Low triiodothyronine syndrome is associated with platelet function in patients with nephrotic syndrome

SUMMARY OBJECTIVE The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.

RESUMO OBJETIVO O objetivo deste estudo foi investigar os efeitos da síndrome do baixo triiodotironina (LT3S) na função plaquetária e nos fatores de coagulação em pacientes com síndrome nefrótica (SN). MÉTODOS Pacientes com síndrome nefrótica primária foram divididos em dois grupos, função tireoidiana normal (grupo A) e LT3S (grupo B), com base na presença ou não de LT3S. Indivíduos saudáveis foram selecionados como grupo de controle (grupo C). A função de coagulação do sangue foi analisada em cada grupo. A função de ativação plaquetária (CD62P, CD63) foi determinada por citometria de fluxo. A taxa de agregação plaquetária foi detectada por um método óptico usando adenosina difosfato e ácido araquidônico como indutores. RESULTADOS A proporção de síndrome nefrótica primária com LT3S foi de 23,2% (69/298). Em comparação com o grupo C, o grupo A apresentou níveis mais altos de CD62P e PAgTADP, e o grupo B apresentou maiores CD62P, CD63, PAgTAA e PAgTADP; a diferença teve significância estatística (P < 0,05). Não houve diferença significativa na patologia renal entre o grupo A e o grupo B (X2 = 4,957, P = 0,421). Em comparação com o grupo A, a proteína em urina de 24 horas, CD63, PAgTAA e PAgTADP foram maiores no grupo B, já APTT e Alb foram mais baixos. A diferença apresentou significância estatística (P < 0,05). A análise de regressão logística mostrou uma associação entre LT3S e CD36 (OR: 3,516; 95% IC: 1,742~8,186; P = 0,004) e PAgTAA (OR: 0,442; 95% IC: 1,001~1,251; P = 0,037). CONCLUSÃO Pacientes com síndrome nefrótica estão propensos à síndrome do baixo triiodotironina (LT3S). Pacientes com LT3S podem ter ativação plaquetária anormal e aumento da agregação plaquetária.

Insulin resistance and glucose levels in subjects with subclinical hypothyroidism

Objective: To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism

Study Design: Comparative cross-sectional study

Place and Duration of Study: Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology [AFIP], Rawalpindi, from December 2015 to September 2016

Methodology: Subjects referred for executive screening of apparently healthy population [without any known history of diabetes, hypertension, heart disease or other chronic ailments], were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism

Results: Median [IQR] insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 [n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mlU/L] and group-2 [n=26, 13%, Thyroid Stimulating Hormone: 3.51 -15 mlU/L] were 7.6 [6.70] vs. 11.4 [13.72, p=0.040] and 1.77 [1.79] vs. 2.8 [3.07, p=0.071]

The median differences for fasting plasma glucose were 5.0 [1.0] in group-1 vs. 5.0 [1.47] for Group-2 [p=0.618], and glycated hemoglobin was 5.60 [1.1] vs. 5.60 [1.7, p=0.824]. Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median [IQR] 86.67 [92.94]] than group-1 [111.6 [189.64, p= 0.040]]

Conclusion: Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism

Nonthyroidal illnesses syndrome in full-term newborns with sepsis

ABSTRACT Objective To assess hormonal changes in nonthyroidal illness syndrome (NTIS) in full-term newborns (NT) with sepsis. Materials and methods We included 28 NT with sepsis divided into 2 groups according to the time of normalization of serum and clinical indicators of infection: group A(A), 16 NT with improvement in up to 8 days; and group B(B), 12 NT improvement after 8 days. Among the 28 NT, 15 NT progressed to septic shock, with 5 NT group A and 10 NT in group B. NT were excluded when they showed severe sepsis and asphyxia, and congenital malformations, as well as those whose mothers had thyroid disease and IUGR. Results 17 NT (60.7%) presented NTIS. Low T3 was observed in NTIS in 10 NT (58.8%), and low T4 and T3 in 5 NT (29.5%), all of them with septic shock. Two NT showed mixed changes (11.7%). After sepsis was cured, there was no hormonal change, except in 3 NT. Administration of dopamine, furosemide, and corticosteroids did not affect the results. Conclusions This study indicates that nonthyroidal illness syndrome may be transiently present during sepsis in full-term newborns, especially in cases of prolonged sepsis. Low T3 can occur without changes in reverse T3 (different from adults), and low T4 and T3 occur mainly in patients with septic shock. Arch Endocrinol Metab. 2015;59(6):528-34.

Serum thyroid hormone profile in critically Ill children.

Objective. To study thyroid hormone profile in critically ill children and its correlation to disease severity and clinical outcome. Methods. Total serum triiodothyronine (T3), thyroxine (T4) and TSH were estimated at admission and discharge from PICU/ just before death. Results. Mean T3 levels in cases were significantly lower than controls and lower in patients who expired, both at admission and just prior to death. Mean T4 levels were lower in cases, and just prior to death. Mean TSH levels were not different in cases and controls; or in survived and expired cases. When both T3 and T4 are low, mortality risk increases 30 times. Serum T3, T4 and TSH values improved in patients who survived unlike in those who expired. Age, sex, duration of hospital stay, ventilation, inotropic support, and PICU stay did not show any correlation with patient outcome or thyroid hormone profile. PRISM score at 24 hours and T4 levels in the second sample were significant predictors of survival. Conclusion. T3 levels reflect the patient’s clinical status, T4 levels can predict survival.

Relation between thyroid hormone concentration and serum levels of interleukin-6 and interleukin-10 in patients with nonthyroidal illness including chronic kidney disease

We evaluated relations between interleukins [IL] IL-6 and IL-10 and euthyroid sick syndrome [ESS] in patients with nonthyroidal illness [NTI]. Sixty patients and 20 healthy volunteers were recruited. The patients had either chronic kidney disease [CKD], congestive heart failure [CHF], or acute myocardial infarction [MI], distributed equally in 3 subgroups. Serum levels of IL-6 and IL-10, thyroid stimulating hormone [TSH], total T4, and T3 were determined. In the 60 patients with NTI, we detected a significantly lower T3 and T4 levels compared to controls, while TSH level was within the reference range. Also, IL-6 level was substantially higher than that in controls [P < .001] and correlated with T3 [r = -0.620, P < .001] and T4 [r = -0.267, P < .001]. Similarly was IL-10 level [P < .001] that correlated with T3 [r = -0.512, P < .001], but not with T4. The ILs correlated positively with each other [r = 0.770, P < .001]. Only IL-6 was a predictor of low T3 [P = .001]. The proportion of patients with subnormal T3, T4, and TSH levels was highest in those with MI along with greatest IL-6 and IL-10 levels compared to patients with CHF and CKD. Patients with CKD showed the least disturbance in IL-6 and IL-10 despite the lower levels of T3, T4, and TSH in a higher proportion of them compared to patients with CHF. The high frequency of ESS in patients with NTI may be linked to IL-6 and IL-10 alterations. Perturbation of IL-6, and not IL-10, might be involved in the pathogenesis of ESS along with other key players as suggested by our findings in CKD

Perfil dos hormônios tireoidianos nas síndromes coronarianas agudas / Thyroid hormone profile in acute coronary syndromes

OBJETIVO: Descrever o perfil hormonal tireoidiano em pacientes com síndromes coronarianas agudas (SCA), e nos grupos: 1) angina instável e/ou infarto agudo do miocárdio sem supradesnivelamento de segmento ST (AI/IAM sem supra ST); 2) infarto agudo do miocárdio com supradesnivelamento do segmento (IAM com supra ST), e nos pacientes que evoluíram ou não a óbito conforme os grupos. MÉTODOS: Foram estudados prospectivamente setenta pacientes portadores de SCA, internados na unidade coronariana do Hospital dos Servidores do Estado/RJ. As amostras sangüíneas foram coletadas nos primeiro, quarto e sétimo dias de internação. Exame clínico e eletrocardiograma foram realizados no período de internação. RESULTADOS: Dos 70 pacientes admitidos, 13 (18,6 por cento) apresentaram a "síndrome do eutireoidiano doente" (SED), que consiste na queda do hormônio T3 e ou T3 livre, aumento do hormônio T3 reverso (rT3) e inalteração dos hormônios TSH, T4 e T4 livre. Nos pacientes do grupo IAM com supra ST, observaram-se elevação precoce e maiores médias do hormônio tireoidiano T3 reverso (rT3) e menores médias dos hormônios T3 e T3 livre. Nos coronariopatas que evoluíram a óbito, observamos achados hormonais condizentes com os encontrado na SED, com valores médios expressivos dos hormônios rT3 e T3. CONCLUSÃO: Os resultados apresentados neste estudo mostram a importância do reconhecimento da "síndrome do eutireoidiano doente" nos pacientes coronariopatas, sugerindo associação com pior prognóstico nos pacientes com síndrome coronariana aguda.

OBJECTIVE: To describe thyroid hormone profile in patients with acute coronary syndromes (ACS), divided into two groups: 1) unstable angina and/or non-ST-segment elevation acute myocardial infarction (UA/NSTEMI); 2) ST-segment elevation acute myocardial infarction (STEMI), as well as in patients that progressed or not to death, according to the groups. METHODS: Seventy ACS patients admitted to the coronary care unit of the Hospital dos Servidores do Estado, Rio de Janeiro, were prospectively studied. Blood samples were collected on day 1 and on days 4 and 7 following admission. Clinical evaluation and electrocardiograms were performed during hospitalization. RESULTS: Of the 70 patients admitted, 13 (18.6 percent) had "euthyroid sick syndrome" (ESS), a condition characterized by decreased serum T3 and/or free T3, increased serum reverse T3 (rT3), plus normal serum TSH, T4, and free T4. Patients belonging to the STEMI group showed early elevations, in addition to higher mean reverse T3 (rT3) and lower mean T3 and free T3 levels. In coronary heart disease patients that progressed to death, hormonal findings were consistent with those found in the ESS, with more expressive rT3 and T3 mean values. CONCLUSION: Our results show the importance of recognizing the "euthyroid sick syndrome" in coronary heart disease patients, suggesting an association with poorer prognosis in patients with acute coronary syndrome.

An evaluation of thyroid hormone status and oxidative stress in undialyzed chronic renal failure patients.

Chronic renal failure (CRF) patients on prolonged dialysis have been found to have significant alteration in their thyroid status, but little is known about the same in undialyzed CRF patients. Oxidative stress has been implicated as the key player in altering the levels of thyroid hormone in euthyroid sick syndrome. This study was performed to evaluate the levels of oxidative stress and thyroid status in undialyzed CRF patients. A case control study was performed on 20 undialyzed CRF patients and 20 control subjects. There was a significant decrease in the levels of T3, T4, total protein and albumin levels in CRF patients when compared to control. There was a significant increase in the level of malondialdehyde and total antioxidant status in CRF patients when compared with control subjects. The present study confirms oxidative stress along with altered thyroid status in CRF patients.

Prevalence and pattern of sick euthyroid syndrome in acute and chronic non-thyroidal illness--its relationship with severity and outcome of the disorder.

BACKGROUND: Non-thyroidal illness is a common cause of alterations in thyroid hormone economy in absence of underlying intrinsic thyroid disorder. OBJECTIVE: To study the prevalence and pattern of alterations in thyroid hormone economy in various non-thyroidal illnesses in our region and also to correlate these alterations with the severity and outcome of the non-thyroidal illness. MATERIAL AND METHODS: We analyzed circulating T3, T4, TSH in 382 patients with non-thyroidal illness (285 acute and 97 acute on chronic) and correlated the alterations with severity and outcome of the non-thyroidal disorder. The patients had one or more organ failure at the time of enrollment to the study. The hormones were estimated at the onset of sickness, and at 3rd and 24th week. T3, T4 and TSH in 75 age and sex matched euthyroid subjects were taken as controls. RESULTS: T3 (mean +/- SEM) was significantly reduced at the onset of illness, in both acute and chronic patient groups (1.61 +/- 0.05 nmol/l) compared to that in the controls (3.17 +/- 0.06 nmol/l). In spite of clinical improvement in most instances, T3 continued to remain low in the 3rd week (1.49 +/- 0.11 nmol/ l) but increased (2.14 +/- 0.09 nmol/l) in 24th week. Low T3 was found in 93 (32.6%) cases with acute illness in 20 (20.6%) cases with chronic illness. A combination of low T3 and T4 was found in 35 (12.3%) of cases with acute and 15 (15.5%) with chronic illness. Although serum TSH showed noticeable fall and rise in some individuals, no significant difference in mean TSH was observed during any period of illness compared to that in the controls. Severity of illness correlated with decrease in T3 (r=0.58) and T4 (r=0.38). A low T3 and T4 with low or undetectable TSH were associated with increased mortality. At the onset of acute illness low T3 was seen in 113 (29.6%, low T3 -low T4 in 50 (13.1%), high T4 in 28 (7.3%) lowT3-lowT4- low TSH in 10 (2.6%) and low T4 alone in 4 (1%) patients. Fifty one 1 (13.4%) of our patients demonstrated alterations in TSH in presence of normal T3 and T4-26 patients had decreased TSH while as 25 had increased TSH. Of 118 patients who followed at 24 weeks, 11 (9.3%) had low T3, 7(5.9%) had low T3- low T4 and 13 (11%) had elevated TSH. CONCLUSION: Pattern and prevalence of sick euthyroid syndrome in this part of the world, a recognized iodine deficient region, appears to be similar to that reported elsewhere. Important finding in our study was higher percentage of TSH elevation, which we believe to reflect the underlying iodine deficiency state of our community. Besides a significant number of subjects persisted with alterations in thyroid functions even after 6 months of therapy. Though the severity of thyroid hormone derangement correlated with severity of sickness, the derangement was similar in acute vs. acute on chronic nonthyroidal illnesses.

Circulating IL-8 and IL-10 in Euthyroid Sick Syndromes following Bone Marrow Transplantation

It is generally agreed that euthyroid sick syndromes (ESS) are associated with an increased production of cytokines. However, there has been scarce data on the relationship thyroid hormone changes and cytokines among the patients undergoing bone marrow transplantation (BMT). Because interleukin-8 (IL-8) has been identified as a potent proinflammatory and interleukin-10 (IL-10) as an antiinflammatory cytokine, we studied the relation between thyroid hormone parameters and these cytokines following BMT. We studied 80 patients undergoing allogeneic BMT. Serum T3 decreased to nadir at post-BMT 3 weeks. Serum T4 was the lowest at the post-BMT 3 months. Serum TSH sharply decreased to nadir at 1 week and gradually recovered. Serum free T4 significantly increased during 3 weeks and then returned to basal level. Mean levels of serum IL-8 significantly increased at 1 week after BMT. Mean levels of serum IL-10 significantly increased until 4 weeks after BMT. No significant correlation was found between serum thyroid hormone parameters and cytokines (IL-8, IL-10) after adjusting steroid doses during the entire study period. In conclusion, ESS developed frequently following allogeneic BMT and cytokine levels were increased in post-BMT patients. However, no significant correlation was found between serum thyroid hormone parameters and these cytokines.

Valor preditivo da dosagem das iodotironinas na avaliaçäo prognóstica de doentes graves / Predictiove value of the measurement of iodotironines on the prognosis of patients with severe nonthyroidal illness

Os valores das dosagens de T3 e de T4 diferenciaram os pacientes com boa e ma evoluçao durante a internaçao em unidade de terapia intensiva. Objetivo. Procurar indicadores para o prognóstico de doentes graves por meio do estudo seqüencial dos níveis séricos dos hormonios tiroidianos. Métodos. Os autores mediram as iodotironinas (T3, T4 e rT3) por ocasiao da entrada e da alta de 42 pacientes internados em unidade de terapia intensiva. Verificaram, também, os dados referentes à última coleta de outros 17 doentes, transferidos para a UTI após o início do quadro clínico. Resultados. Comparando pacientes que evoluíram bem com aqueles que foram a óbito, observaram, nos primeiros, níveis iniciais normais de T4 em 76 por cento dos casos, valores que se mantiveram estaveis ou se elevaram em 65 por cento dos pacientes durante a internaçao, de tal forma que níveis normais de T4 estavam presentes em 70 por cento dos casos por ocasiao de sua alta. Ao contrario, 56 por cento dos pacientes que evoluíram mal ja apresentavam T4 inicial baixo, que diminuiu ainda mais de 95 por cento dos pacientes durante a internaçao, notando-se valores baixos em 81 por cento dos casos por ocasiao da ultima amostra. Os valores de T3 e T4 em conjunto também diferenciaram os pacientes com boa e m evoluçao. Conclusao. Os autores sugerem que a observaçao dos níveis séricos das iodotironinas pode oferecer importante subsídio na avaliaçao prognóstica de doentes em estado grave.

Immunochemiluminometric assay for measurement of thyrotropin in various thyroid disorders.

The measurement of serum TSH concentration by the new ICMA had good precision and was more efficacious than RIA, IRMA and IEMA in distinguishing hyperthyroid patients from euthyroid subjects. Moreover, the measurement of serum TSH by ICMA was less interfered by high concentrations of hCG in sera of patients with trophoblastic disease. However, the assay needs special equipment and the cost is currently higher than other available methods.