Subclinical Thyroid Dysfunction and Frailty Among Older Men

CONTEXT Both subclinical thyroid dysfunction and frailty are common among older individuals, but data on the relationship between these 2 conditions are conflicting. OBJECTIVE The purpose of this study was to assess the cross-sectional and prospective associations between subclinical thyroid dysfunction and frailty and the 5 frailty subdomains (sarcopenia, weakness, slowness, exhaustion, and low activity). SETTING AND DESIGN The Osteoporotic Fractures in Men Study is a prospective cohort study. PARTICIPANTS Men older than 65 years (n = 1455) were classified into 3 groups of thyroid status: subclinical hyperthyroidism (n = 26, 1.8%), subclinical hypothyroidism (n = 102, 7.0%), and euthyroidism (n = 1327, 91.2%). MAIN OUTCOME MEASURES Frailty was defined using a slightly modified Cardiovascular Health Study Index: men with 3 or more criteria were considered frail, men with 1 to 2 criteria were considered intermediately frail, and men with no criteria were considered robust. We assessed the cross-sectional relationship between baseline thyroid function and the 3 categories of frailty status (robust/intermediate/frail) as well as the prospective association between baseline thyroid function and subsequent frailty status and mortality after a 5-year follow-up. RESULTS At baseline, compared with euthyroid participants, men with subclinical hyperthyroidism had an increased likelihood of greater frailty status (adjusted odds ratio, 2.48; 95% confidence interval, 1.15-5.34), particularly among men aged <74 years at baseline (odds ratio for frailty, 3.63; 95% confidence interval, 1.21-10.88). After 5 years of follow-up, baseline subclinical hypothyroidism and hyperthyroidism were not consistently associated with overall frailty status or frailty components. CONCLUSION Among community-dwelling older men, subclinical hyperthyroidism, but not subclinical hypothyroidism, is associated with increased odds of prevalent but not incident frailty.

Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study.

BACKGROUND Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. PATIENTS Elderly participants with VTE. METHODS In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid stimulating hormone levels (TSH=4.50-19.99 mIU/l), and subclinical hyperthyroidism (SHyper) as TSH<0.45, both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. rVTE incidence rate was 7.2 (95% confidence interval:2.7-19.2) per 100 patient-years in SHypo, 0.0 (0.0-7.6) in SHyper and 5.9 (4.4-7.8) in euthyroid participants. In multivariate analyses, the sub-hazard ratio [SHR] for rVTE was 0.00 (0.00-0.58) in SHyper and 1.50 (0.52-4.34) in SHypo compared to euthyroids, without increased thrombophilic biomarkers. SHyper (HR 0.80,0.23-2.81) and SHypo (HR 0.99,0.30-3.29) were not associated with mortality. CONCLUSION In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers. This article is protected by copyright. All rights reserved.

Concentrations of PCBs, DDT and thyroid hormones in gray (Halichoerus grypus) and ringed (Phoca hispida) seals

The high levels of polychlorinated biphenyls (PCBs) and DDT in gray seal (Halichoerus grypus) and ringed seal (Phoca hispida botnica) in the Baltic Sea have been associated with pathological disruptions, including bone lesions and reproductive failures. The underlying environmental and toxicological mechanisms leading to these pathological changes are not yet fully understood. The present study investigated the relationship between the individual contaminant load and bone- and thyroid-related effects in adult gray seals (n = 30) and ringed seals (n = 46) in the highly contaminated Baltic Sea and in reference areas (Sable Island, Canada, and Svalbard, Norway). In the gray seals, multivariate and correlation analyses revealed a clear relationship between circulating 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, and thyroid hormone (TH) levels and hepatic PCB and DDT load, which suggests contaminant-mediated disruption of the bone and thyroid homeostasis. Contaminants may depress 1,25(OH)2D levels or lead to hyperthyroidism, which may cause bone resorption. In the ringed seals, associations between circulating 1,25(OH)2D, THs, and hepatic contaminants were less prominent. These results suggest that bone lesions observed in the Baltic gray seals may be associated with contaminant-mediated vitamin D and thyroid disruption.

Induction of Graves-like disease in mice by immunization with fibroblasts transfected with the thyrotropin receptor and a class II molecule.

Graves disease is an autoimmune thyroid disease characterized by the presence of antibodies against the thyrotropin receptor (TSHR), which stimulate the thyroid to cause hyperthyroidism and/or goiter. By immunizing mice with fibroblasts transfected with both the human TSHR and a major histocompatibility complex class II molecule, but not by either alone, we have induced immune hyperthyroidism that has the major humoral and histological features of Graves disease: stimulating TSHR antibodies, thyrotropin binding inhibiting immunoglobulins, which are different from the stimulating TSHR antibodies, increased thyroid hormone levels, thyroid enlargement, thyrocyte hypercellularity, and thyrocyte intrusion into the follicular lumen. The results suggest that the aberrant expression of major histocompatibility complex class II molecules on cells that express a native form of the TSHR can result in the induction of functional anti-TSHR antibodies that stimulate the thyroid. They additionally suggest that the acquisition of antigen-presenting ability on a target cell containing the TSHR can activate T and B cells normally present in an animal and induce a disease with the major features of autoimmune Graves.

Hipertiroidismo: Experiência de uma Consulta de Endocrinologia Pediátrica

Introdução: O hipertiroidismo pode ter múltiplas etiologias, das quais se destaca a doença de Graves. Embora persista alguma controvérsia, a terapêutica de primeira linha na doença de Graves deve ser adequada às características do doente e, sempre que possível, adaptada aos seus valores e preferências. Objetivo: Caracterizar os doentes com hipertiroidismo seguidos numa consulta de Endocrinologia Pediátrica. Métodos: Estudo retrospetivo com revisão dos processos clínicos dos doentes acompanhados em consulta entre 2001 e 2013. Analisadas variáveis demográficas, clínicas, estudo complementar, opções terapêuticas e evolução. Resultados: Dos 13 doentes incluídos, 85% foram do sexo feminino e a mediana da idade ao diagnóstico foi de 14 anos. Relativamente à etiologia, 77% tinham doença de Graves, 8% hipertiroidismo autoimune com anticorpos anti-recetores da tirotropina (TRAb) negativos, 8% bócio multinodular tóxico e 8% hipertiroidismo neonatal transitório. Na sintomatologia de apre- sentação destacam-se: ansiedade/irritabilidade (46%), sudorese (31%), palpitações (31%) e fraqueza/cansaço (31%); e os seguintes sinais: bócio (77%), perda ponderal (62%) e taquicardia (54%). Apresentavam anticorpos antitiroideus positivos 92% dos doentes e TRAb positivos 85%. A primeira opção terapêutica foi maioritariamente o tiamazol (92%). Uma doente recidivou após suspensão do antitiroideu e foi submetida a terapêutica com 131I. O doente com bócio multinodular foi submetido a tiroidectomia por suspeita de tumor folicular na citologia aspirativa. Conclusão: Os dados obtidos são concordantes com a literatura. A terapêutica com tiamazol apresenta risco reduzido de reações adversas, mas baixa probabilidade de remissão, pelo que, em casos selecionados, o tratamento definitivo deve ser considerado.

Patologia tiroideia e infertilidade feminina

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A discussion of cases in the 2001 RCPA-AQAP chemical pathology case report comments program

Aim: We present a descriptive analysis of the 10 case reports distributed in the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program to assess the quality of interpretative commenting in clinical biochemistry in 2001. Method: Participants were asked to comment on a given set of biochemistry results attached with brief clinical details. All responses received were translated into key phrases and graphically presented on a histogram. An expert panel was asked to evaluate the appropriateness of the key phrases and to propose a suggested composite comment. Results: While the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate or misleading. As comments on laboratory reports may affect clinical management of patients, it is important that these comments reflect accepted practice and current guidelines. Conclusion: The Patient Report Comments Program may play an important role in continuing education and possibly in quality assurance of interpretative commenting.

Increased calcium influx mediates increased cardiac stiffness in hyperthyroid rats

Cardiac remodeling (hypertrophy and fibrosis) and an increased left ventricular diastolic stiffness characterize models of hypertension such as the SHR and DOCA-salt hypertensive rats. By contrast, hyperthyroidism induces hypertrophy and hypertension, yet collagen expression and deposition is unchanged or decreased, whereas diastolic stiffness is increased. We determined the possible role of increased calcium influx in the development of increased diastolic stiffness in hyperthyroidism by administering verapamil (15 mg/[kg(.)d] orally) to rats given triiodothyronine (T-3) (0.5 mg/[kg.d] subcutaneously for 14 d). Administration of T3 significantly increased body temperature (control: 36.7 +/- 0.2 degrees C; T-3: 39.6 +/- 0.2 degrees C), left ventricular wet weight (control: 2.09 +/- 0.02 mg/kg; T-3 3.07 +/- 0.07 mg/kg), systolic blood pressure (control: 128 +/- 5 mmHg; T-3: 156 +/- 4 mmHg), and left ventricular diastolic stiffness (control: 20.6 +/- 2.0; T-3: 28.8 +/- 1.4). Collagen content of the left ventricle was unchanged. Contractile response to noradrenaline in thoracic aortic rings was reduced. Relaxation in response to acetylcholine (ACh) was also reduced in T-3-treated rats, whereas sodium nitroprusside response was unchanged. Verapamil treatment of hyperthyroid rats completely prevented the increased diastolic stiffness and systolic blood pressure while attenuating the increased body temperature and left ventricular weight; collagen content remained unchanged. ACh response in thoracic aortic rings was restored by verapamil. Thus, in hyperthyroid rats, an increased calcium influx is a potential mediator of the increased diastolic stiffness independent of changes in collagen.

Prevalence of subclinical thyroid dysfunction and its relation to socioeconomic deprivation in the elderly:a community-based cross-sectional survey

Context: Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment. Objective: The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. Design, Setting, and Participants: A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom. Exclusions: Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. Outcome Measure: Tests of thyroid function (TSH concentration and free T 4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. Explanatory Variables: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004) Analysis: Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction Results: A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained. Conclusions: Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population. Copyright © 2006 by The Endocrine Society.

“Syndrome in syndrome”: Wernicke syndrome due to afferent loop syndrome. Case report and review of the literature

Wernicke syndrome is a rare neurological pathology due to a deficit in vitamin B1. The syndrome is common among alcohol abusers, patients with malignant tumor or gastrointestinal diseases, those who undergo hemodialysis or long-term peritoneal dialysis, pregnant women with hyperemesis, women who breast-feed, patients with hyperthyroidism or anorexia nervosa or gastric or jejunal-ileal bypass surgery for obesity, patients submitted to gastric surgery or prolonged total parenteral nutrition or prolonged intravenous therapy. We report a case of Wernicke syndrome due to afferent loop syndrome characterized by incoercible vomiting.

Postoperative Treatment in a Patient After Hemithyroidectomy: the Therapeutic Challenges of a Hidden Thyrotropinoma

Objectives: We report the unusual case of a patient with a thyrotropinoma, discovered after a hemithyroidectomy for a suspicious thyroid nodule, and its therapeutic challenges. Materials and methods: In a patient who underwent hemithyroidectomy for cold thyroid nodule, hyperthyroid symptoms persisted, despite stopping levothyroxine treatment. Further investigation was carried out through the following laboratory tests: thyroid-stimulating hormone (TSH) test; free thyroxine (fT4) test; and the thyrotropin releasing hormone (TRH) test. A pituitary magnetic resonance imaging (MRI) scan and genetic analysis was also carried out. The test results confirmed the diagnosis of a thyrotropinoma. Results: Treatment with long-acting somatostatin analogues normalised thyroid hormones and symptoms of hyperthyroidism. Conclusion: The diagnostic approach to the thyroid nodule should include a detailed clinical and biochemical examination. Initial biochemical evaluation by TSH alone does not allow detecting inappropriate TSH secretion that may increase the risk of thyroid malignancy. In case of a thyrotropinoma, the ideal treatment consists of combined care of central and peripheral thyroid disease.

Unexpected Complication of a Multinodular Goitre

Multinodular goitre is the most common thyroid gland disorder. It can cause hyperthyroidism and mechanical complaints such as tracheal compression or dysphagia. We report a unique case of a patient with a toxic multinodular goitre presenting with a deep venous thrombosis of the left arm due to direct local compression of blood flow.

Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen.

Background: Mycobacterium tuberculosis and human immunodeficiency virus (HIV) are known to cause abnormal thyroid function. There is little information on whether HIV infection aggravates alteration of thyroid function in patients with MDRTB. Objectives: This study was carried out to determine if HIV co-infection alters serum levels of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH) in patients with MDR-TB patients and to find out the frequency of subclinical thyroid dysfunction before the commencement of MDR-TB therapy. Methods: This observational and cross-sectional study involved all the newly admitted patients in MDR-TB Referral Centre, University College Hospital, Ibadan, Nigeria between July 2010 and December 2014. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined using ELISA. Results: Enrolled were 115 patients with MDR-TB, out of which 22 (19.13%) had MDR-TB/HIV co-infection. Sick euthyroid syndrome (SES), subclinical hypothyroidism and subclinical hyperthyroidism were observed in 5 (4.35%), 9 (7.83%) and 2 (1.74%) patients respectively. The median level of TSH was insignificantly higher while the median levels of T3 and T4 were insignificantly lower in patients with MDR-TB/HIV co-infection compared with patients with MDRT-TB only. Conclusion: It could be concluded from this study that patients with MDR-TB/HIV co-infection have a similar thyroid function as patients having MDR-TB without HIV infection before commencement of MDR-TB drug regimen. Also, there is a possibility of subclinical thyroid dysfunction in patients with MDR-TB/HIV co-infection even, before the commencement of MDR-TB therapy.

Characterization of bone pathologies in the ins2+/akita mouse, a new model for diabetes insulindependent: contribution for a better understanding of the disease in humans

Tese de Doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016