women at 4 months postpartum (n = 57) had lower median urinary iodine concentration (85 µg/L vs 133 µg/L, P = .004) and higher thyroglobulin serum concentration (22.3 µg/L vs 11.8 µg/L, P = .032) than non-exclusively breastfeeding women (n = 25). Concentrations of thyroid hormones were unaffected. CONCLUSIONS: This pilot study suggests that lactating women in southwest Sweden present mildly inadequate iodine intake, mainly among non-iodine supplement users and exclusively breastfeeding mothers. Studies on the coverage of the iodine fortification program in breastfeeding women are warranted.

Lower 68 Ga-DOTATOC uptake in nonfunctioning pituitary neuroendocrine tumours compared to normal pituitary gland-A proof-of-concept study.

OBJECTIVES: 68  Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of 68  Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of 68  Ga-DOTATOC PET in the most common PitNET, ie non-functioning (NF)-PitNET. DESIGN/PATIENTS: NF-PitNET patients (n = 9) and controls (n = 13) were examined preoperatively with 68  Ga-DOTATOC PET for 45 min after tracer injection in dynamic list mode. Tumor specimens were collected during surgery in patients. MRI and PET images were co-registered using PMOD software. The maximum standard uptake value (SUVmax ) was analyzed in manually outlined regions of interest (ROI) around the tumor in patients and around the pituitary gland in controls. Immunohistochemical analyses were conducted on tumor specimens for assessment of tumor cell type and SSTR expression. RESULTS: Median SUVmax (IQR) was lower in patients than in controls (3.9 [3.4-8.5] vs 14.1 [12.5-15.9]; P < .01]. In ROC analysis, the area under the curve was 0.87 (P < .01) for SUVmax , with 78% sensitivity and 92% specificity. Immunohistochemical analysis showed NF-PitNETs were of gonadotroph (n = 7) and corticotroph (n = 2) origin. SSTR expression was high for SSTR3, low-to-moderate for SSTR2, and low for SSTR1 and SSTR5. CONCLUSIONS: This proof-of-concept study shows that 68 Ga-DOTATOC PET can be used to differentiate between normal pituitary tissue and NF-PitNET.

Correlations of water iodine concentration to earlier goitre frequency in Sweden-an iodine sufficient country with long-term iodination of table salt.

BACKGROUND: Before iodination of Swedish table salt in 1936, iodine deficiency resulting in goitre and hypothyroidism was common. Sweden has become iodine sufficient, as shown in a national survey in 2007, proving its iodination fortification programme effective for the general population. The objective of this study was to collect drinking water from water treatment plants nationally and test if water iodine concentration (WIC) correlated to urinary iodine concentration (UIC) of school-aged children in a national survey 2007 to former goitre frequency in 1929 and to thyroid volume data in 2007. METHODS: In 2012, 166 treatment plants, located in 57% (166 of 290) of all Swedish municipalities, were asked to collect drinking water samples of approximately 10 ml. In 2007, tap water samples of the same volume were collected from 30 randomly selected schools for the national survey. Analysis of WIC was done in both treatment plants in 2012 (n = 166) and tap water in 2007 (n = 30). The correlation of WIC to the children's UIC and thyroid volume after iodination was tested based on data from the national survey in 2007. The association of WIC to former goitre frequency was tested based on pre-iodination data, derived from a map of goitre frequency drawn in 1929. RESULTS: The median WIC from water treatment plants was 4.0 µg/L (range 0-27 µg/L). WIC was similar in coastal and inland areas, for both ground and surface water. WIC correlated with historical goitre areas and was lower in the goitre areas than in non-goitre areas (p < 0.001). WIC in the same municipalities as the schools correlated with the UIC of children (p < 0.01), but not with their thyroid volume. CONCLUSIONS: WIC still contributes to iodine nutrition in Sweden, but iodination overrides the goitre effect.

[Patient needs at the heart of the national hyperthyroidism guideline]. / Patientens behov i fokus i vårdprogram för hypertyreos.

Hyperthyroidism is a common disease that primarily affects women of all ages, and in addition to physical symptoms, mental symptoms are common, such as mental fatigue, anxiety, difficulty concentrating and mood changes. A common opinion is that the patient is recovered once the thyroid disorder is treated. However, many patients will experience persistent brain fatigue and mental problems, even after normal thyroid function is restored. Patients want to live as good a life as possible despite their illness, and in healthcare, they request interventions for rehabilitation. A new guideline for hyperthyroidism was launched in January 2023 that highlights many of these aspects, including the mental symptoms and the patient's perspective on hyperthyroidism. In this article, we want to address the patient's needs and how we can meet them in healthcare to increase their participation, confidence and quality of life, with continuity throughout the entire care process.

[Hyperthyroidism - a classic disease]. / Hypertyreos är inte bara endokrinologens angelägenhet.

Hyperthyroidism presents with various forms of generalized symptoms. Primary care physicians as well as other specialists should have this in mind when meeting patients with symptoms such as palpitations, sweating, fatigue and weight loss. Thyroid-stimulating hormone (TSH) is a highly specific test and useful in ruling out hyperthyroidism. The severity of the disease determines the pace of management. Primary care is often involved in detection of hyperthyroidism but also takes part in the work of rehabilitation and the lifelong hormonal substitution that is necessary for 2/3 of all patients. Subclinical hyperthyroidism, characterized by low TSH levels but normal levels of T4 and T3, is associated with increased mortality by 24 percent and risks of cardiovascular disease, atrial fibrillation and osteoporosis. Treatment depends on age, presence of comorbidity and TSH-levels. In addition to specific endocrinological treatment, person-centered care is crucial during active disease and rehabilitation. The first Swedish care program for hyperthyroidism aims to enhance care efficiency and equity.

[Treatment of Graves' disease is moving towards precision medicine]. / Behandling av Graves sjukdom.

This is the first national guideline in hyperthyroidism to harmonise and update clinical practice according to what is evidence based and direct care from patients' needs. We present 4 articles in Läkartidningen of different views of the guideline, including family care perspectives, patient care perspectives and perspectives on ophthalmology. This article concerns treatment of Graves' disease and includes endocrinological, surgical and oncological perspectives on what is established practice, but also news in the national guideline that remain to be fully implemented in Sweden in the years to come. News are precision medicine using the GREAT score, preoperative calcium/D vitamin treatment, individualized levothyroxine treatment after thyroid surgery, uniformed levothyroxine replacement strategy, access to national patient information and national guidelines on radiation protection and treatment schemes for radioactive iodine. A national guideline is the creation of many persons' views, including patient representatives, and the recommendations have undergone a thorough national review process from stakeholders. It is a guideline with future perspectives for an improved care.

[Four perspectives on Graves' orbitopathy - from the point of view of the patient, general practitioner, endocrinologist, and ophthalmologist]. / Endokrin oftalmopati ur fyra olika perspektiv.

Graves' orbitopathy is a common complication of Graves' disease. The mild form dominates, whereas moderate to severe and sight threatening forms are rarer. They require quick, adequate care, involving cooperation between county hospitals and the regional hospital, and adequate diagnostics and choice of treatments of treatments. A new national guideline for hyperthyroidism has been published in Sweden in January 2023, where these aspects are highlighted. The present guideline requires implementation regionally, as all components are not in place, but reflects the needs of patients. This article highlights important aspects for patients such as information, to be listened to, accessibility and adequate care, but also defines actions necessary in primary care where patients most often seek help at first. Lastly, important medical and practical aspects are reviewed by the endocrinologist and the ophthalmologist.

The relationship between mental fatigue, depression, and cognition in Graves' disease.

Objective: Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves' disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism. Methods: A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment. Results: During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies. Conclusion: Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.

Patient needs and care: moves toward person-centered care for Graves' disease in Sweden.

Patients with Graves' disease (GD) not only need appropriate medical care, but they also need to be cared for. The aim of this review is to examine the literature on GD patient needs, expectations, perceptions, and quality of life. We will also present methods for patient care, define gaps in knowledge, and suggest factors that can be introduced into the regular care of GD patients. Patient information, teamwork with thyroid/contact nurses, education of personnel and patients, quality of life measurements, and the formation of a rehabilitation program have enough evidence to be implemented into regular care. However, visualizing patient needs through person-centered care requires further evaluation in GD patients before being implemented in routine care. We conclude that considerable improvement in nursing can be achieved in relation to GD.

Fracture Incidence in Graves' Disease: A Population-Based Study.

Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR = 2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.

The metabolic consequences of thyroxine replacement in adult hypopituitary patients.

The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2 years of GH replacement. CH patients (CH, n = 1080) were compared with TSH sufficient patients (TSHsuff n = 515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤ 1.18 µg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥ 1.58 µg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1 µg/kg/day increase of thyroxine dose, body weight decreased 1.0 kg, BMI 0.3 kg/m(2), and WC 0.65 cm. The GH sensitivity of the CH group was higher (0.76 ± 0.56 SDS/mg GH) than that of TSHsuff patients (0.58 ± 0.64 SDS/mg GH), P < 0.001. The middle thyroxine dose (1.19-1.57 µg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125 µg thyroxine/day for hypopituitary patients of 50, 70 or 90 kg weight, respectively.

A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease.

CONTEXT: Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. OBJECTIVE: This work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes. METHODS: Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4 ±â€…4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. RESULTS: Patients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3'-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes. CONCLUSION: Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.

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 (131I). This preference for ATD is in line with most countries/regions, with the exception of USA and the Middle East/North Africa, where 131I 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 131I 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.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism.

Background: The treatment efficacy of antithyroid drug (ATD) therapy, radioactive iodine (131I), or surgery for Graves' hyperthyroidism is well described. However, there are a few reports on the long-term total outcome of each treatment modality regarding how many require levothyroxine supplementation, the need of thyroid ablation, or the individual patient's estimation of their recovery. Methods: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003 and 2005 (n = 2430). The patients were invited to participate in a longitudinal study spanning 8 ± 0.9 years (mean ± standard deviation) after diagnosis. We were able to follow 1186 (60%) patients who had been treated with ATD, 131I, or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities, and lifestyle factors through questionnaires and a review of the individual's medical history records. Results: At follow-up, the remission rate after first-line treatment choice with ATD was 45.3% (351/774), with 131I therapy 81.5% (324/264), and with surgery 96.3% (52/54). Among those patients who had a second course of ATD, 29.4% achieved remission (vs. the 45.3% after the first course of ATD). The total number of patients who had undergone ablative treatment was 64.3% (763/1186), of whom 23% (278/1186) had received surgery, 43% (505/1186) had received 131I therapy, including 2% (20/1186) who had received both surgery and 131I. Patients who received ATD as first-line treatment and possibly additional ATD had 49.7% risk (385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23% (81/351) of the initially ATD treated in remission, in 77.3% (204/264) of the 131I treated, and in 96.2% (50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7% (423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was 25.3%. Conclusion: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3% chance of ultimately avoiding ablative treatment and only a 40% chance of eventually being euthyroid without thyroid medication. Surprisingly, 1 in 4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus, has unexpected long-term consequences for many patients.

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.