Ecos da ETA 2017

  Grupo de Estudo da Tiroide da SPEDM
  com o apoio Merck, s.a.

3.º dia marcado pela apresentação de oito posters portugueses

No terceiro dia foram apresentados oito posters de autores portugueses:

O Serviço de Endocrinologia do CHSJ levou a Belgrado três trabalhos:

- Um que pretendeu avaliar a relação entre a função tiroideia, a autoimunidade e o risco cardiovascular na doença de Graves.

- Um caso clínico de metastização óssea de um carcinoma papilar da tiroide.

- Um terceiro que procurou avaliar a relação entre a função tiroideia, a autoimunidade, a insulinorresistência e o risco cardiovascular na tiroidite autoimune.

Por sua vez, o Serviço de Endocrinologia do CHVNG/E apresentou um trabalho com o objetivo de avaliar o impacto das novas guidelines da ATA sobre tiroide e gravidez, comparando a prevalência do hipotiroidismo subclínico na gravidez usando os novos ou os antigos valores de referência de TSH para o trimestre.

O Hospital Egas Moniz apresentou um póster em que foram analisadas as características clínicas, radiológicas e histológicas de 6 carcinomas anaplásicos daquele Serviço de Endocrinologia.

E, finalmente, o Serviço de Endocrinologia do CHUC apresentou três trabalhos:

- Um caso clínico de um doente com carcinoma diferenciado da tiroide com anticorpos antitiroglobulina positivos, em que foi questionado o seu doseamento como marcador tumoral.

- Um caso clínico de um doente com microcarcinoma papilar da tiroide que desenvolveu metástases ósseas.

- Um estudo que pretendeu avaliar a eficácia e a toxicidade dos inibidores da tiroxina cinase em doentes com carcinoma da tiroide avançado.
P3-01-123
CARDIOVASCULAR RISK FACTORS IN GRAVES‘ DISEASE ACCORDING TO THYROID FUNCTION AND AUTOIMMUNITY

Sofia Castro Oliveira1, Celestino Neves1, João Sérgio Neves1, Helena Greenfield2, Oksana Sokhatska3, César Esteves1, Miguel Pereira1, José Luís Medina2, Luís Delgado3, Davide Carvalho4
1Department of Endocrinology, Diabetes and Metabolism, São João Hospital Center. Faculty of Medicine of Porto University, Porto, Portugal, 2Faculty of Medicine of Porto University, Porto, Portugal, 3Immunology Department, São João Hospital, Faculty of Medicine, University of Porto, Porto, Portugal, 4Department of Endocrinology, Diabetes and Metabolism, São João Hospital Center. Faculty of Medicine of Porto University, Institute for Research and Innovation in Health (I3s), Porto, Portugal

Introduction: Thyroid hormones modulate the metabolism of the lipoproteins and glucose. The objective of our study was to evaluate the relationship between thyroid function, autoimmunity and the cardiovascular risk factors in Graves’ disease.

Material and Methods: We performed a retrospective study, which included 126 patients with Graves’ disease in their first cycle of treatment with metimazol. We evaluated thyroid function (FT3, FT4, TSH), autoimmunity (TRAB), and the levels of total cholesterol, LDL, HDL, triglycerides, apolipoprotein (apo) A1, apo B, lipoprotein Lp(a), reactive C protein (CRP), homocysteine, vitamin B12, folic acid, glucose and insulin with OGGT and markers of insulin resistance such as HOMA-IR (Homeostasis Model Assessment for Insulin Resistance). The patients were divided into a TRAB positive and a TRAB negative group and into groups with clinical hyperthyroidism, subclinical hyperthyroidism and normal thyroid functions. For the statistical analysis we employed Spearman correlation, t-tests and Mann-Whitney tests. Data are presented as mean ± standard deviation or median (25-75th percentile) according to distribution.

Results: In the total group the mean age was 44.9 ±15.2 years, with a predominance of the female sex (92.9%). The mean body mass index was 26.0±4.7 kg/m2. We observed a positive correlation between the levels of TSH and apo B (r=0.236; p=0.016) and a negative correlation between the levels of TRAB and apo B (r=-0.211; p=0.030. The FT3 and FT4 levels were positively correlated with the fasting insulin levels (r=0.268; p=0.008 and r=0.226; p=0.025, respectively) and with HOMA-IR (r=0,258;p=0,010 and r=0,259; p=0,010, respectively). Compared to the normal subgroup, the group with clinical hyperthyroidism had significantly lower apo B levels (70.9±25.8 vs. 89.8±24.0 mg/dL; p=0.007), and higher levels of HOMA-IR [2.09 (1.29-4.53) vs. 1.55 (0.96-2.13); p=0.023] and CRP [0.57(0.20-0.93) vs. 0.20 (0.07-0.38) mg/L; p=0.005]. In the clinically hyperthyroid group we observed a negative correlation between FT4 and apo B (r=-0.520; p=0.039) and a positive correlation between TSH and HDL cholesterol (r=0.618;p=0.004). Compared to the subgroup with negative TRAB, the positive TRAB subgroup had significantly lower levels of apo B (80.3±23.9 vs. 89.7±23.8 mg/dL; p=0.047) and TSH [0.180 (0.002-1.080) vs. 1.020 (0.235-2.055) µUI/mL; p<0.001]. In the TRAB positive group, the levels of FT3 and FT4 were positively correlated with the fasting insulin levels (r=0.402; p=0.008 and r=0.368; p=0.015, respectively) and with HOMA-IR (r=0.396; p=0.009 and r=0.388; p=0.010, respectively).

Conclusion: In Graves’ disease the relationships between thyroid function, autoimmunity, insulin resistance and lipid profile may contribute to increased cardiovascular risk.
P3-04-146
CHORDOMA AS A DISGUISE OF PAPILLARY THYROIDE CARCINOMA – A CASE REPORT

Daniela Magalhães1, Cláudia Costa2, Maria João Matos2, Ana Paula Santos2, Isabel Azevedo3, Cristina Sanches4, Hugo Duarte5, Mariana Afonso6, Manuel Jacome6, Isabel Torres2
1Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, E.P.E., Faculty of Medicine, University of Porto, Instituto de Investigação e Inovação Em Saúde, University of Porto, Porto, Portugal, 2Endocrinology Department of Instituto Português de Oncologia Do Porto, Porto, Portugal, 3Medical Oncology Department of Instituto Português de Oncologia Do Porto, Porto, Portugal, 4General Surgery Department of Instituto Português de Oncologia Do Porto, Porto, Portugal, 5Nuclear Medicine Department of Instituto Português de Oncologia Do Porto, Porto, Portugal, 6Pathology Department of Instituto Português de Oncologia Do Porto, Porto, Portugal

Introduction: Bone is the second most common site of distant metastasis from thyroid cancer. The incidence of bone metastasis in papillary thyroid carcinoma is 1-7%.

Case Report: A 62-year-old male presented with a 9x7.5x9 cm bulky mass on the sacrum with soft tissue density on CT, leading to extensive lytic lesion of most of the sacred vertebrae and extending to the left iliac, suggestive of chordoma. His past medical history was significant for type-2 diabetes, renal lithiasis, smoking and chronic alcoholism. He underwent total sacretectomy with partial excision and reconstruction of the left iliac. The anatomopathological examination revealed sacro-coccygeal involvement by predominantly papillary (follicular variant) thyroid carcinoma, with foci of non-differentiated (insular) carcinoma. Thyroid ultrasonography showed a solid nodule of 20 mm in the right lobe and two solid hypoechogenic nodules of 11 and 9 mm in the left lobe, the smallest with coarse calcifications. 18F-FDG-PET revealed a hypermetabolic focus in thyroid left lobe consistent with malignant neoplasia. He underwent total thyroidectomy. Histological examination revealed follicular and oxyphilic variants of multifocal papillary carcinoma, with dimensions ranging from 2 to 15 mm, without signs of hematogenic, lymphatic or perineural permeation nor invasion of the capsule or extrathyroidal extension, with resection margins uninvolved by neoplasia (pT1b[m]NxM1R0). Radioactive iodine (131I) was then performed. Post-therapy scintigraphy showed hyperfixation in the remnant of the sacrum and lower lumbar spine, bilateral iliac and anterior cervical region. TSH-stimulated thyroglobulin was 24490 ng/mL. Follow-up MRI shows recurrence and progression of the pelvic tumor lesion.

Conclusions: We present a rare case of a well differentiated thyroid carcinoma without other histological signs of unfavourable prognosis beyond multifocality presenting as osteolytic bone metastasis mimicking a chordoma. Bone metastasis are associated with a poor prognosis and, because overall survival is improved by complete resection, its early diagnosis and treatment is important.


P3-05-157
EVALUATION OF THE INTERRELATIONSHIPS BETWEEN THYROID FUNCTION, AUTOIMMUNITY, INSULIN RESISTANCE, LIPID PROFILE, HOMOCYSTEINE AND C-REACTIVE PROTEIN IN PATIENTS WITH AUTOIMMUNE THYROIDITIS

Celestino Neves1, João Sérgio Neves1, Sofia Castro Oliveira1, Oksana Sokhatska2, César Esteves1, Miguel Pereira1, José Luís Medina3, Luís Delgado2, Davide Carvalho4
1Department of Endocrinology, Diabetes and Metabolism, São João Hospital Center. Faculty of Medicine of Porto University, Porto, Portugal, 2Immunology Department, São João Hospital, Faculty of Medicine, University of Porto, Porto, Portugal, 3Faculty of Medicine of Porto University, Porto, Portugal, 4Department of Endocrinology, Diabetes and Metabolism, São João Hospital Center. Faculty of Medicine of Porto University, Institute for Research and Innovation in Health (I3s), Porto, Portugal

Introduction: Since thyroid dysfunction has a major prevalence in the general population, it is essential to understand and establish the association between different levels of TSH, autoimmunity and an increased cardiovascular risk.

Objective: To evaluate the relationship between thyroid function, autoimmunity, insulin resistance and cardiovascular risk factors in patients with autoimmune thyroiditis (AIT).

Methods: We defined three groups based on TSH levels: TSH <2.5 µUI/ ml, TSH 2.5 to 5.0 µUI/ml and TSH >5.0 µUI/ml. We analyzed the levels TSH, FT4, FT3, total cholesterol, HDL, LDL, apolipoprotein A1 (ApoA1), ApoB, Lipoprotein (a) [Lp(a)], homocysteine, anti-Tg, anti-TPO, CRP, folic acid and vitamin B12 levels, insulin resistance markers comprising HOMA-IR and WBISI (Whole-Body Insulin Sensitivity Index). For the statistical analysis we employed Spearman correlation, t-tests and Mann-Whitney tests. Data are presented as mean ± standard deviation or median (25-75th percentile) according to distribution.

Results: Within our sample of 353 subjects with AIT 94% were female. The mean age was 47.0±16.3 years. Two hundred and fifty-three individuals belonged to the group TSH <2.5 while the group TSH 2.5-5.0 comprised 62 individuals, and the group TSH>5.0 comprised 27 individuals. There were no significant differences regarding the mean age or the mean BMI between groups. The group TSH>5.0 presented higher levels of HOMA-IR when compared to the other two groups [2.96 (1.76-4.59) in the group TSH>5.0 vs 1.86 (0.97-2.56) in the group TSH 2.5-5.0 and 1.58 (1.06-2.46) in the group TSH <2.5, p=0.002]. Regarding the total group, we found significant negative correlations between TSH and age (r=0.183, p=0.001), FT3 and both HDL (r=0.118, p=0.028) and ApoA1 (r=0.129, p=0.024), and also between FT4 and IGI (r=0.112, p=0.045). TSH was positively correlated with HOMA-IR (r=0.146, p=0.018), and negatively correlated with WBISI (r=-0.146, p=0.018) in the total group. Concerning the group TSH <2.5, positive correlations were observed between TSH and HDL (r=0.136, p=0.031), and between FT4 and both CRP (r=0.136, p=0.037). Anti-TPO antibodies were positively correlated with total cholesterol (r=0.141, p=0.026) while anti-Tg positively correlated with ApoB (r=0.165, p=0.013) and showed negative correlations with HDL (r= -0.139, p=0.028) in the group TSH<2.5. We found negative correlation in the group TSH 2.5-5.0 between anti-Tg and total cholesterol (r=0.371, p=0.004, ApoB (r=-0.342, p=0.022), and Lp(a) (r=-0.470, p=0.001), and positive correlations between FT3 and HDL (r=0.358, p=0.030), and vitamin B12 (r=0.398, p=0.024).

Conclusions: Our results suggest that thyroid autoimmunity may affect lipid profile independent of thyroid function in patients with AIT.
P3-06-163
TSH REFERENCE RANGES IN THE ASSESSMENT OF THYROID FUNCTION DURING PREGNANCY

Catarina Machado1, Patrícia Tavares1, Sara Monteiro1, Gustavo Rocha1, Marta Barbosa1, Maria João Oliveira1
1Centro Hospitalar de Vila Nova de Gaia/Espinho, Epe, Vila Nova de Gaia, Portugal

Introduction: Pregnancy has an important impact on thyroid function and thyroid disorders in pregnancy are common. For women with no previous thyroid disease, new guidelines recommend using population and trimesterlings specific reference ranges for serum TSH. If these reference ranges are not available, an upper reference limit of 4,0uUI/mL may be used.

Objectives: To compare the prevalence of subclinical hypothyroidism in pregnancy using an upper reference of TSH of 4,0uUI/mL versus previous cutoffs of 2,5uUI/mL for the first trimester and 3,0uUI/mL for the second and third trimesters.

Methods: Retrospective review of pregnant women with no previous thyroid disease, referred to endocrinology consultation following thyroid dysfunction detected during pregnancy in the last 4 years.

Results: 160 women were included, mean age 30,7±6,5 years. 65 (40,6 %) patients were referred in the first trimester (mean TSH 4,7±2,8uUI/mL), 66 (41,3%) in the second (mean TSH 5,0±1,6uUI/mL) and 29 (18,1%) in the third (mean TSH 4,7±1,6uUI/L). 96 patients (60%) had TSH above 4,0uUI/mL. Iodine supplementation led to normalization of TSH in 27 (16,9%) women. Levothyroxine was given to 106 patients (66,3%): 38,7%, 51,9% and 9,4% in the first, second and third trimester, respectively. If an upper reference limit of 4,0uUI/mL was used for TSH, 64 patients would have been characterized as euthyroid and treatment with levothyroxine would have been avoided in 28 patients (26,4%): 12 in the first trimester, 14 in the second and 2 in the third. Of these, 17,9% (n=5) needed levothyroxine supplementation after pregnancy, the majority of which was diagnosed in the first trimester. There was no association between subclinical hypothyroidism and adverse pregnancy outcomes.

Conclusion: In this study, using a TSH cutoff of 4uUI/mL following 2017 ATA guidelines would reduce the incidence of hypothyroidism in 40%. Nonetheless, 5 women (17,9%) who needed treatment with levothyroxine after pregnancy would have been missed.
P3-02-125
CLINICAL, RADIOLOGICAL AND HISTOLOGICAL CHARACTERISTICS OF SIX ANAPLASTIC THYROID TUMOURS
Catarina Roque1, Catarina Saraiva1, Clotilde Limbert1, Marlene Carriço1, Carlos Vasconcelos1
1Endocrinology Department Hem Chlo, Lisbon, Portugal

Objectives: Investigate clinical, radiological and histological findings of anaplastic carcinomas (AC) over a 4-year period.

Methods: All FNAC from 1/01/2013-1/01/2017 were retrospectively investigated. Patients with histological confirmation of AC were included. Clinical files provided age, sex, symptoms, signs, thyroid function, autoimmunity and stage. Ultrasound, tomography scans, histological and surgical reports were evaluated.

Results: Among 4928 FNAC, 6 were histologically proven AC. Femaleto-male ratio was 2:1 and the age range 56-87 years. Hypothyroidism and subclinical-hyperthyroidism were each reported once, the remainder were euthyroid. None had demonstrable autoimmunity. All patients presented a previously undiagnosed goitre with local symptoms, except for one. Stony-hard consistency was described in 4/6, fixation in 2/6 and lymphadenopathy in 1/6. Dysphagia was the commonest complaint (4/6), followed by dysphonia (2/6) or pain (2/6) with a progression of 1-4 months. Most glands were multinodular (4/6). The aspirated nodes had 47-96mm, were hypoechoic and heterogeneous, 3 had cystic degeneration, 3 were exophytic, 2 showed macrocalcifications. Homolateral adenopathy and extrathyroidal invasion was reported in 3 US. On contrasted-CT all patients had extrathyroidal extension and lymphadenopathy. Compression of respiratory and digestive structures was observed in 3/6 and 4 had displacement of the vascular sheath. All patients had thoracic involvement, by mediastinal lymphadenopathy (3/6) and/or pulmonary nodules (4/6). Stage IVc was common (4/6), followed by IVb (2/6). These 2 patients had poorlydifferentiated components in their tumours. The most dominant subtype was giant-cell, followed by spindle cell. The most extensively disseminated case had a sarcomatoid variant with osteoclast-like cells and immunohistochemistry positivity for desmin+AML+vimentin.

Conclusions: The rare AC may show characteristic clinical and radiological features, enough to suspect the diagnosis even when FNAC result is “malignant” but not suggestive of AC. CT shows clear superiority to US on the detection of local and distant disease, making it indispensable in preoperative evaluation of suspicious cases.
P3-02-127
THYROGLOBULIN ANTIBODIES – A TUMOUR MARKER? CLINICAL CASE
Cristina Ribeiro1, Gracinda Costa2, Miguel Melo3, Joana Saraiva4, Diana Catarino2, Francisco Carrilho2
1Endocrinology University Hospital, Coimbra, Portugal, 2Coimbra, Portugal, 3Instituto de Investigação e Inovação Em Saúde (I3s), Institute of Pathology and Immunology of the University of Porto (Ipatimup), Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, 4University and Hospital Center of Coimbra, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

Introduction: Thyroglobulin (Tg) is a specific and sensitive tumor marker of differentiated thyroid cancer Thyroglobulin Antibodies (TgAb) negative. The presence of TgAb limits this usefulness of Tg. We’ll present a clinical case documenting the utility of TgAb as a tumor marker in these situations.

Clinical Case: A woman, 59 years, submitted to total thyroidectomy in 2000 with “multicentric papillary cancer, with high cells”, followed by I131 ablation. Afterwards, Tg remained undetectable (<0,2 ng/ml), but TgAb positive (22-743 UI/ml). In 2005, limphnode cervical methastases were excised. From 2005 till 2013, Tg and TgAb became undetectable. After 2013, TgAb levels were progressively higher: 21-48-84 UI/ml with undetectable Tg (<0,04 ng/ml). In june 2015, I13 (136mCi) was administrated with “slight cervical fixation”. In february 2017, after TgAb – 773 UI/ml, she performed 18 FDGPET: “Bilateral hypermetabolic pulmonary methastases”.

Discussion: This clinical case demonstrates both the interference of TgAb in Tg measurement and their clinical utility as a tumor marker in differentiated thyroid carcinoma.


P3-02-129
BONE METASTASES IN PAPILLARY THYROID MICROCARCINOMA: AN UNUSUAL CASE
Joana Saraiva1, Cristina Ribeiro2, Miguel Melo1, Lúcia Fadiga2, Gracinda Costa1, Francisco Carrilho2
1University and Hospital Center of Coimbra; Faculty of Medicine, University of Coimbra, Portugal, 2University and Hospital Center of Coimbra, Portugal

Introduction: Most papillary microcarcinomas have an indolent course with high survival rates. Distant metastases are exceedingly rare (<1%). Bone metastases when occur are usually osteolytic and radiodine therapy is rarely curative.

Case Report: We present the case of a 78-year-old woman who underwent total thyroidectomy in 2010 for a bifocal papillary thyroid microcarcinoma (1200micra and 910micra)-T1aNxMx. After surgery: TSH 1.9uUI/ mL (0.4-4), fT4 0.9ng/dlL (0.8-1.9), thyroglobulin (Tg) 9.2ng/mL and negative anti-Tg antibodies (TgAbs). Radioidine was not given. Patient maintain follow-up in her medical assistant during 5 years. In 2016 she was sent to our Thyroid Oncology clinic because of thyroid remnant of 13mm in neck ultrasonography, with no cervical adenopathies. Analitically: TSH 2.5uUI/mL, fT4 1.5ng/dL, Tg 2621ng/dl and negative TgAbs. She was submitted to fine needle aspiration of hypoecogenic nodular area in the remaining right thyroid lobe with 1.6x0.8cm which showed no evidence of papillary carcinoma. In February 2016, after recombinant TSH, she was submitted to 18F-FDG PET/ CT and radiodine therapy (71mCi). The post-therapy whole body scan (WBS) and 18F-FDG-PET/CT showed four bone metastases (skull, D6, L5 and left iliac spine) that, despite increased glycolytic metabolism, maintain some iodine uptake. Subsequently she received two more radioiodine treatments in 07/2016 (191mCi) and 01/2017 (167mCi). Last post-therapy WBS showed that the bone lesions preserved their radiodine uptake capacity but with less uptake, reduced size and with significant increase in mineral density. Tg levels progressively reduced to 641ng/ml in last evaluation.

Conclusion: This case indicated that, despite the excellent prognosis, papillary microcarcinomas need to maintain proper follow-up. Although bone metastases traditionally have a poorer response to radioidine our patient has presented a good response and more treatments will probably be performed.
P3-03-135
TYROKISE KINASE INHIBITORS IN ADVANCED THYROID CANCER – EXPLORATORY ANALYSIS OF A CENTER EXPERIENCE
Diana Martins1, Joana Saraiva1, Cristina Ribeiro1, Miguel Melo1, Diana Oliveira1, Adriana Lages1, Mara Ventura1, Nelson Cunha1, Lúcia Fadiga1, Diana Catarino1, Francisco Carrilho1
1Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

Background: Tyrosine kinase inhibitors (TKIs) are an established therapeutic option for patients with advanced thyroid cancer (ATC), with documented efficacy and prolonged PFS in this setting. However, class-related adverse effects may affect quality of life and limit the clinical usage.

Objective: Investigate the efficacy and toxicity of TKIs administered outside clinical trials in patients with ATC.

Methods: Retrospective analysis of a cohort of patients with ATC. Primary endpoints were progression-free survival (PFS) and overall survival (OS) at 2 years of follow-up. Drug withdrawal and dosage reduction caused by drug toxicity were also reported.

Results: We identified a small sample of 8 patients with ATC selected for TKIs therapy in our Center; five women and three men, median age of diagnosis 47 yr (range, 14–70 yr). Five patients (62.5%) presented follicular thyroid carcinomas, one papillary and two had medullary thyroid carcinomas. Seven patients were treated with sorafenib and one with vandetanib on first line therapy; one patient initiated lenvatinib on second line therapy. Median time of treatment was approximately 17 months. Most frequent toxicities observed were hand-foot syndrome (50%, n=4) and diarrhea (37.5%, n=3); two patients withdrawn treatment for adverse events and other two were subject to dose reductions. Median PFS was 24 months, with median OS at 5 yr of follow-up of 88%.

Conclusions: TKIs as sorafenib and vandetanib appear to be effective on ATC patients (median PFS of 24 months). Additionally, observed toxicities were acceptable in the majority of patients, with only two cases of drug discontinuation required, assuring the level of evidence of this therapeutic option.

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