Objective
Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, ...the sex‐, age‐ and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors. Therefore, we aimed to examine how the association between incident hyperthyroidism and AF was affected by IF increasing the population iodine intake from moderate‐mild iodine deficiency to low adequacy.
Design, Patients and Measurements
Incident hyperthyroid patients were included at the date of first inpatient or outpatient diagnosis, and AF diagnoses within 3 months before to 6 months after the index date were identified in Danish nationwide registers, 1997–2018. The relative risk (RR) of AF each calendar year (reference: 1997; IF introduced: 2000) was analyzed in Poisson regression models adjusted for age, sex, educational level, geographic region, and comorbidities.
Results
Overall, in 62,201 patients with incident hyperthyroidism 7.9% were diagnosed with AF. There was a minor nonsignificantly increased risk of AF during the first years after IF followed by a gradual decrease to RR 0.76 (0.62–0.94) in 2017. There were no statistically significant differences in the development in the risk of AF by sex, age group, or geographic region.
Conclusions
Results indicate that IF may reduce the risk of concomitant AF in hyperthyroid patients. If these results are confirmed, IF may not only reduce the population incidence of hyperthyroidism but also reduce the burden of morbidity in the remaining hyperthyroid patients.
Iodine intake affects the occurrence of thyroid disorders. However, the association of iodine intake with longevity remains to be described. This led us to perform a 20 years’ follow-up on ...participants from the Randers–Skagen (RaSk) study. Residents in Randers born in 1920 (n 210) and Skagen born in 1918–1923 (n 218) were included in a clinical study in 1997–1998. Mean iodine content in drinking water was 2 µg/l in Randers and 139 µg/l in Skagen. We collected baseline data through questionnaires, performed physical examinations and measured iodine concentrations in spot urine samples. Income data were retrieved from Danish registries. We performed follow-up on mortality until 31 December 2017 using Danish registries. Complete follow-up data were available on 428 out of 430 of participants (99·5 %). At baseline, the median urinary iodine concentration was 55 µg/l in Randers and 160 µg/l in Skagen residents. Participants were long-term residents with 72·8 and 92·7 % residing for more than 25 years in Randers and Skagen, respectively. Cox regression showed that living in Skagen compared with Randers was associated with a lower hazard ratio (HR) of death in both age- and sex-adjusted analyses (HR 0·60, 95 % CI 0·41, 0·87, P = 0·006), but also after adjustment for age, sex, number of drugs, Charlson co-morbidity index, smoking, alcohol and income (HR 0·60, 95 % CI 0·41, 0·87, P = 0·008). Residing in iodine-replete Skagen was associated with increased longevity. This indicates that long-term residency in an iodine-replete environment may be associated with increased longevity compared with residency in an iodine-deficient environment.
Summary
Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common can often be demonstrated in serum. The effect of ...public iodization programmes on antibody prevalence is uncertain.
Aim To measure the concentrations of thyroid autoantibodies in the Danish population before and after mandatory iodization of salt.
Methods Two identical cross‐sectional population studies were performed before (Cohort 1 (C1), year 1997–1998, n = 4649, median urinary iodine 61 μg/l) and 4–5 years after (Cohort 2 (C2), year 2004–2005, n = 3570, median urinary iodine 101 μg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO‐Ab and Tg‐Ab using sensitive assays.
Results Antibodies were more frequent in C2 than in C1: TPO‐Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg‐Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO‐Ab: OR (95% CI): 1·80 (1·59–2·04) and Tg‐Ab: 1·49 (1·31–1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies.
Conclusion The prevalence of both TPO‐Ab and Tg‐Ab was higher 4–5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long‐term effects of increased iodine intake on thyroid autoimmunity in the population.
Summary
Thyroid hormones are important regulators of foetal development, and in recent years, there has been much focus on the screening and treatment of pregnant women for even small aberrations in ...thyroid function tests. We searched PubMed for publications on thyroid function and pregnancy outcomes including child cognition, and included references from the retrieved articles. Both small aberrations in thyroid function tests in early pregnancy and an increase in risk of pregnancy complications may be caused by a functional change in the uteroplacental unit. Thus, the association found in several studies between small thyroid test abnormalities and pregnancy complications may be due to confounding, and thyroid hormone therapy will have no effect. On the other hand, screening of thyroid function in early pregnancy may identify 200–300 women with undiagnosed overt hypothyroidism per 100 000 pregnancies, which is at least five times more than the number of hypothyroid newborns identified by screening. A number of studies indicate that untreated overt thyroid disease in pregnancy may lead to complications. The potential benefit of screening and early therapy is supported by evidence, indicating that even severe maternal hypothyroidism does not lead to neurocognitive deficiencies in the child, if the condition is detected and treated during the first half of pregnancy. Screening and therapy for overt thyroid dysfunction in early pregnancy may be indicated, rather than focusing on identifying and treating small aberrations in thyroid function tests.
Summary Background & aims Iodine fortification is widespread. Systematic monitoring of iodine fortification programs should be carried out to secure an optimal fortification level. Our aim was to ...investigate the effectiveness of the Danish iodine fortification program by comparing iodine excretion at baseline and at 11-year follow-up, and to study determinants for any change in iodine intake including dietary habits, education, life style factors and health parameters. Methods A follow-up study based on the Danish DanThyr cohort examined in 1997–1998 just before iodine fortification was introduced, and reexamined in 2008–2010. In total, 2465 (59.1%) adult participants were reexamined. Results Median (IQR) iodine concentration in urine had increased by 19 (−25–68) μg/L to 83 (47–133) μg/L. Estimated 24-h iodine excretion had increased by 36 (−21–95) μg/24-h to 134 (93–206), and calculated total iodine intake (diet plus supplements) had increased by 16 (−18–48) μg/day. Iodine excretion had increased significantly in all age and gender groups, but was still below the recommended amount at follow-up. The increase in iodine excretion was positively associated with changes in milk intake, with changes in the use of iodine supplements, and with bread intake at follow-up. Salt intake, education, self-rated health, smoking, alcohol intake and physical activity were not associated with the increase in iodine excretion. Conclusions The strategy to combat iodine deficiency in Denmark seems to be working because the fortification led to increased urinary iodine excretion in (almost) all participants. However, the level of iodine fortification of salt is too low.
Iodine deficiency is still common in some European countries. In Denmark an iodine fortification programme was introduced in 1998 and a monitoring programme was established prior to iodization. This ...study reports the change in urinary iodine excretion caused by fortification and investigates determinants of iodine intake after fortification. Iodine excretion in casual urine samples was assessed in 4649 subjects in 1997–8 and in 3570 comparable subjects in 2004–5 in women 18–22, 25–30, 40–45 and 60–65 years of age and in men 60–65 years of age living in Aalborg (western part of Denmark) or Copenhagen (eastern part of Denmark). These areas had moderate and mild iodine deficiency, respectively, before iodine fortification. All subjects filled in a FFQ and a questionnaire regarding lifestyle factors. Iodine excretion, expressed as the estimated 24 h urinary iodine excretion and as urinary iodine concentration, increased significantly in all age and sex groups. However, the iodine intake was still below the recommended in the youngest age groups in both cities and in women 40–45 years of age living in Aalborg. Intake of milk and salt had strong significant direct associations with iodine excretion (P < 0·001). It is concluded that although the median iodine intake in the whole study population is at the recommended level, some groups still have an intake below the recommended. It is important to have a moderate milk intake to obtain a sufficient iodine intake in Denmark.
To investigate the association between serum TSH, total T4 and various patient characteristics when hypothyroidism is diagnosed in a population, and to study how age, sex and serum T4 levels ...influenced pituitary TSH response.
A computer-based register linked to laboratory databases prospectively identified all patients with new, biochemically overt hypothyroidism (n = 685) in an open cohort in Denmark. The diagnosis was verified in each patient, and disease was classified into nosological type. Serum TSH and total T4 were recorded at the time of diagnosis in untreated patients with spontaneous autoimmune hypothyroidism (n = 578).
In untreated primary, spontaneous autoimmune hypothyroidism, we observed a four fold difference in average serum TSH levels between the youngest (0-20 years: TSH = 100 mU/l) and the oldest (80+ years: TSH = 24.4 mU/l) group of patients. No age dependent variation was observed in serum total T4. Log TSH showed an inverse linear correlation with age. An inverse linear correlation was present between log TSH and total T4 in both young and old patients, but for all total T4 values we observed lower median serum TSH values in elderly patients.
For the same degree of thyroid failure, the serum TSH is lower among the elderly. This is most likely caused by a decrease in the hypothalamic/pituitary response to low serum T4. A certain increase in serum TSH may indicate more severe hypothyroidism in an old than in a young patient, and longer time may be needed after thyroid hormone withdrawal before elderly patients with thyroid cancer reach sufficiently high TSH values to allow for an effective radio-iodine treatment.
Some degree of hypothyroidism is common in the elderly. It affects 5-20% of women and 3-8% of men. The occurrence varies with genetics with a high prevalence in Caucasians, and the disease is more ...common in populations with a high iodine intake. The common causes of hypothyroidism are autoimmune destruction of the thyroid gland and previous thyroid surgery or radioiodine therapy. Various types of medication, including amiodarone, cytokines and lithium, often induce hypothyroidism. Symptoms may be atypical and measurement of serum thyroid-stimulating hormone (TSH) levels should be part of biochemical testing for undiagnosed medical conditions in elderly subjects. The finding of an elevated serum TSH level should be confirmed by repeated testing and supplemented with measurements of serum levels of thyroxine (T(4)) and thyroid peroxidase antibodies to verify, quantify and subclassify the abnormality. The recommended and appropriate replacement therapy for hypothyroidism is levothyroxine sodium. The initial replacement dose should be low if heart disease is suspected. Because of the long half-life of levothyroxine sodium small dosage adjustments may be performed by adding or withdrawing a tablet once or twice weekly. Levothyroxine sodium is only partly absorbed after oral ingestion, and food, minerals, drugs and tablet composition influence absorption. Studies performed a few years ago suggested that a combination of levothyroxine sodium and liothyronine may improve clinical results, but recent more comprehensive studies have not supported this hypothesis. Accordingly, liothyronine replacement is not documented to be of benefit. If liothyronine is added to replacement, the liothyronine dose should be kept low, within the physiological range and, preferably be administered twice daily. Thyroid hormone therapy has no beneficial effect above placebo in elderly individuals with normal serum TSH levels and T(4) levels. The major risk of levothyroxine sodium therapy is over-replacement, with anxiety, muscle wasting, osteoporosis and atrial fibrillation as adverse effects. Subclinical hypothyroidism with elevated serum TSH levels but T(4) levels within the laboratory reference range is a mild variant of overt hypothyroidism. Patients with subclinical hypothyroidism should be informed about the disease and offered the possibility of replacement. Only some patients treated for subclinical hypothyroidism will feel better after therapy. In elderly patients on replacement therapy, care should include estimation of serum TSH level once or twice a year, with small dosage adjustments of levothyroxine sodium to keep serum TSH level within the normal range.
Elucidating the neurobiological effects of sleep and waking remains an important goal of the neurosciences. Recently, animal studies indicated that sleep is important for cell membrane and myelin ...maintenance in the brain and that these structures are particularly susceptible to insufficient sleep. Here, we tested the hypothesis that a day of waking and sleep deprivation would be associated with changes in diffusion tensor imaging (DTI) indices of white matter microstructure sensitive to axonal membrane and myelin alterations.
Twenty-one healthy adult males underwent DTI in the morning 7:30AM; time point (TP)1, after 14 hours of waking (TP2), and then after another 9 hours of waking (TP3). Whole brain voxel-wise analysis was performed with tract based spatial statistics.
A day of waking was associated with widespread increases in white matter fractional anisotropy, which were mainly driven by radial diffusivity reductions, and sleep deprivation was associated with widespread fractional anisotropy decreases, which were mainly explained by reductions in axial diffusivity. In addition, larger decreases in axial diffusivity after sleep deprivation were associated with greater sleepiness. All DTI changes remained significant after adjusting for hydration measures.
This is the first DTI study of sleep deprivation in humans. Although previous studies have observed localized changes in DTI indices of cerebral microstructure over the course of a few hours, further studies are needed to confirm widespread DTI changes within hours of waking and to clarify whether such changes in white matter microstructure serve as neurobiological substrates of sleepiness.
Elucidating the neurobiological effects of sleep and wake is an important goal of the neurosciences. Whether and how human cerebral blood flow (CBF) changes during the sleep-wake cycle remain to be ...clarified. Based on the synaptic homeostasis hypothesis of sleep and wake, we hypothesized that a day of wake and a night of sleep deprivation would be associated with gray matter resting CBF (rCBF) increases and that sleep would be associated with rCBF decreases. Thirty-eight healthy adult males (age 22.1 ± 2.5 years) underwent arterial spin labeling perfusion magnetic resonance imaging at three time points: in the morning after a regular night's sleep, the evening of the same day, and the next morning, either after total sleep deprivation (n = 19) or a night of sleep (n = 19). All analyses were adjusted for hematocrit and head motion. rCBF increased from morning to evening and decreased after a night of sleep. These effects were most prominent in bilateral hippocampus, amygdala, thalamus, and in the occipital and sensorimotor cortices. Group × time interaction analyses for evening versus next morning revealed significant interaction in bilateral lateral and medial occipital cortices and in bilateral insula, driven by rCBF increases in the sleep deprived individuals and decreases in the sleepers, respectively. Furthermore, group × time interaction analyses for first morning versus next morning showed significant effects in medial and lateral occipital cortices, in anterior cingulate gyrus, and in the insula, in both hemispheres. These effects were mainly driven by CBF increases from TP1 to TP3 in the sleep deprived individuals. There were no associations between the rCBF changes and sleep characteristics, vigilant attention, or subjective sleepiness that remained significant after adjustments for multiple analyses. Altogether, these results encourage future studies to clarify mechanisms underlying sleep-related rCBF changes.
•How cerebral blood flow changes during the sleep-wake cycle remains to be clarified.•We examined cerebral blood flow after wake, sleep, and sleep deprivation.•There were morning-to-evening increases in cerebral blood flow.•These changes were reversed by a night of sleep.•A night of sleep deprivation was associated with further cerebral blood flow increases.
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