Introduction: Non-thyroidal illness syndrome commonly occurs during acute systemic illnesses and is characterized by suppressed or inappropriately normal thyroid-stimulating hormone with low or low-normal thyroid hormone levels. This biochemical pattern may obscure or delay the diagnosis of underlying hyperthyroidism, especially in mild or borderline cases. Acute stroke is a recognized trigger of non-thyroidal illness syndrome, yet its masking effect on hyperthyroidism is under-recognized in clinical practice. Case: A 58-year-old Malay male with cardiovascular risk factors presented with an acute ischemic stroke involving the left occipital lobe and right internal capsule. He developed new-onset atrial fibrillation (CHA₂DS₂-VASc 3) and mild left ventricular systolic dysfunction. Initial thyroid function tests during the acute stroke phase showed mildly suppressed thyroid-stimulating hormone (TSH) (0.30 mIU/L) with high-normal free T4 (21.2 pmol/L), interpreted in the context of acute illness. The patient was clinically stable without overt thyrotoxic features. One month post-stroke, repeat testing revealed further TSH suppression (0.09 mIU/L) and rising free T4 (27.6 pmol/L). Detailed history uncovered prior Graves’ disease in 2019 with treatment default. Examination revealed a small diffuse goiter without ophthalmopathy. The biochemical evolution following recovery from acute illness confirmed recurrent hyperthyroidism previously masked by nonthyroidal illness syndrome. Conclusion Acute stroke can induce cytokine-mediated suppression of the hypothalamic-pituitary-thyroid axis and altered peripheral deiodination, leading to misleading thyroid function tests. In this case, non-thyroidal illness syndrome blunted the biochemical severity of hyperthyroidism, delaying recognition despite high-risk features such as atrial fibrillation and prior Graves’ disease. Reliance on a single thyroid function test during acute illness may therefore result in underdiagnosis.
Euthyroid Sick Syndromes ; Ischemic Stroke ; Hyperthyroidism

OBJECTIVE: To study the incidence rate of non-thyroidal illness syndrome (NTIS) in critically ill children with or without sepsis and the association of NTIS with interleukin-6 (IL-6) and interleukin-10 (IL-10). METHODS: A retrospective analysis was performed on the medical data of 97 children with sepsis (sepsis group) and 80 non-sepsis children with bacterial infection (non-sepsis group). The correlations of IL-6 and IL-10 with the thyroid function parameters triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were analyzed. RESULTS: There were no significant differences in age and sex between the sepsis and non-sepsis groups (P>0.05). Compared with the non-sepsis group, the sepsis group had a significantly higher Sequential Organ Failure Assessment score, a significantly longer length of hospital stay, and a significantly higher rate of use of ventilator (P<0.05). As for inflammation markers, the sepsis group had significantly higher levels of C-reactive protein, procalcitonin, and IL-6 than the non-sepsis group (P<0.05). As for thyroid function parameters, the sepsis group had significantly lower levels of T3, T4, free T3, free T4, and TSH than the non-sepsis group (P<0.05). Compared with the non-sepsis group, the sepsis group had significantly higher incidence rates of NTIS, low T3 and T4, and low TSH (P<0.001). The correlation analysis revealed that IL-6 level was not correlated with T3, T4, and TSH levels in children with or without sepsis (P>0.05), but the pooled analysis of the two groups showed that IL-6 level was negatively correlated with T3 and T4 levels (P<0.001). CONCLUSIONS Children with sepsis have a higher incidence rate of NTIS than those without sepsis. The high level of IL-6 may be associated with the development of NTIS.
Child ; Critical Illness ; Euthyroid Sick Syndromes ; Humans ; Interleukin-10/blood* ; Interleukin-6/blood* ; Retrospective Studies ; Sepsis ; Thyrotropin ; Thyroxine

PURPOSE: We compared thyroid hormone profiles in children with nephrotic syndrome (NS) during the nephrotic phase and after remission. METHODS: This study included 31 pediatric NS patients. The thyroid hormone profiles included serum levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and free T4. RESULTS: Of the 31 patients, 16 (51.6%) showed abnormal thyroid hormone profiles: 6 had overt hypothyroidism, 8 had subclinical hypothyroidism, and 2 had low T3 syndrome. The mean serum T3, T4, and free T4 levels in the nephrotic phase and after remission were 82.37±23.64 and 117.88±29.49 ng/dL, 5.47±1.14 and 7.91±1.56 µg/dL, and 1.02±0.26 and 1.38±0.23 ng/dL, respectively; the levels were significantly lower in the NS nephrotic phase (P=0.0007, P<0.0001, and P=0.0002). The mean serum TSH levels during the nephrotic phase and after remission were 8.05±3.53 and 4.08±2.05 µIU/ mL, respectively; they were significantly higher in the nephrotic phase (P=0.0005). The urinary protein/ creatinine ratio during the nephrotic phase was significantly correlated with serum T3, T4, and free T4 levels (r=-0.5995, P=0.0032; r=-0.5797, P=0.0047; r=-0.5513, P=0.0078) as well as with TSH levels (r=0.5022, P=0.0172). A significant correlation was found between serum albumin and serum T3 levels during the nephrotic phase (r=0.5385, P=0.0018) but not between serum albumin and T4, TSH, or free T4 levels. These significant correlations all disappeared after remission. CONCLUSION: Abnormal thyroid hormone profile findings were observed in 51.6% of pediatric patients with NS. Thyroid hormone levels normalized after remission, regardless of levothyroxine therapy.
Child ; Creatinine ; Euthyroid Sick Syndromes ; Humans ; Hypothyroidism ; Nephrotic Syndrome ; Serum Albumin ; Thyroid Gland ; Thyroid Hormones ; Thyrotropin ; Thyroxine ; Triiodothyronine

With the generalized use of highly sensitive thyroid stimulating hormone (TSH) and free thyroid hormone assays, most thyroid function tests (TFTs) are straightforward to interpret and confirm the clinical impressions of thyroid diseases. However, in some patients, TFT results can be perplexing because the clinical picture is not compatible with the tests or because TSH and free T4 are discordant with each other. Optimizing the interpretation of TFTs requires a complete knowledge of thyroid hormone homeostasis, an understanding of the range of tests available to the clinician, and the ability to interpret biochemical abnormalities in the context of the patient's clinical thyroid status. The common etiologic factors causing puzzling TFT results include intercurrent illness (sick euthyroid syndrome), drugs, alteration in normal physiology (pregnancy), hypothalamic-pituitary diseases, rare genetic disorders, and assay interference. Sick euthyroid syndrome is the most common cause of TFT abnormalities encountered in the hospital. In hypothalamic-pituitary diseases, TSH levels are unreliable. Therefore, it is not uncommon to see marginally high TSH levels in central hypothyroidism. Drugs may be the culprit of TFT abnormalities through various mechanisms. Patients with inappropriate TSH levels need a differential diagnosis between TSH-secreting pituitary adenoma and resistance to thyroid hormone. Sellar magnetic resonance imaging, serum α-subunit levels, serum sex hormone-binding globulin levels, a thyrotropin-releasing hormone stimulation test, trial of somatostatin analogues, and TR-β sequencing are helpful for the diagnosis, but it may be challenging. TFTs should be interpreted based on the clinical context of the patient, not just the numbers and reference ranges of the tests, to avoid various pitfalls of TFTs and unnecessary costly evaluations and therapies.
Diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; Euthyroid Sick Syndromes ; Homeostasis ; Humans ; Hyperthyroidism ; Hypothyroidism ; Magnetic Resonance Imaging ; Physiology ; Pituitary Neoplasms ; Rare Diseases ; Reference Values ; Sex Hormone-Binding Globulin ; Somatostatin ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyrotropin-Releasing Hormone

Critical illness can be associated with transient alterations in circulating thyroid hormone concentrations, indicating the presence of non-thyroidal illness (NTI). NTI is well described in humans, but there are few reports on its occurrence and prognostic significance in dogs. This retrospective study assessed the occurrence of NTI in a population of dogs with systemic inflammatory response syndrome (SIRS) and investigated its association with disease severity (APPLE(fast) scores). A total of 41 SIRS dogs were included and were divided by SIRS origin (non-septic SIRS, n = 10; septic SIRS, n = 41) and final outcome (survivors, n = 37; non-survivors, n = 4). Healthy, age-matched dogs (n = 15) were included as controls. Serum thyroid hormone levels including total T3, free T3, total T4, and reverse T3 were measured upon admission. Compared to controls, there were significant changes in serum thyroid hormone concentrations in SIRS dogs, suggesting the presence of NTI. Septic SIRS dogs had higher APPLE(fast) scores and lower serum thyroid hormones concentrations than those in non-septic SIRS and control dogs. In conclusion, NTI was frequent in dogs with SIRS and may be associated with the presence of sepsis or high illness severity.
Animals ; Critical Illness* ; Dogs* ; Euthyroid Sick Syndromes ; Humans ; Retrospective Studies* ; Sepsis ; Systemic Inflammatory Response Syndrome* ; Thyroid Gland* ; Thyroid Hormones*

BACKGROUND: Critical illness that requires major surgery is often associated with non-thyroidal illness syndrome (NTIS). The characteristic feature of NTIS is low serum triiodothyronine (T3) levels, and in severe illness, the levels of serum thyroxine (T4) are also low in the absence of a rise in thyroid stimulating hormone (TSH). However, little is known about the changes in thyroid hormones during and after liver transplantation (LT). This study was conducted in order to evaluate the intra- or postoperative changes in thyroid hormones. METHODS: Twenty-two patients who underwent LT were enrolled. Serum levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), free T3 (FT3) and free T4 (FT4) were measured immediately after the induction of anesthesia (T1), at the end of the anhepatic period (T2), at the end of the surgical procedure (T3), and at 24 hours (T4) and 120 hours postoperatively (T5). RESULTS: The mean levels of T3, T4, FT3, FT4 and TSH were significantly decreased throughout the study when compared with the T1 value. The mean levels of T3, T4 FT3 and TSH were below the normal range from T2, T4 and T5. CONCLUSIONS: We suggest that LT may induce NTIS by at least postoperative day 5. In the future, longer follow-up studies, and the effects of thyroid hormones on the prognosis and determination of the advantages and disadvantages of T3 replacement therapy to these patients will be required.
Anesthesia ; Critical Illness ; Euthyroid Sick Syndromes ; Humans ; Liver Transplantation* ; Prognosis ; Reference Values ; Thyroid Hormones* ; Thyrotropin ; Thyroxine ; Triiodothyronine

Thyroid hormone is important in brain development. Thus, thyroid hormone deficiency during the critical period of brain development results in severe cognitive and motor dysfunctions. Along with the development of intensive care for premature infants, the survival rates of premature babies and the long-term complications associated with neurodevelopment and motor function have increased. Premature infants differ from full-term infants in terms of the change in thyroid hormone level after birth because of the immaturity of their hypothalamus-pituitary-thyroid axis. Therefore, the diagnostic and therapeutic criteria for hypothyroidism in premature infants still remain unclear. In addition, as the thyroid function of premature infants can be affected by various diseases or drugs, periodic thyroid function tests are required. Although transient hypothyroxinemia is known to spontaneously recover in most infants, some studies have shown further complications associated with neurodevelopmental disorders. Accordingly, although thyroid hormone therapy in preterm infants has been introduced, its efficacy is yet controversial. In order to understand the thyroid abnormalities observed in premature infants or patients in neonatal intensive care units, this article intends to present a comprehensive review of the physiology of the thyroid gland, transient hypothyroxinemia/delayed thyroidstimulating hormone elevation, and euthyroid sick syndrome that affects thyroid function.
Axis, Cervical Vertebra ; Brain ; Critical Period (Psychology) ; Euthyroid Sick Syndromes ; Humans ; Hypothyroidism ; Infant ; Infant, Newborn* ; Infant, Premature ; Critical Care ; Intensive Care Units, Neonatal ; Parturition ; Physiology ; Survival Rate ; Thyroid Diseases ; Thyroid Function Tests ; Thyroid Gland*

Euthyroid Sick Syndromes ; blood ; etiology ; Female ; Gestational Age ; Humans ; Hypothyroidism ; blood ; etiology ; Infant, Newborn ; Infant, Premature ; Male ; Risk Factors ; Sex Factors ; Thyronines ; blood ; Triiodothyronine ; blood

OBJECTIVETo investigate the influencing factors of transient hypothyroxinemia (THT) and low T3 syndrome (LT3S) in premature infants.

METHODWe have studied 418 premature infants whose gestational age was between 26 and 36 weeks.Serum thyronine (T4), triiodothyronine (T3) and thyrotropin (TSH) of them were detected on the fourteenth day approximately after birth. The patients were divided according to their serum T4, T3 and TSH into 3 groups (transient hypothyroxinemia, low T3 syndrome and normal). Then 20 Perinatal factors which may be associated with THT and LT3S were collected. The factors were analyzed by using Chi-square test and Logistic regression.

RESULTForty-nine infants were found suffering from THT, 35 infants suffering from LT3S, and 334 infants in normal group. The prevalence rate of THT was 11.7%, and the prevalence rate of LT3S was 8.4%. Among the 20 factors, the factors related to the incidence of THT were male gender (OR = 1.863, 95%CI 0.966-3.594), albumin (OR = 2.401, 95%CI 1.294-4.455), dopamine (OR = 3.295, 95%CI 1.110-9.783) and those related to the incidence of LT3S were male gender (OR = 2.592, 95%CI 1.171-5.736), gestational age ≤ 28 wk (OR = 3.503, 95%CI 1.275-9.627).

CONCLUSIONMale gender, albumin and dopamine are perinatal risk factors of THT, meanwhile, male gender and gestational age ≤ 28 wk are perinatal risk factors of LT3S.With the use of risk factors identified in our study, it may be possible to separate infants having the highest risk of THT and LT3S, so as to form optimizing treatment strategies.

Case-Control Studies ; Dopamine ; adverse effects ; Euthyroid Sick Syndromes ; blood ; epidemiology ; etiology ; Female ; Gestational Age ; Humans ; Hypothyroidism ; blood ; epidemiology ; etiology ; Infant, Newborn ; Infant, Premature ; blood ; Infant, Premature, Diseases ; blood ; epidemiology ; etiology ; Logistic Models ; Male ; Risk Factors ; Sex Factors ; Thyroid Function Tests ; Thyronines ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

PURPOSE: The purpose of this study was to evaluate short-term thyroid dysfunction and related risk factors in pediatric patients who underwent hematopoietic stem cell transplantation (HSCT) during childhood. METHODS: We studied 166 patients (100 boys and 66 girls) who underwent HSCT at the Catholic HSCT Center from January 2004 through December 2009. The mean age at HSCT was 10.0+/-4.8 years. Thyroid function of the patients was tested before and during 3 months of HSCT. RESULTS: Out of 166 patients, 165 (99.4%) underwent allotransplantation. Acute graft-versus-host disease (GVHD, grades II to IV) developed in 76 patients. Conditioning regimens before HSCT include total body irradiation (n=57), busulfan (n=80), and reduced intensity (n=29). Forty-five (27.1%) had thyroid dysfunction during 3 months after HSCT (29 euthyroid sick syndrome [ESS], 6 subclinical hyperthyroidism, 4 subclinical hypothyroidism, 3 hypothyroxinemia, 2 overt hyperthyroidism, and 1 high T4 syndrome). In a univariate logistic regression analysis, age at HSCT (P=0.002) and acute GVHD (P=0.009) had statistically significant relationships with thyroid dysfunction during 3 months after HSCT. Also, in a univariate logistic regression analysis, ESS (P=0.014) showed a strong statistically significant association with mortality. CONCLUSION: In our study 27.1% patients experienced thyroid dysfunction during 3 months after HSCT. Increase in age and acute GVHD may be risk factors for thyroid dysfunction during 3 months after HSCT. There was a significant association between ESS and mortality.
Busulfan ; Child ; Euthyroid Sick Syndromes ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Hyperthyroidism ; Hypothyroidism ; Logistic Models ; Risk Factors ; Thyroid Gland ; Whole-Body Irradiation