Administration Of Levothyroxine Research Articles

Combined levothyroxine and propylthiouracil treatment in children with MCT8 deficiency: A multi-center case series of 12 patients.

To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing MCT8 deficiency and identify optimal therapeutic dosages. This multi-center case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024. The study focused on treatment safety and outcomes, analyzing baseline and last encounter biochemical, metabolic, and anthropometric parameters. Statistical analyses included Wilcoxon Signed Ranks tests and Generalized Estimated Equations to assess effects on thyroid and metabolic markers, and Receiver Operating Characteristics curves to predict optimal dose. Patients showed a significant reduction in serum total T3 (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and FT4 concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/Kg/day, while LT4 increased FT4 concentration by 40% from baseline at an average dose of 4.3 μg/Kg/day. TSH concentration was undetectable on treatment. No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group but 6 of 8 patients for whom this data was available had an increase in weight (z score). There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation. Combined treatment with PTU and LT4 normalized serum T3, FT4, TT4 in patients with MCT8 deficiency. Individualized dose adjustments were crucial for achieving therapeutic goals, indicating the need for personalized treatment plans.

Cardioprotective effect of Vitamin D on cardiac hypertrophy through improvement of mitophagy and apoptosis in an experimental rat model of levothyroxine -induced hyperthyroidism.

Mitochondria are known to be involved in mediating the calorigenic effects of thyroid hormones. With an abundance of these hormones, alterations in energy metabolism and cellular respiration take place, leading to the development of cardiac hypertrophy. Vitamin D has recently gained attention due to its involvement in the regulation of mitochondrial function, demonstrating promising potential in preserving the integrity and functionality of the mitochondrial network. The present study aimed to investigate the therapeutic potential of Vitamin D on cardiac hypertrophy induced by hyperthyroidism, with a focus on the contributions of mitophagy and apoptosis as possible underlying molecular mechanisms. The rats were divided into three groups: control; hyperthyroid; hyperthyroid + Vitamin D. Hyperthyroidism was induced by Levothyroxine administration for four weeks. Serum thyroid hormones levels, myocardial damage markers, cardiac hypertrophy indices, and histological examination were assessed. The assessment of Malondialdehyde (MDA) levels and the expression of the related genes were conducted using heart tissue samples. Vitamin D pretreatment exhibited a significant improvement in the hyperthyroidism-induced decline in markers indicative of myocardial damage, oxidative stress, and indices of cardiac hypertrophy. Vitamin D pretreatment also improved the downregulation observed in myocardial expression levels of genes involved in the regulation of mitophagy and apoptosis, including PTEN putative kinase 1 (PINK1), Mitofusin-2 (MFN2), Dynamin-related Protein 1 (DRP1), and B cell lymphoma-2 (Bcl-2), induced by hyperthyroidism. These results suggest that supplementation with Vitamin D could be advantageous in preventing the progression of cardiac hypertrophy and myocardial damage.

Characterization of the thyroid hormones level in urine by liquid chromatography coupled to mass spectrometry focus in the antidoping field.

This paper aims to study the metabolism of thyroid hormones (TH) in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was applied to samples collected before and after the administration of sodium triiodothyronine (T3) and sodium levothyroxine (T4) to a euthyroid volunteer and to samples of athletes declaring and not declaring thyroid supplementation. Samples were analyzed by LC-MS/MS after enzymatic hydrolysis, liquid-liquid, and solid-phase extractions. Ratios between T3/thyronine and T4/3,3'-T2 may be used for the detection of the administration of exogenous T3 in urine. Meanwhile, 3-T1 concentrations may be used to detect exogenous T4 administration. Nevertheless, these markers may not work properly in hypothyroid population, as athletes seem to be. The levels of T3 and T4 of athletes were lower than those of a euthyroid state even when they are under administration of TH supplements. The HTP axis high efficiency does not allow observing differences between athletes who do not declare and those who declare having used TH supplementation by direct measurements of T3 and T4 in urine. The detection of TH administration in urine (triiodothyronine and levothyroxine) may work when dealing with euthyroid individuals. Nevertheless, in individuals with hypothyroidism where the tendency is toward the maintenance of homeostasis, and it may be not possible to detect their consumption by applying cut-off values.

Identification of a novel nonsense SLC16A2 gene mutation in an infant with severe neurologic phenotype: A case report.

Allan-Herndon-Dudley syndrome (AHDS) results from a pathogenic variant in the hemizygous subunit of the SLC16A2 gene, which encodes monocarboxylate transporter 8 and follows an X-linked recessive pattern. AHDS manifests as neuropsychomotor developmental delay, intellectual disability, movement disorders, and thyroid hormone abnormalities. It is frequently misdiagnosed as cerebral palsy or hypothyroidism. A 9-month-old male infant exhibited poor head control, hypodynamia, motor retardation, hypertonic limbs, and thyroid abnormalities. Despite levothyroxine supplementation and rehabilitation therapy, no improvements were observed. Whole-exome sequencing identified a novel nonsense mutation in SLC16A2 (c.124G > T, p.E42X), which unequivocally established the diagnosis. AHDS was confirmed. Levothyroxine treatment commenced early in infancy, followed by 3 months of rehabilitation therapy, starting at 5 months of age. The combined administration of levothyroxine and methimazole was initiated at 1 year and 10 months of age, respectively. While improvements were noted in thyroid hormone levels, neurological developmental delays persisted. AHDS should be considered in patients presenting with atypical neurological features and thyroid hormone abnormalities such as elevated triiodothyronine and decreased thyroxine levels. The early utilization of exome sequencing aids in prompt diagnosis. The identified SLC16A2 nonsense mutation correlates with severe neurological phenotypes and adds to the spectrum of genetic variations associated with AHDS.

Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant.

With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed. Exclusion criteria included patients who were not solid organ donors, patients who were not declared brain dead (donation after circulatory death), and patients who did not receive steroids in their hospital course. Levothyroxine and steroid administration, the number of organs donated, the types of organs donated, and demographic information were recorded. Univariate analyses were performed with P < 0.05 considered to be statistically significant. A total of 88 patients met inclusion criteria, 69 (78%) of whom received levothyroxine and steroids (ST/LT group) vs 19 (22%) receiving steroids without levothyroxine (ST group). No differences were observed between the groups for gender, race, pertinent injury factors, age, or other hormone therapies used (P > 0.05). In the ST/LT group, 68.1% (n = 47) donated a high yield (3-5) of organ types per donor compared to 42.1% (n = 8) in the ST group (P = 0.038). There was no difference in the total number of organ types donated between the groups (P = 0.068). This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population. Limitations to this study include the retrospective design and the relatively small number of organ donors who met inclusion criteria. This study is unique in that it mitigates steroid administration as a confounding variable and focuses specifically on the adjunctive use of levothyroxine.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report

BackgroundAlthough vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported.Case presentationAn 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 μg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 μIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient’s disease course was stable with continued thyroid and adrenal corticosteroid supplementation.ConclusionsHerein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial

We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N= 57) or standard HFrEF therapy alone (control group, N= 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24weeks (70.08± 85.76m vs. 27.73± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p<0.001). Improvements in New York Heart Association (NYHA) classification (p= 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p= 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.

Levothyroxine attenuates behavioral impairment and improves oxidative stress and histological alteration 3-nitropropionic acid induced experimental Huntington’s disease in rats

Huntington’s disease (HD) is a neurodegenerative disorder characterized by degeneration of the striatum; it results in oxidative stress and motor deficits. Thyroid hormones regulate oxidative metabolism. In the present study, we evaluated the effect of administration of levothyroxine (LT-4) on neurobehavioral, oxidative stress, and histological changes in a rat model of HD. Forty-eight Wistar male rats were divided into the following six groups (n = 8): Group 1 (control) received physiological saline intraperitoneally (ip). Groups 2 and 3 received L-T4,30 and L-T4100 (μg/kg, ip, respectively) daily for 7 days. Group 4 (HD) received 3-nitropropionic acid (3-NP) (25 mg/kg, ip) daily for 7 days. Groups 5 and 6 received L-T4,30 and L-T4100 (μg/kg, ip, respectively) 30 min after 3-NP (25 mg/kg, ip) injection for the same duration. On the 8th day, behavioral parameters were evaluated with the Rotarod, Narrow beam walk, and Limb withdrawal tests. Oxidative markers such as Malondialdehyde (MDA) and Glutathione (GSH) levels and Superoxide dismutase (SOD) activity, in striatum tissue were measured. Moreover, striatum tissues were analyzed by Hematoxylin-eosin staining for histological alterations. We found that 3-NP administration caused motor incoordination and induced oxidative stress increased but reduced free radical scavenging. Also, increased amounts of lipid peroxides caused striatal damage as shown by histopathological evaluation. Administration of L-T4 led to increased falling time in the Rotarod, but reduced the time taken in Narrow beam walking and Limb withdrawal test. Furthermore, L-T4 increased antioxidant activity, decreased lipid peroxidation and ameliorated 3-NP-induced degeneration in neurons.

Identifying Thyroid Dysfunction Using Standard Laboratory Testings – A Systematic Review

Thyroid dysfunction includes various thyroid-related illnesses, with subclinical hypothyroidism or hyperthyroidism at the initial stage. Blood TSH and T4 levels indicate a neutral ground between clinical conditions. Following guidelines for levothyroxine administration based on thyroid hormonal levels is beneficial for hypothyroid patients. TSH, a measurable signal, is crucial for assessing thyroid activity, with reference ranges determined by testing facilities. However, elevated TSH levels require consideration of the patient's history and lifestyle before intervention. A Machine Learning-based Thyroid Dysfunction Identification (ML-TDI) model was developed to screen individuals for medicinal intervention. Despite its prevalence and health consequences, thyroid dysfunction often goes undiagnosed. The study used standard laboratory data and machine learning algorithms to identify thyroid dysfunction, suggesting the potential for technology-driven screenings during routine medical procedures. However, assessing the benefits and risks of widespread thyroid illness evaluation requires well-conducted randomized trials.

Impact of levothyroxine therapy for maternal subclinical and overt hypothyroidism on early child neurodevelopment: A prospective cohort study.

Treatment indication of maternal subclinical hypothyroidism (SCH) is undetermined, despite the wide administration of levothyroxine for maternal overt hypothyroidism (OH). This study aimed to evaluate the therapeutic effect of levothyroxine for maternal SCH and OH in real-world practice, with a focus on early child neurodevelopment. Prospective cohort study. Pregnant women diagnosed with SCH at the first antenatal visit were enroled and compared to those diagnosed with OH. Thyroid follow-ups were conducted during pregnancy. Early child neurodevelopment was assessed using the Gesell Development Diagnosis Scale (GDDS) at 1, 3, 6, 12and 24 months of age. From January 2012 to December 2013, a total of 442 pregnant women were included in final analysis, among whom 194 and 248 were assigned to the SCH and OH groups, respectively. The percentage of levothyroxine therapy at the first antenatal visit was significantly lower in the SCH group than that in the OH group (91.24% vs. 97.58%, p < .01), with a similar treatment rate at delivery (99.4% vs. 100%, p > .05). Notably, GDDS scores were lower in the SCH group than those in the OH group at 6 months to 2 years of age, which was confirmed by subgroup analyses and sensitivity analyses. Children born with maternal SCH demonstrated slightly lower neuropsychological scores at 6 months to 2 years of age compared to those with maternal OH in the clinical practice. The therapeutic effect of maternal SCH on the child neurodevelopment requires further exploration.

The effect of low- and high-dose levothyroxine on the expression, protein level, and function of P-glycoprotein in mice

The study was investigated the effect of different doses of levothyroxine on the mRNA expression, protein level and function of Pgp. Mice were divided into 6 groups as control, low dose levothyroxine, high dose levothyroxine, fexofenadine, low dose levothyroxine+fexofenadine and high dose levothyroxine+fexofenadine. Mice received levothyroxine at doses of 8 and 80 µg/kg daily for 21 days. Fexofenadine was administered at dose of 40 mg/kg at the 24 h following the last administration of levothyroxine. The mRNA levels and protein level of Pgp in liver and small intestine were determined by RT-PCR and western blot analysis, respectively. Plasma concentrations of fexofenadine were determined using HPLC. Levothyroxine at low and high doses caused an insignificant increase intestinal mRNA expression of mdr1a, while high dose levothyroxine+fexofenadine caused a significant increase. Levothyroxine caused a dose-dependent decrease in intestinal mRNA expression of mdr1b. In liver, levothyroxine caused a dose-dependent increase in the mRNA expression of mdr1a. Fexofenadine significantly reduced the effect of levothyroxine on mRNA expression of mdr1a in liver. Levothyroxine increased the protein level of Pgp in liver and decrease in intestines. Low dose levothyroxine significantly increased the plasma concentration of fexofenadine. The effects of levothyroxine on the mRNA expression of mdr1a and b in small intestine and liver and protein level of Pgp varied depending on the dose, tissue type, and fexofenadine administration.

Effect of levothyroxine administration on oxidative stress and cytokine levels in rats with experimental hypothyroidism

In this study, it was aimed to determine the effects of levothyroxine (L-T4) administration on serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and serum total antioxidant capacity (TAC), serum total oxidant capacity (TOC), oxidative stress index (OSI) and superoxide dismutase (SOD) activity, liver malondialdehyde (MDA) and the effects of cytokines on tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in rats with experimental hypothyroidism. In the study, 48, 39-day-old, male Wistar albino rats were randomly divided into 3 groups containing 16 rats in each as control, hypothyroid and levothyroxine (L-T4) treated hypothyroid group. The rats in the control group were injected with 1 mL of saline and the rats in the hypothyroid group were injected via intraperitoneal (i.p.) route with 6-n-propyl thiouracil (PTU) at a dose of 10 mg/kg/day for 28 days. In the levothyroxine treated group, after induction of hypothyroidism 5 µg of levothyroxine diluted in 1 mL of sodium chloride (NaCl) administered via i.p. route for 15 days. At the end of the study, serum and liver samples were taken from the rats. In hypothyroidism group, serum fT3, fT4 and TAK levels as well as SOD (P&lt;0.001) activity decreased statistically compared to the control group while serum TSH, TOC, OSI (P&lt;0.001), liver MDA (P&lt;0.01), TNF-α and IL-6 (P&lt;0.001) levels increased significantly. The decreased serum fT3, fT4, TAC levels and SOD (P&lt;0.001) activity in the hypothyroidism group increased with levothyroxine administration whereas the increased serum TSH, TOC, OSI and tissue MDA (P&lt;0.01), TNF-α and IL-6 (P&lt;0.001) levels were found to be decreased and approached to control levels. In conclusion, it has been shown that levothyroxine administration is effective against PTU-induced hypothyroidism in rats, inhibits lipid peroxidation and increases antioxidant status, minimizes the levels of inflammatory markers and protects against PTU-induced liver damage in rats. Because, the potential therapeutic use of levothyroxine in the treatment of hypothyroidism is thought to be appropriate.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

THE DILEMMA OF USE OF THE LEVOTHYROXIN IN PATIENTS WITH HEART FAILURE (literature review and own data)

Systematization of literature data on the use of thyroid hormones in patients with heart failure and the results of own research are given. The therapy of levothyroxine in patients with heart failure, at the moment of time, remains still an "open book". Several questions remain unsolved: regimen, doses and schedule of levothyroxine use, consequences of this therapy. It is necessary to conduct large, multicenter, prospective, placebo-controlled studies, which should provide information on the safety and impact of levothyroxine on the long-term prognosis of these patients. Our study shows that the long-term administration of levothyroxine in patients with heart failure and accompanying hypothyroidism has a dose-dependent positive effect on the value of the left ventricular ejection fraction and on the course of heart pathology. The maximum ejection fraction of the left ventricle is observed in patients who took the drug in a dose &gt; 1.2 μg/kg. The use of the drug in a dose &gt; 0.53 μg/kg leads to a probable decrease in the frequency of re-hospitalization within 2 years due to decompensation of heart failure.

Critically ill severe hypothyroidism: a retrospective multicenter cohort study

BackgroundSevere hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients.MethodsWe conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure.ResultsEighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality.ConclusionsSH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Thyroid Ewing sarcoma and rectal administration of levothyroxine

Thyroid Ewing sarcoma and rectal administration of levothyroxine

Munchausen syndrome with factitious hypoglycemia due to deliberate insulin analog administration and factitious hyperglycemia in a patient with hypothyroidism

BackgroundHypoglycemic syndrome is a potentially life-threatening condition that can lead to the disruption of brain and internal organ functions, and in severe cases to irreparable consequences or death. Factitious hypoglycemia (FH) is the deliberate use of insulin preparations or oral hypoglycemic drugs with the aim of lowering blood glucose levels into the pathologically-hypoglycemic range. Deliberate administration of insulin analogs may be difficult to prove because they might not have epitopes or containing low affinity epitopes that are the targets of antibodies used in particular assay kits.Case presentationA 34 years old woman was admitted to the Endocrinology Research Centre in September 2021 with a diagnosis of hypothyroidism and diabetes mellitus. Upon admission she complained of high glycemia indexes up to a maximum of 34 mmol/l ( 612 mg/dl), high TSH and low free T4 ( fT4) concentrations, despite reporting regular levothyroxine administration at a dose of 200 mcg per day. Under nursing supervision, her fT4 was rapidly normalized suggesting non-compliance as the cause of low thyroid hormone milieu. Glycemic fluctuations from 33 to 2.1 mmol/l (594 to 38 mg/dl) according to glucometer measurements were observed against the background of Lis-Pro insulin therapy, while no hyperglycemia was registered in venous blood and in the interstitial fluid concomitantly with the values found by glucometer. It was assumed that the patient’s fingers were intentionally contaminated with glucose solution. Factitious hypo- and hyperglycemia were suspected. During yet another episode of hypoglycemia (1.86 mmol/L, 33 mg/dl) venous blood was drawn. Low to low-normal insulin and C-peptide values were found: 2.2 µU/ml (Roche kit) and 1.18 ng/ml, respectively. Therefore, insulin concentration in the same sample was re-tested with another kit (Abbott) and a significantly elevated value of 89.9 µU/ml was detected. Based on these results, FH was confirmed due to exogenous administration of an insulin analog undetectable by the Roche kit.ConclusionThis clinical example illustrates to draw attention to multiple manipulations employed by subjects with Munchhausen Syndrome. In addition, this diagnosis may be further complicated by the laboratory use of immunoassay kits incapable of detecting some insulin analogs.

Comparison of Postoperative Unfavorable Events in Patients with Low-Risk Papillary Thyroid Carcinoma: Immediate Surgery Versus Conversion Surgery Following Active Surveillance.

Background: Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) was initiated at Kuma Hospital in 1993 and has gradually spread worldwide. We previously demonstrated that AS is associated with a much lower incidence of unfavorable events than immediate surgery (IS). However, conversion surgery (CS) raises concerns about increased surgical complications due to advanced disease. In this study, we conducted a comparative analysis of unfavorable events after IS and CS. Methods: Between 2005 and 2019, 4635 patients clinically diagnosed with low-risk PTMC at Kuma Hospital were enrolled. Of these, 2896 underwent AS (AS group), and the remaining 1739 underwent IS (IS group). To date, 242 patients (0.8%) in the AS group have undergone CS for various reasons (CS group). Results: The incidence of unfavorable events, such as levothyroxine administration after surgery, postoperative hematoma, transient/persistent hypoparathyroidism, and transient/persistent vocal cord paralysis, did not differ between the CS and IS groups. None of the patients in the CS group had permanent vocal cord paralysis; however, this occurred in 15 patients (0.9%) in the IS group and was caused by accidental injury in 4 patients and carcinoma invasion in 11 patients. The incidence of surgery, levothyroxine administration, postoperative hematoma, transient/permanent hypoparathyroidism, and vocal cord paralysis was significantly higher (p < 0.001) in the IS group than in the AS group. There were no differences in the incidence of lymph node recurrence and overall mortality between the AS and IS groups. None of the patients in the AS and IS groups showed distant metastasis or died from thyroid carcinoma. Conclusions: There were no differences in the incidence of unfavorable events between the CS group and the IS group. Although none of the CS and AS groups had permanent vocal cord paralysis, accidental injury of the recurrent laryngeal nerve occurred in four patients (0.2%) in the IS group. The IS group had a significantly higher incidence of unfavorable events than the AS group. The prognoses of patients in both the AS and IS groups were excellent. Therefore, we recommend AS as the first-line management for low-risk PTMC.

ODP517 Successful Treatment of Myxedema Coma after SARS-CoV-2 infection with Combination Oral Levothyroxine and Liothyronine

Abstract Introduction Myxedema coma (MC) is a rare, extreme form of hypothyroidism. It can be triggered by numerous factors including severe illness, trauma and infection. With the emergence of COVID, one may ask if COVID infection can lead to myxedema coma. Prompt infusion of levothyroxine is the consensus treatment. However, in areas where the IV form is unavailable, oral levothyroxine and liothyronine can be an option. Case This is a case of a 64-year-old Filipino female with no known comorbidities, no history of neck radiation or thyroid surgery. She was hospitalized for 28 days a month prior to this admission for severe COVID and and was discharged well. One day after discharge, she was noted to have decrease in sensorium with no other apparent cause. On examination, the patient was unresponsive with a blood pressure of 60/40 mmHg, heart rate of 52 bpm, temperature 36°C and oxygen saturation of 96% at 7lpm. Examination of the neck showed no mass or scar, and the rest of systemic exam was unremarkable. Her initial bloodwork showed: Hemoglobin 7 gm/dl, Creatinine 2.4 mg/dl, sodium 132 mmol/L and RBS 66 mg/dl. Thyroid stimulating hormone was 33.26 uIU/mL (NV 0.55 - 4.78 uIU/mL), free thyroxine (T4) level of 0. 07 ng/dl (NV 0.89-1.76 ng/dL) and a random serum cortisol 37.3 ug/dL. Anti-TPO was negative. IV hydrocortisone 100mg was administered until adrenal insufficiency was ruled out. Due to the unavailability of IV formulations, a loading dose of 100mcg of levothyroxine tablet and 25mcg liothyronine tablet was given thru NGT. Intensive supportive care was given. Adjustment of levothyroxine dosage was based on clinical response. The patient responded well to treatment and was discharged improved after 3 weeks. The temporal relationship between the patient's clinical manifestations and her recent infection, in the absence of other risk factors, made the authors consider that her myxedema coma was most likely precipitated by COVID. The proposed mechanism is via the ACE2 receptors highly expressed in the thyroid gland. SARS-CoV-2 hijacks these receptors in order to enter the thyroid, destroy follicular cells and stop the ability to produce T3 and T4. Conclusion Myxedema coma occurs when a precipitating factor disrupts thyroid hormone regulation and it bears a grim prognosis. Among patients with COVID and even those who have recovered, an increased suspicion of hypothyroidism is necessary to diagnose the condition at a stage that is early enough to avoid myxedema coma. In areas where parenteral levothyroxine is not available, this case shows that administration of combination oral levothyroxine and liothyronine for myxedema may be successful. Presentation: No date and time listed

ODP478 Effects of peripheral iodothyronine deiodinases on thyroid hormone economy: Insights from the overexpressing mice

Abstract Background In peripheral tissues, triiodothyronine (T3) production and consequent thyroid hormone actions are mainly regulated by iodothyronine deiodinases (DIOs) classified into 3 types: D1, D2, and D3. Although thyroid hormone economy in the DIO-deficient mice and patients carrying genetic variants of DIOs was well clarified, a condition of DIOs upregulation was not enough elucidated. We aimed to investigate effects of peripheral DIOs on thyroid hormone economy and consequent thyroid hormone action using novel DIO-overexpressing mice that were not yet generated. Methods We cloned coding sequences of human DIOs with FLAG-tag and HiBiT-tag sequences into a pcDNA3.1 vector. To obtain full-length proteins, we modified these vectors by cloning selenocysteine insertion sequence of each DIO (SECIS vectors). Western blot analyses and HiBiT lytic assay using HEK293T cells revealed that SECIS vectors expressed full-length proteins with substantial activity. Subsequently, in vivo transfections of pLIVE-based SECIS vectors into male C57BL/6J mice were performed by hydrodynamic gene delivery to generate mice overexpressing DIOs (D1, D2, and D3 mice). Results First, we verified that DIOs were successfully overexpressed in the livers using HiBiT lytic assay as well as RT-PCR. Analyses of multiple organs of D3 mice assured that full-length protein was not significantly expressed in the heart, the kidney, and the skeletal muscle. RT-PCR analyses also suggested that the pituitary glands and the thyroid glands were not transfected. We evaluated thyroid hormone economy of DIO-overexpressing mice compared to Empty mice transfected with pLIVE-Empty vector. D1 mice did not have changes in serum thyroid hormone levels, whereas D2 mice had higher serum fT3 levels. Clearer changes were found in D3 mice. They had hypothyroidism with higher serum rT3 levels. Correspondingly, in their livers, rT3 concentration was higher and T3-responsive genes were downregulated. We elucidated by adding the cohort with levothyroxine (LT4) administration because DIO-overexpressing mice had liver T4 insufficiency probably due to consumption by DIOs. Comparisons between the DIO-overexpressing mice with and without LT4 administration revealed that D2 mice presented upregulation of T3-responsive genes by LT4 administration distinct from Empty mice. Conclusions We generated DIO-overexpressing mice that expressed human DIOs predominantly in the liver. They provided physiological evidence to integrate the phenotypes of the knockout mice and specific clinical situations. D2 mice seemed to recruit T3 into the circulation as well as in the liver. D3 mice had an overt phenotype characterized by consumptive hypothyroidism. In addition, D3 mice are expected to be a novel hypothyroidism model that does not involve disruption of thyroidal hormone secretion. DIO-overexpressing mice can be generated by single injections of plasmid vectors of interest and can contribute to progress in the field of thyroid hormone economy and action. Presentation: No date and time listed