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Biomedical subjects

G F Maberly

Publications and source records attributed to G F Maberly.

At least 19 recordsLinked to original sources
PubMed1999

Randomized clinical trial comparing different iodine interventions in school children.

OBJECTIVE: The purpose of this trial was to compare three different iodine interventions. DESIGN: School children aged 8-10 years were randomized into one of three groups: group A was provided with iodized salt by researchers with an iodine concentration of 25 ppm; group B purchased iodized salt from the market; and group C was similar to group B with the exception that they were given iodized oil capsules containing 400 mg iodine at the beginning of the study. Salt iodine content was measured bimonthly for 18 months and indicators of iodine deficiency were measured at baseline and 6, 9, 12 and 18 months after randomization. RESULTS: The prevalence of abnormal thyroid volumes, based on the World Health Organization (WHO) body surface area reference >97th percentile, was 18% at baseline and declined to less than 5% by 12 months in groups A and C, and to 9% after 18 months in group B. Results for goitre by palpation were similar. The median urinary iodine was 94 microg l(-1) at baseline and increased in all groups to > 200 microg l(-1) at the 6-month follow-up. CONCLUSIONS: In this population of school children with initially a low to moderate level of iodine deficiency, the group receiving salt with 25 ppm (group A) was not iodine deficient on all indicators after 18 months of study. When the iodine content of the salt varied, such as in group B, by 18 months thyroid sizes had not yet achieved normal status.

Child↗
PubMed1998

Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994)

Iodine deficiency in a population causes increased prevalence of goiter and, more importantly, may increase the risk for intellectual deficiency in that population. The National Health and Nutrition Examination Surveys [NHANES I (1971-1974) and (NHANES III (1988-1994)] measured urinary iodine (UI) concentrations. UI concentrations are an indicator of the adequacy of iodine intake for a population. The median UI concentrations in iodine-sufficient populations should be greater than 10 microg/dL, and no more than 20% of the population should have UI concentrations less than 5 microg/dL. Median UI concentrations from both NHANES I and NHANES III indicate adequate iodine intake for the overall U.S. population, but the median concentration decreased more than 50% between 1971-1974 (32.0+/-0.6 microg/dL) and 1988-1994 (14.5+/-0.3 microg/dL). Low UI concentrations (<5 microg/dL) were found in 11.7% of the 1988-1994 population, a 4.5-fold increase over the proportion in the 1971-1974 population. The percentage of people excreting low concentrations of iodine (UI, <5 microg/dL) increased in all age groups. In pregnant women, 6.7%, and in women of child-bearing age, 14.9% had UI concentrations below 5 microg/dL. The findings in 1988-1994, although not indicative of iodine deficiency in the overall U.S. population, define a trend that must be monitored.

Adolescent↗
PubMed1997

Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods.

The measurement of urinary iodine in population-based surveys provides a biological indicator of the severity of iodine-deficiency disorders. We describe the steps performed to validate a simple, inexpensive, manual urinary iodine acid digestion method, and compare the results using this method with those of other urinary iodine methods. Initially, basic performance characteristics were evaluated: the average recovery of added iodine was 100.4 +/- 8.7% (mean +/- SD), within-assay precision (CV) over the assay range 0-0.95 mumol/L (0-12 micrograms/dL) was < 6%, between-assay precision over the same range was < 12%, and assay sensitivity was 0.05 mumol/L (0.6 microgram/dL). There were no apparent effects on the method by thiocyanate, a known interfering substance. In a comparison with five other methods performed in four different laboratories, samples were collected to test the method performance over a wide range of urinary iodine values (0.04-3.7 mumol/L, or 0.5-47 micrograms/dL). There was a high correlation between all methods and the interpretation of the results was consistent. We conclude that the simple, manual acid digestion method is suitable for urinary iodine analysis.

Arsenic↗
PubMed1997

Use of thyroid stimulating hormone testing in newborns to identify iodine deficiency.

Iodine deficiency has traditionally been associated with goiter and cretinism. More recently, iodine deficiency has been recognized as the leading worldwide cause of preventable intellectual impairment. Intellectual and neurologic deficits occur because of a lack of thyroid hormone during critical phases of brain development. More sensitive biologic tests may be useful in determining the true extent of iodine deficiency in populations. Thyroid stimulating hormone (TSH) levels among urban newborns from countries with known iodine deficiency problems were determined using a sensitive whole-blood spot assay. Results found prevalences of high TSH (> 5 mU/L whole blood units using a sensitive monoclonal assay) ranging from 32-80% compared with a prevalence of 3% usually found in iodine-replete areas. These findings suggest that developing brains of newborns are at risk from the detrimental effects of iodine deficiency in these urban areas. The results presented suggest the need for effective intervention programs in urban areas as well.

Developing Countries↗
PubMed1994

Iodine deficiency disorders: contemporary scientific issues.

Iodine deficiency is the leading cause of preventable intellectual impairment and is associated with a spectrum of neurologic and developmental pathology. More than one billion people are at risk. The developing fetus, newborn, and young child are the most susceptible to the effects of an iodine-deficient diet. If intervention is not initiated in a timely fashion, the pathophysiologic abnormalities become resistant to treatment and permanent intellectual, neurologic, and somatic deficits result. The technology of iodine deficiency intervention is well established. Iodized salt, the preferred method, is easy to produce, administer in physiologic doses, and is cost effective. The distribution of iodized salt and social marketing are key to a successful iodine deficiency elimination program. In remote regions, iodized oil is a useful interim intervention. However, it is clear that technology is not enough. Any national effort to eliminate iodine deficiency must extend far beyond the Ministry of Health. The program will require the full participation of a range of national government ministries and agencies and the full support and participation of local or regional governments.

Child Health Services↗
PubMed1991

The neurology of endemic cretinism. A study of two endemias.

Endemic cretinism is the most severe manifestation of dietary iodine deficiency. Two forms of the syndrome are traditionally described: neurological and myxoedematous. Although this classification highlights the important neurological sequelae of the disorder it implies that myxoedematous cretins have an alternative mechanism. Further, the nature of the neurological deficit associated with both types of endemic cretinism has received scant attention in recent times considering that it remains a common disorder in many parts of the world. The nature and extent of the neurological deficit found in endemic cretinism was investigated in 104 cretins from a predominantly myxoedematous endemia in western China and in 35 cretins from central Java, Indonesia, a predominantly neurological endemia. We found a similar pattern of neurological involvement in nearly all cretins from both endemias, regardless of type (myxoedematous or neurological), and of current thyroid function. Hallmarks of the neurological features included mental retardation, pyramidal signs in a proximal distribution and extrapyramidal signs. Many patients exhibited a characteristic gait. This probably reflected pyramidal and extrapyramidal dysfunction, although joint laxity and deformity were important contributing factors. Other frequently encountered clinical features were squint, deafness, and primitive reflexes. Cerebral computerized tomography (CT) revealed basal ganglia calcification in 15 of 50 subjects. The presence of basal ganglia calcification was confined to cretins with severe hypothyroidism. Otherwise, cerebral CT scanning demonstrated only minor abnormalities which did not contribute to the localization of the clinical deficits. We conclude that the same neurological disorder is present in both types of endemic cretinism reflecting a diffuse insult to the developing fetal nervous system. These clinical findings support the concept of maternal and fetal hypothyroxinaemia, arising from severe iodine deficiency, as the primary pathophysiological event in endemic cretinism. Differences between the two types of cretinism may be explained by continuing postnatal thyroid hormone deficiency in the myxoedematous type, which results in impaired growth, skeletal retardation and sexual immaturity.

Adult↗
PubMed1990

Supplementary iodine fails to reverse hypothyroidism in adolescents and adults with endemic cretinism.

The efficacy of supplemental iodine in correcting hypothyroidism in adults and older children with endemic myxedematous cretinism is not known. To investigate this issue we administered im iodized oil (1.5 mL) to 28 hypothyroid endemic cretins (TSH, greater than 5 mIU/L) from western China, aged 14-52 yr (mean = 29 SD = 11 yr). Clinical examination, intelligence testing (Hiskey Nebraska Test of Learning Aptitude and the Griffiths Mental Development Scales), and thyroid function tests were performed before and 6 months after iodine supplementation. We found that signs of thyroid hormone deficiency, dwarfism, and delayed sexual maturity persisted after iodine supplementation. Further, mental disability and other clinical features of neurological damage were not altered by treatment. The mean serum concentration of total T4 before treatment was 75 nmol/L (SD = 40) and fell after iodized oil administration to 56 nmol/L (SD = 29; P less than 0.001). Mean serum levels of TSH before and after iodine showed a paradoxical fall [85 mIU/L (SD = 102) and 46 mIU/L (SD = 46), respectively]. Serum TSH levels decreased into the normal range (less than 5 mIU/L) in only 1 of 28 patients (4%). We conclude that iodine supplementation does not reverse thyroid hormone deficiency or its sequelae in adolescents and adults with endemic myxedematous cretinism. Iodized oil in this age group of patients with endemic cretinism does not appear to be beneficial and should be used with caution.

Adolescent↗
PubMed1989

Endemic cretinism: possible role for thyroid autoimmunity.

Thyroid atrophy, rather than goitre, is a characteristic feature of myxoedematous cretinism but its cause and nature are unknown. In this study, purified IgG fractions of serum from patients with myxoedematous endemic cretinism inhibited thyrotropin-induced DNA synthesis in guineapig thyroid segments in a sensitive cytochemical bioassay. IgG from patients with euthyroid neurological endemic cretinism or from normal subjects did not inhibit thyroid growth. Furthermore, in myxoedematous subjects, the presence of the thyroid-growth-blocking immunoglobulins showed a positive relation with thyroid atrophy found on ultrasound. These findings provide a pathogenic basis for the variable clinical expression of endemic cretinism.

Adolescent↗
PubMed1989

Iodine deficiency impairs intellectual and neuromotor development in apparently-normal persons. A study of rural inhabitants of north-central China.

Intelligence was measured by means of the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales in a sample of 369 patients from iodine-deficient rural villages (Baihuyao), iodine-sufficient rural villages (Huanglo) and urban populations to test for the damaging effects of iodine deficiency on the development of the nervous system in the presumed healthy section of a community. In urban school-children who were aged seven to 14 years (n = 78), a normal range of measured intelligence was found (mean +/- SD intelligence-quotient score, 107.0 +/- 18.3). By comparison, intelligence-quotient scores were lower in all rural cohorts (a rural suppression effect) but the distribution of intelligence-quotient scores showed a further shift to the left in the iodine-deficient township. In Baihuyaon villagers who were aged 30-35 years (n = 50), who were born during the period of severe iodine deficiency, 72% of villagers had an intelligence-quotient score of less than 70 compared with 41% (P less than 0.05) of villagers who were aged 28-35 years from Huanglo, a rural iodine-sufficient control group (n = 49). Although measured intelligence was higher in Baihuyaon children whose mothers had received iodized salt - 44% of seven- to 14-year-old children had intelligence-quotient scores of less than 70 (n = 141)--it remained significantly depressed compared with rural (n = 51) and urban (n = 78) control subjects (18% and 4%, respectively). These findings were consistent with other parameters (that is, the persistently-high rate of goitre), which indicated that the salt-iodization programme was inadequate. In the iodine-deficient village, lower intelligence-quotient scores showed a relationship with the detection by audiometry of nerve deafness and with the presence of abnormal neurological signs. The latter included spasticity and pyramidal signs which were of a similar pattern to the neurological deficits that have been demonstrated in overt neurological cretins. We conclude that iodine deficiency imposes a further suppressive effect on the intellectual performance of rural inhabitants, and results in a shift of the entire population distribution of cognitive skills to a lower level.

Adolescent↗
PubMed1989

Thyroid autoimmunity in endemic goitre caused by excessive iodine intake.

The pathophysiology of endemic goitre caused by excessive iodine intake is not well defined. By interacting with the immune system, iodine excess may trigger the development of autoimmune thyroid disease such as lymphocytic Hashimoto's thyroiditis (LT). In an attempt to examine this further, we compared the presence of thyroid autoantibodies in 29 goitrous children, from an iodine excess area, and in 26 healthy children, from an iodine sufficient area, of north central China. Serum was tested for antimicrosomal (MAb), anti-thyroglobulin (TgAb), second colloid antigen antibodies (CA2-Ab) and TSH binding inhibitory immunoglobulins (TBII). Affinity chromatographically purified IgG was tested for thyroid growth-stimulating activity (TGI) by two different methods: a sensitive cytochemical bioassay (CBA) using guinea-pig thyroid explants and a mitotic arrest assay (MAA) employing a continuous rat thyroid cell line (FRTL-5). We found no increased prevalence of LT in patients with endemic iodine goitre. The levels of MAb, TgAb and CA2-Ab did not differ significantly between the two groups of children. Further, TBII were not present in either group. Thyroid growth-stimulating immunoglobulins (TGI) were the major autoantibodies found in children with goitres caused by iodine excess. In the CBA, 12 of 20 (60%) goitrous children and 0 of 12 (0% P less than 0.05) healthy children were positive for TGI. Similar results were found in the MAA, and a good correlation between results of the CBA and MAA was found (P = 0.003). Maximal TGI activity in dose-response CBA showed a good relation with clinical goitre size (r = 0.63; P less than 0.05) indicating a possible pathophysiological role for these antibodies. We conclude that endemic iodine goitre is not associated with Hashimoto's lymphocytic thyroiditis. Nevertheless, autoimmune growth factors such as TGI may play a primary role in the pathogenesis of thyroid growth in this condition.

Adolescent↗
PubMed1989

Effects of protracted hypothyroidism on pituitary function and structure in endemic cretinism.

Pituitary function and structure were assessed in 69 endemic cretins from western China. In hypothyroid cretins (TSH greater than 10 mIU/l), CT imaging of the pituitary revealed adenoma in five of 20 (25%) and partially empty sella (PES) in a further eight of 20 (40%). The majority of tumours were microadenomas and showed a relation with higher levels of serum TSH but not with duration of hypothyroidism. Dynamic pituitary testing with TRH and GnRH in four patients with adenoma on CT gave a flat TSH response but significant rises in serum PRL, GH, LH and FSH concentrations. Hyperprolactinaemia (greater than 350 mIU/l) was present in hypothyroid cretins only (13 of 26; 50%) and serum PRL showed a curvilinear relation with serum TSH levels (r = 0.7, P less than 0.0001). Hypogonadism was seen in approximately half the cretins with high PRL levels. Our data suggest that severe protracted thyroid hormone deficiency may result in thyrotrophin adenomas of the pituitary gland. Disturbances of growth, puberty, and sexual function in endemic cretins are explained by the secondary effects of thyroid hormone deficiency on pituitary function.

Adenoma↗
PubMed1988

A comparative study of neurological and myxedematous endemic cretinism in western China.

Endemic cretinism occurs in areas of severe iodine deficiency and is manifested by two major clinical patterns, myxedematous and neurological. The relationship between these types and the factors responsible for the clinical variability are not clear. We examined 69 endemic cretins, aged 4-52 yr, categorized clinically at the beginning of the study into the three traditional types of endemic cretins, myxedematous (n = 25), neurological (n = 15), and the mixed form (n = 29), from a previously unreported endemia in Qinghai Province, China. These patients underwent detailed endocrine and neurological examination, including intelligence assessment using the Hiskey-Nebraska Test of Learning Aptitude or the Griffiths Mental Development Scales, audiometry (in a subset of 37 patients); thyroid function testing and thyroid ultrasonography; and radiology of the skull, hand, and hip. We found that categorization of the cretins into the conventional types did not reflect the pathophysiology of the condition, since an identical pattern and intensity of neurological, intellectual, and audiometric deficits were common to and equally present in all three types of endemic cretins regardless of their thyroid function. Gait disorder (in 99%) and pyramidal signs such as patellar hyper-reflexia (in 91%) were the most common neurological abnormalities. There was no difference in mean intelligence test scores among the three groups [overall mean intelligence score (Hiskey or Griffiths tests), 28.8 +/- 12.8 (SD)]. The differing clinical manifestations of cretinism could be explained by the length and severity of thyroid hormone deficiency. Myxedematous cretins were severely thyroid hormone deficient, and as a result sexually immature, dwarfed, and had retarded skeletal maturity. They had clinical and sonographic thyroid atrophy, rather than goiter. Although neurological cretins were euthyroid, linear growth arrest lines (demonstrated radiologically) in the long bones of these cretins suggested previous hypothyroidism. Furthermore, all cretins were growth retarded when compared with peers of similar age and race. Our data therefore suggest that the different clinical types of endemic cretinism are in fact the same disorder phenotypically modified by the length and severity of postnatal hypothyroidism. The neurological manifestations are interpreted as reflecting the effects of maternal and fetal hypothyroxinemia, secondary to severe iodine deficiency, on the developing nervous system.

Adolescent↗
PubMed1987

Storage conditions and stability of thyrotropin and thyroid hormones on filter paper.

We evaluated the effects of temperature and humidity on thyroid hormones (T4, T3) and thyrotropin (TSH) measured in blood spots dried on filter paper. RIAs for T4 and T3 blood spots were optimized to measure these analytes over the neonatal and euthyroid adult reference intervals. Sensitivities of the T3 and T4 assays were 0.5 and 10 nmol/L, respectively. A blood-spot immunoradiometric assay for TSH involving magnetizable particles was developed with a sensitivity of 6 milli-int. units/L. Control sera stored at -20 degrees C, 4 degrees C, room temperature, 37 degrees C, and at external ambient temperatures for 36 days showed no significant change in measured concentrations of TSH or T3 during 30 days or for T4 at -20 and 4 degrees C. T4 markedly declined in blood spots stored at room temperature (either high or low humidity), 37 degrees C, or ambient temperature. TSH and T3 in blood spots evidently are stable at temperatures likely to be encountered during storage or transport, but blood spots for T4 assay must be stored between -20 and 4 degrees C.

Drug Stability↗
PubMed1986

Diagnostic value of thyrotropin concentrations in serum as measured by a sensitive immunoradiometric assay.

A new, highly sensitive immunoradiometric thyrotropin (TSH) assay involving solid-phase-coupled monoclonal antibodies (Boots-Celltech Sucrosep IRMA-TSH) has been evaluated in a wide variety of patients with thyroidal and nonthyroidal illnesses and the results compared with those obtained by conventional diagnostic TSH RIAs. The sensitivity of the present assay ranged from 0.036 to 0.1 milli-int. unit/L (mean 0.056). TSH, measurable in serum of each of 128 euthyroid patients, ranged from 0.1 to 6.3 milli-int. units/L (mean 1.7, SD 1.1). Similar concentrations were found in 15 healthy pregnant women. TSH was undetectable in 27 hyperthyroid patients, of whom six were tested with thyroliberin stimulation and failed to respond. The mean TSH concentration measured in 62 seriously ill hospital patients of 2.7 (SD 2.5) milli-int. units/L was significantly higher (p less than 0.05) than in the euthyroid patients. Basal values and peak TSH responses to thyroliberin testing correlated well (r = 0.63, n = 48), irrespective of clinical diagnosis. We conclude that the present assay readily discriminates between euthyroid and hyperthyroid patients and should replace conventional TSH RIAs in diagnostic laboratories.

Adolescent↗
PubMed1986

Immunoradiometric assay with use of magnetizable particles: measurement of thyrotropin in blood spots, to screen for neonatal hypothyroidism.

We adapted a commercial immunoradiometric assay (IRMA) to measure thyrotropin in filter-paper blood spots. Two 3-mm blood spots are used for each standard and sample. These are incubated for 2 h with radiolabeled antibody and for 30 min with magnetic antibody, followed by a 10-min separation procedure. Assay sensitivity is 6 milli-int. units/L. Coefficients of variation (precision profile of the standard curve) ranged from 4.3 to 9.6%. The coefficient of correlation (r) between thyrotropin concentrations in the blood spots and in serum was 0.93. Pre-elution of the blood spots is necessary for short incubation time. Short incubation time, little need for specialized equipment, the high precision and sensitivity characteristic of IRMA, and ease of collection, transport, and storage of the blood-spot samples make this assay suitable for neonatal hypothyroid screening.

Humans↗
PubMed1985

A reappraisal of the binding characteristics of human thyroxine-binding globulin for 3,5,3'-triiodothyronine and thyroxine.

The binding characteristics of T4 and T3 to dilute plasma were studied separately in five normal euthyroid subjects with normal levels of thyroxine-binding globulin (TBG). Scatchard analyses of these data revealed similar mean affinity constants for T4 [2.0 +/- 0.7 (SD) X 10(9) M-1] and T3 (2.0 +/- 0.7 X 10(9) M-1), but a 5-fold higher capacity for T4 (0.75 +/- 0.18 mol T4/mol TBG) than for T3 (0.14 +/- 0.06 mol T3/mol TBG). Similar results were obtained using various assay buffers, pH concentrations, or separation methods. This characteristic pattern of T4 and T3 binding was retained by thyroid hormone free plasma, with the only difference being a slight parallel shift to the left of the Scatchard plots for both T4 and T3. The calculated affinities (Ka) for T4 and T3 were 5.2 X 10(9) M-1 and 5.2 X 10(9) M-1, respectively. High affinity T4 and T3 binding was abolished in plasma selectively depleted of TBG, but was retained after selective depletion of either prealbumin or albumin. Highly purified TBG, prepared from normal serum, demonstrated binding characteristics for T3 and T4 similar to dilute plasma. Displacement of [125I]T4 from dilute plasma by unlabeled T3 or T4 revealed a binding potency of T3 relative to T4 of 9%. Binding affinities derived from analog displacement studies appear invalid as these calculations assume equal binding capacities of TBG for T4 and T3. It seems clear from these studies, that the binding characteristics of human TBG are inconsistent with a single competitive binding site for thyroid hormones.

Autoradiography↗
PubMed1983

Plasma contamination accounts for thyroid hormone binding in nuclear protein extracts from human mononuclear cells.

Plasma protein contamination accounted for high affinity thyroid hormone binding to a nuclear protein extract from human blood mononuclear cells. The degree of contamination was directly related to the number of times the cells were washed before the nuclear protein was extracted. After three washes, no specific binding was detected. Plasma contamination was estimated to be 0.3-0.5 microliter/assay tube. The TBG concentration in this volume of plasma was consistent with the concentration of 0.2 micrograms/ml measured by RIA in the nuclear extract. Total specific binding of [125I] T4 and [125I] T3 can be attributed to plasma contamination, as 0.3 microliter of plasma gave identical binding. Furthermore, a TBG antiserum abolished specific T4 and T3 binding to the nuclear protein extract. These data are consistent with TBG being the major plasma contaminant. In fourteen normal, euthyroid subjects, the higher mean maximum binding capacity (MBC) for T4 (1.63 +/- 0.27 SD) compared to T3 (0.25 +/- 0.21 pmol/mg protein; P less than 0.001) and the same binding affinity (Ka, 2.0 +/- 0.7 x 10(9)/mol) for both T4 and T3 are the same as found in plasma. The higher MBC for T4 (5.8 +/- 1.0) and T3 (0.69 +/- 0.2 pmol/mg protein) in two hypothyroid subjects are consistent with the higher mean TBG concentration of 28 +/- 5 micrograms/ml compared to the level in ten normal subjects (19.2 +/- 1.8 micrograms/ml; P less than 0.001). In two subjects with low normal TBG concentrations of 15 micrograms/ml, the T4 maximum specific binding of 9% was lower than found in normal subjects 16.6 +/- 7.6%. We conclude that the methodology described previously and used in this study is invalid for measuring thyroid hormone nuclear receptor status in humans.

Blood Proteins↗