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Biomedical subjects

Stig Andersen

Publications and source records attributed to Stig Andersen.

13 recordsLinked to original sources

Geographical clustering and maintained health in individuals harbouring the mutation for Greenland familial cholestasis: A population-based study.

OBJECTIVE: Cholestasis Familiaris Groenlandica, a severe variant of progressive familial intrahepatic cholestasis type 1 (Byler disease), carries an autosomal recessive trait, and the mutation has been located. The disease is relatively common among Inuit in East Greenland. The aim of the study was to assess the carrier frequency and the possible impact on health in populations in East Greenland. MATERIAL AND METHODS: A population-based study comprising 324 Inuit and non-Inuit subjects, aged 50-69 years, living in the Ammassalik district of East Greenland was carried out to analyse the presence of the mutation on ATP8B1 at 18q21. Bilirubin and gamma-glutamyl transpeptidase levels in serum were measured, a physical examination was performed, which included body height and weight, and calculation of BMI. RESULTS: The participation rate was 96%. None of the subjects was homozygous and 12% of Inuit were heterozygous for the mutation. Harbouring the mutation did not influence height (p = 0.26), weight (p = 0.89), BMI (p = 0.65), frequency of self-reported disease (p = 0.17), or differ with gender (p = 0.57). A marked geographical clustering was found (p = 0.002) and heterozygocity for the mutation varied from 5% in a southern to 23% in a northern settlement where 1 out of 75 children could be calculated to have the disease. A physical investigation identified none with jaundice or signs of liver disease. Bilirubin and gamma-glutamyl transpeptidase levels in serum were lower among mutation-positive compared with mutation-negative Inuit. CONCLUSIONS: Heterozygosity for Greenland familial cholestasis is common among the Inuit in East Greenland but it is not a risk factor for disease in the carrier.

Adenosine Triphosphatases↗

Changes in iodine excretion in 50-69-y-old denizens of an Arctic society in transition and iodine excretion as a biomarker of the frequency of consumption of traditional Inuit foods.

BACKGROUND: Iodine intake in Greenland has been hypothesized to exceed 10 times the recommended amount. The transition from a traditional Arctic society may change the iodine intake, but no field studies have been performed. OBJECTIVE: We aimed to ascertain iodine intakes, factors affecting iodine intake in circumpolar populations, and the usefulness of urinary iodine excretion as a biomarker for validation of Inuit food-frequency questionnaires. DESIGN: Data were collected in a cohort study of 4 Greenland population groups: Inuit living in the capital city, the major town, and settlements in East Greenland and non-Inuit. Supplement use and lifestyle factors were evaluated with questionnaires, and dietary habits were ascertained with a food-frequency questionnaire. Iodine was measured in spot urine samples. RESULTS: One percent of the population of Greenland was invited, and the participation rate was 95%. Less than 5% of Inuit but 55% of non-Inuit had urinary iodine excretion < 50 microg/24 h. Median urinary iodine excretion declined with the degree of decrease in the traditional lifestyle: it was 198, 195, 147, and 58 microg/24 h among Inuit in settlements, town, and city and in non-Inuit, respectively (P < 0.001). Participants were divided into diet groups calculated from Inuit food frequency. Iodine excretion decreased with increasing intake of imported foods (P < 0.001). In regression models, type of diet and the subject's lifestyle, sex, weight, ethnicity, and intake of iodine-containing supplements affected urinary iodine excretion. CONCLUSIONS: Circumpolar non-Inuit are at risk of iodine deficiency. Departure from the traditional Inuit diet lowers iodine intake, which should be monitored in Arctic societies. Urinary iodine excretion may be a useful biomarker of traditional Inuit food frequency.

Aged↗

Ethnic differences in bone mineral density between inuit and Caucasians in north Greenland are caused by differences in body size.

Data on bone mineral density (BMD) in living Inuit are limited and BMD measurements in Arctic Inuit using Dualenergy X-ray Absorptiometry (DXA) are lacking. Ethnicity may be important for bone mass. The aim of this study was to validate DXA in rural Arctic Greenland, to measure BMD in Greenland Inuit and Caucasians, and to estimate the importance of ethnicity for BMD. We measured the BMD in 80 healthy subjects living in Ilulissat and Saqqaq in North Greenland twice in both distal forearms and in both heels using peripheral DXA (pDXA). Participants were stratified by origin (Inuit[settlement])/Caucasians, n = 33 [19]/28), gender (men/women, n = 37/43), and age (30-39/40-49, n = 32/48). Caucasians were bigger than Inuit (men/women, height p < 0.001/p < 0.001; weight p = 0.01/ p = 0.026), but had similar BMI (p = 0.42/0.70). Triplicate pDXA measurements showed individual CV% = 0.16-1.79%; overall CV% = 1.1% (forearm)/1.0% (heel). Data followed the normal distribution (p = 0.65-0.99) with identical variances between Inuit and Caucasians (p = 0.12-0.63). Mean BMD in right forearm/left forearm/right heel/left heel was: Inuit men 0.570/0.568/0.549/0.536 g/cm2; Inuit women 0.484/0.474/0.473/0.464 g/cm2; Caucasian men 0.580/0.570/0.646/0.638 g/cm2; Caucasian women 0.495/0.496/0.552/0.553 g/cm2. An ethnic difference in heel BMD (p < 0.001) disappeared when adjusted for weight (p = 0.30). No difference was found in forearm BMD. In conclusion, pDXA is feasible and reliable in rural Greenland. Ethnic differences in BMD are small and may reflect differences in body size.

Absorptiometry, Photon↗

Hypothyroidism in the elderly: pathophysiology, diagnosis and 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.

Aged↗

Gender diversity in developing overweight over 35 years of Westernization in an Inuit hunter cohort and ethno-specific body mass index for evaluation of body-weight abnormalities.

OBJECTIVE: To establish an Inuit body mass index (BMI) norm from a healthy, not malnourished, pure Inuit population and to investigate the development of overweight in the Inuit in Greenland. DESIGN: Longitudinal study with 35 years follow-up on overweight among Inuit in Greenland. METHODS: The heights and weights of 97% of all inhabitants in Eastgreenland in 1963 (n=1852) were recovered recently and BMI calculated. We obtained similar data in 96% of the 50-69-year-old population in Eastgreenland in 1998 and in a random sample of 25% of individuals aged 50-69 years in the capital Nuuk (n=535). RESULTS: Overweight or obesity, as defined by the World Health Organization (WHO), was found in 30% of all men and 22% of all women in Eastgreenland in 1963, and in 31% of young Inuit hunters in 1963. Such high rates were incompatible with a hunter's way of living. Inuit-specific BMI norms from data on healthy Inuit aged 20-29 years in 1963 were computed: men, 20.2-27.9; women, 17.9-27.7. These differed from the WHO classification (P<0.001). Using the Inuit-specific BMI norm for the classification of 50-69-year-old Inuit in 1963 and 1998, the fraction of overweight men increased by over six times (4.0 to 25.6%; P<0.001), and overweight increased with Westernization (P=0.001). The fraction of overweight women by the Inuit BMI norm doubled from 1963 to 1998 (14.0 to 30.7%; P<0.001) while median BMI remained unaltered (P=0.22) because the fraction of slim women more than doubled (3.5 to 9.0%; P<0.001). CONCLUSION: A steep increase in the fraction of overweight Inuit men and women calls for intervention. Westernization predicted increased BMI. In women the increased number of obese people was accompanied by an increased fraction of slim people. This illustrates that transition can be modified and indicates that monitoring of populations in transition should observe gender differences. Finally, the historical data argue against the global applicability of the WHO delineation of normal BMI.

Adult↗

Body proportions in healthy adult Inuit in East Greenland in 1963.

OBJECTIVES: It is important to know the starting point when describing changes in Inuit in transition. STUDY DESIGN: The original charts of 1,852 individuals from the epidemiological investigation in East Greenland around 1963 performed by Littauer and colleagues were recovered recently. They included height, weight and a physical investigation. METHODS AND RESULTS: The focus of this paper was adult Inuit body proportions in 1963 by ten-year age groups excluding participants with disabilities affecting body build. Relatively stable values were seen in both genders with age. Median values in men/women aged 20 years and above were: height 164/153.5 cm, weight 64/54 kg and BMI 23.7/23.1. Men aged 50 years and above had a little lower height and weight than young men. Women aged 40-49 years had a higher weight and BMI, but this evened out in the older age groups. Median BMI was relatively high compared to WHO definition. CONCLUSIONS: The data from 1963 gives a starting point for evaluating changes in Inuit body build and the prevalence of overweight. Furthermore, they indicate a need for Inuit-specific normal BMI delineation.

Adult↗

Feasibility of Dual-Energy X-ray Absorptiometry in Arctic field studies.

BACKGROUND: Bone strength decreases with age. Bone mineral density (BMD) is a measure of bone strength. Data on BMD in present-day Inuit are limited, and data on circumpolar populations using Dual Energy X-ray Absorptiometry (DEXA scanning) are lacking. OBJECTIVES: Our aims were to validate DEXA scanning for use in field studies in the Arctic region and to obtain data on BMD in Greenland Inuit. METHODS: We measured BMD in 52 healthy Inuit living in Ilulissat and Saqqaq in North Greenland using a portable peripheral DEXA scanner. The measurement sites were forearms and calcaneal bones. Two measurements were performed at both radii and both calcanei. Triplicate measurements were performed in eleven Inuit. RESULTS: The portable scanner fitted into a standard bag suitable for transportation in the arctic winter. Imprecision was well within 2% for all calibrations. CV% were 0.16% to 1.79% in the forearms and 0.38% to 1.53% in the heels. The overall CV% was 1.09% in forearm and 1.01% in heel. Mean BMD in men was 0.569 g/cm2 in forearms and 0.542 in heel. In women it was 0.479 in forearms and 0.468 in heel. CONCLUSION: DEXA scanning is a feasible, reliable and comfortable method in rural Greenland. BMD values are now available for Greenland Inuit.

Absorptiometry, Photon↗

Humic substances in drinking water and the epidemiology of thyroid disease.

Thyroid diseases are common in all populations but the type and frequency depends on environmental factors. In Denmark geographical differences in iodine intake are caused by different iodine contents of drinking water, which varies from < 1 to 139 microg iodine per litre. Comparative epidemiologic studies have demonstrated considerable differences in type and occurrence of thyroid disease with more goitre and hyperthyroidism in Aalborg with water iodine content around 5 microg/L, and more hypothyroidism in Copenhagen with water iodine around 20 microg/L. In Denmark, iodine in ground water is bound in humic substances, which have probably leached from marine sediments in the aquifers. Interestingly, humic substances in water from other parts of the world have goitrogenic properties, especially humic substances from coal and shale. Humic substances are heterogeneous mixtures of naturally occurring molecules, produced by decomposition of plant and animal tissues. The effect of humic substances in drinking water on the epidemiology of thyroid disease probably depends on the source of aquifer sediments.

Chelating Agents↗

Biologic variation is important for interpretation of thyroid function tests.

Large variations exist in thyrotropin (TSH) and thyroid hormones in serum. The components of variation include preanalytical, analytical, and biologic variation. This is divided into between- and within-individual variation. The latter consists of circadian and seasonal differences although there are indicators of a genetically determined starting point. The ratio of within- to between-individual variation describes the reliability of population-based reference ranges. This ratio is low for serum TSH, thyroxine (T(4)) and triiodothyronine (T(3)) indicating that laboratory reference ranges are relatively insensitive to aberrations from normality in the individual. Solutions are considered but reducing the analytical variation below the calculated analytical goals of 7%, 5% and 12% for serum T(3), T(4), and TSH does not improve diagnostic performance. Neither does determination of the individual set-point and reference range. In practice this means that population-based reference ranges are necessary but that it is important to recognize their limitations for use in individuals. Serum TSH responds with amplification to minor alterations in T(4) and T(3). A consistently abnormal TSH probably indicates that T(4) and T(3) are not normal for the individual even when inside the laboratory reference range. This underlines the importance of TSH in diagnosis and monitoring of thyroid dysfunctions. Also, it implies that subclinical thyroid disease may be defined in purely biochemical terms. Under critical circumstances such as pregnancy where normal thyroid function is of importance for fetal brain development, subclinical thyroid disease should be treated. Even TSH within the reference range may be associated with slightly abnormal thyroid function of the individual. The clinical importance of such small abnormalities in thyroid function in small children and pregnant women for brain development remains to be elucidated.

Circadian Rhythm↗

Thiocyanate in food and iodine in milk: from domestic animal feeding to improved understanding of cretinism.

Transport of iodine in the mammary gland into breast milk plays a central role in various fields of prevention of thyroid diseases. First, a sufficient content of iodine in the mother's milk is necessary for normal brain development in the breastfed child. This is attained by expression during lactation in the mammary gland of the sodium iodide symporter (NIS), also responsible for iodine transport in the thyroid. Milk iodine content varies with the iodine intake of the mother, and urinary iodine excretion in groups of mothers seems to be a valuable indicator of the iodine status of their breastfed children. Second, iodine in dairy products provides a considerable part of iodine intake in many populations. Thiocyanate from rapeseed feeding of cows decreases milk iodine content, probably by competitive inhibition of NIS in the mammary gland. Alterations in feeding of dairy cows may alter the iodine content of consumer milk, and this may influence the risk of thyroid diseases in the population. Thiocyanate inhibition of iodine transport into milk may also be operative in humans with a high thiocyanate intake. This could further impair iodine status in breastfed children in low-iodine intake areas of the world. It can be speculated that a low-iodine content of mother's milk because of inhibition of NIS in the mammary gland may be one factor of importance for development of myxedematous cretinism.

Animal Feed↗

Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease.

High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual. We undertook a longitudinal study of variation in thyroid function tests in 16 healthy men with monthly sampling for 12 months using standard procedures. We measured serum T(4), T(3), free T(4) index, and TSH. All individuals had different variations of thyroid function tests (P < 0.001 for all variables) around individual mean values (set points) (P < 0.001 for all variables). The width of the individual 95% confidence intervals were approximately half that of the group for all variables. Accordingly, the index of individuality was low: T(4) = 0.58; T(3) = 0.54; free T(4) index = 0.59; TSH = 0.49. One test result described the individual set point with a precision of +/- 25% for T(4), T(3), free T(4) index, and +/- 50% for TSH. The differences required to be 95% confident of significant changes in repeated testing were (average, range): T(4) = 28, 11-62 nmol/liter; T(3) = 0.55, 0.3--0.9 nmol/liter; free T4 index = 33, 15-61 nmol/liter; TSH = 0.75, 0.2-1.6 mU/liter. Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual. Because serum TSH responds with logarithmically amplified variation to minor changes in serum T(4) and T(3), abnormal serum TSH may indicate that serum T(4) and T(3) are not normal for an individual. A condition with abnormal serum TSH but with serum T(4) and T(3) within laboratory reference ranges is labeled subclinical thyroid disease. Our data indicate that the distinction between subclinical and overt thyroid disease (abnormal serum TSH and abnormal T(4) and/or T(3)) is somewhat arbitrary. For the same degree of thyroid function abnormality, the diagnosis depends to a considerable extent on the position of the patient's normal set point for T(4) and T(3) within the laboratory reference range.

Adult↗

Iodine in drinking water in Denmark is bound in humic substances.

OBJECTIVE: The iodine intake level is important for the occurrence of thyroid disorders in a population. We have previously found that iodine in drinking water is related to iodine excretion but whether iodine is present as iodide or bound in other molecules remains unknown. DESIGN: We measured iodine in drinking water from 22 locations in Denmark. Six locations were selected by iodine content for further tap water analysis (Skagen 140 micro g/l, Samsoe 56 micro g/l, Nykoebing S. 50 micro g/l, Nakskov 40 micro g/l, Ringsted 38 micro g/l, Copenhagen 19 micro g/l). METHODS: HPLC size exclusion before (Skagen) and after (all sites) freeze drying and measurement of absorbance (280 nm) and iodine in fractions, and fluorescence spectroscopy of bulk organic matter in Skagen drinking water. RESULTS: Iodine content was unaltered after 3 Years (P=0.2). All samples contained organic molecules with characteristics similar to humic substances. Most iodine eluted with humic substances (Skagen 99%, Ringsted 98%, Nykoebing S. 90%, Copenhagen 90%, Samsoe 75%, Nakskov 40%). Changing pH and ionic strength and preincubation with iodide indicated that iodine was bound in humic substances. Humic substances may affect thyroid function but differ with geology. Geological and geochemical data agree with tap water humic substances having been released from marine deposits. Iodine is abundant in the marine environment and marine deposits are particularly rich in iodine. Correlation analysis (r=0.85, P=0.03) conform to iodine in drinking water, suggesting marine humic substances at the source rock. CONCLUSION: Iodine in Danish drinking water varied considerably. In drinking water with a high iodine content, the iodine mainly eluted with humic substances derived from marine source rock. We hypothesize that iodine in drinking water in general suggests coexisting humic substances of marine origin.

Denmark↗

Iodine content of traditional Greenlandic food items and tap water in East and West Greenland.

OBJECTIVES: The iodine intake level is important for the occurrence of thyroid disorders in a population. The iodine intake in Greenland has been proposed to be more than ten times the recommended level. However, no measurements have been performed to determine the iodine content of Greenlandic food items, drinking water, and beverages available in East and West Greenland. STUDY DESIGN: Food samples were collected at the local market, kalaalimineerniarfik, in Nuuk and Ammassalik, and tap water was obtained from all towns in Greenland. Beverages were purchased at Kalaallit Niuerfiat KNI Pisiniarfik. RESULTS: Iodine content of seal, whale, wild fowl, reindeer, and musk ox varied between 4 and 195 microg/kg with low values for terrestrial animals (< 10 microg/kg) and higher values for marine animals (10-195 microg/kg). The iodine content of fish varied from 9 microg/kg in freshwater fish to 1,380 microg/kg in a sample of cod. The iodine content of sea mammals was: blubber 130 microg/kg; viscera 70 microg/kg; meat 21 microg/kg. No difference was observed between animals from East Greenland and West Greenland (P > 0.1). Iodine content of tap water was below 3.3 microg/l for all towns. Two sorts of beer had a high iodine content, up to 240 microg/l. The iodine content of all other beverages was 5-38 microg/l. CONCLUSIONS: We found a relatively high iodine content in marine animals but low iodine content in tap water and beverages in Greenland. The food and drinking water evaluated in the present study indicate adequate iodine intake in this area and do not support the notion that Greenland is an area of excessive iodine intake.

Animals↗