Subclinical Hyperthyroidism Research Articles

Subclinical hypothyroidism as an independent predictor of cardiovascular prognosis in left ventricular thrombus patients.

Left ventricular thrombus (LVT) is associated with an increased risk of adverse cardiovascular events, and thyroid hormones are known to affect the cardiovascular system in various ways. However, subclinical thyroid dysfunction still deserves to be emphasized, and its impact on the prognosis of patients with LVT is rare but needs to be investigated. We used retrospective data from patients diagnosed with LVT at Fuwai Hospital over the past 10 years to assess the relationship between thyroid functional status and prognosis of LVT using multivariate Cox proportional hazards models, and validated the improved predictive effect of including thyroid function in the prognostic assessment of LVT using receiver operating characteristic (ROC) curves. Subclinical hypothyroidism was significantly associated with a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) (HR 1.774, 95% CI: 1.053-2.989; p = 0.031) and cardiovascular death (HR 1.986, 95%CI: 1.110-3.553; p = 0.021) in LVT patients, whereas no significant correlation was observed in the subclinical hyperthyroidism group. In addition, including thyroid function in the prognostic consideration of LVT patients would contribute to the predictive effect of MACCEs (AUC for 1 year: 0.715; AUC for 2 years: 0.745; AUC for 3 years: 0.684). Subclinical hypothyroidism can be used as an independent predictor of MACCEs in patients with LVT, and there is a clinical value in using subclinical hypothyroidism as an important factor suggesting a poor prognosis in patients with LVT.

Neurological and psycho-emotional manifestations of hyperthyroidism during pregnancy

Background. Hyperthyroidism is a state of thyroid hormone excess, which increases the metabolic rate and causes symptoms including anxiety and tremor. Graves’ disease is the most common etiology in developed countries. Excessive levels of thyroid hormones can impact mood, energy levels, and overall well-being. It is crucial to differentiate between symptoms related to thyroid function and clinical depression. The purpose of the study was to investigate the neurological and psycho-emotional manifestations of hyperthyroidism during pregnancy. Materials and methods. An examination of 50 pregnant women with subclinical and overt hyperthyroidism and 20 healthy women (control group) in the second trimester of pregnancy using the method of standardized multivariate personality study was carried out. Results. Based on the results of the study, it can be argued that pregnant women with thyrotoxicosis have changes in the psycho-emotional sphere: psychological maladaptation to the disease, an increase in the level of anxiety with hypochondriac tendencies, neuroticism, a decrease in intellectual performance and activity, a pronounced feeling of depression, anxiety, low mood. The identified criteria allow us to attribute these changes to the personality pattern or to the manifestations of a pathological neurotic state in conditions of mal­adaptation. The specific condition and behavior of pregnant women with thyrotoxicosis requires timely diagnosis and appropriate correction, which will contribute to the normalization and improvement of the psychological state, prevent the development of chronic stress and the occurrence of perinatal complications. Conclusions. Pregnant women with thyrotoxicosis have changes in the psycho-emotional sphere: psychological maladaptation to the disease, an increase in the level of anxiety with hypochondriac tendencies, neuroticism, a decrease in intellectual performance and activity, a pronounced feeling of depression and anxiety.

ASSESSMENT OF THYROID FUNCTION DISORDERS AMONG THE SUBJECTS ATTENDING CENTRAL LABORATORY OF A TERTIARY CARE HOSPITAL: AN OBSERVATIONAL, CROSS-SECTIONAL STUDY

Objective: Thyroid disorders are the most common endocrine disorders worldwide and India is not an exception. Several factors may determine the prevalence of thyroid dysfunction including age, gender, geographical and ethnic background, and most importantly iodine intake. Therefore, data related to thyroid disorders from one population cannot be extrapolated to another. In this study, we aimed to assess the disorders of thyroid function among the subjects attending the central laboratory of a tertiary care hospital. Methods: This observational, cross-sectional study was conducted in the Department of Pharmacology and the Department of Biochemistry of the same institute over a period of 3 months. All subjects of either sex attending the central laboratory of the institute for estimating thyroid function on their outpatient visit during the study period were included. Subjects who were on any medications known to alter the thyroid hormone status or diagnosed with a thyroid disorder and/or on therapy were excluded. A pre-designed and pre-tested data collection form was used for taking interviews to collect relevant data including sociodemographic characteristics, comorbid conditions, thyroid illness, and investigational reports. Results: A total of 132 subjects were included in the study. The majority of them were female (72.27%) and residents of urban areas (52.27%). The most common comorbid conditions and presenting symptoms were hypertension (25.76%) and fatigue (46.97%), respectively. The majority of the subjects were found to be euthyroid (81.81%). About 18.19% of the study subjects were having thyroid disorders, most commonly subclinical hypothyroidism (SCH) (13.64%), followed by primary hypothyroidism (2.27%), secondary hyperthyroidism (1.52%), and subclinical hyperthyroidism (0.76%). Thyroid disorders were mainly found in females, such as primary hypothyroidism (66.67%), SCH (66.67%), and subclinical hyperthyroidism (100%). The majority of the thyroid disorders were found in the age group of 26–50 years (20.27%), where females were found to have more primary hypothyroidism (3.17%), and SCH (12.70%). Conclusion: The findings of our study call for a review of current practices regarding thyroid disorders to include active screening of thyroid function among the subjects at greater risks and an emphasis on regular monitoring of the thyroid status.

Thyroid Dysfunction in Postmenopausal Women Attending General Health CheckUp at a Tertiary Care Center in Kathmandu: A Cross-Sectional Study

Introduction: Thyroid disorders are increasingly prevalent, with a higher incidence in women, particularly postmenopausal women. Symptoms of menopause, such as irritability, hot flushes, fatigue, and weight gain, often overlap with those of thyroid dysfunction, complicating diagnosis. Identifying thyroid dysfunction in this population is crucial for improving their overall health and preventing complications like cardiovascular diseases, which are associated with untreated thyroid disorders. Methodology: A hospital-based, retrospective, cross-sectional study was conducted involving 170 postmenopausal women attending a general health check-up at a tertiary care center in Kathmandu. Ethical approval was obtained from the IRC, and data were collected on thyroid function, including the incidence of subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism. Data were analyzed using SPSS, with descriptive and inferential statistics used to assess the prevalence of thyroid dysfunction and its potential impact on cardiovascular risk and overall health. Results: The average age of participants was 60.59 years. Among the study population, clinical thyroid disorders were observed in 3.53% of participants, with clinical hyperthyroidism at 1.18% and clinical hypothyroidism at 2.35%. Subclinical thyroid disorders were more prevalent, with subclinical hypothyroidism affecting 11.76% and subclinical hyperthyroidism 4.12% of the participants. Conclusion: The study highlights the importance of screening for thyroid disorders in postmenopausal women, as 3.53% of participants had clinical thyroid conditions and 15.88% had subclinical disorders. Early detection and treatment of these conditions are crucial for improving patient outcomes and preventing related health complications.

Female Reproductive System and Thyroid Dysfunction: Findings from a 12-Year Follow-Up in the Tehran Thyroid Study.

Background: The impact of thyroid dysfunction (TD) on the female reproductive system has been extensively documented. While there is evidence suggesting that alteration in female reproductive status may affect thyroid function, conflicting results have prevented definitive conclusions. This study aimed to investigate the associations of parity, spontaneous abortion (mentioned as abortion throughout this study), and menopause status with the prevalence and incidence of TD. Methods: From the Tehran thyroid study population, 2711 participants were included in the cross-sectional analysis to explore associations between female reproductive status and TD. Overall, 2191 participants with euthyroid were included in the survival study and followed up in 3-year intervals. Multinomial logistic regression was adopted in cross-sectional analysis and multivariable Cox proportional hazard model was used to determine associations between the incidence of TD with parity, abortion, and menopause status, adjusting for age, smoking, body mass index, and thyroid peroxidase antibodies positivity. Results: At the baseline, multiple parities (≥4) were significantly associated with overt hypothyroidism (odds ratio [OR] = 1.12; confidence interval [CI] 1.0-1.26) and subclinical hyperthyroidism (OR = 1.11 [CI 1.03-1.21]). Furthermore, multiple abortions were associated with overt hyperthyroidism (OR = 2.09 [CI 1.02-4.26]). Over the course of the study, multiple parities were significantly associated with the incident subclinical and clinical hypothyroidism. Conversely, a history of abortion was associated with a reduced risk of incident overt hypothyroidism. We found no significant association between menopause status and the prevalence or incidence of either hypothyroidism or hyperthyroidism. Conclusions: Our results suggest that the female reproductive system may be associated with thyroid function. Parity and abortion are associated with the occurrence of TD. A deeper understanding of the underlying mechanisms of the cellular and molecular alterations in signaling cascades during pregnancy is necessary to fully elucidate these associations.

Outcomes of Radiofrequency Ablation for Autonomously Functioning Thyroid Adenomas-Mayo Clinic Experience.

Autonomously functioning thyroid nodules (AFTNs) constitute 5% to 7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves' disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of postprocedural hypothyroidism and other surgery and radiation-related complications. This work aimed at assessing the efficacy of radiofrequency ablation (RFA) as an alternative treatment option for resolving hyperthyroidism and the nodule volume rate reduction (VRR) and its associated adverse events. A total of 22 patients underwent RFA for a solitary AFTN. Seventy-two percent (n = 16) had subclinical hyperthyroidism, 9% (n = 2) had overt hyperthyroidism, and 18% (n = 4) were biochemically euthyroid on antithyroid medication. Average pretreatment TSH was 0.41 mIU/L (SD = 0.98) and free T4 1.29 ng/dL (SD = 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n = 20) and average VRR (61.13%) was achieved within 3 to 6 months following the ablation. Except for 1 nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and 2 developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. RAI and/or surgery represent the standard of care for toxic adenomas, but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise, it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.

Prevalence of thyroid dysfunction in namakkal district -A hospital based study

Thyroid disorders are most common endocrine disorder in India but the prevalence studies on these dysfunction is limited. All subjects who visited the hospital for a period of four months to have thyroid function tests (TFTs) on their first outpatient visit were included in the study. Thyroid disordrs were present in 22.11 % of the total 2510 subjects . The prevalence rate was higher in females (64.8%) than males (35.2%) with (p=0.0003).The prevalence of hypothyroidism in the study population was 64.32 % (n = 357). In our study those with primary hypothyroidism were predominant (55.18 %, 197 out of 357) and 43.1 % (154 out of 357) were having sub clinical hypothyroidism and 6 of 357 were having secondary hypothyroidism. The prevalence rate of hyperthyroidism was 52.6 % (n-188) . The majority were subclinical hyperthyroidism (65.90 % , 124 out of 188) ,30.8 % (58 out of 188) had primary hyperthyroidism and3% ( 6 out of 188) had secondary hyperthyroidism. In our study thyroid function abnormalities were noted in 15.73 % of all subjects. Thyroid disorders were common in age of >20 years than 20-40 ,40-60 and and >60 year categories. The prevalence of primary hypothyroidism was found to be higher than subclinical hypothyroidism, while in hyperthyroidism subclinical condition was predominant compared to primary hyperthyroidism.

Treatment of Subclinical Hyperthyroidism and Incident Atrial Fibrillation.

Treating overt hyperthyroidism prevents atrial fibrillation (AF). Though subclinical hyperthyroidism (SH) has been associated with AF, it is unknown whether treating SH prevents AF. We aimed to identify the association between treating SH and incident AF. In a pharmacoepidemiologic retrospective cohort study, patients diagnosed with SH between 2000 and 2021 were followed. Outpatients ≥ 18 years with biochemical SH and without prior AF, hypothyroidism, thyroid cancer, pituitary disease, or pregnancy were included. The primary outcome was incident AF. Secondary outcomes were ECG and echocardiographic features associated with AF. Of 2169 patients screened, 360 (131 treated and 229 untreated) were followed up for a mean of 4.27 years. In the treated and untreated groups, AF occurred in 4 (3.1%) and 15 (6.6%) patients (p = 0.15), and AF incidence was 0.8% and 1.4%/year (p = 0.31), respectively. The hazard ratio (HR) for treatment as a time-dependent variable was 0.60 (95% CI 0.19-1.92; p = 0.39). As some cases of AF were documented nearly simultaneously with SH treatment, a sensitivity analysis was performed reassigning two patients diagnosed with AF < 30 days after starting SH treatment to the untreated group. Here, in the treated and untreated groups, AF occurred in 1.6% and 7.4% (p = 0.02), and AF incidence was 0.4% and 1.8%/year (p = 0.02), respectively. The HR was 0.25 (0.06-1.13; p = 0.07). There were no differences in ECG or echocardiographic features. There was an overall trend towards lower incidence and prevalence of AF following treatment of SH, supporting the need for larger scale studies.

New onset of Graves' disease after controlled ovarian stimulation: A case report and brief literature review.

De novo onset of Graves' disease (GD) after controlled ovarian stimulation (OS) is exceptional. Only one case of progression to GD after OS in a patient with pre-existing subclinical hyperthyroidism has been reported. We describe the case of a patient with neither previous thyroid disorders nor autoimmunity who developed GD after OS for primary infertility. A 40-year-old woman with primary infertility underwent four cycles of OS. Her thyroid function performed before the last cycle was unremarkable (thyroid stimulating hormone [TSH] 1.9 mU/L, fT4 1.3 ng/dL, fT3 2.4 pg/mL), and thyroid autoimmunity was negative (anti-thyroperoxidase antibodies and anti-thyroglobuline antibodies). Six weeks after the last cycle she developed overt thyrotoxicosis (TSH < 0.005 mU/L, fT4 4.79 ng/dL, fT3 15.6 pg/mL) with anti-thyrotropin receptor antibodies (TRAb) positivity (9.2 IU/L). She was diagnosed with GD and anti-thyroid therapy was instituted. After 1 year of treatment, thyroid function was still suboptimal (TSH 0.2 mU/L, fT4 1.04 ng/dL, fT3 2.2 pg/mL), and TRAb titer still elevated (8.75 IU/L). Despite her desire to achieve pregnancy, a further cycle of OS was postponed until complete remission of thyroid dysfunction and withdrawal of anti-thyroid therapy. Although TSH assay after OS is not recommended in euthyroid women without autoimmunity, in the presence of hyperthyroid symptoms throughout OS it is advisable to evaluate thyroid function and TRAb. It is advisable to carefully evaluate the course of GD before proceeding with further courses of OS that could lead to its exacerbation or recurrence. In cases where a strong desire for pregnancy persists, thyroidectomy may be proposed.

Subclinical Hyperthyroidism and Cardiovascular Disease.

Background: In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary: We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion: The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

6418 Treatment of Subclinical Hyperthyroidism and Incident Atrial Fibrillation

Abstract Disclosure: M. Jay: None. P. Huan: None. N. Cliffe: None. J. Rakoff: None. E. Morris: None. P. Kavsak: Advisory Board Member; Self; Roche Diagnostics, QuidelOrtho, Siemens. Consulting Fee; Self; QuidelOrtho, Roche Diagnostics. Grant Recipient; Self; QuidelOrtho. Speaker; Self; Abbott Laboratories. Other; Self; Siemens(Other Research Support (includes receipt of drugs, supplies, equipment or other in-kind support), Speaker/Honoraria)). M. Luthra: Advisory Board Member; Self; Bayer, Inc., Novonordisk. Consulting Fee; Self; Bayer, Inc., Novonordisk. Speaker; Self; Lilly/BI alliance, Novonordisk, Sanofi. Z. Punthakee: None. Background: Treating overt hyperthyroidism prevents atrial fibrillation (AF). Though subclinical hyperthyroidism (SH) has been associated with AF risk, it is unknown whether treating SH prevents AF. Objective: We aimed to identify the association between treating SH and incident AF in outpatients. Methods: In a retrospective chart review, 2169 patients ≥ 18 years, diagnosed with SH between 2000-2021 were identified using the regional biochemistry database. After excluding those with prior AF, hypothyroidism, thyroid cancer, pituitary disease, and pregnancy, 360 patients categorized as treated (n=131) or untreated (n=229) were analyzed. The primary outcome was incident AF. Incidence rates were compared between the two groups over the time since SH treatment start for the treated group, and time since diagnosis of SH for the untreated group. Pharmacoepidemiologic Cox analysis adjusted for age and hypertension, with treatment as a time dependent covariate was used to account for untreated time in the treated group. Secondary outcomes were AF prevalence, P wave duration on ECG, as well as ventricular and ascending aorta diameters on echocardiogram. We included sensitivity and subgroup analyses. Results: Mean age of patients with SH was 55.19 years, 78% were female, 43% had toxic nodules and 14% had Grave’s disease. Amongst the 19 patients who developed AF, 58% had toxic nodules and no patient had Grave’s disease. In the treated and untreated groups, AF occurred in 3.1% and 6.6% (p=0.15) and AF incidence was 0.8 and 1.4 %/year (p=0.31), respectively. The hazard ratio (HR) was 0.60 (95% CI 0.19-1.92; p=0.39). In the subgroup of patients with free T4 (FT4) ≥ 15 pmol/L, AF incidence was 0.5 and 3.0 %/yr in the treated and untreated groups, respectively (p=0.01), while adjusted HR was 0.185 (95% CI 0.022-1.59, p=0.12). In those with TSH ≤ 0.1 mU/L, treatment was not associated with AF incidence. As some cases of AF were documented nearly simultaneously with treatment of SH, a sensitivity analysis was performed reassigning 2 patients diagnosed with AF &amp;lt;30 days after starting SH treatment to the untreated group. Here, in the treated and untreated groups, AF occurred in 1.6% and 7.4% (p=0.02), and AF incidence was 0.4 and 1.8 %/year (p=0.02), respectively. The HR was 0.25 (0.06-1.13; p=0.07). In the treated versus untreated groups, the mean p wave duration, ventricular diameter, and ascending aorta diameter were 73.47 vs 73.42 ms (p=0.99), 4.29 vs 4.34 cm (p=0.86), and 3.33 vs 3.23 cm (p=0.58), respectively. Conclusions: We report the first study assessing the effect of treating SH in preventing incident AF. There was an overall trend towards lower AF following treatment of SH. Lack of statistical significance may be related to small sample size, supporting the need for larger scale studies. These data suggest the etiology of SH (toxic nodules) and FT4 levels could be factored into treatment decisions. Presentation: 6/2/2024

8062 Uncommon Presentation of Multiple Myeloma as a Rapidly Growing Thyroid Goiter Initially Thought to be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

8062 Uncommon Presentation Of Multiple Myeloma As A Rapidly Growing Thyroid Goiter Initially Thought To Be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

7596 Thyroid Function Tests in Breast Cancer Patients Following Immune Checkpoint Inhibitor Treatment: What Happened in a Population with Preexisting Thyroid Dysfunction?

Abstract Disclosure: M. Villanova: None. L. Min: None. Introduction: Thyroid dysfunction occurs commonly following immune checkpoint inhibition, but the etiology remains unclear. Immune checkpoint inhibitor (ICI) is not contraindicated in patients with a preexisting thyroid dysfunction, but little is known about the impact of ICI on thyroid function tests (TFTs) in this setting. This study sought to define TFTs abnormalities following ICI treatment in patients with previous thyroid dysfunction. Methods: We performed a retrospective cohort study of thyroid dysfunction in patients with breast cancer undergoing anti-programmed cell death protein-1/ligand-1 therapy from May 2016 to Dec 2023. Results: A total of 30 patients were included with a mean follow-up of 18 ± 12 months. Two patients (7%) had a history of Graves’ disease, 4 patients (13%) had a post ablative hypothyroidism, and 3 patients (10%) had a post-surgical hypothyroidism. The etiology of the hypothyroidism was not further specified in the remain cases (70%). Twenty-three patients (77%) were treated with levothyroxine at baseline at the mean dose of 1.31 ± 0.68 mcg/kg. Baseline TFTs were available in 27 patients (90%). Twenty-four patients (80%) had at least one TFTs abnormality after initiating ICI treatment. Subclinical hypothyroidism (n = 11) was the most common abnormality, followed by overt thyrotoxicosis (n = 10), subclinical thyrotoxicosis (n =7), and overt hypothyroidism (n = 7). Thirteen out of 16 patients with normal baseline TFTs developed at least one TFTs abnormality after initiating ICI treatment. Subclinical hypothyroidism (n = 6) and overt thyrotoxicosis (n =6) were the most common alterations, followed by subclinical thyrotoxicosis (n = 5), and overt hypothyroidism (n = 3). Three patients with post-ablative hypothyroidism had normal baseline TFTs. Among these, one patient developed an overt thyrotoxicosis, one patient developed a subclinical hypothyroidism followed by overt thyrotoxicosis and one patient had no TFTs alterations. One post-operative hypothyroid patient had a normal baseline TFT and developed a subclinical hypothyroidism followed by overt thyrotoxicosis. Twenty-five patients (83%) were on levothyroxine at the last follow-up at the mean dose of 1.41 ± 0.60 mcg/kg. The dose was higher than that at baseline but did not reach statistical difference (Student T test, P = 0.059). Levothyroxine dosage was adjusted in 16 patients (53%) and 25 patients (83%) achieved normal TFTs at the last follow-up. Conclusion: ICI treatment related TFTs abnormalities were common in patients with preexisting thyroid dysfunction. There were multiple distinct phenotypes. The mechanisms underlying the TFTs abnormalities is not clear. Destructive thyroiditis, medication adherence, or interference with TFT assay by ICI are among the possible etiologies. ICI is not contraindicated in this group of patients but their TFTs should be monitored closely. Presentation: 6/1/2024

9303 Evaluation of The Consistency of Thyroid Indicators Tests in Minimally Invasive Peripheral Blood and Venous Blood

Abstract Disclosure: Z. Zhu: None. Y. Huang: None. Z. Cao: None. L. Zhang: None. D. Wang: None. S. Wang: None. J. Zhang: None. Y. Gao: None. Y. Zhang: None. Background The detection of thyroid indicators is of high demand in clinical and epidemiological screenings. Compared with existing venous blood tests, peripheral fingertip blood tests are less invasive and have a lower blood collection volume, which is the basis for point-of-care tests of thyroid indicators. Objective To explore the feasibility of minimally invasive and micro blood collection tests for thyroid disease (TD) patients by evaluating the consistency of thyroid indicators and TD diagnostic efficiency between fingertip blood tests and venous blood tests. Method 63 subjects with or without thyroid dysfunction were consecutively recruited. All subjects underwent serum, plasma and fingertip blood (same day collection) measurements for TSH and TT4 detection via the chemiluminescence method and for TPOAb detection via the electrochemiluminescence immunoassay method. The fingertip blood was centrifuged and diluted after EDTA anticoagulation. Bland–Altman plot, Passing–Bablok regression, and weighted kappa test were used for consistency test; AUC of ROC curve, sensitivity and specificity were used for authenticity evaluation among the three collection and testing methods. Results 43 subjects with euthyroidism and 20 subjects with thyroid dysfunction were included; including 29 (46.03%) females, the average age was 50.98±14.76 years. Bland-Altman plots showed more than 90% of the subjects had TSH and TT4 differences within the 95% limits of agreement between peripheral blood (PB) and venous blood (including serum and plasma). Passing–Bablok regression analyses revealed strong correlations between TSH levels in PB and serum (r=0.888) and plasma (r=0.894) (p&amp;lt;0.05); for TT4, there was a strong correlation between PB and serum (r=0.746), and there was also a moderate correlation between PB and plasma (r=0.664) (p&amp;lt;0.05 for both). Weighted kappa tests were performed for low, normal and high TSH values, indicating strong consistency between PB and serum and between PB and plasma, with coefficients of 0.901 and 0.881, respectively (P&amp;lt;0.001); for TT4, the coefficients between PB and serum, PB and plasma were 0.541 and 0.585 (P&amp;lt;0.001), indicating moderate consistency. Regardless of TPOAb positivity or negativity, the consistency among three blood sample sources was 100%. For euthyroidism (n=43), hyperthyroidism (n=6), subclinical hyperthyroidism (n=9), hypothyroidism (n=1), and subclinical hypothyroidism (n=4), the diagnostic sensitivities of PB were 97.06%, 83.33%, 87.50%, 100%, and 75.00%, respectively; the specificities were 94.74%, 97.87%, 95.74%, 98.11%, and 100.00%, respectively. The AUC of PB ROC curve for determining thyroid dysfunction was 0.944 (95% CI 0.867-1.000). Conclusion PB tests of thyroid indicators has high consistency with venous blood tests, offers sufficient diagnostic efficiency for TD, and is a feasible minimally invasive detection method. Presentation: 6/1/2024

8812 Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center Retrospective Study

Abstract Disclosure: N.B. Luna: None. E. Mendoza: None. S.A. Kho: None. Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center, Retrospective Study Immune checkpoint inhibitors (ICIs) serve as immunomodulatory antibodies, which enhance the immune system and substantially improve the prognosis for patients with advanced malignancies [1]. Referral to endocrinology have been increasing because ICIs were associated with endocrine-related adverse effects including hypothyroidism, hyperthyroidism, diabetes, hypophysitis and adrenalitis. Hence, the study aimed to retrospectively determine the local prevalence and profile of Filipino patients who developed endocrinopathies during ICI therapy at the University of Santo Tomas Hospital (USTH), Manila, Philippines from 2013-2019. A single-center retrospective study of ICI-treated cancer patients with serial biochemical and/or radiologic monitoring of endocrine adverse effects was done upon approval by the Research Ethics Committee. A total of 27 subjects were included with a median age of 60 years and male predominance. Pembrolizumab consisted 93% of the ICIs given. The incidence of thyroid dysfunction was 36% (18% overt hypothyroidism, 9% subclinical hypothyroidism, and 9% subclinical hyperthyroidism). The median time at risk for development of overt hypothyroidism is 4 weeks with median TSH level of 9.05 uIU/mL from baseline level of 3.77 uIU/mL. All patients who had baseline hypothyroidism worsened with increase from baseline levothyroxine dose by 50 to 230% in order to achieve euthyroidism (p 0.037). Serial monitoring was done every 2 weeks until euthyroidism. ICIs were temporarily put on hold in 75%. Diabetes (p 0.05), renal carcinoma (p 0.001) and dose of 200mg (p 0.42) were associated to developing overt hypothyroidism. Checking of glycemic levels was not routine among non-diabetic patients. Fifteen percent of diabetic patients had worsening of control (median HbA1c 8.5% [8-9] and 23% were newly diagnosed pre-diabetes (median fasting glucose 114mg/dL [104-120]). With the available imaging results, there were no abnormal adrenal metabolic uptake on PET scan and no evidence of hypophysitis in pituitary MRI. In conclusion, overt hypothyroidism is a common occurrence during ICI therapy (18%). Worsening occurred among all patients with hypothyroidism at baseline. New-onset pre-diabetes and worsening of glycemic control were seen in 15 and 23%, respectively. Serial clinical and biochemical monitoring is important and referral to endocrinology should be made if deemed necessary. [1] L Agrawal, A Bacal, S Jain, V Singh, N Emanuele, Ma Emanuele &amp; F Meah (2020) Immune checkpoint inhibitors and endocrine side effects, a narrative review, Postgraduate Medicine, 132:2, 206-214, DOI: 10.1080/00325481. 2019. 1709344 Presentation: 6/1/2024

8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent

Abstract Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None. Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children. Presentation: 6/2/2024

7583 Evaluation of The Consistency of Thyroid Indicators Tests in Minimally Invasive Peripheral Blood and Venous Blood

Abstract Disclosure: Z. Zhu: None. Y. Huang: None. Z. Cao: None. L. Zhang: None. D. Wang: None. S. Wang: None. J. Zhang: None. Y. Gao: None. Y. Zhang: None. Background: The detection of thyroid indicators is of high demand in clinical and epidemiological screenings. Compared with existing venous blood tests, peripheral fingertip blood tests are less invasive and have a lower blood collection volume, which is the basis for point-of-care tests of thyroid indicators. Objective To explore the feasibility of minimally invasive and micro blood collection tests for thyroid disease (TD) patients by evaluating the consistency of thyroid indicators and TD diagnostic efficiency between fingertip blood tests and venous blood tests. Method 63 subjects with or without thyroid dysfunction were consecutively recruited. All subjects underwent serum, plasma and fingertip blood (same day collection) measurements for TSH and TT4 detection via the chemiluminescence method and for TPOAb detection via the electrochemiluminescence immunoassay method. The fingertip blood was centrifuged and diluted after EDTA anticoagulation. Bland–Altman plot, Passing–Bablok regression, and weighted kappa test were used for consistency test; AUC of ROC curve, sensitivity and specificity were used for authenticity evaluation among the three collection and testing methods. Results 43 subjects with euthyroidism and 20 subjects with thyroid dysfunction were included; including 29 (46.03%) females, the average age was 50.98±14.76 years. Bland-Altman plots showed more than 90% of the subjects had TSH and TT4 differences within the 95% limits of agreement between peripheral blood (PB) and venous blood (including serum and plasma). Passing–Bablok regression analyses revealed strong correlations between TSH levels in PB and serum (r=0.888) and plasma (r=0.894) (p&amp;lt;0.05); for TT4, there was a strong correlation between PB and serum (r=0.746), and there was also a moderate correlation between PB and plasma (r=0.664) (p&amp;lt;0.05 for both). Weighted kappa tests were performed for low, normal and high TSH values, indicating strong consistency between PB and serum and between PB and plasma, with coefficients of 0.901 and 0.881, respectively (P&amp;lt;0.001); for TT4, the coefficients between PB and serum, PB and plasma were 0.541 and 0.585 (P&amp;lt;0.001), indicating moderate consistency. Regardless of TPOAb positivity or negativity, the consistency among three blood sample sources was 100%. For euthyroidism (n=43), hyperthyroidism (n=6), subclinical hyperthyroidism (n=9), hypothyroidism (n=1), and subclinical hypothyroidism (n=4), the diagnostic sensitivities of PB were 97.06%, 83.33%, 87.50%, 100%, and 75.00%, respectively; the specificities were 94.74%, 97.87%, 95.74%, 98.11%, and 100.00%, respectively. The AUC of PB ROC curve for determining thyroid dysfunction was 0.944 (95% CI 0.867-1.000). Conclusion PB tests of thyroid indicators has high consistency with venous blood tests, offers sufficient diagnostic efficiency for TD, and is a feasible minimally invasive detection method. Presentation: 6/1/2024

6537 Recurrent Graves Thyrotoxicosis After Prolonged Radioiodine-Induced Hypothyroidism

Abstract Disclosure: H.K. Deveaux: None. A. Gundeti: None. K. Mitrollari: None. A.P. Calimag: None. T. Yasmeen: None. Radioactive iodine (I-131) ablation (RAI) is one of the effective therapies for Graves’ disease (GD). Successful treatment is indicated by sustained, irreversible hypothyroidism requiring lifelong replacement for which recurrence of disease rarely develops. Recurrent hyperthyroidism is a rare development without apparent predisposition. Here, we describe a case of recurrent thyrotoxicosis after 36 years of RAI.70-year-old female PMH atrial fibrillation (AFib) on apixaban s/p cardioversion, HTN, HFpEF, Pulmonary HTN, and Graves’ Disease s/p RAI ablation 36 years ago with RAI-induced hypothyroidism. The patient was initially on levothyroxine for post-ablative hypothyroidism and stopped taking levothyroxine around 2019. NM scintigraphy done in 2019 showed an abnormal I-123 thyroid uptake and scan with the five-hour radioiodine thyroid uptake showed mildly hyperthyroid. On the thyroid scan, there is a note of a prominent pyramidal lobe with some thyroid gland asymmetry. In 2022, the patient was admitted for new-onset AFib and was noted to have subclinical hyperthyroidism with TSH 0.157, fT4 1.4, TrAb&amp;gt;40, and TSI 34.8. The patient was started on methimazole, which she stopped one month later. During this admission, the patient presented secondary to a mechanical fall and was found to be in AFib with a rapid ventricular rate. Her labs were significant for TSH&amp;lt;0.008 fT4 4.2, TrAb &amp;gt;40. Methimazole was restarted with maximal doses of diltiazem and metoprolol for rate control. Thyroid ultrasound demonstrated an enlarged, heterogeneous thyroid gland with increased vascularity and multiple bilateral TR3 thyroid nodules.Hyperthyroidism affects approximately 1.2% of the population. GD involves autoantibodies activating the thyrotropin receptor, increasing synthesis and release of thyroid hormone and is for 50-60% of cases with a 5-to-10-fold preference for females. RAI ablation is preferred, being inexpensive, with a cure rate approaching 100%. The incidence of transient hypothyroidism post-RAI varies from 9-17%. Retrospective studies have observed hyperthyroidism within the first 12 months post-RAI; however, some cases have seen a resurgence as late as 22 years later. Recurrent hyperthyroidism is an uncommon occurrence with various postulated aetiologies, such as inadequate dosing/incomplete ablation with residual cells remaining viable and regenerating in the setting of increased TSIiv, Marine-Lenhart syndrome (MLS), or an unclear mechanism associated with autoimmunity in the presence of TSI. Hyperthyroidism rarely recurs in GD after successful post-ablative treatment with RAI. Our case, while an uncommon presentation and underlying aetiology yet to be determined, illustrates the importance of continued surveillance, even after successful treatment.‌ Presentation: 6/3/2024

7639 A Rare Cause of Lung Adenocarcinoma with Metastasis to the Thyroid

Abstract Disclosure: E. Echevarria-Torres: None. C.G. Yap: None. K.E. Izuora: None. A rare cause of lung adenocarcinoma with metastasis to the thyroid. Metastasis to the thyroid gland from non-thyroid malignancies is rare. When metastasis occurs, presenting symptoms are typically nonspecific, representing a diagnostic challenge. With the goal of raising awareness, we present a case of lung adenocarcinoma with metastasis to the thyroid. An 85-year-old man with a history of hypertension, hyperlipidemia and 60 years smoking history presented to the endocrine clinic for evaluation of subclinical hyperthyroidism. On the physical exam, there was fullness in the right thyroid area which on ultrasound showing a large right thyroid nodule occupying the entire lobe. There was also a solid 4.5 cm x 3.4 cm x 4.6 cm nodule in the mid-anterior left thyroid lobe. Fine needle aspiration cytology of right nodule revealed malignant cells and cell block material positive for TTF-1 (Thyroid Transcription Factor 1) concerning for malignancy. The left thyroid nodule cytology was consistent with benign follicular nodule. Chest CT ordered for surgical planning showed right upper lobe pleural-based lung opacity measuring 3.7 cm x 2.9 cm with supra clavicular lymphadenopathy. Biopsy of lung mass and supra clavicular lymph nodes revealed primary lung adenocarcinoma involving the lymph nodes consistent with stage Iva (cT3NxM1b). The patient was referred to oncology for further management. Discussion: Metastatic lesions to the thyroid gland account for less than 1 % of all malignant thyroid tumors with most cases found on autopsy. This is hypothesized to be due to the rich blood supply and high iodine content of the thyroid gland. Thyroid metastasis usually presents several years after initial diagnosis and treatment of non- thyroid malignancy. Patients can present with enlarging thyroid nodules, neck swelling, dysphagia and, in rare instances, upper airway obstruction. We present a rare case of lung cancer with metastasis into the thyroid. The thyroid nodule initially palpated upon physical exam led to eventual thyroid ultrasound and subsequently to his diagnosis of lung adenocarcinoma after findings of lung nodule which was biopsied and showed primary lung adenocarcinoma. TTF-1 was also positive which is typically expressed by lung adenocarcinomas. Treatment for thyroid metastasis is surgery, along with treatment of primary malignancy. The earlier the diagnosis and treatment the more favorable the prognosis. Radiotherapy and chemotherapy are other means to reduce the recurrence. Thyroid hormone replacement will be warranted post operatively for hypothyroidism. We present this uncommon case to raise awareness about the presentation of thyroid metastasis to enhance timely diagnosis and intervention. Presentation: 6/1/2024