A practical contemporary approach to decision-making on subclinical hypothyroidism

ABSTRACT Subclinical hypothyroidism (Shypo) is an increasingly frequent condition in common medical practice. Its diagnosis continues to pose a challenge since a series of non-thyroidal and temporary conditions can elevate serum TSH levels. In addition, the consequences of Shypo are still up for debate. Although detrimental cardiovascular effects have been consistently demonstrated in the young, they are less evident in older adults (65-79 years), and even more so in the oldest old (≥80 years). In the absence of evidence of any benefits of treating Shypo in patients' clinical manifestations and unfavorable outcomes, the most effective decision-making approach should include a thorough investigation of the patient's condition integrating all relevant clinical data, such as TSH levels, age, quality of life, comorbidities, cardiovascular risk, safety, and personal preferences. The decision-making process needs to take into account the risk of levothyroxine overtreatment and the resulting adverse consequences, such as reduction of bone mineral density, heart failure, and atrial fibrillation. Hence, current evidence suggests that individuals with TSH > 10 mU/L, who test positive for TPO Ab or are symptomatic may benefit from levothyroxine treatment. However, a more cautious and conservative approach is required in older (≥65 years of age), and oldest-old (≥80 years) patients, particularly those with frailty, in which the risk of treatment can outweigh potential benefits. The latter may benefit from a wait-and-see approach.

Hipotiroidismo subclínico en pacientes con enfermedad renal crónica que concurren a centros de salud pública de la ciudad de Posadas, Misiones / Sub-clinical hypothyroidism in patients with chronic renal disease attending health centres in Posadas, Misiones, Argentina

Los objetivos del presente trabajo fueron: 1) determinar la frecuencia de hipotiroidismo subclínico (HSC) en pacientes con enfermedad renal crónica (ERC), y 2) evaluar los cambios en la función renal de pacientes con ERC e HSC luego del tratamiento con levotiroxina. Se estudió a 182 pacientes, 99 con ERC y 83 sin ERC (grupo control), entre 20 y 70 años de edad, de ambos sexos, atendidos en centros de salud y consultorios hospitalarios de Posadas, Misiones. La frecuencia de HSC en el grupo con ERC fue del 28,3% y en el grupo control 14,5% (p = 0,025). Los pacientes con ERC e HSC fueron derivados al servicio de endocrinología, donde luego de 3 meses de tratamiento con levotiroxina, se revaluó la función renal, observando en todos los pacientes disminución en los niveles de creatinina sérica y aumento del índice de filtrado glomerular. Sobre la base de estos hallazgos se podría recomendar el estudio de la función tiroidea a todo paciente con ERC de causa desconocida, considerando al HSC entre las posibles causas de deterioro de la función renal.

The objectives of the present study were: 1) to determine the frequency of Subclinical Hypothyroidism (SCH) in patients with Chronic Renal Disease (CKD), and 2) to evaluate the changes in renal function in patients with CKD and SCH after treatment with levothyroxine. A total of 182 patients were studied, 99 with CKD and 83 without CKD (control group), with ages between 20 and 70 years old, of both sexes, attending health centres and hospital clinics in Posadas, Misiones, Argentina. The frequency of SCH was 28.3% in the CKD group, and 14.5% in the control group (P=.025). Patients with CKD and SCH were referred to medical endocrinology, where after three months of treatment with levothyroxine, renal function was evaluated, after which a decrease in serum creatinine levels and an increase in the glomerular filtration rate were observed in all patients. Based on these findings, the study of thyroid function should be recommended for all patients with CKD of unknown cause, considering SCH among the possible causes of impaired renal function.

Gender, race and socioeconomic influence on diagnosis and treatment of thyroid disorders in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Thyroid diseases are common, and use of levothyroxine is increasing worldwide. We investigated the influence of gender, race and socioeconomic status on the diagnosis and treatment of thyroid disorders using data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of civil servants (35-74 years of age) from six Brazilian cities. Diagnosis of thyroid dysfunction was by thyrotropin (TSH), and free thyroxine (FT4) if TSH was altered, and the use of specific medications. Multivariate logistic regression models were constructed using overt hyperthyroidism/hypothyroidism and levothyroxine use as dependent variables and sociodemographic characteristics as independent variables. The frequencies of overt hyper- and hypothyroidism were 0.7 and 7.4%, respectively. Using whites as the reference ethnicity, brown, and black race were protective for overt hypothyroidism (OR=0.76, 95%CI=0.64-0.89, and OR=0.53, 95%CI=0.43-0.67, respectively, and black race was associated with overt hyperthyroidism (OR=1.82, 95%CI=1.06-3.11). Frequency of hypothyroidism treatment was higher in women, browns, highly educated participants and those with high net family incomes. After multivariate adjustment, levothyroxine use was associated with female gender (OR=6.06, 95%CI=3.19-11.49) and high net family income (OR=3.23, 95%CI=1.02-10.23). Frequency of hyperthyroidism treatment was higher in older than in younger individuals. Sociodemographic factors strongly influenced the diagnosis and treatment of thyroid disorders, including the use of levothyroxine.

Should a family history of papillary thyroid carcinoma indicate more aggressive therapy in patients with this tumor? / História familiar de carcinoma papilífero de tireoide deve indicar terapia mais agressiva em pacientes com este tumor?

Objective To determine whether the currently recommended therapy for papillary thyroid carcinoma (PTC) that show no classical factors indicating a poor prognosis is also effective in cases with a family history of this tumor. Subjects and methods: Forty-two patients were studied; 10 were submitted to lobectomy and 32 to total thyroidectomy, including 23 without lymph node dissection and 9 with lymph node dissection. None of the patients received radioiodine or was maintained under TSH suppression. Results No case of recurrence was detected by imaging methods and there was no increase in thyroglobulin or antithyroglobulin antibodies during follow-up (24 to 72 months). Conclusion The treatment usually recommended for patients with PTC does not need to be modified in the presence of a family history of this tumor if no factors indicating a poor prognosis are present (tumor ≤2 cm, non-aggressive histology, no extensive extrathyroid invasion or important lymph node involvement, complete tumor resection, no evidence of persistent disease after surgery). .

Objetivo Avaliar se a terapia atualmente recomendada para o carcinoma papilífero de tireoide (CPT) sem fatores clássicos de pior prognóstico é efetiva também nos casos em que existe história familiar deste tumor. Sujeitos e métodos: Foram avaliados 42 pacientes; dez foram tratados com lobectomia e 32 com tireoidectomia total, sendo 23 sem dissecção de linfonodos e 9 com dissecção linfonodal. Nenhum paciente recebeu radioiodo ou foi mantido com TSH suprimido. Resultados Nenhuma recidiva nos métodos de imagem foi observada, nem incremento da tireoglobulina ou anticorpos antitireoglobulina durante o seguimento (24 a 72 meses). Conclusão Em pacientes com CPT, sem fatores de pior prognóstico (tumor ≤2 cm, histologia não agressiva, sem invasão extratireoidiana extensa ou acometimento linfonodal importante, ressecção tumoral completa, sem indícios de doença persistente após a cirurgia), o tratamento usualmente recomendado não precisa ser modificado quando há história familiar desse tumor. .

Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia / The Brazilian consensus for the clinical approach and treatment of subclinical hypothyroidism in adults: recommendations of the thyroid Department of the Brazilian Society of Endocrinology and Metabolism

INTRODUÇÃO: O hipotireoidismo subclínico (HSC), definido por concentrações elevadas do TSH em face de níveis normais dos hormônios tireoidianos, tem elevada prevalência no Brasil, particularmente entre mulheres e idosos. Embora um número crescente de estudos venha associando o HSC com maior risco de doença arterial coronariana e de mortalidade, não há ensaio clínico randomizado sobre o benefício do tratamento com levotiroxina na redução dos riscos e o tratamento permanece controverso. OBJETIVO: Este consenso, patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia e desenvolvido por especialistas brasileiros com vasta experiência clínica em tireoide, apresenta recomendações baseadas em evidências para uma abordagem clínica do paciente com HSC no Brasil. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, a busca das evidências disponíveis na literatura foi realizada inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força da evidência, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão e a experiência brasileira. RESULTADOS: Os temas abordados foram definição e diagnóstico, história natural, significado clínico, tratamento e gestação, que resultaram em 29 recomendações para a abordagem clínica do paciente adulto com HSC. CONCLUSÃO: O tratamento com levotiroxina foi recomendado para todos os pacientes com HSC persistente com níveis séricos do TSH > 10 mU/L e para alguns subgrupos especiais de pacientes.

INTRODUCTION: Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial. OBJECTIVE: This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil. MATERIALS AND METHODS: After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience. RESULTS: The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH. CONCLUSION: Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values > 10 mU/L and for certain patient subgroups.

Disfunção tiróidea e amiodarona / Thyroid dysfunction and amiodarone

Apesar de a maioria dos doentes tratados com amiodarona permanecer em eutiroidia, alguns desenvolvem hipertiroidismo (HPEIA) ou hipotiroidismo (HPOIA) induzidos pela amiodarona. Os autores apresentam uma análise retrospectiva dos processos de dez doentes com disfunção tiróidea induzida pela amiodarona. Verificou-se que seis doentes eram mulheres e que o tempo médio de toma da amiodarona foi de 17,7 meses. O HPOIA foi o mais frequente (seis doentes). Dos doentes com HPEIA, dois tinham HPEIA tipo 2, um tipo 1 e um tipo 3. Sintomas sugestivos de disfunção tiróidea ocorreram em cinco doentes, a maioria com HPOIA. No HPEIA, a clínica mais comum foi exacerbação da arritmia de base (três doentes). A interrupção da amiodarona e administração de levotiroxina foi a terapêutica escolhida em 83,3% dos casos de HPOIA, enquanto a tionamida associada a corticoide com suspensão da amiodarona foi opção em 75% dos casos de HPEIA. Registraram-se três óbitos, todos com HPEIA. O HPEIA constituiu uma complicação potencialmente fatal. A clínica pode ser vaga, pelo que a monitorização da função tiróidea é obrigatória.

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

Miopatía grave de curso agudo en un paciente con hipotiroidismo reciente y asintomático / Severe myopathy in a hypothyroid patient: report of one case

Diffuse muscular involvement is common in hypothyroidism and ranges from asymptomatic elevation of creatine kinase levels to severe muscle weakness and rhabdomyolysis. We report a 74 years old male that developed a progressive muscle weakness without muscle pain, during the course of an hypothyroidism secondary to a silent thyroiditis. Laboratory showed a TSH of 149 uUI/ml, a thyroxin of 1.5 ug/dl a free thyroxin of less than 0.15 ng/dl and a creatine kinase of 4345 U/l. Treatment with levothyroxine rapidly reverted the muscular alterations.

Carcinoma de tireóide na infância e adolescência / Thyroid carcinoma in children and adolescents

Aproximadamente 10 por cento das neoplasias de tireóide aparecem abaixo dos 21 anos e representam 3 por cento das neoplasias da infância, com predomínio em meninas (2F:1M). São papilíferos em 90 por cento casos e mais freqüentemente bilaterais, multifocais e de maior dimensão. Invasão de cápsula e metástases ganglionar ou pulmonar são mais freqüentes que no adulto. O efeito carcinogênico da radiação é especialmente importante na criança pré-púbere. Em 5 por cento dos casos de PTC existe história familial. Genes como o RET/PTC, RAS e BRAF estão habitualmente envolvidos na gênese do processo. A apresentação clínica pode ser nódulo cervical (90 por cento casos) sem que represente um fator de pior prognóstico. O US e a PAAF são procedimentos diagnósticos valiosos. O tratamento deve ser cirúrgico (tireoidectomia total com esvaziamento ganglionar) seguido de PCI e radioterapia ablativa. A substituição com L-tiroxina deve objetivar a supressão crônica do TSH. O prognóstico ao longo prazo é melhor que no adulto. A quantificação da Tg plasmática também é útil na detecção da doença residual.

Approximately 10 percent of thyroid cancers are present in patients less than 21 years of age, representing 3 percent of all cancers of children and adolescents, with predominance in females 2:1 in relation to males. Thyroid cancers in this age group are usually papillary (90 percent), bilateral, multifocal and bigger in size compared to adults. Capsule invasion and lymphatic and pulmonary metastases are more frequent in children. Radiation sensitivity seems to represent an important factor in prepubertal patients. Familial history is reported in 5 percent of the cases. Genes such as RET/PTC, RAS and BRAF are usually involved in thyroid carcinogenesis in this age group. Cervical adenomegaly is a common clinical presentation, but does not represent a poor prognostic factor in children. Ultrasound and fine needle aspiration biopsy are valuable diagnostic procedures. Surgery is the preferred treatment including thyroidectomy and ganglionary excision, followed by ablative radioiodine therapy. L-thyroxine replacement with suppressive dosage should be employed targeting chronic TSH suppression. Long-term prognosis is usually better in children when compared with adults. Plasma thyroglobulin measurement is also useful to detect residual thyroid cancer disease.

Miocardiopatía hipoclacémica secundaria a hipoparatiroidismo postiroidectomía: Caso clínico / Hypocalcemic cardiomyopathy secondary to hypoparathyroidism after a thyroidectomy: Report of one case

Calcium plays a central role in ventricular function. We report a 37 year-old woman with chronic hypoparathyroidism and hypocalcemia secondary to a thyroidectomy performed when she was 18 years old, as treatment for a Graves Basedow's disease. She did not have previous cardiac symptoms and rapid progressive congestive heart failure developed after the beginning of levothyroxin supplementation for post operative hypothyroidism. Echocardiography revealed severe systolic and diastolic left ventricular dysfunction, mitral and tricuspid valve insufficiency, systolic pulmonary hypertension, left atrial enlargement and pericardial effusion. Calcium supplementation in addition to diuretics, captopril and digoxin were followed by rapid clinical improvement. Follow up until 18 months showed persistent left ventricular dilatation and systolic dysfunction, with improvement of all the other ecocardiographic findings.

Comparative study of the effectiveness of thyroxine and steroids on reduction of neonatal morbidity: outcome at 20 months follow-up

This study analyzes health, growth and neurodevelopmental outcome of infants who received prenatal corticosteroids with or without thyroxine for fetal lung maturation. During a 12 month period infants from a prospective double blind study who received either steroids or steroids combined with thyroxine for pulmonary maturation and who had reached 18 months of age were recalled for evaluation of health status, growth parameters and neurodevelopmental outcome using the Bayley Scales 2nd edition (BSID-II). Mental developmental index (MDI), psychomotor developmental index (PDI), language developmental age (LDA), cognitive developmental age (CDA), and behavioral rating scales (BRS) were compared for the two treatment groups. The Hollingshead Socioeconomic Status Index was determined for each infant. Of a total of 134 patients enrolled during the study period, 66 patients return for follow up. Data from 60 patients was included in the final analysis. Of these, 32 had received the combination regimen and 28 had solely received only steroids. Demographics and neonatal morbidity were similar in both groups. No statistical differences in growth parameters, hospital admissions, respiratory problems, surgical procedures or frequency of infections were found. Neurodevelopmental parameters (MDI, PDI) were similar in both treatment groups, although, below normal in both groups. Language delay was more common in infants who received prenatal corticosteroids. There were no difference in the incidence of neurologic abnormalities. The addition of thyroxine to steroids did not affect growth or neuro-developmental outcome of the infants at 18 to 22 postnatal age.

Estudo de adesäo ao tratamento do hipotiroidismo / Study of adhesion at the hypothyroidism treatment

Para avaliarmos o impacto da adesäo no controle do hipotiroidismo em nosso meio, estudamos 100 portadores de hipotiroidismo mal controlados (Mo de TSH: 12U/L) acompanhados no HC-UNICAMP e no HUCFF-UFRJ, 80 mulheres e 20 homens de nível sócil-econômico e cultural similar. Após serem examinados e orientados quanto à importância de seu uso adequado, os pacientes recebiam hormônio tiroidiano em uma das 4 apresentaçöes comercialmente disponíveis em nosso meio, de forma aleatória e em dose similar à anteriormente prescrita, por um período médio de 3 meses. Os 25 pacientes de cada grupo possuíam características clínicas e sócio-econômico-culturais semelhantes com renda per capita mensal em torno de U$100,00 (X2:NS). Mensalmente os doentes eram examinados por um mesmo médico. Realizávamos um controle do número de comprimidos restantes e embalagens vazias, dosagens de TSH e de T4 livre. Nossos resultados mostram que 82 por cento dos pacientes näo aderiam ao tratamento proposto, faltando aos retornos (36 por cento dos casos) e/ou näo seguido corretamente a prescriçäo médica (66 por cento dos casos). Os níveis de TSH foram controlados em 77 pacientes ao término do estudo, independente da formulaçäo de tiroxina prescrita (X2 de pacientes controlados?grupo: NS). Dezesseis pacientes apresentaram níveis de TSH diminuídos no 1§ retorno, sugerindo que usavam doses inferiores às prescritas antes do medicamento ser-lhes fornecido. Concluímos que podemos controlar portadores de hipotiroidismo adequadamente com qualquer uma das apresentaçöes disponíveis no mercado nacional quando o paciente adere ao esquema terapêutico proposto.