The Nonthyroidal Illness Syndrome

Georgetown University, Washington, Washington, D.C., United States
Endocrinology & Metabolism Clinics of North America (Impact Factor: 3.4). 10/2007; 36(3):657-72, vi. DOI: 10.1016/j.ecl.2007.04.007
Source: PubMed


This article briefly summarizes thyroid function alterations generally seen in the euthyroid sick syndrome, provides an overview of specific thyroidal adaptations during several clinical conditions and secondary to specific pharmacologic agents, and discusses the current controversy in thyroid hormone treatment of nonthyroidal illness.

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    • "The same experimental design as applied in the present study induced significant increase in serum adrenocorticotropic hormone (ACTH), enlarged zona fasciculata of adrenal cortex , which was accompanied by increase in serum corticosterone level in comparison to the control values (Milo sevicét al., 2003, 2005). Stimulated pituitary-adrenal axis and elevated glucocorticoid levels may affect thyroid functioning in vivo by affecting its hypothalamic-pituitary regulation (Haugen, 2009), directly by affecting thyroid tissue , or by modulating deiodinase enzymes activity and conversion of T 4 to T 3 (Adler and Wartofsky, 2007). Data on the effects of CL exposure on pituitarythyroid axis are incomplete and mostly limited to determinations of serum hormone concentrations: elevated serums free T 4 (Singh et al., 1969) accompanied by decreased TSH (Vinogradova et al., 2009) levels were reported in serum of male and female rats exposed to CL conditions, starting from the first month of life until their natural death. "
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    ABSTRACT: Light regulates numerous physiological functions and synchronizes them with the environment, in part by adjusting secretion of different hormones. We hypothesized that constant light (CL) would disturb pituitary-thyroid axis. Our aim was to determine morphological and functional changes in this endocrine system in such extreme conditions and, based on the obtained results, to propose the underlying mechanism(s). Starting from the thirtieth postnatal day, female Wistar rats were exposed to CL (600 lx) for the following 95 days. The controls were maintained under the regular laboratory lighting conditions. After decapitation, pituitaries and thyroids were prepared for further histomorphometric, immunohistochemical, and immunofluorescence examinations. Concentration of thyroid stimulating hormone (TSH), total T4 and T3 (TH) were determined. Thyroid tissue of light-treated rats was characterized by microfollicular structure. We detected no change in total thyroid volume, localization and accumulation of thyroglobulin, thyroid peroxidase, and sodium-iodide symporter in the follicular epithelium of CL rats. The volume of follicular epithelium and activation index were increased, while volume of the colloid and serum levels of TH decreased. In the pituitary, the relative intensity of TSH β-immunofluorescence signal within the cytoplasm of thyrotrophs increased, but their average cell volume and the relative volume density decreased. Serum TSH was unaltered. We conclude that exposure of female rats to CL induced alterations in pituitary-thyroid axis. Thyroid tissue was characterized by microfollicular structure. Serum TH levels were reduced without accompanying increase in serum TSH. We hypothesize that increased secretion and clearance of TH together with unchanged or even decreased hormonal synthesis, resulted in decreased serum TH levels in CL group. We assume this decrease consequently led to increased synthesis and/or accumulation of pituitary TSH. However, decreased average TSH cell volume and relative volume density, together with unchanged serum TSH, point to additional, negative regulation of thyrotrophs. J. Morphol., 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Oct 2014 · Journal of Morphology
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    • "In general, this syndrome presents as low or low normal peripheral triiodothyronine (T3) and thyroxine (T4) levels with TSH level in the normal range. There is a blunting of the TSH response to TRH and decrease or abolition of the early morning TSH surge (De Groot, 2006; Adler and Wartofsky, 2007). Controversy continues over the thyroid status of these patients: altered hypothalamic regulation is implicated with TSH levels inappropriately low for the thyroid hormone levels (De Groot, 2006). "
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    ABSTRACT: The co-morbidity of mood disturbance, in a proportion of patients, is now described across a wide range of chronic disease states. Similarly, a ‘Low Thyroid Syndrome’ is also reported in a proportion of individuals with chronic diseases. Here, we report on central changes in an animal model of inflammatory stress in which altered social behaviour, representing social disability, persists in a sub-group of rats following injury. We showed in an earlier study that rats with social disability following injury have significantly decreased peripheral thyroid hormones, with no increase in Thyroid Stimulating Hormone (TSH). Only rats identified by behavioural change showed changes in hypothalamic gene expression. In whole hypothalamus extracted RNA, relative expression of mRNA for Thyrotrophin-releasing hormone (TRH) was significantly down-regulated in disabled rats (p = 0.039) and deiodinase 3 up-regulated (p = 0.006) compared to controls. Specifically in the paraventricular nucleus (PVN), numbers of immunoreactive cells for deiodinase 3-like and thyroid hormone receptor beta-like proteins were decreased in the sub-group with disability compared to the control group (p = 0.031 and p = 0.011 respectively). In rats with behavioural change post-injury, down-regulation of TRH provides an explanation for the failure of the hypothalamo-pituitary-thyroid (HPT) axis to respond to the post-injury decrease in thyroxine. Decreased local expression of deiodinase 3 protein, resulting in a local increase in T3, offers an explanation for down regulation of TRH in the hypophysiotrophic TRH neurons. It is possible that, in a sub-group of animals identified behaviourally, a mechanism resulting in hypothalamic down-regulation of the HPT axis persists following inflammatory injury.
    Full-text · Article · Aug 2014 · Brain Research Bulletin
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    • "Measurements of rT3 had been considered useful in differentiating non thyroidal illness (high rT3) from secondary hypothyroidism (low TSH), which should be associated with low rT3. Subsequent studies however showed that rT3 does not accurately distinguish the two states [13]. "
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    ABSTRACT: Background The non thyroidal illness syndrome (NTIS) represents a risk factor for prolonged mechanical ventilation in mechanically ventilated, critically ill patients admitted to the ICU. It is unclear, whether the NTIS is only a biochemical prognostic marker or it actually contributes to the development and progression of respiratory failure. Aim To assess the thyroid function in patients with respiratory failure and to evaluate the impact of thyroid dysfunction as well as thyroid hormone replacement therapy on patients’ outcome. Patients and methods The study was conducted on 100 patients (51 females and 49 males), they were divided into two groups, Group A (respiratory failure group), who were admitted to the Respiratory ICU (RICU) and group B (non-respiratory failure group) who were admitted to the Inpatient Chest Department of Zagazig University Hospitals Egypt. The respiratory failure group (Group A) included sixty-four (64) patients with respiratory failure (according to ABG parameters) 30 males and 34 females. They included 30 patients with acute exacerbation of COPD, 5 patients with acute severe bronchial asthma, 5 patients with severe pneumonia, 4 patients with acute pulmonary embolism, 8 patients with ARDS and 12 patients with acute exacerbation of IPF. This respiratory failure group included 43 patients who were on invasive mechanical ventilation and 21 respiratory failure patients who were non-mechanically ventilated. Group (B) included thirty-six (36) patients without respiratory failure according to ABG parameters as a control group (19 males and 17 females). There were 11 patients with acute exacerbation of COPD, 10 patients with exacerbated bronchial asthma, 6 patients with exacerbated IPF, 6 patients with pneumonia and 3 patients with acute pulmonary embolism. All patients were subjected to calculation of APACHE Π score, PaO2/FiO2 ratio and estimation of thyroid hormones (TSH, free T3 and free T4) at the 1st, 3rd and 10th day of admission. Those who were still having ESS at the 10th day (16 patients) and were not improving clinically, were subdivided randomly into two subgroups. Each of them comprised 8 patients. One group was given l-thyroxin replacement therapy (The replacement group) beside conventional appropriate management. The other group (8 patients) was followed by conventional appropriate management only without replacement therapy (The non-replacement group). l-Thyroxine 100 μg daily is administered for 7 weeks. At the 7th week, a fourth set of thyroid hormone estimation was done for the patients of the replacement and non-replacement groups. Patients’ outcome was assessed after 7 weeks of admission and labeled as the following: 1-death, 2-successfully treated and discharged. Results Respiratory failure patients showed evidence of euthyroid sick syndrome (ESS) at the 1st, 3rd and 10th days of admission with a frequency of 31.2%, 79.6% and 43.7% respectively while none of the control group showed evidence of (ESS) and the difference was statistically significant. There were highly significant negative correlation between serum levels of free T3 and TSH and each of the duration of mechanical ventilation and length of ICU stay. There was significant negative correlation between APACHE Π score and serum level of freeT3 in the respiratory failure group. There was non significant impact of thyroid hormone levels on patients’ outcome. There was non significant difference in the levels of thyroid hormones between replacement and non replacement groups at the 7th week of the study. Conclusion A state of hypothyroidism or euthyroid sick syndrome (ESS) is commonly found among patients with respiratory failure and this is related to the severity of the disease. ESS represents a risk factor for prolonged mechanical ventilation and length of ICU stay. l-thyroxin replacement therapy has no significant impact on patients’ outcome.
    Preview · Article · Apr 2014
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