Physician-led medication reviews in polypharmacy patients treated with at least 12 medications in a type 2 diabetes outpatient clinic: A randomised trial.

AIMS: Medication reviews can be used to promote appropriate pharmacotherapy and negate the harmful consequences of polypharmacy. This study aimed to evaluate the effect of physician-led medication reviews and increased cross-sectoral communication as a supplement to standard care in a type 2 diabetes outpatient clinic. METHODS: This pragmatic randomised clinical trial enrolled patients with type 2 diabetes treated with at least 12 medications. The subjects were randomised to either standard care (standard care consultation at the outpatient clinic) or standard care plus a medication review consultation and increased cross-sectoral communication. The primary outcome was the number of medications used after six months. Health-related quality of life was quantified using the EuroQoL 5-dimension 5-level (EQ5D-5 L) questionnaire. RESULTS: We recruited 50 participants with a median age of 72 (IQR 67-75) years. The mean number of medications per patient changed from 17.9 to 14.3 in the intervention group and 17.6 to 17.2 in the control group (rate ratio 0.81). The reasons for discontinuations were medication no longer indicated (60%), safety issues (20%), efficacy issues (15%) or patient preferences (5%). There was a significant difference in the change in health-related quality of life (EQ5D-5 L index score) in favour of the intervention (0.111, 95% CI 0.001 to 0.221). CONCLUSIONS: Physician-led medication reviews and increased cross-sectoral communication in patients with type 2 diabetes treated with at least 12 medications reduced the number of medications used and improved health-related quality of life. Implementing and further investigating similar interventions as standard care seems reasonable.

Does Subclinical Hypothyroidism Add Any Symptoms? Evidence from a Danish Population-Based Study.

BACKGROUND: Few studies have scrutinized the spectrum of symptoms in subclinical hypothyroidism. METHODS: From 3 Danish Investigation on Iodine Intake and Thyroid Diseases (DanThyr) cross-sectional surveys performed in the period 1997 to 2005, a total of 8903 subjects participated in a comprehensive investigation including blood samples and questionnaires on previous diseases, smoking habits, alcohol intake, and education. From the 3 surveys we included patients with subclinical hypothyroidism (n = 376) and euthyroid controls (n = 7619). We explored to what extent patients with subclinical hypothyroidism reported 13 previously identified hypothyroidism-associated symptoms (tiredness, dry skin, mood lability, constipation, palpitations, restlessness, shortness of breath, wheezing, globus sensation, difficulty swallowing, hair loss, dizziness/vertigo, and anterior neck pain). In various uni- and multivariate regression models we searched for circumstances predicting why some patients have more complaints than others. RESULTS: Subclinically hypothyroid patients did not report higher hypothyroidism score [(median, interquartile range), 2 (0-4) vs 2 (0-4), P = .25] compared with euthyroid controls. Within the group of subclinical hypothyroid patients, comorbidity had the highest impact on symptoms (tiredness, shortness of breath, wheezing; all P < .001); TSH level had no impact on symptom score; and younger age was accompanied by higher mental burden (tiredness, P < .001; mood lability, P < .001; restlessness, P = .012), whereas shortness of breath was associated with high body mass index (P < .001) and smoking (P = .007). CONCLUSION: Patients with a thyroid function test suggesting subclinical hypothyroidism do not experience thyroid disease-related symptoms more often than euthyroid subjects. In subclinical hypothyroidism, clinicians should focus on concomitant diseases rather than expecting symptomatic relief following levothyroxine substitution.

Effect of Metformin vs. Placebo in Combination with Insulin Analogues on Bone Markers P1NP and CTX in Patients with Type 2 Diabetes Mellitus.

Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.

Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification.

OBJECTIVE: To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. DESIGN: We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 µg/g) that was in effect from year 2001. RESULTS: The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. CONCLUSION: Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.

Polypharmacy and medication deprescribing: A survey among multimorbid older adults in Denmark.

Polypharmacy is common among multimorbid adults and associated with increased morbidity and mortality. Excessive polypharmacy (ie, ≥10 medicine) is strongly associated with inappropriate medication use, but little is known about attitudes toward deprescribing in patients with excessive polypharmacy. We surveyed 100 Danish individuals aged 65 years and above with ≥10 prescribed medications, using the validated Patients' Attitudes Towards Deprescribing (PATD) instrument. Most participants (81, 81%) thought they took a large number of medications, and 79 (79%) believed that their medications were necessary. Even so, 85 (85%) reported that they would be willing to stop taking one or more of their regular medications if their doctor told them they could, and 11 (11%) felt that they took at least one regular medication that they no longer needed. When presented with visual presentation of various amounts of tablets and capsules, 62 (62%) of participants reported that they would be comfortable taking fewer medications than they did. Forty-two (42%) participants had experience with stopping a regular medication. Almost all participants (92%) wanted to receive follow-up by various means if a medication was discontinued. Forty-one (41%) participants were interested in a consultation at an outpatient clinic specializing in polypharmacy. Overall, the answers to the PATD questionnaire suggest that our cohort of Danish, multimorbid outpatients with extensive polypharmacy have a high confidence in their healthcare providers for medication-related decisions, even though some feel that they are taking more medications than they would like to and feel that some medications may be unnecessary. Our results underline the need for healthcare providers to offer medication reviews in patients with multimorbidity.

Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study.

BACKGROUND: Clinic-based studies have indicated that older hypothyroid patients may present only few symptoms. METHODS: In this population-based study of hypothyroidism, we investigated how the power of symptom presence predicts overt hypothyroidism in both young and older subjects. We identified patients newly diagnosed with overt autoimmune hypothyroidism in a population (n = 140, median thyroid-stimulating hormone, 54.5; 95% confidence interval [CI], 28.3-94.8; median total T4, 37; 95% CI, 18-52) and individually matched each patient with 4 controls free of thyroid disease (n = 560). Participants filled out questionnaires concerning the presence and duration of symptoms. We compared the usefulness of hypothyroidism-associated symptoms in predicting overt hypothyroidism in different age groups (young: <50 years, middle age: 50-59 years, old: ≥60 years) also taking various confounders into account. RESULTS: In young hypothyroid patients, all 13 hypothyroidism-associated symptoms studied were more prevalent than in their matched controls, whereas only 3 of those (tiredness, shortness of breath, and wheezing) were more prevalent in old patients. The mean numbers of symptoms presented at disease onset were 6.2, 5.0, and 3.6 at the ages of 0 to 49 years, 50 to 59 years, and 60+ years, respectively. In young versus old people with 0 to 1 symptoms, the odds ratio for being hypothyroid was 0.04 (95% CI, 0.007-0.18) versus 0.34 (95% CI, 0.15-0.78) (reference all other groups). In young versus old subjects reporting ≥4 symptoms, the odds ratio for being hypothyroid was 16.4 (95% CI, 6.96-40.0) versus 2.22 (95% CI, 1.001-4.90). Receiver operating characteristic analyses revealed that the symptom score was an excellent tool for predicting hypothyroidism in young men (area under the receiver operating characteristic curve, 0.91; 95% CI, 0.82-0.998), whereas it was poor in evaluating older women (area under the receiver operating characteristic curve, 0.64; 95% CI, 0.54-0.75). CONCLUSION: Hypothyroid symptom score is a good discriminating tool to identify hypothyroidism in young patients but fails to identify hypothyroidism in the elderly. Thus, thyroid function should be tested on wide indications in old age.

Serum thyroglobulin as a biomarker of iodine deficiency in adult populations.

OBJECTIVE: To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID). DESIGN AND METHODS: Two identical cross-sectional studies were performed before (C1a: 1997-98, n = 4649) and after (C2: 2004-05, n = 3570) the Danish mandatory iodine fortification (IF) of salt (2000). Additionally, a follow-up study of C1a was performed after IF (C1b: 2008-10, n = 2465). The studies took place in two regions with mild (Copenhagen) and moderate (Aalborg) ID before IF. Serum Tg was measured by immunoradiometric method and investigated as outcome variable in multivariate models. RESULTS: Multiple factors were associated with serum Tg. Some were directly related to iodine intake (cohort, urinary iodine concentration (UIC) level and region), and some were likely mediators of iodine intake effects on Tg (thyroid nodularity, thyroid size and autonomy with low TSH). Others were caused by Tg assay interference (Tg-Ab positivity), aggravation of ID (childbirths and smoking) or TSH stimulation of the thyroid. Estimated 24-h urinary iodine excretion was a more sensitive predictor of Tg than UIC. Iodine supplement users had low median Tg values compared with nonusers both before and after IF. CONCLUSIONS: Multiple factors should be taken into consideration when evaluating Tg as a marker of ID in adult populations, and the Tg results may depend on the assay used. Still, Tg is a sensitive marker of ID. We suggest including a reference population with known sufficient iodine intake when Tg is used to evaluate ID.

Parity and 11-Year Serum Thyrotropin and Thyroid Autoantibody Change: A Longitudinal Population-Based Study.

BACKGROUND: A role for female reproductive factors in the pathogenesis of thyroid autoimmunity has been suggested. This study investigated the prospective association between parity, abortion, use of oral contraceptive pill (OCP), and use of hormone replacement therapy (HRT), and 11-year change in serum thyrotropin (TSH), as well as change in thyroid peroxidase autoantibody (TPOAb) status. METHODS: A random sample of 4649 people aged 18-65 years participated in a population-based study in the period 1997-1998. In the study presented here, 1749 non-pregnant women with no history of thyroid disease were included who participated in the 11-year follow-up examination in the period 2008-2010. Gynecological exposures were reported in a self-administered questionnaire at baseline and follow-up. TSH and TPOAb were measured at baseline and follow-up. Increased TPOAb status during follow-up was defined as a TPOAb below the assay cutoff (<30 kIU/L) at baseline and a TPOAb ≥30 kIU/L at follow-up. Multiple linear regression models were used, adjusted for age, smoking status, and urinary iodine excretion. RESULTS: An inverse association was found between the number of years on HRT and the risk (odds ratio) of increased TPOAb status during follow-up (0.735 [confidence interval 0.558-0.968], p = 0.03). However, this association was not statistically significant when applying the Bonferroni adjusted significance level. The remaining reproductive factors showed no statistically significant association with risk of increased TPOAb during follow-up. Furthermore, parity, abortions, use of OCP, HRT use, age at menarche, and being pre- or postmenopausal were not significantly associated with 11-year TSH change. CONCLUSIONS: No statistically significant association was found between the studied female reproductive measures and 11-year risk of TSH or TPO change. A possible protective role for HRT in the etiology of thyroid autoimmunity, however, deserves further research.

Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study.

BACKGROUND: It is generally accepted that patients suffering from hypothyroidism may express few symptoms, but this has not been studied in a population-based study design. OBJECTIVES: To study the array of symptoms as they are reported in newly diagnosed overt autoimmune hypothyroidism using a population-based case-control design. METHODS: Patients with new overt autoimmune hypothyroidism (n=140) and their individually matched thyroid disease-free controls (n=560) recruited from the same population underwent a comprehensive program and self-reported a number of symptoms. We identified the symptoms associated with overt hypothyroidism and calculated positive (LR+) and negative (LR-) likelihood ratios as well as diagnostic odds ratios (DORs) as measures for the association between disease state and symptoms. RESULTS: Among 34 symptoms investigated, 13 symptoms were statistically overrepresented in hypothyroidism. Hypothyroid patients suffered mostly from tiredness (81%), dry skin (63%), and shortness of breath (51%). Highest DORs (95% CI) were reported for tiredness (5.94 (3.70-9.60)), hair loss (4.58 (2.80-7.51)), and dry skin (4.09 (2.73-6.16)). A hypothyroidism-component-score was defined as the number of hypothyroidism-associated symptoms (range: 0-13). LR+ for participants with a hypothyroidism-component-score of 0 was 0.21 (0.09-0.39), meaning that the post-test probability was lowered to 21% of what it was before asking for symptoms. LR+ for scores of 1-2/3/4-6/7-9/10-13 were: 0.47 (0.30-0.72)/1.16 (0.70-1.87)/1.90 (1.29-2.45)/3.52 (2.30-5.36)/6.29 (2.30-17.7). CONCLUSIONS: None of the individual symptoms of hypothyroidism had high LRs or DORs. Thus, neither the presence nor absence of any individual hypothyroidism symptom was reliable in the decision making of who should have their thyroid function tested. Therefore, even minor suspicion should lead to a blood test.

Thyroid nodules in an 11-year DanThyr follow-up study.

CONTEXT: Limited longitudinal data are available on changes in the thyroid gland structure in a population and how this is influenced by iodine fortification (IF). OBJECTIVE: Our objective was to clarify how IF influenced thyroid gland structure in 2 regions with different iodine intake at baseline (Copenhagen, mild iodine deficiency [ID]; Aalborg, moderate ID). DESIGN AND SETTING: We conducted a longitudinal population-based study (DanThyr) where participants were examined before (1997) and after (2008) the Danish mandatory IF of salt (2000). PARTICIPANTS: We examined 2465 adults, and ultrasonography was performed by the same sonographers using the same equipment, after controlling performances. MAIN OUTCOME MEASURE: Change in thyroid gland structure was evaluated. RESULTS: The follow-up period saw an increased prevalence of multinodularity (9.8%-13.8 %, P < .001), especially in the previously moderate ID region of Aalborg (9.1%-15.4%, P < .001), whereas no change in prevalence was seen for solitary nodules (5.6%-5.1%, P = .34). In individual participants, changes in thyroid structure and disappearance of thyroid nodules during the 11 years was common with an overall normalization rate of 21.2 (95% confidence interval [CI] = 17.9-24.9) per 1000 person-years. Solitary nodules had a significantly higher normalization rate than multiple nodules (normalization rate ratio 0.47 [95% CI = 0.32-0.67]). A regional difference (Aalborg vs Copenhagen) was seen between normalization rates of multiple nodules (normalization rate ratio 0.29 [95% CI = 0.12-0.64]), but not for solitary nodules (normalization rate ratio 0.81 [95% CI = 0.53-1.21]). CONCLUSIONS: Changes in the thyroid gland structure with both appearance and disappearance of thyroid nodules are common after an iodization program.

Thyroid function and body weight: a community-based longitudinal study.

OBJECTIVE: Body weight and overt thyroid dysfunction are associated. Cross-sectional population-based studies have repeatedly found that thyroid hormone levels, even within the normal reference range, might be associated with body weight. However, for longitudinal data, the association is less clear. Thus, we tested the association between serum thyrotropin (TSH) and body weight in a community-based sample of adult persons followed for 11 years. METHODS: A random sample of 4,649 persons aged 18-65 years from a general population participated in the DanThyr study in 1997-8. We included 2,102 individuals who participated at 11-year follow-up, without current or former treatment for thyroid disease and with measurements of TSH and weight at both examinations. Multiple linear regression models were used, stratified by sex and adjusted for age, smoking status, and leisure time physical activity. RESULTS: Baseline TSH concentration was not associated with change in weight (women, P = 0.17; men, P = 0.72), and baseline body mass index (BMI) was not associated with change in TSH (women, P = 0.21; men, P = 0.85). Change in serum TSH and change in weight were significantly associated in both sexes. Weight increased by 0.3 kg (95% confidence interval [CI] 0.1, 0.4, P = 0.005) in women and 0.8 kg (95% CI 0.1, 1.4, P = 0.02) in men for every one unit TSH (mU/L) increase. CONCLUSIONS: TSH levels were not a determinant of future weight changes, and BMI was not a determinant for TSH changes, but an association between weight change and TSH change was present.

Development of autoimmune overt hypothyroidism is highly associated with live births and induced abortions but only in premenopausal women.

CONTEXT: The 1-year postpartum period is often accompanied by increased risk for thyroid disease. OBJECTIVE: The objective of the study was to investigate the role of reproductive risk factors in the development of autoimmune overt hypothyroidism in the years after the 1-year postpartum period. DESIGN, SETTING, AND SUBJECTS: In a population study, we included Danish women with new autoimmune overt hypothyroidism not diagnosed within the first year after a pregnancy (n = 117; median age 53.0 y) and age- and region-matched euthyroid controls from the same population (n = 468). MAIN OUTCOME MEASURES: In conditional multivariate logistic regression models, we analyzed the associations between the development of autoimmune hypothyroidism and age at menarche/menopause, years of menstruations, pregnancies, spontaneous and induced abortions, live births, and years on oral contraceptives and postmenopausal hormone replacement therapy, also taking various possible confounders into account. RESULTS: In multivariate regression models with no event as reference, the odds ratios (ORs) for hypothyroidism [95% confidence interval (CI)] after one/two/three or more live births were 1.72 (0.56-5.32)/3.12 (1.14-8.48)/4.51 (1.65-12.3) and 1.02 (0.57-1.81)/2.70 (1.27-5.75) after one/two or more induced abortions. Findings were valid only for women having hypothyroidism diagnosed before the age of 55 years. We found no association between disease development and other reproductive risk factors investigated. CONCLUSIONS: Previous live births and induced abortions were major risk factors for the development of autoimmune overt hypothyroidism in women aged up to 55 years. The increased risk for hypothyroidism after giving birth extends longer than just to the 1-year postpartum period, and numbers of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women.

Mandatory iodine fortification of bread and salt increases iodine excretion in adults in Denmark - a 11-year follow-up study.

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.

Determinants of serum T4 and T3 at the time of diagnosis in nosological types of thyrotoxicosis: a population-based study.

OBJECTIVE: To characterize thyroid hormone levels at the time of diagnosis in the nosological types of thyrotoxicosis diagnosed in the population and to analyze determinants for serum thyroxine (T4) and tri-iodothyronine (T3). DESIGN: Population-based study of thyrotoxicosis at disease onset. METHODS: In the period 1997-2000, we prospectively identified all patients diagnosed with incident primary overt thyrotoxicosis in a Danish population cohort and classified patients into ten well-defined nosological types of disease (n=1082). Untreated levels of serum T3, T4, and T3:T4 ratio were compared and related to sex, age, level of iodine deficiency, smoking status, alcohol intake, iodine supplement use, co-morbidity, and TSH receptor antibodies (TRAbs) in multivariate models. RESULTS: Graves' disease (GD) patients had much higher levels of T3 and higher T3:T4 ratio at diagnosis compared with other thyrotoxic patients, but with a profound negative association between hormone levels and age. In GD, patients diagnosed in the area with more severe iodine deficiency had lower levels of T3 and T4. TRAb-negative GD patients had biochemically mild thyrotoxicosis. Higher age was also associated with lower degree of biochemical thyrotoxicosis in nodular toxic goiter. We found no association between serum T3 and T4 and sex, smoking habits, iodine supplements, alcohol intake, or co-morbidity in any type of thyrotoxicosis. CONCLUSIONS: The study gives new insight into the hormonal presentation of thyrotoxicosis and showed that young age, positive TRAb levels, but also residency in the area with higher iodine intake was positively associated with biochemical disruption in GD.

Graves' hyperthyroidism and moderate alcohol consumption: evidence for disease prevention.

BACKGROUND: We recently demonstrated that moderate alcohol consumption is associated with a considerable reduction in the risk of autoimmune hypothyroidism, similar to findings in other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. We aimed to study a possible association between alcohol intake and autoimmune Graves' hyperthyroidism. DESIGN: This is a population-based, case-control study. METHODS: In a well-defined Danish population (2,027,208 person-years of observation), we prospectively identified patients with new overt thyroid dysfunction and studied 272 patients with Graves' hyperthyroidism. For each patient, we recruited four age-gender-region-matched controls with normal thyroid function (n = 1088). MEASUREMENTS: Participants gave detailed information on current and previous alcohol intake as well as other factors to be used for analyses. The association between alcohol intake and development of hyperthyroidism was analysed in conditional multivariate Cox regression models. RESULTS: Graves' patients had a lower reported alcohol consumption than controls (median units of alcohol (12 g) per week: 2 vs 4, P < 0·001). In a multivariate regression model, alcohol consumption was associated with a dose-dependent reduction in risk for development of overt Graves' hyperthyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1-2 units of alcohol per week were as follows: 0 units/week 1·73 (1·17-2·56), 3-10 units/week 0·56 (0·39-0·79), 11-20 units/week 0·37 (0·21-0·65), ≥21 units/week 0·22 (0·08-0·60). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with the type of alcohol consumed (wine vs beer), smoking habit, age, gender or region of inhabitancy. CONCLUSIONS: Moderate alcohol consumption is associated with a considerable reduction in the risk of Graves' disease with hyperthyroidism--irrespective of age and gender. Autoimmune thyroid disease seems to be much more dependent on environmental factors than hitherto anticipated.

Moderate alcohol consumption may protect against overt autoimmune hypothyroidism: a population-based case-control study.

OBJECTIVE: Alcohol consumption is an important protective risk factor for many autoimmune diseases. We wished to study the association between alcohol consumption and autoimmune hypothyroidism. DESIGN: Population-based, case-control study, 1997-2001, Denmark. METHODS: Patients with newly diagnosed autoimmune overt hypothyroidism (n=140) were prospectively identified in a population (2 027 208 person-years of observation), and their matched controls with normal thyroid function (n=560) were recruited simultaneously from the same population. Participants gave information on alcohol intake, smoking, previous diseases, education, and family history of hypothyroidism. The association between alcohol intake and development of hypothyroidism was analyzed in conditional regression models. RESULTS: Hypothyroid cases had reported a lower alcohol consumption than controls (median units of alcohol (12 g) per week: 3 vs 5, P=0.002). In a multivariate regression model, alcohol consumption was associated with a reduction in risk for development of overt autoimmune hypothyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1-10 units of alcohol per week were as follows: 0 units/week, 1.98 (1.21-3.33); 11-20 units/week, 0.41 (0.20-0.83); and ≥21 units/week, 0.90 (0.41-2.00). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with type of alcohol consumed (wine vs beer), sex, or region of inhabitancy. CONCLUSIONS: Alcohol consumption seems to confer considerable protection against development of overt autoimmune hypothyroidism irrespective of sex and type of alcohol consumed.

Smoking cessation is followed by a sharp but transient rise in the incidence of overt autoimmune hypothyroidism - a population-based, case-control study.

BACKGROUND: Current smoking is associated with a low prevalence of thyroid autoantibodies. On the other hand, smoking withdrawal enhances thyroid autoantibody level and may be a risk factor for the development of hypothyroidism. The aim of this study was to assess the association between smoking habits (smoking cessation in particular) and development of autoimmune hypothyroidism. DESIGN: Population-based, case-control study. PARTICIPANTS: Cases (n = 140) newly diagnosed with primary autoimmune overt hypothyroidism were identified prospectively by population monitoring (2,027,208 person-years of observation) of all thyroid function tests performed in the two well-defined geographical areas. Individually, age-, sex- and region-matched euthyroid controls (n = 560) were simultaneously included from the same population. MEASUREMENTS: Participants gave details on smoking habits including smoking withdrawal and other lifestyle factors. Smoking habits were verified by measuring urinary cotinine (a nicotine metabolite). RESULTS: Incident hypothyroidism was very common in people who had recently stopped smoking: OR vs never smokers (95%-CI); quit smoking <1 years, 7·36 (2·27-23·9); 1-2 years, 6·34 (2·59-15·3); 3-10 years, 0·75 (0·30-1·87); >10 years, 0·76 (0·38-1·51). Results were consistent in both sexes and irrespective of age. Within two years after smoking cessation, the percentage of hypothyroid cases attributable to cessation of smoking was 85%. The current smoking was not associated with altered risk of developing overt hypothyroidism [OR, 0·92 (0·57-1·48)]. CONCLUSIONS: The risk of having overt autoimmune hypothyroidism diagnosed is more than 6-fold increased the first 2 years after cessation of smoking. Clearly, smoking cessation is vital to prevent death and severe disease. However, awareness of hypothyroidism should be high in people who have recently quit smoking, and virtually any complaint should lead to thyroid function testing.

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.

Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study.

OBJECTIVE: Few population-based studies have described the epidemiology of subtypes of hyperthyroidism. DESIGN: A prospective population-based study, monitoring two well-defined Danish cohorts in Aalborg with moderate iodine deficiency (n=311 102) and Copenhagen with only mild iodine deficiency (n=227 632). METHODS: A laboratory monitoring system identified subjects with thyroid function tests suggesting overt hyperthyroidism (low s-TSH combined with high s-thyroxine or s-triiodothyronine). For all subjects, we collected information on medical history, thyroid scintigraphy and thyroid hormone receptor antibody (TRAb) measurement. Information was used to disprove or verify primary overt hyperthyroidism and to subclassify hyperthyroidism into nosological disorders. RESULTS: From 1997 to 2000 (2 027 208 person-years of observation), we verified 1682 new cases of overt hyperthyroidism. The overall standardized incidence rate (SIR) per 100 000 person-years was 81.6, and was higher in Aalborg compared with Copenhagen (96.7 vs 60.0, P<0.001), giving an SIR ratio (SIRR (95% confidence interval (CI))) between moderate versus mild iodine-deficient areas of 1.6 (1.4-1.8). Nosological types of hyperthyroidism (percentage/SIRR (95% CI)): multinodular toxic goitre (MNTG) 44.1%/1.9 (1.6-2.2), Graves' disease (GD) 37.6%/1.2 (0.99-1.4), solitary toxic adenoma (STA) 5.7%/2.4 (1.3-3.5), 'mixed type' hyperthyroidism (TRAb-positive, scintigraphicly multinodular) 5.4%/6.0 (3.0-12), subacute thyroiditis 2.3%/0.9 (0.4-1.4), postpartum thyroid dysfunction 2.2%/1.6 (0.8-3.0), amiodarone-associated hyperthyroidism 0.8%/7.1 (1.1-65), hyperthyroidism after thyroid radiation 0.7%/12.3 (0.8-50), lithium-associated hyperthyroidism 0.7%/0.97 (0.4-4.8) and hyperthyroidism caused by various other factors 0.7%. Lifetime risk for overt hyperthyroidism was 10.5%/6.5%/2.4% (females/all/males). CONCLUSION: Hyperthyroidism was common in Denmark with MNTG and GD as dominating entities. The higher incidence of hyperthyroidism in the most iodine-deficient region was caused by higher frequency of MNTG, 'mixed-type', STA and amiodarone-associated hyperthyroidism.