Low T4 Levels Research Articles

Correlation analysis of FT3/FT4 and frailty in elderly patients with coronary heart disease.

In previous studies on thyroid hormones and frailty, most of the target population were elderly, and there were relatively few studies on elderly patients with coronary heart disease (CHD). Inflammation, oxidative stress, and haemodynamic instability in cardiovascular disease (CVD) can influence fluctuations in thyroid hormone (TH) levels and increase the incidence of frailty. The purpose of the present study was to explore the effect of TH on the risk of frailty in elderly patients with CHD. The Fried scale was used to assess the frailty of participants. The predictive value of TH for frailty was determined using the patient's operating characteristic curve. Multivariate logistic regression model was utilised to analyse the relationship between TH and frailty. A total of 277 elderly patients with CHD were included in the study, of whom 29.96% were in a state of frailty. Free triiodothyronine (FT3)/free thyroxine (FT4) predicted frailty with the largest area under the curve of 0.634. Unordered multinomial logistic regression analysis showed that a lower T3 level was a risk factor for pre-frailty (p < 0.05). Lower levels of T3, FT3, and FT3/FT4 were risk factors for frailty (p < 0.05) after adjusting for demographic variables and blood indexes. The predictive value of FT3/FT4 for frailty was more accurate than that of a single index. Moreover, T3 ≤ 1.095 nmol/L, FT3 ≤ 4.085 pmol/L, and FT3/FT4 ≤ 0.336 were shown to be the influencing factors of frailty, while T3 ≤ 1.095 nmol/L is an independent risk factor pre-frailty. Clinicians should focus on timely identification of the risk of frailty in order to improve patient quality of life and to reduce the risk of complications.

7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency

Abstract Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None. Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention. Presentation: 6/2/2024

8278 Myxedema Coma With COVID-19 Infection

Abstract Disclosure: R. Kalas: None. V. Manohar: None. N.S. Bapat: None. Y. Kim: None. Myxedema coma is a rare medical emergency that occurs in severe hypothyroidism with a mortality rate reaching 60%. The hallmarks include depressed mental status and hypothermia, but hypotension, hyponatremia, bradycardia, and hypoventilation can also occur. This complication can occur in patients with a longstanding history of severe hypothyroidism especially when precipitated by an acute event such as infection, myocardial infarction, or surgery. Prompt recognition and treatment of the condition is important to prevent fatal outcomes. We present a case of myxedema coma in the setting of COVID-19 infection and nonadherence to medication. A 91-year-old woman with history of hypothyroidism, hypertension, coronary artery disease, cardiomyopathy, and chronic obstructive pulmonary disease presented with dyspnea. Her home medications included levothyroxine 75 mcg daily, which she reported not taking for at least 3 weeks. Vital signs revealed a normal heart rate and blood pressure of 84 beats/min and 137/78 mmHg, but the patient was hypothermic to 35.7 °C. On exam, she was somnolent. Labs were notable for markedly elevated TSH level of 111 (0.380 - 4.700 uIU/mL), low free T4 level of 0.57 (0.93 - 1.70 ng/dL), random cortisol level of 25.5 (6.2-18.4 ug/dL), and positive SARS-COV-2 PCR test. Chest x-ray revealed bilateral lower lung parenchymal consolidations and arterial blood gas revealed a pH of 7.29 and pCO2 of 52.5 (35-45 mm Hg), indicating hypercapnia. She was treated for COVID pneumonia and given concern for COVID induced myxedema coma she was given IV levothyroxine 100 mcg for 2 days, after which the patient’s hypothermia and somnolence improved, with an improved repeat free T4 level 0.87 ng/dL. She was subsequently transitioned to oral levothyroxine 112 mcg daily and discharged after improvement of her COVID symptoms. Myxedema coma is a rare complication of decompensated hypothyroidism, frequently triggered by an infection. Thyroid hormone plays an important role in regulating both the innate and adaptive immune systems. As a result, individuals with hypothyroidism are at increased risk of acquiring infections, which can further lead to myxedema coma. COVID-19 infection has been associated with thyrotoxicosis, thyroiditis and hypothyroidism. Given the associated high mortality rate, regardless of the underlying precipitant, prompt diagnosis and early administration of thyroid hormone replacement therapy is crucial to improve outcomes. Presentation: 6/3/2024

7078 Diagnostic Obstacles in Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma (TSH-oma): A Case Report

Abstract Disclosure: V.A. Mendpara: None. P.P. Rao: None. M.D. Lundholm: None. Background: Thyroid-stimulating hormone-secreting pituitary adenoma (TSH-oma) is a rare cause of hyperthyroidism, forming 0.5-3% of all functioning pituitary tumors and &amp;lt;1% of hyperthyroid cases. Here, TSH secretion is autonomous and unresponsive to the normal negative feedback of thyroid hormones, leading to inappropriate TSH, T4 and T3 elevation. In the absence of clinical symptoms it can be difficult to distinguish between thyroid hormone resistance (THR) and lab errors. Clinical Case: A 44-year-old Swahili-speaking female with a history of type 2 diabetes was admitted for hypoglycemia requiring insulin adjustment. In her workup, thyroid function tests were obtained, revealing normal or low TSH (0.28 mIU/L) and high free T4 levels (2.7 ng/dL). At outpatient follow-up, repeat labs showed elevated TSH, T3 and FT4 (5.22 mIU/L, 377 ng/dL and 4.7 ng/dL, respectively). She reported weight loss, occasional palpitations, and chronic insomnia but denied other symptoms. Graves' antibodies (TSI, TSHR Ab) were negative. On exam, she had a 30-40 gm, smooth, non-tender thyroid without adenopathy, and a BMI of 23 kg/m2. The initial differential diagnosis included TFT lab error, THR or TSH-oma. A FT4 by equilibrium dialysis was high at 7.8 ng/dL (1.1-2.4 ng/dL). N-telopeptide (NTX) and sex hormone-binding globulin (SHBG) were elevated, consistent with a true hyperthyroid state. Genetic testing for THR posed time and cost barriers. Elevated alpha-subunit levels (87 ng/mL, normal ≤1.8 ng/mL) with normal levels of other pituitary hormones prompted a pituitary MRI, unveiling a 4.7 cm suprasellar bilobed pituitary mass abutting the optic chiasm and invading the cavernous and sphenoidal sinuses. She denied peripheral vision loss or headaches. Hyperthyroidism was managed with methimazole until surgical intervention for the TSH-oma. A transsphenoidal resection was performed with histopathological confirmation of a TSH-staining pituitary adenoma. She was started on levothyroxine for central hypothyroidism thereafter. Discussion: It is challenging to find the cause of abnormal TFTs when patients are asymptomatic and the differential includes THR, lab errors or TSH-oma. Inaccurate diagnosis can lead to delays in care or unnecessary thyroid ablation or pituitary surgery. Conversely, early identification and appropriate treatment of TSH-omas can prevent neurological and endocrinological complications, such as optic chiasm compression, visual disturbances, headache and hypopituitarism. Despite a lack of convincing symptoms of hyperthyroidism, we used confirmatory labs (NTX, SHBG) to rule in biochemical hyperthyroidism along with alpha-subunit testing and pituitary MRI to solidify the TSH-oma diagnosis, leading to surgical intervention. This case highlights the vital steps in the diagnosis of a TSH-oma, emphasizing the need for logical evaluation and differentiation of this rare condition. Presentation: 6/1/2024

7314 The Thyroid Tetralogy: Hypothyroidism, Graves' Disease, AFTN, and Thyroid Cancer in a Single Patient

Abstract Disclosure: F. Sajid: None. F. Mohammadrezaei: None. K. Tiwari: None. J. Shapiro: None. F. Mohsin: None. T. Lin: None. Introduction: In this case, we explore a rare and complex situation involving a patient's shift from hypothyroidism to hyperthyroidism. This transition led to the diagnosis of Marine Lenhart Syndrome (MLS), an uncommon condition characterized by the coexistence of Graves' disease and autonomously functioning thyroid nodules (AFTNs). Adding to the complexity of the case, the patient was also diagnosed with papillary thyroid carcinoma (PTC). Case Presentation: A 47-year-old woman with a history of hypothyroidism, treated with levothyroxine for 14 years, presented with palpitations, weight loss, and insomnia for a few months. Her levothyroxine dose was gradually reduced and eventually discontinued by her primary care physician due to low TSH and high free T4 levels. Post-discontinuation, her symptoms were improving. Laboratory tests showed TSH 0.01 mIU/mL (0.39-4.08), Thyroglobulin (TG) 72 ng/mL (3-40), Free T4 2.5 ng/dL (0.8-1.8), Free T3 11.5 ng/dL (0.2-0.5ng/dL). Furthermore, Thyrotropin Receptor Antibody (TRAb), and Thyroid Peroxidase Antibody (TPO Ab) were positive leading to a diagnosis of Graves' Disease and initiation of Methimazole. After three months on Methimazole, her TSH remained suppressed with normalized free T4 and T3 levels. A thyroid ultrasound revealed bilateral nodules, with a calcified well-circumscribed nodule in the right mid-pole. A Radioactive iodine uptake (RAIU) scan showed a hyperfunctioning right mid-pole thyroid nodule. Fine-needle aspiration biopsy was consistent with Bethesda V, suggestive of possible malignancy. Consequently, she underwent a total thyroidectomy, with pathology confirming multifocal classic PTC, stage pT1bN0. Post-surgery, she developed hypothyroidism and was started on levothyroxine. Four weeks later, her TSH remain suppressed, other thyroid function tests and calcium levels were within normal range: TSH 0.01 mIU/mL, Free T4 1.0 ng/dL, TG 4.6 ng/mL, Thyroglobulin antibodies 1 IU/mL (less than or equal to 1), PTH intact 43 pg/mL (16-77), and Calcium 8.9 mg/dL (8.6-10.2). Conclusion: This case represents a complex and unusual medical scenario where a patient transitioned from hypothyroidism to hyperthyroidism, ultimately leading to the diagnosis of MLS in conjunction with PTC. The exact mechanism behind this transition is not fully understood. In the management of hypothyroidism, adjustments in thyroxine dosage are common, but significant tapering of the dose should prompt further investigation. The presence of PTC in AFTNs is considered rare, as AFTNs are typically characterized as hot nodules, implying they are hyperfunctioning and generally considered to be less likely malignant compared to cold nodules. This case underscores the need for comprehensive evaluation and follow-up in patients with thyroid disorders, especially when there is a change in thyroid function or the presence of nodules. Presentation: 6/3/2024

6430 SAT-534 Evaluating the Effectiveness of Combined T4 and T3 Therapy or Desiccated Thyroid Versus T4 Monotherapy in Hypothyroidism: A Systematic Review and Meta-Analysis

Abstract Disclosure: M. Nassar: None. A. Hassan: None. M.T. Desouki: None. S. Ramadan: None. M.A. Hassan: None. A. Chaudhuri: None. Background: Many patients with hypothyroidism experience persistent symptoms despite normalized TSH levels, which highlights the need for alternative treatment strategies. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics, including the 36-point thyroid symptom questionnaire (TSQ-36), Beck Depression Inventory (BDI) scores, and General Health Questionnaire (GHQ)-28 scores. Methods: A systematic literature search was conducted using a Boolean strategy on the following databases: Embase, Medline/PubMed, and Web of Science. The search included results from the inception of each database until 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid Extract," OR "Natural Desiccated Thyroid," OR "Nature-Throid," "Desiccated Thyroid," OR "NP Thyroid," OR "Synthroid," OR "Levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs. We excluded non-English articles. Results: Initially, 6,394 records were identified. After removing 477 duplicate records, 5,917 records underwent title and abstract screening, excluding 5,874 records. The full texts of the remaining 43 articles were examined for eligibility, excluding 27 articles. Ultimately, 16 studies met the inclusion criteria and were incorporated into our analysis. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4+T3 revealed a significant reduction in free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63) compared to T4 monotherapy. Total T3 levels increased significantly in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in heart rate, SHBG, TSH, lipid profile, TSQ-36, or BDI score. DTE significantly increased serum total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly decreased serum total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed a modest increase in TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in heart rate, SHBG, lipid profile, TSQ-36, GHQ-28, or BDI score. Conclusions: Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended. Presentation: 6/1/2024

Low T3 Syndrome is Associated with Imbalance of Bone Turnover Biomarker in Patients with Type 2 Diabetes.

To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome). This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome. The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), β C-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level. This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.

The effect of diabetes on the alevel of thyroid gland hormones in patients with uncontrolled type 2 diabetes in Thi-Qar Province,Iraq.

Background: Diabetes mellitus and thyroid dysfunction represent two prominent endocrine disorders frequently encountered in clinical practice. The objective of this research was to examine the prevalence of hypothyroidism among hospitalized individuals diagnosed with type 2 diabetes mellitus, along with its associated factors. Methods: A total of 120 in patients suffering from type 2 diabetes mellitus were admitted to the metabolic diseases unit. The findings of this investigation indicated a notable elevation of T3 and T4 levels in patients with uncontrolled diabetes (GI) when compared to those with controlled diabetes (GII) and the control group. Conversely, the levels of TSH exhibited a significant reduction in patients with uncontrolled diabetes (GI) relative to both the controlled diabetic patients (GII) and the control group. Utilizing a significance threshold of (P ≤ 0.05), this study revealed a substantial decrease in the concentrations of thyroid hormones, alongside a reduction in thyroid stimulating hormone levels in patients with uncontrolled diabetes when contrasted with the controlled diabetic patients and the control group.. Aims of Study: Evaluation the risk degree of developing of metabolic disorders complications in patients with DM and their prevalence in Thi-Qar province. Conclusion: It was concluded from this study that there is a clear relationship between high blood glucose levels and low T3 and T4 levels.

A Critical Investigation of Sick Euthyroid Syndrome in Chronic Heart Failure Patients: Addressing the Need for Accurate Thyroid Assessment.

Background The body undergoes numerous metabolic changes during severe illness or physiological stress to protect itself by lowering metabolism and reducing overall demands. This evolutionary adaptation dates back to early human development, long before the advent of ICU facilities and advanced treatments. One such protective mechanism is Sick Euthyroid Syndrome (SES), also known as Non-thyroidal Illness Syndrome (NTIS). SES commonly occurs in critically ill patients and is frequently observed in conditions such as heart failure, chronic kidney disease, and severe sepsis. This syndrome is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. Typically, these patients exhibit low serum levels of triiodothyronine (T3), normal or low levels of thyroxine (T4), and normal or low thyroid-stimulating hormone (TSH) levels. SES is believed to be an adaptive response to illness, aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress. This original article delves into SES's prevalence and clinical impact in these settings. Materials and methods The study aims to determine the prevalence of SES in patients with long-standing heart failure, elucidate the relationship between thyroid function and heart failure severity, and assess its impact on various hematological and clinical parameters. This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, a 2011-bed hospital, over one and a half years. This study included 70 patients with chronic heart failure, aged 18 years and above, defined by a left ventricular ejection fraction of 40% or less and a Boston criteria score of 8 or more. Patients were excluded if they had a history of thyroid dysfunction, clinical sepsis, or were taking thyroid-affecting drugs. Results The study provides important insights into the prevalence and impact of SES in long-standing heart failure patients. It found that a significant 44.29% of these patients exhibited low T3 levels, highlighting the substantial occurrence of SES in this population. Additionally, the study revealed a negative correlation between N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, Boston score, and total T3, suggesting that as indicators of heart failure severity worsen, total T3 levels may decrease further. Another key finding is the high prevalence of anemia among heart failure patients, with a notable gender disparity: 92.11% of male patients were affected compared to 50% of female patients. Conclusion The study concluded that SES is significantly prevalent among long-standing heart failure patients, further indicating that thyroid suppression increases with the severity of heart failure. Recognizing SES can guide tailored treatments, prompting intensive monitoring and optimized heart failure management.Additionally, the study found a high prevalence of anemia, particularly among male patients, highlighting the need for gender-specific considerations in managing heart failure. These findings underscore the importance of routine thyroid function assessments and regular monitoring of anemia in heart failure patients. Future research should focus on improving clinical outcomes through comprehensive management of both thyroid function and anemia in these patients.

Amenorrhea as a presentation of Cushing's syndrome.

Menstrual cycle abnormalities are common in premenopausal females with Cushing's syndrome, although the underlying mechanism is poorly understood. Signs and symptoms found in Cushing's syndrome overlap with polycystic ovarian syndrome (PCOS). The patient is a 33-year-old female previously diagnosed by a gynecologist with PCOS and treated with oral contraceptive pills (OCPs) for 2 years. She then discontinued her OCPs without consulting a clinician, resulting in amenorrhea for 6 months, for which she presented. She also had symptoms of depression and anxiety but had no other signs and symptoms of Cushing's syndrome, except a plethoric face. Initial lab work showed evidence of central hypogonadism (low luteinizing hormone, follicle-stimulating hormone, and estrogen), so a complete anterior pituitary hormone workup was done. Her thyroid-stimulating hormone was also low with a low free T4 level. Prolactin level was normal, but surprisingly, her AM cortisol level was high. The Cushing's syndrome workup revealed non-suppressed cortisol after a 1 mg dexamethasone suppression test and positive 24-h urine cortisol with suppressed adrenocorticotrophic hormone. A CT scan of her adrenal glands revealed a left adrenal adenoma. She underwent a left adrenalectomy, after which her menstrual cycles became regular again, and pituitary function has recovered. In Cushing's syndrome, female patients can have menstrual abnormalities due to the high cortisol levels, which can affect gonadotrophin levels. We encourage clinicians to include Cushing's syndrome in the differential diagnosis of patients with central hypogonadism.

Low free T3 level may predict the severity of acute pancreatitis

ABSTRACT Objectives To demonstrate that deterioration in thyroid function tests can serve as an indicator of severity and prognosis in acute pancreatitis despite a healthy thyroid gland. Methods This study is a retrospective, single-center study. Patients diagnosed with acute pancreatitis between May 2020 and June 2021 were evaluated. Acute pancreatitis was diagnosed and classified according to the 2012 revised Atlanta criteria. Patients were categorized into Non-Thyroidal Illness Syndrome and euthyroid groups and compared in terms of biochemical parameters and scoring systems such as Ranson, Glasgow, Balthazar and BISAP scores. Results A total of 152 patients were included in the study. Eighty-three patients (54%) were euthyroid, with free triiodothyronine (T3), free thyroxine (T4), and Thyroid-stimulating hormone (TSH) levels within normal limits. Sixty-nine patients (46%) had Non-Thyroidal Illness Syndrome with low serum free T3 levels and low/normal TSH levels. As expected, free T3 was significantly lower in the Non-Thyroidal Illness Syndrome group than in the euthyroid group (1.5 ± 0.04 vs 2.6 ± 0.04, respectively, p < 0.0001). In the Non-Thyroidal Illness Syndrome group, Ranson score (3.35 ± 0.2 vs 2.11 ± 0.18 p < 0.0001), Glasgow (2.4 ± 0.2 vs 1.3 ± 0.1, p < 0.0001), Atlanta (p = 0.007), and Balthazar (2.1 ± 0.1 vs 1.4 ± 0.1, p = 0.001) scores were significantly higher than euthyroid group. Conclusion Non-Thyroidal Illness Syndrome provides insight into the prognosis of acute pancreatitis. Free T3 values are a significant parameter that may indicate the prognosis of acute pancreatitis. We believe that free T3 could be incorporated into an ideal scoring system in a disease such as acute pancreatitis, where early determination of prognosis is known to significantly reduce mortality.

Ultra-Low Anti-Müllerian Hormone Levels in Recurrent Cystic Ovarian Neoplasm: A Case Report

Fertility has been a major issue in the management of cystic ovarian neoplasm. This case report presents an extreme case of ultra-low AMH levels in a young female with recurrent cystic ovarian neoplasm and analyzes the potential causes. A twenty-two-year-old female presented with stomach discomfort. The patient had undergone two surgeries for ovarian neoplasm within the last six years. The patient had another abdominal lump suspected to be a residual tumor mass. After further examination, the patient was diagnosed with cystic ovarian neoplasm. The laboratory findings showed low T4 levels, increased TSH levels, and ultra-low AMH levels (0.023 ng/mL). Management of cystic ovarian neoplasm should concern the effect on fertility. The AMH level can be used for pre-treatment counseling in these patients.

#2334 Elevated serum admission creatinine in acute heart failure hospitalizations: lifting the veil to understand outcome differences

Abstract Background and Aims Organ crosstalk in heart failure and kidney dysfunction is prevalent and is associated to a high event rate. In this setting elevated serum creatinine (sCr) at acute decompensated heart failure (ADHF) admissions is a strong risk factor for poor outcomes. Current accepted cardiorenal syndrome (CRS) classification is based on timing and initial organ dysfunction and fails at capturing its nature and prognosis. We sought to describe patient (P) profile and outcomes in P hospitalized for ADHF with high admission sCr in function of current CRS classification and assess for stratifying predictors. Method We conducted an observational, analytical and cross-sectional study, with prospective and consecutive data acquisition. We included P over 18 years-old, who were admitted to the Intensive Care Telemetry Unit in our Hospital between July, 2011 and Dec, 2023 due to ADHF. P who received a heart transplant during index admission or those on chronic dialysis were excluded. Clinical, epidemiological and biochemical variables were registered. Renal dysfunction was defined under admission sCr &amp;gt;1.4 mg/dl and divided according to Ronco et al classification, as initially cardiac (type 2) or renal (type 4) origin. We constructed multivariate logistic and survival regression models, with selection of relevant predictors by resampling and regularization of a Lasso regression model. Statistical significance was considered with a 5% of alpha error level. Analysis was conducted using R (R Core Team, 2023). Results A total of 1868 consecutive P were included. P population consisted in type 2: 124 and type 4: 258 P, respectively. We found no differences in gender (p = 0.47), while type 4 were older (75 ± 12 vs 71 ± 12; p &amp;lt; 0.01). Ventricular dysfunction was more severe in type 2 (left ventricular ejection fraction 34 ± 17 vs 41 ± 16%; p &amp;lt; 0.001). While ischaemic heart disease was more prevalent in type 4 (32.8 vs 23.5%; p = 0.001), idiopathic cardiomyopathy was more frequent in type 2 (18.8 vs 7.2%; p = 0.001). Clinical phenotypes differed between groups, being clinical hypoperfusion more frequent in type 2 (32.4 vs 12.3%; p &amp;lt; 0.001). Admission sCr was higher in type 4 (1.9 [0.8] vs 1.6 [0.58] mg/dl; p &amp;lt; 0.001), as was 1st day natriuresis (81 vs 67 mEq; p = 0.01). Both groups experienced a similar diuretic resistance rate (21.2 vs 17.1%; p = 0.34), while type 4 received rescue ultrafiltration more frequently (11.3 vs 3.5%; p &amp;lt; 0.01). Type 2 received a higher inotropic support rate (47.1 vs 19.5%; p &amp;lt; 0.01) and had a longer length of stay (9 vs 7 days; p = 0.01). In-hospital (11.8 vs 11.3%; p = 0.99); 6-month and 1-year mortality rates (66.8 vs 72.8% and 55.1 vs 64.6% respectively; p = 0.3). In a similar way, 1-month (94.8 vs 94.7%), 6-month (72 vs 74.7%) and 1-year readmission rates (59.2 vs 60.9%; p = 0.6) were similar in both groups. A multiple logistic regression model (AUCROC 0.82) identified admission sCr (OR 2.6; CI 95% 2.2-3.2; p &amp;lt; 0.001), inotropic need (OR 1.87; CI 95% 1.4-2.6; p &amp;lt; 0.001), anasarca phenotype (OR 1.63; CI 95% 1.06-2.5; p = 0.02), moderate to severe right ventricular dysfunction (OR 1.4; CI 95% 1.03-1.9; p = 0.03) as independent predictors for a descending sCr behavior during hospitalization, while the lower T3 levels were associated with less probability for a descent of sCr (OR 0.21; CI 95% 0.1-0.46; p &amp;lt; 0.001). Conclusion Organ crosstalk in ADHF hospitalizations was associated with a high event rate. One-year mortality and readmission rates were similar in both groups. Renal support therapies were more frequent under lower kidney reserve conditions. Ventricular dysfunction and systemic congestion phenotype are relevant to a better understanding for potential reversibility at the admission time and may promote actions for outcome enhancing.

#1080 Low-T3 syndrome: “endemic” in hemodialysis patients?

Abstract Background and Aims In hemodialysis patients, low-T3 syndrome is more prevalent than in the general population and was found to be associated with malnutrition and inflammation. Although evidence suggest that low free T3 (fT3) levels predict cardiovascular and all-cause mortality, low-T3 syndrome is usually not treated. The aim of this single-center retrospective observational study was to determine the prevalence of thyroid axis derangements and examine the relationship between thyroid hormones and biochemical and clinical variables in our hemodialysis (HD) patients cohort. Method Patients on thrice-weekly maintenance HD for at least 6 months were enrolled. Patients taking amiodarone, levothyroxine or methimazole were excluded. Data about age, sex, ethnicity, hemodialysis vintage, type of dialysis (bicarbonate dialysis/online hemodiafiltration/acetate-free-biofiltration/hemofiltration with endogenous reinfusion/expanded hemodialysis) were obtained from medical records and values of fT3, fT4, TSH, albumin, LDL, hemoglobin—routinely checked for every patient during hemodialysis sessions—were acquired. Continuous variables are expressed as median and IQR or mean ± SD and categorical variables as absolute value or percentage. The normality of data distribution was tested by Sapiro-Wilk test. Correlations were studied with Pearson and Spearman. T-test and Mann-Whitney U test were performed to compare continuous and categorical variables. Statistical significance was reached with p &amp;lt; 0.05. Results A total of 57 patients on thrice-weekly maintenance HD were enrolled. Most of them were male (70.2%), Caucasians (89.5%), with a mean age of 69 ± 14 years and with a median dialytic vintage of 63 [29; 113] months. Hypertension was the most frequent comorbidity and more than half of the patients was either affected by ischemic, hypertensive or dilatative cardiomyopathy. Most of the patients underwent bicarbonate hemodialysis (42.1%) and overall 57.9% of the study population was treated by convective techniques. Hemoglobin, albumin, LDL cholesterol, fT3 and fT4 values was normally distributed, while those of TSH and PCR were not. A very high prevalence of low-T3 syndrome (75%) was found, 5 patients showed subclinical hypothyroidism and only in a minority of patients thyroid function tests were normal (12%) (Fig. 1). A significant negative correlation between fT3 and age (p = 0.041) and a positive one between TSH and dialytic vintage (p = 0.017) were found (Table 1). In addition, a significant positive correlation between albumin and fT3 was detected, supporting the known association between low T3 and malnutrition. Interestingly, PCR negatively correlated with fT3 and positively with fT4. Patients treated by diffusive techniques showed no statistically significant difference of thyroid hormone levels compared to convective therapies (Table 1). Conclusion Low-T3 syndrome affects the great majority of patients in our hemodialysis population, with a prevalence even higher than that provided by literature. Our investigations confirm that older patients seem to show lower fT3 levels and a longer hemodialysis vintage may correlate with higher TSH levels. The association with inflammation was also confirmed. Considering the known impact on cardiovascular and all-cause mortality already demonstrated, it is important to routinely check thyroid hormones in HD. In addition, further studies should be performed in order to establish the possible impact of the therapeutic correction of this hormonal derangement on hemodialysis patients’ mortality and cardiovascular outcomes.

Thyroid status in patients with early stages of cancer of various localization

Purpose of the study. To determine the thyroid status of primary cancer patients in the early stages of uterine body cancer, kidney cancer, breast cancer, skin melanoma and lung cancer without a history of endocrine pathology.Patients and methods. The content levels of thyroid-stimulating hormone (TSH), thyroid hormones (THs) T4 and T3 of total and free forms were determined in the blood serum by RIA method in 132 patients with breast cancer, uterine body cancer, lung cancer, kidney cancer and skin melanoma (average age 55 years). The comparison group consisted of practically healthy donors.Results. Only in skin melanoma, serum TSH levels were reduced by 1.5 times (p &lt; 0.05). The T4 content was reduced by 1.4–1.7 times (p &lt; 0.05) in uterine body cancer and kidney cancer, increased in lung cancer patients and 16 % of breast cancer patients by 1.4–1.7 times though (p &lt; 0.05). A 1.3–1.5‑fold low (p &lt; 0.05) T3 level was found in breast cancer, kidney cancer, and skin melanoma, while an 1.6‑fold increase (p &lt; 0.05) was found in uterine body cancer. The revealed changes in THs by the type of clinical hyperthyroidism are an increase of 1.8 times (p &lt; 0.05) FT3 on the background of low TSH in the blood in patients with skin melanoma, and by the type of hyperthyroxinemia in patients with lung cancer and breast cancer, consisting in increased concentrations of T4 and FT3, and with free and total T3 levels in patients uterine body cancer, as well as FT4, without changes in TSH in the blood serum of patients, may be associated with the features of malignant pathology, since it is known that THs are proliferation stimulants and can build up in tumors.Conclusion. The development of a malignant tumor even in the early stages of the disease is perceived by the body as a threat for homeostasis and the response to the occurrence of neoplasm is the reaction of the hypothalamicpituitary-thyroid regulatory axis. As an outcome, patients develop euthyroid disorder syndrome.

Expression of hTERT and Lp-PLA(2) genes is increased in primary hypothyroidism.

ObjectiveSightly low serum free T4 levels are associated with longer life expectancy. However, hypothyroidism is associated with increased risk of inflammation and vascular complications. Therefore, relation of thyroid hormones (THs) with life expectancy seems to be complex. This study was carried out in an effort to understand the contribution of THs in inflammation and aging. Methodology15 cases of treatment naïve primary hypothyroidism and 15 age and sex matched euthyroid controls were recruited. mRNA expression of Telomerase (hTERT), leucocyte telomere length (LTL) and Lipoprotein associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation and risk predictor of cardiovascular events were measured by qPCR in whole blood. ResultExpression of hTERT was found to be 6.95 times higher in the cases as compared to the controls. mRNA expression of Lp-PLA(2) was also 3.3 times higher in cases. LTL in euthyroid was approximately 81% of the length in hypothyroid patients. ConclusionA higher expression of hTERT indicates that hypothyroidism confers better cell survival in peripheral leucocytes inspite of the presence of vascular inflammation. However causal relationship cannot be ascertained with these results.

(O-05) ESTRADIOL LEVELS IN MEXICAN MEN WITH ERECTILE DYSFUNCTION

Abstract Introduction and Objective Erectile dysfunction is associated with various psychological and physiological causes, including hormone levels such as testosterone. The role of estradiol in male sexual function is controversial, and studies reporting its impact on erectile function have been inconsistent. The aim of this study was to describe the levels of testosterone and estradiol in Mexican men with erectile dysfunction, based on the severity of dysfunction. Materials and Methods Hormonal levels of TSH, T3, T4, LH, FSH, total and free testosterone, and estradiol were measured in men over 18 years of age with erectile dysfunction, attending a clinic in Mexico. Clinical variables were analyzed, estimating measures of central tendency and dispersion for numerical variables, and absolute and relative frequencies for categorical variables. The proportion of men with abnormal levels of estradiol and testosterone was calculated based on the severity of erectile dysfunction. Results A total of 70 participants were included. The average age was 53.9 years old (+/- 11.8); 18.5% had severe dysfunction, 65.7% had moderate dysfunction, 14.2% had mild to moderate dysfunction, and 1.4% had mild dysfunction. 35.7% were diabetic, and 34.2% were hypertensive. 62.8% had abnormal levels in at least one of the evaluated hormones: 5.7% had low TSH levels; 2.8% had low T3 levels; 1.4% had low T4 levels; 5.7% had low and 7.1% had high total testosterone levels; 12.8% had low and 2.8% had high free testosterone levels; 17.1% had high prolactin levels; 1.4% had low and 10% had high LH levels; 5.7% had high FSH levels. Estradiol level was high in 6 men (8.5%), 1 had mild-moderate and 5 moderate dysfunction; 8 men had low estradiol levels (11.42%), 1 had mild-moderate, 4 moderate and 3 severe dysfunction. Conclusions Alteration on the levels of Estradiol was common in the analyzed group of patients with erectile dysfunction, especially in men with moderate dysfunction, observed in 12.8% of them. Financing Boston Medical Group.

Thyroid hormone deprival and TSH/TSHR signaling deficiency lead to central hypothyroidism-associated intestinal dysplasia

BackgroundCentral hypothyroidism (CH) is characterized by low T4 levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related intestinal maldevelopment. In particular, the roles of TH and TSH/TSHR signaling in CH-related intestinal maldevelopment are poorly understood. Herein, we utilized Tshr−/− mice as a congenital hypothyroidism model with TH deprival and absence of TSHR signaling. MethodsThe morphological characteristics of intestines were determined by HE staining, periodic acid–shiff staining, and immunohistochemical staining. T4 was administrated into the offspring of homozygous mice from the fourth postnatal day through weaning or administrated after weaning. RT-PCR was used to evaluate the expression of markers of goblet cells and intestinal digestive enzymes. Single-cell RNA-sequencing analysis was used to explore the cell types and gene profiles of metabolic alternations in early-T4-injected Tshr−/− mice. Key findingsTshr deletion caused significant growth retardation and intestinal maldevelopment, manifested as smaller and more slender small intestines due to reduced numbers of stem cells and differentiated epithelial cells. Thyroxin supplementation from the fourth postnatal day, but not from weaning, significantly rescued the abnormal intestinal structure and restored the decreased number of proliferating intestinal cells in crypts of Tshr−/− mice. Tshr−/− mice with early-life T4 injections had more early goblet cells and impaired metabolism compared to Tshr+/+ mice. SignificanceTH deprival leads to major defects of CH-associated intestinal dysplasia while TSH/TSHR signaling deficiency promotes the differentiation of goblet cells and impairs nutrition metabolism.

To study thyroid profile in CKD patients in Eastern Uttar Pradesh

Chronic kidney disease (CKD) remains a universal pandemic that has evolved into a serious public health problem that imposes a significant socioeconomic burden. Thyroid profile is disrupted in CKD patients due to aberrant thyroid hormone metabolism. The purpose of our study was to assess thyroid function in people who had chronic renal disease (CKD).According to the inclusion-exclusion criteria, this cross-sectional observational research enrolled 150 chronic renal disease patients.All patients who met the above criteria underwent a detailed history as well as a general and systemic examination. Thyroid function tests, USG entire abdomen, chest X-ray, ECG, and 2D Echocardiogram, were performed. There were 84 men and 66 women among the 150 CKD patients. Thyroid hormone abnormalities were found in 93.3 % of the individuals. 14.7 % of the participants had hypothyroidism, 14.7 % had low T3 and T4 readings, 10% had low T4 values alone, 38 % had low T3 only, and 17% had subclinical hypothyroidism. Low T3 levels (58 %) were the most prevalent thyroid anomaly, with or without low T4 or elevated TSH levels. Low T3 levels were more common in patients with advanced CKD.Thyroid hormone abnormalities are linked to different stages of chronic renal disease.

Glycerol Phenylbutyrate Treatment of 2 Patients With Monocarboxylate Transporter 8 Deficiency.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. We treated 2 monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, vital signs, anthropometric measurements, and neurocognitive functions. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P321L mutation. The effects of GPB were compared to the effects of DITPA and TRIAC, thyromimetic medications that the patients had received in the past. NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment reduced high T3 and increased low T4 levels. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neurocognitive improvement was observed, in hyperreflexia score and in cognitive functions. Serum metabolites did not exceed the toxic range, but elevated liver transaminases were observed. In the first report of GPB treatment in MCT8 deficiency we found an improvement in TH profile and body mass index, with minor neurodevelopmental changes.