Low Triiodothyronine Syndrome in Patients With Radiation Enteritis

Fan, Shiqing; Ni, Xiaoqing; Wang, Jian; Zhang, Yongliang; Shen, Tao; Chen, Mimi; Li, Yousheng; Li, Jieshou

doi:10.1097/md.0000000000002640

Cited by 6 publications

(10 citation statements)

References 35 publications

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“…The lower SPINA-GD (step-up deiodinase activity) and SPINA-GT (thyroid secretory capacity) are likely to reflect thyroid allostasis responses, and the lower protein binding of thyroid hormones, as shown by the lower TT3/FT3 and TT4/FT4 ratios, may potentially result in higher metabolism/degradation of thyroid hormones. Thyroid allostasis-altered responses have been found in NTIS associated with cardiac disease ( 37 ), radiation enteritis ( 60 ) and enterocutaneous fistulas ( 98 ). The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the more complex alterations associated with chronic illness frequently lead to type 1 thyroid allostasis (where energy demands exceed the sum of energy intake and energy mobilized from stores) ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

“…SPINA-GD and -GT were calculated as SPINA-GD = [β 31 × ( K M1 + FT4) × TT3]/(α 31 × FT4) and SPINA-GT = [β T × ( D T + TSH) × TT4]/(α T × TSH). Constants in the equations were as follows: β 31 = 8 × 10 –6 /s, K M1 = 5 × 10 –7 mol/L, α 31 = 0.026/L, β T = 1.1 × 10 −6 /s, D T = 2.75 mU/L, and α T = 0.1/L ( 59 , 60 ). The rT3/TT3 ratio was also calculated as a proxy for a metabolic shift.…”

Section: Methodsmentioning

confidence: 99%

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Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

Ruiz-Núñez

Tarasse

Vogelaar³

et al. 2018

Front. Endocrinol.

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Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21–69 years, 21 males) and 99 age- and sex-matched controls (19–65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation. Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%). FT3 below the reference range, consistent with the “low T3 syndrome,” was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00–6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of “non-thyroidal illness syndrome” and “low T3 syndrome” experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

Ruiz-Núñez

Tarasse

Vogelaar³

et al. 2018

Front. Endocrinol.

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“…Characteristic patterns of NTIS have been described in a multitude of acute and chronic somatic illnesses including states of shock ( 284 ), circulatory arrest ( 285 , 286 ), respiratory failure ( 65 ), community-acquired pneumonia ( 287 ), sepsis ( 288 ), chronic respiratory ( 289 , 290 ) and cardiovascular ( 61 , 64 , 66 , 291 , 292 ) disease, renal failure ( 293 – 298 ), COPD ( 289 ), gastrointestinal diseases ( 299 – 301 ), autoimmune diseases ( 71 , 302 , 303 ), and cancer ( 130 , 290 , 304 ). Phenotypes of NTIS with high and high-normal FT4 concentrations have been described in dementia and frailty in elderly persons ( 305 ).…”

Section: Thyroid Allostasis In Various Physiological and Pathologicalmentioning

confidence: 99%

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

Hoermann²,

et al. 2017

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The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions.

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“…Multiple trials demonstrated SPINA-GD to be reduced in NTIS ( 57 , 69 – 71 ). One of these trials also reported that SPINA-GD predicts postoperative atrial fibrillation and correlates to age, total atrial conduction time (PA-TDI interval), as well as to concentrations of B-type natriuretic peptide (BNP) and 3,5-T2 ( 57 ).…”

Section: Measures Of Thyroid Function and Peripheral Hormone Metabolimentioning

confidence: 99%

“…In the original validation study, gonadotropic insufficiency and lower peak concentrations of growth hormone and cortisol in pituitary stimulation tests were associated with significantly diminished TSHI ( 74 ). Recently, it was demonstrated that the TSHI is also reduced in patients with NTIS and thyrotropic adaptation ( 69 ).…”

Section: Estimated Parameters For Pituitary Functionmentioning

confidence: 99%

Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research

Landgrafe-Mende²,

et al. 2016

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Although technical problems of thyroid testing have largely been resolved by modern assay technology, biological variation remains a challenge. This applies to subclinical thyroid disease, non-thyroidal illness syndrome, and those 10% of hypothyroid patients, who report impaired quality of life, despite normal thyrotropin (TSH) concentrations under levothyroxine (L-T4) replacement. Among multiple explanations for this condition, inadequate treatment dosage and monotherapy with L-T4 in subjects with impaired deiodination have received major attention. Translation to clinical practice is difficult, however, since univariate reference ranges for TSH and thyroid hormones fail to deliver robust decision algorithms for therapeutic interventions in patients with more subtle thyroid dysfunctions. Advances in mathematical and simulative modeling of pituitary–thyroid feedback control have improved our understanding of physiological mechanisms governing the homeostatic behavior. From multiple cybernetic models developed since 1956, four examples have also been translated to applications in medical decision-making and clinical trials. Structure parameters representing fundamental properties of the processing structure include the calculated secretory capacity of the thyroid gland (SPINA-GT), sum activity of peripheral deiodinases (SPINA-GD) and Jostel’s TSH index for assessment of thyrotropic pituitary function, supplemented by a recently published algorithm for reconstructing the personal set point of thyroid homeostasis. In addition, a family of integrated models (University of California-Los Angeles platform) provides advanced methods for bioequivalence studies. This perspective article delivers an overview of current clinical research on the basis of mathematical thyroid models. In addition to a summary of large clinical trials, it provides previously unpublished results of validation studies based on simulation and clinical samples.

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Low Triiodothyronine Syndrome in Patients With Radiation Enteritis

Cited by 6 publications

References 35 publications

Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research

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