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Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available. Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys. Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms. LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit.

INTRODUCTION: Thyrotropin receptor stimulating antibodies (TRAb) are responsible for Graves’ disease (GD) manifestations. Other thyroid antibodies, namely thyroperoxidase (TPOAb) and thyroglobulin (TGAb) antibodies are highly prevalent in GD, but their roles in GD presentation and evolution are controversial. [...]

PURPOSE: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves' hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether 'Block and Replace' (B + R) and 'Titration' (T) regimes are equivalent in terms of frequency of euthyroidism and Graves' Orbitopathy (GO) during ATD therapy. METHODS: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution's policy. RESULTS: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27-0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. CONCLUSION: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

PURPOSE: Patients with Graves' orbitopathy can present with asymmetric disease. The aim of this study was to identify clinical characteristics that distinguish asymmetric from unilateral and symmetric Graves' orbitopathy. METHODS: This was a multi-centre study of new referrals to 13 European Group on Graves' Orbitopathy (EUGOGO) tertiary centres. New patients presenting over a 4 month period with a diagnosis of Graves' orbitopathy were included. Patient demographics were collected and a clinical examination was performed based on a previously published protocol. Patients were categorized as having asymmetric, symmetric, and unilateral Graves' orbitopathy. The distribution of clinical characteristics among the three groups was documented. RESULTS: The asymmetric group (n = 83), was older than the symmetric (n = 157) group [mean age 50.9 years (SD 13.9) vs 45.8 (SD 13.5), p = 0.019], had a lower female to male ratio than the symmetric and unilateral (n = 29) groups (1.6 vs 5.0 vs 8.7, p < 0.001), had more active disease than the symmetric and unilateral groups [mean linical Activity Score 3.0 (SD 1.6) vs 1.7 (SD 1.7), p < 0.001 vs 1.3 (SD 1.4), p < 0.001] and significantly more severe disease than the symmetric and unilateral groups, as measured by the Total Eye Score [mean 8.8 (SD 6.6) vs 5.3 (SD 4.4), p < 0.001, vs 2.7 (SD 2.1), p < 0.001]. CONCLUSION: Older age, lower female to male ratio, more severe, and more active disease cluster around asymmetric Graves' orbitopathy. Asymmetry appears to be a marker of more severe and more active disease than other presentations. This simple clinical parameter present at first presentation to tertiary centres may be valuable to clinicians who manage such patients.

Pregnancy is a condition leading to an important strain on thyroid morphology and function.A normal functioning of the thyroid gland in the mother is essential for the early fetal development, since the fetal thyroid does not produce thyroid hormones until the end of the first trimester (approximately 12 to 14 weeks).The impact of thyroid dysfunction (and especially hypothyroidism) during pregnancy is well documented and has been associated with a number of obstetrical complications, such as premature delivery, low birth weight and even fetal death. In view of all changes in thyroid physiology during pregnancy the ATA (American Thyroid Association) guidelines recommend using trimester- and population-specific normality ranges, to define thyroid dysfunction. It is proposed to determine them in pregnant women without thyroid antibodies (TPO) and without severe iodine deficiency. Due to the few numbers of randomized clinical trials, there is still no consensus whether all pregnant women should be screened or only women at risk for the development of thyroid dysfunction during pregnancy.Thyroid dysfunction during pregnancy is caused in most cases by the presence of thyroid autoimmunity (TAI) and also the altered pregnancy outcomes in most studies are associated with the presence of TAI.Besides the presence of TAI, other factors might also change, influence and/or modify thyroid function. When we started our research, there were only few studies that investigated the impact of other variables, such as iron, BMI, smoking habit and/or the background of the pregnant women on the prevalence of thyroid dysfunction during the first trimester of pregnancy.The aims of the thesis were therefore, to investigate: • the association between the iron reserve status (ferritin levels), thyroid (dys)function and autoimmunity, corrected for confounders such as age, BMI, smoking habit and the time of blood sampling;• the impact of the ethnic background of the pregnant woman on thyroid func, Doctorat en Sciences médicales (Médecine), info:eu-repo/semantics/nonPublished

This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing-remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described. However, practical clinical guidance in case of abnormal thyroid-related findings prior to or after alemtuzumab treatment is currently lacking. Therefore, a Belgian taskforce consisting of MS and thyroid experts was created in 2016, with the objective of issuing a clinical thyroid management algorithm based on available scientific evidence and personal experience with regard to alemtuzumab treatment-related thyroid adverse events.

1. Clinical assessment of Graves’ orbitopathy Graves’ orbitopathy (GO) is the most frequent extrathyroid complication in Graves’ disease. Natural history, described by Rundle, features an initial inflammatory or active phase in which acute episodes and spontaneous remissions alternate, then a fibrotic phase, with regression within 12–18 months. Diagnosis is based on symptoms and ocular signs. Clinical examination must therefore be rigorous; in case of doubt, the ophthalmologist's opinion is determining. Various classifications assess clinical signs: most widely used are the EUGOGO (European Group Of Graves’ Orbitopathy) and VISA (Vision, Inflammation, Strabismus, Appearance) classifications, the former (http://www.eugogo.eu.proxy.bib.ucl.ac.be) in Europe and the latter (http://www.thyroideyedisease.org.proxy.bib.ucl.ac.be) more often in the US and Canada. Both have limitations; they are not interchangeable, and each patient must consistently be monitored on one or the other. Expert discussions are ongoing, and alternative classifications are offered to improve assessment [1], [2]. Delayed diagnosis and treatment impair ocular progression [3]. Optimal treatment depends on activity status and severity [4]. Clinical activity score (CAS) ≥3/7 indicates active status. Severity is graded as mild, moderate-to-severe or very severe (sight-threatening). Table 1 shows activity and severity criteria. [...]

Hyperthyroid Graves’ disease (GD) is an autoimmune thyroid disease caused by stimulating thyrotropin (TSH) receptor antibodies (TRAb). As early as the 1940s, the three components of the current therapeutic armamentarium for hyperthyroidism were already available: antithyroid drugs and radioiodine treatment as recent innovations, and thyroidectomy since the early part of the century. For years, clinical research has tried to improve the dilemma: conservative medical restoration of euthyroidism – with a 50% risk of subsequent relapse – or removal/ radical inactivation of thyroid tissue at the expense of another disease, a definitive one, hypothyroidism [...]

À l’instar des années précédentes, l’année 2016 a été riche de nouveautés et d’innovations diagnostiques et thérapeutiques dans les domaines des pathologies endocriniennes, du diabète et des maladies métaboliques. Nous avons volontairement choisi de n’illustrer ici que celles qui, aujourd’hui déjà, ont modifié la prise en charge de ces pathologies, que ce soit par le médecin spécialiste ou le médecin généraliste. Tous les lecteurs devraient donc y trouver quelque intérêt. Ainsi dans le domaine du diabète, nous vous parlons de la nouvelle convention INAMI, d’un nouveau système remboursé de mesure en continu du taux de glucose interstitiel par capteur, des progrès technologiques impressionnants des nouvelles pompes à insuline ainsi que des bénéfices importants de l’utilisation des inhibiteurs des transporteurs SGLT-2 (les ‘glucorétiques’) en termes de complications cardiovasculaires et rénales chez le patient diabétique de type 2. Au plan des pathologies métaboliques, les inhibiteurs de la PCSK9 sont maintenant remboursés dans l’hypercholestérolémie familiale hétérozygote et certains analogues du GLP-1 sont disponibles pour un traitement efficace de l’obésité. Dans le domaine des pathologies thyroïdiennes, l’hypothyroxinémie maternelle isolée de la grossesse est aujourd’hui mieux caractérisée et de nouvelles recommandations ont été émises en 2016 concernant le diagnostic et le traitement de l’ophtalmopathie thyroïdienne. Enfin, concernant l’endocrinologie générale, de nouvelles recommandations clarifient et simplifient la prise en charge de l’incidentalome surrénalien dont la fréquence de découverte ne fait que croître, à l’ère d’une imagerie abdominale de plus en plus performante, [Innovations in endocrinology, diabetology, and nutrition: what 2016 brought us ?] The year 2016 was again full of novelties, with numerous diagnostic and therapeutic innovations in the fields of endocrine diseases, diabetes, and metabolic disorders. In this article, we deliberately chose to only discuss those which have already improved the current management of such diseases, be it for specialists or general practitioners. The article should therefore be interesting for every reader. In the field of diabetes, we have here reported on the main features of the new agreement between social security system, physicians, and diabetic patients (“Convention INAMI”). We have also reported on a newly reimbursed system for continuous measurement of interstitial glucose through a sensor, on the impressive technological advances in modern insulin pumps, as well as on the significant cardiovascular and renal benefits of SGLT2 transporter inhibitors in Type 2 diabetes patients. As for metabolic pathologies, the PCSK9 inhibitors are now reimbursed in heterozygous familial hypercholesterolemia, and specific GLP-1 analogues are available for an effective treatment of obesity. In the field of thyroid diseases, isolated maternal hypothyroxinemia during pregnancy is now better characterized, and new recommendations have been issued regarding the diagnosis and treatment of Grave’s ophthalmopathy. Finally, as regards general endocrinology, new recommendations clarify and simplify the management of adrenal incidentaloma, whose detection frequency continually increases in the era of common and more efficient abdominal imaging.

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Isolated hypothyroxinemia (IH) is defined as a thyroxine level in the lower 5th (severe IH) or 10th percentile (mild IH) of the pregnancy-related reference range and a normal TSH. The etiology of IH remains unknown. This review aims to evaluate the biochemical criteria used to define IH in different published studies and to discuss potential maternal as well as fetal outcomes and whether treatment during early pregnancy can prevent the eventual adverse effects. For the current literature a better standardization of free thyroxine assays is needed, as well as the use of appropriated trimester-specific reference intervals for thyroid function tests. Today no study demonstrates a benefit from treating early pregnant IH women on perinatal and fetal outcomes.

BACKGROUND/AIMS: The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. METHODS: Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. RESULTS: The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). CONCLUSIONS: These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

La survenue d’une dysfonction thyroïdienne sévère suite à l’administration de produits de contraste iodés est probablement peu fréquente mais comme l’utilisation d’examens radiologiques utilisant ces agents est de plus en plus répandue, il est important pour tout clinicien de bien connaitre ce type de complications et de les détecter précocement. Dans cet article, nous discutons de l’évaluation des risques spécifiques à chaque patient et des méthodes de prévention de l’hyperthyroïdie induite par les produits de contraste iodés, [Prevention of iodine-induced hyperthyroidism] Although the prevalence of severe contrast-induced thyroid dysfunction is low, clinicians must be aware of thyroid-specific complications that can arise with the widespread use of contrast-enhanced imaging techniques. This article aimed to discuss how to evaluate the specific risks in various patients, along with the appropriate procedures for preventing iodine- induced hyperthyroidism