Chantal Daumerie

Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO

Summary of consensus a. All patients with GO should (Fig. 1):Be referred to specialist centers;Be encouraged to quit smoking;Receive prompt treatment in order to restore andmaintain euthyroidism.b. Patients with sight-threatening GO should be treatedwith i.v. GCs as the first-line treatment; if the responseis poor after 1–2 weeks, they should be submitted tourgent surgical decompression.c. The treatment of choice for moderate-to-severe GO isi.v. GCs (with or without OR) if the orbitopathy isactive;surgery(orbitaldecompression,squintsurgery,and/or eyelid surgery in this order) should beconsidered if the orbitopathy is inactive.d. In patients with mild GO, local measures and anexpectant strategy are sufficient in most cases, buttreatment may be justified if QoL is affectedsignificantly. In memoriam This document is dedicated to the memory of MarkPrummel (1956–2005), one of the founders ofEUGOGO, who greatly contributed to expanding ourunderstanding of clinical and therapeutic aspects of GO.

Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on management of Graves' orbitopathy.

Luigi Bartalena, Lelio Baldeschi, Alison J. Dickinson, Anja Eckstein, Pat Kendall-Taylor, Claudio Marcocci, Maarten P. Mourits, Petros Perros, Kostas Boboridis, Antonella Boschi, Nicola Curro, Chantal Daumerie, George J. Kahaly, Gerasimos Krassas, Carol M. Lane, John H. Lazarus, Michele Marino, Marco Nardi, Christopher Neoh, Jacques Orgiazzi, Simon Pearce, Aldo Pinchera, Susanne Pitz, Mario Salvi, Paolo Sivelli, Matthias Stahl, Georg von Arx, and Wilmar M. Wiersinga

2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking.

Anxiety and depression, attention, and executive functions in hypothyroidism.

BACKGROUND Divergences in cognitive disturbances in hypothyroidism reported in the literature are a result of a methodological bias. METHODS By using a precise methodology, we examined attention and executive functions in hypothyroidism, verified the presence of anxiety and depressive symptoms in hypothyroidism, and examined the possible link between these symptoms and the cognitive disturbances (searching for attentional bias for words with a negative emotional valence). We administered a battery of cognitive tests to 23 participants who had undergone thyroidectomy for thyroid carcinoma: for the first time in an euthyroid state, then 3 weeks later (still in the euthyroid state) to assess the test/retest effect, and finally 4 weeks later in an hypothyroid state. We compared their performance with that of a group of 26 control participants who were also administered the same cognitive tests, also 3 times. RESULTS In hypothyroidism, the thyroid participants were more anxious and depressed than the controls and presented attentional and executive disturbances that reflected general slowing and difficulties in using their capacities of inhibition. However, they did not exhibit an attentional bias for words with a negative emotional valence. CONCLUSIONS Contrary to what was expected, symptoms of anxiety and not symptoms of depression interfered with the cognitive performance of participants in hypothyroidism.

Quantification of cells expressing the thyrotropin receptor in extraocular muscles in thyroid associated orbitopathy.

Background/aim: Thyroid associated orbitopathy (TAO) and Graves’ disease (GD) have an autoimmune pathogenesis, possibly related to the thyrotropin receptor (TSHR). The aim of this study was to determine whether TSHR immunoreactivity is correlated with disease severity or serum TSHR antibody (TRAB) levels. Methods: Orbital tissues from 30 patients with TAO were compared with those of 20 patients with strabismus and four with non-thyroid orbital inflammation. TSHR was detected by immunohistochemistry and TRAB were measured by radioreceptor assay. Results: No TSHR immunoreactivity was detected in the 24 control orbital tissues, whereas in all TAO biopsies elongated fibroblast-like cells, expressing TSHR, were present. These cells were located between the muscle cells, which were separated by oedema in the acute phase but fibrous tissue in the chronic phase of disease. Semi-thin sections showed numerous mast cells present in the chronic phase and in close contact with adipocytes. The number of TSHR immunostained cells was high in early disease, decreased with disease duration, and was positively correlated with TRAB levels at the onset of TAO. Conclusion: TSHR immunoreactivity was demonstrated specifically in TAO orbits which highlights the importance of TRAB early in the pathogenesis.

Contributions of the video-assisted approach to thyroid and parathyroid surgery.

Abstract Background: The authors report their initial experience with partial and total thyroidectomy, and neck exploration for hyperparathyroidism using the video-assisted approach. Patients and methods: Between June 1999 and March 2001, 114 patients underwent a thyroid (n = 57) or parathyroid (n = 57) operation using a video-assisted cervical approach. Video-assisted neck exploration was conducted in all cases under general anaesthesia leading to a partial or total thyroidectomy, and to a selective adenoma removal in PHPT or to a subtotal parathyroid resection in SHPT. Results: In the thyroid group: the mean cranio-caudal and transversal diameter of the resected specimen were respectively 4.9 ± 0.9 and 2.8 ± 0.6 cm, and mean total lobar weight was 11.7 ± 5.8g. Conversion to conventional surgery was required in 5 patients (8,8%). The mean operative time was 133,9 ± 26,9 and 86,5 ± 22,5 minutes for total and partial thyroidectomy respectively. The laryngeal nerve was identified in 96% of cases. The mean length of skin incision was 24.0 ± 2 mm. There were 3 cases of postoperative hypocalcemia, and 2 cases of postoperative hoarseness. The postoperative hospital stay was less than 24 hours for 72.7% of patients. The pain intensity at day one (VAS) was 2.1 ± 1.3. In the parathyroid group: seven of the 44 patients who underwent PHPT (15.9%) and 4 of the 13 patients who underwent surgery for SHPT (30.8%) were converted to a conventional surgical technique. The mean operative time in PHPT and SHPT was 47.3 ± 22.3 minutes and 136.8 ± 18.7 minutes, respectively. Recurrent laryngeal nerve was identified in 53.1% of the patients. The median diameter and weight of the resected parathyroid glands were 1.5 cm (range 0.8–2.7) and 0,9 g (range 0.5–7), respectively. The length of skin incision was 24 ± 2mm. All but 2 patients are currently cured. Postoperative complications included hematoma and transient hoarseness each in one patient (1.75%). The median pain intensity at day one (VAS) was 0.5 (range: 0 to 3.6). In the PHPT group, the postoperative hospital stay was less than 24 hours for 56.7% of the patients, and less than 48 hours for 91.9% of them. Conclusion: The video-assisted approach for thyroid and parathyroid surgery is feasible, safe and effective in selected cases. Benefits for the patients should be further assessed in future prospective comparative trials.

PREGO (presentation of Graves’ orbitopathy) study: changes in referral patterns to European Group On Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012

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.

PREDICTIVE FACTORS OF THYROID CARCINOMA IN NON-TOXIC MULTINODULAR GOITRE

Abstract The management of nontoxic multinodular goitre (NMNG) remains controversial. The challenge for the clinician is to identify the small proportion of NMNG patients with associated thyroid carcinoma who would thus benefi t from surgery. We studied retrospectively the medical records of 80 patients with NMNG and coexisting thyroid carcinoma who underwent total thyroidectomy. Eighty total thyroidectomy patients with NMNG whose histology was benign were then randomnly chosen as controls. In univariate analysis, the following parameters were signifi cantly more frequent in the carcinoma group: rapid growth of the goitre (p=0.002), presence of microcalcifi cations (p=0.01), hypoechogenicity (p=0.02), firm consistency of a nodule (p=0.03), and presence of a dominant cold nodule on scintigraphy (p=0.03). In the multiple regression analysis, the variables signifi cantly associated with carcinoma were rapid growth (Odds ratio (OR) = 4.13, 95% confi dence interval(CI):1.72-9.89), hypo-echogenicity (OR = 3.11, 95% CI : 1.13-8.51) and the presence of a dominant nodule (OR = 2.26, 95% CI :1.06-4.79)). In the cancer group, tumour size was positively correlated with compression signs (p=0.01), age (p=0.02), the presence of a dominant nodule on scintigraphy (p=0.02), and with rapid growth (p=0.04). Concerning nodule size estimated on US (ultrasound), the majority (65%) of patients without carcinoma had nodules < 3 cm, whereas 73% of patients with clinical thyroid carcinoma (≥ 1cm on histology) had nodules with a diameter of ≥ 3 cm on US (p=0.02). In conclusion, our study suggests that surgical treatment of NMNG should be proposed in the presence of rapid nodular growth, compression signs, dominant nodule on scintigraphy, nodule size ≥ 3 cm and hypo-echogenicity.

To Treat or Not to Treat Euthyroid Autoimmune Disorder during Pregnancy

Background: Subclinical autoimmune hypothyroidism during pregnancy is associated with an increased risk of miscarriage and has a deleterious effect on fetal development. The aim of this study was to evaluate a screening and treatment strategy of subclinical hypothyroidism, and to establish normal ranges of thyroid-stimulating hormone (TSH) and thyroxine (T4) during pregnancy. Methods: A retrospective study was carried out on 784 consecutive files of pregnant women; the files were systematically searched for thyroid function and antithyroid antibodies in order to determine the effect and the prevalence of anti-thyroid peroxidase antibodies (TPO-Ab) during pregnancy, and to evaluate treatment with levothyroxin (LT4) in TPO-Ab carriers. Results: Among the 75 TPO-Ab-positive patients, 42 received LT4 treatment during pregnancy. Although the range of TSH serum levels was wide, the mean TSH level was significantly higher in TPO-Ab-positive women (3 vs. 1 mIU/l, p < 0.01). No significant difference in the obstetrical complications rate was observed between TPO-Ab-positive and TPO-Ab-negative populations. Conclusions: Our study provides information on normal ranges of serum TSH and free T4 for Belgian pregnant women receiving iodide supplementation. Based on our results, we suggest supplementation of TPO-Ab-positive pregnant women with 50 μg/day of LT4, unless their TSH levels are lower than 1 mIU/l, to avoid the risk of hypothyroidism during pregnancy.

Hypothyroidism and Major Depression: A Common Executive Dysfunction?

Little is known about the possible link between the cognitive disorders associated with hypothyroidism and those encountered in depression. This study examines attentional and executive functions as well as the intensity of anxiety and depressive symptoms in hypothyroidism and major depression and the possible link between these symptoms and cognitive disturbances. This study confirms the existence of psychomotor slowing associated with attentional and executive disturbance in major depression as well as in hypothyroidism. However, while depressed subjects manifested a conscious bias with material of negative emotional valence, no such bias was found in the hypothyroid subjects. While the hypothyroid state is accompanied by anxiety/depressive symptoms, it seems that the latter are too discrete for an attentional bias to be observed with material with a negative emotional valence.