Hyperthyroid Patients Research Articles

Proteomics and transcriptomics combined reveal specific immunological markers in autoimmune thyroid disease

ObjectiveThe pathogenesis of AITD remains unclear to date. This study employs a combination of proteomics and transcriptomics analysis to identify and validate specific immune response markers in patients with hyperthyroidism and hypothyroidism, thereby providing a scientific basis for the clinical diagnosis and treatment of AITD.MethodsBy collecting serum and whole blood tissue samples from patients with hyperthyroidism, hypothyroidism, and healthy controls, this study utilizes a combination of transcriptomics and proteomics to analyze changes in immune-related signaling molecules in patients. Specific biomarkers were identified, and the ELISA method was employed to determine the expression levels of these clinical markers and their correlation with clinical features of the patients, ultimately establishing a predictive model.ResultsTranscriptomic and proteomic analyses were conducted to identify differentially expressed genes and proteins in patients with hyperthyroidism and hypothyroidism compared to healthy controls. Enrichment analysis revealed that these differentially expressed genes and proteins are primarily associated with immune function, antigen-antibody binding, and alterations in immune cells. Through the combined analysis of transcriptomics and proteomics, key genes IGHG3, ISG15, and ZNF683 were identified. ELISA results from clinical patient serum samples indicated that the levels of IGHG3 were significantly higher in both the hyperthyroid and hypothyroid groups compared to the control group (P<0.05). Additionally, the serum levels of ISG15 in the hyperthyroid group were greater than those in both the control and hypothyroid groups (P<0.05), while the serum levels of ZNF683 in the hypothyroid group exceeded those in the control and hyperthyroid groups (P<0.05). Furthermore, all three biomarkers correlated with the thyroid function of the patients. Prediction models for hyperthyroid and hypothyroid patients were constructed using IGHG3, ISG15, and ZNF683, demonstrating good performance metrics and decision effect.ConclusionIn patients with hyperthyroidism and hypothyroidism, significant changes primarily occur in immune function and immune cells when compared to healthy individuals. Key signaling molecules were identified: ISG15 for hyperthyroidism, ZNF683 for hypothyroidism, and IGHG3 common to both conditions. These findings provide new biomarkers for the diagnosis and monitoring of clinical patients, thereby offering a scientific basis for research on AITD and personalized treatment approaches.

Linsitinib inhibits IGF-1-induced cell proliferation and hyaluronic acid secretion by suppressing PI3K/Akt and ERK pathway in orbital fibroblasts from patients with thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO), an autoimmune disorder of the retrobulbar tissue, is present in up to 50 percent of Graves's hyperthyroidism patients. Insulin-like growth factor 1 receptor (IGF-1R) has received attention as a target for the development of therapeutic agent for TAO. IGF-1R and TSHR (thyroid stimulating hormone receptor) interact with each other to form a physical or functional complex, further promoting the development of TAO. Linsitinib, OSI-906, is an inhibitor of IGF-1R and has been reported to inhibit cell proliferation of several tumor cells. Linsitinib has been receiving attention not only for its anticancer effect, but also for its anti-inflammatory effects. It has been reported that linsitinib reduces infiltration of inflammatory cells in orbital tissues, resulting in the reduction of muscle edema and adipose tissues in an experimental murine model for Graves' disease. In the current study, we investigated the issue of whether linsitinib inhibits the IGF-1-induced proliferation of orbital fibroblasts (OFs) via the suppression of phosphatidylinositol 3-kinase (PI3K) / Akt and extracellular signal-regulated kinase (ERK) pathway. Our results showed that pretreatment with linsitinib inhibited IGF-1-induced cell proliferation and hyaluronic acid secretion in the OFs of TAO patients. In addition, our results showed that pretreatment with linsitinib inhibited IGF-1-induced phosphorylation of IGF-1Rβ at Tyr1135, Akt at Ser473, and ERK in the OFs of patients with TAO. These results indicate that linsitinib inhibits IGF-1-induced cell proliferation and hyaluronic acid secretion in the OFs of TAO patients by suppressing the PI3K/Akt and ERK pathways, validating the use of linsitinib as a novel therapeutic agent for TAO.

Increased Lower Urinary Tract Symptoms in Male Hyperthyroid Patients

Increased Lower Urinary Tract Symptoms in Male Hyperthyroid Patients

Management of perioperative thyrotoxicosis - what to do when standard therapy is contraindicated or fails?

Current guidelines recommend that hyperthyroid patients should be rendered euthyroid prior to surgical procedures. These guidelines rely heavily on the use of ATDs as the primary medication, and do not give recommendations for patients who have contraindications to ATDs, or for whom standalone ATD treatment is inadequate. To evaluate the efficacy and safety of adjunctive pharmacological therapy and/or therapeutic plasma exchange (TPE) in the perioperative management of patients with thyrotoxicosis who were intolerant to ATD or for whom standalone ATD therapy was inadequate to achieve euthyroidism prior to surgery. A comprehensive search of MEDLINE, Google Scholar, Embase and CENTRAL up to 31 December 2023 retrieved 12,876 records. After screening titles, abstracts and full manuscripts, 16 reports were enrolled. The study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Patients were primarily female (78.5%), aged between 35 and 52 years. The predominant thyroid condition was Graves' disease (89.7%). Majority underwent thyroidectomy (99.3%). Patients treated pre-operatively with 2nd line pharmacotherapy with/without therapeutic plasma exchange (TPE) underwent surgery safely with no reports of perioperative thyroid storm. Pre-operative treatment achieved mean percentage reduction of free thyroxine and free triiodothyronine levels of 52.6 ± 8.2% and 68.1 ± 9.3% respectively. One study reported a patient who suffered from myocardial infarction and tachyarrhythmia and subsequently demised. Preoperative management of hyperthyroidism with second line pharmacotherapy and/or TPE can be effectively and safely implemented in patients with intolerance to or ineffective treatment with ATDs. The treatment modalities were generally safe, though some complications were observed.

Rapid ventricular response atrial fibrillation in an uncontrolled hyperthyroidism patient

Hyperthyroidism, defined as elevated blood levels of thyroid hormone with reduced levels of thyroid-stimulating hormone (TSH). Atrial fibrillation (AF) is the most common cardiac complication in patients with hyperthyroidism. There is several pathophysiology of AF in hyperthyroidism such as an increase atrial pressure, ischemia, and ion disturbance of the myocardium. In hemodynamically unstable patients should be carried out electric cardioversion. The choice of rate or rhythm control is determined based on the case. Beta-blockers inhibit sympathetic activity in the AV node so that it can inhibit the ventricular rate. Antithyroid drugs are widely used in the management due to restoration of euthyroidism is fundamental in the management of hyperthyroidism related AF.

A higher incidence of cardiovascular complications in hyperthyroid patients with Graves’ disease in comparison to hyperthyroid patients with subacute thyroiditis

Background: Hyperthyroidism, as well as systemic inflammation, are associated with a higher incidence and complications of cardiovascular disease. Both in Graves’ disease and subacute thyroiditis, patients are hyperthyroid. However, in Graves’ disease, there is an autoimmune process in the thyroid, and in subacute thyroiditis, hyperthyroidism is accompanied by systemic inflammation. It is not known if the rate of cardiovascular complications is higher in the course of Graves’ disease or subacute thyroiditis.. Methods: We performed a retrospective study of all hyperthyroid patients newly diagnosed with Graves’ disease or subacute thyroiditis between January 1st 2018 and December 31st 2021 at the Department of Nuclear Medicine, University Medical Centre Ljubljana. Cardiovascular complications in the period 3 months before or after diagnosis were registered. Values are expressed as mean (SD).. Results: The sample analysis included 1028 patients (247 with subacute thyroiditis, 781 with Graves’ disease). The two groups did not significantly differ by sex, age, and body mass index. A cardiovascular complication was registered in 78 patients; the incidence was significantly higher in Graves’ disease than in subacute thyroiditis (74 vs. 4, p<0.001). Compared to patients with subacute thyroiditis, patients with Graves’ disease had significantly lower TSH: 0.010 (0.006) vs. 0.024 (0.044) mIU/L (p<0.001), higher free T4: 44.1 (26.6) vs. 37.0 (14.7) pmol/L (p<0.001), higher incidence of diabetes: 4.3 vs. 0.4% (p=0.001), arterial hypertension: 12.2 vs. 5.7% (p=0.004) and smoking: 26.7 vs. 8.7% (p<0.001). In a logistic regression model, a significantly higher likelihood for cardiovascular complications was found in Graves’ disease vs. subacute thyroiditis (odds ratio 5.82, p=0.001), in patients with arterial hypertension (odds ratio 2.83, p=0.002), and in those with higher body mass index (odds ratio 0.92, p=0.043).. Conclusion: We report a higher incidence of cardiovascular complications in hyperthyroid patients with Graves’ disease in comparison to hyperthyroid patients with subacute thyroiditis. Patients with Graves’ disease were more severely hyperthyroid and had more adverse cardiovascular risk factors.

Iodine-131 combined with plasma exchange treatment in Graves’ hyperthyroidism patients with severe liver injury whose average MELD scores > 20

Iodine-131 combined with plasma exchange treatment in Graves’ hyperthyroidism patients with severe liver injury whose average MELD scores > 20

A prospective observational study on thyroid dysfunction in women with abnormal uterine bleeding: In a Teritary care hospital

Background: One of the most common diseases in gynecology, abnormal uterine bleeding (AUB) has a major negative impact on women's quality of life. Unusual bleeding in women can be brought on by thyroid conditions. The purpose of the study is to determine how common thyroid abnormalities are in women who have irregular uterine bleeding. It also looks at the menstrual patterns linked to thyroid disorders. The study concluded that hypothyroidism patients have menorrhagia, hyperthyroidism patients may experience dysmenorrhea, and thyroid dysfunction may result in irregular uterine hemorrhage. Materials and procedures: Premenopausal women with abnormal uterine bleeding (AUB) participated in a prospective observational study conducted in the gynecology department of a tertiary care hospital in Trivandrum between November 2022 and April 2023 (a period of six months). Result: Of the 75 patients who were chosen, 71 (94.7%) had AUB-induced hypothyroidism and 4 (5.3%) had AUB-induced hyperthyroidism. Regarding the menstrual pattern, 83.1% of patients with hypothyroidism and 100% of patients with hyperthyroidism reported experiencing menorrhagia or dysmenorrhea. The study concludes that there is a considerable correlation between thyroid issues and abnormal uterine hemorrhage. The majority of female AUB patients exhibit both hyperthyroidism and hypothyroidism. The most common menstrual pattern linked to hypothyroidism was menorrhagia. Dysmenorrhea was thought to be the most prevalent monthly abnormality in hyperthyroidism.

Estimation of Selected Metals in the Tissues of Prostate Carcinoma Patients

It Indicated that the Prostate cancer is common it affects nearly one-third of male over the age of 45. For two fundamental reasons, prostate cancer (PCa) is a serious health issue and a good prospect for tissue-scale, individualized modeling of cancer progression. In vivo validation might be allowed due to its compact size and the ability to measure serum PSA, a for prostate cancer blood biomarker can be diagnosed with support if certain markers identified by immunohistochemistry on tissue sections can aid in the diagnosis of adenocarcinoma that is primary in the prostate gland or metastatic. The biology of prostate cancer can be deeply understood by the gene identification and gene patterns expression. Using the Affymetrix Uranium95a, U95b, and Uranium95c chip sets (37,777 genes and expression sequence tags), Comprehensive gene expression is performed study on 152 hompsapien samples, which were from men of all ages and included cancer tissues, prostate tissues next to tumors, and prostate tissue of donor. In the prostate tissues, the majority of metals show a random distribution; nevertheless, patients show comparatively more unpredictability than controls. However, our findings indicate that the pattern of gene expression in cancer-related tissues is altered to such an extent that it resembles the effects of a cancer field. In contrast to controls, PCA and CA demonstrated how hazardous metals interfered with the critical metals' normal physiological and metabolic roles in the prostate tissues of both patient groups. In comparison to hyperthyroid patients and controls, hypothyroid patients' prostate tissues had greater mean levels of Fe, Ni, Cr, and Hg. Additionally; we discovered that by employing a unique model, Prostate cancer aggressiveness can be predicted by gene expression patterns.

Ultrasound-guided percutaneous microwave ablation of primary hyperthyroidism: security and efficacy analysis

Objectives This study aimed to analyze the safety, efficacy, and application prospects of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperthyroidism. Methods Eight patients with primary hyperthyroidism who underwent ultrasound-guided glandular volume reduction between January 2021 and December 2022 were included in this study. Pre- and postablative examinations, including grayscale ultrasound, contrast-enhanced ultrasound (CEUS), laboratory examination, antithyroid drug (ATD) dosage, and quality of life (QoL) assessment via Thyroid-Specific Patient-Reported Outcome Short-Form (ThyPRO-39), were analyzed retrospectively. The main ultrasound follow-up times were 1, 3, 6, and 12 months after ablation. Thyroid function was reviewed 1 week after ablation, and the subsequent reexamination time was determined according to the patient’s specific test results and ATD adjustment. The final efficacy was comprehensively analyzed according to the patient’s medication status, thyroid function, thyroid volume, and QoL score. Results All 8 patients successfully received MWA for primary hyperthyroidism, and none of them experienced serious complications. By the end of the follow-up, 5 of the 8 patients had stopped taking ATDs, 3 of the 8 patients had reduced ATD dosages, and all of them maintained stable thyroid function. Although descriptive analysis was performed because of the small sample size, patients’ thyroid volume reduction, and obvious improvements in goiter symptoms, hyperthyroid symptoms, anxiety, etc., were observed during our follow-up. Conclusion Ultrasound-guided MWA for reducing thyroid gland volume in primary hyperthyroidism patients is a new, safe, and effective minimally invasive treatment method that is a good choice for patients who cannot or refuse traditional treatment methods.

Correlation between serum uric acid level and atrial fibrillation in patients with hyperthyroidism on medical data analysis context of IoT.

Dysfunctions in metabolism and endocrine systems are outcomes of disruptions in human physiological processes, often leading to disease onset. External factors can hinder the human body's innate capacity for self-regulation and healing, particularly when immune responses are compromised, allowing these factors to interfere with normal bodily functions directly. To explore the effect of uric acid expression water in blood on the occurrence of atrial fibrillation in patients with hyperthyroidism, the expression level of uric acid in the blood and other physiological indexes were compared between patients with no symptoms of atrial fibrillation and patients with hyperthyroidism with symptoms of atrial fibrillation, to find the correlation between them. A group of 112 hyperthyroidism patients who were admitted to our hospital from September 2019 to March 2020 were chosen and split into two groups. The control group consisted of 56 individuals (21 men and 35 women) aged between 16 and 86 years old, with an average age of 46.23 years (± 7.63). The observation group consisted of 56 individuals (24 males and 32 females) between 15 and 79 years, with an average age of 53.44 years (± 8.91). In the patients who were not treated with drugs before hospitalization the disease course and symptoms varied. The patients' clinical medical and demographic data were recorded and the patients' physiological indexes were obtained through blood tests and analysis. The differences between the two groups were analyzed by renal function, blood lipid index, thyroid function, and cardiac ultrasound, and these influencing factors were analyzed by regression analysis. The research adhered to ethical norms and ensured clear data presentation by using a rigorous technique to compare uric acid levels and physiological indicators among various patient groups. The study concentrated on the validation, repeatability, and contextual interpretation of data to provide a robust and rigorously scientific comparison. The most common is the increase of uric acid in the blood, which can induce other diseases, and atrial fibrillation is one of the most common diseases of cardiovascular diseases.

Genetic predisposition to thyroid dysfunction: a case–control study investigating TSHR gene polymorphism (rs2268458) in Indians

BackgroundVariations in the TSHR gene have been implicated in a spectrum of thyroid diseases. Previous studies have implicated variations in the TSHR gene, including SNPs rs179247, rs12101255, and rs2268458, in thyroid diseases, but their association with hypothyroidism and hyperthyroidism in the Indian population has not been investigated.AimIn this study, we aimed to examine the relationship between candidate SNP rs2268458 and susceptibility to hypothyroidism and hyperthyroidism in the Indian population. We carried out a case–control genetic screening of the TSHR gene.MethodsWe analyzed the variant of the TSHR gene using the PCR–RFLP technique in a total of 318 participants, including 130 controls and 188 individuals with thyroid disorders (124 hypothyroid and 64 hyperthyroid). Demographic information was collected, and biochemical parameters were assessed using enzymatic methods. Statistical analysis was performed using SPSS-23.ResultsThe SNP rs2268458 demonstrated a significant association with hypothyroid and hyperthyroid patients (p-value < 0.05). Using the dominant genetic model, we calculated an odds ratio of 3.52 (confidence interval: 2.09–5.93, p-value: 0.0001) for the risk of hypothyroidism and an odds ratio of 2.34 (confidence interval: 1.26–4.31, p-value: 0.0001) for the risk of hyperthyroidism.ConclusionThis pioneering study in the Indian population reveals a significant association between the C allele of TSHR gene SNP rs2268458 and an increased risk of developing both hypothyroidism and hyperthyroidism. Our findings suggest that the C allele may be a common genetic risk factor for thyroid dysfunction in Indians.

The effect of TSH on kidney function

Background: The thyroid gland plays a vital role in the regulation of many physiological processes, including kidney function. Aim: The purpose of this study was to investigate the relationship between thyroid-stimulating hormone (TSH) and kidney function in male and female patients with hyperthyroidism, as well as in healthy control subjects. Method: A total of 60 participants from Najaf city, Iraq, were included in the study. This included 10 male and 10 female control subjects, as well as 20 male and 20 female patients with hyperthyroidism. Blood samples were collected from all participants and analyzed for TSH, urea, and creatinine levels. Result: The results showed a significant increase in TSH levels in both male and female patients with hyperthyroidism compared to control subjects. Urea levels were also significantly higher in hyperthyroidism patients compared to controls, while creatinine levels were not significantly different. In addition, there was a significant difference in the effects of TSH on kidney function between male and female patients with hyperthyroidism. Female patients with hyperthyroidism had significantly higher levels of urea and lower levels of creatinine compared to male patients with hyperthyroidism. These findings suggest a direct effect of TSH on kidney function and highlight the need for regular monitoring of kidney function in individuals with hyperthyroidism, particularly women. Further research is needed to fully understand the mechanisms behind the gender differences observed in this study and to develop targeted interventions for both men and women with thyroid disorders. Conclusion: our study provides valuable insights into the relationship between TSH and kidney function and highlights the need for multidisciplinary care and targeted interventions for individuals with thyroid disorders to prevent or minimize the risk of kidney dysfunction.

Magnitude of cardiac abnormality and its associated factors among hyperthyroidism patients on follow-up at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

BackgroundThyroid hormones have an effect on every organ system, in particular, the heart responds to minimal changes in serum thyroid hormone level. Thyroid hormone causes a lot of changes in the cardiovascular system, such as increased heart rate, contractility, systolic hypertension, changes in peripheral vascular resistance, atrial fibrillation (AF), and hypercoagulability from the direct effect of thyroid hormone on cardiac myocyte and /or due to increased metabolic state. However, the magnitude of such heart abnormalities and its associated factors were not well studied in Ethiopia.ObjectiveTo determine the magnitude of cardiac abnormality and its associated factors among hyperthyroidism patients on follow-up at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia, 2022.MethodsAn institution-based cross-sectional study was carried out among 318 hyperthyroid patients who were on follow-up at the endocrine clinic of TASH, Addis Ababa, Ethiopia from June to October 2022. The data were collected using a pretested structured interviewer administered questionnaire. The data were entered into the computer using EpiData version 3.1 and analyzed using SPSS version 25 software. Bivariable and multivariable logistic regression models were fitted to determine the association between the independent and dependent variables. Adjusted odds ratio with its 95% confidence interval and p-value < 0.05 were used to declare the presence and strength of statistically significant associations.ResultIn this study a total of 318 hyperthyroid patients were participated, most (90.9%) of them were females. The overall prevalence of heart failure among hyperthyroid patients was 17.0% (95% CI = 13.0, 21.6). More than half (52.7%) and one third (33.2%) of the participants showed abnormal electrocardiographic and echocardiographic findings respectively. Marital status (not married) [AOR = 2.37, 95% CI (1.03, 5.44)], pattern of hyperthyroidism [AOR = 13.09, 95% CI (4.70, 36.41)], being Asthmatic [AOR = 7.63, 95% CI (1.55, 37.52)], type of medication [AOR = 3.49, 95% CI (1.11, 11.02)] and duration of treatment [AOR = 4.95, 95% CI (2.05,11.99)] were significantly associated with cardiac abnormality.ConclusionA significant portion of hyperthyroid patients overburdened by cardiac abnormalities. Being unmarried, overt hyperthyroid, Asthmatic, long stay on treatment and type of treatment were significantly associated with cardiac abnormality. Hence, attention should be given for cardiac abnormalities while treating hyperthyroid patients.

Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease

Background &amp; Objective: Graves’ disease (GD) is an autoimmune condition that targets the thyroid gland, resulting in excessive stimulation and synthesis of thyroid hormones. Excessive synthesis of these hormones can lead to symptoms such as loss of body weight, accelerated heart rate, irritability, reduced tolerance to heat, and excessive perspiration. Alpha-Klotho (KL), a protein crucial for physiological processes, is also involved in GD. The defective immunological condition of GD patients may increase Klotho expression, and the enhanced expression of fibroblast growth factor-23 (FGF23) in GD may be linked to the disease pathophysiology. We investigated serum levels of KL and FGF23 in Iraqi patients with Graves’ disease, analyzing correlations with clinical status and evaluating their potential as biomarkers for disease activity. Methodology: We conducted this cross-sectional study at The National Diabetes Center, Mustansiriyah University, between December 2022 and April 2023. The study involved 103 patients diagnosed with GD, and 103 patients, aged 21-70 y, as a control group. Patients with multinodular goiter, single thyroid nodules, thyroiditis, pregnant women, and those on medications or oral contraceptives, were excluded. Result: clinical significance of FGF23 and Klotho (KL) levels in patients with Graves’ disease (GD) compared to a control group. Results indicate that the median of KL levels are significantly higher in GD patients (KL = 6.31) compared to the control group (KL = 2.40), with a highly significant difference (P &lt; 0.001). In contrast, differences in median of FGF23 levels between GD patients (149) and controls (86.05) were not statistically significant (P = 0.07). Furthermore, KL levels were significantly higher in hyperthyroid patients compared to other thyroid statuses (P = 0.023), while FGF23 levels did not significantly differ across thyroid statuses (P = 0.255). Additionally, the study found a strong correlation between TRAb levels and both KL (r = 0.291, P &lt; 0.001) and FGF23 (r = 0.211, P = 0.003), and between KL and FGF23 directly (r = 0.412, P &lt; 0.001). These findings suggest that while KL may be a significant biomarker in GD, FGF23 relevance appears limited in this context. Conclusion: In Graves’ Disease patients have significantly higher levels of KL and FGF23 compared to controls, suggesting a distinct pathophysiological role for these biomarkers in mineral homeostasis and thyroid hormone regulation. Abbreviations: AITD - Autoimmune thyroid diseases; KL - Alpha-Klotho; FGF23 - fibroblast growth factor-23; GD - Graves’ disease; HT - Hashimoto's thyroiditis; IGF-1R - Insulin-like Growth Factor-1 Receptor; Keywords: Autoimmune Thyroid Disorders, Hyperthyroidism, Graves’ disease, Alpha-Klotho Citation: Rashid MF, Alammar HAJ, Rahmah AM. Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease. Anaesth. pain intensive care 2024;28(5):836−841. DOI: 10.35975/apic.v28i5.2567 Received: June 16, 2024; Reviewed: July 07, 2024; Accepted: July 18, 2024

8732 Hypercalcemia: When It’s Not PTH, Why Not Blame Your Neighbor?

Abstract Disclosure: D. Misra: None. M.R. Brennan: None. L. Misra: None. A 60-year-old female with a history of recently diagnosed hyperthyroidism, hypertension, and seizure disorder presents with a four-month history of neck swelling and pain. The patient was diagnosed with hyperthyroidism four months prior to admission and was started on methimazole 10 mg three times a day for two months, then instructed to decreased to 10 mg daily. In addition to the four months of neck swelling and pain, the patient also endorsed difficulty swallowing, palpitations, constipation, and bilateral ankle edema. Vital signs were stable other than a heart rate in the low 100s. Physical exam revealed a fixed painful L sided neck mass with no signs of airway compromise and bilateral exophthalmos. Labs revealed TSH &amp;lt;0.01 uIU/mL, Free T4 2.1 ng/dL, TSI was elevated (&amp;gt;40) IU/L. potassium 3.2 mmol/L, hypomagnesemia 1.3 mg/dL, troponin of 55 ng/l and hemoglobin 9.3 g/dL. The patient had a calcium of 10.6 mg/dL and an ionized calcium of 5.73 mg/dL with a normal PTH (34 pg/mL) and a low Vitamin D (22 ng/mL). A CT of the neck was performed showing marked thyromegaly with innumerable subcentimeter hypodense nodules in both lobes and a dominant 1.1 nodule in right lobe. Initial therapy involved correction of the electrolytes, telemetry monitoring, and a consultation to the endocrine service. The endocrine team started the patient on methimazole 10mg/daily and ordered a thyroid scan. Scintigraphy was performed and was consistent with Graves’ disease. On Day #2 the patient’s vital signs had normalized and the patient was able to swallow and tolerate a regular diet, The scan showed an enlarged thyroid with diffuse nodular character and moderate hyperemia consistent with diffuse thyroiditis. The scan also described a multinodular goiter with the largest nodule measuring 2.2 cm. She was discharged on Day #3 on methimazole 10mg daily and asked to follow up with endocrinology. Graves’ disease is a common cause of hyperthyroidism and is caused by autoantibodies that increase the production of thyroid hormone. Along with classic symptoms of hyperthyroidism, our patient had hypercalcemia. This was non-PTH mediated and in the absence of other signs or symptoms of a malignancy or granulomatous process, the hypercalcemia is likely due to her hyperthyroid state. Hyperthyroidism-associated hypercalcemia is a rare complication in hyperthyroid patients but should not be forgotten when evaluating non-PTH mediated hypercalcemia as it can be corrected easily with appropriate medications or in this case with the correction of the hyperthyroidism. Consideration of this etiology may also reduce the number of extraneous labs and imaging when no other common etiology is found. Presentation: 6/2/2024

7588 Coexistent Toxic Nodular Goiter And Primary Hyperparathyroidism (PHPT), A Combo With Diagnostic And Management Implications

Abstract Disclosure: D. Dave: None. A. Bhan: None. S.D. Rao: None. About 17-84% of patients with PHPT have concomitant thyroid disorders, but the prevalence of coexistent hyperthyroidism in PHPT varies 9-14 %. A vast majority had Graves’ disease with only 3 cases of toxic multinodular goiter (MNG) and PHPT reported in the literature as of 2022 ([1]). We present a rare case of coexistent toxic MNG and PHPT. Case Description: A 68y woman presented with recent 23 kg unintended weight loss and palpitations, but no other symptoms. Denied having kidney stones or fractures. On examination she had fine tremors of hands, MNG without exophthalmos. An ultrasound showed multinodular MNG with cystic lesions. A diagnosis of toxic MNG was made. Laboratory results were: TSH (&amp;lt;0.01 uIU/mL), free T4 1,68 ng/dL (normal: 0.61-1.44 ng/ml), high serum Ca (11.0 - 11.4 mg/dl) over 4y, but PTH was unavailable prior to the visit when it was 107 pg/ml and 89 pg/ml after 3 months of antithyroid therapy. Despite clinical and biochemical euthyroidism after 3 months, serum Ca and PTH levels remained high (11.4 mg/dl and 89 pg/ml respectively). Because she had pulmonary embolism a few years ago, we deferred parathyroidectomy until complete remission of hyperthyroidism. Discussion: Hypercalcemia is the biochemical hallmark of PHPT but can occur in 2-10% of patients with hyperthyroidism alone but only 1% of those will have coexistent PHPT. When these two conditions coexist, hypercalcemia is moderate to severe, and an occasional patient may present with hypercalcemic crisis (2). Prior to the availability of PTH assays, it was a challenge to diagnose coexistent PHPT. Hypercalcemia in hyperthyroidism responds to propranolol but not in PHPT, although the response is variable (3). With the availability of sensitive PTH assays, this maneuver is not necessary. In most cases, current PTH assays distinguish hypercalcemia of hyperthyroidism with suppressed PTH from coexistent PHPT in whom PTH level is non-suppressed or elevated. Monitoring serum Ca and PTH levels during therapy of hyperthyroidism would be useful as normalization of serum Ca and PTH has occasionally been reported (4). In our patient, serum Ca and PTH levels remained high with 3-months of methimazole and atenolol. The impact of both conditions on bone and mineral metabolism are profound, with fractures and kidney stones. Since kidney stones are uncommon in hyperthyroidism, presence of kidney stone in a hyperthyroid hypercalcemic patient should alert the possibility of PHPT. Similarly, significant decrease in bone density in such patient also raises the possibility of PHPT. Prompt diagnosis and appropriate treatment of both conditions is necessary to avoid irreversible complications.

6651 A Traceable Clinical Free Thyroxine Assay Based on Equilibrium Dialysis ID-LC/MS/MS

Abstract Disclosure: D. Spector: None. L. Zhang: None. A. Ribera: None. A. Doty: None. C. Tse: None. O. Sugahara: None. N. Vazquez: None. U. Danilenko: None. H.W. Vesper: None. Accurate diagnosis and effective treatment of thyroid diseases rely on reliable thyroid function tests. Serum free thyroxine (FT4) immunoassays (IAs) are most commonly used for FT4 measurements in clinical practice. However, FT4 IAs have not been standardized with large variations between different assay platforms. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for CDC standardization program to support the standardization of clinical assays for patient care. In the current study, we aim to develop a routine clinical FT4 assay based on ED-LC/MS/MS that is traceable to the RMP. ED-LC/MS/MS analysis was performed using a commercially available micro-ED plate. FT4 in dialysate was extracted with a 96-well C18 SPE plate. FT4 in the samples was quantitated by using LC/MS/MS in positive ion mode. The assay was calibrated with the certified primary reference material. By using RMP as a reference, we compared the analysis of 40 single donor sera between the ED-LC/MS/MS assay and FT4 IA on Roche e401platform. ED-LC/MS/MS assay could resolve T4, T3, reverse triiodothyronine (rT3), and other interferences in the samples with C18 chromatography in 4 min. The linear range of the routine FT4 assay was from 0.5-100 pg/mL covering clinically relevant FT4 concentrations including hypo-, hyperthyroid patient samples. The intra and inter-run CV% of the assay in 20 days was 3.72 and 5.25%, respectively. The effect of minor changes to the method conditions was studied. It was determined that serum/buffer ratios from 1:1 to 1:2 in the ED inserts, speeds of shaker for ED, and ED incubation time, did not influence the FT4 measurement. However, elevated ED temperature at 38°C could result in a more than 10% increase in FT4 values. A microplate format for the procedures of ED and SPE is amiable to the application of an automation system which significantly improves the throughput of the procedure. Method comparison showed good agreement between ED-LC/MS/MS assay and RMP in Deming regression analysis with a slope close to 1, while there was significant bias of IA from RMP. ED-LC/MS/MS assay was also applied for pregnancy serum samples with minimal difference on the FT4 measurement from RMP. We have developed a routine clinical FT4 assay that is traceable to RMP. The accuracy, precision, and sensitivity of the assay are suitable for high-throughput FT4 measurements in clinical laboratories and large epidemiologic studies. We demonstrate that the developed method can provide accurate FT4 measurements in patients including pregnant women. Presentation: 6/3/2024

B-021 Impact of Assay Conditions on FT4 Measurement Accuracy of Equilibrium Dialysis LC/MS/MS Clinical Assay

Abstract Background Reliable FT4 measurements are vital for accurate diagnosis and effective management of thyroid disorders. However, currently used FT4 immunoassays (IAs) lack standardization, leading to significant variations between platforms. Equilibrium dialysis (ED) coupled with LC-MS/MS analysis, considered the gold standard for FT4 measurement, has been adopted as a reference measurement procedure (RMP) for IA standardization. This study aimed to establish a high-throughput version of the routine clinical FT4 assay based on ED-LC/MS/MS technology and assess the impact of altered assay conditions on measurement accuracy. Methods A commercially available micro-ED plate was employed for ED-LC/MS/MS analysis. FT4 extraction from the dialysate was performed by utilizing a 96-well C18 SPE plate, followed by FT4 quantitation via LC-MS/MS in positive ion mode. Certified primary reference material was used to calibrate the assay. To evaluate assay robustness, the effects of minor method modifications were studied, including incubation time of ED, serum/buffer ratios in ED inserts, ED incubation temperature, shaker speed during ED, serum sample dilution ratio, and dialysate sample dilution ratio. Additionally, short-term and long-term stability of serum FT4 were assessed. Results The developed ED-LC/MS/MS assay successfully resolved T4, T3, reverse triiodothyronine (rT3), and other interferences within 4 minutes using C18 chromatography. The assay's linear range (0.5-100 pg/mL) encompassed clinically relevant FT4 concentrations across hypo- and hyperthyroid patient samples. Excellent agreement was observed between the routine assay based on ED-LC/MS/MS and CDC RMP with a Deming regression slope near 1 (95%CI: 0.87-1.06). Furthermore, serum/buffer ratios from 1:1 to 1:2.5 in ED inserts, shaker speeds from 75 to 150 rpm, and ED incubation times from 16 to 20 hours did not significantly affect FT4 measurement. However, elevated ED temperature (38°C) led to a more than 10% increase in FT4 values. Serum FT4 remained stable when exposed to room temperature for 12 hours, five freeze-thaw cycles, and -70°C storage for 1.5 years. Additionally, dilution of sera by up to 3-fold before ED did not alter FT4 measurement results. Diluting dialysate samples at least 3 times prior to SPE extraction proved accurate for samples exceeding the calibration curve range. Conclusions In conclusion, we successfully developed a routine clinical FT4 assay based on ED-LC/MS/MS that generates data comparable to the RMP. The assay exhibits robustness, with several altered conditions not significantly impacting measurement accuracy. This high-throughput and accurate assay demonstrates suitability for both clinical laboratories and large-scale epidemiological studies. Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.

Haemodynamics of hyperthyroidism: increased cardiac work and findings related to vasodilatation.

Hyperthyroidism increases cardiovascular morbidity and mortality, but the underlying mechanisms are not fully understood. In this study we compared non-invasive haemodynamics between 20 hyperthyroid patients and 60 euthyroid subjects. The measurements were performed median 6 days after the initiation of antithyroid medication when the patients were still hyperthyroid. Three controls matched for age, sex, body mass index, and smoking status were selected for each patient. Recordings were performed during rest and passive head-up tilt using whole-body impedance cardiography, radial pulse wave analysis, and finger blood pressure measurements. Systolic and diastolic blood pressures in the aorta and radial artery were similar in hyperthyroid and euthyroid subjects, while finger blood pressure was 16/12 mmHg lower in hyperthyroidism (p<0.001). Pulse wave velocity and aortic pulse pressure were similar, but radial pulse pressure was ~5 mmHg higher in hyperthyroidism (p=0.040) due to augmented amplification (p=0.045). Systemic vascular resistance was reduced (-18%), whereas heart rate (+19 beats/min), cardiac index (+28%), and left cardiac work (+31%) were increased in hyperthyroidism (p<0.001). Subendocardial viability ratio, reflecting the balance between coronary perfusion and pressure load, was reduced by 19% in hyperthyroidism (p<0.001). Compared with euthyroid subjects, hyperthyroid patients presented with reductions in systolic and diastolic finger blood pressures (p<0.001), and higher increase in heart rate (p=0.014) during upright posture. Hyperthyroid patients exhibited hyperdynamic circulation, reduced vascular resistance, reduced peripheral but not central blood pressure, and higher pulse pressure amplification. Furthermore, left cardiac workload was increased in parallel with unfavourable changes in coronary perfusion conditions.