Prevention in thyroidology.
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Health Policy↗
Biomedical subjects
Peter Laurberg
Publications and source records attributed to Peter Laurberg.
Risk factors for goiter and thyroid nodules.
The occurrence of thyroid diseases is determined by interplay between genetic and environmental factors. The major environmental factor that determines goiter prevalence is iodine status, but other environmental factors influencing entire populations have been identified such as goitrogens in food and drinking water. Less focus has been on individual environmental factors and the interplay between factors. The goiter prevalence is higher in certain groups in the population. The variation in goiter prevalence between the genders is well known with a higher occurrence among women. The association with age is probably dependent on iodine status, because it seems that the zenith of goiter prevalence appears earlier in life the more severe iodine deficiency the population is exposed to. The association with individual risk factors has been investigated in some studies, especially the association with tobacco smoking. In iodine-deficient areas, a strong association between tobacco smoking and goiter prevalence is found, whereas the association is less pronounced in iodine-replete areas. This was predictable from experimental studies showing thiocyanate to be the mediator of the goitrogenic effect of tobacco smoke acting as a competitive inhibitor of iodine uptake. The association with alcohol intake has only been investigated in few studies, but a low occurrence of goiter among alcohol consumers has been found. The mechanism of this association is not known. Increased goiter prevalence during pregnancy has been reported, and recently a long-term goitrogenic effect of pregnancies has also been shown. As demonstrated for tobacco smoking, this association is dependent on iodine status, because the association has only been found in areas with a suboptimal iodine intake. This indicates pregnancy-induced goiter to be the result of exacerbation of existing iodine deficiency. Recently, the use of oral contraceptives has been shown to be associated with a markedly reduced prevalence of goiter, although experimental studies have previously shown proliferative effects of estrogens on thyrocytes. Some implications for prevention of thyroid disease could be suggested. Discussion of smoking habits should be included in a consultation for goiter with a motivation to quit smoking. Iodine deficiency has particularly strong goitrogenic effects during pregnancy and for the sake of the mother as well as the fetus, sufficient iodine supply should be ensured to all pregnant women. The difference in age maximum in goiter prevalence suggests that monitoring of iodine deficiency disorders should ideally include a spectrum of age groups.
Female↗
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↗
Relations between various measures of iodine intake and thyroid volume, thyroid nodularity, and serum thyroglobulin.
BACKGROUND: Iodine intake can be measured in various ways, and each method may have advantages and disadvantages. OBJECTIVE: We sought to investigate the potential associations of various measures of iodine intake with thyroid volume, prevalence of thyroid nodules, and serum thyroglobulin. We also sought to identify, if possible, groups at risk of thyroid disease because of their food choices. DESIGN: This cohort study included 4649 randomly selected subjects with mild-to-moderate iodine deficiency; the subjects lived in 2 cities in Denmark. Iodine intake was estimated by using a food-frequency questionnaire and by measuring iodine excretion in spot urine samples. Thyroid volume and nodularity were measured with ultrasonography. RESULTS: In multiple linear regression models, significant inverse relations were found between thyroid volume and estimated 24-h iodine excretion, iodine intake from diet plus supplements, iodine intake from diet/kg body wt, and milk intake (P = 0.001 for all), but not urinary iodine excretion measured as a concentration (P = 0.40). All measures of iodine intake were significantly related to serum thyroglobulin concentration (P <or= 0.002), but only some measures of iodine intake were significantly related to the prevalence of thyroid nodules. CONCLUSIONS: Even in a geographic area where mild iodine deficiency is common, a significant relation between iodine intake and thyroid volume was found. All measures of iodine intake, except iodine excretion measured as a urinary concentration, predicted thyroid volume. Serum thyroglobulin concentration appears to be a good marker of iodine status. Subgroups with low intakes of milk and milk products had an increased risk of thyroid disease.
Adult↗
Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey.
Around 3-4 billion people in the world are covered by iodine supplementation programs to prevent developmental brain damage and other iodine deficiency (ID) disorders. Mild ID is associated with more hyperthyroidism and less hypothyroidism in the population than a high iodine intake. Knowledge of the iodine intake levels where the shifts in incidences occur is important for planning of iodine supplementation programs. A computer-based register linked to thyroid diagnostic laboratories was used to continuously identify all new cases of overt hyper- and hypothyroidism in two population cohorts with moderate and mild ID, respectively (Aalborg, n = 310,124; urinary iodine, 45 micro g/liter; and Copenhagen, n = 225,707; urinary iodine, 61 micro g/liter). The investigation was initiated before iodization of salt in Denmark and was part of the monitoring program. In 1997-1998, the incidence rate of overt hyperthyroidism was high in the area with the lowest iodine intake (92.9/100,000 per year) compared with the area with only mild ID (65.4/100,000 per year). Standardized rate ratio was 1.49, and 95% confidence interval was 1.22-1.81. The opposite relationship was present for overt hypothyroidism (moderate ID, 26.5/100,000 per year; mild ID, 40.1/100,000 per year; standardized rate ratio, 0.73; 95% confidence interval, 0.55-0.97). The different incidence rates were confirmed during each of the two following years. The results of this prospective investigation of the incidence of overt hyper- and hypothyroidism suggest that iodine supplementation of a population may increase the incidence of overt hypothyroidism, even if the population is moderately iodine-deficient. In such a population, the increase in risk of hypothyroidism should be weighed against the risk of ID disorders such as hyperthyroidism due to multinodular toxic goiter. The optimal level of iodine intake to prevent thyroid disease may be a relatively narrow range around the recommended daily iodine intake of 150 micro g.
Adolescent↗
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↗
Parity is associated with increased thyroid volume solely among smokers in an area with moderate to mild iodine deficiency.
OBJECTIVE: Pregnancy has been suggested as part of the explanation of the gender difference in the prevalence of goitre, but opposing results have been reported on the association between pregnancy and goitre. We investigated the association between parity and thyroid volume and a possible impact of iodine deficiency and tobacco smoking on this association. DESIGN: A comparative, cross-sectional study of 3712 women randomly sampled from the general population in two geographical areas with moderate and mild iodine deficiency. METHODS: The participants answered questionnaires with an obstetric anamnesis, and ultrasonography of the thyroid was performed. Data were analysed in linear models and logistic regression analysis to adjust for age, iodine status, use of oral contraceptives and smoking habits. Women with present or recent pregnancies were excluded from the analyses. RESULTS: A higher thyroid volume was found among parous than among nulliparous women (P=0.007). The association between parity and thyroid volume was strongest in the youngest age groups, in the region with the most severe iodine deficiency, and among smokers. No association was found between parity and the prevalence of solitary or multiple thyroid nodules. Number of births, age at menarche or menopause, the number of fertile years, and age at first childbirth were not associated with thyroid volume. CONCLUSION: Pregnancy increases thyroid volume, particularly when combined with tobacco smoking and iodine deficiency. The effect is probably reversible seen over a spectrum of several years.
Adolescent↗
Increased risk of osteoporotic fractures in patients with Cushing's syndrome.
OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.
Adrenal Glands↗
Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial.
OBJECTIVE: To evaluate the effect of physiological adult growth hormone (GH) replacement on bones. DESIGN: Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment. METHODS: Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined. RESULTS: IGF-I levels increased from 63.2 microg/l (+/-10.1) to 193.6 (+/- 25.8) microg/l (mean (+/-s.e.)) (P<0.001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P<0.001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of +/- 1.8 (+/- 3.8) in the GH-treated group vs an increase of 1.0 (+/-2.9)) in the placebo-treated group (P=0.002). CONCLUSIONS: No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group. This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.
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↗
Global or Gaelic epidemic of hypothyroidism?
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Denmark↗