Thyroid cancer has a multifactorial aetiology resulting from the interaction of genetic and environmental factors. Several low penetrance susceptibility genes have been identified but their effects often vary between different populations. Somatic point mutations and translocations of the REarranged during Transfection (RET) proto-oncogene are frequently found in thyroid cancer. The aim of this case-control study was to determine the effect of four well known RET single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma. A total of 545 Portuguese patients and 543 controls were genotyped by PCR and restriction enzyme analysis, for the following SNPs: G691S (exon 11, rs1799939 G/A), L769L (exon 13, rs1800861 T/G), S836S (exon 14, rs1800862 C/T), and S904S (exon 15, rs1800863 C/G). The minor allele of S836S was overrepresented in patients with papillary thyroid carcinoma (PTC) when compared to controls (OR 1.57; 95% CI 1.05–2.35; p = 0.026). The GGTC haplotype was also overrepresented in PTC (OR 2.51; 95% CI 1.07–5.91; p = 0.029). No associations were found in follicular thyroid carcinoma (FTC). Multivariate logistic regression analysis showed no differences regarding gender, age at diagnosis, lymph node or distant metastasis. However, a near significant overrepresentation of the minor alleles of G691S and S904S was found in patients with tumours greater than 10 mm of diameter at diagnosis. These data suggest that the RET S836S polymorphism in exon 14 and the GGTC haplotype are risk factors for PTC, but not FTC, and that the G691S/S904S polymorphisms might be associated with tumour behaviour.

Objective: To evaluate the influence of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on blood glucose levels at diagnosis of gestational diabetes mellitus (GDM) and obstetric/neonatal outcomes. Subjects and methods: Retrospective cohort study including 462 women with GDM and singleton pregnancy delivered in our institution between January 2015 and June 2018 and grouped according to BMI/GWG. Results: The diagnosis of GDM was more likely to be established in the 1st trimester (T) in women with [...] ABSTRACT Objective: To evaluate the influence of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on blood glucose levels at diagnosis of gestational diabetes mellitus (GDM) and obstetric/neonatal outcomes. Subjects and methods: Retrospective cohort study including 462 women with GDM and singleton pregnancy delivered in our institution between January 2015 and June 2018 and grouped according to BMI/GWG. Results: The diagnosis of GDM was more likely to be established in the 1st trimester (T) in women with

ResumoObjetivoA hiperplasia congénita da suprarrenal não clássica (HCSRNC) é uma das doenças autossómicas recessivas mais frequentes que, na grande maioria dos casos, ocorre por deficiência da enzima 21‐hidroxilase (21‐OH). Com o presente artigo pretende‐se fazer uma revisão sobre os aspetos relevantes desta doença na prática clínica diária, em especial nas áreas da pediatria, endocrinologia e obstetrícia.MétodosFoi efetuada uma revisão bibliográfica através da base de dados eletrónica MEDLINE de artigos publicados entre 1990‐2013. Foram utilizadas as palavras‐chave: «hiperplasia da suprarrenal não clássica» e «deficiência de 21‐hidroxilase».ConclusõesA apresentação clínica da HCSRNC é variável, desde a ausência completa de sintomas até à existência de um ou vários sintomas relacionados com o excesso de androgénios, como pubarca precoce, hirsutismo, oligomenorreia, acne ou infertilidade. O diagnóstico é confirmado através da prova de estimulação com tetracosactídeo. O tratamento deve ser efetuado apenas se houver sintomatologia, deve ser individualizado e tem como objetivos principais evitar uma puberdade precoce com encerramento epifisário prematuro, regularizar os ciclos menstruais, promover a fertilidade e atenuar o acne e hirsutismo.AbstractAimNonclassical congenital adrenal hyperplasia is one of the most common autosomal recessive disorders and, in the majority of cases, is due to 21‐hydroxylase (21‐OH) enzyme deficiency. With this article we intend to review the relevant aspects of this disease in daily clinical practice, particularly in the areas of pediatrics, endocrinology and obstetrics.MethodsA bibliographic review was performed through the electronic database MEDLINE, for articles published between 1990 and 2013. The keywords used were “nonclassical adrenal hyperplasia” and “21‐hydroxylase deficiency.”ConclusionsThe clinical presentation of nonclassical adrenal hyperplasia is variable: it can be asymptomatic or cause symptoms related to androgen excess as premature pubarche, hirsutism, oligomenorrhea, acne or infertility. The diagnosis is confirmed by a tetracosactide stimulation test. Treatment is reserved for symptomatic individuals, must be individualized and its main goals are to avoid premature pubarch with premature epiphyseal fusion, to regulate the menstrual cycles, to promote fertility and to reduce hirsutism and acne

ResumoObjetivoO feocromocitoma é um tumor raro com origem no tecido cromafim. Para avaliar a epidemiologia característica e abordagem destes tumores, foi efetuado um estudo multicêntrico retrospetivo em doentes com feocromocitoma.Material e métodosEstudo retrospetivo, desenvolvido em 12 centros, incluiu 176 doentes tratados entre 1986‐2011. Efetuado um questionário que incluiu dados epidemiológicos, clínicos, doseamentos laboratoriais, exames de localização, estudo genético, preparação pré‐operatória e cirurgia. De acordo com a data de diagnóstico, os doentes foram divididos em 2 períodos de tempo, 1986‐2000 e 2001‐2011, e alguns dados foram comparados.ResultadosCento e cinco mulheres e 70 homens, idade média 51,9±15,2 anos. Em 172 doentes, a apresentação clínica foi: 31% incidentalomas, 10% paroxismos típicos, 18% hipertensão persistente e 5% detetados durante rastreio genético. Onze por cento tinham outros sintomas clínicos de feocromocitoma e 25% uma mistura de 2 ou mais quadros clínicos. Os exames laboratoriais mais frequentes foram as catecolaminas urinárias e seus metabolitos urinários.Em 154 doentes, foi localizado por TAC em 84%, RMN em 41% e a cintigrafia com MIBG em 55%. A dimensão média do tumor foi 55,3±33,7mm, 56% na suprarrenal direita e 7% bilateral. O tratamento pré‐operatório em 126 casos foi: fenoxibenzamina em 65% dos doentes e associada a um betabloqueador em 29,3%.Em 170 doentes, 91 efetuaram laparotomia (54%) e 74 laparoscopia (44%). Cinco doentes não efetuaram cirurgia. Em 9 doentes foi diagnosticado feocromocitoma maligno, 3 na altura do diagnóstico inicial e 6 durante o seguimento (após 6‐192 meses).Em 19 doentes foi efetuado o diagnóstico de uma síndrome genética.ConclusõesTrinta e um por cento dos tumores foram detetados como incidentalomas. A suprarrenal direita foi mais atingida. Observou‐se um aumento do n° de diagnósticos de feocromocitoma e um melhor estudo e estadiamento nos doentes diagnosticados entre 2001 e 2011 comparativamente com os diagnosticados entre 1986 e 2000. Dado que a malignidade se pode manifestar tardiamente, o seguimento destes doentes deve ser para toda a vida.AbstractObjectivePheochromocitoma is a rare tumor arising from the chromaffin tissue. To have an idea of the epidemiology, characteristics and management of this tumors it was performed a multicentric retrospective evaluation of patients with pheochromocitoma.Material and methodsTwelve endocrine departments participated, reviewed the data of 176 patients, between 1986 and 2011. A questionaire included data on epidemiological, clinical, laboratory, radiological, genetic study, preoperative treatment and surgery. According to year of diagnosis the patients were divided in two groups, 1986‐2000 and 2001‐2011, and some data were compared.Results105 female and 70 male, with 51.9±15.2 years. The clinical presentation of 172 patients were: 31% discovered incidentally; 10% had the typical spells; 18% had persistent hypertension and 5% discovered in a genetic screening; 11% other clinical symptom of pheochromocytomas and 25% had a mixture of two or more clinical presentation. The most often laboratory assays evaluated were the urinary catecholamines and their urinary metabolites.In 154 patients, the localization was by CT in 84%, MR in 41% and MIBG scintigraphy in 55%. The mean dimension of the tumor was 55.3±33.7mm, 56% at the right adrenal, and 7% bilateral. The preoperative treatment in 126 cases was: phenoxybenzamine in 65% of the patients, and associated to a β blocker in 29.3%.In 170 patients, the surgical approach was laparotomy in 91(54%) and laparoscopy in 74(44%); 5 patients had no surgery. 9 patients had the diagnosis of malignant pheochromocitoma: at the diagnosis in 3 cases, or during the follow up (after 6 to 192 months) in 6.In 19 patients a genetic syndrome was found.Conclusions31% of the patients discovered as a incidentalomas. The right adrenal was more affected. Between 2001 and 2011 more patients were diagnosed with pheochromocitoma and their sudy and staging were improved comparing with the period between 1986 and 2000. Given that the malignancy in a pheochromocitoma can be a late finding life long follow‐up is mandatory

ResumoA disfunção tiroideia provocada pelos inibidores de tirosina-cinase (ITC) é um importante efeito adverso desta classe farmacológica. Com o objetivo de avaliar a prevalência de hipotiroidismo nos doentes tratados com ITC entre 2003-2012 na nossa instituição, foi efetuada uma revisão dos processos clínicos destes doentes. Foram avaliados 107 doentes, 56% do sexo masculino. Em 27 doentes foi utilizado erlotinib, em 30 imatinib, em 17 sunitinib, em 15 lapatinib, em 7 sorafenib, em um gefitinib e em 10 doentes mais de um ITC (8 imatinib + sunitinib, um sunitinib + sorafenib, um imatinib + dasatinib). Dos 107 doentes, 59 (55%) efetuaram estudo da função tiroideia, nos quais foi documentado hipotiroidismo em 35,6% (21 doentes). O hipotiroidismo foi observado após um tempo médio (±DP) de tratamento de 9,3±5,8 meses. Foi iniciada terapêutica com levotiroxina em 11 doentes. Foi detetado hipotiroidismo em 57, 46 e 17% dos doentes tratados com sunitinib, lapatinib e sorafenib, respetivamente. Dos doentes tratados com mais de um ITC, 75% apresentaram hipotiroidismo, sendo que em todos estes casos de hipotiroidismo um dos ITC era o sunitinib. Dos doentes sob erlotinib, imatinib ou gefitinib, em monoterapia que fizeram doseamento de hormonas tiroideias, nenhum apresentou hipotiroidismo. Este estudo apresenta como limitação um baixo número de doentes em cada subgrupo, no entanto, o hipotiroidismo parece ser mais frequente em doentes sob sunitinib e lapatinib. Atendendo à elevada prevalência de hipotiroidismo em doentes medicados com ITC será aconselhável efetuar o doseamento de hormonas tiroideias antes e durante o tratamento de forma periódica.AbstractThyroid dysfunction is an important adverse effect of tyrosine kinase inhibitors (TKI). To assess the prevalence of hypothyroidism in patients treated with TKI at our institution between 2003 and 2012, we reviewed their clinical records. One hundred and seven patients were evaluated, 56% male. Erlotinib was used in 27 patients, imatinib in 30, sunitinib in 17, lapatinib in 15, sorafenib in 7, gefitinib in 1 and more than one TKI in 10 patient (8 imatinib+sunitinib, 1 sunitinib+sorafenib, 1 imatinib+dasatinib). Of 107 patients, 59 (55%) performed thyroid function evaluation, in which hypothyroidism was documented in 35.6% (21 patients). Hypothyroidism was detected after a mean (±SD) time of 9.3±5.8 months of therapy. Levothyroxine was initiated in 11 patients. Hypothyroidism occurred in 57%, 46% e 17% of the patients treated with sunitinib, lapatinib and sorafenib, respectively. Seventy five percent of the patients treated with more than one TKI presented hypothyroidism and in all cases one of TKI was sunitinib. Of the patients receiving erlotinib, imatinib or gefitinib monotherapy that underwent thyroid function evaluation, none had hypothyroidism. The main limitation of the study is the low number of patients in each subgroup, however hypothyroidism seems to be more prevalent in patients on sunitinib or lapatinib. With the high prevalence of hypothyroidism in patients under TKI it is recommended to perform thyroid function assessment before and periodically during the treatment