Implementation of a biopsy protocol to improve detection of esophageal eosinophilia: a Danish registry-based study.

BACKGROUND : In the North Denmark Region (580 272 inhabitants), only 0-4 cases of possible eosinophilic esophagitis (EoE) were identified annually in 1999-2010, suggesting underdiagnosis. This study aimed to increase the diagnosis of EoE by introducing a regional biopsy protocol for patients with dysphagia. METHODS : In 2011, leaders of regional endoscopy units attended a consensus meeting where a biopsy protocol was proposed. The national pathology registry was used to identify patients with esophageal eosinophilic inflammation during 2007-2017. RESULTS : Discussion resulted in consensus on a protocol to take eight biopsy samples in dysphagia patients (four biopsies from 4 cm and 14 cm above the esophagogastric junction-"4-14-4 rule") regardless of the macroscopic appearance, and to code eosinophilia systematically in the pathology registry. A pictogram showing the 4-14-4 rule was sent to all endoscopy units. The number of patients with esophageal eosinophilia detected per year increased 50-fold after the protocol was implemented in 2011 (median of 1 [interquartile range 0-3] vs. 52 [47-56]; P < 0.001), and the number of biopsy samples per patient doubled (median 4 [4-5] vs. 8 [6-9]; P < 0.04). Of 309 patients diagnosed with esophageal eosinophilia in 2007-2017, 24 % had erosive esophagitis or Barrett's esophagus, and 74 % had EoE. CONCLUSIONS : A consensus-based biopsy protocol and improved coding of eosinophilia in the pathology registry resulted in a 50-fold increase in patients diagnosed with esophageal eosinophilia/year. These patients can now receive treatment. The effort to establish the protocol and change the culture of endoscopists and pathologists was minimal.

Reliability of thyroglobulin in serum compared with urinary iodine when assessing individual and population iodine nutrition status.

The occurrence of thyroid disorders relies on I nutrition and monitoring of all populations is recommended. Measuring I in urine is standard but thyroglobulin in serum is an alternative. This led us to assess the reliability of studies using serum thyroglobulin compared with urinary I to assess the I nutrition level and calculate the number of participants needed in a study with repeated data sampling in the same individuals for 1 year. Diet, supplement use and life style factors were assessed by questionnaires. We measured thyroglobulin and thyroglobulin antibodies in serum and I in urine. Participants were thirty-three Caucasians and sixty-four Inuit living in Greenland aged 30-49 years. Serum thyroglobulin decreased with rising I excretion (Kendall's τ -0·29, P=0·005) and did not differ with ethnicity. Variation in individuals was lower for serum-thyroglobulin than for urinary I (mean individual CV: 15·1 v. 46·1 %; P<0·01). It required 245 urine samples to be 95 % certain of having a urinary I excretion within 10 % of the true mean of the population. For serum-thyroglobulin the same precision required 206 samples. In an individual ten times more samples were needed to depict I deficiency when using urinary I excretion compared with serum-thyroglobulin. In conclusion, more participants are need to portray I deficiency in a population when using urinary I compared with serum-thyroglobulin, and about ten times more samples are needed in an individual. Adding serum-thyroglobulin to urinary I may inform surveys of I nutrition by allowing subgroup analysis with similar reliability.

Hypothyroidism and pregnancy loss: comparison with hyperthyroidism and diabetes in a Danish population-based study.

BACKGROUND: Hypothyroidism is a common endocrine disease. The frequency of pregnancy loss in women with known hypothyroidism as opposed to women with a later diagnosis of hypothyroidism has not been evaluated and compared with other common endocrine diseases. DESIGN: Population-based cohort study using Danish nationwide registers. PARTICIPANTS: All pregnancies in Denmark, 1997-2008, resulting in live birth (n = 732 533), spontaneous abortion (n = 112 487) or stillbirth (n = 2937) were identified together with information on maternal hypothyroidism, hyperthyroidism and diabetes. METHODS: Cox model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (95%CI) for spontaneous abortion and stillbirth, reference: no hypo- or hyperthyroidism or diabetes (n = 824 310). RESULTS: We identified 4951 pregnancies where maternal hypothyroidism was diagnosed before the pregnancy (group 1) and 2464 pregnancies where maternal hypothyroidism was diagnosed in the 2-year period after the pregnancy (group 2). In group 1, 825 pregnancies (16·7%) resulted in spontaneous abortion which was more frequent than in nonexposed (13·2%), (aHR 1·19 (95%CI 1·12-1·27)), and of the same magnitude as in hyperthyroidism (17·2%, P = 0·5) and diabetes (17·5%, P = 0·2) diagnosed before the pregnancy. In group 2, the frequency was 12·2% (aHR 0·92 (0·84-1·02)). In group 2, 16 pregnancies (0·65%) resulted in stillbirth which was more frequent than in nonexposed (0·36%), (aHR 1·81 (1·11-2·97)), of the same magnitude as in hyperthyroidism (0·82%, P = 0·5) and less frequent than in diabetes (2·9%, P < 0·001) diagnosed after the pregnancy. In group 1, the frequency was 0·40% (aHR 1·11 (0·68-1·82)). CONCLUSIONS: Hypothyroidism increased the risk of both early and late pregnancy loss as did hyperthyroidism and in particular diabetes. We hypothesize that undetected or insufficiently treated maternal disease in the pregnancy may be of causal importance.

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.

Maternal thyroid function in pregnancy may program offspring blood pressure, but not adiposity at 20 y of age.

BACKGROUND: Experimental evidence exists indicating that maternal thyroid hormones during pregnancy may affect the metabolic set point and cardio-vascular function in the offspring. The objective of this study was to investigate the association between maternal thyroid function in week 30 of gestation and offspring adiposity and blood pressure at 20 y. METHODS: The study was based on the follow up of a Danish birth cohort from 1988 to 1989 (n = 965). A blood sample was drawn from the pregnant women in week 30 of gestation (N = 877). In 2008-2009, the offspring were followed up with self-reported anthropometrics (N = 645) and a clinically measured blood pressure (N = 425). Multiple linear regressions were used to estimate the association between maternal thyroid function and offspring BMI, waist circumference, and blood pressure. RESULTS: Offspring of subclinical hypothyroid women had higher systolic blood pressure (adjusted difference = 3.6, 95% confidence interval: 0.2, 7.0 mmHg) and a tendency toward higher diastolic blood pressure (adjusted difference = 2.3, 95% confidence interval: -0.2, 4.9 mmHg) compared to offspring of euthyroid women. No association was found with offspring BMI and waist circumference. CONCLUSION: Maternal thyroid function during third trimester of pregnancy may affect long-term blood pressure in the offspring.

Can Elastography Predict Growth of Incidental Thyroid Nodules? A Pilot Two-Year Follow-Up Study.

The objective of this study was to examine the ultrasonography (US) and ultrasound elastography (USE) features of thyroid incidentalomas in a population exposed to iodine deficiency and to investigate whether baseline elasticity scores (ES) predicted changes in thyroid nodule US characteristics. We conducted a two-year follow-up pilot study of thyroid incidentalomas by US and USE. One sonographer performed the US and USE examination on the same apparatus at baseline and at follow-up. We evaluated 83 incidental thyroid nodules detected in a population study. The follow-up period saw no change in median thyroid nodule diameter (p = 0.18) or in the prevalence of thyroid nodule US characteristics (hypoechoic: p = 0.05; solid nodule: p = 1.00; microcalcifications: p = 0.55). Individual changes in thyroid nodule diameter (>20%) were seen in 23% (11% had decreased, and 12% had increased in diameter). Changes in ES were frequently observed; 37% changed from ES A + B to ES C + D, and 27% changed from ES C + D to ES A + B. In a multivariate logistic regression model, we found no association between baseline ES and individual changes in nodule size. In an area with mild iodine deficiency and a high prevalence of thyroid nodules, thyroid USE performed on thyroid incidentalomas did not predict individual changes in thyroid nodule size.

Foetal programming by maternal thyroid disease.

Foetal programming is an emerging concept that links a wide range of exposures during foetal life to later development of disease. Thyroid disorders are common in women of reproductive age, and careful management of pregnant women suffering from thyroid disease is important considering the crucial role of thyroid hormones during early brain development. It is possible that maternal thyroid dysfunction in pregnancy may lead to structural and/or functional changes during foetal brain development. Such an effect could later predispose the offspring to an increased risk of neurologic or psychiatric disease. We recently observed that children born to mothers with thyroid dysfunction had an increased risk of developing seizure disorders, autism spectrum disorders, attention-deficit hyperactivity disorders and psychiatric disease in adolescence and young adulthood. In the review, we discuss the concept of potential foetal programming by maternal thyroid disease.

Gender differences in symptoms of hypothyroidism: a population-based DanThyr study.

OBJECTIVES: We examined the gender-specific symptom prevalences in hypothyroidism and in healthy controls and explored the extent to which symptoms indicative of thyroid status may be different in women and men. DESIGN AND METHODS: Patients newly diagnosed with overt autoimmune hypothyroidism (n = 140) and controls free of thyroid disease (n = 560) recruited from the same population participated in a population-based study of The Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr). Participants underwent a comprehensive programme including blood tests and completion of questionnaires. The gender-specific distribution of 13 hypothyroidism-associated symptoms and a simple combined score (0-13) was explored in conditional uni- and multivariate models taking into account a broad spectrum of possible confounders. Diagnostic odds ratios (DORs) were calculated as measures for the association between participant status (case vs control) and presence of symptoms (yes vs no). RESULTS: In overt autoimmune hypothyroidism, 94·9% of women and 91·3% of men (P = 0·62) reported at least one of the hypothyroidism-associated symptoms, with tiredness as the most common symptom followed by dry skin and shortness of breath. In contrast, women free of thyroid disease self-reported at least one hypothyroidism-associated symptom considerably more often than men (73·7% vs 51·1%, P < 0·001). DORs (±SEM) for 0-1/2-3/4-13 symptoms were 0·07 (0·04-0·10)/2·15 (1·57-2·94)/7·99 (6·15-10·4) in men and 0·21 (0·16-0·28)/0·62 (0·58-0·66)/1·99 (1·90-2·09) in women. CONCLUSION: The presence of symptoms is more indicative for overt autoimmune hypothyroidism in men than in women, and presumably persistent symptoms after therapy of hypothyroidism will be more common in women.

Misclassification of iodine intake level from morning spot urine samples with high iodine excretion among Inuit and non-Inuit in Greenland.

Iodine nutrition is commonly assessed from iodine excretion in urine. A 24 h urine sample is ideal, but it is cumbersome and inconvenient. Hence, spot urine samples with creatinine to adjust for differences in void volume are widely used. Still, the importance of ethnicity and the timing of spot urine samples need to be settled. We, thus, collected 104 early morning spot urine samples and 24 h urine samples from Inuit and non-Inuit living in Greenland. Diet was assessed by a FFQ. Demographic data were collected from the national registry and by questionnaires. Iodine was measured using the Sandell-Kolthoff reaction, creatinine using the Jaffe method and para-amino benzoic acid by the HPLC method for the estimation of completeness of urine sampling and compensation of incomplete urine samples to 24 h excretion. A population-based recruitment was done from the capital city, a major town and a settlement (n 36/48/20). Participants were seventy-eight Inuit and twenty-six non-Inuit. The median 24 h iodine excretion was 138 (25th-75th percentile 89-225) µg/97 (25th-75th percentile 72-124) µg in Inuit/non-Inuit (P= 0.030), and 153 (25th-75th percentile 97-251) µg/102 (25th-75th percentile 73-138) µg (P= 0.026) when including compensated iodine excretion. Iodine excretion in 24 h urine samples increased with a rising intake of traditional Inuit foods (P= 0.005). Iodine excretion was lower in morning spot urine samples than in 24 h urine samples (P< 0.001). This difference was associated with iodine intake levels (P< 0.001), and was statistically significant when the iodine excretion level was above 150 µg/24 h. In conclusion, the iodine intake level was underestimated from morning spot urine samples if iodine excretion was above the recommended level.

Ethnicity is important for creatinine excretion among Inuit and Caucasians in Greenland.

BACKGROUND: Human nutrition, contamination and renal function are commonly assessed by the analysis of urine. A complete 24-hour urine sample is the ideal but it is inconvenient and unreliable. Thus, spot urine sampling with creatinine adjustment is widely used. Stratification for age and gender is recommended. Still, ethnicity may influence creatinine excretion. METHODS: We collected 104 24-h urine samples among Inuit and non-Inuit living in Greenland. Completeness of sampling was checked by using para-amino benzoic acid (PABA) that also allowed for compensation of creatinine excretion when sampling was incomplete. We measured creatinine using the Jaffe method and PABA by the HPLC method. RESULTS: Participants were recruited from the capital city, a major town and a settlement (n = 36/48/20). They were aged 30-69 years with 78 Inuit and 26 non-Inuit. Inuit were smaller than non-Inuit (Caucasians): height, 163 vs. 177 cm, p < 0.001; weight, 71 vs. 84 kg, p = 0.001 with similar BMI. Creatinine excretion was lower in Inuit compared to non-Inuit (men, 1344/1807 mg/24 h; women 894/1259 mg/24 h; p = 0.002; 0.02). It was influenced by age (p < 0.001), gender (p < 0.001), weight (p = 0.001) and ethnicity (p = 0.030) while not by the intake of the protein-rich Inuit diet in the adjusted analysis. Creatinine excretion was described by: Inuit men, 1925 mg - (13.1 × age); Inuit women, 1701 mg - (17.0 × age). CONCLUSION: Inuit and Caucasians have different creatinine excretion. It is recommended to stratify by ethnicity in addition to adjustment for age and gender when using creatinine correction of spot urine samples.

Thyroid malignancy markers on sonography are common in patients with benign thyroid disease and previous iodine deficiency.

OBJECTIVES: The purpose of this study was to evaluate the characteristics of benign thyroid nodules on sonography and ultrasound elastography in a population exposed to iodine deficiency. METHODS: We conducted a prospective systematic evaluation of preoperative thyroid sonography and elastography in patients assigned for surgical excision of benign thyroid nodules. Two experienced sonographers performed all sonographic and elastographic examinations. Thyroid nodules were evaluated by 7 generally accepted sonographic malignancy risk markers and assigned an elasticity score on elastography. The final diagnosis of a benign thyroid nodule was based on histopathologic analysis of resected thyroid gland tissue. RESULTS: We evaluated 232 thyroid nodules in 105 patients (86 women and 19 men). In total, 57% of the examined nodules had 1 or 2 malignancy risk markers present, and 24% did not have any markers present. A solid nodule larger than 15 mm was the most common malignancy risk marker observed (63%), followed by low elasticity (33%), microcalcifications (26%), and hypoechogenicity (15%). In an analysis stratified according to the number of nodules (solitary versus multiple), low elasticity was described more frequently in solitary nodules (61.9% versus 30.4%; P= .004). A large nodular volume was a predictor (P < .05) of microcalcifications and intranodular vascularization, whereas an absent halo sign and a solid nodule were found less frequently in nodules with larger volumes. CONCLUSIONS: Our results show that routine preoperative malignancy risk evaluation of presumably benign thyroid nodules is of little value when performed on patients exposed to iodine deficiency.

Smoking reduces the risk of hypothyroidism and increases the risk of hyperthyroidism: evidence from 450,842 mothers giving birth in Denmark.

OBJECTIVE: Smoking may influence on the occurrence of thyroid disease, but studies have led to inconsistent results. In Denmark, information on maternal smoking during pregnancy is registered by midwives, and we investigated the association between maternal smoking as reported during pregnancy and the subsequent maternal risk of having hyper- or hypothyroidism diagnosed. DESIGN: Population-based cohort study. PARTICIPANTS: Using Danish nationwide registers, we identified mothers giving birth in Denmark, 1996-2008, and studied their first pregnancy in the study period. MEASUREMENTS: Information on maternal smoking during the pregnancy and maternal diagnosis of hyper- or hypothyroidism was obtained from the Danish National Hospital Register (DNHR) and prescription of thyroid medication from the Danish National Prescription Register (DNPR). Cox proportional hazards model was used to estimate hazard ratio (HR) with 95% confidence interval (95% CI) for onset of maternal hyper- or hypothyroidism after birth of the child in multivariate analyses adjusting for potential confounders. RESULTS: Among mothers included (n = 450 842), altogether 89,022 (19·7%) reported that they were smokers during the first pregnancy in the study period, and 8905 (2·0%) developed hyper (n = 3389)- or hypothyroidism (n = 5516) after birth of the child. Maternal smoking was associated with a subsequent decreased risk of developing hypothyroidism (adjusted HR 0·75 (95% CI 0·70-0·81)) and an increased risk of hyperthyroidism (1·38 (1·27-1·49)). CONCLUSIONS: Danish nationwide registration of maternal smoking during pregnancy adds further evidence to an association between smoking and thyroid dysfunction; smoking reduced the risk of hypothyroidism and increased the risk of hyperthyroidism.

Psychiatric disease in late adolescence and young adulthood. Foetal programming by maternal hypothyroidism?

OBJECTIVE: Lack of maternal thyroid hormones during foetal brain development may lead to structural abnormalities in the brain. We hypothesized that maternal hypothyroidism during the pregnancy could programme the foetus to development of psychiatric disease later in life. DESIGN: Danish nationwide register study. PARTICIPANTS: Singletons live-born 1980-1990. MEASUREMENTS: Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval for offspring redemption of ≥2 prescriptions of a psychiatric drug from age 15 to 31 years. RESULTS: Among 542 100 adolescents and young adults included, altogether 3979 (0·7%) were born to mothers with hypothyroidism registered before 1996. In crude analyses, the use of a psychiatric drug was more frequent in late adolescence and young adulthood when the mother had hypothyroidism (P < 0·001); however, several possible confounders had to be taken into account. For example, mothers with hypothyroidism often also had a psychiatric registration (38·5% vs 27·7%, P < 0·001) and the use of psychiatric drugs changed over time. After adjustment for confounders including birth year, maternal age and maternal psychiatric history, maternal hypothyroidism was associated with an increased risk of having redeemed prescriptions of anxiolytics [aHR 1·23 (1·03-1·48)] and antipsychotics [aHR 1·22 (1·03-1·44)] in late adolescence and young adulthood. For antidepressants, aHR was 1·07 (0·98-1·17). CONCLUSIONS: The association between maternal hypothyroidism and the use of a psychiatric drug in late adolescence and young adulthood was partly confounded by maternal psychiatric history, but foetal programming by maternal hypothyroidism may be part of the mechanisms leading to the use of anxiolytics and antipsychotics.

Iodine excretion has decreased in Denmark between 2004 and 2010--the importance of iodine content in milk.

Fortification with the essential trace element iodine is widespread worldwide. In the present study, results on iodine excretion and intake of iodine-rich foods from a cross-sectional study carried out in 2004-5, 4 to 5 years after the implementation of mandatory iodine fortification, were compared with data in a study carried out in 2008-10. The 2008-10 study was a follow-up of a cross-sectional study carried out before iodine fortification was implemented. Participants in the cross-sectional studies were randomly selected. Both studies were carried out in the cities of Aalborg and Copenhagen in Denmark. The median urinary iodine concentration decreased in women from 97 µg/l (n 2862) to 78 µg/l (n 2041) (P< 0.001). The decrease persisted after adjustment for age, city and education, and if expressed as estimated 24 h iodine excretion. The prevalence of users of iodine containing dietary supplements increased from 29.4 to 37.3 % (P< 0.001). The total fluid intake increased in women (P< 0.001), but the intake of other iodine-rich foods did not change. The median urinary iodine concentration did not change in men (114 µg/l (n 708) and 107 µg/l (n 424), respectively), while the total fluid intake decreased (P= 0.001). Iodine content was measured in milk sampled in 2000-1 and in 2013. The iodine content was lower in 2013 (12 (sd 3) µg/100 g) compared with that in 2000-1 (16 (sd 6) µg/100 g) (P< 0.001). In conclusion, iodine excretion in women has decreased below the recommended level. The reason might probably, at least partly, be a decreased content of iodine in milk.

Recommended number of participants in iodine nutrition studies is similar before and after an iodine fortification programme.

BACKGROUND: Iodine fortification programs have been applied in many iodine deficient regions. Iodine excess is also unfavourable, and it is recommended to monitor iodine status by measuring urinary iodine concentration (UIC). The number of samples needed in such monitoring depends on the variation in UIC. However, it is not known if variation in UIC differs according to iodine levels. AIM AND METHOD: We aimed to describe the effect of an iodisation program on the individual and group-based variation in UIC in spot urine samples. Group 1 (G1, n = 16) was studied before, and group 2 (G2, n = 21) was studied after an iodine fortification program was implemented. Individual urine samples were collected monthly for one year, 13 samplings. RESULTS: G1s (207 samples) median (interquartile range) UIC was 50 (37-67) µg/L, and G2 (265 samples) was 98 (69-139) µg/L. Median individual coefficient of variation (CV) was 38% in G1 and 40 % in G2 (p = 0.55), whereas the group-based CV was 50% in G1 and 53% in G2. No trend was seen between mean UIC and variation in UIC, neither at the individual (p = 0.36) nor at the group level (p = 0.43). Based on data from both groups, approximately 100 samples were needed to reliably estimate the UIC in a population. CONCLUSION: In two groups studied before and after an iodine fortification program was implemented and with different UIC levels, variation in UIC was comparable both at the individual level and according to UIC level. When mild iodine deficiency is corrected, the number of samples needed to reliably estimate the UIC in a population is unaffected.

Forty-five year trends in overweight and obesity in an indigenous arctic Inuit Society in transition and spatiotemporal trends.

OBJECTIVES: Overweight and obesity associate with increased morbidity and premature death. Westernization of societies heralds rising obesity rates. A steep increase in body mass index (BMI) and overweight in Greenland from 1963 to 1998 led us to follow-up on height, weight, BMI, and rates of overweight among populations in Greenland and assess time trends between different stages of transition. METHODS: BMI was calculated from height and weight measured on Inuit and non-Inuit aged 50 through 69 years surveyed in 1963, 1998, and 2008 in Ammassalik district in East Greenland and in 1998 and 2008 in the capital Nuuk in West Greenland. RESULTS: A total of 1,186 were surveyed in 1963 (52 men/63 women), 1998 (309/226), and 2008 (297/239). BMI increased with time (P < 0.001; 1963/1998/2008 23.3/24.3/26.2 kg/m(2) ). In addition, BMI increased with urbanization in Inuit men (P = 0.001; settlements/town/city, in 1998, 23.9/24.9/25.5 kg/m(2) ; in 2008, 25.0/26.0/27.0 kg/m(2) ) while not in Inuit women (P = 0.18). The number of overweight Inuit (BMI >27 kg/m(2) ) increased with time in men (4.0/25.6/33.2% in 1963/1998/2008, P = 0.001) and in women (13.6/30.7/37.3%, P = 0.001). BMI was above 30 kg/m(2) in 2.0/10.8/17.5% of all Inuit men in 1963/1998/2008 (P = 0.003) and in 8.3%/23.0/24.5% of all Inuit women (P = 0.02) respectively. CONCLUSIONS: Overweight and obesity rates rise with time and with societal transition in Greenland. Settlements and town are catching up with the city where the rate of increase is diminishing, although there were gender differences.

Screening for overt thyroid disease in early pregnancy may be preferable to searching for small aberrations in thyroid function tests.

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.

Serum selenium is low in newly diagnosed Graves' disease: a population-based study.

CONTEXT: Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease. OBJECTIVE: To compare serum selenium (s-Se) values in patients with newly diagnosed autoimmune thyroid disease and controls from the Danish population. DESIGN AND SETTINGS: S-Se was measured in triplicate by a fluorimetric method. PARTICIPANTS: Patients with newly diagnosed Graves' disease (GD) (n = 97) or autoimmune overt hypothyroidism (AIH) (n = 96), euthyroid subjects with high serum levels of thyroid peroxidase antibody (TPO-Ab) (TPO-Ab > 1500 U/ml, n = 92) and random controls (n = 830). MAIN OUTCOME MEASURE: Differences in s-Se values. RESULTS: S-Se was lower in patients with GD than in controls (mean (SD), GD: 89·9 µg/l (18·4); controls: 98·8 µg/l (19·7), P < 0·01). This was confirmed in a multivariate logistic regression model adjusting for age, sex, mineral supplements, smoking, geographical region and time of sampling (P < 0·01). In a linear model, s-Se was similar in patients with AIH (mean (SD): 98·4 µg/l (24·9)) and in controls (P = 0·86). In the multivariate model however, s-Se was marginally lower in patients with AIH compared to controls (P = 0·04). There was no significant difference in s-Se between euthyroid participants with high TPO-Ab and random controls (linear: P = 0·97; multivariate: P = 0·27). CONCLUSION: Patients with newly diagnosed GD and AIH had significantly lower s-Se compared with random controls. Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially 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.

Vitamin D status in North Greenland is influenced by diet and season: indicators of dermal 25-hydroxy vitamin D production north of the Arctic Circle.

Vitamin D status, as measured by serum 25-hydroxy vitamin D (s-25OHD), is important to human health. Dermal 25OHD production depends on UVB light that is influenced by latitude. We aimed to identify factors important to the production of s-25OHD in Arctic people and investigated subjects living in the town of Ilulissat and the settlement of Saqqaq in North Greenland (70°N) during the four seasons. Participants were enrolled with a balanced representation of non-Inuit and Inuit in Ilulissat and Inuit in Saqqaq, men and women, aged 30-39 and 40-49 years. Supplement use, hours spent outdoors and other lifestyle factors were determined by questionnaires. Scores of traditional Inuit food intake were computed from a FFQ at inclusion, and frequencies of intake were recorded at each visit. s-25OHD concentration was measured. There were sixty-four Inuit and thirty-three non-Inuit participants. Inuit food score < 40 % was found in 87, 64 and 48 % of non-Inuit, Inuit in Ilulissat and Inuit in Saqqaq participants, respectively (P= 0·009). Inuit diet associated positively with s-25OHD (P< 0·001). s-25OHD concentration was lower in non-Inuit than in Inuit participants (spring/summer/autumn/winter/average: 30·3 v. 36·8/43·2 v. 44·7/43·6 v. 48·6/32·8 v. 43·5/39·0 v. 44·6 nmol/l, P= 0·002/0·62/0·19/ < 0·001/0·011, respectively). s-25OHD levels differed with season (Inuit, P< 0·001; non-Inuit, P< 0·001) as did diet (Inuit, P< 0·001; non-Inuit, P< 0·001) and hours spent outdoors (Inuit, P< 0·001; non-Inuit, P= 0·012). s-25OHD level was influenced by diet (P< 0·001), season (P< 0·001), origin (P= 0·001), residence (P= 0·013) and sex (P= 0·026). We conclude that the season influenced vitamin D status in Arctic populations beyond diet, ethnicity and vitamin intake. This suggests dermal 25OHD production at a high latitude of 70°N.