Best Practice & Research Clinical Endocrinology & Metabolism

Preface

Michael Zimmermann — 2010-02-01

Iodine deficiency has multiple adverse effects in humans due to inadequate thyroid hormone production that are termed the iodine deficiency disorders. Globally, it is estimated that two billion individuals have an insufficient iodine intake. About 50% of Europe remains mildly iodine deficient, and iodine intakes in other industrialised countries, including the United States and Australia, have fallen in recent years.

Epidemiology of iodine deficiency: Salt iodisation and iodine status

Maria Andersson, Bruno de Benoist, Lisa Rogers — 2010-02-01

Universal salt iodisation (USI) and iodine supplementation are highly effective strategies for preventing and controlling iodine deficiency. USI is now implemented in nearly all countries worldwide, and two-thirds of the world's population is covered by iodised salt. The number of countries with iodine deficiency as a national public health problem has decreased from 110 in 1993 to 47 in 2007. Still one-third of households lack access to adequately iodised salt. Iodine deficiency remains a major threat to the health and development of populations around the world, particularly in children and pregnant women in low-income countries. Data on iodine status are available from 130 countries and approximately one-third of the global population is estimated to have a low iodine intake based on urinary iodine (UI) concentrations. Insufficient control of iodine fortification levels has led to excessive iodine intakes in 34 countries. The challenges ahead lie in ensuring higher coverage of adequately iodised salt, strengthening regular monitoring of salt iodisation and iodine status in the population, together with targeted interventions for vulnerable population groups.

Iodine intake as a determinant of thyroid disorders in populations

2010-02-01

Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations, hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison, the most serious association between disease and the level of iodine intake in a population.In less severe iodine deficiency, the normal thyroid gland is able to adapt and keep thyroid hormone production within the normal range. However, the prolonged thyroid hyperactivity associated with such adaptation leads to thyroid growth, and during follicular cell proliferation there is a tendency to mutations leading to multifocal autonomous growth and function.In populations with mild and moderate iodine deficiency, such multifocal autonomous thyroid function is a common cause of hyperthyroidism in elderly people, and the prevalence of thyroid enlargement and nodularity is high. The average serum TSH tends to decrease with age in such populations caused by the high frequency of autonomous thyroid hormone production.On the other hand, epidemiological studies have shown that hypothyroidism is more prevalent in populations with a high iodine intake. Probably, this is also a complication to thyroid adaptation to iodine intake. Many thyroid processes are inhibited when iodine intake becomes high, and the frequency of apoptosis of follicular cells becomes higher. Abnormal inhibition of thyroid function by high levels of iodine is especially common in people affected by thyroid autoimmunity (Hashimoto's thyroiditis).In populations with high iodine intake, the average serum thyroid-stimulating hormone (TSH) tends to increase with age. This phenomenon is especially pronounced in Caucasian populations with a genetically determined high tendency to thyroid autoimmunity. A small tendency to higher serum TSH may be observed already when iodine intake is brought from mildly deficient to adequate, but there is at present no evidence that slightly elevated serum TSH in elderly people leads to an increase in morbidity and mortality.Conclusion: Even minor differences in iodine intake between populations are associated with differences in the occurrence of thyroid disorders. Both iodine intake levels below and above the recommended interval are associated with an increase in the risk of disease in the population. Optimally, iodine intake of a population should be kept within a relatively narrow interval where iodine deficiency disorders are prevented, but not higher. Monitoring and adjusting of iodine intake in a population is an important part of preventive medicine.

Iodine deficiency in pregnancy, infancy and childhood and its consequences for brain development

Alida Melse-Boonstra, Nidhi Jaiswal — 2010-02-01

Iodine deficiency during foetal development and early childhood is associated with cognitive impairment. Randomised clinical studies in school-aged children encountered in the literature indicate that cognitive performance can be improved by iodine supplementation, but most studies suffer from methodological constraints. Tests to assess cognitive performance in the domains that are potentially affected by iodine deficiency need to be refined. Maternal iodine supplementation in areas of mild-to-moderate iodine deficiency may improve cognitive performance of the offspring, but randomised controlled studies with long-term outcomes are lacking. Studies in infants or young children have not been conducted. The best indicators for iodine deficiency in children are thyroid-stimulating hormone (TSH) in newborns and thyroglobulin (Tg) in older children. Urinary iodine may also be useful but only at the population level. Adequate salt iodisation will cover the requirements of infants and children as well as pregnant women. However, close monitoring remains essential.

Cretinism revisited

Zu-Pei Chen, Basil S. Hetzel — 2010-02-01

Endemic cretinism includes two syndromes: a more common neurological disorder with brain damage, deaf mutism, squint and spastic paresis of the legs and a less common syndrome of severe hypothyroidism, growth retardation and less severe mental defect.Both conditions are due to dietary iodine deficiency and can be prevented by correction of iodine deficiency before pregnancy.Endemic cretinism is now included in the spectrum of the effects of iodine deficiency in a population termed the ‘iodine deficiency disorders (IDDs)’, which also includes a wide range of lesser degrees of cognitive defect that can be prevented by the correction of iodine deficiency.Iodine deficiency is now recognised by the World Health Organization (WHO) as the most common preventable cause of brain damage with in excess of 2 billion at risk from 130 countries.A global United Nations (UN) programme of prevention has achieved 68% household usage of iodised salt by the year 2000 compared with less than 20% prior to 1990.

Assessment of nodular goitre

Massimo Tonacchera, Aldo Pinchera, Paolo Vitti — 2010-02-01

Nodular goitres are enlargements of the thyroid gland. In the absence of thyroid dysfunction, autoimmune thyroid disease, thyroiditis and thyroid malignancy, they constitute an entity described as non-toxic nodular goitre, which occurs both endemically and sporadically. In the early phase of goitrogenesis, goitres are diffuse and, with time, such goitres tend to become nodular. Concomitantly, thyroid function often becomes autonomous, and therefore the patients gradually develop hyperthyroidism. Some non-toxic goitre patients have no symptoms at all, or just complaints of cosmetic disfigurement. In the diagnostic evaluation protocol, neck palpation and several imaging methods are available: ultrasonography (US), the new developed US elastography, scintigraphy, computed tomography (CT) scan and magnetic resonance imaging (MRI). Fine-needle aspiration biopsy (FNAB) provides the most direct and specific information about a thyroid nodule. Recently, a combination of cytology and molecular testing has shown significant improvement in the diagnostic accuracy and allowed for better prediction of malignancy in thyroid nodular disease.

Neonatal TSH screening: is it a sensitive and reliable tool for monitoring iodine status in populations?

Mu Li, Creswell J. Eastman — 2010-02-01

Iodine deficiency is the most common cause of preventable brain damage in the newborn. The indicators for assessing iodine nutritional status include urinary iodine excretion, thyroid size, thyroid stimulating hormone (TSH) and thyroglobulin (Tg) concentrations in the blood. Neonatal TSH concentration is increased when the supply of thyroid hormone and iodine from the maternal circulation to the foetus has been compromised. The World Health Organization (WHO) has suggested that when a sensitive assay is used on samples collected 3–4 days after birth, a <3% frequency of TSH concentrations >5mIUl−1 indicates iodine sufficiency in a population. However, many studies have attempted to apply the frequency of neonatal TSH values >5mIUl−1 in determining population iodine status and monitoring intervention programmes, and although some have proven to be successful, most have provided conflicting or uncertain data. This is due to the many technical issues that remain unresolved on the use of neonatal TSH screening for monitoring iodine status, making it doubtful as a sensitive and reliable quantitative tool. More research is required to resolve these issues. In the interim, WHO should consider withdrawing its current guidelines for neonatal TSH screening for monitoring iodine deficiency in populations.

Methods for determination of iodine in urine and salt

Pieter L. Jooste, Emmerentia Strydom — 2010-02-01

Good quality data on iodine concentrations in urine and salt samples are indispensable for the efficient management of national salt iodisation programmes and for evaluating iodine interventions. Most of the analytical methods for urinary iodine concentration are based on the manual spectrophotometric measurement of Sandell–Kolthoff reduction reaction catalysed by iodine using different oxidising reagents in the initial digestion step. Other analytical methods include semi-quantitative methods, a microplate method, automated methods; and the technologically advanced methods include the inductively coupled plasma mass-spectrometer method.Iodine in salt is determined quantitatively by the titration method, colorimetrically by the WYD iodine checker or by a technologically advanced potentiometric method. Worldwide, titration is the method of choice because of its accuracy, ease of operation and low cost. Rapid test kits are suitable for qualitative use in situations where iodised salt need to be distinguished from non-iodised salt, preferably with titration back-up.

The challenges of iodine supplementation: a public health programme perspective

Juliawati Untoro, Arnold Timmer, Werner Schultink — 2010-02-01

An adequate iodine intake during pregnancy, lactation and early childhood is particularly critical for optimal brain development of the foetus and of children 7–24 months of age. While the primary strategy for sustainable elimination of iodine deficiency remains universal salt iodisation, the World Health Organization and the United Nations Children's Fund recommend a complementary strategy of iodine supplements as a temporary measure when salt iodisation could not be implemented. This article aims to review current evidence on efficacy and implications of implementing iodine supplementation as a public health measure to address iodine deficiency. Iodine supplementation seems unlikely to reach high coverage in a rapid, equitable and sustained way. Implementing the programme requires political commitment, effective and efficient supply, distribution and targeting, continuous education and communication and a robust monitoring system. Thus, universal salt iodisation should remain the primary strategy to eliminate iodine deficiency.

The challenges of implementing and monitoring of salt iodisation programmes

Kevin M. Sullivan — 2010-02-01

Assuring adequate iodine nutrition is key to preventing iodine deficiency disorders (IDDs). The primary strategy to assuring adequate iodine nutrition in most populations is through the iodisation of salt. The challenges of implementing and monitoring salt iodisation programmes are described. In particular, issues relating to legislation, regulation and enforcement are presented, as well as the integration of this information with household-based surveys on the proportion of households using iodised salt and the iodine status of the population.

Iodine excess

Hans Bürgi — 2010-02-01

Several mechanisms are involved in the maintenance of normal thyroid hormone secretion, even when iodine intake exceeds physiologic needs by a factor of 100. The sodium–iodide symporter system contributes most to this stability. Faced with an iodine excess, it throttles the transport of iodide into the thyroid cells, the rate-limiting step of hormone synthesis. Even before the iodine symporter reacts, a sudden iodine overload paradoxically blocks the second step of hormone synthesis, the organification of iodide. This so-called Wolff–Chaikoff effect requires a high (≥10−3 molar) intracellular concentration of iodide. The block does not last long, because after a while the sodium–iodide symporter shuts down; this allows intracellular iodide to drop below 10−3 molar and the near-normal secretion to resume. In some susceptible individuals (e.g., after radio-iodine treatment of Graves' disease or in autoimmune thyroiditis), the sodium–iodide symporter fails to shut down, the intracellular concentration of iodide remains high and chronic hypothyroidism ensues. To complicate matters, iodine excess may also cause hyperthyroidism. The current explanation is that this happens in persons with goitres, for example, after long-standing iodine deficiency. These goitres may contain nodules carrying a somatic mutation that confers a ‘constitutive’ activation of the TSH receptor. Being no more under pituitary control, these nodules overproduce thyroid hormone and cause iodine-induced hyperthyroidism, when they are presented with sufficient iodine. These autonomous nodules gradually disappear from the population after iodine deficiency has been properly corrected. More recent studies suggest that chronic high iodine intake furthers classical thyroid autoimmunity (hypothyroidism and thyroiditis) and that iodine-induced hyperthyroidism may also have an autoimmune pathogenesis.

The impact of common micronutrient deficiencies on iodine and thyroid metabolism: the evidence from human studies

Sonja Y. Hess — 2010-02-01

Deficiencies of micronutrients are highly prevalent in low-income countries. Inadequate intake of iodine impairs thyroid function and results in a spectrum of disorders. Other common deficiencies of micronutrients such as iron, selenium, vitamin A, and possibly zinc may interact with iodine nutrition and thyroid function. Randomised controlled intervention trials in iodine- and iron-deficient populations have shown that providing iron along with iodine results in greater improvements in thyroid function and volume than providing iodine alone. Vitamin A supplementation given alone or in combination with iodised salt can have a beneficial impact on thyroid function and thyroid size. Despite numerous studies of the effect of selenium on iodine and thyroid metabolism in animals, most published randomised controlled intervention trials in human populations failed to confirm an impact of selenium supplementation on thyroid metabolism. Little evidence is available on interactions between iodine and zinc metabolism.

Perchlorate, iodine and the thyroid

Angela M. Leung, Elizabeth N. Pearce, Lewis E. Braverman — 2010-02-01

In pharmacologic doses, perchlorate inhibits thyroidal iodine uptake and subsequently decreases thyroid hormone production. Although pharmacologic doses may be used in the treatment of hyperthyroidism, recent literature has focussed on the detection of low levels of perchlorate in the environment, groundwater and foodstuffs and their potential adverse effects on human thyroid function. This is of particular concern to the developing foetus and infant, whose normal neurodevelopment depends on adequate iodine intake for the production of thyroid hormones. Further research is needed to clarify the potential health effects of low-level chronic environmental perchlorate exposure. The health impact of environmental perchlorate may be dependent upon adequate iodine intake and should be interpreted in combination with other environmental exposures that are also potential thyroidal endocrine disruptors.

Iodine in Enteral and Parenteral Nutrition

Michael B. Zimmermann, Catherine M. Crill — 2010-02-01

Iodine deficiency (ID) has multiple adverse effects on growth and development due to inadequate thyroid hormone production. Methods for assessment of iodine nutrition in individuals include the urinary iodine concentration (UI), thyroid size and thyroid function tests. The UI measured in several repeat 24-h urine samples can detect inadequate iodine intake in individuals receiving enteral or parenteral nutrition (PN) and allow for iodine supplementation before the onset of hypothyroidism. A daily dose of 1 μg iodine/kg body weight is currently recommended for children receiving PN, but this is far below their requirements. Daily iodine requirements in adults receiving enteral nutrition or PN are estimated to be 70–150 μg, but most PN formulations do not contain iodine. Despite this, ID has been unlikely because absorption from iodine-containing skin antiseptics and other adventitious sources can provide sufficient iodine. However, if chlorhexidine replaces iodine-containing antiseptics for catheter care, ID may occur during long-term PN, and periodic testing of UI and thyroid function may be prudent. Infants may be particularly vulnerable to ID because of their small thyroidal iodine store. In this review, we describe three recent patients (an infant, a child and an adult) who developed ID and thyroid hypofunction during PN.

Keyword index

2010-02-01