Low Thyroxine Research Articles

Effect of climatic factors on sexual maturity Labeo rohita fish

<p>This study examined the varying levels of thyroxine hormone impact (at doses of 2, 10, and 50 µg g-1 BW) as an environmentally responsive hormone on the fatty acid and sexual steroid profiles in male Labeo rohita fish. Each treatment group comprised six male fish with an average weight of 5.4 ± 0.58 kg. Blood samples were collected from male rohu fish pre-and post-injection, as well as following sperm retrieval from the caudal peduncle. Biotechnical parameters were evaluated post-fertilization. Among male breeders, the pituitary treatment and the 50 µg g-1 BW thyroxine treatment exhibited the highest levels of estradiol, testosterone, 17-alpha hydroxyprogesterone, cortisol, LH, as well as testicular protein and fat content. Whereas the lowest levels were observed in the LHRH recipient and control groups (p < 0.05). Moreover, the saturated fatty acids C16:0 and C18:0, monounsaturated fatty acids C18:1n9c and C24:1n9, along with polyunsaturated fatty acids C20:3n6 and C22:6n3 in male breeders, were found to be the predominant fatty acids in the testes under hormonal treatment. The pituitary treatment and the 50 µg g-1 BW thyroxine treatment demonstrated a greater total percentage of testicular fatty acids compared to other interventions (p < 0.05). These findings emphasize the heightened efficacy of pituitary hormone and subsequent thyroxine hormone administration at a dose of 50 µg g-1 BW, relative to lower thyroxine doses and LHRH. The aforementioned treatment can increase the levels of sex hormones that are important for sexual responsiveness, emphasizing their pivotal role in facilitating successful artificial reproduction in male Rohu breeders.</p>

A confusing situation in the clinic: isolated maternal hypothyroxinemia

Isolated maternal hypothyroxinemia (IMH) is a common problem in the clinic. There is a normal maternal thyroid stimulating hormone (TSH) level with a low maternal free thyroxine (FT4) level. The aim of this review is to explain IMD in the light of current literature and to contribute to clinicians in the management of IMH. Iodine deficiency is the most important factor in etiology. The effects of IMH on the pregnant woman and the fetus are not clear. However, it is a serious concern among serious clinicians, especially considering the importance of the effect of thyroid hormones on fetal brain development. As for the treatment of IMH, the number of studies conducted is not sufficient and there is no consensus and evidence on levothyroxine treatment. However, there is a consensus on iodine supplementation and it is recommended to take 250 mg of iodine daily. As a result, IMH is a problem that should be taken seriously during pregnancy and care should be taken regarding its diagnosis and treatment. Additionally, more research is needed on the effects and treatment of IMH on pregnant and fetal health

Before Low Serum Cortisol Can Be Attributed to SARS-Cov-2 Infection, Alternative Causes Must Be Ruled Out

We read with interest Banu et al.,’s article about a cross-sectional study of adrenal function using blood levels of cortisol and adrenocorticotropic hormone (ACTH) in 91 patients with acute SARS-CoV-2 infection. It was found that 27% of patients with severe COVID-19, 26% with mild COVID-19 and 4% with moderate COVID-19 had adrenal insufficiency. Decreased cortisol reserve was found in 6.6% of all patients. It was concluded that the adrenocortical response was impaired in a significant number of non-critically ill COVID-19 patients, with the percentage being highest in patients with severe COVID-19 disease.1 The study is impressive, but some points should be discussed. The major limitation of the study is that imaging of the pituitary gland and hypothalamus was not performed. To rule out pituitary adenoma, hypophysitis, pituitary apoplexy, pituitary abscess, sellar tuberculoma, or hypothalamic stroke or bleeding, magnetic resonance imaging (MRI) of the pituitary gland and the hypothalamus with contrast agent must be performed. Like any other infection, SARS-CoV-2 infection can trigger the appearance of symptoms of a pituitary pathology.2 A second limitation is that imaging of the suprarenal glands was not performed. To assess whether there was adrenal atrophy, adenoma, ischemia, bleeding, or carcinoma, adrenal imaging is mandatory. 3 A third limitation is that current medication was not reported. Several medications are known to affect serum cortisol levels, making it imperative to know all medications regularly taken by the included patients. Ketoconazole, isilodrostat, vitamin D and omega-3 fatty acids in particular are known to be able to reduce cortisol levels in the blood.4 A fourth limitation is that no ACTH stimulation test was performed to determine whether primary or secondary suprarenal insufficiency was present. Determining cortisol levels alone without ACTH stimulation testing is not reliable with regard to cortical adrenal function. A fifth limitation is that serum dehydroepiandrosterone (DHEA) levels were not measured. Since DHEA is the antagonist of cortisol and decreases with age, it is conceivable that high levels of DHEA promoted the reduction of serum cortisol.5 Since low thyroxine levels may be associated with low cortisol levels,6 it would also be desirable to know whether thyroid function was normal or abnormal in the included patients. In summary, the excellent study has limitations that should be addressed before drawing final conclusions. Clarifying the weaknesses would strengthen the conclusions and could improve the study. Serum cortisol levels may be low not only due to SARS-CoV-2 infection but also due to several other causes. Before adrenal insufficiency can be attributed solely to inadequate cortical cortisol production, the entire hypothalamic-pituitary-adrenal axis must be thoroughly examined.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.

Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS).

Post-acute COVID-19 vaccination syndrome (PACVS) is a chronic disease triggered by SARS-CoV-2 vaccination (estimated prevalence 0.02%). PACVS is discriminated from the normal post-vaccination state by altered receptor antibodies, most notably angiotensin II type 1 and alpha-2B adrenergic receptor antibodies. Here, we investigate the clinical phenotype using a study registry encompassing 191 PACVS-affected persons (159 females/32 males; median ages: 39/42 years). Unbiased clustering (modified Jaccard index) of reported symptoms revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (>80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, and vasomotor dysfunction; (ii) cardiovascular impairment; and (iii) cognitive impairment, headache, and visual and acoustic dysfunctions were also frequently represented. Notable abnormalities of standard serum markers encompassing increased interleukins 6 and 8 (>80%), low free tri-iodine thyroxine (>80%), IgG subclass imbalances (>50%), impaired iron storage (>50%), and increased soluble neurofilament light chains (>30%) were not associated with specific symptoms. Based on these data, 131/191 participants fit myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and simultaneously also several other established dysautonomia syndromes. Furthermore, 31/191 participants fit none of these syndromes. In conclusion, PACVS could either be an outlier of ME/CFS or a dysautonomia syndrome sui generis.

Post-gastric sleeve gastrectomy mixed Wernicke's and Hashimoto's encephalopathies with brain atrophy: A case-report from Qatar

We present a case of a 21-year-old male patient who presented with progressive dizziness, gait instability, and ataxia of 1-week duration. Three months prior to presentation, the patient underwent Laparoscopic Sleeve Gastrectomy (LSG). His workup showed a very low level of thiamine, high thyroid-stimulating hormone (TSH) level, and very low free thyroxine (T4). The patient was diagnosed with Wernicke Encephalopathy (WE) post LSG, exacerbated by Hashimoto Encephalopathy (HE), given the history of an underlying uncontrolled Hashimoto's thyroiditis (HT).

Resistance To Thyroid Hormone Receptor Alpha Due to Heterozygous Pathogenic Variant in THRA Gene: A Case Report from India

Background: Thyroid Hormone Receptor Alpha (THRA) gene mutation is a thyroid hormone resistance syndrome characterized by non-responsiveness of target tissues to the active form of TH (T3). Clinical Description: We describe a heterozygous missense variant in exon 8 of THRA gene detected in a 2-month-old female with clinical phenotype of hypothyroidism, low free thyroxine, elevated free triiodothyronine &amp; normal levels of thyroid stimulating hormone. Management &amp; Outcome: Clinical improvement in linear growth, motor development domain, hypotonia &amp; constipation were noted with levothyroxine therapy but insufficiencies in cognitive and fine motor skills may remain. Conclusion: THRA gene mutation should be considered in patients with features of clinical hypothyroidism and elevated free T3, decreased/ normal free thyroxine &amp; normal thyroid-stimulating hormone levels.

Low thyroxine serves as an upstream regulator of ecophysiological adaptations in Ansell's mole-rats.

About 10% of all rodent species have evolved a subterranean way of life, although life in subterranean burrows is associated with harsh environmental conditions that would be lethal to most animals living above ground. Two key adaptations for survival in subterranean habitats are low resting metabolic rate (RMR) and core body temperature (Tb). However, the upstream regulation of these traits was unknown thus far. Previously, we have reported exceptionally low concentrations of the thyroid hormone (TH) thyroxine (T4), and peculiarities in TH regulating mechanisms in two African mole-rat species, the naked mole-rat and the Ansell's mole-rat. In the present study, we treated Ansell's mole-rats with T4 for four weeks and analyzed treatment effects on the tissue and whole organism level with focus on metabolism and thermoregulation. We found RMR to be upregulated by T4 treatment but not to the extent that was expected based on serum T4 concentrations. Our data point towards an extraordinary capability of Ansell's mole-rats to effectively downregulate TH signaling at tissue level despite very high serum TH concentrations, which most likely explains the observed effects on RMR. On the other hand, body weight was decreased in T4-treated animals and Tb was upregulated by T4 treatment. Moreover, we found indications of the hypothalamus-pituitary-adrenal axis potentially influencing the treatment effects. Taken together, we provide the first experimental evidence that the low serum T4 concentrations of Ansell's mole-rats serve as an upstream regulator of low RMR and Tb. Thus, our study contributes to a better understanding of the ecophysiological evolution of the subterranean lifestyle in African mole-rats.

Low Free Thyroxine (FT4) in critically ill juvenile systemic lupus erythematosus: a diagnostic approach

Introduction: Thyroid dysfunction was frequent in systemic lupus erythematosus (SLE) patients, which may present as euthyroid, hypothyroid, or hyperthyroid states. Critical conditions have a higher chance of euthyroid sick syndrome due to alterations in the hypothalamic-pituitary-thyroid (HPA) axis. Renal impairment was associated with an increased risk of low FT4 due to proteinuria followed by thyroid loss. Case Description: We reported one patient, a 15-year-old girl, who complained of shortness of breath and revealed acute respiratory distress syndrome, valve regurgitation, and pericardial effusion. She also felt joint pain over the leg and odor urination. Further evaluation showed non-scaring alopecia, pyuria, proteinuria &gt;0.5 gram/24 hours, urinary cast, and acute kidney injury stage failure. ANA (IF) pattern: scattered with titer 1:100, ANA profile indicated Smith (Sm) antigen (+) and C3 108.3 mg/d, which fulfilled Systemic Lupus International Collaborating Clinics (SLICC) 2015 and European League Against Rheumatism (EULAR) 2019 criteria for SLE. On the fourth day of treatment, the patient had acute confusion, hypothermia, and sinus bradycardia, while the investigation of FT4 hormone was 0.45 ng/dL, TSH 2.39 uIu/ml, which revealed euthyroid sick syndrome. After treatment with a high dose of methylprednisolone, cyclophosphamide, rituximab, levothyroxine, a phosphodiesterase inhibitor, and a diuretic, she deteriorated and passed away. Conclusion: The higher prevalence of thyroid dysfunction in juvenile SLE patients necessitates further attention. Lupus nephritis, increased creatinine level, detection of Smith (Sm) antigen, and critical condition were also at higher risk of low FT4 in juvenile SLE patients. This condition may have a worsened prognosis with prompt diagnosis and treatment.

Understanding and approach of Ayurveda management towards a unique case of Hashimoto Thyroiditis - A Case Report

Hashimoto thyroiditis is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis, is an autoimmune disease in which thyroid cells are destroyed via cell and antibody-mediated immune processes. It is the most common cause of hypothyroidism in developed countries. The Pathophysiology of Hashimoto Thyroiditis involves the formation of antithyroid antibodies that attack the thyroid tissue, causing progressive fibrosis. The condition is sometimes not diagnosed until late in the disease process. The most common laboratory findings demonstrate elevated Thyroid-Stimulating Hormone (TSH) and low Thyroxine (T4) levels, coupled with increased anti thyroid peroxidase (anti-TPO) antibodies. In Ayurveda, it can be correlated with Rasavaha Sroto Vikara, Dhatwagnimandya, Vataja Pandu, Pittavruta Vata based on symptoms. Case Report: In this present study a female patient aged 37 years, known case of Hashimoto Thyroiditis since 8 years was treated with Shiro Takradhara, Sarvanga Abhynaga, Virechana and specific Shamanaushadhi’s as per signs and symptoms. Results: After 2 months of treatment there was a significant reduction in the signs and symptoms of the disease with 70% improvement in the condition.

Hypothyroxinemia and weight velocity in preterm infants.

Hypothyroxinemia of prematurity (HOP) is characterized by low free thyroxine (FT4) associated with low or normal thyroid stimulating hormone (TSH). The objective of this study is to define FT4 and TSH values in very preterm infants (<32 weeks postmenstrual age, PMA) and correlate hypothyroxinemia and levothyroxine treatment with growth velocity at 28 days and 36 weeks PMA. Preterm neonates <32 weeks PMA admitted to the regional neonatal intensive care unit (NICU) at the Children's Hospital of Georgia (USA) between January 2010 and July 2022 were routinely screened for hypothyroxinemia. FT4 and TSH values were obtained on 589 eligible neonates between day of life (DOL) 4 and 14. Growth velocity (g/kg/day) from DOL 14 to DOL 28 and 36-weeks PMA were calculated for each neonate and potential explanatory variables (PMA, sex, and race) were incorporated into multivariate regression models to identify associations between HOP and growth velocity. In 589 preterm infants, PMA at birth was strongly associated inversely with FT4 (R=0.5845) and modestly with TSH (R=0.2740). Both FT4 and gestational age, but not TSH or levothyroxine treatment, were associated with growth velocity at 28 days of life and at 36 weeks PMA. We provide a large data set for identifying FT4 and TSH measurements and identify hypothyroxinemia of prematurity as a potential mediator of slow postnatal growth in very preterm infants.

Clinical and molecular analyses of isolated central congenital hypothyroidism based on a survey conducted in Japan.

Central congenital hypothyroidism (CH) can occur as an isolated deficiency or as part of combined pituitary hormone deficiency. Unlike primary CH, central CH cannot be detected by newborn screening (NBS) using dry filter paper blood TSH levels, and early diagnosis remains challenging. In this study, the clinical and genetic backgrounds of patients with isolated central CH were determined through a questionnaire-based survey among members of the Japanese Society for Pediatric Endocrinology. The known causes of isolated central CH were studied in 14 patients, including six with previously reported patient data. The results revealed IGSF1 and TBL1X pathogenic variants in nine and one patient, respectively. All six patients with low free thyroxine (FT4) levels detected in NBS carried IGSF1 pathogenic variants. Five patients with isolated central CH diagnosed after 3 months of age were variant-negative, except for one female patient with a heterozygous IGSF1 variant. Two of the four variant-negative patients and a variant-positive patient were diagnosed with pituitary hypoplasia. One and two patients with IGSF1 variant had obesity and intellectual disability, respectively. Left amblyopia was identified in the patient with a TBL1X variant. The study revalidated that IGSF1 variants comprise the most frequent pathogenic variant in patients with isolated central CH in Japan. The neonatal period is the optimal time for the diagnosis of central CH, particularly IGSF1 abnormalities, and the introduction of T4 screening should be considered in the future, taking cost-effectiveness into consideration.

FRI502 Myxedema Coma With An Unusual Pattern Of Thyroid Function Tests Due To Amiodarone-induced Hypothyroidism

Abstract Disclosure: S. Nguyen: None. B. Force: None. R. Schneider Aguirre: None. Introduction: Myxedema coma is an endocrine emergency characterized by severe hypothyroidism resulting in altered mental status or coma, hypothermia, cardiovascular compromise, pulmonary edema or pleural effusions, and/or gastrointestinal hypomotility, classically in the context of an elevated TSH and low thyroxine levels. Amiodarone use is associated with alteration of thyroid function tests and could cloud the laboratory presentation of myxedema coma. Here we present a case of myxedema coma in a patient with amiodarone-induced hypothyroidism with an elevated free T4 (FT4) and low total T3 (TT3). Clinical Case: A 64-year-old female with a history of chronic systolic heart failure, persistent atrial flutter treated with amiodarone, cerebrovascular accident, hypertension, chronic kidney disease stage 4, but not hypothyroidism, presented with constipation, confusion and lethargy worsening over 3 days. On initial evaluation, she was minimally responsive, hypothermic to 95.6 °F and bradycardic to low 50s. She was intubated for airway protection and vasopressors were started due to concern for cardiogenic shock. Exam was notable for coarse facial features, edema and cold extremities. A bedside echocardiogram showed reduced cardiac function from baseline. Her TSH was 40.65 uIU/mL (RR, 0.45-5.33 uIU/mL), FT4 1.79 ng/dL (RR 0.64-1.42 ng/dL), total T4 14.30 mcg/dL (RR 6.09-12.23 mcg/dL), TT3 70 ng/dL (RR 87-178 70 ng/dL). Sodium was 135 mmol/L (RR 136-145 mmol/L), serum glucose was 42 mg/dL, (RR 70-110 mg/dL), and eGFR was 18 mL/min/1.73 m2 (baseline eGFR 28 mL/min/1.73 m2). Evaluations for myocardial infarction and infectious etiology were initiated and ultimately negative. While elevated FT4 is not characteristic of myxedema coma, the overall constellation of stupor, constipation, bradycardia, hyponatremia, hypoglycemia, decreased eGFR and decreased cardiac function, in the setting of an elevated TSH and low TT3, made the diagnosis of myxedema coma extremely likely. The patient was started on levothyroxine 200 mcg IV daily and hydrocortisone 100 mg IV every 8 hours. After 16-20 hours on this regimen, the patient was weaned off sedation and vasopressors, extubated, and recovered baseline mental status. Hydrocortisone was stopped and on day 3 of hospitalization, she was transitioned to oral levothyroxine 88 mcg daily. Due to premature ventricular contractions her dose was decreased to 50 mcg orally daily five days after her initial presentation to the hospital. During this time, the TSH decreased to 3.59 uIU/mL and the FT4 rose to 2.83 ng/dL. Conclusion: We conclude that in patients treated with amiodarone, myxedema coma can still occur even if T4 levels are normal or elevated, likely due to decreased T4 to T3 conversion. In these cases, elevated TSH and a clinical picture consistent with severe hypothyroidism are more reliable indicators if the (free) T4 levels are unexpectedly elevated. Presentation: Friday, June 16, 2023

A-059 Evaluation of Free Thyroxin Levels in Patients with Low Thyroxin Binding Globulin Concentrations: Is There Interference in the FT4 Indirect Method?

Abstract Background Thyroxine-binding globulin (TBG) is the major carrier of thyroid hormones in serum. Variations in the serum concentration of TBG determine proportional variations in the total serum concentrations of T4 and T3, without implying changes in function, as long as the free fraction remains normal. Several common clinical conditions lead to significant alterations in TBG levels, the most important factor behind low levels being genetic defects. As TBG is encoded by a gene located on the X chromosome, the defects are more easily manifested in males. Differences in FT4 concentrations were observed in sera from subjects with TBG abnormalities, when FT4 are measured by different immunoassays, specially at extremes of TBG concentrations. The objective of this study was to evaluate FT4 levels by indirect method in patients with low TBG concentrations. Methods We analyzed blood samples requesting serum TBG, TSH and FT4 levels from patients admitted to a private reference clinical laboratory in Brazil, from January 01, 2017 to December 31, 2022. Anonymized data on laboratory tests was available from a database of the local Laboratory Information System. All the patients included had TSH within the reference range, 0.4–4.3 mUI/mL (ECLIA, Modular, Roche). FT4 was measured by ECLIA (0.7–1.8 ng/dL) and TBG by ICMA, Immulite, Siemens, 13–39 mcg/mL. Results 357 patients with low TBG levels were evaluated, 220 (62%) men, 137 (38%) women; mean age 35 yrs (19 d to 88 yrs). They were divided in six groups according TBG levels (mcg/mL): &amp;lt;3.5–17 (M 15, F2); 3.5 to 6.0 - 26 (M 20, F 6); 6.1 to 8.0 - 30 (M 25, F 5); 8.1 to 9.9 - 59 ( M 32, F 27); 10.0 to 11.9 - 139 (M 78, F 61); 12.0 to 12.9 - 86 (M 50, F 36). Three patients had FT4 levels above 1.8 (1.85; 1.87 and 1.96) ng/mL, all them male, with TBG levels &amp;lt;3.5; 5.79 and 9.53 ng/mL, respectively. Conclusion FT4 Indirect methods are developed taking into account the presence, in the serum, of a thyroxine binding capacity within the normal range, a fact that does not occur in individuals with extreme TBG deficiency. In this study, we found only one slightly elevated FT4 value among 17 patients with TBG values below 3.5 mcg/mL, suggesting little interference of very low TBG levels in this indirect free T4 method.

Hormonal imbalance in patients with chronic kidney disease in the pre-dialysis and dialysis periods (part 2)

In the previous article, we presented the results of literature review showing the changes in hormone concentrations (parathyroid hormone, insulin, growth factor, prolactin) in patients with chronic renal failure (CRF) at the pre-dialysis and dialysis stages, described pathological relationships between renal failure and serum hormones concentrations, as well as changes in their biological effects. In this article, that continues the general topic, we provide the results of literature review that shows changes in serum concentrations of thyroid, adrenal, sex hormones and the features of the functioning of hypothalamus-pituitary-peripheral glands axis in patients with CRF. The presence of close pathogenic interactions of renal functional condition with hormonal activity of the thyroid gland was evaluated, as well as the ability of thyroid gland to influence the CRF progression both during pre-dialysis and dialysis sta­ges of CRF. Most patients with CRF have low serum triiodothyronine and thyroxine levels. It means that CRF is a pathological condition associated with thyroid hypofunction that progressively worsening as glomerular filtration rate decreases. For patients receiving dialysis treatment, hypothyroidism is associated with higher mortality. Secondary adrenal insufficiency is usually progresses in patients on renal replacement therapy. Non-diagnosed chronic adrenal failure may be life-threating that’s why the analysis of adrenal function is especially actual for patients on both pre-­dialysis and dialysis stages of CRF. Secondary adrenal insufficiency caused by long-lasting treatment with corticoids is a diagnostic problem for patients on dialysis treatment, because many nephrological diseases are treated by corticoids, and immunosuppressive therapy protocols used after the kidney transplantation are usually include prednisone. As the endocrine dysfunction progresses in patients with CRF, sexual dysfunction develops due to sex hormone imbalance. Abnormal androgen concentration is a typical fin­ding in CRF. A negative correlation was found between endogenic testosterone concentration and CRF stages I–V that indicated an abnormal profile of male sex hormones. There are gender-specific features of the development and progression of clinical symptoms of hormonal imbalance. The number of experimental studies show that continuous estradiol treatment may prevent the development of glomerulosclerosis. The results of clinical trials concluded that lower CRF progression and the lower incidence of CRF observed in young females compared to males, as well as the absence of gender protection in post-menopausal period, shows the important role of female sex hormones.

Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone

Chronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination.Se status and SELENOP-aAb prevalence was compared by combining European CFS patients (n = 167) and healthy controls (n = 545) from different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP showed linear correlations across the samples without reaching saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6–15.6% in CFS versus 0.9–2.0% in controls, depending on cut-off for positivity. The linear correlation between Se and GPx3 activity was absent in SELENOP-aAb positive patients, suggesting impaired Se supply of kidney. A subgroup of paired control (n = 119) and CSF (n = 111) patients had been characterized for TH and biochemical parameters before. Within this subgroup, SELENOP-aAb positive patients displayed particularly low deiodinase activity (SPINA-GD index), free T3 levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios. In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2 (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) μg/L). The data indicate that SELENOP-aAb associate with low deiodination rate and reduced activation of TH to active T3.We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se transport and reduce selenoprotein expression in target tissues. Hereby, TH activation decreases as an acquired condition not reflected by thyrotropin and T4 in blood. This hypothesis opens new diagnostic and therapeutic options for SELENOP-aAb positive CFS, but requires clinical evidence from intervention trials.

1573-P: Association of Thyroid Hormone Levels with NAFLD in Recent-Onset Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a growing health concern associated with obesity and type 2 diabetes (T2D). Thyroid hormones are important regulators of lipid homeostasis. Indeed, people with hypothyroidism are at greater risk for NAFLD and it has been suggested that humans with T2D are more likely to develop hypothyroidism. However, little is known about the relationship of thyroid function with NAFLD in type 1 diabetes (T1D) and T2D. We hypothesized that (i) low free thyroxin (fT4) and high thyroid-stimulating hormone (TSH) levels are associated with increased hepatocellular lipid content (HCL) and (ii) that fT4 and TSH can identify persons at high-risk for hepatic steatosis in people with recent-onset diabetes. We examined people with T1D (n=358) or T2D (n=596) and 175 healthy participants of the German Diabetes Study (GDS). First, validation of the fatty liver index (FLI) against quantification of HCL by 1H-magnetic resonance spectroscopy revealed a close correlation (ß=0.715, p&amp;lt;0.001; n=446). Second, FLI negatively correlated with fT4 in males (ß=−0.139, p&amp;lt;0.01), but not in females with T2D (ß=−0.086, p=0.26). Likewise, TSH associated positively with FLI in males (ß=0.116, p&amp;lt;0.05), but not in females with T2D (ß=−0.057, p=0.45). TSH and FLI were differently associated between males and females before (p&amp;lt;0.05), but not after (p=0.82) adjustment for BMI. Finally, fT4 had a low diagnostic precision for steatosis (by FLI) as derived from the respective area under the receiver operating curve (0.57, 95% CI [0.53;0.62]; p&amp;lt;0.001) in T2D and was not significant in other groups. TSH had no diagnostic precision for steatosis in any groups. In conclusion, FLI can be used as a surrogate measure of HCL in recent-onset diabetes. The correlation of FLI with lower thyroid function in male T2D suggests a sex-specific interaction between thyroid and liver lipid metabolism, which is mainly driven by body mass. Both, fT4 and TSH offer no relevant efficacy to detect steatosis at least in recent-onset diabetes. Disclosure N. Saatmann: None. M. Schön: None. O.P. Zaharia: None. M. Huttasch: None. K. Strassburger: None. S. Trenkamp: None. Y. Kupriyanova: None. V. Schrauwen-Hinderling: None. S. Kahl: None. V. Burkart: None. R. Wagner: Speaker's Bureau; Novo Nordisk, Sanofi. Advisory Panel; Daiichi Sankyo. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis. Consultant; TARGET PharmaSolutions, Inc. Research Support; Sanofi.

Association between serum-free thyroxine level and all-cause mortality in critically ill patients: a retrospective study from MIMIC-IV.

Low thyroxine (T4) levels have been observed in critically ill patients; however, controversial results regarding T4 supplemental therapy are reported. The association between serum free T4 (FT4) levels and mortality in critically ill patients has not been fully established and needs to be clarified. Data from the Medical Information Mart for Intensive Care (MIMIC)-IV were collected and analyzed. The association between FT4 level and 30-day mortality after ICU admission was analyzed using Kaplan-Meier curves, spline smoothing fitting, martingale residuals of the null Cox model, and restricted cubic spline (RCS). Logistic regression, Cox regression, and receiver operating characteristic curve (ROC) were used to uncover the relationship and predictive value of serum FT4 and 30-day mortality in critically ill patients. In the final analysis, 888 patients were enrolled, and the serum FT4 levels were divided into four groups. A significant difference in 30-day mortality was observed between the four groups. Kaplan-Meier curves also presented significantly higher 30-day mortality in groups 1 and 2 (p < 0.0001). Further multivariance logistic regression showed that group 1 with FT4 levels lower than 0.7 μg/dl can predict 30-day mortality (odds ratio (OR) = 3.30, 95% confidence interval (CI) = 1.04-11.31). Spline smoothing fitting analysis showed a "V"-shaped line between 30-day mortality and FT4 level within 0-3 μg/dl. Further RCS analysis showed that the risk of death decreased rapidly as FT4 levels increased when serum FT4 levels were lower than 1.2 μg/dl and started to become flat afterward. The area under the ROC of the lower FT4 level to predict 30-day mortality was 0.833 (95% CI = 0.788-0.878). Both multivariant Cox regression and logistic regression showed that FT4 levels lower than 1.2 μg/dl can independently predict 30-day mortality when adjusted for other potential confounders (HR = 0.34, 95% CI = 0.14-0.82; OR = 0.21, 95% CI = 0.06-0.79, respectively), but its predictive power disappeared when adjusted for T3 or total T4. Serum FT4 levels were significantly negatively associated with 30-day mortality when they were lower than 1.2 μg/dl and could predict the risk of 30-day mortality. A higher FT4 level is potentially related to increased 30-day mortality.

Increased prevalence of nodular thyroid disease in patients with Klinefelter syndrome

PurposeThyroid dysfunction in patients with Klinefelter syndrome (KS) remains an unresolved issue. Although low free thyroxine (FT4) levels within the normal range and normal thyroid stimulating hormone (TSH) levels have been reported, there is currently no data on nodular thyroid disease in this population. This study aims to evaluate the results of thyroid ultrasound (US) examinations in KS patients compared with healthy controls.MethodsA cohort of 122 KS and 85 age-matched healthy male controls underwent thyroid US screening and thyroid hormone analysis. According to US risk-stratification systems, nodules ≥1 cm were examined by fine needle aspiration (FNA).ResultsThyroid US detected nodular thyroid disease in 31% of KS compared to 13% of controls. No statistical differences in the maximum diameter of the largest nodules and in moderate and highly suspicious nodules were found between patients and the control group. Six KS patients and two controls with nodules underwent FNA and were confirmed as cytologically benign. In line with published data, FT4 levels were found significantly near the lower limit of the normal range compared to controls, with no differences in TSH values between the two groups. Hashimoto’s thyroiditis was diagnosed in 9% of patients with KS.ConclusionsWe observed a significantly higher prevalence of nodular thyroid disease in KS compared to the control group. The increase in nodular thyroid disease is likely linked to low levels of FT4, inappropriate TSH secretion, and/or genetic instability.

MAFLD in Patients with Cushing's Disease Is Negatively Associated with Low Free Thyroxine Levels Rather than with Cortisol or TSH Levels.

This study aims to analyze the clinical characteristic of metabolic associated fatty liver disease (MAFLD) in patients with active Cushing's disease (CD) and determine associations of thyroid hormones with MAFLD. Patients with active CD were included in this cross-sectional study. All subjects were assessed for hepatic steatosis by abdominal ultrasonography and thyroid functions. Demographic and clinical characteristic parameters were collected for correlation analysis and logistic analysis. 290 individuals with active CD were included in Huashan hospital from January 2014 to February 2022. We found that the prevalence of CD with MAFLD was 33.79%. The MAFLD group had a lower level of FT4 and a higher level of FT3/FT4 but no difference in levels of cortisol, 24 h UFC, TSH, TT4, TT3, and FT3. Correlation analysis showed positive associations of TSH, TT4, TT3, FT3, and FT3/FT4 with BMI. In age-, BMI-, sex-, cortisol-, and 24 h UFC-adjusted analysis, FT4 was independently associated with MAFLD in patients with CD. This association remained similar even after adjusting for the presence of metabolic syndrome components. Lower FT4 levels were associated with higher risk of MAFLD in patients with CD. FT4 may be used as a helpful indicator to predict MAFLD and provide novel ideas for the treatment of MAFLD in patients with CD in the future.