Five-year incidence and progression of thyroid dysfunction in an older population.

BACKGROUND: Very few studies have assessed both the incidence and progression of thyroid dysfunction in a single older population-based cohort. In this study, we aimed to assess the 5-year incidence, progression and risk factors for development of thyroid dysfunction in an older Australian population. METHODS: The Blue Mountains Eye Study is a longitudinal population-based cohort study. During 1997-1999, 1768 participants (≥ 55 years) had thyroid function assessed. After excluding participants reporting any form of treatment for their thyroid condition at baseline, 951 participants (91.4%) without thyroid dysfunction and 54 (5.4%) with thyroid dysfunction were re-examined 5 years later. Thyroid dysfunction was defined using serum thyrotropin (thyroid stimulating hormone (TSH)) screen, followed by serum free T4 assessment. RESULTS: The overall 5-year incidence of thyroid dysfunction was 4.7% (95% confidence interval (CI) 3.4-6.1). Obesity (body mass index ≥ 30 kg/m(2) ) and serum TSH > 2 mIU/L at baseline predicted incident overt hypothyroidism (odds ratio (OR) 4.05, CI 1.74-9.41) and (OR 5.46, CI 1.16-25.67) respectively. The 5-year incidence of subclinical hypothyroidism was significantly higher in women than in men, 2.5% versus 0.7% (P= 0.03). Progression to overt hypothyroidism was observed in 17.9% of subjects with subclinical hypothyroidism over 5 years. CONCLUSIONS: The 5-year incidence of thyroid dysfunction in this older population was relatively low, and was associated with obesity and serum TSH level > 2 mIU/L at baseline. Over one in six persons with subclinical hypothyroidism progressed to overt thyroid dysfunction over the 5-year period. Our findings highlight the need for appropriate management of subclinical hypothyroidism among older people.

Prevalence of thyroid disease in an older Australian population.

AIM: To determine the prevalence of thyroid disease in an older Australian population in a population-based cross-sectional study. BACKGROUND: Community-living subjects, aged 49 years or older, in two Blue Mountains postcodes were invited to participate in an eye, nutrition and health study between 1997 and 2000. METHODS: Three thousand five hundred and nine of the 4489 identified persons participated. Fifty-seven per cent of 3504 who completed questionnaires were women; their mean age was 66.8 years. Thyroid-stimulating hormone (TSH) was measured in 2665 subjects (76% of those completing the questionnaire). The main outcome measures were serum TSH and free thyroxine levels, serum lipids, urate and sugar levels and questionnaire responses. RESULTS: The prevalence of recognized thyroid disease (either self-reported history of thyroid disease or current thyroxine treatment) was 10% (95% confidence interval (CI) 8.9-11.1%). An additional 3.6% (95%CI 2.9-4.3%) of participants had unrecognized thyroid disease (abnormal TSH). The TSH was abnormal in 7.1% (95%CI 5.8-8.4%) of women and 3.7% (95%CI 2.6-4.8%) of men. Sixty-five per cent of those with an abnormal TSH did not report a history of thyroid disease, whereas 25% of those taking thyroxine replacement therapy had an abnormal TSH level. The prevalence of hypothyroidism increased with increasing age in women. The mean fasting cholesterol was 0.36 mmol/L (95%CI 0.15-0.57) higher in hypothyroid subjects than in euthyroid subjects. CONCLUSION: Thyroid disease in older Australian women is relatively common and may be undiagnosed. Ongoing monitoring of patients on thyroxine replacement therapy is important, given that 25% of treated patients had an abnormal TSH.

Re-emergence of iodine deficiency in Australia.

Iodine is an essential nutrient for human growth and development. The thyroid gland is dependent upon iodine for production of thyroid hormone. It is a common perception that iodine deficiency is not a major public health concern in mainland Australia, with sporadic studies carried out about a decade ago showing average urinary iodine excretion levels of around 200 microg/day. Recent evidence, however, has shown that the consumption of iodine is declining in Australia. A similar situation has occurred in the USA. The present study was designed to evaluate the urinary iodine excretion (UIE), as the indicator of iodine nutrition, in samples obtained from various demographic groups in the Sydney metropolitian area, namely: schoolchildren, healthy adult volunteers. pregnant women and patients with diabetes. Urinary iodine in spot urine sample was measured in a Technicon II autoanalyser using an in-house, semiautomated method. The results in this communication show that all four study groups had the median UIE below 100 microg/L. the criteria set by the World Health Organization for iodine repletion, and confirm what has been described previously, that iodine deficiency has reemerged in Sydney, Australia. One of the major causes of the reduced iodine intake is the reduction of iodine in milk since the dairy industry replaced iodine-rich cleaning solutions with other sanitisers. Secondly, less than 10% of the population are currently using iodised salt. A national survey into the iodine nutrition status in Australia is urgently required as part of the establishment of a systematic surveillance and legislation is required to iodise all edible salt.

Study of biochemical prevalence indicators for the assessment of iodine deficiency disorders in adults at field conditions in Gujarat (India).

The main objective of this study was to assess the severity of iodine deficiency disorders (IDD) in the adult populations of the Baroda and Dang districts from Gujarat, western India using biochemical prevalence indicators of IDD. The other aim of this study was to establish a biochemical baseline for adequate iodine intake as a result of program evolution in the face of multiple confounding factors, like malnutrition and goitrogens responsible for goiter. A total of 959 adults (16-85 years) were studied from two districts (Baroda and Dang) and data was collected on dietary habits, anthropometric and biochemical parameters such as height, weight, urinary iodine (UI) and blood thyroid stimulating hormone (TSH). Drinking water and cooking salt were analyzed for iodine content. All subjects, irrespective of sex and district, showed median UI = 73 microg/L and mean blood TSH +/- SD = 1.59+/-2.4 mU/L. Seven per cent of the studied population had blood TSH values > 5 mU/L. Females in Baroda and males from Dang district were more affected by iodine deficiency as shown by a lower median UI. Mean TSH was significantly higher in women from both districts as compared to men (P = 0.001). The blood spots TSH values > 5 mU/L were seen in 20% of women from Dang. The normative accepted WHO values for UI and TSH for the severity of IDD as a significant health problem are not available for target population of adults. Urinary iodine normative limits and cut-offs are established for school-aged children. Blood spot TSH upper limit and cut-off values are available for neonate populations. The IDD has not been eliminated so far, as more than 20% of both male and female subjects had UI < 50 microg/L. Males were more malnourished than females in both districts (P < 0.05). Pearl millet from Baroda contained flavonoids like apigenin, vitexin and glycosyl-vitexin. Dang district water lacked in iodine content. Iodine deficiency disorder is a public health problem in Gujarat, with the Baroda district a new pocket of IDD. High amounts of dietary flavonoids in Baroda and Dang, malnutrition and an additional lack of iodine in Dang water account for IDD.

Biochemical assessment of iodine deficiency disorders in Baroda and Dang districts of Gujarat State.

OBJECTIVE: (i) To assess the severity of Iodine Deficiency Disorders (DD) in Baroda and Dang Districts of Gujarat, using biochemical prevalence indicators of IDD; and (ii) To establish a biochemical baseline, in a sub-sample of the large population of Gujarat, that could be used to monitor the effectiveness of iodine replacement program. METHODS: 1,363 children (<1-15 years) were studied and data was collected on dietary habits, anthropometric and biochemical parameters such as height, weight and urinary iodine (UI) and blood TSH respectively. BSA and BMI were calculated. Drinking water and salt were analyzed for iodine content. RESULTS: Median true urinary iodine was 65 microg/I (interquartile-range 38-108). Mean TSH was 2.08 mU/1 (SD +/- 2.06) and 6% of the studied population had whole blood TSH values > 5 mU/1. Females from both districts were affected more by iodine deficiency as evidenced by lower true urinary iodine and higher mean TSH levels. The interfering substances were significantly higher in Baroda boys and Dang girls as compared to their counterparts (< 0.001). Boys were more malnourished than girls as evidenced by lower BMI. Dang district was more severely affected by IDD as compared to Baroda. Drinking water in Dang district was lacking in iodine content. Iodine in salt varied at around 7 to 2000 PPM. CONCLUSIONS: IDD is a public health problem in Gujarat. Baroda district is a new pocket of IDD. Dang district is the worse affected. The expression of IDD in these two districts of Gujarat revealed interplay of multiple factors.

Thyroid ultrasonography consistently identifies goiter in adults over the age of 30 years despite a diminished response with aging of the thyroid gland to the effects of goitrogenesis.

Iodine deficiency is a national health problem in India and we have recently reported on the severity of IDD in adults and children in Gujarat province. The aim of this study was to determine the utility of thyroid ultrasonography to detect goiter in adults from an iodine-deficient population of Gujarat. We studied 472 adults selected by random household surveys. Data were collected on height, body weight, mid-upper arm circumference, thigh circumference, triceps skinfold thickness, thyroid size (palpation and ultrasonography), and diet. Casual urine samples for iodine (UI) and blood spots for TSH estimation were obtained. Endemic goiter is a major public health problem in Gujarat State, India and is probably caused by multiple factors including iodine deficiency, malnutrition, and other dietary goitrogens. These results indicate that thyroid US consistently detects goiter in adults despite a diminished thyroidal response to variable goitrogenic stimuli.

Iodine induced lymphocytic thyroiditis in the BB/W rat: early and late immune phenomena.

The effect of iodine excess on thyroid function and on the immunological sequence of events leading to lymphocytic thyroiditis (LT) was studied in the NB subline of BB/W rats to determine the mechanisms by which the level of iodine intake influences the development of LT in this animal model. Iodine supplemented water (500 micrograms/l, Group 1 or 500 mg/l, Group 2) or non-iodine supplemented tap water (Group 3) was given to breeding pairs and their offspring ad libitum. A Wistar rat group, also given tap water (Group 4) served as controls. To determine the immunological sequence of events, the phenotypic nature of the infiltrating thyroid lymphocytes was examined by specific immunoperoxidase staining in BB/W and Wistar rats at 6, 9, 12, and 15 weeks. Antigen-presenting cells and class II (Ia) antigen expression on thyrocytes were also examined. The first immunological event apparent in the iodine-treated BB/W rats was a sharp increase in the number of Ia positive dendritic cells at 9 weeks compared with control BB/W and Wistar rats. In the iodine excess groups dendritic cells were associated with scattered areas of lymphocytic infiltration, comprising predominantly T helper cells (W3/25). T suppressor cells (OX 8) and IL-2 receptor positive activated T-cells (OX 39) were both present in small numbers. B-cells (OX 12) were absent. In addition, thyrocytes did not exhibit Ia antigen expression. By contrast, lymphocytic infiltration was not found at 9 weeks in control BB/W rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Ontogeny of insulin binding in different regions of the rat brain.

Insulin binding was measured on crude mitochondrial or plasma membranes prepared from different rat brain regions during postnatal development. In the cerebral cortex and brainstem, insulin binding decreased 60-70% between birth and the adult period. In the cerebellum, insulin binding doubled in the first 10 postnatal days and then decreased 40% in the adult, while in the olfactory bulb, insulin binding changed little during postnatal development. Postnatal reductions of insulin binding in cerebral cortex and brainstem were from a loss of binding sites and not from a change in binding affinity. Of the major postnatal developmental processes, maximal insulin binding was most closely associated with neuronogenesis, less closely with gliogenesis and not with synaptogenesis, neural process formation or myelination.

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.

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.

Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants.

The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics. Serial monitoring of urinary iodine excretion and serum thyrotropin and thyroxine levels was undertaken from birth for the first 4 weeks of life. Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants. Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group. The mean serum thyroxine level in these 9 infants (44.1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83.1 nmol/l) and in the non-exposed control group (83.0 nmol/l); thyroxine levels fell before serum thyrotropin rose. These disturbances in thyroid function correlated positively with urinary iodine excretion and hence iodine absorption. Thyroid function had returned to normal by the time of discharge from hospital. It is concluded that iodine absorption, from topical iodine-containing antiseptics, may cause hypothyroidism during a critical period of neurological development in the newborn infant. The routine use of iodine antisepsis in VLBW infants should be avoided because of this effect.

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.

Effect of starvation on insulin receptors in rat brain.

To determine the effect of starvation on brain insulin receptors, rats were fed 4 g of chow/day for 14 days and then P2 fraction membranes were prepared from different brain regions. Compared to the fed state, there was an 18% reduction of insulin binding in olfactory bulbs from starved animals, but no change in the cerebellum, frontal cortex, amygdala, medial hypothalamus or lateral hypothalamus. A 15% reduction of olfactory bulb insulin binding was obtained by totally starving animals for four days. When membrane content was measured using the plasma membrane marker Na/K ATPase, insulin binding decreased by 26% and 14% in olfactory bulb membranes from starved and totally starved animals, respectively. The starvation-induced change in olfactory bulb binding was due to a loss of binding sites and not a decrease in binding affinity. Non-specific catabolism of protein and a change in the composition of membranes following starvation were excluded as causes for this effect. As streptozotocin induced diabetes had no effect on brain insulin binding, it was concluded that hypoinsulinaemia associated with starvation had not caused the reduction in olfactory bulb binding. Under similar conditions of starvation and diabetes, insulin binding in liver plasma membranes increased 26% and 38%, respectively. At 8 and 14 days of starvation, the reductions in olfactory bulb insulin binding and body weight were similar. On refeeding for three days, there was no increase in insulin binding, although body weight increased 7%. On refeeding for eight days, olfactory bulb insulin and body weight had returned to near normal.(ABSTRACT TRUNCATED AT 250 WORDS)

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.