Determinants of folate status in pregnant women: results from a national cross-sectional survey in Belgium.

BACKGROUND/OBJECTIVES: Folic acid deficiency during pregnancy can lead to neural tube defects (NTD) in the fetus. Folate status was determined in a representative sample of Belgian pregnant women and determinants of folate status were assessed. SUBJECTS/METHODS: The women were selected using a multi-stage proportionate-to-size sampling design. Blood samples were collected and a questionnaire was completed face-to-face with a study nurse. Erythrocyte (red blood cell (RBC)) folate concentration was measured by chemoluminescence. RESULTS: In total, 1311 pregnant women participated and women with a lower socio-economic status were well represented. Median RBC folate concentration was 436 ng/ml (95% confidence interval=425-452 ng/ml) among first trimester and 496 ng/ml (95% confidence interval=474-515 ng/ml) among third trimester women. Few women had a RBC folate concentration below 140 ng/ml, indicating depletion of folate stores. In the first trimester, 39% of women had a RBC concentration below 400 ng/ml, whereas 15% of the first trimester women had a RBC concentration below 300 ng/ml. Among women in the first trimester, 69.1% reported taking folic acid-containing supplements of which 41.2% started taking them before pregnancy. For third trimester women, these percentages were 76.2% and 21.9%, respectively. In both trimesters, folate status increased significantly with education level and was significantly higher among women who planned the pregnancy and who did not smoke. CONCLUSIONS: It was found that 39% of the first trimester pregnant women had a folate status that might not be optimal to prevent NTD. Some groups of women need to be targeted as they are at higher risk of inadequate folate status.

Simulation of total dietary iodine intake in Flemish preschool children.

The aim of the present study was to calculate the distribution of total iodine intake among Flemish preschoolers and to identify the major sources contributing to iodine intake. A simulation model using a combination of deterministic and probabilistic techniques was utilised. Scenario analyses were performed to assess iodine intake via dairy products, industrially added iodised salt in bread and discretionarily added iodised household salt. Relevant data from 3-d estimated dietary records of 696 preschoolers 2·5-6·5 years old were used. Usual iodine intakes were calculated using the Iowa State University method. With a more generalised utilisation of iodised salt in bread (44 % of the bakers in 2011 instead of 12 % in 2002), mean iodine intake increased from 159 to 164 µg/d using the McCance and Widdowson's food composition table and from 104 to 109 µg/d using the German food composition table. The percentage of preschoolers with an iodine intake below the estimated average requirement (65 µg/d) decreased from 5-12 to 4-9 %, while the percentage of preschoolers with an iodine intake above the tolerable upper intake level (300 µg/d) remained constant (0·3-4 %). Mean iodine intake via food supplements was 4·2 µg/d (total population) and 16·9 µg/d (consumers only). Both in 2002 and 2011, sugared dairy products, milk and iodised salt (21·4, 13·1, and 8·7 %, respectively in 2011) were the main contributors to total iodine intake. In conclusion, dietary iodine intake could still be improved in Flemish preschoolers. The use of adequately iodised household salt and the more generalised use of iodised salt by bakers should be further encouraged.

Optimization of iodine intake in Belgium.

Mild iodine deficiency (MID) is a long-standing problem in Belgium and was recognized only recently as public health issue by the Ministry of Health (MOH). The main MID-related health problems in Belgium are a high prevalence of thyroid nodules and multinodular goiter. The economic cost of thyroid nodular disease only in Belgium was estimated at about €40 millions per year. The Belgian health authorities adopted a selective strategy to optimize iodine intake through the fortification of bread with iodized salt. A progressive, step-by-step increase of the iodine content of salt was chosen in order to minimize the incidence of hyperthyroidism. MOH monitors this strategy by assessing periodically the urinary iodine concentration in school-aged children and pregnant women, as well as by a yearly follow-up of TSH concentrations in all Belgian newborns. Although the implementation of this strategy was an important step, the main drawback of the current situation is the absence of a legal framework to support the strategy. The utilization of iodized salt in bread on a voluntary basis was endorsed by the bakery industry and MOH. However a legal framework is required to assure the effectiveness and continuity of the program and to avoid a higher than optimal iodine intake in the population.

Determination of urinary iodine by inductively coupled plasma mass spectrometry.

BACKGROUND: Mild iodine deficiency is endemic in many countries of Europe including Belgium. Fast, accurate and specific methods for quantification of urinary iodine are needed. We describe in this report a specific ICP-MS method for the quantification of urinary iodine. METHOD: Samples and iodate calibrators were diluted 20 times into aqueous solution containing triton X-100, 1.5% HCl and (103)Rh as an internal standard. Prior digestion or oxidation was not necessary. Results were compared with those obtained by Sandell-Kolthoff (S-K) spectrophotometric method. RESULTS: Comparison of both methods showed good agreement. The Passing-Bablok regression between both methods was ICP-MS=0.986 (S-K)-7.51. The Bland-Altman difference plot showed a small but significant mean difference of -13.3 microg/L for ICP-MS. The between-day coefficient of variation (CV) was 13% at 89 microg/L. Limit of detection was 4 microg/L and limit of quantification was 20 microg/L. No carryover effect has been observed on series containing up to 50 samples. CONCLUSION: The ICP-MS method described here is fast, accurate and specific for the quantification of urinary iodine. Compared to the S-K method the urinary iodine concentrations measured by the ICP-MS method were slightly, but significantly lower. Consequently, the results of studies using S-K method should be compared with caution with those using the ICP-MS method.

Is the management of thyroid nodules and differentiated thyroid cancer in accordance with recent consensus guidelines? - Results of a national survey.

OBJECTIVE: To assess approaches to patients with a potentially malignant thyroid nodule and patients with differentiated thyroid carcinoma and compare them with the European Consensus and Guidelines by the American Thyroid Association. DESIGN: A survey of the 388 active members of the Belgian Thyroid Club. METHODS: A questionnaire addressing the management of an index case and four clinical variations (including variations in the size of the tumour and histological type). The index case was a 40-year-old euthyroid woman with a 3-cm solitary thyroid nodule. Fine-needle aspiration (FNA) cytology showed cellular aspirates with numerous follicular cells and no colloid. RESULTS: The overall response rate was 41%. For the index case, respondents favoured a right lobectomy. Variations in size and histopathology of the nodule altered the management. In the case of a papillary thyroid carcinoma (PTC) of 3 cm in diameter, a total thyroidectomy and prophylactic central lymph node dissection was preferred. After a lobectomy showing a 3.5-cm follicular thyroid carcinoma (FTC), completion surgery followed by radioiodine administration was the most frequent proposal. For the follow-up of the index case with a low-risk disease, determination of serum thyroglobulin (Tg) after recombinant human TSH (rhTSH) administration was considered by the majority of respondents. For the follow-up of a clinical variation with residual disease, immediate planning of a new treatment was (mistakenly) not considered by a majority of respondents. CONCLUSIONS: In most cases, respondents were in accordance with the guidelines, although there were some unexpected variations.

[The nuclear medicine department and the TEP/Biomedical Cyclotron unit]. / Le Service de Médecine Nucléaire et l'Unité TEP/Cyclotron Biomedical.

During the last 25 years, the clinical and experimental activity in nuclear medicine at Erasme hospital has been influenced by the implementation of positron emission tomography (PET) in 1990 as a method of brain functional investigation. The activity of the PET/biomedical cyclotron unit has been dedicated to various subjects in neurology, neurosciences, psychiatry, oncology and cardiology. This has been made possible by developments in radiochemistry. The radiochemistry laboratory has designed and produced original tracers such as 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)-methyl]guanine (FHPG), a tracer of viral thymidine kinase activity in gene therapy protocols. We have brought new applications of PET, such as its integration into stereotactic neurosurgical and radioneurosurgical techniques in order to improve their diagnostic and therapeutic performance in neurooncology. We have also conducted multiple studies on brain physiology and pathophysiology, in particular with the use of functional and metabolic brain mapping methods and the use of tracers of neurotransmission systems. The Department of nuclear medicine has also performed studies on bone metabolism and investigated in vivo imaging methods of infectious and immune processes.

Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia.

Although the importance of selenium for bone metabolism is unknown, some clinical conditions such as Kashin-Beck osteoarthropathy have been associated with selenium deficiency. Although selenium deficiency induces growth retardation in rats, it has not been established whether this growth inhibition is associated with changes in bone metabolism. We investigated the effect of selenium deficiency on bone metabolism in growing male rats fed a selenium-deficient diet for two generations (Se-). In Se- rats, erythrocyte glutathione peroxidase activity and plasma selenium concentration were strongly reduced compared with pair-fed selenium-adequate rats (Se+). Weight and tail length were reduced by 31% and 13% in the Se- rats, respectively (p < 0.001). The Se- diet was associated with a 68% reduction of pituitary growth hormone (GH; p = 0.01) and a 50% reduction of plasma insulin-like growth factor I (IGF-I; p < 0.001). Plasma calcium was lower and urinary calcium concentration was greater in Se- rats. This group had a 2-fold increase in parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in plasma. Plasma osteocalcin and urinary deoxypyridoline were reduced by 25% and 57% in the Se- rats (p < 0.001). Selenium deficiency resulted in a 23% and 21% reduction in bone mineral density (BMD) of the femur and tibia (p < 0.001) and this effect persisted after adjustment for weight in a linear regression model. A 43% reduction in trabecular bone volume of the femoral metaphysis (p < 0.001) was found in Se- rats. This experimental study shows that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and osteopenia in second-generation selenium-deficient rats.

Kashin-Beck disease and iodine deficiency in Tibet.

We evaluated iodine and selenium status in 575 children between 5 and 15 years with Kashin-Beck disease from endemic and non-endemic areas. Of these 267 (46%) children had goiter. The proportion of subjects with goiter was higher in the villages with Kashin-Beck disease than in the control village. In the villages with Kashin-Beck disease, 105 (23%) of the subjects had a serum thyrotropin greater than 10 mU/l as compared with 3 (4%) in the control village. The percentages of low serum thyroxine values and low serum tri-iodothyronine were greater in the villages where Kashin-Beck disease was endemic than in the control village. The percentages of low urinary iodine concentration were significantly greater in the subjects with Kashin-Beck disease. The results suggest that in areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.

Epidemiological support for a multifactorial aetiology of Kashin-Beck disease in Tibet.

We carried out a cross-sectional study in 12 rural villages in order to identify the risk factors for Kashin-Beck disease in Tibet. Children aged 5-15 years (n=575) were examined and their corresponding houses were visited. Samples were collected in order to study fungal contamination of stored grain and the organic matter content of drinking water. Multivariate analysis was performed using logistic regression and population attributable fractions were computed to estimate the impact of each factor. The following variables were independently associated with the disease: age, gender, low socio-economic status, indicators of a poorly diversified diet, iodine deficiency and small water container size (with higher organic matter levels in small containers). Selenium deficiency was severe in all study subjects. The degree of fungal contamination of barley grain was related to the highest percentage of cases (65%) in a sample of the study population. Higher urinary iodine levels were not associated with decreasing prevalence rates when Alternaria sp. was isolated. The data that we report supports the hypothesis that Kashin-Beck disease occurs as a consequence of oxidative damage to cartilage and bone cells when associated with decreased antioxidant defence. Another mechanism that may coexist is bone remodelling stimulated by thyroid hormones whose actions can be blocked by certain mycotoxins.

Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status.

BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS: Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS: In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.

PIP: Selenium is involved in thyroid hormone metabolism. Kashin-Beck disease is a degenerative osteoarticular disorder endemic to certain areas of Tibet, where selenium deficiency is also endemic. Findings are reported from an investigation of the relationship among serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects aged 5-15 years in 12 villages around Lhasa, Tibet, including 1 control village in which no one had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. 280 (49%) subjects had Kashin-Beck disease, 267 (46%) had goiter, and 7 (1%) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66% had a urinary iodine concentration of less than 2 mcg/dl. Mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects and hypothyroidism was more frequent. Severe selenium deficiency was documented in all villages, with 38% of subjects having serum concentrations of less than 5 ng/ml. When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not.

Rapid phase advance of the 24-h melatonin profile in response to afternoon dark exposure.

To investigate the adaptation of melatonin secretion to an abrupt time shift and the effects of sleep facilitation with a hypnotic, eight subjects were submitted to an 8-h advance shift achieved by advancing bedtimes from 2300-0700 to 1500-2300. Each subject participated in two studies (i.e., placebo and zolpidem). Each study included a baseline period with dim light during waking hours and 2300-0700 bedtimes in total darkness. Blood samples for determination of plasma melatonin were obtained at 20-min intervals for 68 h. Advanced exposure to sleep and darkness resulted in a nearly 2-h advance of melatonin onset, which appeared within 6 h after lights-out during the first shifted night, and an almost 1-h advance of the melatonin offset. No further adaptation occurred during the second shifted sleep period. Zolpidem had no beneficial effects on the adaptation of the melatonin profile. There was no relationship between sleep parameters and the magnitude of the melatonin shifts. Thus the overall advance of melatonin profiles was primarily achieved during the initial exposure to an 8-h period of darkness. The present data suggest that exposure to dark affects human circadian phase.

Evidence against a role for the growth hormone-releasing peptide axis in human slow-wave sleep regulation.

A complex interrelationship exists between sleep and somatotropic activity. In humans, intravenous injections of growth hormone-releasing hormone (GHRH) given during sleep consistently stimulate slow-wave (SW) sleep, particularly when given in the latter part of the night. In the present study, the possible somnogenic effects induced under similar conditions by GH-releasing peptide (GHRP) were investigated in seven young healthy men. Bolus intravenous injections of GHRP-2 (1 microgram/kg body wt) or saline, in randomized order, were given after 60 s of the third rapid-eye-movement period. All GHRP injections were immediately followed by transient prolactin elevations and by GH pulses of a magnitude within or around the upper limit of the physiological range. Except for a nonsignificant tendency to increased amounts of wakefulness during the 1st h after the injection, no effects of GHRP-2 administration on sleep were detected. There was in particular no enhancement of SW sleep. Thus, in contrast to GHRH, late-night single injections of GHRP-2 at a dosage resulting in similar GH elevations have no stimulatory effects on SW sleep. The present data provide evidence against the involvement of the GHRP axis in human SW sleep regulation.

Progressive elevation of plasma thyrotropin during adaptation to simulated jet lag: effects of treatment with bright light or zolpidem.

It is well known that TSH secretion is modulated by sleep and circadian rhythmicity, but effects of abrupt shifts of the sleep-wake and dark-light cycles such as occur in jet lag and shift work have not been investigated. The present study examines alterations in the 24-h profiles of plasma TSH and thyroid hormones following an 8-h advance shift achieved without enforcing prolonged sleep deprivation. The effects of bright light exposure or sleep facilitation with zolpidem were investigated in separate studies performed in the same subjects. Each study involved blood sampling at 20-min intervals for 68 h and included a baseline period with dim light during waking hours and 2300-0700 h bedtimes in total darkness. The 8-h shift was achieved by advancing bedtimes to 1500-2300 h. In the course of adaptation to the shift, TSH levels increased progressively in all three studies because daytime sleep failed to inhibit TSH and nighttime wakefulness was associated with large TSH elevations. The overall elevation of TSH tended to be paralleled by a small increase in T3, but not free T4, levels. In the absence of treatment, mean TSH levels following awakening from the second shifted sleep were more than 2-fold higher than during the same time interval following normal nocturnal sleep (2.10 +/- 0.22 mU/L vs. 1.04 +/- 0.14 mU/L; n = 8, P < 0.001). Bright light exposure limited the overall increase of TSH, and mean TSH levels at the end of the study were lower than in the absence of treatment (P < 0.03). Treatment with zolpidem during the first shifted night limited the overall increase in TSH levels during the following waking period (P < 0.05), but the beneficial effect was no longer significant following the second shifted night. Thus, the jet lag syndrome may be associated with a prolonged elevation of peripheral TSH levels that may be limited by treatment with bright light exposure or hypnotic facilitation of sleep.

Effects of bedtime administration of zolpidem on circadian and sleep-related hormonal profiles in normal women.

Short-acting benzodiazepine hypnotics may phase-shift circadian rhythms and improve adaptation of sleep patterns to abrupt time shifts, depending on the timing of administration. The aim of the present study was to determine whether bedtime administration of zolpidem, a non-benzodiazepine hypnotic, causes alterations in circadian rhythmicity or in the normal interactions between sleep and hormones. Eight normal women (aged 21-33 years) each participated in a baseline study and a study with zolpidem administration. On each occasion, blood samples were obtained at 20-minute intervals for 25 hours, starting at 1000 hours. Zolpidem (10 mg) was given orally at 2245 hours. Zolpidem administration was associated with an increase in stages III + IV sleep. Cortisol, melatonin, thyrotropin and growth hormone profiles were similar in both experimental conditions. In contrast, though remaining in the normal range, the nocturnal elevation of prolactin was enhanced two-fold in all subjects after zolpidem during early sleep, and prolactin levels were still 50% higher than baseline in late sleep. Morning levels were similar in both studies. In conclusion, bedtime administration of 10 mg zolpidem, a standard clinical dosage, systematically induces a transient moderate hyperprolactinemia, but does not alter other sleep-related hormonal secretions or endocrine markers of circadian rhythmicity.

The epidemiology of iodine-deficiency disorders in relation to goitrogenic factors and thyroid-stimulating-hormone regulation.

In children aged 5-7 y from goiter-endemic areas in Ubangi, Zaire, and Ntcheu, Malawi, mean serum thyroxin (T4) concentrations were 53 +/- 49 vs 81 +/- 33 nmol/L (P < 0.05), and thyroid-stimulating hormone (TSH) values were 24.3 +/- 9.6 vs 4.5 +/- 3.3 mU/L respectively (P < 0.01); mean urinary iodine concentrations were 0.14 +/- 0.02 vs 0.09 +/- 0.02 mumol/L, and mean thiocyanate concentrations were 0.33 +/- 0.05 vs 0.17 +/- 0.05 nmol/L, respectively (P < 0.05). Mean serum selenium concentrations were 0.343 +/- 0.176 mumol/L in Ubangi and 0.437 +/- 0.178 mumol/L in Ntcheu (P < 0.05). In two groups of 11 adolescent girls from Ubangi, the mean values for excretion of urinary iodine were 1.31 +/- 0.14 and 0.58 +/- 0.17 mumol/L (P < 0.05) after a meal of cassava or a control meal of rice, respectively. In euthyroid subjects from Ubangi, mean serum TSH for a given serum T4 was approximately twice as high for children aged < 15 y than for those aged 16-25 y. The high frequency of myxedematous cretins observed in Ubangi very probably result from both severe iodine and selenium deficiency together with thiocyanate overload.

Endemic juvenile hypothyroidism in a severe endemic goitre area of Sudan.

OBJECTIVE: The aim of the study was to assess thyroid function, iodine intake and exposure to dietary goitrogens of children living in an area with a high prevalence of goitre, in the region of Darfur, Sudan. DESIGN: In a village where goitre affected approximately 85% of children, a cross-sectional survey of thyroid function was performed in children 0-7 years old. PATIENTS: Twenty neonates and 190 children, aged 1 month to 7 years, were included. MEASUREMENTS: Thyroid hormones, urinary iodide and thiocyanate excretion were measured. RESULTS: Mean +/- SD serum T4 was below the normal range at birth (82 +/- 50 nmol/l) and in the age group less than 2 years (73 +/- 46). Children older than 2 years had even lower serum T4: 37 +/- 37 (P < 0.001) at 3-4 years and 36 +/- 38 (P < 0.001) at 5-7 years. Mean serum TSH was 25.8(6.2-107.7) mU/l at birth, 8.3(2.5-27.8) in the group less than 2 years, 15.3(2.9-79.1) at 3-4 years and 16.4(2.7-98.3) at 5-7 years. The overall prevalence of hypothyroidism (TSH > 50 mU/l) was 24%. Mean urinary thiocyanate was high at birth (107 +/- 69 mumol/l), normal in the group less than 2 years and higher in children older than 2 years (126 +/- 69 mumol/l) (P < 0.001). All age groups had a low urinary iodide concentration. CONCLUSION: Hypothyroidism was very frequent in each age group. The higher frequency of hypothyroidism observed in weaned children (> 2 years) was attributed to the combined effects of iodine deficiency and goitrogens (thiocyanate and glycosylflavones) derived from millet.

Iodine deficiency, other trace elements, and goitrogenic factors in the etiopathogeny of iodine deficiency disorders (IDD).

Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have their main cause in the lack of availability of iodine from the soil linked to a severe limitation of food exchanges. Apart from the degrees of severity of the iodine deficiency, the frequencies and symptomatologies of cretinism and the other IDD are influenced by other goitrogenic factors and trace elements. Thiocyanate overload originating from consumption of poorly detoxified cassava is such that this goitrogenic factor aggravates a relative or a severe iodine deficiency. Very recently, a severe selenium deficiency has also been associated with IDD in the human population, whereas in animals, it has been proven to play a role in thyroid function either through a thyroidal or extrathyroidal mechanism. The former involves oxidative damages mediated by free radicals, whereas the latter implies an inhibition of the deiodinase responsible for the utilization of T4 into T3. One concludes that: 1. Goiter has a multifactorial origin; 2. IDD are an important public health problem; and 3. IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated.