Influence of Thyroid Peroxidase Antibodies Serum Levels in Graves' Disease: A Retrospective Cohort Study.

Purpose Graves' disease (GD) is an autoimmune disorder caused by the presence of antibodies to the thyroid stimulating hormone (TSH) receptor (TRAbs), usually presenting with clinical signs of hyperthyroidism. Previous evidence suggests that higher serum levels of thyroid peroxidase antibodies (TPOAbs) may lead to more sustained remission of hyperthyroidism after treatment with antithyroid drugs (AT). However, doubts about the influence of TPOAbs in Graves' disease outcomes still remain. Methods A retrospective, unicenter cohort study was performed. All patients with GD (TRAbs > 1.58U/L), biochemical primary hyperthyroidism (TSH < 0.4 µUI/mL), and TPOAbs measurement at diagnosis, treated with AT between January 2008 and January 2021, were included for analysis. Results One hundred and forty-two patients (113 women) with a mean age of 52 ± 15 years old were included. They were followed up for 65.4 ± 43.8 months. TPOAbs positivity was present in 71.10% (n=101) of those patients. Patients were treated with AT for a median of 18 (IQR (12; 24)) months. Remission occurred in 47.2% of patients. Patients with remission presented with lower TRAbs and free thyroxine (FT4) levels at the diagnosis. (p-value <0.001, p-value 0.003, respectively). No association was found in the median TPOAbs serum levels of patients who remitted and those who maintained biochemical hyperthyroidism after the first course of AT. Relapse of hyperthyroidism occurred in 54 patients (57.4%). No difference was found in TPOAbs serum levels regarding the patient's relapse. Moreover, a time-based analysis revealed no differences in the relapse rate after 18 months of AT therapy between patients with and without TPOAbs positivity at the diagnosis (p-value 0.176). It was found a weak positive correlation (r=0.295; p-value <0.05) between TRAbs and TPOAbs titters at the moment of Graves' diagnosis. Conclusion In this study, a correlation between TRAbs measurements and TPOAbs titter was described, although no significant association was found between the presence of TPOAbs and the outcomes of patients with GD treated with AT. These results do not support the use of TPOAbs as a useful biomarker to predict remission or relapse of hyperthyroidism in GD patients.

High prevalence of cardiovascular disease and risk factors among type 2 diabetes patients followed in a hospital setting in Portugal: The PICT2RE observational study.

INTRODUCTION AND OBJECTIVES: Portugal is a country with a high prevalence of type 2 diabetes (T2D) and cardiovascular disease (CVD). The prevalence of CVD and cardiovascular (CV) risk factors among T2D patients followed in hospitals in Portugal is not known. The primary objective of this study was to assess the prevalence of CVD and CV risk factors among T2D patients in a hospital setting in Portugal. The clinical management of CVD in the hospital setting was also assessed. METHODS: We performed a non-interventional, multicenter, cross-sectional study with a retrospective phase. T2D patients were consecutively invited to participate. Data were collected retrospectively. RESULTS: A total of 715 patients were included in the study. Mean age and diabetes duration were 66.6 and 17.4 years, respectively. Of these, 286 patients (40.0%) had been diagnosed with CVD, mostly ischemic heart disease (50.4%). All patients had at least one CV risk factor. CVD was significantly associated with hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol, hypertriglyceridemia and smoking. During the three years prior to study inclusion, the incidence of hyperglycemic episodes and T2D complications increased among patients with established CVD, but the numbers of hospitalization episodes and specialist appointments remained stable. An improvement was observed in key cardiometabolic risk factors. CONCLUSIONS: Our study revealed a high prevalence of CVD and CV risk factors among a sample of T2D patients in a hospital setting. Patients with established CVD seem to be adequately managed but further efforts are needed at the prevention stage for better control of risk factors and morbidity.

Parathyroid carcinoma: Single centre experience.

OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

The Effect of Changing Regular Care Provider in Type 2 Diabetes Mellitus: A Retrospective Study.

INTRODUCTION: Several studies have demonstrated the benefits of having a regular care provider on the control of chronic diseases. Our study intends to clarify the effects of the transition to a new diabetologist on metabolic control in type 2 diabetes patients followed-upin a tertiary care setting. MATERIAL AND METHODS: Retrospective study performed in an endocrinology outpatient clinic. We randomly selected 50 type 2 diabetespatients for a control group and 50 for a study group. In the study group, we registered the last evaluation before the physician change (year 0) and at the end of each year (year 1, 2 and 3) with the new doctor. Evaluated variables - body mass index, blood pressure, HbA1c and lipid profile - were compared yearly between groups. RESULTS: There was a decrease in mean HbA1c levels (0.4% - 0.5%, p < 0.05) in year 1 and 2 when compared to year 0 in the study group, but not in the control group. This reduction was superior (0.5% - 1.4%, p < 0.05) in patients whose baseline HbA1c was greater than 7%. The other studied variables did not vary significantly throughout follow-up in either group. DISCUSSION: In our study the transition to a different type 2 diabetes physician was associated with a decrease in mean HbA1c and this difference was greater in less well controlled patients. CONCLUSION: Switching to a new physician may not be harmful and may actually have benefits for the glycemic control of some type 2 diabetes patients.

Introdução: Vários estudos já demonstraram ser benéfico para o controlo de várias doenças crónicas manter seguimento com um mesmo médico assistente de forma prolongada. O nosso estudo pretende esclarecer os efeitos no controlo da doença associados à transição para um novo médico diabetologista em doentes diabéticos tipo 2 seguidos em cuidados de saúde terciários. Material e Métodos: Estudo retrospetivo realizado num serviço de consultas externas de Endocrinologia. Seleccionámos aleatoriamente 50 doentes diabéticos tipo 2 para um grupo controlo e 50 para um grupo estudo. No grupo estudo, registámos a última avaliação antes da mudança de médico (ano 0) e no fim de cada ano (ano 1, 2 e 3) com o novo médico. As variáveis avaliadas ­ índice de massa corporal, tensão arterial, HbA1c e perfil lipídico ­ foram comparadas anualmente entre os grupos. Resultados: Verificou-se uma diminuição na média da HbA1c (0,4% ­ 0,5%, p< 0,05) no ano 1 e 2 por comparação com o ano 0 no grupo estudo, mas não no grupo controlo. Esta redução foi maior (0,5% ­ 1,4%, p < 0,05) em doentes cuja HbA1c basal era superior a 7%. As outras variáveis estudadas não variaram significativamente em qualquer um dos grupos. Discussão: Neste estudo, a transição de doentes diabéticos tipo 2 para um novo médico diabetologista assistente associou-se a uma diminuição na média de HbA1c, de forma mais marcada em doentes com menor controlo metabólico. Conclusão: A mudança para um novo médico diabetologista assistente pode não ser prejudicial e inclusivamente associar-se a benefícios para o controlo glicémico de alguns doentes diabéticos tipo 2.

Renal function markers and metformin eligibility.

BACKGROUND: Metformin is the cornerstone of the pharmacological therapy for type 2 diabetes mellitus (T2DM). It belongs to the biguanide class of drugs and it improves hepatic insulin resistance and enhances GLP-1 and peptide YY secretion. Despite being considered safe regarding hypoglycemic risk, renal dysfunction remains the main obstacle to its use due to the underlying risk of lactic acidosis. In the recent past many authors used creatinine values as the decisive marker when it came to choose between pharmacological agents in DM. Serum creatinine values equal or above 1.4 and 1.5 mg/dL were considered contraindications for metformin use in women and men respectively. Nowadays, creatinine is not the only surrogate of renal dysfunction and formulas such as the MDRD and CKD-EPI, that besides serum creatinine also include variables such as gender, age and race, have replaced serum creatinine as the standard for renal function assessment. Furthermore, since the associations between metformin and lactic acidosis in renal disease are not straightforward, its use has been considered safe down to creatinine clearances of 30 mL/min/1.73 m2. The authors describe a population with T2DM being treated with metformin and evaluate the impact of the solo evaluation of serum creatinine or CKD-EPI on biguanide prescription. METHODS: Retrospective, observational, single-center study. All type 2 diabetic patients with regular follow up in a Central University Hospital Endocrinology-Diabetology Outpatient Clinic who were being treated with metformin and had at least 2 creatinine and estimated glomerular filtration rate (eGFR) measurements in the last decade were included. Patients were stratified according to renal function-based metformin contraindication criteria: creatinine group included patients with serum creatinine levels above 1.4 and 1.5 mg/dL in women and men respectively, and eGFR group included patients with eGFR below 30 mL/min/1.73 m2. The entire population and both groups are described and compared regarding comorbidities, demographic and laboratory data. The authors report the impact of each renal function marker (serum creatinine or eGFR) when used solo regarding metformin prescription eligibility. RESULTS: A total of 2218 patients (61.3% females) with a mean age of 70±12 years is studied. Mean diabetes duration was 11.8±8.8 years. No cases with an eGFR below 30 mL/min/1.73 m2 were identified. On the other hand, in patients with GFR greater than 30 mL/min/1.73 m2, creatinine alone would contraindicate therapy in 274 patients (12.4% of the study population). Comparing Stage 3 chronic kidney disease patients without creatinine contraindication criteria with those with creatinine based contraindication, the data reveals that a higher prevalence of males, with longer diabetes duration, higher target organ damage (cerebrovascular disease, peripheral artery disease, heart failure, neuropathy and retinopathy) and with worse glycemic control were prevalent more in the elevated creatinine group. The use of serum creatinine as the single marker for renal function would significantly reduce metformin eligibility (OR=0.88, 95% CI: 0.8-0.95, P=0.002). CONCLUSIONS: Metformin is the first line pharmacological agent in type 2 diabetes mellitus patients, being associated with significant HbA1c reductions and improvements in both micro and macrovascular outcomes. Avoiding its use due to imprecise renal function markers would potentially render the patient deprived of optimal pharmacological therapy for T2DM. Creatinine contraindication criteria alone are associated with unnecessary under prescription of metformin.

[Vitamin B12 Deficiency in Type 2 Diabetes Mellitus]. / Défice de Vitamina B12 na Diabetes Mellitus Tipo 2.

INTRODUCTION: Type 2 diabetes mellitus is a common disease, affecting up to 13.1% of the Portuguese population. In addition to the known micro and macrovascular complications, drug side effects constitute a major concern, leading to changes in the treatment guidelines, which favor safety over efficacy. Metformin is the first-line pharmacological treatment for most patients with type 2 diabetes mellitus; however, it has been associated with vitamin B12 deficiency in up to 30% of treated patients. The authors describe the prevalence of vitamin B12 deficiency in a diabetic population and explore the possible underlying factors. MATERIAL AND METHODS: Retrospective, observational study. Clinical and laboratory data of type 2 diabetes mellitus patients whose vitamin B12 status was evaluated in the last decade (2005 - 2016) were analyzed. Patients with known malabsorptive syndromes or having undergone bariatric surgery were excluded from the study. Statistical analysis of the data was done and the results were considered statistically significant at p values < 0.05. RESULTS: The study included a total of 1007 patients (58% women) with a mean age of 66.4 ± 12.2 years and 11 ± 10.4 years of type 2 diabetes mellitus duration. These patients had a high prevalence of complications: diabetic renal disease 47.7%, neuropathy 9.2%, retinopathy 14.9%, coronary artery disease 8.4%, cerebrovascular disease 10.9%, and peripheral arterial disease 5.5%. Vitamin B12 deficiency (< 174 ng / dL) was present in 21.4% of the population and this subgroup was older (68.4 vs 65.8 years, p = 0.006), had a longer type 2 diabetes mellitus duration (13.35 vs 10.36 years; p = 0.001), higher prevalence of retinopathy (20.9% vs 13.3%; p = 0.005) and thyroid dysfunction (34% vs 23.7%; p = 0.002). Vitamin B12 deficiency was also more frequent in patients treated with metformin (24.7% vs 15.8%; p = 0.017), antiplatelet agents (25.4% vs 16.2%, p < 0.001), and calcium channel blockers (26.8% vs 18.2%; p = 0.001). After adjustment for possible confounders, the variables associated with B12 deficiency were: metformin, hypothyroidism, age and type 2 diabetes mellitus duration. DISCUSSION: Despite the retrospective design, the results report a high prevalence of vitamin B12 deficiency in the type 2 diabetic population. This study also demonstrates that the B12 deficiency risk is higher in older people, with longer diabetes mellitus duration, hypothyroidism and treated with metformin. CONCLUSION: Further studies are needed to identify the risk factors for the B12 deficit. The recognition of these variables will contribute to optimize the screening and prevention of the B12 deficiency in type 2 diabetes mellitus.

Introdução: A diabetes mellitus tipo 2 é uma entidade comum, afetando até 13,1% da população portuguesa. Para além das conhecidas complicações micro e macrovasculares, as iatrogenias medicamentosas tornaram-se uma crescente preocupação contribuindo para as observadas alterações das recomendações terapêuticas, que cada vez mais privilegiam a segurança em detrimento da eficácia. A metformina é o agente farmacológico de primeira linha na maioria dos doentes com diabetes mellitus tipo 2, contudo, está descrita a associação com défice de vitamina B12 em até 30% dos doentes. Os autores descrevem a prevalência de défice de vitamina B12 numa população diabética e os possíveis fatores associados à mesma. Material e Métodos: Foi efectuado um estudo retrospectivo, observacional no qual foram registados os dados clínico-laboratoriais de doentes com diabetes mellitus tipo 2 com doseamentos de B12 na última década (2005 - 2016). Foram excluídos doentes submetidos a cirurgia bariátrica e com síndromes malabsorptivos conhecidos. Foi efectuada análise estatística dos dados e os resultados foram considerados estatisticamente significativos para p < 0,05. Resultados: Foram estudados 1007 doentes com uma idade média de 66,4 ± 12,2 anos e 11 ± 10,4 anos de evolução da diabetes mellitus tipo 2, das quais 58% eram mulheres. Apresentavam uma elevada prevalência de complicações: doença renal diabética 47,7%, neuropatia 9,2%, retinopatia 14,9%, doença coronária 8,4%, doença vascular cerebral 10,9% e doença arterial periférica 5,5%. O défice de B12 (< 174 ng/dL) foi documentado em 21,4% da população e neste subgrupo constatou-se uma idade mais avançada (68,4 vs 65,8 anos; p = 0,006), maior duração da diabetes (13,35 vs 10,36 anos; p = 0,001), maior prevalência de retinopatia (20,9% vs 13,3%; p = 0,005) e disfunção tiroideia (34% vs 23,7%; p = 0,002). O défice de B12 foi mais frequente nos doentes expostos à metformina (24,7% vs 15,8%; p = 0,017), antiagregantes (25,4% vs 16,2%; p < 0,001) e bloqueadores dos canais de cálcio (26,8% vs 18,2%; p = 0,001). Após ajuste para factores de confundimento, a metformina, hipotiroidismo, idade e anos de evolução da diabetes mellitus tipo 2 mantiveram uma associação estatisticamente significativa, o que não se verificou com a retinopatia e os bloqueadoresdos canais de cálcio. Discussão: Apesar do desenho retrospectivo, os resultados alertam para a elevada prevalência do défice de vitamina B12 na população com diabetes mellitus tipo 2. O presente estudo demonstra que o risco parece ser maior em populações com idades mais avançadas, com maior tempo de evolução da diabetes mellitus, com hipotiroidismo e sob metformina. Conclusão: São necessários mais estudos para que se possam identificar os factores de risco para o défice de B12. O reconhecimento dessas variáveis contribuirá para optimizar o rastreio e prevenção do défice de B12 na diabetes mellitus tipo 2.

Severe Cushing's syndrome and bilateral pulmonary nodules: beyond ectopic ACTH.

Cushing's syndrome is a rare disease that results from prolonged exposure to supraphysiological levels of glucocorticoids. Severe and rapidly progressive cases are often, but not exclusively, attributable to ectopic ACTH secretion. Extreme hypercortisolism usually has florid metabolic consequences and is associated with an increased infectious and thrombotic risk. The authors report on a case of a 51-year-old male that presented with severe Cushing's syndrome secondary to an ACTH-secreting pituitary macroadenoma, whose diagnostic workup was affected by concurrent subclinical multifocal pulmonary infectious nodules. The case is noteworthy for the atypically severe presentation of Cushing's disease, and it should remind the clinician of the possible infectious and thrombotic complications associated with Cushing's syndrome. LEARNING POINTS: Severe Cushing's syndrome is not always caused by ectopic ACTH secretion.Hypercortisolism is a state of immunosuppression, being associated with an increased risk for opportunistic infections.Infectious pulmonary infiltrates may lead to imaging diagnostic dilemmas when investigating a suspected ectopic ACTH secretion.Cushing's syndrome carries an increased thromboembolic risk that may even persist after successful surgical management.Antibiotic and venous thromboembolism prophylaxis should be considered in every patient with severe Cushing's syndrome.

Diabetes insipidus and hypopituitarism in HIV: an unexpected cause.

Central diabetes insipidus (DI) is a rare clinical entity characterized by low circulating levels of antidiuretic hormone (ADH) presenting with polyuria and volume depletion. Pituitary surgery is the most common cause of central DI in adults. Pituitary and hypothalamic disease, particularly invasive neoplasms, rarely cause DI, being idiopathic cases responsible for the majority of non-surgical cases. HIV patients, especially those with poor virulogical control, are prone to the development of CNS neoplasms, particularly lymphomas. These neoplasms usually become manifest with mass effects and seizures. Central DI and hypopituitarism are uncommon initial manifestations of primary CNS lymphomas. The authors describe the case of 29-year-old female, HIV-positive patient whose CNS lymphoma presented with DI. LEARNING POINTS: Central diabetes insipidus has multiple causes and central nervous system lymphomas are not often considered in the differential diagnosis due to their low prevalence.Accurate biochemical diagnosis should always be followed by etiological investigation.The HIV population is at risk for many neoplasms, especially CNS lymphomas.New-onset polyuria in an HIV-positive patient in the absence of focal neurological signs should raise the suspicion for a central nervous system process of neoplastic nature.This clinical entity usually constitutes a therapeutical challenge, often requiring a multidisciplinary approach for optimal outcome.

Down syndrome and Moyamoya disease: unusual cause of stroke.

Down syndrome is a frequent clinical entity, being considered one of the most frequent chromosomal aberrations. It is characterised by a typical clinical phenotype and is associated with a heterogeneous group of organ and system-specific abnormalities. The cardiovascular system is commonly affected and if so, it may be associated with an increased morbidity and mortality. Cerebrovascular events in patients with Down syndrome are multifactorial, being possibly related to congenital heart disease, vascular malformations and traditional cardiovascular risk factors. Moyamoya disease is a rare chronic occlusive vascular disease causing stenosis of the distal portion of the internal carotid artery, which has been associated with Down syndrome. The authors report the case of a 26-year-old woman with Down syndrome who presented with an acute stroke secondary to Moyamoya disease. The case is noteworthy for the rarity of this clinicopathological entity, and serves as a reminder for the possible association between these two conditions.

Diabetes mellitus and acquired haemophilia: new association?

Diabetes mellitus encompasses a group of highly prevalent carbohydrate metabolic disorders with an increasing incidence. Some subtypes are thought to be associated with other immune-mediated diseases. Acquired haemophilia on the other hand is a quite rare autoimmune disease that is thought to be secondary to the emergence of inhibiting anticoagulation factor VIII antibodies (inhibitors) in patients with previously normal haemostatic function. More recently, numerous different diseases have been associated with acquired haemophilia namely immune-mediated diseases, drugs and solid and haematologic neoplasms. The authors report on a case of a patient with new onset acquired haemophilia arising in the setting of diabetic ketoacidosis.

Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Thyroid.

Thyroid lymphomas are rare clinical entities that may result from either the primary intrathyroid de novo or secondary thyroid gland involvement of a lymphoma. Among these, the Hodgkin's subtype is quite uncommon, accounting for 0.6-5% of all thyroid malignancies. The authors report on a 76-year-old female presenting with a thyroid nodule that, upon surgical excision, was found to be a nodular lymphocyte predominant Hodgkin lymphoma of the thyroid. So far, thyroid involvement by this variant has never been reported. Upon reporting on this clinical case, the authors emphasize the difficulties usually found in establishing the diagnosis and in defining the best management strategy. A thorough review of the available literature is done.