Abnormalities Of Thyroid Hormone Metabolism During Systemic Illness: The Low T3 Syndrome In Different Clinical Settings

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Thyroid hormone abnormalities are common in critically ill patients. For over three decades, a mild form of these abnormalities has been described in patients with several diseases under outpatient care. These alterations in thyroid hormone economy are a part of the nonthyroidal illness and keep an important relationship with prognosis in most cases. The main feature of this syndrome is a fall in free triiodothyronine (T3) levels with normal thyrotropin (TSH). Free thyroxin (T4) and reverse T3 levels vary according to the underlying disease. The importance of recognizing this condition in such patients is evident to physicians practicing in a variety of specialties, especially general medicine, to avoid misdiagnosing the much more common primary thyroid dysfunctions and indicating treatments that are often not beneficial. This review focuses on the most common chronic diseases already known to present with alterations in serum thyroid hormone levels. A short review of the common pathophysiology of the nonthyroidal illness is followed by the clinical and laboratorial presentation in each condition. Finally, a clinical case vignette and a brief summary on the evidence about treatment of the nonthyroidal illness and on the future research topics to be addressed are presented.FAPESP (Sao Paulo Research Support Foundation) [2013/03295-1]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Long-term Follow-up Of An 8-year-old Boy With Insulinoma As The First Manifestation Of A Familial Form Of Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.54754-6

Euthyroid sick syndrome in patients with type 2 diabetes mellitus : correlation between inflammatory markers, glycemic control and relationship with cardiovascular disease

Orientadores: Denise Engelbrecht Zantut Wittmann, Marcos Antonio TambasciaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: A síndrome do eutireoidiano doente (SED) é uma entidade caracterizada pela queda das concentrações sanguíneas de triiodotironina nas formas total e livre e aumento da forma reversa. Ocorre principalmente em pacientes portadores de doenças graves e agudas, particularmente dentre aqueles internados em unidade de terapia intensiva. Há descrição desta síndrome em portadores de Diabetes Mellitus, particularmente sob controle glicêmico inadequado. Objetivos: Avaliar as alterações dos hormônios tireoidianos em portadores de DM sob cuidado ambulatorial e a correlação entre concentrações de hormônios tireoidianos e controle glicêmico, presença de complicações crônicas (neuropatia, nefropatia, retinopatia) e marcadores de inflamação sistêmica subclínica, bem como sua relação com presença de eventos cardiovasculares. Metodologia: Estudo transversal avaliando 52 pacientes com diabetes tipo 2 e 52 indivíduos sem diabetes, entre 40 e 75 anos de idade, pareados por sexo, idade e índice de massa corporal. Avaliaram-se dados clínicos e antropométricos, concentrações séricas de hormônios tireoidianos e proteína C reativa, bem como exames laboratoriais que refletem o perfil lipídico e controle glicêmico. Resultados: Cerca de 73% dos pacientes com diabetes e 40% dos indivíduos sem DM apresentaram concentrações séricas diminuídas de T3 total; 25% dos pacientes e apenas 2% dos indivíduos sem DM apresentaram concentrações diminuídas de T3 livre. As concentrações séricas de T3 total (p<0,001), T3 livre (p<0,001) e T4 total (p=0,006) estavam diminuídas em comparação aos de indivíduos sem diabetes. As concentrações de T3 reverso não apresentaram diferença entre os dois grupos. Pacientes com diabetes apresentaram T4 livre mais elevado (p=0,033). As concentrações de T3 reverso foram significativamente diferentes apenas quando comparados os indivíduos com eventos cardiovasculares prévios com aqueles sem tal histórico (p=0,002 dentre os pacientes com diabetes e p=0,037 em relação aos indivíduos sem diabetes). A prevalência de eventos cardiovasculares foi de 25%. Houve correlação entre as concentrações de proteína C reativa e a relação cintura/quadril (p = 0,035) e as concentrações de T3 reverso (p = 0,001). Não houve correlação entre os hormônios tireoidianos e a concentração de hemoglobina glicada. No grupo de pacientes com diabetes, os fatores associados à presença de eventos cardiovasculares na análise multivariada foram sexo masculino (p=0,028) e T3 reverso elevado (p=0,01). A análise da curva ROC do T3 reverso em relação à detecção de eventos cardiovasculares mostrou uma sensibilidade de 84,6% e especificidade de 71,8% (p=0,002), similar à performance da proteína C reativa (sensibilidade = 76,9%; especificidade = 64,1%; p=0,022). Conclusões: O T3 total apresentou-se diminuído em 40% dos indivíduos sem DM e poderia superestimar o diagnóstico de SED se analisado como único parâmetro. Adicionalmente, as concentrações séricas de T3 total e livre e T4 total foram mais baixas no grupo de pacientes com diabetes em relação ao grupo controle. O aumento das concentrações de T3 reverso associou-se à presença de doença cardiovascular e à proteína C reativa elevada. O T3 reverso apresentou correlação com as concentrações de proteína C reativa e foi um preditor independente para eventos cardiovascularesAbstract: Introduction: The non-thyroidal illness is an entity characterized by reduced serum levels of total and free triiodothyronine and a rise in its reverse form. It occurs mainly in critically ill patients. There are descriptions of this syndrome in patients with Diabetes Mellitus, especially those under inadequate glycemic control. Objectives: Evaluate the abnormalities in thyroid hormone levels in individuals with diabetes under standard outpatient care and the correlation of thyroid hormone levels with glycemic control, presence of chronic complications (neuropathy, nephropathy and retinopathy) and subclinical systemic inflammation, as well as its relation with the presence of previous cardiovascular events. Methodology: Cross sectional study involving 52 patients with type 2 diabetes and 52 individuals without the diabetes, between 40 and 75 years of age paired by age, gender and body mass index. We evaluated clinical and anthropometric data, serum levels of thyroid hormones and Creactive protein, as well as laboratory parameters that reflect the lipid profile and glycemic control. Results: Approximately 73% of the patients with diabetes and 40% of individuals without diabetes presented reduced serum levels of total T3. Nearly 25% of the patients and only 2% of the individuals without diabetes presented reduced levels of free T3. The levels of total T3 (p<0.001), free T3 (p<0.001) and total T4 (p=0.006) were lower in patients with diabetes compared with those without diabetes. The levels of reverse T3 did not present any difference between both groups. Patients with diabetes presented higher levels of free T4 (p=0.033). The levels of reverse T3 were significantly different only when comparing individuals with previous cardiovascular events with those without this characteristic (p=0.002 for patients with diabetes and p=0.037 for individuals without diabetes). The prevalence of cardiovascular disease was 25%. There was a correlation between serum levels of C-reactive protein and waist/hip ratio (p=0.035) and levels of reverse T3 (p=0.001). There was no correlation between thyroid hormone levels and glycated hemoglobin. In the group of patients with diabetes, the factors associated with the presence of cardiovascular events on multivariate analysis were male gender (p=0.028) and elevated reverse T3 levels (p=0.01). The ROC curve analysis of reverse T3 for detection of cardiovascular events yielded a sensitivity of 84.6% and a specificity of 71,8% (p=0.002), which was similar to the performance of C-reactive protein (sensitivity = 76.9%; specificity = 64.1%; p=0.022). Conclusions: Total T3 was reduced in 40% of the individuals without diabetes and could overestimate the diagnosis of de non-thyroidal illness syndrome if analyzed as the sole parameter. Additionally, the levels of total and free T3 and total T4 were lower in the group of patients with diabetes than in the control group. Higher reverse T3 levels were associated to the presence of cardiovascular disease and increased C-reactive protein levels. Reverse T3 was an independent predictor of cardiovascular eventsMestradoClinica MedicaMestre em Clinica Medic

Relation of thyroid hormone abnormalities with subclinical inflammatory activity in patients with type and type 2 diabetes mellitus

Orientador: Denise Engelbrecht Zantut WittmannTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: A síndrome do Eutireoidiano doente (SED) caracteriza-se por uma concentração sérica diminuída de triiodotironina e, por vezes, tiroxina. Pode ser observada principalmente em pacientes com doenças agudas e graves, onde se relaciona a uma atividade inflamatória aumentada. Foi descrita mais recentemente em uma variedade de condições clínicas ambulatoriais, inclusive o Diabetes Mellitus (DM). Nestes casos, é relacionada ao mau controle glicêmico. Objetivos: Comparar as características clínicas, perfil hormonal tireoidiano e de inflamação sistêmica entre pacientes portadores de DM tipo 1 e tipo 2 e grupos de indivíduos hígidos sem DM, pareados por sexo, idade e índice de massa corporal (IMC). Metodologia: Estudo transversal avaliando um total de 258 indivíduos assim divididos: 70 pacientes com DM2, 55 pacientes com DM1 e dois grupos de controle com 70 e 63 indivíduos sem DM para os pacientes com DM2 e DM1 respectivamente, pareados por sexo, idade e IMC. Avaliaram-se dados clínicos e antropométricos nos 4 grupos, bem como concentrações séricas de hormônios tireoidianos, TSH, T3 reverso; e proteína C reativa, interleucina-6 (IL-6) e proteína amiloide sérica (SAA) como marcadores inflamatórios. As relações T4livre/T3 livre, T3 livre/T3 reverso e T4 livre/T3 reverso foram usadas como marcadores alternativos para a atividade das desiodases. Resultados: O T3 total e livre mostrou-se diminuído nos pacientes com DM1 e DM2 quando comparados aos seus respectivos grupos de controle (todos p<0,001). O grupo DM1 mostrou concentrações de TSH e T4 total menores que seu grupo de controle (p=0,001 para ambos) e o grupo DM2 concentrações de T4 livre maior que seu grupo de controle (p<0,001). ...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital.Abstract: Introduction: The non-thyroidal illness is characterized by low serum levels of triiodothyronine and, sometimes, thyroxine. It is mainly observed in patients with severe acute diseases, where it is linked to an increased inflammatory activity. Recently, it has been described in a variety of chronic ambulatory conditions, including diabetes mellitus (DM). In these cases, it is related to poor glycemic control. Objectives: Compare the clinical characteristics, thyroid hormone profile e systemic inflammatory markers between patients with type 1 and type 2 diabetes and healthy, non-diabetic individuals, paired by sex, age and body mass index (BMI). Methodology: This was a cross-sectional study involving 258 subjects divided in four groups: 70 patients with T2DM, 55 with T1DM and two control groups with 70 and 63 individuals without DM paired by age, sex and MBI with the T2DM and T1DM patients, respectively. Clinical and anthropometrical data were evaluated in all groups, as well as serum thyroid hormones TSH, reverse T3, C-reactive protein, interleukin-6 (IL-6) and serum amyloid protein (SAA) as markers of inflammation. The relations free T4/ free T3, free T3/ reverse T3 and free T4/ reverse T3 were used as surrogate markers of deiodinase activities. Results: Total and free T3 were lower in patients with T1DM and T2DM compared to their respective control groups (p<0.001 for all)...Note: The complete abstract is available with the full electronic documentDoutoradoClinica MedicaDoutor em Clínica Médica2010/08854-0, 2013//03295-1FAPES

Abnormalities of Thyroid Hormone Metabolism during Systemic Illness: The Low T3 Syndrome in Different Clinical Settings

Thyroid hormone abnormalities are common in critically ill patients. For over three decades, a mild form of these abnormalities has been described in patients with several diseases under outpatient care. These alterations in thyroid hormone economy are a part of the nonthyroidal illness and keep an important relationship with prognosis in most cases. The main feature of this syndrome is a fall in free triiodothyronine (T3) levels with normal thyrotropin (TSH). Free thyroxin (T4) and reverse T3 levels vary according to the underlying disease. The importance of recognizing this condition in such patients is evident to physicians practicing in a variety of specialties, especially general medicine, to avoid misdiagnosing the much more common primary thyroid dysfunctions and indicating treatments that are often not beneficial. This review focuses on the most common chronic diseases already known to present with alterations in serum thyroid hormone levels. A short review of the common pathophysiology of the nonthyroidal illness is followed by the clinical and laboratorial presentation in each condition. Finally, a clinical case vignette and a brief summary on the evidence about treatment of the nonthyroidal illness and on the future research topics to be addressed are presented

Heterotaxy syndrome with agenesis of dorsal pancreas and diabetes mellitus: case report and review of the literature

Heterotaxy syndrome (HS) is a rare congenital condition with multifactorial heritance, characterized by an abnormal arrangement of thoraco-abdominal organs and vessels. Patients present with multiple cardiac, gastrointestinal, hepatosplenic, pancreatic, renal, neurological and skeletal disorders without any pathognomonic alteration. Despite the described increased risk of diabetes mellitus (DM) in patients with altered pancreatic anatomy, just one case was reported in Korea regarding the association of HS and DM in a 13-year-old girl. Our report refers to a 40-year-old female Brazilian patient with a history of DM and HS with polysplenia and agenesis of dorsal pancreas without cardiac abnormalities. She presented a worsening glycemic control associated with weight gain and signs of insulin resistance. After a proper clinical management of insulin and oral medications, our patient developed an improvement in glycemic control. Although it is a rare disease, HS with polysplenia and pancreatic disorders can be associated with an increased risk of DM. This case highlights the importance of investigating DM in patients with HS, especially those with pancreatic anatomical disorders, for proper clinical management of this rare condition63444544