Klaus M. Pedersen

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.

Iodine deficiency in pregnancy in Denmark: Regional variations and frequency of individual iodine supplementation

Iodine requirements are increased during pregnancy and lactation and adequate iodine intake is important for normal brain development of the fetus/newborn child.

Iodine status in neonates in Denmark: regional variations and dependency on maternal iodine supplementation

Nøhr SB, Laurberg P, Børlum K‐G, Pedersen KM, Johannesen PL, Damm P, Fuglsang E, Johansen A. Iodine status of neonates in Denmark: regional variations and dependency on maternal iodine supplementation. Acta Pàdiatr 1994;83:578–82. Stockholm. ISSN 0803–5253

Urinary Iodine Excretion is Low and Serum Thyroglobulin High in Pregnant Women in Parts of Denmark

In the Randers area of Denmark urinary iodine excretion (which reflects iodine intake) was found to be much lower than recommended intake levels, both in women in late pregnancy [52(23–118) pg iodine/g creatinine, median, range, n = 20] and in non‐pregnant controls [42(23–711, n = 20]. Serum thyroglobulin which is high in iodine deficiency was 32.5 pgA (median) (range 10.5–78.0) in the control women and considerably higher in the pregnant women [67.0 pgll (9.0–385)]. This increase was probably due to the extra iodine requirement of pregnancy which was not satisfied with an adequate increase in iodine intake. The results may suggest that pregnant women in this area should receive iodine supplementation and that a general program of iodine supplementation should be considered.

Thyroglobulin in smoking mothers and their newborns at delivery suggests autoregulation of placental iodide transport overcoming thiocyanate inhibition

BACKGROUND Placental transport of iodide is required for fetal thyroid hormone production. The sodium iodide symporter (NIS) mediates active iodide transport into the thyroid and the lactating mammary gland and is also present in placenta. NIS is competitively inhibited by thiocyanate from maternal smoking, but compensatory autoregulation of iodide transport differs between organs. The extent of autoregulation of placental iodide transport remains to be clarified. OBJECTIVE To compare the impact of maternal smoking on thyroglobulin (Tg) levels in maternal serum at delivery and in cord serum as markers of maternal and fetal iodine deficiency. METHODS One hundred and forty healthy, pregnant women admitted for delivery and their newborns were studied before the iodine fortification of salt in Denmark. Cotinine in urine and serum classified mothers as smokers (n=50) or nonsmokers (n=90). The pregnant women reported on intake of iodine-containing supplements during pregnancy and Tg in maternal serum at delivery and in cord serum were analyzed. RESULTS In a context of mild-to-moderate iodine deficiency, smoking mothers had significantly higher serum Tg than nonsmoking mothers (mean Tg smokers 40.2 vs nonsmokers 24.4 μg/l, P=0.004) and so had their respective newborns (cord Tg 80.2 vs 52.4 μg/l, P=0.006), but the ratio between Tg in cord serum and maternal serum was not significantly different in smokers compared with nonsmokers (smoking 2.06 vs nonsmoking 2.22, P=0.69). CONCLUSION Maternal smoking increased the degree of iodine deficiency in parallel in the mother and the fetus, as reflected by increased Tg levels. However, placental iodide transport seemed unaffected despite high thiocyanate levels, suggesting that thiocyanate-insensitive iodide transporters alternative to NIS are active or that NIS in the placenta is autoregulated to keep iodide transport unaltered.

Iodine deficiency influences thyroid autoimmunity in old age – A comparative population-based study

OBJECTIVE To assess thyroid autoimmunity among elderly people living in an area with low iodine intake compared to the sustained recommended iodine intake from a natural source, and to estimate the importance of migration. DESIGN AND SETTING Iodine content of drinking water is highly different in the Danish towns Randers and Skagen. We collected blood and spot urine samples from 430 long-term Randers and Skagen dwellers aged 75-80 years, who filled in a questionnaire. We measured thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in serum and iodine and creatinine in urine. RESULTS Participation rate was 47% (n=212 (men/women 82/130) in Randers; 218 (84/134) in Skagen). Iodine deficiency prevailed in Randers while Skagen dwellers were iodine replete (median urinary iodine 74 μg/24h vs. 184 μg/24h, p<0.001). Thyroid antibodies were more frequent in Randers than in Skagen residents (42% vs. 32%; p=0.006) and more likely with iodine excretion <50 μg/24h (OR, 95%CI: 1.9, 1.1-3.4). Differences between towns increased with longer duration of residence as trends in the occurrence of TGAb and TPOAb were opposite (p<0.001; p=0.007). CONCLUSIONS Thyroid autoantibodies were common in old age, influenced by the iodine intake level, and the lowest frequency was found at the recommended iodine intake level.

Iodine status in Danish pregnant and breastfeeding women including studies of some challenges in urinary iodine status evaluation

Denmark was previously iodine deficient with regional differences. Moderate iodine deficiency appeared in West Denmark and mild iodine deficiency in East Denmark and also Danish pregnant and breastfeeding women suffered from iodine deficiency. The Danish mandatory iodine fortification of salt was introduced in the year 2000 and has increased iodine intake in the Danish population. However, median urinary iodine concentration in the general population and in pregnant and breastfeeding women is still below the level recommended, corresponding to mild iodine deficiency. Certain characteristics may challenge the evaluation of urinary iodine status in pregnancy and during breastfeeding. This review also addresses methodological challenges related to spot urine sampling conditions and the use of iodine supplement and discusses the use of non-pregnant population groups as a proxy for iodine intake in pregnant women.

Iodine Intake in Denmark — Influence on the Pattern of Thyroid Disease

In Denmark a large survey of urinary iodine excretion in 6000 adolescent males from different parts of the country was performed in the sixties by Munkner (1). It demonstrated that iodine excretion was relatively low in general with an average value of 64 μg/day. Values were higher in the eastern part of the country with values in the Copenhagen area of 78 μg/24 h. In Jutland the values were lower being around 40 μg/day in many areas. Subsequently a large survey was initiated by the health authorities to evaluate the prevalence of goitre among schoolchildren all over Denmark. Since only few cases of clinical goitre were found it was concluded that iodine supplementation was unnecessary (unpublished).