Showing papers in "European thyroid journal in 2012"

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

Abstract: Background: Data suggest symptoms of hypothyroidism persist in 5–10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area. Methods: Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large. Results: Suggested explanations for persisting symptoms include: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism.

Thyroid hormone actions in cartilage and bone.

Abstract: Thyroid hormones exert widespread and complex actions in almost all tissues during development, throughout childhood and in adults. The skeleton is an important T3-target tissue that exemplifies these processes, and yet understanding of the specific cellular and molecular mechanisms of T3 action in bone and cartilage remains incomplete. Here, the skeleton is considered as a T3-target tissue. The actions of thyroid hormones during skeletal development and in chondrocytes and growth plate cartilage during post-natal linear growth are outlined. The physiological importance of these actions are discussed in relation to patients with autosomal dominant mutations in genes encoding the thyroid hormone receptors TRα1 and TRβ, and in mice harbouring deletions or mutations of the orthologous genes. The role of thyroid hormones and the control of T3 action in bone turnover and maintenance are also outlined, and T3 action in bone-forming osteoblasts and bone-resorbing osteoclasts discussed. The physiological and functional consequences of T3 action in bone are considered in relation to mutant mouse models and to effects on bone mineral density and fracture susceptibility in humans. Finally, new studies identifying a putative role for thyroid hormone metabolism in articular cartilage maintenance and the pathogenesis of osteoarthritis are considered. The pharmacological context of these new findings is discussed, emphasising the importance of this emerging field of study in thyroid hormone pathophysiology.

2012 European thyroid association guidelines for metastatic medullary thyroid cancer

Abstract: Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC). These 21 recommendations focus on MTC patients with distant metastases and a detailed follow-up protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6–12 months, or at longer intervals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients.

Thyroid function and obesity

Abstract: 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.

The role of the iodothyronine deiodinases in the physiology and pathophysiology of thyroid hormone action

Abstract: Thyroxine (T4) is a prohormone and must be activated to 3,5,3′-triiodothyronine (T3) by either type 1 (D1) or type 2 (D2) selenodeiodinase. A third deiodinase (D3) inactivates T3 or T4 by removal of an inner ring iodine. These reactions require both a deiodinase enzyme and a cofactor, probably a thiol, to reduce the oxidized selenolyl group in the active center of each deiodinase. Thus, deiodination rates depend on both the enzyme and cofactor. The source of most of the circulating T3 is D1-mediated, while D2 provides nuclear receptor-bound hormone. Using sensitive and specific assays, it has become apparent that both D2 and D3 are widespread throughout vertebrate tissues. The complex interactions between the activating D2 and the inactivating D3 in tissues expressing these two enzymes determine the intracellular T3 concentration. This provides enormous flexibility for both developmental and tissue regeneration processes, allowing exquisite control of intracellular T3 concentrations. The endogenous factors regulating the activity of these enzymes, such as the hedgehog proteins, FoxO3, or the wnt/β catenin pathway together with the actions of thyroid hormone transporters, direct adjustments of nuclear receptor-bound T3 which in turn can control the balance between cellular proliferation and differentiation. Their actions provide dynamic flexibility to what appears on the surface to be a very static hormonal system.

2012 European Thyroid Association Guidelines for Genetic Testing and Its Clinical Consequences in Medullary Thyroid Cancer

Abstract: Twenty-five percent of medullary thyroid cancers (MTC) are familial and inherited as an autosomal dominant trait. Three different phenotypes can be distinguished: multiple endocrine neoplasia (MEN) types 2A and 2B, in which the MTC is associated with other endocrine neoplasias, and familial MTC (FMTC), which occurs in isolation. The discovery that germline RET oncogene activating mutations are associated with 95–98% of MEN 2/FMTC syndromes and the availability of genotyping to identify mutations in affected patients and their relatives has revolutionized the diagnostic and therapeutic strategies available for the management of these patients. All patients with MTC, both those with a positive familial history and those apparently sporadic, should be submitted to RET genetic screening. Once an RET mutation has been confirmed in an index patient, first-degree relatives should be screened rapidly to identify the 50% who inherited the mutation and are therefore at risk for development of MTC. Relatives in whom no RET mutation is identified can be reassured and discharged from further follow-up, whereas RET-positive subjects (i.e. gene carriers) must be investigated and a therapeutic strategy initiated. These guideline recommendations are derived from the most recent studies identifying phenotype-genotype correlations following the discovery of causative RET gene mutations in MEN 2 eighteen years ago. Three major points will be discussed: (a) identification of patients and relatives who should have genetic screening for RET mutations, (b) management of asymptomatic gene carriers, and (c) ethics.

The immunopathogenesis of chronic autoimmune thyroiditis one century after hashimoto.

Abstract: Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.R. Rose and E. Witebsky [J Immunol 1956;76:417–427] that this condition is the archetype for autoimmune destruction as a disease mechanism. In the last two decades in particular, there has been huge interest in unravelling the genetic basis for this and related autoimmune disorders. The list of polymorphisms associated with autoimmune thyroid disease grows each year, and in the case of vitiligo, which is frequently found in association with thyroid autoimmunity, we know that 27 separate susceptibility loci account for less than 20% of the heritability of this condition. Environmental and existential factors may turn out to be just as complex in number and in interactions. We can thus imagine a ‘Swiss cheese’ model for the causation of autoimmune thyroid disease, in which the effects of cumulative weaknesses line up – like the holes in slices of cheese – to allow the catastrophic event of autoimmune destruction to occur.

Side effects of anti-thyroid drugs and their impact on the choice of treatment for thyrotoxicosis in pregnancy.

Abstract: Introduction: Hyperthyroidism in pregnancy is a serious condition and its management is complex. Whilst carbimazole/methimazole (CBZ/MMI) and propylthiouracil (PTU) have similar efficacies in controlling hyperthyroidism, their risk of side effects such as major congenital abnormalities and hepatotoxicity are different. Methods: Various combinations of the terms ‘anti-thyroid drugs’, ‘thionamide’, ‘carbimazole’, ‘methimazole’, ‘propylthiouracil’, ‘pregnancy’, ‘side effects’, ‘agranulocytosis’, ‘birth defects’, ‘congenital malformations’, ‘embryopathy’, ‘aplasia cutis’, ‘hepatotoxicity’, ‘hepatic failure’, ‘maternal’ and ‘fetus’ were used to search MEDLINE and the Cochrane library. The references of retrieved papers were also reviewed. Results: There is increasing evidence for a CBZ/MMI embryopathy, whilst data remain lacking for major congenital abnormalities with PTU. In contrast, PTU is associated with increased risk of severe liver injury. Management strategies to reduce these risks by using PTU in the first trimester and CBZ/MMI in the later trimesters remain untested. Conclusion: More evidence is still needed in defining the relative risks between CBZ/MMI and PTU of major congenital abnormalities and severe liver injury in pregnancy. Studies are also needed to establish the suitability of recent management suggestions in switching from PTU to CBZ/MMI after the first trimester. Major adverse outcomes secondary to CBZ/MMI and PTU are rare, and inadequately treated hyperthyroidism poses a far greater risk.

Oxidative stress in graves' disease.

Abstract: Increased reactive oxygen species (ROS) generation and the consequent oxidative damage are involved in the development of several diseases, including autoimmune diseases. Graves' disease is an autoimmune disorder characterized by hyperthyroidism and, less frequently, orbitopathy. Hyperthyroidism is characterized by increased oxidative stress. Untreated hyperthyroidism is associated with an increase of several parameters of oxidative stress and in most studies (but not all) by an increase of antioxidant defense enzymes. Restoration of euthyroidism with antithyroid drug is associated with a reversal of the biochemical abnormalities associated with oxidative stress. Animal and human studies suggest that increased ROS may directly contribute to some clinical manifestation of the disease, including orbitopathy. Antioxidants administered alone improve some clinical signs and symptoms of hyperthyroidism and, when associated with antithyroid drugs, induce a more rapid control of clinical manifestations and a faster achievement of euthyroidism. A large randomized clinical trial has shown that antioxidant supplementation (selenium) may also be beneficial for mild Graves' orbitopathy.

Is Thyroid Autoimmunity per se a Determinant of Quality of Life in Patients with Autoimmune Hypothyroidism

Abstract: Purpose: To evaluate the relationship between thyroid variables and health-related quality of life (QoL) in patients with autoimmune hypothyroidism, using the thyroid-specific QoL questionnaire ThyPRO. Methods: In a cross-sectional study, responses to the ThyPRO from 199 outpatients with autoimmune hypothyroidism were analyzed in relation to thyroid volume, thyroid function and markers of thyroid autoimmunity. Based on a classical QoL framework, we hypothesized that physiological dysfunction caused specific physical and psychological symptoms, which affected functioning and well-being, and consequently participation in life and QoL. These hypotheses were tested through multiple regression and multivariate path analysis models. Results: None of the thyroid function tests were associated with QoL scores. However, in the pairwise regression, the thyroid peroxidase antibody (TPOAb) level was associated with several QoL outcomes: Goitre Symptoms (p = 0.024), Depressivity (p = 0.004), Anxiety (p = 0.004), Emotional Susceptibility (p =

2012 European Thyroid Association Guidelines for the Management of Familial and Persistent Sporadic Non-Autoimmune Hyperthyroidism Caused by Thyroid-Stimulating Hormone Receptor Germline Mutations

Abstract: All cases of familial thyrotoxicosis with absence of evidence of autoimmunity and all children with persistent isolated neonatal hyperthyroidism should be evaluated for familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) or persistent sporadic non-autoimmune hyperthyroidism (PSNAH). First, all index patients should be analysed for the presence/absence of a thyroid-stimulating hormone (TSH) receptor (TSHR) germline mutation, and if they display a TSHR germline mutation, all other family members including asymptomatic and euthyroid family members should also be analysed. A functional characterization of all new TSHR mutations is necessary. Appropriate ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences, especially in children. Therefore, in children the diagnosis of FNAH or PSNAH needs to be established as early as possible in the presence of the clinical hallmarks of the disease.

Genotype and phenotype predictors of relapse of graves' disease after antithyroid drug withdrawal.

Abstract: Background: For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. Methods: To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. Results: Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). Conclusion: Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.

Thyroid Hormone Replacement Therapy: Three ‘Simple’ Questions, Complex Answers

Abstract: Current guidelines recommend that hypothyroid patients should be treated with levothyroxine, which in the vast majority of the cases leads to resolution of the symptoms and normalization of serum free T4 (FT4), T3 and TSH levels However, a small group of hypothyroid patients remain symptomatic for neurocognitive dysfunction despite normal serum FT4 and TSH, which could be explained by localized brain hypothyroidism More than half of the T3 in the brain is produced locally via the action of the type II deiodinase (D2) and variability/defects in this pathway could explain the residual symptoms If this rationale is correct, adding liothyronine to the replacement therapy could prove beneficial However, with a few exceptions, several clinical trials failed to identify any beneficial effects of combined therapy More recently, the results of a large clinical trial revealed a better neurocognitive outcome with combined therapy only in hypothyroid patients carrying a polymorphism in the DIO2 gene This obviously needs to be confirmed by other groups but it is tempting to speculate that combined levothyroxine and liothyronine has a place in the treatment of hypothyroidism, for some

Greater Efficacy of Total Thyroidectomy versus Radioiodine Therapy on Hyperthyroidism and Thyroid-Stimulating Immunoglobulin Levels in Patients with Graves' Disease Previously Treated with Antithyroid Drugs

Abstract: Aims: We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid-stimulating immunogl

Thyroid Cancer: Role of RET and Beyond

Abstract: Specific thyroid cancer histotypes, such as papillary and medullary thyroid carcinoma, display genetic rearrangements or point mutations of the RET gene, resulting in its oncogenic conversion. The molecular mechanisms mediating RET rearrangement with other genes and the role of partner genes in tumorigenesis have been described. In addition, the RET protein has become a molecular target for medullary thyroid carcinoma treatment.

High prevalence of papillary thyroid microcarcinoma in danish patients: a prospective study of 854 consecutive patients with a cold thyroid nodule undergoing fine-needle aspiration.

Abstract: We aimed to investigate the diagnostic accuracy of ultrasound (US)-guided fine-needle aspirates (FNAs) obtained from 854 consecutive Danish patients with a scintigraphically cold thyroid nodule in a borderline iodine-deficient area. Clinical, sonographic, and pathological findings in patients with a cold thyroid nodule undergoing US-guided FNA were prospectively registered. 408 patients underwent thyroid surgery, resulting in 50 cancers and in addition 37 patients had an incidental finding of papillary thyroid microcarcinomas. Based on the diagnostic FNA, we found sensitivity and specificity for malignancy of 73.9 and 99.2%, respectively. The positive and negative predictive values of a diagnostic FNA for malignancy were 89.5 and 97.7%. We identified 6 false-negative and 2 false-positive diagnoses. Solid versus cystic feature of the nodule, as well as >2 high-risk US features, were predictive for malignancy. Cancer incidence was 13% among females and 9% among males. The accuracy of a diagnostic set-up based on clinical examination, scintigraphy, US, and US-guided FNA was determined with a 48% rate of histopathological validation in the cohort. The overall thyroid cancer incidence has increased worldwide, but our results suggest that the most frequent occurring cancer is an incidental papillary thyroid microcarcinoma of which the clinical significance has yet to be established.

Alcohol Consumption as a Risk Factor for Autoimmune Thyroid Disease: A Prospective Study

Abstract: Background: Alcohol consumption has been identified as a protective factor for some autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus

European thyroid association guidelines on L-t4 + L-t3 combination for hypothyroidism: a weary step in the right direction.

Abstract: This issue of the European Thyroid Journal features the European Thyroid Association (ETA) guideline on the use of L-T4 + L-T3 (levothyroxine + liothyronine) in the treatment of hypothyroidism [1]. Some time ago, the first author of the guideline invited me to speak at the annual ETA meeting on the very same topic. It was 5 years after the Bunevicius paper [2], which had already been followed by several larger studies aiming to address the question of whether combination treatment was more effective than L-T4 monotherapy. The newer studies at the time [3, 4, 5, 6] had confirmed my own personal clinical experience that tired patients on L-T4 continued to be tired patients on L-T4 + L-T3 . I made a few rather cynical remarks during my presentation, which got me some laughs by the audience. Unaware that I was speaking to anyone but colleagues, I was confronted at the end of my talk by an angry lady, who turned out to be a patient representative. She made sure I noted that her views and personal experience were very different to what I had portrayed. I had unintentionally offended a hypothyroid patient, which I regretted terribly, but after a lengthy discussion with her, which continued with occasional emails for several months, I was delighted to be asked to act as medical advisor for her thyroid patient-led organization. We remain friends and respect each other, though our views are still different.

Breastfeeding and antithyroid drugs: a view from within.

Abstract: The aim of this communication is to provide information regarding the use of antithyroid drugs (ATD) during lactation. Three ATD are used today: propylthiouracil (PTU), methimazole (MMI) and carbimazole (CMZ). The latter is a prodrug which is bioactivated to MMI. PTU is transferred in small amounts (0.025%) into milk. These amounts were considered nonsignificant for inducing adverse effects for the suckling infant. The amount of MMI excreted in milk is equal to MMI levels in serum. Due to its lower concentrations in milk, PTU was used for decades as the treatment of choice during breastfeeding. Recent studies have demonstrated that physical development, intelligence scores and thyroid status of children whose mothers had received MMI while breastfeeding were similar to those of healthy children. These new data offered clinicians an alternative drug approach. Several hepatic dysfunction studies have been published so far. Clinical manifestations varied from mild to severe hepatic failure, liver transplantation or death. Most PTU cases were more severe, idiosyncratic and not dose related. We recommend that PTU should not be prescribed for thyrotoxicosis during lactation. MMI should be used instead, in doses up to 30 mg/day, while PTU should be used in special cases for a restricted time period.

A Case of Propylthiouracil-Induced Hepatitis during Pregnancy.

Abstract: A 32-year-old with no pre-existing liver disease was diagnosed with Graves' disease at week 4 of pregnancy Thyroid-stimulating hormone was undetectable with elevated free thyroxine levels and positive thyroid receptor antibodies She was started on a reducing regime of propylthiouracil (PTU) At week 20 in pregnancy, she became jaundiced Initial bloods revealed: bilirubin 91 μmol/l, alanine aminotransferase 1,796 IU/l, alkaline phosphatase 200 IU/l, international normalized ratio 12, and albumin 33 g/l A presumptive diagnosis of PTU-induced hepatitis was made PTU was immediately discontinued and best supportive care instigated Serum markers for autoimmune and viral hepatitis were negative, abdomen ultrasound, ferritin and caeruloplasmin were normal Although her alanine aminotransferase began to fall, her bilirubin continued to rise, peaking at 378 Two weeks after PTU cessation she became thyrotoxic and was started on a reducing regime of carbimazole Her thyroid function stabilized and liver function tests continued to improve with carbimazole stopped at week 32 Growth scans remained normal with delivery of a healthy baby at 38 weeks This report highlights that good outcomes can be achieved in PTU-induced hepatitis in pregnancy Patients on PTU should be warned of the potential risk of hepatic failure and advised to seek medical advice immediately if they develop jaundice

Pre-Conception Counselling in Graves' Disease

Abstract: Risks to mother, fetus and neonate from untreated Graves' hyperthyroidism during gestation are compelling reasons for recommending pre-conception counselling. Pre-conception counselling should include discussion as to the optimum treatment of Graves' hyperthyroidism in women wishing to become pregnant. Thyrotropin receptor antibodies remain elevated following radioiodine therapy, so medical or surgical treatment may be preferred to avoid fetal or neonatal hyperthyroidism. A TSH level <2.5 mIU/l must be achieved in women receiving LT4 before conception. The patient should be reassured that both she and the fetus can be maintained in a euthyroid state and that neonatal hyperthyroidism can be readily managed with a good outcome. The risks of antithyroid drug therapy during gestation should be fully discussed with emphasis on the very low risk (although real) of liver disease with propylthiouracil treatment and embryopathy with methimazole or carbimazole therapy. While propylthiouracil is the preferred drug for the first trimester, if it is not available other thionamides may be given. Breast-feeding while on antithyroid drugs is not contraindicated provided the dose of drug is low. The patient should also be advised of the importance of thyroid monitoring in the post-partum period.

The Vitamin D Receptor in Thyroid Development and Function

Abstract: Background and Objective: Vitamin D is known to modulate thyroid neoplastic and autoimmune disease. We investigated the role of the vitamin D receptor (VDR) in normal thyroid development and function (thyrocytes and C cells). Methods: The thyroid phenotype of VDR knockout mice was studied in comparison to wild-type controls. The mice were fed a normal diet or a calcium-rich diet to circumvent effects induced by hypocalcemia. Results: Thyroid morphology was unaltered in VDR knockout mice. Also, expression of different parameters of thyrocyte function was comparable (immunohistochemistry). C cell physiology was, however, affected in the absence of the VDR, resulting in increased thyroidal calcitonin expression (immunohistochemistry), paralleled by increased serum calcitonin levels, but only in normocalcemic mice. To study a possible effect of vitamin D status on basal calcitonin levels in humans, serum calcitonin concentrations were compared between vitamin D-deficient and -sufficient patients (serum 25-OH vitamin D3 ≤10 and ≥40 ng/ml, respectively), but no difference was observed. Conclusions: In mice, the VDR is redundant for normal thyrocyte function, but not for C cell function, where it mediates the negative control of calcitonin by 1,25-dihydroxyvitamin D3. In patients, vitamin D status does not affect basal serum calcitonin levels. A study in healthy individuals is needed to confirm these findings.

Histological diagnosis of thyroid disease using ultrasound-guided core biopsies.

Abstract: Background: Thyroid core biopsies obtained with ultrasound (US)-guided needles are an alternative to conventional fine-needle aspiration and, according to various authors, have greater sensitivity and specificity. The technique is inexpensive, rapid and reliable with a low rate of complications, similar to conventional fine-needle aspiration procedures. Objectives: This paper critically reviews the methodology for obtaining samples and processing them in the pathology laboratory. Methods: Accumulated experience with 1,065 cases of US-guided core biopsy of the thyroid gland in a 15-year period. Results: US-guided core biopsy is a useful, inexpensive and safe method in the histological diagnosis of thyroid gland pathology. Thyroid samples obtained this way are not a substitute for fine-needle aspiration cytology. Indeed, some authors assert that the best results are obtained by combining the two approaches, the methods being complementary. Conclusions: To take best advantage of the findings from these techniques, pathologists must know which types of diagnoses can be made and the fundamentals of how and, lastly, what cannot be diagnosed and the reasons why. Best results are obtained with a multidisciplinary approach in a hospital committee composed of endocrinologists, surgeons, radiologists and pathologists, who analyse and provide a background on each case.

Use of t4, t4 + t3, and t3 in the dutch population in the period 2005-2011.

Abstract: As chairman of the Dutch Association of Graves' Patients, I was recently invited to speak at a symposium on personalized medicine. The organizers had asked me to present figures on the use of thyroid hormone (especially the combination of T4 and T3) in the Netherlands. With the help of the Royal Netherlands Society of Pharmacy (Koninklijke Nederlandse Maatschappij ter bevordering der Farmacie), we approached the Foundation Pharmaceutical Indicators (Stichting Farmaceutische Kengetallen). They were able to provide us with key figures on the use of thyroid hormone in the Netherlands over the period 2005–2011 (courtesy of F. Griens). The Foundation collected prescription data from 843 public pharmacies, which had not changed the unique patient identification numbers in the period 2005–2011. The pharmacies linked to the Foundation constitute a representative sample of all pharmacies in the country. The figures obtained from the 843 pharmacies were extrapolated to all Dutch pharmacies, serving the total population of the Netherlands. The number of persons using any thyroid hormone medication increased by 53% in the period 2005–2011; the proportion of the total Dutch population using thyroid hormone increased by 49%, whereas the Dutch population size in the same period increased by 2.1% (table ​(table1).1). Distinguishing between the various thyroid hormone preparations, the number of persons using only T4 increased by 53%, those using the combination of T4 + T3 increased by 67%, and those using T3 only increased by 36%. Among the persons using thyroid hormones, the proportion of only T4 users gradually but consistently decreased from 99.05% in 2005 to 98.98% in 2011. An opposite trend was observed in the T4 + T3 users, which slowly but steadily increased from 0.82% in 2005 to 0.90% in 2011. The proportion of only T3 users did not show a specific trend – it was 0.13% in 2005 and 0.12% in 2011. The assembled data also allowed to analyse whether prescriptions were made by general physicians (GPs) or specialists (table ​(table2).2). With regard to prescriptions for T4 there was a clear trend that in the period 2005–2011, T4 prescriptions by GPs became more frequent (from 79% of all T4 prescriptions in 2005 to 90% in 2011), whereas T4 prescriptions by specialists decreased (from 21 to 10%). The annual proportion of persons starting on T4 fluctuated between 19 and 21% of all thyroid hormone users. Initiation of T4 treatment by GPs increased (from 62% in 2005 to 71.5% in 2011) at the expense of initiation by specialists (from 38% in 2005 down to 28.5% in 2011). With regard to T3 prescriptions, a similar picture emerges. The proportion of T3 prescriptions by GPs rises from 52% in 2005 to 68% in 2011, under a simultaneous fall in T3 prescriptions by specialists from 48 to 32%. The annual proportion of persons starting T3 fluctuated between 0.38 and 0.49% of all thyroid hormone users. Initiation of T3 treatment was done by GPs in 37% in 2005, but had increased to 45.5% in 2011; the figures for specialists declined from 63 to 54.5%. Table 1 Thyroid hormone medication in the Dutch population in the period 2005–2011 Table 2 Prescriptions for T4 and T3 in the Dutch population in the period 2005–2011 in % Two conclusions can be drawn. The number of persons using thyroid hormone medication increased substantially in the period 2005–2011. And the proportion of thyroid hormone medication prescribed by GPs steadily increased in this period, whereas the proportion prescribed by specialists decreased. How can these remarkable trends be explained? We offer a few causal mechanisms. First, the growth of the Dutch population size between 2005 and 2011 will have contributed to the increased number of persons taking thyroid hormone. However, this provides only a partial explanation because the relative increase of thyroid hormone users exceeds by far the relative increase of population size. Second, the composition of the Dutch population is changing with a strong increase of the ageing population. As the incidence of Hashimoto's hypothyroidism increases with advancing age, a greying population will increase the use of thyroid hormones. Nevertheless, this cannot be the whole explanation because the effect of the ageing population is just three times greater than the effect of the general population growth. Third, the Dutch College of General Practitioners (Nederlands Huisartsen Genootschap) published in 2006 guidelines for the diagnosis and treatment of thyroid function disorders [1,2]. At the implementation of the guidelines, specific attention was drawn to the condition of subclinical hypothyroidism. It is plausible that the guidelines to a large extent have contributed to the increased use of thyroid hormone, also explaining the shift in prescription behaviour away from the specialists towards the GPs. In further support of this explanation is the introduction of specific software used by laboratories serving GPs. The GP can cross the box ‘tiredness’, which automatically results in a few laboratory tests including TSH. Many GPs express their amazement when the assay indicates hypothyroidism. However, we would like to suggest a fourth explanation, which we call the Google hypothesis. Many subjects have vague non-specific complaints, and are inclined to look on the internet what might be wrong. In doing so, it is not unusual to arrive at websites related to thyroid diseases. In the Netherlands, the websites of the thyroid patient associations (Thyroid Foundation Netherlands, Dutch Association of Graves' Patients, Hypo but not Happy) are consulted by more than 10,000 individual visitors per week. It might well be that these visitors subsequently consult their GP with the specific request to determine thyroid function. In this respect it is noteworthy to mention that the relative increase in users of the combination therapy of T4 + T3 (as recommended by the Hypo but not Happy group in particular cases) is greater than the relative increase of only T4 users. The combination therapy appears to be described increasingly by GPs. Indeed, the GP guidelines in a footnote mention the possibility to use this treatment modality. We do not know if our explanations account for the whole increase of thyroid hormone use, nor do we know whether this definite trend in increasing use of thyroid hormones will go on or stop within a few years.

What’s in the Image Pituitary Metastasis from Papillary Carcinoma of the Thyroid: A Case Report and a Comprehensive Review of the Literature

Abstract: A 67-year-old female patient presented with visual field impairment and hyperprolactinemia. Imaging revealed a sellar and suprasellar mass and during the evaluation of the sellar lesion, papillary thyroid carcinoma (PTC) was diagnosed by fine-needle aspiration biopsy in a long-standing euthyroid multinodular goiter. The patient did not have a previous history of PTC. Total thyroidectomy confirmed the diagnosis of PTC. Due to progressive visual loss, she underwent transcranial surgery for decompression of the optic chiasm. Pituitary metastasis from PTC was confirmed, histologically and immunohistochemically. In literature, overall 13 cases, including ours, with PTC metastasis to the sellar region have been reported. Most were women, with a median age of 56 years. Two thirds of patients were previously diagnosed with PTC. The presence of other distant metastases was confirmed in less than half of the patients. Only 2 and our patient had immunohistochemical confirmation of PTC metastasis to the sellar region. The presenting signs and symptoms included: visual field defects, ophthalmoplegia, and anterior pituitary hormone deficiencies. In conclusion, this is a rare case of metastatic PTC to the sellar region unequivocally confirmed by immunohistochemistry in whom the disease first presented with a sellar and suprasellar mass.

Relative impact of iodine supplementation and maternal smoking on cord blood thyroglobulin in pregnant women with normal thyroid function.

Abstract: Objective: To assess the impact on cord blood (CB) thyroglobulin (Tg) of early iodine supplementation during pregnancy. Methods: A total of 111 healthy pregnant women with normal thyroid function were included in a prospective randomized study and divided into two groups with (150 µg/day) or without iodine supplementation started during the first trimester. Maternal smoking was assessed qualitatively by self-reported statements and quantitatively by cotininuria. Exhaustive thyroid tests were performed at delivery in the mother and in CB. Results: Third-trimester ioduria documented compliance with iodine supplementation (160 vs. 76 µg/l in controls). CB Tg was not different between the iodine and control groups (median 77 vs. 79.5 ng/ml, respectively) and did not correlate with maternal ioduria. CB Tg was higher in newborns from smoking mothers (114 vs. 64.7 ng/ml) and correlated with self-reported smoking status more than with maternal cotininuria. Nonsmokers had no difference in CB Tg whether they took iodine supplementation or not, as opposed to smokers, who tended to benefit from supplementation. Conclusions: Iodine supplementation does not significantly impact CB Tg in healthy nonsmoker pregnant women selected for normal thyroid function, as opposed to maternal smoking. CB Tg appears to be a marker of in utero tobacco exposure. In areas of mild iodine deficiency, iodine supplementation could especially benefit the fetuses of smokers.

Management of Hyperthyroidism in Pregnancy: Results of a Survey among Members of the European Thyroid Association

Abstract: Background: An optimal management of maternal hyperthyroidism is important for positive pregnancy outcome, and to this end, the Endocrine Society published their guidelines in 2007.

Thyroid consequences of the fukushima nuclear reactor accident.

Abstract: Background: A special report, ‘The Fukushima Accident’, was delivered at the 35th Annual Meeting of the European Thyroid Association in Krakow on September 11, 2011, and this study is the follow-up of the special report. Objectives: To present a preliminary review of potential thyroid consequences of the 2011 Fukushima nuclear reactor accident. Methods: Numerous new data have been presented in Japanese, and most of them are available on the website from each research institute and/or from each municipality. The review was made using these data from the website. Results: When individual radiation doses were expressed as values in more than 99% of residents, radiation doses by behavior survey in evacuation and deliberate evacuation areas were less than 10 mSv in the first 4 months, and internal radiation doses measured by whole body counters were less than 1 mSv/year. Individual thyroid radiation doses were less than 50 mSv (intervention levels) even in evacuation areas. As for health consequences, no one died and no one suffered from acute effects. The thyroid ultrasound examination is in progress and following examination of almost 40,000 children, 35% of them have nodules and/or cysts but no cancers. Conclusions: Countermeasures against radiation must consider current individual measured values, although every effort must be taken to reconstruct radiation doses as precisely as possible. At present, the difference of thyroid radiation dose between Chernobyl and Fukushima appears to be due to the strict control of milk started within a week after the accident in Fukushima. Since the iodine-131 plume moved around in wide areas and for a long time, the method of thyroid protection must be reconsidered.

Large discrepancy in the results of sensitive measurements of thyroglobulin antibodies in the follow-up on thyroid cancer: a diagnostic dilemma.

Abstract: During follow-up on patients treated for differentiated thyroid cancer, thyroglobulin (Tg) antibodies can interfere with the Tg assay, making the use of Tg less reliable as a tumor marker. &l