FT4 Levels Research Articles

A screening study of high-risk groups for liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease

The purpose of this study was to explore the correlation between Hashimoto’s thyroiditis and Metabolic dysfunction-associated fatty liver disease (MAFLD), and at the same time to screen high-risk groups for liver fibrosis in MAFLD, find out the high-risk related indicators. The physical examination population was included as the study subjects and was grouped according to the diagnostic criteria for MAFLD. APRI > 1 or NFS > 0.676 or FIB-4 > 2.67were used to assess people at high risk of liver fibrosis, and logistic regression analysis was used to identify risk factors associated with high risk of liver fibrosis in MAFLD. ROC curves are used to look for indicators of diagnostic value. The proportion of people with Hashimoto’s thyroiditis was lower in the MAFLD group. The MAFLD high-risk group for liver fibrosis had higher TSH levels, lower FT3 and FT4 levels, higher TGAB levels, and differences in biochemical markers. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients. ROC curve analysis showed that the AUC of age was 0.741 (0.721–0.761), and the optimal stage value was 57.5 years, while the AUC of AST was 0.729 (0.707–0.751), and the optimal cut-off value was 39.5 U/L. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients.The age is greater than or equal to 57.5 years, or the AST is greater than or equal to 39.5 U/L, indicating that the MAFLD patients are at high risk of liver fibrosis.

Understanding Hypothyroidism: Causes, Symptoms, Diagnosis, and Treatment Options for Optimal Thyroid Health

Hypothyroidism is a condition where your thyroid gland doesn’t produce enough thyroid hormone leading to symptoms like fatigue, weight gain, and feeling cold. Globally, the lack of iodine in the environment is the leading cause of hypothyroidism. However, in regions where there is enough iodine, Hashimoto’s thyroiditis, an autoimmune disorder is the most common cause. Risk factors include having a family history of thyroid disease, being over 6o years and being female. Diagnosis done with a simple blood test that measures the levels of serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH). High TSH and FT4 levels usually indicate Hypothyroidism. Even daily medication with synthetic thyroid hormone (levothyroxine), regular follow up with your doctor is important to monitor your TSH level and adjust the dosage of medication as needed.

Blood levels of zearalenone, thyroid-stimulating hormone, and thyroid hormones in patients with colorectal cancer

Mycotoxins are secondary metabolites produced by various species of mold fungi commonly found in plant materials. Zearalenone (ZEN) adversely affects the endocrine system. This study aimed to determine whether thyroid-stimulating hormone (TSH), procalcitonin (PCT), free triiodothyronine (fT3), and free thyroxine (fT4) levels are altered during natural zearalenone mycotoxicosis in patients diagnosed with sigmoid colon cancer (SCC) or colorectal cancer (CRC). A study was conducted on women and men diagnosed with SCC or CRC accompanied by the presence or absence (Patients Without ZEN – PWZ group) of ZEN in the blood. The PWZ group consisted of 17 patients with symptoms of SCC and CRC in whom ZEN and its metabolites were not detected in peripheral blood. The experimental (empirical) groups included a total of 16 SCC and CRC patients who tested positive for ZEN, but not its metabolites. TSH values in both sexes were within the upper limit of the reference range (0.27 – 4.2 μIU/mL) adopted by the hospital laboratory and corresponded to the upper second tertile and the lower third tertile. PCT values demonstrated that SCC and CRC were accompanied by a systemic or local bacterial infection. All mean values of fT3 were in the middle of the reference range, and the mean values of fT4 were within the upper reference limit. The fT3/fT4 prognostic marker was somewhat above the cut-off point of 0.22. These results indicate that in postmenopausal women and andropausal men who were diagnosed with SCC and CRC and were exposed to food-borne ZEN, higher values of the prognostic marker (fT3/fT4) were associated with an unfavorable prognosis. The study also revealed that the more distal the neoplastic lesions in the colon, the higher the percentage of both thyroid hormones, regardless of the patient's sex. The presence of ZEN in the diet alters thyroid activity in patients diagnosed with SCC and CRC.

Exploring the role of plasmapheresis prior to thyroidectomy in managing thyrotoxicosis: a comprehensive scoping review.

A thyroid storm is the most extreme and life-threatening presentation of thyrotoxicosis. Thyroidectomy can be used for definitive treatment. It should be performed after euthyroidism is accomplished. The use of therapeutic plasma exchange (TPE) is a last resort option in cases where standard pharmacological therapy proves to be ineffective. Due to its rare prevalence, there are limited data evaluating the usefulness and efficacy of TPE as a bridging therapy to thyroidectomy. The absence of relevant literature prompted us to conduct a scoping review. The following bibliographic databases were searched for articles dated 30 November 2023: Medline, EMBASE, Web of Science and Google Scholar. The search identified 1047 records, of which 42 articles were accepted with a total of 234 patients. The dominant indications for TPE were side effects due to conventional treatment. The mean fT4 level decreased 51.9% of baseline after TPE, while the mean fT3 level decreased 66.6% of baseline. The main side effects observed with FFP were allergic reactions, while the use of an albumin solution was associated with perioperative bleeding. Based on the limited data available in the literature, we recognize plasmapheresis as an effective treatment option for reducing thyroid hormone levels prior to thyroidectomy in patients with thyrotoxicosis. Available data suggest that it might be reasonable to limit the number of sessions in favor of an earlier surgical intervention. To reduce the risk of bleeding, FFP may be a better option as a replacement fluid, especially in the session prior to thyroidectomy.

Approach to Newborns with Elevated TSH: A Different Perspective from the International Guidelines for Iodine-Deficient Countries.

Lowering of thyroid-stimulating hormone (TSH) cutoffs in newborn screening programs has created a management dilemma by leading to more frequent detection of neonates with elevated TSH concentrations due to false-positive results, transient neonatal hyperthyrotropinemia (NHT), and milder forms of congenital hypothyroidism. Current consensus guidelines recommend starting treatment if the venous TSH level is >20 mU/l in the face of a normal free thyroxin (FT4) level, which is an arbitrary threshold for treatment decisions. In countries such as Türkiye, where transient NHT may be more common due to iodine deficiency and/or overload, putting this recommendation into daily practice may lead to unnecessary and over treatments, long-term follow-ups, and increased workload and costs. In this review, we addressed alternative approaches for infants with elevated TSH concentrations detected at newborn screening. Our management approach can be summarized as follows: Infants with mild NHT (TSH<20 mU/l) should be followed without treatment. In moderate NHT (TSH 20-30 mU/l), treatment or monitoring decisions can be made according to age, TSH trend and absolute FT4 level. Moderate cases of NHT should be treated if age at confirmatory testing is >21 days or if there is no downward trend in TSH and FT4 level is in the lower half of age-specific reference range in the first 21 days. In in-between cases of moderate NHT, thyroid ultrasound can guide treatment decision by determining mild cases of thyroid dysgenesis that require life-long treatment. Otherwise, monitoring is a reasonable option. Infants with compensated hypothyroidism (TSH>30 mU/l) and persistent hyperthyrotropinemia (>6-10 mU/l after neonatal period) should receive L-thyroxine treatment. But all treated cases of isolated TSH elevation should be closely monitored to avoid overtreatment, and re-evaluated by a trial off therapy. This alternative approach will largely eliminate unnecessary treatment of infants with transient NHT, mostly caused by iodine deficiency or excess, and will reduce workload and costs by preventing unwarranted investigation and long-term follow-up.

Roxadustat has risks of reversible central hypothyroidism in patients undergoing hemodialysis: a single-center retrospective cohort study

Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, has proven efficacy in the treatment of renal anemia; however, evidence indicates that it may cause central hypothyroidism. The prevalence and reversibility of roxadustat-induced central hypothyroidism in patients undergoing hemodialysis remain unclear. Here, we retrospectively analyzed thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels in 51 patients (mean age: 72.3 ± 10.7 years; 58.8% male) undergoing hemodialysis before, during, and after halting roxadustat treatment. TSH levels were significantly decreased from a median of 2.46 (interquartile range:1.60–4.51) mU/L before roxadustat treatment to 1.36 (0.72–2.41) mU/L during treatment (p < 0.001), and improved to 2.56 (1.78–4.63) mU/L after halting roxadustat (p < 0.001). Similarly, FT4 levels decreased from 1.11 (0.97–1.24) ng/dL before roxadustat treatment to 0.92 (0.71–1.03) ng/dL during treatment (p < 0.001) and improved to 1.05 (0.93–1.17) ng/dL after halting roxadustat (p < 0.001). FT3 levels were 2.04 (1.78–2.31) pg/mL before starting roxadustat, 1.97 (1.69–2.27) pg/mL during treatment, and 1.90 (1.63–2.18) pg/mL after halting roxadustat, with no significant difference between each group. Moreover, 2.0% of patients exhibited extremely low TSH levels (≤0.1 mU/L) and low TSH levels (>0.1 mU/L to <0.4 mU/L) before starting roxadustat and that percentage increased to 5.9% and 7.8%, respectively, during treatment. After roxadustat cessation, extremely low or low TSH levels recovered in all patients. Taken together, the results indicate that roxadustat can cause reversible central hypothyroidism in patients undergoing hemodialysis.

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. Retrospective cohort study. Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

12602 The Effect of Three-Month Semaglutide Treatment on Serum TSH and Thyroid Hormones in Individuals with Obesity

Abstract Disclosure: P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. A.J. Kretowski: None. L. Szczerbinski: None. Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a crucial role in managing obesity and diabetes, significantly influencing glycemic control and weight management. Previous studies showed that GLP-1 RAs therapy affects thyroid-stimulating hormone (TSH) levels; however, they were limited by small sample sizes and did not extensively cover newer agents like semaglutide. Thus, the aim of this study was to assess the impact of a three-month semaglutide treatment on thyroid hormones and TSH levels in individuals with obesity, without diabetes, and examine the relationship of these changes with weight loss. Methods: We analyzed data from 290 patients participating in the GAROS study, excluding those on medications affecting thyroid function or with a known history of thyroid disease. All participants underwent a three-month treatment with oral semaglutide, followed by a three-month discontinuation phase. Measurements of TSH, free triiodothyronine (fT3), free thyroxine (fT4), and body weight were taken at baseline, at the end of the treatment period, and three months post-treatment discontinuation. To compare changes in TSH, fT3, and fT4 levels, as well as weight, across the study timelines we used non-parametric tests due to the non-normal distribution of the data. We also employed multiple linear regression models to evaluate the association between thyroid hormone changes and weight loss, both in the aggregate and stratified by sex. Results: Initial fT3, fT4, and TSH levels were 3.13 pg/ml (SD=0.38), 0.94 ng/dl (SD=0.10), and 1.64 mIU/l (SD=0.82), respectively. Post-treatment, fT3 decreased on average by 0.33 pg/ml (p&amp;lt;0.001), TSH by 0.32 mIU/l (p&amp;lt;0.001), and fT4 increased by 0.06 ng/dl (p&amp;lt;0.001). Upon discontinuation, fT3 and fT4 levels did not fully return to baseline values but showed a significant shift in that direction (p&amp;lt;0.001 for fT3 and p=0.006 for fT4, compared to baseline). Conversely, TSH levels adjusted back to their baseline values (p=0.26). Notably, changes in fT4 levels, unlike fT3 and TSH, were significantly negatively associated with weight changes during (p=0.030) and post-treatment (p=0.008), across sex-stratified analyses. Conclusions: Semaglutide treatment significantly alters thyroid hormones and TSH levels in patients with obesity, with some effects reversible post-discontinuation. Except for fT4, these hormonal changes appear to be independent of the weight loss effects of semaglutide. Although the magnitude of these alterations might not be clinically significant, they do imply that GLP-1 RAs may have additional physiological effects. The exact nature of the interaction between semaglutide and thyroid function, however, remains to be fully elucidated, highlighting the need for further research to clarify these mechanisms. Presentation: 6/2/2024

8124 Prevalence and Characteristics of Patients with Hypothyroidism in the Danish Blood Donor Study

Abstract Disclosure: N.L. Frisk: None. J.R. Shorter: None. O.B. Pedersen: None. L.T. Dalgaard: None. Introduction: While impaired thyroid function leading to subclinical hypothyroidism and overt hypothyroidism is common in Denmark, the knowledge about the paths by which patients’ progress to impaired thyroid function is limited. Undiagnosed hypothyroidism as well as subclinical hypothyroidism constitute serious risk factors for development of cardio metabolic disease. The Danish Blood Donor Study (DBDS) is a large longitudinal cohort and biobank containing information and samples dating more than 10 years back. Blood donors donate blood every 3-6 months and each time provide a sample for research. Research question: The aim of the study was to obtain up-to-date information about prevalence and characteristics of patients with hypothyroidism in a Danish longitudinal cohort of blood donors. Methodology: The study employed a cross-sectional design. Hypothyroidism was defined based on at least two prescriptions of levothyroxine (LT4) and used for calculations of prevalence. Case numbers were compared to all controls that were currently not being prescribed LT4 nor anti-thyroid drugs (carbimazole, propylthiouracil, thiamazole). We compared cases of hypothyroidism to two different control (ctrl) groups: 1) All the participants of the DBDS having TSH levels in the normal range, and 2) Normothyroid participants matched to hypothyroid cases based on age and sex. Incidence was determined based on DBDS participants developing hypothyroidism after being enrolled into the DBDS during a 10-year follow-up. Men and women were compared separately among cases and controls. Students’ t-test was used to compare cases and controls, and corrected using Bonferroni. Major results: There were 3397 cases of hypothyroidism and 153791 ctrl subjects in the DBDS, giving a prevalence of 2.2%. 85% of cases were female, while among ctrl 50% were female. Average age of cases was 52±13 years (mean±SD) for women and 58±13 for men, while ctrls were 45±13 and 48±14 years, respectively (both P&amp;lt;0.001). BMI among cases were: 25.8±4.7 for women and 26.8±3.9 kg/m2, while cases were 25.1±4.4 and 26.0±3.6, respectively (both P&amp;lt;0.001). TSH levels were, for female cases: 4.6±4.0 iu/mL and 5.7±4.9 for men, while ctrls were 1.8±1.1 and 1.7±1.1, respectively (both P&amp;lt;0.001). Free (F) T4 levels were, for female cases: 14.4±6.4pmol/L and male: 14.0±4.6, while ctrls were: 14.8±4.5 and 15.0±3.9 respectively (P&amp;lt;0.003 for females, P&amp;lt;0.0001 for males), while FT3 levels were for cases: 4.3±1.7 and 4.3±1.4 pmol/L and 4.5±2.0 and 4.7±1.5 for ctrls (both P&amp;lt;0.0001). Conclusion: Hypothyroidism is less prevalent among blood donors than reported in the general Danish population, which is accordance with ‘the healthy donor’ bias. Hypothyroid donors were on average older and with higher BMI than normothyroid controls. Donors with hypothyroidism were generally well regulated, but despite that FT4 and FT3 levels were lower than ctrls. Presentation: 6/1/2024

The Adverse Effects of Anxiety and Depression on Pregnant Women with Hypothyroidism in Late Pregnancy.

Maternal depression and anxiety during pregnancy are significant public health concerns commonly reported worldwide among pregnant women. This study aimed to investigate the impact of anxiety and depression on thyroid function, pregnancy outcomes, and sleep quality among pregnant women with hypothyroidism in the later stages of pregnancy. Eighty cases of pregnant women with hypothyroidism in late pregnancy who were treated at Zhangjiakou First Hospital from January 2021 to October 2023 were selected for this retrospective study. The pregnant women in late pregnancy were divided into four groups according to the scores on the Hospital Anxiety and Depression Scale (HADS): control group with 20 cases, anxiety group with 18 cases, depression group with 22 cases, and anxiety-depression group with 20 cases. A comparison was made among the four groups regarding general information of pregnant women in late pregnancy, HADS scale scores, levels of free thyroxine (FT4, FT3), thyroid-stimulating hormone (TSH), occurrence of adverse pregnancy outcomes, and sleep quality at different time periods. There was no statistically significant difference in comparing general information among the four groups of pregnant women in late pregnancy (p > 0.05). There were statistically significant differences in HADS depression and HADS anxiety scores (p < 0.05), levels of FT4, FT3, TSH in pregnant women in late pregnancy postpartum (p < 0.05), occurrence of adverse pregnancy outcomes (p < 0.05), and comparison of sleep quality of pregnant women in late pregnancy at 1, 3, and 5 months of follow-up among the groups (F = 5.735, 23.930, 11.573, p < 0.05). Anxiety and depression significantly impact thyroid function, pregnancy outcomes, and sleep quality in pregnant women with hypothyroidism in late pregnancy, which is detrimental to the health of pregnant women in late pregnancy. Therefore, necessary interventions are needed.

6415 Resistance to Thyroid Hormone -A Challenge to Manage

Abstract Disclosure: A. Altaf: None. F. Iqbal: None. E. Hamoudeh: None. C. Coyne: None. K. Anne: None. L. Buckley: None. Background: Resistance to thyroid hormone (RTH) or Refetoff syndrome was first introduced in 1967. It is an autosomal dominant or recessive genetic disease with a mutation in the thyroid hormone receptorβ (THR-β) gene or the thyroid hormone receptorα (THR-α) gene. The distinguishing biochemical feature of RTHβ is an elevated level of circulating free thyroid hormones with normal or high TSH concentration and decreased peripheral tissue response to thyroid hormone. Common signs and symptoms in patients with RTHβ are short stature, attention deficit disorder, and resting tachycardia and many patients might be asymptomatic. Case: We report a case of a 36-year-old patient with past medical history of congenital bilateral hearing loss, atrial fibrillation, CHF, and slow learning/comprehending who presented to the ER with shortness of breath and atrial fibrillation with tachycardia. Admission labs revealed elevated TSH 3.9, elevated fT4 3.28, and elevated TT3 205. He reported that for the past year, he has been on levothyroxine 50mcg for abnormal TSH. Levothyroxine was stopped and the patient was discharged on methimazole 10mg daily. Further workup revealed negative thyroglobulin and thyroid peroxidase antibodies. Thyroid ultrasound with Doppler demonstrated a mildly hypervascular thyroid gland without evidence of nodules. Brain MRI was negative for any pituitary abnormalities. HAMA testing continued to show elevated TSH. Patient was followed by cardiology and due to continued atrial fibrillation, had multiple cardioversions and was managed on a beta blocker. Due to his atrial fibrillation, endocrinology service continued his methimazole till his genetic testing came positive for an autosomal dominant heterozygous pathogenic mutation in THRB c.1373 T&amp;gt;C (p. Val458Ala). His thyroid hormones and TSH continue to be elevated. Currently, he is not on thyroid medication and getting monitored. The need for multiple cardioversions for atrial fibrillation in this patient makes resistance to thyroid hormone management challenging. Discussion: Hyperthyroidism is commonly mistaken for RTH. However, the lack of TSH suppression should be further investigated. Most patients with RTHβ are adequately compensated by the increased endogenous supply of thyroid hormone showing increased serum fT3 and fT4 levels and normal or near normal TSH levels. Beta Blockers like atenolol cannot inhibit the conversion of T4 to T3 and can be used for RTHβ with tachycardia. Triiodothyroaceticacid (TRIAC) or dextrothyroxine (DT4) have also been used to treat thyrotoxicosis. In summary, treatment for RTHβ remains a challenge for clinicians, especially in patients with atrial fibrillation and many patients are misdiagnosed and managed as hyperthyroidism. Presentation: 6/3/2024

6768 A Rare Presentation of Primary Adrenal Insufficiency with Hypertension &amp; Hypokalemia

Abstract Disclosure: A.M. San Hernandez: None. R. Alshantti: None. G. Espinoza Mercado: None. J.L. San Hernandez: None. Introduction: Adrenal Insufficiency is caused by the failure of the adrenal cortex to produce glucocorticoids +/- mineralocorticoids. This can be due to a defect in the adrenal cortex, or in the hypothalamic pituitary axis. The clinical manifestations are usually non-specific, ranging from mild vague symptoms to life threatening crisis. Therefore, diagnosis requires a high level of suspicion by providers. Unusual presentations of primary adrenal insufficiency (PAI) with hypertension and hypokalemia have been rarely described in the literature. We present a rare case of PAI with hypertension and hypokalemia. Case Presentation: A 68 years old female with a medical history of rheumatoid arthritis, hypothyroidism on Levothyroxine, chronic transaminitis, and bicytopenia presented to the hospital with a 6 weeks history of generalized weakness, loss of appetite, weight loss, and dizziness. Patient denied any diuretic or steroid use within the last 2 years. On arrival, she was afebrile, hypertensive (168/84mmHg), with normal oxygenation and pulse. Physical examination was unremarkable with normal volume status. Initial laboratory results showed low sodium 116 mEq/L, low serum osmolality 247 MEQ/kg, normal potassium 3.6 mEq/L, Creatinine 0.3 mg/dL &amp; BUN 9 mg/dL. She was initially started on IVF normal saline. Further workup revealed normal TSH &amp; FT4 levels. Urine study showed urine osmolality (477 MOSM/KG), &amp; urine sodium (127 mEq/L). Given these findings, SIADH was suspected and fluid restriction was started. Sodium level continued to be low with minimal improvement to 120 mEq/L, potassium levels also dropped (3.3-3.2 mEq/L), requiring daily replacement. BP remained elevated ranging from 150s to 160s systolic and 80s to 90s diastolic. Hypertension was controlled with her home medication Amlodipine. Although atypical presentation with hypertension &amp; hypokalemia, the diagnosis of adrenal insufficiency was considered. Laboratory evaluation showed low morning cortisol 5.2 ug/dL, with album level 3.5 g/dL. Cosyntropin stimulation test showed 1.3 ug/dL (at baseline), 9.9 (30 min post administration), and 14.4 (1 hour post administration); results confirming PAI. ACTH, Renin, Aldosterone, &amp; DHEAS levels were normal. CT adrenal was normal. Patient was started on hydrocortisone; some of her symptoms &amp; Na level improved. Further investigation of the etiology of PAI and possible hyperaldosteronism is pending outpatient follow up. Conclusion: Adrenal insufficiency is a life threatening condition with serious consequences if diagnosis is missed. It manifests by a wide spectrum of symptoms and signs, some can be masked by the presence of other comorbid conditions leading to atypical presentations. Our case highlights the importance of maintaining a high level of suspicion of adrenal insufficiency in patients with atypical presentation, including those with hypertension &amp; hypokalemia. Presentation: 6/3/2024

7637 Characteristics of Thyroid Nodules Among Adolescents and Adults in Medina, Saudi Arabia

Abstract Disclosure: R. Alradadi: None. M. Sindi: None. O. Alrehaili: None. S. Alanazi: None. S. Alahmadi: None. F. Mansuri: None. A. Zain: None. Background: Thyroid Nodules are common clinical finding, with a prevalence of about 20% in young adults and around 70% in the elderly population. A significant increase in the incidence rate of Thyroid Cancer in our population has been noted, over the past 30 years. The aim of the study is to define the characteristics of Thyroid Nodules in adolescents and adults in our region compared to what published worldwide. Method: A retrospective chart review, conducted at our Health Institution. The study included adolescents and adult who had Thyroid Nodules and was seen in the outpatient endocrine clinic in the period between 2018 and 2022, using non-probability consecutive sampling. Patient medical records provided demographic, medical, and laboratory data, and the analysis employed SPSS for statistical assessment​​. Data collection conducted from October through December of 2023 Result: Out of the total sample of 552 patients, there were 84.8% females. More than half of the patients (55.9%) were between 36-55 years of age. 57.4% of patients were overweight or obese. 56.4% presented with goiter. FT3, FT4 and TSH levels were normal among 88.4%, 78% and 83.3% respectively. Anti TPO antibodies were reported in 14.2% as compared to thyroglobulin antibodies in 2.2%.Follicular neoplasm/suspected neoplasm was detected among 8.15% of the sample. Papillary thyroid carcinoma [27/41] was the most frequent finding with positive FNA. Multiple nodules were more prevalent 38.8% as compared to solitary nodules in 34.1%. The right sided nodules were mostly solid 49.2% while hypervascularity was noted in 9.1% and51.4% were of more than 1.5cm. In contrast, left lobe nodule 37% were found to be solid and 6.2% showed hypervascularity and size was more than 1.5cm in 45% of the left nodules Conclusion: The vast majority of adults and adolescents with thyroid nodule were female as expected based on what reported from previous studies. Preexisting Thyroid Diseases present in only small number of patients 15.4 %. Anti-TPO antibody was more predominant than Thyroglobulin Antibody. Follicular neoplasm/suspected neoplasm was detected among 8.15% of the sample. Papillary thyroid carcinoma was the most frequent finding among the positive FNA results. Presentation: 6/3/2024

5125 Severe Gestational Thyrotoxicosis Leading to Unwarranted Treatment

Abstract Disclosure: C. Bell: None. L.A. Barbour: None. Introduction: Gestational transient thyrotoxicosis (GTT) is the most common cause of thyrotoxicosis in pregnancy yet is often confused with Graves’. Although usually mild, we present a severe case leading to the unsupported use of anti-thyroid drugs (ATDs), which could have resulted in fetal hypothyroidism if continued. Case: A 30-year-old female G1P0 at 10 wks with a single gestation presented with 4 wks of vomiting, palpitations, and weight loss. She had no history of thyroid disease. She was diaphoretic and ill-appearing and had a non-tender, smooth normal-sized thyroid, a stare without exophthalmos, and a fine tremor. TSH was &amp;lt; 0.01, FT4 5.57 ng/dL (0.89-1.76), and TT3 201 ng/dL (60-181). TPO Ab 51 (&amp;lt; 60). TRAb, TSI Ab, and TgAb were negative. β-hCG level was 334,106 mIU/mL. She was diagnosed with GTT and briefly hospitalized for dehydration but was re-hospitalized 2 wks later with worsening symptoms and 25 lb weight loss. Unexpectedly, her FT4 and TT3 rose to 6.24 ng/dL and 339, respectively. A thyroid ultrasound showed mildly increased vascularity. PTU was started for seronegative Graves’ at 50 mg tid with metoprolol. After 3 days, her FT4 improved to 3.59 ng/dL and TT3 was 176. Further consultation recommended stopping PTU. She was sent home with metoprolol. Her symptoms and FT4 levels improved. FT4 was normal and hCG levels dropped to 54,821 by 18 wks. Discussion: GTT is caused by a transient elevation in T4 due to direct hCG stimulation of the TSH receptor. It is more common with multiple or molar gestations and hyperemesis gravidarum, also mediated by hCG. It typically results in mild thyrotoxicosis, highlighting the uniqueness of this case. Only a couple of case reports exist where GTT presented as severe thyrotoxicosis or thyroid storm and persisted this long. It is critical to distinguish GTT from Graves’ given their different outcomes and treatment. GTT is commonly misdiagnosed as Graves’ as both result in thyrotoxic labs and symptoms and can present in 1st trimester. GTT typically presents at 8-10 wks and lasts until 14-16 wks when hCG levels fall, but Graves’ may also improve by 2nd trimester due to the immune suppression of pregnancy. It is also possible for both to co-exist. hCG levels &amp;gt;100,000 are associated with GTT but due to the variable sialylation of hCG, which changes its affinity to the TSH receptor and half-life, they are unreliable diagnostically. Key clues supporting GTT include no goiter, exophthalmos, or symptoms pre-pregnancy, negative TRAb and TSI, and, notably, a lower T3/T4 ratio compared to Graves’, as seen in this case. To conclude, GTT is often mistaken for Graves’ but inappropriate use of ATDs can result in fetal hypothyroidism and does not improve outcomes. Although the severity of our case is unusual, accurate distinction from Graves’ by endocrinologists is crucial to ensure optimal maternal-fetal outcomes. Presentation: 6/1/2024

7385 Prevalence of Central Hypothyroidism in Cushing Syndrome and Thyroid Function Tests After Cushing Treatment

Abstract Disclosure: T. Kunavisarut: None. A. Sriwijitkamol: None. Cushing syndrome can be associated with thyroid dysfunction. We investigated the association between Cushing syndrome and thyroid dysfunction. We conducted a retrospective study at Siriraj Hospital in Thailand and analyzed thyroid function tests in 80 Cushing's patients. The inclusion criteria were patients diagnosed with Cushing syndrome with thyroid function tests recorded at diagnosis of Cushing syndrome. Patients who had an abnormal thyroid function test at diagnosis of Cushing syndrome must have a thyroid function test after treatment of Cushing syndrome. Of the 80 patients, sixty-five patients (81.2%) had normal thyroid function at diagnosis, 12 patients (15%) had central hypothyroidism and three patients (3.8%) had subclinical hyperthyroidism.Interestingly, among 12 patients who had central hypothyroidism, eight patients (66.7%) were diagnosed with Cushing disease. Three patients (25%) were diagnosed with adrenal Cushing syndrome and one patient (8.3%) was diagnosed with ectopic Cushing syndrome. This finding suggested that central hypothyroidism may not be exclusively due to the mass effect of the pituitary tumor on the normal pituitary because adrenal Cushing syndrome and ectopic Cushing syndrome can also cause central hypothyroidism. Among 12 patients with central hypothyroidism at diagnosis of Cushing syndrome, nine patients (75%) normalized their thyroid function after remission of Cushing syndrome without Levothyroxine replacement. Moreover, patients with central hypothyroidism had significantly higher median 24-hour urine-free cortisol levels than euthyroid patients (1030.5 ug/day vs. 404.5 ug/day, p=0.017), indicating a potential correlation between cortisol excess and low FT4 levels. These findings suggest that hypercortisolism in Cushing syndrome can suppress the hypothalamic-pituitary-thyroid axis, but this suppression is often reversible with successful Cushing's treatment. This study highlights the importance of central hypothyroidism, which can occur in all types of Cushing syndrome. If the patients did not have hypothyroid symptoms, Levothyroxine replacement may not be necessary. For patients who already received Levothyroxine and had normal thyroid function tests, Levothyroxine can be carefully tapered and potentially discontinued because successful Cushing syndrome treatment can ultimately normalize thyroid function tests. Presentation: 6/1/2024

7235 Papillary Thyroid Carcinoma in a Hyperfunctioning Thyroid Nodule

Abstract Disclosure: J. Yang: None. P.V. Nadkarni: None. Background: The prevalence of malignancy in a hyperfunctioning or hot thyroid nodule is considered to be low. According to the 2015 American Thyroid Association Guidelines, no cytologic evaluation is routinely recommended for hyperfunctioning nodules since they are rarely associated with malignancy (1). We present a case of a 71-year-old female with a hot nodule containing papillary thyroid cancer. Clinical Case: A 71-year-old female with Type 1 diabetes mellitus and coronary artery disease on dual antiplatelet therapy was found to have a 1.5 cm firm, non-tender right-sided thyroid nodule on a routine physical exam. Laboratory tests demonstrated low TSH &amp;lt;0.01 (normal 0.36 - 3.74 m[IU]/L) and FT4 level elevated at 1.62 (normal 0.76 -1.46 ng/dL). She noticed palpitations and started on low dose Methimazole. Thyroid ultrasound results showed a 2.1 x 2.0 x 2.0 cm right inferior lobe thyroid nodule. This thyroid nodule appeared mixed cystic and solid, hypoechoic, not taller than wide, with ill-defined margins and peripheral calcifications (ACR TI-RADS risk category: TR4). Nuclear medicine thyroid uptake scan demonstrated focally increased activity in the right lower pole corresponding with her right inferior thyroid nodule seen on ultrasound. Remainder of the gland appeared suppressed. She was recommended for ultrasound-guided fine needle aspiration biopsy of her right inferior thyroid nodule, given concerning characteristics on ultrasound findings despite results consistent with a hot nodule. Timing of her antiplatelet therapy was coordinated with her cardiologist, and her biopsy procedure scheduled after she stopped dual antiplatelet therapy. Her FNA results showed clusters of follicular cells with nuclear and architectural atypia, suspicious for papillary thyroid carcinoma. She underwent right thyroid lobectomy. Surgical pathology revealed 2 foci of papillary thyroid carcinoma, follicular variant (2.0 cm, 0.1 cm) and confined to the thyroid. All regional lymph nodes were negative for tumor. Methimazole was discontinued post-operatively, and she started Levothyroxine suppression therapy. Discussion: We present a rare association of papillary thyroid carcinoma presenting as a hot thyroid nodule. Though uncommon, detection of a hyperfunctioning thyroid nodule does not exclude the possibility of thyroid carcinoma and warrants careful evaluation. Clinicians should retain a high index of suspicion particularly when ultrasonography demonstrates findings suspicious for malignancy and consider additional evaluation with fine needle aspiration. Reference: (1) Haugen BR, Alexander EK, Bible KC et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. Presentation: 6/2/2024

7786 Successful Use of Lithium in Hyperthyroidism Following a Carbimazole-Induced Agranulocytosis: A Case Report

Abstract Disclosure: J.G. Sazon: None. D.V. Bawal: None. J.V. Chua: None. J. Reyes: None. Graves' disease (GD) constitutes a significant proportion of global thyrotoxicosis cases. Carbimazole is an ATD with a notably and a rare yet severe complication of ATD with substantial adverse implications for health, is agranulocytosis. This condition is reversible if recognized early and treated accordingly. We report a case of successful use of lithium prior to radioiodine ablation (RAI) in management of thyrotoxicosis in the context of Carbimazole-induced agranulocytosis. This is a case of a 38-year-old female newly-diagnosed with Graves' Disease presenting with palpitations. Diagnostics showed FT4 &amp;gt;100 (11.9 – 21.6 pmol/L), TSH at &amp;lt;0.005 (0.270 – 4.200 mIU/L) and positive TSH receptor antibodies (TRAb) at 13.9 IU/L (normal value: &amp;lt;1.76 IU/L). Electrocardiogram revealed Atrial Fibrillation. She was initiated on Carbimazole 30 mg/tab OD, Apixaban 10 mg/tab OD, and Bisoprolol 10mg/tab OD. After 28 days of drug-intake, she developed fever (TMax 38.5°C) and work-up revealed severe neutropenia with an ANC of 0. Peripheral blood smear showed agranulocytosis. A seven-day course of piperacillin-tazobactam and moxifloxacin was administered, along with G-CSF at a dose of 300ug BID. Subsequently, was scheduled for Radioactive Iodine (RAI) therapy for definitive treatment. In the interim, with persistent tachycardia and elevated thyroid function tests (FT3 22.20 pmol/L, FT4 47.24 pmol/L) Lithium 450mg/tab BID and Prednisone 40mg/day was initiated, providing significant relief from hyperthyroid symptoms. RAI was administered with a dose of 24mci. Ten days post-RAI, thyroid hormone levels further improved. Four weeks after RAI, repeat tests revealed hypothyroidism. Levothyroxine was initiated at 12.5 mcg and gradually adjusted. Pre-RAI administration of lithium serves to mitigate alterations in serum thyroid hormone concentrations and augments the efficacy of RAI therapy. In this study, the utilization of lithium aimed to regulate thyrotoxicosis and preemptively curtail the elevation of FT4 levels. Lithium emerges as a particularly suitable therapeutic option for patients experiencing adverse effects related to ATDs prior to undergoing definitive therapies such as RAI or thyroidectomy. Furthermore, imperative to the prevention of agranulocytosis, an enhanced understanding of its deleterious effects through patient education is deemed vital. Presentation: 6/2/2024

8640 Thyroid Orbitopathy in Pregnancy

Abstract Disclosure: Z. Maisonet -Feliciano: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. L. El Musa Penna: None. J. Segarra-Villafane: None. I.C. Arroyo: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. Thyroid orbitopathy, often associated with Graves' disease, is characterized by the inflammation and swelling of ocular tissues. Its occurrence or exacerbation during pregnancy is infrequent, primarily due to the immunosuppressive state inherent in pregnancy. In most instances, the immunosuppression associated with pregnancy leads to a reduction in TRAb levels, although they continue to be present in women who have an active form of the disease. The course and severity of ocular manifestation do not always correlate with thyroid hormone levels. Strict control of thyroid function is crucial in patients with thyroid eye disease. This report sheds light on the rare occurrence of thyroid orbitopathy during pregnancy, a condition that complicates treatment due to potential risks to both the mother and the child. In this case, a 35-year-old pregnant woman with no prior history of thyroid issues exhibited symptoms of hyperthyroidism in her first trimester, including unintended weight loss, anxiety, and tremors in the upper limbs. She also presented with ocular discomfort, diplopia, and eyelid lag. Thyroid tests confirmed Graves Disease, with a significant elevation in Thyroid Stimulating Immunoglobulin (TSI): 243 %, Free thyroxine (T4): 1.08 ng/dl and Triiodothyronine (T3): &amp;gt;1.89 units and decreased Thyroid Stimulation Hormone (TSH): 0.001 uIU/ml. Ophthalmic examination revealed mild Graves orbitopathy due to bilateral exophthalmos (measured by Hertel’s exophthalmometer) 21mm on both sides, Marginal reflex distance (MDR) 1: right eye 9 mm and left 7mm. MDR 2: right eye 6mm and left eye 7mm. Right upper eyelid retraction, lagophthalmos of the right eye, limitation in the upward movement of the left eye, and vertical diplopia on extreme gazes without signs of orbital compression. Considering her normal FT4 levels and the mild nature of her hyperthyroidism, the decision was made to prioritize the mother's treatment while minimizing fetal risk, thus opting not to initiate antithyroid medication but to closely monitor her thyroid function. Symptomatic management of her orbitopathy was provided including lubricating eye drops and an eye patch. Throughout the progression of her pregnancy, her TSI levels exhibited a decreasing trend while FT4 remained within normal limits. Following delivery, there was a notable improvement in her ocular symptoms, and her TSH started increasing up to normal values of 1.29 uIU/ml and FT4 remained in range. This report underscores the importance of recognizing uncommon presentations of autoimmune thyroid conditions, such as thyroid orbitopathy, during pregnancy. It emphasizes the complexities and necessary considerations in treating these cases. A collaborative approach involving endocrinology, ophthalmology, and obstetrics is essential to safeguard the health of both the mother and the fetus. Presentation: 6/1/2024

8232 Therapeutic Plasma Exchange as a Bridge to Total Thyroidectomy in a Patient with Refractory Thyroid Storm

Abstract Disclosure: A. Sridhar: None. T. Chaudhary: None. S. Patil: None. A. Prabha Kumar: None. K. Djekidel: None. B.C. Jameson: None. Background: Thyroid storm is a rare life-threatening complication of hyperthyroidism with a mortality rate of 10-30%. Therapeutic plasma exchange (TPE) could be a bridge to definitive total thyroidectomy in patients with refractory disease who fail conventional therapy. Clinical case: Patient is a 31-year-old male with a past medical history of untreated hypertension, anxiety, alcohol use, substance abuse and a family history of Graves’ disease. He presented with complaints of breathing difficulty, back and shoulder pain for the past 1 day. In the ED he was found to be in respiratory distress with a rate of 40/min. He was started on a non-rebreather mask and was eventually intubated due to worsening distress. He was tachycardic with a heart rate of 130/min and had elevated blood pressure at 170/105 mm Hg. Physical examination was significant for diaphoresis, accessory respiratory muscle use, and diffuse swelling on the front of the neck. His blood work was significant for hemoglobin 11.1g/dL, TSH &amp;lt;0.01 uIU/mL, FT3 &amp;gt;32.6 pg/ml, FT4&amp;gt;7.8 ng/dL and urine drug screen was negative. Chest X-ray showed mild perihilar vascular congestion due to pulmonary edema. CT neck showed nonspecific diffuse enlargement of the thyroid gland without dominant thyroid nodule. The patient was admitted to the ICU for management of thyroid storm likely from Graves’ disease. Burch-Wartofsky Point Scale score on admission was 60. Endocrinology was consulted and the patient was started on IV hydrocortisone 100 mg and IV Methimazole 20 mg every 8 hours, propranolol 60 mg every 6 hours, and iodine drops 300 mg every 6 hours after the first dose of methimazole. Since repeat FT4 after 48 hours showed no improvement, he was switched to Propylthiouracil (PTU) with a loading dose of 500mg every 4 hours for 2 doses followed by 250 mg every 6 hours and cholestyramine 4 g orally 4 times daily to reduce enterohepatic circulation of thyroid hormone. After 3 days of PTU, the patient’s FT3 was improving but FT4 continued to be elevated. ENT was consulted for total thyroidectomy, but the patient required preparation to improve FT4 levels prior to surgery. He was transferred to a tertiary care center on Day 6 of admission to undergo TPE. After 3 sessions of TPE serum FT3 and FT4 decreased, patient’s mentation improved, and he was extubated on Day 10 of admission. He received a total of 5 sessions of TPE and underwent total thyroidectomy on Day 15 of admission without complications. Postoperatively he was started on oral Levothyroxine 125 mcg once daily and calcitriol 0.25 mcg twice daily. Patient continues to follow up with Endocrinology clinic for thyroid function monitoring and medication adjustment. Conclusion: Given the high mortality rate associated with thyroid storm, early recognition of refractory disease is imperative. Bridging with TPE while awaiting total thyroidectomy improved clinical outcomes in our patient and should be considered in such cases. Presentation: 6/3/2024

5114 Establishment of Thyroid Storm Mouse Model and Therapeutic Effects of Ghrelin

Abstract Disclosure: C. Kurimoto: None. Y. Furukawa: None. T. Akamizu: None. A. Doi: None. K. Takeshima: None. S. Morita: None. H. Iwakura: None. H. Ariyasu: None. H. Furuta: None. M. Nishi: None. T. Matsuoka: None. Context: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, is caused by a combination of thyrotoxicosis and severe physical stresses. Infection is the most common triggering factor. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. Further, TS has limited therapeutic options. Objectives: We aimed to confirm the hypercytokinemia in patients with TS, establish a TS model mouse by triiodothyronine and lipopolysaccharide administration, and explore the therapeutic effects of ghrelin on TS. Methods: We evaluated serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. As a TS model, C57BL/6 mice were titrated with triiodothyronine and lipopolysaccharide to develop a lethal model with approximately 30% survival at 24 hours. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin on these parameters. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease without TS (55.7 ± 69.0 vs. 3.13 ± 1.41 pg/mL, P &amp;lt; .05, n=4 each). Next, we titrated the doses of T3 and LPS, aiming to achieve a survival rate of approximately 30% at 24 hours after administration. Two out of five mice in the T3 3.0 mg/kg group died, while none of the eight mice in the T3 1.0 mg/kg group died. Therefore, we determined that the appropriate T3 dose for the TS mouse model is 1.0 mg/kg, which is not lethal when administered alone. In the T3 1.0 mg/kg group (n=8), serum FT3 levels were approximately three times higher (15.3 ± 4.5 vs. 4.5 ± 0.7pg/ml) than those in the control group (n=8). Next, different doses of LPS was added to the T3 group. Survival at 24 hours post-dose was 60% in the T3 + LPS 0.2 mg/kg group (n=5) and 33% in the T3 + LPS 0.5 mg/kg group (n=5), while survival was 100% in the LPS 0.5 mg/kg alone group (n=5),. Based on these findings, the dosage for the murine TS model was determined to be “triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg”. This TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin at 300 µg/kg improved the survival rate to 66.7% (P &amp;lt; .01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We confirmed the hypercytokinemia in patients with TS. Next, we established a lethal model simulating TS by inducing “thyrotoxicosis” by exogenous administration of thyroid hormones, and by inducing “sepsis” by intraperitoneal administration of LPS. The model mice exhibited similar pathophysiological status to human TS associated with induction of serum IL-6 and other biomarkers, which were improved by ghrelin. Presentation: 6/1/2024