Stress-induced hashitoxicosis: case report and relative HLA serotype and genotype

SUMMARY OBJECTIVE Even though stress has been long known as a provocative factor for Graves' disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION This case demonstrates that, similarly to Graves' disease, Hashitoxicosis can also be triggered by stressful life events.

RESUMO OBJETIVO Mesmo que o estresse seja conhecido há muito tempo como um fator provocativo para a doença de Graves, sua relação com a tireoidite de Hashimoto é mais controversa. Estudos sobre esse tema são escassos. O objetivo deste artigo é relatar um caso de Hashitoxicose induzida por estresse. RESULTADOS Aqui nós relatamos um caso de Hashitoxicose induzido por um evento psicológico estressante em uma mulher de 28 anos com tireoidite de Hashimoto. Ela permaneceu estável eutireoidiana por 12 anos. Ela veio a nossa observação pela primeira vez em abril de 2016, enquanto eutireoidiana. Voltou após 11 meses por causa de fadiga e palpitações, na ausência de dor no pescoço. Testes de função tireoidiana revelaram uma tireotoxicose moderada (TSH indetectável; T4F 36,94 pmol/L, valores normais 9,0-24,46; FT3 13,50 pmol/L, valores normais 3,07-6,14) com anticorpos negativos para o receptor de TSH. Nos últimos três meses ela experimentou um evento psicológico estressante. Os marcadores inflamatórios foram negativos e a contagem de leucócitos foi normal. A ultrassonografia da tireoide revelou um aumento modesto da vascularização. Hipotireoidismo subclínico transitório ocorreu após sete semanas e se recuperou espontaneamente. Na última visita, a paciente ainda estava em eutireoidismo. (TSH 1,01 mU/L; FT4 9,22 pmol/L; FT3 3,98 pmol/L). Também realizamos a sorotipagem e a genotipização do HLA. CONCLUSÃO Este caso demonstra que, similarmente à doença de Graves, também a Hashitoxicose pode ser desencadeada por eventos estressantes da vida.

Association between BRAF (V600E) mutation and clinicopathological features of papillary thyroid carcinoma: a Brazilian single-centre case series

ABSTRACT Objectives: We aimed to investigate the prevalence of the BRAF (V600E) mutation in consecutive cases of papillary thyroid carcinoma (PTC) in patients diagnosed and treated at the Hospital Sao Rafael (Salvador, BA, Brazil) and evaluate its association with clinical and pathological characteristics of PTC. Subjects and methods: We retrospectively enrolled in the study a total of 43 consecutive PTC patients who underwent total thyroidectomy. We performed DNA extraction from formalin-fixed paraffin-embedded (FFPE) tumour tissue samples. Polymerase chain reaction (PCR) and direct sequencing were used to determine BRAF (V600E) mutation status. Univariate and multivariate logistic regression analyses were employed to identify independent associations. Results: The prevalence of BRAF (V600E) mutation was 65.1% (28/43). A high frequency of older patients (p value: 0.004) was observed among the BRAF-mutated PTC group and, in contrast, a low frequency of concurrent Hashimoto's thyroiditis (HT) (p value: 0.011) was noted. Multivariate analysis confirmed that older age (OR: 1.15; 95% CI: 1.00 - 1.33; p value: 0.047) and HT (OR: 0.05; 95% CI: 0.006-0.40; p value: 0.005) were independent factors associated with BRAF (V600E) mutation. Conclusion: We found a high prevalence of BRAF (V600E) mutation in PTC cases. Older age and no concurrent HT were independently associated with BRAF (V600E) mutation.

Association between C1q gene polymorphisms and autoimmune thyroid diseases

ABSTRACT Objective In the present study, we aimed to assess the associations of C1q gene polymorphisms with autoimmune thyroid diseases (AITD) susceptibility. Subjects and methods A set of 1,003 AITD patients (661 with Graves' disease and 342 with Hashimoto's thyroiditis) and 880 ethnically- and geographically-matched controls from Chinese Han population were included. Five common single nucleotide polymorphisms (SNPs) (rs294185, rs292001, rs682658, rs665691 and rs294179) in C1q gene locus were genotyped. Frequencies of genotypes and alleles were compared between patients and controls, and haplotype analysis was also performed. Results There was no statistically significant difference between AITD patients and controls in the frequencies of alleles of rs294185 (P = 0.41), rs292001 (P = 0.71), rs682658 (P = 0.68), rs665691 (P = 0.68) and rs294179 (P = 0.69). There was also no statistically significant difference between AITD patients and controls in the frequencies of genotypes of rs294185 (P = 0.72), rs292001 (P = 0.89), rs682658 (P = 0.83), rs665691 (P = 0.90) and rs294179 (P = 0.43). Stratified analyses showed that none of those five SNPs in C1q gene were associated with Graves' disease or Hashimoto's thyroiditis (all P values > 0.05). Haplotype analysis revealed that there were no obvious genetic associations of C1q gene polymorphisms with AITD susceptibility. Conclusions We, for the first time, identified the associations between C1q gene SNPs and AITD, and our findings suggested that five common SNPs in C1q gene were not associated with AITD susceptibility in Chinese Han population.

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74 percent of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.

HLA-DQB1*05 association with Hashimoto's thyroiditis in children of Northern Greek origin.

In order to investigate HLA-DRB1 and HLADQB1 gene polymorphisms in Northern Greek pediatric population with Hashimoto's thyroiditis (HT), we analyzed the distribution of these alleles in 17 patients and in 181 healthy subjects using polymerase chain reaction. No significant association was detected between HT and alleles analyzed. However, HLA-DQB1*05 was significantly increased in patients with age of diagnosis > 10 years (87.5%) compared to those with age of diagnosis <or= 10 years (33.3%) (P=0.05). These results question the role of sexual maturity in combination with HLA-DQB1*05 as predisposing factor for the onset of HT in Northern Greek children and adolescents.

20 years of RET/PTC in thyroid cancer: clinico-pathological correlations

The RET/PTC oncogene has been isolated almost twenty years ago. During these years, the research has given a final answer to several questions. In fact, it has been demonstrated that: a) RET/PTC is an early event in the process of thyroid carcinogenesis and has a critical role in the generation of the papillary carcinoma; b) RET/PTC activation is essentially restricted to the papillary histotype and to the Hürthle thyroid tumors; c) its incidence increases after exposure to radiations. However, some questions have not found a final answer yet: a) which is the real frequency of RET/PTC activation? Likely it is around 20 percent, but this point is still questionable; b) which other gene modifications are required to lead a thyroid cell carrying a RET/PTC oncogene to the malignant phenotype?, and c) is there any correlation between RET/PTC activation and clinical parameters? We hope that these questions will have a clear answer in the near future.

O oncogene RET/PTC foi isolado há quase 20 anos atrás. Durante esses anos de pesquisa várias questões foram solucionadas. Na verdade, já foi demonstrado que: a) o RET/PTC é um evento precoce no processo da carcinogênese da tiróide e tem um papel crítico na geração do carcinoma papilífero; b) a ativação do RET/PTC está restrita essencialmente ao histotipo papilar e aos tumores de Hürthle; c) sua incidência aumenta após a exposição à radiação. Entretanto, algumas questões permanecem ainda sem uma resposta final: a) qual é a real freqüência de ativação do RET/PTC? Provavelmente em torno de 20 por cento, mas este número ainda é questionável; b) quais outras modificações gênicas são necessárias para transformar uma célula tiroidiana que possui oncogene RET/PTC no fenotipo maligno?; e c) existe alguma correlação entre a ativação do RET/PTC e parametros clínicos? Esperamos que essas questões sejam solucionadas em futuro próximo.