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Biomedical subjects

F Delange

Publications and source records attributed to F Delange.

At least 37 records · Page 2Linked to original sources
PubMed2000

Congenital central isolated hypothyroidism caused by a homozygous mutation in the TSH-beta subunit gene.

We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6-11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3; competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin-releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age 15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH stimulation slightly increased serum TSH using two immunometric assays, from less than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single nucleotide deletion in codon 105 producing a frame shift that results in a truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of the 5 terminal residues. This mutation was previously reported in one Brazilian and two German families. The abnormal, and presumably biologically inactive, TSH can be detected in serum using appropriate antibodies. Its relatively small amount in serum is due to either reduced secretion or rapid degradation. The occurrence of the same mutation in three families of different ethnic origin suggests that this mutation may be prevalent in the population. Common ancestry or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware that neonatal screening of congenital hypothyroidism based on blood spot TSH measurement will not detect this rare but severe genetic defect.

Adolescent↗
PubMed2000

The potential repercussions of maternal, fetal, and neonatal hypothyroxinemia on the progeny.

The adequate functioning of both the maternal and fetal thyroid glands play an important role to ensure that the fetal neuropsycho-intellectual development progresses normally. Three sets of clinical disorders are considered, that may eventually lead to impaired brain development. Firstly, in infants with a defect of glandular ontogenesis (congenital hypothyroidism), the participation of maternal thyroid hormones to the fetal circulating thyroxine environment is normal and, therefore, risk of brain damage results exclusively from the insufficient hormone production by the abnormal fetal thyroid gland. Secondly, when it is only the maternal thyroid gland that is functionally deficient (autoimmune hypothyroidism), the severity and temporal occurrence of maternal underfunction will both drive the resulting consequences for impaired fetal neuronal development. Clinical situations of this type may obviously take place already during early gestation (in women with known but untreated hypothyroidism) or appear only during later gestational stages (in women who have AITD and remain euthyroid during the first half of gestation). Lastly, in conditions with iodine deficiency, both maternal and fetal thyroid functions are affected and, therefore, it is primarily the degree and precocity of the maternal hypothyroxinemia due to iodine deficiency during pregnancy that will drive the potential repercussions for fetal neurological development. In the present review, we summarize available data and develop our present concepts concerning the complex feto-maternal thyroid relationships and the potential impacts of thyroid function abnormalities on the ideal development of the offspring.

Developmental Disabilities↗
PubMed2000

Silent iodine prophylaxis in Western Europe only partly corrects iodine deficiency; the case of Belgium.

OBJECTIVE: Belgium is one of the Western European countries in which no program of iodine-deficiency correction using iodized salt has been implemented, in spite of well-documented mild iodine deficiency. In 1995, the median urinary iodine concentration was 55 microg/l (normal: 100-200) and the prevalence of goiter was 11% (normal: below 5%) in representative samples of schoolchildren aged 6-12 years. Based on these results, the authors of the present study and others had emphasized to health professionals and to the public the necessity for iodine supplementation. The objective of this study was to evaluate as to whether these efforts had resulted in an improvement in the status of iodine nutrition. DESIGN: We performed a national survey of the status of iodine nutrition in Belgium based on the determination of thyroid volume, obtained by ultrasonography, and urinary iodine concentrations in schoolchildren. METHODS: A mobile van equipped with an ultrasound instrument, a computer and a deep-freeze visited 23 schools selected from across the country. The sample included 2855 schoolchildren (1365 boys and 1490 girls) aged 6-12 years. RESULTS: The results show a homogeneous situation in the whole country, with a median urinary iodine concentration of 80 microg/l and a goiter prevalence of 5.7%. Urinary iodine slightly decreases with age in girls and reaches a critical value of 59 microg/l at the age of 12 years, together with a goiter prevalence of 18.4%. CONCLUSION: Iodine nutrition has improved slightly in Belgium but mild iodine deficiency continues, with public-health consequences. The improvement indicates silent iodine prophylaxis, as no official salt-iodization measures have been taken. Silent iodine prophylaxis only partly corrects iodine deficiency in Western Europe. Active measures, including the implementation of a program of salt iodization, are urgently required.

Aging↗
PubMed2000

Iodine supplementation: benefits outweigh risks.

In 1990, iodine deficiency affected almost one-third of the world population and was the greatest single cause of preventable brain damage and mental retardation. Following a resolution adopted by the World Summit for Children in 1990. major programmes of iodine supplementation were implemented by the governments of the affected countries with the support of major donors. Iodisation of salt was recognised as the method of choice. Nine years later, by April 1999, 75% of the affected countries had legislation on salt iodisation and 68% of the affected populations had access to iodised salt. The prevalence of iodine deficiency disorders decreased drastically in most countries and the deficiency disappeared completely in some such as Peru. This result constitutes a public heath success unprecedented with a non-infectious disease. However, occasional adverse effects occurred. The principle effect is iodine-induced hyperthyroidism which occurs essentially in older people with autonomous nodular goitres, especially following iodine intake that is too rapid and of too massive an increment. The incidence of the disorder is usually low and reverts spontaneously to the background rate of hyperthyroidism or even below this rate after 1 to 10 years of iodine supplementation. The possible occurrence of iodine-induced thyroiditis in susceptible individuals has not been clearly demonstrated by large epidemiological surveys. Iodine supplementation is followed by an increased prevalence of occult papillary carcinoma of the thyroid discovered at autopsy but the prognosis of thyroid cancer is improved due to a shift towards differentiated forms of thyroid cancer that are diagnosed at earlier stages. Iodine-induced hyperthyroidism and other adverse effects can be almost entirely avoided by adequate and sustained quality control and monitoring of iodine supplementation which should also confirm adequate iodine intake. Available evidence clearly confirms that the benefits of correcting iodine deficiency far outweigh the risks of iodine supplementation.

Dietary Supplements↗
PubMed1999

Risks of iodine-induced hyperthyroidism after correction of iodine deficiency by iodized salt.

Biochemical signs of hyperthyroidism, or even overt and possibly lethal clinical hyperthyroidism were reported in 2 severely iodine-deficient African countries (Zimbabwe and Democratic Republic of Congo, RDC) soon after the introduction of iodized salt. The 2 countries had access to iodized salt produced in Botswana, as well as 5 other countries in the region, namely Cameroon, Nigeria, Kenya, Tanzania, and Zambia. Therefore, a multicenter study was conducted in these 7 countries to evaluate whether the occurrence of iodine-induced hyperthyroidism (IIH) after the introduction of iodized salt was a general phenomenon or corresponded to specific local situations in the 2 affected countries. Two or 3 areas with a past history of severe iodine deficiency that had recently been supplemented with iodized salt were selected in each of the 7 countries. The prevalence of goiter was determined in 4423 schoolchildren in these areas and the concentration of urinary iodine in 2258. Salt factories and health structures were visited for the evaluation of the quality of iodized salt and the possible occurrence of IIH. The study showed that iodine deficiency had been eliminated in all areas investigated, and that the prevalence of goiter had markedly decreased since the introduction of iodized salt. This is a remarkable achievement in terms of public health. However, some areas were now exposed to iodine excess due mostly to a poor monitoring of the quality of the iodized salt and of the iodine intake of the population. In these areas or countries, IIH occurred only when the introduction of iodized salt had been of recent onset (<2 years), namely in Zimbabwe and RDC. In conclusion, the risk of IIH after correction of iodine deficiency is closely related to a recent excessive increment of iodine supply.

Africa↗
PubMed1999

Neonatal thyroid screening as a monitoring tool for the control of iodine deficiency.

In conditions of iodine deficiency, the frequency distribution of neonatal thyroid-stimulating hormone (TSH) is shifted towards elevated values. Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore constitutes the only indicator that allows prediction of brain damage, which is the main complication of iodine deficiency. This paper reviews studies on neonatal thyroid function in iodine deficiency and confirms the former statement by WHO/UNICEF/ICCIDD that the frequency of neonatal TSH above 5 mU/L blood is below 3% in conditions of normal iodine supply, that a frequency of 3-19.9% indicates mild iodine deficiency and that frequencies of 20-39.9% and above 40% indicate moderate to severe iodine deficiency, respectively. Neonatal thyroid screening appears as a particularly sensitive index in the monitoring of iodine supply at a population level.

Congenital Hypothyroidism↗
PubMed1998

Hydrogen bonding changes of internal water molecules in rhodopsin during metarhodopsin I and metarhodopsin II formation.

Rhodopsin is a 7-helix, integral membrane protein found in the rod outer segments, which serves as the light receptor in vision. Light absorption by the retinylidene chromophore of rhodopsin triggers an 11-cis-->all-trans isomerization, followed by a series of protein conformational changes, which culminate in the binding and activation of the G-protein transducin by the metarhodopsin II (Meta II) intermediate. Fourier transform IR difference spectroscopy has been used to investigate the structural changes that water, as well as other OH- and NH-containing groups, undergo during the formation of the metarhodopsin I (Meta I) and Meta II intermediates. Bands associated with the OH stretch modes of water are identified by characteristic downshifts upon substitution of H2(18)O for H2O. Compared with earlier work, several negative bands associated with water molecules in unphotolysed rhodopsin were detected, which shift to lower frequencies upon formation of the Meta I and Meta II intermediates. These data indicate that at least one water molecule undergoes an increase in hydrogen bonding upon formation of the Meta I intermediate, while at least one other increases its hydrogen bonding during Meta II formation. Amino acid residue Asp-83, which undergoes a change in its hydrogen bonding during Meta II formation, does not appear to interact with any of the structurally active water molecules. Several NH and/or OH groups, which are inaccessible to hydrogen/deuterium exchange, also undergo alterations during Meta I and Meta II formation.

Amino Acid Substitution↗
PubMed1998

Iodine supplementation of laying hen feed: a supplementary measure to eliminate iodine deficiency in humans?

Iodine deficiency still exists in many countries worldwide, to a certain degree this is also true for Germany. Food of animal origin can be a good source for iodine depending on the feed. To investigate the possible use of laying hen feed enriched with iodine, we conducted a feeding experiment with 40 laying hens receiving feed with different amounts of iodine either as KIO3 or in the form of seaweed. Iodine concentration in eggs increased significantly depending on iodine intake after a 2 week period. Seaweed could also be used as an iodine source by the hens. A subsequent consumption study with 24 volunteers showed that eggs enriched with iodine can increase human's iodine excretion and therefore improve human's iodine supply. This new strategy is thought to accompany salt iodization programs, not to replace them.

Animals↗
PubMed1998

The prevention and management of iodine-induced hyperthyroidism and its cardiac features.

Review of available literature and experience supports a recommended daily iodine intake of 150 microg for adults, 200 microg during pregnancy, 50 microg for the first year of life, 90 microg for ages 1 to 6, and 120 microg for ages 7 to 12. The amount of iodine added to salt in fortification programs should be adjusted to achieve these intakes. Iodine-induced hyperthyroidism (IIH) is an occasional consequence of the correction of iodine deficiency, occurring most frequently in older subjects with multinodular goiter. This complication is usually mild and self-limited, but may be serious and occasionally lethal. The most important clinical manifestations are cardiovascular. Thyrotoxicosis can aggravate pre-existing cardiac disease and can also lead to atrial fibrillation, congestive heart failure, worsening of angina, thromboembolism, and rarely, death. In the absence of pre-existing cardiac disease, treatment of thyrotoxicosis usually returns cardiac function to normal. Heightened awareness on the part of the health sector will promote early detection and prompt treatment of IIH. Monitoring should be an important part of a successful program of iodization, and in addition it offers the best opportunity for recognizing and treating IIH. Further research to improve the characterization and prevention of IIH is strongly encouraged. The most important conclusion is that IIH, while an issue that needs serious address, is not a reason to stop iodine supplementation in deficient regions. The benefits to the community from correcting iodine deficiency and avoiding its associated disorders far outweigh the damage from IIH.

Cardiovascular Diseases↗
PubMed1998

Screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control.

Neonatal thyroid screening using serum thyrotropin (TSH) as the primary screening test detects not only permanent sporadic congenital hypothyroidism, whose incidence is about 1 per 4000 births, but also compensated or transient primary hypothyroidism, whose incidence can be as high as 1 in 10 neonates and whose main cause is iodine deficiency. Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore, constitutes the only indicator that allows prediction of possible impairment of mental development at a population level, which is the main consequence of iodine deficiency. Therefore, the World Health Organization (WHO), United Nations International Children's Emergency Fund (UNICEF), and the International Council for Control of Iodine Deficiency Disorders (ICCIDD) included neonatal TSH as one of the indicators for assessing iodine deficiency disorders (IDD) and their control. In the absence of iodine deficiency, the frequency of neonatal TSH above 5 mU/L whole blood (or 10 mU/L serum) is less than 3%. A frequency of 3%-19.9% indicates mild IDD. Frequencies of 20%-39.9% and above 40% indicate moderate and severe IDD, respectively. Neonates exhibit elevated serum TSH more frequently than adults for a similar degree of iodine deficiency. Consequently, they appear hypersensitive to the effects of iodine deficiency. This characteristic is explained by a particularly low iodine content of the thyroid of neonates and, consequently, by an accelerated turnover rate of their intrathyroidal iodine reserves. This turnover rate is 1% in adults. It is 17% in the neonate in conditions of iodine repletion, but is as high as 62% and 125% in conditions of moderate and severe iodine deficiency, respectively. Such an accelerated turnover rate requires thyroid hyperstimulation by TSH that is morphologically evidenced even in moderately iodine deficient neonates. Neonatal screening using primary TSH is implemented in most countries with mild IDD where it detects the cases of sporadic, permanent congenital hypothyroidism and where it is also used as a monitoring tool for IDD evaluation and control. However, the implementation of such programs in countries affected by moderate or severe IDD is still insufficient because of lack of resources of the countries. This should be considered in the framework of the external support often provided to these countries for the implementation of programs of universal salt iodization. Monitoring of these programs in order to achieve the goal of sustainable elimination of IDD now constitutes an absolute priority.

Adult↗
PubMed1998

[Iodine intake in the Belgian population is insufficient].

This paper reviews all presently available data on iodine nutrition in Belgium. All age groups have an iodine intake below the recommendations by WHO. The main consequences are subclinical hypothyroidism with goiter during pregnancy and a risk of transient hypothyroidism resulting in minor brain damage in the neonate. Moreover the cost of therapy of IDD in Belgium is about one billion BEF of which some 75% could be avoided by well controlled and monitored iodine prophylaxis in the country. Such a program should be implemented.

Adolescent↗
PubMed1997

Modulation of the metarhodopsin I/metarhodopsin II equilibrium of bovine rhodopsin by ionic strength--evidence for a surface-charge effect.

The effects of ionic strength on formation and decay of metarhodopsin II (MII), the active photointermediate of bovine rhodopsin, were studied in the native membrane environment by means of ultraviolet/ visible and Fourier-transform infrared (FTIR) spectroscopy. By increasing the concentration of KCl in the range from hypotonic to 4 M, the apparent pKa of the metarhodopsin I(MI)/MII equilibrium is shifted by approximately pH three, in favor of the MII intermediate. In addition, the apparent rate of MII formation is enhanced by an increase in ionic strength (about twofold in the presence of 2 M KCl). MIII decay is independent of the salt concentration. Attenuated-total-reflectance/FTIR data show that the high-salt conditions have no effect on the rigidity of the membrane matrix and do not induce structural changes in the intermediates themselves. Different salts were tested for their ability to shift the MI/MII equilibrium; however, no clear ion dependence was observed. We interpret these results as an indication for direct involvement of the cytosolic surface charge in the regulation of the photochemical activity of bovine rhodopsin.

Animals↗
PubMed1997

Neonatal screening for congenital hypothyroidism: results and perspectives.

Systematic screening for congenital hypothyroidism in the neonate constitutes a major progress in the prevention of mental retardation, as the condition occurs in 1/4,000 newborns and necessarily results in brain damage if not properly detected and treated during the first days of life. Screening and diagnostic and therapeutic procedures are discussed, as well as outcome and prognosis of the affected infants. Primary thyroid-stimulating hormone screening is almost universally recommended. Early therapy (within 14 days) with appropriate doses of thyroxine (about 10 micrograms/kg/day) will prevent any brain damage even in case of evidence of fetal hypothyroidism, as thyroxine of maternal origin will reach the fetus and largely protect him. Neonatal thyroid screening is also a particularly sensitive monitoring tool in the evaluation of the effects and of the correction of iodine deficiency at the population level.

Adolescent↗
PubMed1997

Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency.

Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7-15 years in one to fifteen sites in The Netherlands. Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 micrograms/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.

Adolescent↗