Levothyroxine Therapy Research Articles

Real-world derived weight-based levothyroxine doses to achieve optimal thyrotropin target in different degrees of autoimmune hypothyroidism

Abstract Purpose All patients with overt and severe subclinical hypothyroidism (SCH), and some with mild SCH require levothyroxine (L-T4) therapy. The present study aims to report real-world derived weight-based L-T4 doses to achieve optimal–low normal–thyrotropin target in different degrees of autoimmune hypothyroidism. Methods This was a retrospective study of patients with autoimmune hypothyroidism. Inclusion criteria were consistent achievement of optimal TSH target (0.3 to 2.5 µIU/L) using a stable L-T4 dose for at least 6 months. Patients were classified into 4 groups: group 1; mild SCH, group 2; severe SCH, group 3; overt hypothyroidism, and group 4; hypothyroidism with unknown initial TSH and free T4. Weight-based L-T4 doses were calculated for each group. Results Eighty-seven, 95, 75, and 91 patients met the inclusion criteria for groups 1–4, respectively. Weight-based L-T4 dose was the lowest in group 1 (1 ± 0.25 µg/kg/day), was the highest in group 3 (1.4 ± 0.29 µg/kg/day), while in groups 2 (1.2 ± 0.26 µg/kg/day), and 4 (1.2 ± 0.31 µg/kg/day) were not statistically different from each other. There was a significant decrease in weight-based L-T4 dose with increasing body weight categories in groups 1 and 2, and a significant difference between those less than 60 or ≥ 60 years of age in group 3. Conclusion Real-world derived weight-based L-T4 doses to achieve optimal TSH target are 1, 1.2, and 1.4 µg/kg/day for patients with mild, severe SCH, and overt autoimmune hypothyroidism, respectively. Age and body weight subcategories can better fine-tune required doses.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25µg levothyroxine intervention group (G25, 69 women), and 50µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Posttreatment symptoms in hypothyroidism and correlations with thyroid-stimulating hormone and free triiodothyronine and free thyroxine: A ThyPRO-based follow-up study

ABSTRACT Background: Treatment of primary hypothyroidism with levothyroxine does not fully alleviate its symptoms. Though there have studies to correlate levels of tri-iodothyronine with symptomatology, its role still remains controversial. Aims: To study symptoms of hypothyroidism before and after levo-thyroxine therapy using ThyPRO 39 scores and to correlate these with thyroid hormone levels. Materials and Methods: This quasi-experimental study was conducted at the in and outpatients' departments of Internal Medicine and Endocrinology of St John's Medical College Hospital. Patients were enrolled if they were aged over 18 years and were diagnosed with hypothyroidism (TSH&gt;/= 10 IU/l). Pregnant ladies and patients who had undergone radioiodine therapy or were diagnosed with thyroid cancers were excluded. Results: A total of 46 (F=28) patients were enrolled into the study. The mean age of the study group was 41.63 +/-SD 12.078 years.Among hypothyroid symptoms at diagnosis, Tiredness and Emotional Susceptibility had the highest effect size. Tiredness, Cognitive complaints and Depressive symptoms had significant negative correlation with fT3.While Goitre, Tiredness, and Cognitive complaints showed significant association with TSH, no correlations were noted with fT4 and many scores. There was a statistically significant negative correlation between fT3 and post therapy domain scores of Goitre, Tiredness, Impaired Daily Life and Impaired Social Life. There was a significant difference in the QoL domain between those with and without co-morbidities, the latter group having lower scores signifying better QoL. Conclusion: Symptoms of hypothyroidism may have a correlation with fT3 levels. Larger well-designed studies with supplementation of T3(triiodothyronine) and correlation with symptoms and tissue levels of fT3 will give conclusive answers.

Heart rate in newborns is associated with age, sex and maternal levothyroxine therapy.

To evaluate the definition and causes of neonatal bradycardias. This retrospective study included 135 term-born newborns referred for 24-hour Holter monitoring due to bradycardia. Bradycardia was defined as either a heart rate below 80 beats per minute (standard definition) or a heart rate below our recently published age-specific reference values for neonatal heart rate. The mean (SD) age was 6.1 (1.3) days. With standard definition, 107 newborns (79%) had bradycardia, whereas only 20 (15%) had a minimum heart rate lower than the age-specific reference. Younger newborns had lower heart rates. Each day increased the minimum, mean and maximum heart rate by 1.8 (95% CI: 1.0, 2.6), 4.2 (95% CI: 3.0, 5.3) and 2.1 beats per minute (95% CI: 0.3, 3.8), respectively. Male sex and maternal levothyroxine medication were negatively associated with the mean and maximum heart rate. None of the newborns had a cardiac cause for low heart rate. Among term newborns with bradycardias, younger age, male sex and maternal levothyroxine medication were associated with a lower heart rate on Holter monitoring. Given the age-related increase in heart rate, the 80 beats per minute limit as a universal threshold for abnormal heart rate in newborns appears inappropriate.

Screening factors affecting proper levothyroxine therapy among patients with primary hypothyroidism: a cross-sectional study.

Primary hypothyroidism, the most common form of hypothyroidism, requires effective patient understanding and management for successful long-term treatment. This study aimed to investigate the influence of patient knowledge, attitude, practice (KAP), depression, and medication adherence on treatment response in primary hypothyroidism. A cross-sectional observational study was conducted at Al Hassan Metabolism, Endocrine, and Diabetes Center (HMEDC) in Iraq between September 2022 and March 2023. We enrolled 111 patients with signs and symptoms of primary hypothyroidism over 6 months. A validated questionnaire assessed patient knowledge, attitude, practice (KAP), depression, and medication adherence. Thyroid-stimulating hormone (TSH) levels were measured to assess treatment response. Data were analyzed using SPSS v26, with categorical variables presented as percentages. The student's t-test was used to assess statistical significance, with P - valuess below 0.05 considered significant and P - values below 0.01 considered highly significant. The mean age of patients was 45 ± 11.9 years. Approximately 34% of patients had insufficient knowledge, and 30% indicated a positive attitude towards their treatment. A total of 35% of patients had excellent practice. There was no statistically significant association between KAP and age or gender. There was a significant positive correlation between higher levels of education and improved KAP scores. A total of 44.1% of participants reported moderate depression, and 58% demonstrated adherence to levothyroxine (LT4) treatment. Despite good adherence, the combination of fair knowledge and moderate-to-severe depression resulted in suboptimal outcomes for replacement treatment.

Impact of levothyroxine therapy for maternal subclinical hypothyroidism on infant’s neurodevelopment

Impact of levothyroxine therapy for maternal subclinical hypothyroidism on infant’s neurodevelopment

Sustained Euthyroidism during Thionamide Antithyroid Drug Treatment: Comparison of Short- and Long-term Methimazole Therapy

Background: Extended low serum thyrotropin (TSH) levels may increase the risk of cardiovascular events in patients with hyperthyroidism. Objectives: This study aimed to compare the time spent with sustained normal TSH concentration following short- and long-term methimazole treatment. Methods: A total of 258 patients with Graves’ hyperthyroidism completed 18 - 24 months of methimazole therapy and were randomized to discontinue treatment (n = 128, short-term group) or continue an additional 36 - 102 months of methimazole therapy (n = 130, long-term group). Clinical and laboratory evaluations were performed every 6 months for 132 months after randomization. Results: There was no difference in serum-free thyroxine, triiodothyronine, and TSH concentrations between the 2 groups at the time of randomization. Of 128 patients in the short-term group, 5 left in follow-up, 2 became hypothyroid, 67 (54%) had a relapse of hyperthyroidism, and only 54 (44%) were euthyroid at the end of the study. Among 130 patients on the long-term methimazole therapy, 4 were left in follow-up, 24 developed hyperthyroidism, 4 developed hypothyroidism, and 98 (78%) were euthyroid 132 months post-randomization. Total time spent on euthyroidism was 90.4% ± 8.1% of the study period in the short-term and 95.8% ± 7.0% in the long-term treatment groups (P &lt; 0.001). The lowest time spent in euthyroidism (74.6% ± 6.4% of the study period) belonged to 29 (24%) patients in the short-term group under levothyroxine therapy because of fluctuation in serum TSH. Patients in both groups with hyperthyroidism relapse who chose methimazole therapy spent &gt;90% of the study time in euthyroidism. Conclusions: In patients with Graves' hyperthyroidism, sustained normal serum TSH levels were more common in the long term as compared to the short-term methimazole treatment.

To compare the efficacy and safety of 5 days a week levothyroxine versus daily replacement therapy in hypothyroid patients: An experience from a tertiary care center in Central India

Introduction: Hypothyroidism is a common endocrine disorder and associated with several complications if not diagnosed and managed. Levothyroxine (LT4) replacement therapy is the treatment of choice. Levothyroxine has a long half-life of 6–7 days and hence can be given intermittently keeping the weekly dose the same. Aim: The aim of the study was to compare the efficacy and safety of 5 days a week levothyroxine versus daily replacement therapy in patients with hypothyroidism and to identify the patient’s satisfaction level at the end of the trial. Methods: This was a prospective cohort study in which patients diagnosed with hypothyroidism and having stable thyroid function in the last 6 months with a minimum of two normal thyroid profile reports on the same LT4 dose were shifted 5 days a week LT4 (keeping the total weekly dose the same) after informed consent. Then, patients were followed up at regular intervals, and biochemical analysis of thyroid profile was done at 12 and 24 weeks or Si Opus Sit (SOS)according to clinical judgment. Results: One hundred and fifty patients with hypothyroidism were included in the study with a male-to-female ratio of 4:21. The mean age of our patients was 40.6 ± 8.58 years. The mean duration of hypothyroidism was 5.9 ± 3.01 years. The mean thyroid-stimulating hormone, T4, and T3 at baseline were 3.22 + 0.91 μIU/mL, 8.71 + 1.91 μg/dL, and 0.93 + 0.04 ng/mL, and at 12 weeks and 24 weeks were 3.62 ± 0.82 μIU/mL, 8.01 ± 2.01 μg/dL, and 1.2 ± 0.05 ng/mL and 3.33 ± 0.79 μIU/mL, 8.36 ± 1.99 μg/dL, and 0.88 ± 0.03 ng/mL, respectively. One hundred and twenty-seven patients did not require any dose adjustment. There was no significant difference in thyroid profile. Conclusion: Five days a week levothyroxine replacement regimen is noninferior to daily levothyroxine replacement regimen in treating patients with hypothyroidism and can be conveniently prescribed. Furthermore, 5 days regimen increased the compliance and satisfaction level in patients with hypothyroidism.

Efficacy of a levothyroxine dosage regimen based on serum thyrotropin level, for primary hypothyroidism. An open label dose finding study.

There are no guidelines on individualized initial levothyroxine dosage in primary hypothyroidism. This prospective observational study was done to assess whether a predetermined dose of levothyroxine based on Thyroid Stimulating Hormone (TSH) levels would be able to make the patient euthyroid during a period of six weeks and to find other factors which influence the levothyroxine requirement. Newly diagnosed patients with primary hypothyroidism or those patients who were not on levothyroxine therapy were divided into TSH-based groups-Group 1, 5-9.99, Group 2, 10-29.99, Group 3, 30-99.99 and Group 4, >100 μIU/ml and treated with an initial levothyroxine dose of 25,50,75 and100 μg/day for next six weeks. Factors correlating with levothyroxine requirement were determined. Of the 171 patients who were included 142 completed the study, 34,46,28 and 34 patients were included in groups 1 to 4, respectively. Normalization of TSH with the above criteria was achieved in 111 (78.7%) out of 141 patients, and 91%, 67%, 75%, and 82% respectively in the 4 groups. Among adequately replaced patients pre-treatment TSH level (r = 0.81), T4 level (r = 0.61), and body weight (r = 0.19) correlated with the levothyroxine requirement. Based on these factors predicted initial dose (μg/day) was found to be 0.54 (Body Weight [Kg]) +0.47 (TSH [μIU/m]) - 1.4 (Total T4 [μg/dl]) +17.79 or 0.27 (Body Weight) +0.553 (TSH) +21. Serum thyrotropin-based categorization for initial levothyroxine dose leads to euthyroidism in nearly four of five patients with primary hypothyroidism. The dose required for adequate replacement of levothyroxine has correlation with pre-treatment serum TSH levels serum thyroxine levels and body weight.

Supplementing liothyronine to levothyroxine therapy for management of hypothyroidism: Current clinical practice and beyond

Supplementing liothyronine to levothyroxine therapy for management of hypothyroidism: Current clinical practice and beyond

HASHIMOTO THYROIDITIS IN PEDIATRICS: INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT WITH CONSIDERATIONS OF CANCER RISK

This systematic review comprehensively examines the pathogenesis, diagnosis, management, and cancer risk of Hashimoto's thyroiditis in pediatric populations. We searched the literature using PubMed, Web of Science, and critical medical journals, focusing on studies published within a specified timeframe. Inclusion criteria targeted studies on pediatric populations, while exclusion criteria filtered out irrelevant studies. Data extraction and synthesis highlighted key findings: genetic predispositions and environmental triggers such as selenium levels and gut microbiota alterations contribute to Hashimoto’s Thyroiditis pathogenesis. Diagnostic challenges arise from the often subtle and nonspecific clinical presentation, necessitating thorough clinical evaluations and diagnostic testing, including TSH, free T4, thyroid antibodies, and ultrasound. Management strategies involve levothyroxine therapy, dietary considerations, and lifestyle modifications tailored to individual patient needs. Additionally, the review discusses the controversial but significant potential association between Hashimoto’s Thyroiditis and increased thyroid cancer risk, emphasizing the need for vigilant long-term monitoring. This synthesis provides critical insights to inform clinical practice and future research directions.

Особенности поражения щитовидной железы у пациентов с синдромом Дауна

Aim. To demonstrate the prevalence and structure of thyroid diseases in children with Down syndrome (DS), and to analyze the features of their diagnosis and treatment. Key points. Thyroid gland pathology in DS includes congenital hypothyroidism (CH), subclinical hypothyroidism (SH), chronic autoimmune thyroiditis (CAT), and diffuse toxic goiter (DTG). Thyroid diseases are more common and occur earlier in individuals with DS than in the general population; their presence is independent of gender. SH is identified in 7–40% of patients with DS, but progresses to overt hypothyroidism in less than half of the cases. Various clinical guidelines recommend that patients with DS should have their thyroid-stimulating hormone (TSH) levels monitored regularly, every 6–12 months, and, if necessary, their free thyroxine and thyroid peroxidase antibodies. The treatment of CH, CAT, and DTG in DS patients is the same as in patients without DS. Most researchers advocate against levothyroxine therapy for SH, as there is no evidence of benefit from early treatment, and elevated TSH levels are often mild and transient. Conclusion. The high prevalence and wide spectrum of thyroid pathology in patients with DS necessitate regular monitoring of hormone levels. The complexity of interpreting isolated TSH elevation can complicate treatment decisions. In recent years, a more justified strategy of “watchful waiting” along with more frequent laboratory tests has become more prevalent. Keywords: Down syndrome, congenital hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, diffuse toxic goiter (Graves disease).

Rapid levothyroxine absorption test for assessment of nonadherence to levothyroxine treatment: a case series of six patients

Background: Failure to treat persistent hypothyroidism despite the use of adequately prescribed doses of levothyroxine should be evaluated for malabsorption and nonadherence to medication. Previous literature suggested that orally administered levothyroxine showed maximum absorption at or near 2 hours. This rapid absorption suggests the use of a 2-hour levothyroxine absorption test as an alternative to long, cumbersome protocols. Limited data are available measuring free thyroxine (FT4) levels at 2 hours after oral administration of 1,000 mcg of levothyroxine. Case Presentation: Six patients who continued to have hypothyroidism despite taking ostensibly high doses of levothyroxine underwent a 2-hour protocol levothyroxine absorption test. All patients were given 1,000 mcg of levothyroxine, and serum levels of thyroid-stimulating hormone (TSH), FT4, and free triiodothyronine (FT3) were measured at 0, 60, and 120 minutes. All patients showed an increasing trend in FT4 in subsequent samples at 60 and 120 minutes, compared to baseline values, providing strong evidence of peak levothyroxine absorption at 2 hours. Five patients had raised baseline TSH levels, indicating nonadherence to treatment, and one had normal baseline TSH levels, indicating adherence to levothyroxine therapy on prior test scheduling, with increased FT3 and FT4 levels in subsequent samples at 60 and 120 minutes. Conclusion: We conclude that the rapid levothyroxine absorption test, using a 2-hour protocol, is a more convenient method to differentiate nonadherence from malabsorption. Moreover, scheduling the patient will result in adherence to levothyroxine therapy in some patients.

C-reactive Protein Levels in Patients With Autoimmune Hypothyroidism Before and After Levothyroxine Treatment.

Hypothyroidism is one of the most common endocrine disorders. Most patients with hypothyroidism have autoimmune thyroiditis (Hashimoto's), characterized by elevated concentrations of anti-thyroperoxidase (ATPO) antibodies. Both overt hypothyroidism (OH) and subclinical hypothyroidism (SH) have been associated with cardiovascular risk factors, including markers of inflammation. High-sensitivity C-reactive protein (hs-CRP) is a veridical marker of systemic inflammation. Even a minor increase in hs-CRP is considered a cardiovascular risk; therefore, evidence of a beneficial effect of levothyroxine treatment on hs-CRP could be an argument in favor of therapy for SH. To assess hs-CRP levels in patients with hypothyroidism and evaluate levothyroxine treatment's effect on hs-CRP. This is a cohort study in which patients with hypothyroidism were evaluated before and after treatment with levothyroxine. 37 patients (17 with OH and 20 with SH) and 38 healthy controls were included in the study. hs-CRP was measured at the baseline visit, then after 2 and 4 months of levothyroxine therapy at a dose necessary to achieve euthyroidism as evidenced by a normal level of thyroid-stimulating hormone (TSH). hs-CRP was significantly increased in OH (p < 0.001) and SH (p = 0.001) at baseline as compared to controls. hs-CRP significantly decreased in SH (2.2±1.6 mg/L at baseline visit, 1.4±1.1 mg/L after 2 months of levothyroxine treatment, P = 0.017) and tended to decrease in OH (2.3±1.6 mg/L at baseline visit, 1.6±1.1 mg/L after 4 months of levothyroxine treatment, P = 0.067*). Patients with hypothyroidism have increased hs-CRP levels compared to a healthy control group and, thereby, a moderately increased cardiovascular risk. Achievement of euthyroidism by levothyroxine treatment decreased the levels of hs-CRP in patients with hypothyroidism.

The negative impact of levothyroxine treatment on urinary luteinizing hormone measurements in pediatric patients with thyroid disease.

Previous studies suggest urinary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements by immunofluorometric assays (IFMA) as noninvasive alternatives to serum assays for puberty assessment. However, these studies excluded patients with other endocrine disorders and those taking medications. Besides, the recent discontinuation of IFMA manufacturing is a concern. We explored the utility of luminometric assays (LIA) for urinary gonadotropins and thyroid-stimulating hormone (TSH) determinations in euthyroid patients with thyroid pathologies. We used LIA and IFMA assays to measure serum and first-morning-voided (FMV) urine LH, FSH, and TSH concentrations in euthyroid patients with various thyroid disorders. Of the 47 euthyroid patients with normal serum TSH (S-TSH) levels, 14 were receiving levothyroxine therapy. FMV total urinary LH (U-LH) concentrations correlated significantly with those measured in serum using either LIA (r=0.67, P<.001) or IFMA (r=0.83, P=.003) in patients not receiving levothyroxine treatment; however, no significant correlation could be detected in patients receiving levothyroxine regardless of the assay method (for LIA: r=0.50, P=.08 and IFMA r=0.44, P=.15). Urinary TSH (U-TSH) concentrations correlated poorly with those in serum in both the untreated and the treated groups (r=-0.13, P=.49, and r=-0.45, P=.11, respectively). FMV total U-LH determinations by LIA can be used to assess pubertal development in patients with thyroid pathology, provided the euthyroid patient is not on levothyroxine treatment. U-TSH measurements by LIA cannot replace invasive S-TSH measurements at least in patients with normal S-TSH levels. Further research may reveal the utility of U-TSH determinations in patients with elevated S-TSH levels.

Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.

Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post-thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid-related disorders.

Assessing the cardiovascular effects of levothyroxine use in an ageing United Kingdom population (ACEL-UK) protocol: a cohort and target trial emulation study

BackgroundSubclinical hypothyroidism is diagnosed when serum thyroid stimulating hormone levels are higher whilst free thyroxine levels remain within their respective reference ranges. These reference ranges are uniformly applied in all adults, despite serum thyroid stimulating hormone levels naturally increasing with age. Research has found that mildly elevated thyroid stimulating hormone levels may be associated with some benefits in ageing patients, including reduced mortality and better cardiorespiratory fitness. Levothyroxine is typically prescribed to patients with hypothyroidism, but no conclusive evidence exists on whether levothyroxine therapy is beneficial or detrimental in older subclinical hypothyroid patients. Despite this, prescriptions for levothyroxine are increasing year-on-year. This study aims to determine if receiving levothyroxine affects the cardiovascular and bone health outcomes of subclinical patients in primary care aged 50 years and over.MethodsThis project includes a retrospective cohort analysis and a target trial emulation study using electronic patient records collected between 2006 and 2021 and recorded in The Health Improvement Network database. The primary outcome of this study is to compare the cardiovascular outcomes of subclinical hypothyroid patients aged over 50 years treated with levothyroxine compared to those untreated. Secondary outcomes are bone health and all-cause mortality outcomes. Descriptive and inferential statistics will both be employed to analyse the data. Secondary analysis will explore confounding factors, including age, sex, smoking status, body mass index, co-morbidities, and levothyroxine dosage.DiscussionThere needs to be a greater understanding of the potential risks of the current treatment for older patients with subclinical hypothyroidism in a primary care setting. We will investigate the clinical importance of this issue and whether older subclinical hypothyroid patients have poorer outcomes when treated. Clarifying this concern may help address the healthcare resource implications of ageing patients being misclassified as having mild hypothyroidism, as these patients are more likely to repeat their blood tests. This could reduce prescription wastage and improve patient outcomes and quality of life in the ageing population.Trial registrationNot applicable.

Abstract 16717: Managing Myxedema Coma: A Challenging Case of Cardiogenic Shock Culminating in Orthotopic Heart Transplantation

Background: Myxedema coma (MC) is a rare manifestation of severe hypothyroidism often seen in elderly female patients. While the sequelae of MC can lead to multi-organ involvement and eventual failure, irreversible Heart Failure (HF) is rarely seen. This case culminated in orthotopic heart transplant (OHT) for definitive treatment. Case Presentation: A 23-year-old male presented with worsening RUQ abdominal pain for 2 weeks. In the ED, he had PEA arrest and with ROSC, he was admitted to the CCU for presumed cardiogenic shock, with labs remarkable for lactate 7.5 mmol/L, pro-BNP 6104 pg/mL, and markedly elevated serum creatinine and LFTs. The patient exhibited HF symptoms for 9 months before admission, manifesting as worsening LE edema, fatigue, and weight gain. He was also noted to have untreated hypothyroidism with repeat TSH of 857 μIU/mL on admission, indicating MC as a potential trigger for worsening HF. TTE revealed severe biventricular dysfunction with global hypokinesis and LVEF of 10-15%. Inotropic support was initiated with dobutamine, with RHC showing CVP 11 mmHg, RV 23/11 mmHg, PA 32/22 mmHg, PCWP 25 mmHg, and CI 2.3 LPM/m 2 . Subsequent deterioration in CI and MVO2 necessitated IABP placement and vasopressor support, and later rescue VA-ECMO with atrial septostomy, aiming for OHT. Endocrine evaluation confirmed primary hypothyroidism, and the patient received high-dose levothyroxine, T3, and stress-dosed steroids. While there have been instances where cardiac consequences of myxedema HF were reversed by thyroid administration, his significantly dilated left ventricular internal dimension at end diastole, as well as complications of ECMO (bleeding) expedited his transplant evaluation. OHT was successfully performed on hospital day 14. Continuous improvement in thyroid function studies was observed throughout the treatment course with levothyroxine therapy. Discussion: Worsening HF in the setting of MC, particularly in a male patient, is an uncommon presentation that requires prompt action. This patient required mechanical support as an eventual bridge to OHT with simultaneous treatment for hypothyroidism, illustrating the complexity of the case and the interventions necessary for a positive outcome in an uncommon clinical scenario.

Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma.

Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

When Hormones are Being Difficult: A Rare Case and the Literature Review of Pembrolizumab-Induced Polyendocrinopathy.

Immune Checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab, and ipilimumab are monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA4) or program death (PD)1 and its ligand PDL1. Agents targeting PD1, such as pembrolizumab, have shown widespread efficacy in the past and are also associated with a wide range of immune-related adverse events (irAEs), including endocrine toxicities. A 31-year-old female with a medical history significant for Stage IIb Breast cancer on chemo and immunotherapy (pembrolizumab) presented with nausea, vomiting, and generalized abdominal pain. Laboratory studies showed a blood glucose level of 356 mg/dl, elevated Anion gap 18 meq/L, beta-hydroxybutyrate 46 mg/d, and low C-peptide levels <0.10 ng/ml. The patient was treated for Diabetic Ketoacidosis (DKA). Further testing revealed high Thyroid Stimulating Hormone (TSH) levels along with elevated thyroid peroxidase levels of 38 IU/L. After discharge from the hospital on insulin and levothyroxine therapy, the patient reported increasing fatigue and further testing revealed low cortisol levels <0.5 mcg/dl with elevated ACTH consistent with primary adrenal insufficiency. The patient was started on hydrocortisone therapy with improvement in symptoms. Endocrine toxicities are not uncommon in patients receiving pembrolizumab, but polyendocrinopathy in a relatively rare side effect of pembrolizumab. Only a few cases of pembrolizumab-induced polyendocrinopathy have been reported so far which we have mentioned in this article. While patients are on immunotherapy, close monitoring for clinical signs & symptoms can lead to an early diagnosis, substantially improving morbidity and mortality.