Allan Carlé

Iodine intake as a determinant of thyroid disorders in populations

UNLABELLED 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 (Hashimotos 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 intake before and after mandatory iodization in Denmark: results from the Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr) study

Iodine deficiency is still common in some European countries. In Denmark an iodine fortification programme was introduced in 1998 and a monitoring programme was established prior to iodization. This study reports the change in urinary iodine excretion caused by fortification and investigates determinants of iodine intake after fortification. Iodine excretion in casual urine samples was assessed in 4649 subjects in 1997-8 and in 3570 comparable subjects in 2004-5 in women 18-22, 25-30, 40-45 and 60-65 years of age and in men 60-65 years of age living in Aalborg (western part of Denmark) or Copenhagen (eastern part of Denmark). These areas had moderate and mild iodine deficiency, respectively, before iodine fortification. All subjects filled in a FFQ and a questionnaire regarding lifestyle factors. Iodine excretion, expressed as the estimated 24 h urinary iodine excretion and as urinary iodine concentration, increased significantly in all age and sex groups. However, the iodine intake was still below the recommended in the youngest age groups in both cities and in women 40-45 years of age living in Aalborg. Intake of milk and salt had strong significant direct associations with iodine excretion (P < 0.001). It is concluded that although the median iodine intake in the whole study population is at the recommended level, some groups still have an intake below the recommended. It is important to have a moderate milk intake to obtain a sufficient iodine intake in Denmark.

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population

Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO‐Ab) and thyroglobulin antibody (Tg‐Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain.

Thyroglobulin as a marker of iodine nutrition status in the general population

OBJECTIVE The iodine status of a population is traditionally evaluated by either urinary iodine (UI) excretion or by some measure of thyroid volume and the prevalence of goitre. In this prospective study of a mandatory iodization programme, we aimed to evaluate serum thyroglobulin (Tg) as a marker of iodine status in the population. METHODS Two identical cross-sectional studies were performed before (1997-1998, n=4649) and after (2004-2005, n=3570) the initiation of the Danish iodization programme in two areas with mild and moderate iodine deficiency. Serum Tg was measured from blood samples. Thyroid volume was measured by ultrasonography. RESULTS Before iodization, the median serum Tg was considerably higher in moderate than in mild iodine deficiency. Iodization led to a lower serum Tg in all examined age groups. The marked pre-iodization difference in Tg level between the regions was eliminated. The prevalence of Tg above the suggested reference limit (40 microg/l) decreased from 11.3 to 3.7% (P<0.0001). Using bootstrapping, we demonstrated a higher efficacy of Tg than of thyroid volume to show a difference between pre- and post-iodization values. CONCLUSION We found serum Tg to be a suitable marker of iodine nutrition status in the population. The results may suggest that the Danish iodization programme has led to a sufficient iodine intake, even if the median UI excretion is still marginally low according to WHO criteria.

Hypothyroidism in the Elderly: Pathophysiology, Diagnosis and Treatment

Some degree of hypothyroidism is common in the elderly. It affects 5–20% of women and 3–8% of men. The occurrence varies with genetics with a high prevalence in Caucasians, and the disease is more common in populations with a high iodine intake.The common causes of hypothyroidism are autoimmune destruction of the thyroid gland and previous thyroid surgery or radioiodine therapy. Various types of medication, including amiodarone, cytokines and lithium, often induce hypothyroidism.Symptoms may be atypical and measurement of serum thyroid-stimulating hormone (TSH) levels should be part of biochemical testing for undiagnosed medical conditions in elderly subjects. The finding of an elevated serum TSH level should be confirmed by repeated testing and supplemented with measurements of serum levels of thyroxine (T4) and thyroid peroxidase antibodies to verify, quantify and subclassify the abnormality.The recommended and appropriate replacement therapy for hypothyroidism is levothyroxine sodium. The initial replacement dose should be low if heart disease is suspected. Because of the long half-life of levothyroxine sodium small dosage adjustments may be performed by adding or withdrawing a tablet once or twice weekly. Levothyroxine sodium is only partly absorbed after oral ingestion, and food, minerals, drugs and tablet composition influence absorption.Studies performed a few years ago suggested that a combination of levothyroxine sodium and liothyronine may improve clinical results, but recent more comprehensive studies have not supported this hypothesis. Accordingly, liothyronine replacement is not documented to be of benefit. If liothyronine is added to replacement, the liothyronine dose should be kept low, within the physiological range and, preferably be administered twice daily.Thyroid hormone therapy has no beneficial effect above placebo in elderly individuals with normal serum TSH levels and T4 levels. The major risk of levothyroxine sodium therapy is over-replacement, with anxiety, muscle wasting, osteoporosis and atrial fibrillation as adverse effects.Subclinical hypothyroidism with elevated serum TSH levels but T4 levels within the laboratory reference range is a mild variant of overt hypothyroidism. Patients with subclinical hypothyroidism should be informed about the disease and offered the possibility of replacement. Only some patients treated for subclinical hypothyroidism will feel better after therapy.In elderly patients on replacement therapy, care should include estimation of serum TSH level once or twice a year, with small dosage adjustments of levothyroxine sodium to keep serum TSH level within the normal range.

The TSH upper reference limit: where are we at?

The diagnosis of subclinical hypothyroidism—serum TSH levels above and T4 levels within the laboratory reference ranges—depends critically on the upper limit of the TSH reference interval. Calls have been made to lower the current upper TSH reference limit of 4.0 mU/l to 2.5 mU/l to exclude patients with occult hypothyroidism. However, data from population studies do not indicate that the distribution of TSH is altered owing to inclusion of such individuals. The opposite suggestion has also been put forward; the TSH upper reference limit is often too low, especially in the elderly, in women and in white individuals, which may lead to unnecessary or even harmful therapy. Studies in elderly individuals have shown that although aging may be associated with increased TSH levels, paradoxically, overt hypothyroidism in this population may be associated with a less robust TSH response than in young individuals. This Review highlights the interindividual and intraindividual variability of TSH levels and discusses the current controversy that surrounds the appropriateness of reference ranges defined on the basis of age, race, sex and amount of iodine intake. Moreover, the current evidence on lowering or increasing the upper limit of the TSH reference interval is reviewed and the need to individualize levothyroxine treatment in patients with elevated TSH levels is discussed.

Serum selenium is low in newly diagnosed Graves’ disease: a population‐based study

Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease.

Smoking cessation is followed by a sharp but transient rise in the incidence of overt autoimmune hypothyroidism – A population‐based, case–control study

Current smoking is associated with a low prevalence of thyroid autoantibodies. On the other hand, smoking withdrawal enhances thyroid autoantibody level and may be a risk factor for the development of hypothyroidism. The aim of this study was to assess the association between smoking habits (smoking cessation in particular) and development of autoimmune hypothyroidism.

Thyroid Function and Obesity

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail.

Lower prevalence of mild hyperthyroidism related to a higher iodine intake in the population: prospective study of a mandatory iodization programme

Objective  Marked differences in pattern of thyroid dysfunction are seen in populations with different iodine intakes. We evaluated the influence of a higher iodine intake on thyroid hormone levels and the prevalence of thyroid dysfunction in the Danish population.