Charlotte Cerqueira

Iodine intake as a determinant of thyroid disorders in populations

UNLABELLED Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations, hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison, the most serious association between disease and the level of iodine intake in a population. In less severe iodine deficiency, the normal thyroid gland is able to adapt and keep thyroid hormone production within the normal range. However, the prolonged thyroid hyperactivity associated with such adaptation leads to thyroid growth, and during follicular cell proliferation there is a tendency to mutations leading to multifocal autonomous growth and function. In populations with mild and moderate iodine deficiency, such multifocal autonomous thyroid function is a common cause of hyperthyroidism in elderly people, and the prevalence of thyroid enlargement and nodularity is high. The average serum TSH tends to decrease with age in such populations caused by the high frequency of autonomous thyroid hormone production. On the other hand, epidemiological studies have shown that hypothyroidism is more prevalent in populations with a high iodine intake. Probably, this is also a complication to thyroid adaptation to iodine intake. Many thyroid processes are inhibited when iodine intake becomes high, and the frequency of apoptosis of follicular cells becomes higher. Abnormal inhibition of thyroid function by high levels of iodine is especially common in people affected by thyroid autoimmunity (Hashimotos thyroiditis). In populations with high iodine intake, the average serum thyroid-stimulating hormone (TSH) tends to increase with age. This phenomenon is especially pronounced in Caucasian populations with a genetically determined high tendency to thyroid autoimmunity. A small tendency to higher serum TSH may be observed already when iodine intake is brought from mildly deficient to adequate, but there is at present no evidence that slightly elevated serum TSH in elderly people leads to an increase in morbidity and mortality. CONCLUSION Even minor differences in iodine intake between populations are associated with differences in the occurrence of thyroid disorders. Both iodine intake levels below and above the recommended interval are associated with an increase in the risk of disease in the population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher. Monitoring and adjusting of iodine intake in a population is an important part of preventive medicine.

Cohort Profile: The Health2006 cohort, Research Centre for Prevention and Health

Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, The Capital Region of Denmark, Denmark, National Allergy Research Centre, Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Denmark, Danish Research Centre for Chemical Sensitivities, Gentofte University Hospital, University of Copenhagen, Copenhagen, Denmark, Hagedorn Research Institute and Steno Diabetes Centre, Gentofte, Denmark, The Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark and Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

Predictors of Change in Serum TSH after Iodine Fortification: An 11-Year Follow-Up to the DanThyr Study

CONTEXT Few data are available on the effect of iodine fortification on thyroid function development in a population. OBJECTIVE Our objective was to evaluate changes in thyroid function after iodine fortification in a population and to identify predictors for changes in serum TSH. DESIGN AND SETTING A longitudinal population-based study of the DanThyr C1 cohort examined at baseline (1997-1998) and reexamined 11 yr later (2008-2010). The mandatory program for iodization of salt was initiated in 2000. PARTICIPANTS A total of 2203 individuals, with no previous thyroid disease, living in two areas with different levels of iodine intake, with measurement of TSH and participation in follow-up examination were included in the analysis. MAIN OUTCOME MEASURE Change in serum TSH was evaluated. RESULTS During the 11-yr follow-up, mean TSH increased significantly from 1.27 mU/liter [95% confidence interval (CI) = 1.23-1.30] to 1.38 mU/liter (CI = 1.34-1.43) (P < 0.001). The most pronounced increase was observed in the area with the highest iodine intake [1.30 mU/liter (CI = 1.25-1.35) to 1.49 mU/liter (CI = 1.43-1.55), P < 0.001], whereas the increase was not significant in the low-iodine-intake area [1.24 (CI = 1.19-1.29) to 1.28 (CI = 1.23-1.34), P = 0.06)]. Change in TSH was positively associated with the presence of thyroid peroxidase antibody at baseline (P < 0.001) and negatively associated with baseline thyroid enlargement (P < 0.001) and multiple nodules (P < 0.001). CONCLUSIONS Even small differences in the level of iodine intake between otherwise comparable populations are associated with considerable differences in TSH change at the 11-yr follow-up. Multinodular goiter predicted a less pronounced TSH increase during follow-up, which may be explained by iodine-dependent activity of autonomous nodules.

Association of Iodine Fortification with Incident Use of Antithyroid Medication—A Danish Nationwide Study

CONTEXT Iodine-induced hyperthyroidism has been reported in the early phases of almost all iodine fortification programs, depending on prior iodine intake in the population, the amount of fortification, and the rate of change. OBJECTIVE The aim of the study was to monitor the effect of the Danish iodine fortification program on incidence of hyperthyroidism as measured by the incident use of antithyroid medication. DESIGN We conducted a register study. Using the unique identification number of all Danes, we linked data from the Register of Medicinal Product Statistics and the Civil Registration register on an individual level. All dispensing of antithyroid medication from 1995 to 2007 was studied. The place of residency was used to divide patients into mildly and moderately iodine-deficient groups. MAIN OUTCOME MEASURE We measured the incident use of antithyroid medication. RESULTS In the region with moderate iodine deficiency, the number of incident users of antithyroid medication increased 46% in the first 4 yr of iodine fortification. The use increased the most among the youngest age group (younger than 40 yr) and the oldest age group (older than 75 yr). In the mildly iodine-deficient region, the number of incident users increased only 18%, and only in the youngest age groups (below 40 and 40-59 yr). After 4 yr of fortification, the incidence rates started to fall and reached baseline, for most groups, 6 yr after onset of fortification. CONCLUSIONS This study shows that iodine fortification induced a temporary, modest increase in the incidence of hyperthyroidism as measured by use of antithyroid medication. A new steady state has not yet evolved.

Estimating salt intake in a Caucasian population: can spot urine substitute 24-hour urine samples?

Background A simple and valid alternative for 24-hour urine collection to estimate populational 24-hour urinary sodium excretion would be desirable for monitoring sodium intake in populations. Aim To assess the validity of the predicted 24-hour urinary sodium excretion using spot urine and two different prediction methods in a Danish population. Methods Overall, 473 Danish individuals provided a para-aminobenzoic acid-validated complete 24-hour urine collection and a spot urine sample. Data were collected in the DanThyr study (248 women aged 25–30 years and 60–65 years) and the Inter99 study (102 men and 113 women aged 30–60 years), respectively. The measured 24-hour urine sodium excretion was compared with the predicted 24-hour sodium excretion from a causal urine specimen, using both the Tanaka prediction method and a prediction model developed in a Danish population. Results The measured 24-hour sodium excretion (median, 5th to 95th percentile) was men 195 (110 to 360) and women 139 (61 to 258), whereas the predicted 24-hour sodium excretion for the Tanaka model was men 171 (117 to 222) and women 153 (92 to 228) and for the Danish model was men 207 (146 to 258); women 134 (103 to 163). The Spearman correlation between predicted and measured 24-hour sodium excretion was 0.39 and 0.49 for the Tanaka and the Danish model, respectively. For both prediction models, the proportion of individuals classified in the same or adjacent quintile was 74% for men and 64% for women. Conclusions Both prediction models gave a reasonable classification of individuals according to their sodium excretion. However, the median daily sodium intake was estimated more precisely by the Danish model, especially among men.

Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?

Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995–2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9–162.9). When stratified by sex and age-group (00–39, 40–64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

The Danish Adult Diabetes Registry

Aim of the database The aim of the Danish Adult Diabetes Registry (DADR) is to provide data from both the primary health care sector (general practice [GP]) and the secondary sector (specialized outpatient clinics) to assess the quality of treatment given to patients with diabetes. The indicators represent process and outcome indicators selected from the literature. Study population The total diabetes population in Denmark is estimated to be ~300,000 adult diabetes patients. Approximately 10% have type 1 diabetes, which is managed mainly in the secondary sector, and 90% have type 2 diabetes with the majority (80%) being treated in primary health care. In 2014, DADR included data from a total of 70,826 patients. Main variables The following variables are assessed: date of analysis as well as the outcome for hemoglobin A1c, blood pressure, lipids, urinary albumin–creatinine ratio, smoking status, glucose-, blood pressure-, and lipid-lowering treatment (yes/no), insulin pump treatment (yes/no), and date of last eye and foot examination. Descriptive data In 2014, the annual report included data regarding over 38,000 patients from outpatient clinics, which is assumed to have included almost all patients in this setting, and >32,000 from GPs, reflecting improved but still limited coverage from this setting. The annual results are published in a compiled report of Danish Diabetes Care, which included DADR, data from the pediatric diabetes database, and the national ophthalmological diabetes database. The annual report is published, which included data on national, regional, and local level (individual outpatient clinics and corresponding GPs). This allows a comprehensive overview of diabetes care in Denmark. Conclusion The database covers an increasing fraction of patients with diabetes in Denmark, and the structure for full coverage is in place. Annual reporting has helped to ensure focus on the quality of diabetes treatment in the primary and secondary health care. Furthermore, it is an important resource for Danish register-based diabetes research.

Danish Registry of Childhood and Adolescent Diabetes

Aim The aims of the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) are to monitor and improve the quality of care for children and adolescents with diabetes in Denmark and to follow the incidence and prevalence of diabetes. Study population The study population consists of all children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (<18 years of age) will be included. Main variables The variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis. Descriptive data The number of children diagnosed with diabetes is increasing with ∼3% per year mainly for type 1 diabetes (ie, 296 new patients <15 years of age were diagnosed in 2014). The disease management has changed dramatically with more children treated intensively with multiple daily injections, insulin pumps, and increased number of self-monitored blood glucose values per day. These initiatives have resulted in a significant improvement in HbA1c over the years and a decrease in the number of children experiencing severe hypoglycemia, diabetic nephropathy, and retinopathy. Conclusion The systematic collection of data in DanDiabKids documents improved quality of care over the last 12 years, despite a substantial increase in the number of patients cared for by pediatric departments in Denmark, fulfilling the purpose of the registry.

Nationwide trends in surgery and radioiodine treatment for benign thyroid disease during iodization of salt

OBJECTIVE Iodization of salt was introduced in Denmark in 1998 because of mild-to-moderate iodine deficiency (ID). The aim of this study was to analyze the utilization rate of surgery and radioiodine therapy for benign thyroid disorders before and after the introduction of iodization, and to study a possible association between the changes and the raised iodine intake. DESIGN A nationwide register study. METHODS Information on operations and radioiodine treatments for benign thyroid disorders was extracted from nationwide registers in the years 1990 to 2007. Treatment rates are presented for surgery and for radioiodine separately, and as a combined rate, both nationwide and split by the regions of prior mild and moderate ID. RESULTS A total of 65 605 treatments were identified: 26 456 operations and 39 149 radioiodine treatments. In the first years of iodization (1998-2000; rate ratio 2000/1997), the combined treatment rate increased with 2.5% (95% confidence interval (CI): -1.8-7.1). Split by prior ID level, the increase was seen in the region of moderate ID, but a decrease was seen in the region of mild ID. After 2000, the combined rate decreased, and ended up being 11.1% (95% CI: 7.1-15.0) lower in 2007 than before iodization (rate ratio 2007/1997). The changes were primarily due to changes in the use of radioiodine therapy as the surgery rates remained almost constant. CONCLUSIONS Iodization seemed to be associated with a temporary increase in the utilization rate of surgery and radioiodine therapy in the region of prior moderate ID, probably as a result of treatment of iodine-induced hyperthyroidism, but the rates ended up being lower than before iodization.

The Danish Schizophrenia Registry

Aim of database To systematically monitor and improve the quality of treatment and care of patients with schizophrenia in Denmark. In addition, the database is accessible as a resource for research. Study population Patients diagnosed with schizophrenia and receiving mental health care in psychiatric hospitals or outpatient clinics. During the first year after the diagnosis, patients are classified as incident patients, and after this period as prevalent patients. Main variables The registry currently contains 21 clinical quality measures in relation to the following domains: diagnostic evaluation, antipsychotic treatment including adverse reactions, cardiovascular risk factors including laboratory values, family intervention, psychoeducation, postdischarge mental health care, assessment of suicide risk in relation to discharge, and assessment of global functioning. Descriptive data The recorded data are available electronically for the reporting clinicians and responsible administrative personnel, and they are updated monthly. The registry publishes the national and regional results of all included quality measures in the annual audit reports. External researchers may obtain access to the data for use in specific research projects by applying to the steering committee. Conclusion The Danish Schizophrenia Registry represents a valuable source of informative data to monitor and improve the quality of care of patients with schizophrenia in Denmark. However, continuous resources and time devoted is necessary to maintain the integrity of the registry and the validity of the data.