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Purpose Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. Methods The study included 51 patients with an advanced neuroendocrine tumour who received 177Lu-DOTATATE treatment during 2006 – 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 – 8.2 GBq) was given at intervals of 6 – 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. Results A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p

IntroductionThe incidence of hyperthyroidism has been reported in various countries to be 23–93/100 000 inhabitants per year. This extended study has evaluated the incidence for ∼40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country.MethodsAll patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003–2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered.ResultsA total of 2916 patients were diagnosed withde novohyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed.ConclusionThe incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.

ObjectiveThe objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs.Design and methodsThe design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period.ResultsPatient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment.TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (PComparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study.In patients without TAO, there were no differences in QoL related to mode of treatment.ConclusionsThe QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.

Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO).The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs.We conducted a randomized trial (TT 96) with a follow-up of 4 yr. PATIENTS, SETTING, AND INTERVENTION: Patients with a recent diagnosis of Graves' hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T(4) was given in both groups.Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P0.001).The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism.Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.

Background: The thyroid’s ability to enrich and store iodine has implications for thyroid cancer genesis, progression, and treatment. The study objective was to investigate thyroid iodine content (TIC) in tumoral and extratumoral tissue in patients with papillary thyroid cancer (PTC) as opposed to thyroid healthy controls using two different techniques: X-ray fluorescence (XRF) and time-of-flight secondary ion mass spectrometry (TOFSIMS). Methods: Tissue samples from 10 patients with normal thyroids and 7 patients with PTC were collected. TIC was quantified with XRF, and the iodine stores were located on a histological level with TOF-SIMS. Results: Mean TIC in controls was 0.6 mg=mL (range 0.3–1.2 mg=mL). For the cancer patients, the mean TIC was 0.8 mg=mL (range 0.2–2.3 mg=mL) in extratumoral thyroid tissue, but no iodine was detected in the tumors. TOF-SIMS investigation of the PTC patients showed significantly higher TIC in extratumoral tissue than in tumoral tissue. Iodine in the extratumoral tissue was predominantly located in the follicle lumen with a variation in concentration among follicles. Conclusions: XRF and TOF-SIMS are two complementary methods for obtaining insight into content and localization of iodine in the thyroid. XRF can be used in vitro or in vivo on a large number of samples or patients, respectively. TOF-SIMS on the other hand provides detailed images of the iodine location. The combined information from the two methods is of value for further studies on iodine metabolism in thyroid malignancy.

Sweden has a long-standing salt iodization program; however, its effects on iodine intake have never been monitored on a national level. The objective of this study was to evaluate iodine nutrition in the Swedish population by measuring the urinary iodine concentration (UIC) in a national sample of Swedish school-age (6-12 years of age) children.A stratified probability proportionate to size cluster sampling method was used to obtain a representative national sample of school-age children from 30 clusters. Spot urine samples were collected for UIC analysis using a modified Sandell-Kolthoff method.The median UIC of the children (n=857) was 125 microg/l (range 11-757 microg/l). The proportion of children with a UIC100 microg/l was 30.0% and the proportion of children with a UIC50 and300 microg/l was 5.5 and 3.0%, respectively.The iodine nutritional status of the Swedish population is adequate. Iodized table salt remains the main dietary source of iodine in Swedish diet. Recommendations to reduce total salt intake in the population urge increased use of iodized salt in the production of processed foods. Pregnant and lactating women with high iodine requirements may still be at risk for low iodine intake. This study will serve as the basis for future monitoring of iodine nutritional status in Sweden.

The thyroid gland is unique in that it stores a large amount of iodine, an element suitable for x-ray fluorescence analysis (XRF). Knowledge of the amount of iodine stored in the thyroid in the iodine pool may contribute to the understanding of thyroid diseases and possibly predict treatment outcome. XRF is a non-invasive method which can be used for direct evaluations of the iodine pool in vitro as well as in vivo. However, in contrast to in vitro studies, which involve a measurement geometry that is well known and can be carefully controlled, complications may arise when using the technique in vivo. In this study, Monte Carlo (MC) simulations were used for finding an optimal measurement geometry regarding source and detector collimator apertures. The relative importance of primary and scattered radiation in the production of iodine Kα x-rays for a simulated thyroid gland at different depths in the neck was investigated. The results showed that incoherently scattered radiation may be a considerable contributor of Kα photons in commonly encountered in vivo geometries. Calibrations should thus be performed with precise knowledge of the measurement geometry and it is important that corrections are made for primary photon fluence but also for photon scattering in the neck. Copyright © 2007 John Wiley & Sons, Ltd.

Radioiodine and most cytostatic treatments are contraindicated in pregnancy. Still, inadvertent therapy does occur. Radioiodine was given to two pregnant women with Graves' disease and thyroid cancer respectively, both in their 20th gestational week. Routine pregnancy tests based on urinary beta-hCG had failed to indicate pregnancy in both cases.Estimation of doses to the foetuses and foetal thyroids. Scrutiny of pregnancy testing.Doses to foetal thyroids were ablative (250-600 Gy). Total foetal dose in the Graves' patient was 100 mGy and compatible with survival, whereas a foetal dose of approximately 700 mGy together with induced hypothyroidism was fatal for the foetus of the cancer patient. Routine pregnancy tests may fail early and late in pregnancy. The possibility of pregnancy should be considered in all fertile women before therapy with radionuclides or cytostatic regimens, and a clinical investigation undertaken on wide indications with determination of serum beta-hCG, preferably together with an ultrasound examination.

Iodine is enriched and stored in the thyroid gland. Due to several factors, the size of the thyroid iodine pool varies both between individuals and within individuals over time. Excess iodine as well as iodine deficiency may promote thyroid cancer. Therefore, knowledge of iodine content and distribution within thyroid cancer tissue is of interest. X-ray fluorescence analysis (XRF) and secondary ion mass spectrometry (SIMS) are two methods that can be used to assess iodine content in thyroid tissue. With both techniques, choice of sample preparation affects the results. Aldehyde fixatives are required for SIMS analysis while a freezing method might be satisfactory for XRF analysis. The aims of the present study were primarily to evaluate a simple freezing technique for preserving samples for XRF analysis and also to use XRF to evaluate the efficacy of using aldehyde fixatives to prepare samples for SIMS analysis. Ten porcine thyroids were sectioned into four pieces that were either frozen or fixed in formaldehyde, glutaraldehyde, or a modified Karnovsky fixative. The frozen samples were assessed for iodine content with XRF after 1 and 2 months, and the fixed samples were analyzed for iodine content after 1 week. Freezing of untreated tissue yielded no significant iodine loss, whereas fixation with aldehydes yielded an iodine loss of 14–30%, with Karnovsky producing the least loss.

Radioiodine treatment for thyroid disease has been given for half a decade in Sweden. The most common indication for treatment is hyperthyroidism, when iodine uptake is high. The situation in which radioiodine treatment is used in thyroid cancer is less favourable and measures therefore have to be taken to optimize the treatment. Treatment should be performed early in the course of the disease to achieve the highest possible differentiation. Before treatment the iodine and goitrogen intake should be kept low. Stimulation of the thyrocytes by thyroid-stimulating hormone (TSH) should be high. It is conventionally achieved by thyroid hormone withdrawal rendering the patient hypothyroid, or by the recently available recombinant human TSH (rhTSH) which can be recommended for ablation of the thyroid remnant after thyroidectomy and for treatment of metastases in fragile patients unable to undergo hypothyroidism. Finally, stunning--the negative effect of a prior test dose from radioactive iodine--should be avoided.

We present a case in which a patient with disseminated well-differentiated papillary thyroid cancer developed severe thyroid-associated ophthalmopathy. Eight years after initial surgery and ablative radioiodine therapy the patient was found to have multiple pulmonary metastases. The metastases showed poor uptake of radioiodine. An attempt was made to use 13-cis-retinoic acid in order to achieve a redifferentiation of the thyroid cancer cells before recombinant human thyrotropin (rhTSH) stimulated radioiodine therapy. The treatment did not improve the uptake of radioiodine. However, approximately 2 weeks after completion of the treatment the patient experienced discomfort in her eyes and then over the next months she developed a severe ophthalmopathty. The analyses of TSH receptor antibodies and S-thyroglobulin simultaneously showed a pronounced increase. An association between therapy given and severe ophthalmopathy cannot be excluded.

Micropatterns induced by sheep grazing, were studied in three consecutive years in a Festuca rubra-dominated salt marsh in a grazing trial with five different stocking rates (0, 1.5, 3, 4.5 and 10 sheep ha-1). The micropatterns were formed by a mosaic of short and tall F. rubra stands on a scale of square decimeters. Permanent transects of 2 m × 10 m were used to study the stability of these patterns, and to analyze interactions between the vegetation, the marsh elevation and the sheep. Micropatterns occurred only in the lightly to moderately grazed paddocks (1.5–4.5 sheep ha-1) with the highest spatial diversity in the 3 sheep ha-1 transect. When grazing was excluded, micropatterns did not develop; nor did they develop in the traditionally and most intensively grazed paddock (10 sheep ha-1). Detailed observations in one year showed that crude-protein content did not differ between green leaves from the short and tall stands, whereas in vitro digestibility was slightly higher in the short stands. In the same year, tiller density and length of full-grown leaves increased substantially in both stands from May to September. At the same time, sheep preference shifted from tall to short stands, which suggests an interplay between intake rate and digestibility in the sheep selectivity. Seven years after establishment of the grazing trial, the 10 sheep ha-1 transect still showed a smooth relief typical of the starting point of the other transects. These transects developed a more hummocky topography, with the highest spatial diversity occurring on the 1.5 sheep ha-1 transect. Marsh elevations were on average up to 3 cm lower in the short than in the tall stands, which indicates that the somewhat lower-elevated patches were grazed more intensively than the higher-elevated patches. In most cases, micropatterns changed from one year to the other, probably due to weather fluctuations. The incidence of tall stands was influenced by the rainfall balance. If the incidences of both the short and the tall stands were around 50%, however, the micropatterns showed a clear correlation with the marsh elevation. The rainfall balance seemed therefore a decisive factor for a possible correspondence between micropatterns in two consecutive years. Elevation differences were so subtle that greater than average sedimentation during a winter season could change the elevation pattern. Hence both rainfall balance and winter sedimentation counteracted the stability of the micropatterns. During our three-year study period, micropatterns were only stable in one out of six possible paired comparisons. This low micropattern stability contrasts with other studies in inland environments, which shows that in more dynamic environments, abiotic processes are likely to overrule summer grazing in determining vegetation patterns.

Objectives. To study the clinical outcome of treatment of hyperthyroid patients with radioiodine. Design. Records of patients treated for hyperthyroidism with radioiodine from 1989 to 1992 were examined in 1994, and a questionnaire was sent to patients 70 years with Graves' disease (GD) and toxic nodular goitre (TNG) to obtain information regarding thyroxine substitution, smoking habits and present state of health. Setting. Outpatients in a thyroid unit; follow-up by primary care. Subjects. Seven hundred and fifty-four patients with hyperthyroidism treated with radioiodine, 327 receiving the questionnaire, 72% response rate. Intervention. Radioiodine treatment using a delivered absorbed dose method, aiming at an absorbed dose to the thyroid of 100–120 Gy. Main outcome measures. Statistical analysis of clinical records and results from questionnaire. Results. Only 10% of the patients needed more than one treatment. At the time of follow-up, thyroxine supplementation was given to 178 (93%) of the GD and to 21 (47%) of the TNG patients. Smoking was more common in GD patients than in the general population (44% vs. 26%; P

SummaryObjectives To study hyperthyroidism in long-term iodine sufficiency (IS), as iodine supply affects its occurrence. Design Prospective descriptive study. Patients In 2003–2005, all referred cases of subclinical (SH) and overt hyperthyroidism (OH) were registered at diagnosis from a population (n = 631 239) in Gothenburg, Sweden. Measurements Information on age, gender, smoking, thyroid associated ophthalmopathy (TAO), thyroid hormones and TSH receptor antibodies (TRab) was collected. Incidences were calculated. SH and OH cases with Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA) were compared. In GD, TRab+ and TRab− cases and patients with (TAO+) and without TAO (TAO−) were compared. Results The total incidence (n/100 000/year) of hyperthyroidism was 27·6; OH 23·8; SH 3·8; GD 21·4; TMNG 4·3; and STA 1·8. SH was more common among TMNG (40·2%) and STA (45·7%) than in GD (5·9%). SH-GD patients were older, more often smokers and had lower TRab levels than OH-GD patients. FreeT4 and T3 levels in GD were higher than in TMNG and STA. FreeT4, T3 and TRab decreased with age in patients with GD, P

Background Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. Methods Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. Results The median accumulated dose was 1.9 Gy (1.5–2.2 Gy) to the hypothalamus and 2.4 Gy (1.8–3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0–9.3 Gy and 33.5–46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. Conclusion In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.

Patients with Graves' disease can be medically prepared before surgery in different ways, which may have various effects on iodine stores. Thyroid specimens were collected at surgery from two patients pretreated with propylthiouracil (PTU) and stable iodine, respectively. A quantitative analysis of iodine content was performed using X-ray fluorescence (XRF) in frozen tissue and a qualitative analysis of aldehyde-fixed material with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS). Iodine concentrations were 0.9 mg/mL and 0.5 mg/mL in the thyroid tissue from the patients treated with PTU and stable iodine respectively. TOF-SIMS showed iodine in the follicle lumina in both. However, in the PTU case, iodine was also seen within the thyrocytes indicating accumulation of iodinated compounds from uninhibited hormone release. XRF and TOF-SIMS can be used to follow iodine distribution within the thyroid and the intricate processes following the different medical treatment alternatives in Graves' disease.

The medical history taken at the first consultation should comprise information about thyroid disease in the family, smoking habits, iodine intake (including for X-ray investigations), external radiation and consumption of herbal medicines (e.g. algae preparations).

The most common causes of thyrotoxicosis are toxic diffuse goitre and toxic multi- or uninodular goitre (see Chaps. 18, 20 and 21). Thyroiditis, with an initial hormone leakage phase from the thyroid gland, is another common cause of thyrotoxicosis (see Chaps. 9, 25 and 26). This chapter deals with thyrotoxicosis due to diseases that directly or indirectly affect thyroid function, but are uncommon and not always easy to diagnose and treat.

Immunological mechanisms are critical for the occurrence and progression of autoimmune thyroiditis (AIT) and diffuse toxic goitre (Graves’ disease), with or without thyroid-associated ophthalmopathy (TAO) (see Chaps. 9 and 18).

Homeostasis of thyroid gland tissue is controlled by many factors (Table 8.1). Thyroid stimulating hormone (TSH) from the pituitary is the most well-known factor that has a direct and indirect effect on the function and growth of the thyrocytes. Other examples of growth stimulating factors are epidermal growth factor (EGF), transforming growth factor α (TGF-α), insulin like growth factor (IGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and the growth inhibiting transforming growth factor β (TGF-β). In addition there are factors that regulate cell death (apoptosis) in the thyroid gland. Furthermore, the availability of iodine has a significant effect on homeostasis. All of these factors can affect thyroid tissue volume and its ability to meet the requirements of the body.

A transient diffuse enlargement of the thyroid can occur during puberty. In countries with suffi cient availability of iodine, a diffuse enlargement of the thyroid can otherwise be caused by autoimmune thyroiditis. From a global perspective, iodine deficiency is the most common cause of goitre in adolescents.

Eye symptoms are a common feature of Graves’ disease, where the symptoms have an underlying immunological cause. Several designations have been used: endocrine ophthalmopathy, dysthyroid orbitopathy, dysthyroid ophthalmopathy, orbitopathy, infiltrative ophthalmopathy and thyroid-associated ophthalmopathy (TAO).

Thyroiditis is a collective name for several inflammatory conditions in the thyroid. In most cases, thyroiditis is caused by autoimmune mechanisms as discussed in Chap. 7. Subacute thyroiditis, which is thought to be triggered by a viral infection, is dealt with in Chap. 26. Bacterial infections of the thyroid are rare. Other causes of inflammatory reaction in the thyroid include treatment with I-131, which is sometimes associated with an inflammatory-like reaction, and external trauma to the thyroid. In some instances, medicines can cause thyroiditis.

Access to an adequate amount of iodine is important if an individual is to fully maintain production of thyroid hormones. In areas with low availability of iodine in food (Fig. 6.1), a deficiency of iodine can result in TSH stimulation of the thyroid and development of goitre. This enables an adult to initially compensate for low iodine supply and maintain adequate hormone production. Iodine deficiency during childhood and adolescence can thereby result in irregular growth of the thyroid and formation of multinodular goitre.

Pregnancy results in physiological changes that affect thyroid function. The management of thyroid disease in a pregnant woman sets particular challenges because diagnosis, treatment and follow-up can vary from that for a nonpregnant patient. It is very important that these patients are cared for correctly right from the start of pregnancy, because the development of the foetus may otherwise be negatively affected. This applies not least to the central nervous system.

Thyroiditis may be due to autoimmune disease or other causes. For a general review of the different forms of thyroiditis, please refer to Chap. 9, in which additional clinical aspects are discussed.

Regulation and metabolism of thyroid hormones is dealt with in detail in Chap. 2. Some medicines can affect regulation and metabolism of thyroid hormones. Medicines such as dopamine and corticosteroids in high doses can impair TSH and thereby the release of thyroid hormones at the hypothalamic level. Conversion of T4 to T3 can be affected by compounds such as corticosteroids and propranolol, a nonselective beta blocker.

Three treatment options are available for patients with hyperthyroidism: antithyroid drugs, surgery and radioiodine therapy. For patients with Graves’ disease all three options can be applied. For patients with toxic nodular goitre or toxic adenoma, treatment with antithyroid drugs is only indicated for a limited time, prior to definitive therapy with one of the other two methods.

Subclinical thyrotoxicosis is defined as a condition with lowered (suppressed) TSH, but T4 and T3 are within their reference ranges. The designation subclinical is somewhat misleading because it has been demonstrated that many patients do in fact have thyrotoxic symptoms but in a milder form than what is in generally referred to as thyrotoxicosis. The designation mild thyrotoxicosis is therefore more frequently used. In Sweden, the prevalence is 2–4% and increases with age.

Hyperthyroidism and thyrotoxicosis are used by many as synonymous terms. However, thyrotoxicosis describes the clinical condition that covers symptoms following high concentrations of the thyroid hormones, T4 and T3, in extrathyroidal tissues, but without regard to the origin of these elevated hormone concentrations.

Subacute thyroiditis, or de Quervain’s disease, which is sometimes called giant-cell thyroiditis or granulomatous thyroiditis, is an inflammatory thyroid disease in which nearly all cases (95%) will fully recover.

Thyroid hormone resistance is defined as a dominant hereditary condition in which the gene for the thyroid hormone receptor protein has mutated so that the normal binding of thyroid hormone on the T3 receptors in the cell nuclei of different organs is reduced. The condition is extremely rare, but important to be familiar with, because a missed diagnosis may result in incorrect treatment of the patient for proposed thyrotoxicosis due to high T4 and T3 concentrations.

International audience; Background/ Objectives: Sweden has had a salt iodination program since 1936. This first national surveillance study on iodine nutrition infers an adequate level of urinary iodine concentration (UIC 125 ug/L) and the aim is now to evaluate thyroid volume (Tvol) in the same national sample. Subjects/ Methods: A stratified probability proportionate to size cluster sampling was used to obtain a representative national sample of Swedish children aged 6-12 years. Median Tvol obtained ultrasonografically and the prevalence of enlarged thyroid glands were compared with an international reference standard. Regional differences were evaluated through comparisons of Tvol between coastal and inland areas, urban and rural regions, and former goitre and non-goitre regions. Results: Tvol correlated to age, body surface area (BSA), weight, height, and BMI for both sexes, (p

This chapter describes the consequences of lifelong iodine supplementation concentrating on adults. The results of studies of various aspects of iodine metabolism and thyroid disease in Sweden have been summarized. Sweden has had iodine supplementation since 1936; thus, an adult in Sweden today has experienced lifelong exposure to iodine. The uptake of iodine in the thyroid gland is lower than in a Swedish population studied 45 years earlier, showing the long-term adaptation to an environment higher in iodine. These figures correspond to an intake of iodine of about 260 μg/day in 2000 compared to 100 μg/day in 1955. The prevalence of goiter is 7% in adults in western Sweden, which is lower than in areas with low iodine intake. The prevalence of thyroid autoimmune disease may be slightly higher than in populations with a low iodine intake. Thyroid cancer incidence has been stable for the period 1971–2006. Intrathyroid iodine levels may vary in a population, which has been iodine-sufficient for a long period. Most of the studies were performed in the small community of Molnlycke in western Sweden where the population studied consists of a fairly homogeneous group that has been stationary in the region.

This chapter reviews the XRF technique, with emphasis on the physical background and clinical applications. Necessary equipment, together with the methodological limitations and benefits, is discussed and a brief guide before starting XRF measurements is also provided. Iodine uptake and excretion can be assessed by 131 I measurements or urinary iodine, whereas information on the amount of iodine stored in the thyroid, in the iodine pool, is not as commonly obtained. The iodine pool can be estimated by noninvasive X-ray fluorescence (XRF) analysis. Depending on the choice of equipment, the iodine estimation can be made quantitatively or by imaging the iodine distribution. The technique involves a radioactive source or an X-ray tube for irradiation of the stable iodine in the thyroid, together with a detector that registers the subsequent emission of characteristic X-ray photons. The method is noninvasive and can be used in vitro as well as in vivo . The equipment consists of a radiation source, a detector, electronics, and a spectroscopy program. The radiation dose involved in a measurement is very low. The areas of special interest are monitoring of iodination programs, identification of individuals with a small iodine pool who are at special risk of developing hypothyroidism in iodine deficiency, and also investigations of mechanisms of thyroid disease in iodine overload.

X-ray fluorescence (XRF) is a non-invasive method for determining the iodine content of the thyroid gland in vivo. In spite of the obvious clinical value of such a method in situations of iodine deficiency or iodine overload, the method has not so far been widely used. The objective was to investigate the applicability of the XRF method in a larger number of subjects.The study comprised 37 individuals, aged 60-65 years, who had spent their entire life with iodine supplementation through iodinated table salt. Individuals with (previous) thyroid disease were excluded. The individual thyroid function had previously been evaluated by measurements of thyroid-related hormones, thyroid volume and 131-Iodine (131I) uptake which indicated a sufficient iodine intake of the population in the area. Iodine in the right thyroid lobe in each subject was examined using XRF.The mean thyroid iodine concentration was 0.4 mg mL(-1), corresponding to a mean total iodine content of 5.2 mg (range 0.9-20.2). There was a pronounced difference between individuals. No correlation was found between iodine concentration and 131I uptake or thyroid volume. Neither was iodine content and 131I uptake correlated.In a population living under iodine-sufficient conditions, a large variation of iodine stored in the thyroid is compatible with euthyroidism. Determination of the iodine pool by XRF investigation is feasible in a clinical setting and the method offers a unique possibility to study the intrathyroidal iodine pool in subjects with thyroid disease. The low radiation dose enables the use of the method in pregnant women and also in young individuals.

BACKGROUND: In Sweden, iodine has been added to table salt (10 mg/kg) since 1936; this amount was increased in 1966 to 50 mg/kg. OBJECTIVE: To investigate a euthyroid Swedish population (n = 44, 60-65 years) with its entire lifespan with iodine supplementation as for 24-h 131-I uptake (24 h IU) and thyroid nodularity (thyroid scintigraphy). To compare the euthyroid 24 h IU with uptake of thyrotoxic individuals, and with observations from 1955. METHODS: The 24 h IU was used in euthyroid individuals after oral administration of 0.1 MBq/2.7 microCi radioiodine and imaging of the thyroid gland was carried out using 99mTc-pertechnetate. RESULTS: In 1999-2000, the mean 24 h IU in the euthyroid individuals was 21% (range 11-33%) and the normal (central 95%) reference interval was 14-30%. Scintigraphy suggested multinodular goitre in three euthyroid individuals. In Graves' patients (n = 53, 50-65 years), the mean 24 h IU was 61% (range 29-89%). In 1955, the 24 h IU in euthyroid individuals was higher (38%, range 10-70%), while hyperthyroid patients had uptake values similar to those recorded in the present investigation (mean 62%, range 40-90%). CONCLUSIONS: The population sample studied had to be small for ethical reasons. We conclude that the reference interval for 24 h IU is 14-30% in this population that had spent its entire lifespan with iodine supplementation. This is lower than that recorded in a Swedish euthyroid population half a century ago having had low-grade table-salt iodine supplementation for 20 years. Values for hyperthyroid patients, however, do not appear to have been affected likewise.

As differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We have proposed, in a previous issue of this Journal, an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. We report here the case of a paradigmatic patient with papillary thyroid carcinoma, with the goal of illustrating the benefits of applying this algorithm in routine clinical practice. We also offer expanded and additional comments on various issues in the management of DTC.

Objective: Because differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, the follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of the disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We sought to develop an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. Methods: We analysed recent literature on the follow-up of DTC. Results: Recent large studies have produced three important findings: (i) in patients with low-risk DTC with no evidence of disease up to the 6- to 12-month follow-up, diagnostic whole-body scan adds no information when serum thyroglobulin (Tg) is undetectable and interference from anti-Tg antibodies is absent; (ii) use of recombinant human thyroid-stimulating hormone to aid Tg measurement is effective and provides greater safety, quality-of-life and work productivity than does levothyroxine withdrawal with its attendant hypothyroidism; and (iii) ultrasonography performed by an experienced operator is the most sensitive means of detecting neck recurrences of DTC. Conclusions: We present a revised follow-up protocol for low-risk patients taking into account the above findings. This protocol should help clinicians enter a new era of monitoring characterized by greater safety, simplicity, convenience and cost savings. European Journal of Endocrinology 150 105–112

We investigated whether recombinant human TSH (rhTSH) safely and effectively induces uptake of high-dose 131-iodine (131I) to ablate thyroid remnant or treat disease, in patients with well-differentiated thyroid carcinoma. Eleven consecutive patients unable to tolerate thyroid hormone withdrawal received one im injection of 0.9 mg rhTSH on 2 consecutive days before receiving 4000 MBq (approximately 108 mCi) radioiodine orally. Eight patients received one, and 3 patients 2 courses. Our series comprised 7 women and 4 men (mean age, 78 yr, range: 56-87 yr). Ten patients had undergone total or near-total thyroidectomy up to 19 yr earlier. rhTSH-stimulated single course radioiodine with the intention to ablate thyroid remnant was performed in 3 patients, with following estimation of radioiodine uptake and TG measurements. Of another 8 patients given this treatment palliatively, 5 had radiological, clinical and/or laboratory response, including: 80% decreased pathological uptake between treatment courses; pronounced decrease in bone pain; diminished symptoms; improved physical condition and quality of life; lower serum TG concentration; and/or normalization of TG recovery test. Two patients with small lung metastases on computed tomography had no detectable radioiodine uptake or other response; they also lacked uptake after withdrawal-stimulated radioiodine treatment. Despite being elderly and frail, patients generally tolerated treatment well; rhTSH caused nausea in one patient and transiently increased pain in bone and soft tissue lesions in another. We conclude that rhTSH-stimulated high-dose radioiodine for remnant ablation or tumor treatment is safe, feasible and seemingly effective, enhancing quality of life and offering reasonable palliation in patients with advanced disease.

Milakovic M, Berg G, Eggersten R, Lindstedt G, Nystrom E (Sahlgrenska University Hospital, Goteborg, Sweden). Screening for thyroid disease of 15–17-year-old schoolchildren in an area with normal iodine intake. J Intern Med 2001; 250: 208–212. Objective. The prevalence of thyroid disease in Swedish schoolchildren is today insufficiently known. The aim of the study was therefore to determine the prevalence of abnormal thyroid function and thyroid autoimmunity in teen-age schoolchildren and to compare the findings with a healthy control group of 60–65-year-old inhabitants from the same community. Setting. A semirural community of approximately 15 000 inhabitants. Design. Cross-sectional study. Main outcome measures. Thyroid volume and serum concentrations of serum thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3′-triiodothyronine (T3), and antithyroperoxidase antibodies (TPOAb). Results. Four schoolchildren (7%, 59 screened) had elevated TPOAb concentration, three of the subjects being girls (8%). One girl with a goitre was overtly hypothyroid and one girl showed borderline-high serum TSH concentration suggesting subclinical autoimmune thyroid disease. One euthyroid boy had a goitre and high concentration of TPOAb. The serum free T3 concentration was significantly higher in 15–17-year-old than 60–65-year-old (7.4 vs. 6.4 pmol L–1, P

Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46 988 Swedish patients exposed to iodine-131 ( 131 |) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0·01-2·226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1·09 (95% confidence interval 0·94-1·25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR=1·08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1·09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131 |. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131 I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131 I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.

Cancer mortality was studied in 10,552 Swedish hyperthyroid patients treated with 131I between 1950 and 1975. The patients were matched with the Swedish Cause-of-Death Register and the cases of 977 patients who died from cancer or leukemia were studied. The patients had been followed up for an average of 15 years (range 0 to 35 years), and the overall standardized mortality ratio (SMR) was 1.09 [95% confidence interval (CI) = 1.03 to 1.16], with a higher risk for women. The highest mortality was seen during the first year after exposure (SMR = 1.15) and decreased for the following 9 years (SMR = 1.04). The risk of dying from a cancer in the digestive tract and respiratory organs was significantly elevated more than 10 years after exposure, as was the overall cancer mortality (SMR = 1.14). No increased risk was seen for leukemia, bladder cancer or breast cancer. Younger patients and those receiving 131I at higher activity had higher SMRs than older patients and those receiving lower activity. Patients with toxic nodular goiter had higher risk than those with Graves' disease. The lack of increasing mortality over time and with increasing activity of 131I administered argues against a carcinogenic effect of 131I. However, in the case of cancers of the stomach, the 131I exposure could have contributed to the excess mortality from these cancers.

Previous electron-microscopical studies from this laboratory have shown that the thyroglobulin molecule can occur in two different conformations, one ovoid and the other cylindrical. Ovoid molecules are characteristic of well-iodinated thyroglobulin whereas cylindrical molecules are found after low-iodine diet or blocking of iodination. The present study was performed in order to elucidate the possible relation between the molecule conformation and the peroxidase-catalyzed reactions that occur in the thyroid in connection with hormone synthesis. Cylindrical thyroglobulin molecules (from PTU-exposed thyroids) were incubated in different media and the proportion of cylindrical and ovoid molecules after incubation was estimated in electron micrographs. It was found that incubation with glucose-glucose oxidase caused an extensive conversion of cylindrical molecules into ovoid molecules. Peroxidase and/or iodide were not necessary for this change of conformation. It is suggested that this in vitro molecule transformation was the result of an oxidation reaction.