Free Thyroxine Research Articles

7102 Pituitary Apoplexy with Eventual Complete Tumour Involution

Abstract Disclosure: A. Ng: None. R. Lai: None. Pituitary apoplexy is an endocrinological emergency resulting from infarction or haemorrhage of the pituitary gland. We present a case of pituitary apoplexy from a non-functioning pituitary macroadenoma, complicated by pituitary insufficiency and subsequent tumour involution. An 80-year-old gentleman presented to the Emergency Department with sudden severe headaches and persistent vomiting and admitted for further evaluation. Computed tomography (CT) imaging of the brain showed a prominent pituitary gland and magnetic resonance imaging (MRI) confirmed a large sellar hyperintense lesion containing blood and proteinaceous material. It measured 1.6 cm by 1.2 cm by 1 cm and indented the optic chiasm. CT angiography did not reveal any aneurysms or intracranial haemorrhage. There were no neurological or visual field deficits at presentation. There was no indication for surgery upon neurosurgical consultation. Initial evaluation of the pituitary axis was consistent with central hypocortisolism (cortisol 75 nmol/L, adrenocorticotropic hormone 1.4 pmol/L [reference range (RR) 1.6-13.9]) and hypoprolactinaemia (prolactin 56 mIU/L, RR 73-351). Luteinising hormone levels were < 1 IU/L (RR 1-9); follicle stimulating hormone levels were 3 IU/L (RR 1-19) and testosterone levels were < 1 nmol/L (RR 5 to 30) as the patient was on androgen deprivation therapy for prostate cancer. Hydrocortisone was started and he was monitored for development of frank diabetes insipidus. He did not require regular desmopressin. He later developed anti-diuretic hormone mediated hyponatraemia (serum sodium nadir of 125 mmol/L, serum osmolality 275 mmol/kg, urine osmolality 390 mmol/kg) that was managed with fluid restriction and solute loading. He also developed central hypothyroidism on day 19 of admission (free thyroxine 11 pmol/L, thyroid stimulating hormone 0.49 mIU/L, RR 0.45-4.5) and oral levothyroxine was started. He was discharged with oral hydrocortisone and levothyroxine replacement. A repeat MRI of the pituitary 2 months later showed complete resolution of the mass and resolution of the mass effects. He was kept on oral hydrocortisone and levothyroxine replacement with regular follow-up.Most pituitary macroadenomas are non-functional, and can present with complications of apoplexy, mass effects or hormonal disturbances. However, the natural history of non-functional macroadenomas is not well known as most are operated on. Spontaneous regression of the tumour can rarely occur, notably in the setting of apoplexy and lymphocytic hypophysitis. Recovery of the pituitary axis may also accompany tumour regression. As spontaneous remission of pituitary macroadenomas may occur, close observation of tumours without visual field defects or significant mass effects may be an alternative to surgery. Presentation: 6/1/2024 12:15:00 PM

7527 Subacute Thyroiditis in First Trimester of Pregnancy: Rare Cause of Thyrotoxicosis

Abstract Disclosure: K. Wilcher: None. A. Gupta: None. Background: Subacute thyroiditis (SAT) is extremely rare in pregnancy with only 8 prior cases reported in the literature. SAT can result in maternal and fetal complications. In this case report, we describe a case of subacute thyroiditis presenting in the first trimester of pregnancy. Case Presentation: A 38-year-old female with past medical history of stillbirth presented with thyrotoxicosis in gestational week 10 of her pregnancy. The patient has a history of stillbirth in gestational week 38 of her first pregnancy requiring cesarean section one year prior to presentation. She was in the process of getting in vitro fertilization (IVF) and had an egg retrieval. During the process, she started on thyroxine 50 mcg daily for blood thyroid-stimulating hormone (TSH) 3.77 mcIU/mL. She became pregnant without the help of IVF and stopped thyroxine. One month later, labs showed low TSH 0.022 mcIU/mL (reference range: 0.4-4.5 mcIU/mL) and high blood free thyroxine (FT4) 1.87 ng/dL (reference range: 0.7-1.8 ng/dL). Repeat labs two weeks later showed low blood TSH 0.012 mcIU/mL, high FT4 2.08 ng/dL, and high blood free triiodothyronine (FT3) 5.2 pg/mL (reference range: 2.3-4.2 pg/mL). She was referred to endocrinology for evaluation. She reported mild intermittent right sided neck pain since diagnosis of pregnancy. She denied any history of viral infection, cough, or fever. She reported symptoms of severe nausea, mild constipation, and mild anxiety. She denied diarrhea, tremors, changes in voice, palpitations, or weight loss. Her family history is significant for hypothyroidism in her father. Physical exam demonstrated a non-tender, symmetric thyroid without enlargement or nodules. Ultrasound showed heterogenous thyroid with an ill-defined heterogenous area in the right lobe appearing pseudo-nodule, and increased vascularity. At this time, the patient was diagnosed with mild gestational hyperthyroidism with a plan to monitor thyroid hormone levels. Repeat labs two weeks later showed low blood TSH 0.005 mcIU/mL, high FT4 2.35 ng/dL, and high FT3 6.4 pg/mL. TSH-receptor antibodies, thyroid stimulating immunoglobulin, and thyroid peroxidase antibodies were normal on testing. In gestational week 16, labs showed normal TSH 2.76 mcIU/mL, low FT4 0.56 ng/dL, and low FT3 2.1 pg/mL. At that time, she started on levothyroxine 75 mcg daily and was diagnosed with subacute thyroiditis. Follow up labs in gestational weeks 18, 20, and 24 showed improvement in TSH and FT4 on thyroid hormone supplementation. Conclusion: This case report discusses the findings of SAT in first trimester pregnancy. Currently, she is in gestational week 28 and still requiring thyroid hormone supplementation. SAT in pregnancy is very rare. This case report significantly contributes to the literature and current knowledge of the prevalence, presentation, and disease process of subacute thyroiditis in first trimester pregnancy. Presentation: 6/2/2024

7988 A Case of Spontaneous Pituitary Hemorrhage in Late Pregnancy

Abstract Disclosure: D. Poudyal: None. G.L. Prince: None. Background: Pituitary apoplexy (PA), caused by hemorrhage into the pituitary gland, is rare. The prevalence in pregnancy is also quite rare, with PA complicating 1 in 10,000 pregnancies. PA usually occurs in patients with pre-existing pituitary adenomas. Spontaneous pituitary hemorrhage (PH) causing PA in the absence of a known adenoma or other precipitating factors is less frequently described. Presenting symptoms of PA are non-specific and can pose diagnostic challenges, yet PA must be managed urgently and decisively due to the risk of life-threatening hormonal deficiencies that can ensue. Physiologic changes in pregnancy pose additional challenges in evaluating and managing patients with possible PA. Here we present a case of spontaneous PH during the third trimester of pregnancy in the absence of pre-existing pituitary pathology or known precipitants. Case presentation: A 31-year-old female, G2P1, with an uncomplicated first pregnancy, presented with acute-onset headache and vision loss at 36 weeks gestation. Her symptoms resolved spontaneously in 45 minutes. MRI brain without contrast showed hemorrhage within the left aspect of the pituitary gland, a mildly displaced infundibulum, but no mass effect on the optic chiasm. MRI brain obtained 1 year prior for headache was unremarkable. Lab work showed an 8AM cortisol of 19 ug/dL (Ref range 3.7 - 19.4 ug/dL), and a total T4 of 11.3 ug/dL (Ref 4.9 - 11.7 ug/dL). Ultimately, interpretation of her cortisol testing was limited by: elevated cortisol-binding globulin in the high-estrogen state of pregnancy, elevated cortisol production by an intact hypothalamic-pituitary-adrenal (HPA) axis during the latter portion of pregnancy, and the lack of validated cutoff values for 8AM serum cortisol levels during pregnancy. In light of these factors and the risk of undiagnosed adrenal insufficiency (AI), she was treated empirically with oral hydrocortisone. Subsequently, she had an uneventful vaginal delivery, supported by stress dosing of her steroids. Postpartum, she had a normal 8AM cortisol level of 14 ug/dL, and she was noted to quickly begin breastfeeding without incident. Conclusion: PA remains a critical diagnosis that cannot be missed in patients presenting with concerning symptoms and signs, in order to identify and treat life-threatening hormonal deficiencies. Pregnancy poses unique challenges in diagnosing hormonal deficiencies such as AI due to normal physiologic changes affecting the HPA axis as well as other pituitary axes. Therefore, the benefit of empiric hydrocortisone treatment likely outweighs any associated treatment risk in cases with consistent symptomatology and radiographic findings. Presentation: 6/2/2024

5150 When Few Options Exist: Graves’ Disease Treated with Potassium Iodide and Levothyroxine Block-and-Replace Therapy

Abstract Disclosure: O. Magvanjav: None. S.K. Majumdar: None. Background: In the US, methimazole and propylthiouracil are effective first-line agents for the treatment of Graves’ disease. However, side effects including liver dysfunction may limit their use. In such instances, alternative non-conventional agents such as potassium iodide (KI) may be considered. Here, we present a case of a patient with Graves’ disease successfully treated with KI, drawing on the example of similar treatment experiences in Japan. Clinical case: Our patient is a 29-year-old woman who presented with a 3-week history of palpitations accompanied by fatigue, heat intolerance, itchiness, insomnia, and unintentional weight loss. Exam was notable for tachycardia (135 bmp), elevated blood pressure (BP) (150/81 mmHg), normal temperature, slight thyromegaly, brisk reflexes, mild anxiousness, and tremulousness. She was found to have a TSH of 0.007 mIU/ml (normal: 0.270-4.200 mIU/ml), elevated free T4 of 5.19 ng/dl (normal: 0.80-1.70 ng/dL), total T3 of 330 ng/dl (normal: 72.0-153.0 ng/dl), total T4 of 12.1 ug/dl (normal: 4.5-11.7 ug/dl), and positive antibodies (TSI 443%; TRAB 5.42 IU/L). A thyroid ultrasound showed diffuse hyperemia and a 1.4 cm right lobe TR3 nodule. She had a normal baseline neutrophil count with mild eosinophilia; a baseline hepatic function panel was not obtained. She was started on methimazole 20 mg daily and metoprolol XL 50 mg daily for symptom control. One week into treatment, a hepatic function panel showed elevated liver enzyme levels: AST 70 U/L (normal: 10-35 U/L) and ALT 223 U/L (normal: 10-35 U/L); previous values from 2 years prior were normal. Repeat levels a few days later showed increasing liver enzyme levels (AST 83 U/L; ALT 268 U/L) despite decreasing thyroid hormone levels. Methimazole was stopped, and she was then seen by a gastroenterologist, who concurred with the possibility of an adverse drug reaction to methimazole. She declined definitive therapy with surgery or radioactive iodine therapy and wanted to pursue alternative and less invasive options. Drawing on a previous successful experience from Japan, we initiated her on KI (50 mg twice daily), which resulted in normalization of her thyroid hormones within two weeks of initiation. She subsequently developed hypothyroidism 2 months later, at which point we initiated block-and-replace therapy with the addition of 50 mcg of levothyroxine. Her liver enzymes normalized with normalization of thyroid hormones. Conclusions: We present a patient with symptomatic Graves’ disease who was successfully treated with KI in the setting of limited treatment options, specifically an adverse reaction to methimazole (transaminitis), and who declined both surgery and radioactive iodine. This case demonstrates that KI may be useful in Graves’ disease as either a bridge to more definitive therapy when thioamides are not tolerated, or perhaps as a treatment option for those most likely to go into remission. Presentation: 6/1/2024

6469 Supplement Misadventures: A Case Of Acute Heart Failure, Cardiogenic Shock, And Hormonal Dysregulation Secondary To Surreptitious Use Of Multiple Hormonal Supplements

Abstract Disclosure: K.N. Grennan: None. S. Thota-Kammili: None. A.L. McKenna: None. C.G. Coyle: None. S.L. Samson: None. Introduction: Supplement misuse in the bodybuilding community is prevalent. With the availability of internet ordering and purchasing, patients have access to hormonal supplements without prescription or regulation. Here we present the case of a patient on self-administered hormonal supplements who presented in acute heart failure leading to cardiogenic shock in the setting of concurrent thyroid, adrenal, and gonadal axis dysfunction. Case Description: A 28-year-old male with no significant medical history was transferred to our hospital after presenting to an outside emergency room with dyspnea, cough, nausea, and a subjective fever. He developed acute hypoxic respiratory failure requiring intubation. Echocardiogram performed showed an ejection fraction (EF) of 10%. He was started on two vasopressors and methylprednisolone 1 g daily for two days, due to concern for myocarditis versus giant cell arteritis. Hormonal work-up showed TSH 0.02 mIU/L (normal range 0.3-4.2), free T4 0.4 ng/dL (0.9-1.7), total T3 48 ng/dL (80-200), FSH <0.3 IU/L (1.2-15.8), LH <0.2 IU/L (1.3-9.6), ACTH <5.0 pg/mL (7.2-63), cortisol 1.7 mcg/dL (2.5-12), estradiol 171 pg/mL (8.0-35), total testosterone 1730 ng/dL (240-950), and prolactin 47 ng/mL (4.0-15.2). He received 10 mg dexamethasone at the outside facility. A medication bag found by his family included online purchases of non-prescribed testosterone cypionate and enanthate, liothyronine, anastrozole, and clomiphene. None were medical grade. He was also taking the anabolic steroid clenbuterol for 3 days prior. Echocardiogram on day 3 of admission showed an improved EF of 36%. Cardiac magnetic resonance imaging (MRI) showed a papillary fibroelastoma and myocarditis. Patient was weaned off vasopressors and the ventilator. He was discharged on levothyroxine 50 mcg daily and hydrocortisone 10 mg twice daily for outpatient reassessment. Transesophageal echocardiogram confirmed diagnosis of papillary fibroelastoma. One month Endocrinology clinic follow-up showed no evidence of posterior pituitary, thyroid, or adrenal axis dysfunction or growth hormone excess, but he continued to have gonadal axis suppression with elevated prolactin and estradiol, the latter thought to be secondary to conversion from testosterone. Pituitary MRI showed no micro or macroadenoma. His EF recovered to 50%. He is pending surgical removal of the aortic valve fibroelastoma. Discussion: With hormonal supplements easily accessible online, it is important for physicians to counsel patients about the dangers of misuse. This case highlights a previously healthy 28-year-old man who presented in critical condition with cardiogenic shock and hypothalamic-pituitary axis dysfunction from supplements he purchased online. There should be targeted educational interventions regarding the harm of supplements aimed at the bodybuilding community to prevent similar cases. Presentation: 6/2/2024

7507 Early Detection of Hyperglycemia Using CGM Despite Reduced Dosing of Teprotumumab

Abstract Disclosure: L. Needleman: None. S.H. Kim: None. A.L. Kossler: None. C. Dosiou: None. Background: In a previous longitudinal observation study, we showed that patients with prediabetes increased HbA1c by a mean of 0.7% and 30% progressed to type 2 diabetes after treatment with teprotumumab for 3 months, or after 4 infusions [1]. However, temporal effects of hyperglycemia and the impact of lower doses of teprotumumab on hyperglycemia are unknown. Clinical case: An 86-year-old woman was diagnosed with Graves’ disease after evaluation for palpitations showed undetectable TSH, free T4 2.31 ng/dL (ref. 0.8-1.8 ng/dL), total T3 252 ng/dL (ref. 76-181 ng/dL), and elevated TSI (5.0, ref. <1.3). Thyroxine levels normalized four weeks after starting methimazole. Nine weeks after the initial presentation she developed diplopia and bilateral proptosis. She was diagnosed with active moderate-to-severe thyroid eye disease (CAS 4/7) and was started on teprotumumab 10 mg/kg intravenously every three weeks. The dose was not increased to 20 mg/kg due to concern for adverse effects given the patient’s age and underlying hearing impairment. At baseline, she had prediabetes based on a HbA1c of 6.0%. Additional risk factors for type 2 diabetes included older age and Asian race [1]. Continuous glucose monitoring (CGM, Dexcom G7) before starting teprotumumab showed 71% time in tight range (TITR, 70-140 mg/dL) with average fasting glucose of 115 mg/dL. Prior to starting teprotumumab, she received counseling for lifestyle modification including carbohydrate moderation. Ten days following her first teprotumumab dose, her TITR reduced to 66%. After three doses of teprotumumab, her proptosis improved by 2 mm, CAS decreased to 1/7, and diplopia resolved. However, the TITR was 59% and average fasting glucose increased to 128 mg/dL. HbA1c also increased to 7.4% and the patient was started on metformin. Conclusion: In this case, teprotumumab increased glucose as early as after the first infusion. Glucose tolerance continued to worsen with subsequent doses, with development of type 2 diabetes, even with reduced dosage of teprotumumab. This case demonstrates that monitoring for teprotumumab-related hyperglycemia can be optimized with use of CGM and that lower doses of teprotumumab do not eliminate the risk of worsening glucose tolerance. Whether hyperglycemia would have been more severe with full dose teprotumumab remains uncertain. Reference: [1] Amarikwa L, Mohamed A, Kim SH, Kossler AL, Dosiou C. Teprotumumab-Related Hyperglycemia. J Clin Endocrinol Metab. 2023 Mar 10;108(4):858-864. Presentation: 6/3/2024

7165 A Case of Severe Myxedema Coma with Levothyroxine Allergy

Abstract Disclosure: A. Rothstein Costris: None. A. Yaseen: None. S. Levy: None. Introduction: Myxedema coma is a life threatening condition with a mortality rate of 25-60%. Untreated, it can lead to fatal physiological changes. The treatment is thyroid hormone replacement therapy, alongside supportive care for complications. Clinical Case: A 65-year-old woman, who has been dealing with untreated hypothyroidism since 2012 and reported allergies to various levothyroxine brands, presented with falls, weakness, and exacerbated leg numbness. During the examination, she exhibited periorbital edema, non-pitting edema in the lower extremities, bradycardia, and hypothermia. The blood work revealed an elevation in TSH levels at 301 uIU/L (0.45-5.33 uIU/mL). The patient was administered IV Synthroid (200 mcg), Atropine, and Hydrocortisone due to concerns about myxedema coma. After four hours, the patient experienced angioedema and hypotension, necessitating intubation. This situation was complicated by a pulseless electrical activity (PEA) arrest. Following cardiopulmonary resuscitation and the administration of epinephrine, the patient achieved return of spontaneous circulation. The allergy team assessed the patient for potential anaphylactic shock from IV Synthroid. Subsequently, the patient was initiated onIV Liothyronine and Hydrocortisone, leading to improvement in mental status over a period of a few weeks, and no adverse effects were reported. Thyroid labs improved to TSH of 53 (0.45-5.33 uIU/mL), FT3 of 3.3 (2.5-4.4 pg/mL) and total T3 of 133 (87-178 ng/dl). Upon discharge, the patient was prescribed Liothyronine, with plans to perform a Levothyroxine desensitization test in the outpatient setting. Conclusion: Myxedema coma is an endocrine emergency. Patients usually present with deteriorating mental status, hypothermia, and multiple organ system abnormalities. The diagnosis relies more on the clinical presentation and physical examination than on laboratory results. Thyroid replacement therapy serves as the cornerstone of treatment, with a preference for T4 due to its greater availability and lower likelihood of adverse events compared to Liothyronine, which may increase the risk of mortality at higher doses. Despite associated risks, incorporating low doses of Liothyronine is still considered in treatment plans, driven by concerns about reduced T4 to T3 conversion in myxedema patients. Hypersensitivity reactions to Levothyroxine are uncommon but may manifest as widespread hives, swelling, eczema-like skin rashes, elevated body temperature, and compromised liver function, with only one case reporting an anaphylactic reaction to Levothyroxine. In summary, the potential for experiencing an anaphylactic reaction to Levothyroxine exists, highlighting the need to contemplate alternative treatments, such as Liothyronine. Desensitization methods can be considered once the patient's condition is stable. Presentation: 6/2/2024

Association of hepatitis B virus and thyroid hormones during pregnancy

This study aims to evaluate the correlation between serum thyroid hormone levels and hepatitis B virus (HBV) DNA and HBV genotypes in pregnant women with chronic hepatitis B. A total of 96 pregnant women with chronic HBV-infected pregnant women between January 2020 and December 2022 were selected as the observational study subjects. About 50 HBV-uninfected pregnant women during the same period were selected as the control group. Serum thyroid hormone levels at different stages of pregnancy, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroperoxidase antibody (TPOAb), and thyroglobulin antibody (TGAb), were compared between the 2 groups. Thyroid hormones levels were also compared between HBV-DNA-positive and HBV-DNA-negative women in the HBV-infected pregnancy group, and to determine the correlation between thyroid hormones levels and HBV-DNA load and HBV genotype in HBV-DNA-positive pregnant women. The TSH levels in mid and late pregnancy and TPOAb levels in early, mid, and late pregnancy of HBV-infected pregnant women were higher than those in the same period in HBV-uninfected pregnant women (P < .05). The TPOAb and TGAb levels in early, mid, and late pregnancy of HBV-DNA-positive pregnant women were higher than those in the same period in HBV-DNA-negative pregnant women (P < .05). The HBV-DNA load and FT3 or FT4 levels were negatively correlated (P < .05), and the HBV-DNA load and TGAb levels were positively correlated (P < .05). However, there was no statistical difference in thyroid hormone levels between different HBV genotypes (P > .05). The thyroid hormone levels will change in pregnant women infected with hepatitis B virus, and there is a certain correlation between HBV-DNA load and thyroid hormone levels. Therefore, timely monitoring of thyroid hormones and HBV-DNA load can provide early prevention and treatment for HBV infection in pregnant women, ensuring the health of pregnant women and fetuses.

Subclinical Hyperthyroidism Enhances Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women.

Metformin treatment decreases elevated concentrations of anterior pituitary hormones. The aim of this prospective, cohort study was to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function. The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55-3 g daily). Plasma glucose, insulin, thyroid-stimulating hormone (TSH), total and free thyroid hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin-like growth factor-1 (IGF-1) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1-IR], and glycated hemoglobin [HbA1c]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA1c in response to metformin treatment. Although metformin decreased HOMA1-IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (-50 ± 20% vs -30 ± 15%). Similar relationships were observed for FSH (-43 ± 21% vs -21 ± 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 ± 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF-1. The obtained results indicate that hyperthyroidism enhances the gonadotropin-lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic-pituitary-thyroid axis in case of its overactivity.

B-113 Beckman Coulter DxI 9000 immunoassay analyzer assay performance meets new CLIA 2024 performance goals with highest proportion of Six Sigma performance amongst all major manufacturers

Abstract Background The Clinical Laboratory Improvement Act (CLIA) proficiency testing (PT) criteria will be updated in July 2024 with some goals tightening by up to 40%. It is assumed, but not known, that all assays and instruments will be able to achieve these goals. Using these new CLIA 2024 goals, estimates of current instrument group performance from an international proficiency testing (PT) survey have shown significant differences in quality, calling into question which assays can achieve the new CLIA goals. Currently, the highest performing diagnostic instrument achieves only 35.2% 6-Sigma, while the majority of instruments have less than 15% 6-Sigma performance indicating a higher probability of future PT failures. Methods Eighteen assays that will be governed by new CLIA 2024 goals were assessed for Sigma metric performance on the DxI 9000 immunoassay analyzer: Alpha Fetoprotein (AFP), Beta hCG, Carcinoembryonic antigen (CEA), Cortisol, Creatine Kinase MB (CK-MB), Estradiol, Ferritin, Folate, Follicle-Stimulating Hormone (FSH), Prolactin, Para-thyroid hormone (PTH), Total Prostate specific antigen (Total PSA), Testosterone, Thyroid Stimulating Hormone (TSH), Total Triiodothyronine (TT3),high sensitivity Troponin I, Total Thyroxine (TT4) and Vitamin B12. Precision and bias were determined following CLSI EP5 and EP9 guidelines, measured across 3 reagent lots. CLIA 2024 PT criteria provides the allowable total error for the standard Sigma-metric calculation: Sigma-metric = (TEa - |bias|) / SD Performance of the other major analyzers was assessed using the methodology introduced in 2006 by Westgard JO and Westgard SA. The Sigma-metric predicts future problems with PT and potential optimization of QC procedure opportunities, including fewer Westgard Rules, control levels, even reduced QC frequency and materials leading to less cost and time saved. Results Half (50%) of the assays on DxI 9000 achieves 6-Sigma, outperforming all other major manufacturers in the market who range from only 5% to 35% 6-Sigma. Further, over 78% of the DxI 9000 performance was 4Sigma and higher. Less than 8% of performance fell below 3-Sigma, which was observed at the extreme ends of the reportable range. Conclusions The DxI 9000 assay performance is well designed to meet CLIA 2024’s new PT criteria and has the highest prevalence of 6-sigma assay performance observed on market when compared to the top 5 major instrument manufacturers. Assays with Sigma metrics at 4-Sigma and higher are unlikely to face analytical PT difficulties and can be optimized for reduced Westgard Rules, control levels, and potentially even QC frequency.

Management of immune-checkpoint inhibitor (ICI)-related thyroid dysfunction: An avenue for quality improvement.

309 Background: Hypothyroidism is a common immune-related adverse effect (irAE) with ICI therapy, occurring in 4-9% of patients treated with PD-1 ICI, and 10-15% of patients treated with dual PD-1/CTLA-4 ICI therapy. Prolonged thyroid dysfunction increases risk for cardiovascular and cerebrovascular events. Consensus guidelines recommend weight-based dosing for thyroid repletion in younger patients and/or without cardiovascular comorbidities. We observed that patients on thyroid repletion are often underdosed compared to guideline recommendations. To formally evaluate this, we performed a retrospective study to determine the percentage of ICI-treated cancer patients who are receiving guideline-recommended thyroid repletion at an urban comprehensive cancer center. Methods: We identified patients who received PD-1 ICI, either singly or in combination with chemotherapy, TKI, or other ICI to identify patients who met the consensus guideline criteria for weight-based dosing of thyroid repletion. Analysis was restricted to ICI-treated patients who had a thyroid stimulating hormone (TSH) level above 10 mU/L following initiation of therapy. For each patient, we collected the patient’s age, weight, and initial prescribed dose of levothyroxine. We also obtained the date of abnormality and normalization for TSH and free thyroxine (T4). Results: 402 patients received ICI, either singly or in combination. 55 patients had TSH > 10 mU/L. 15 patients who did not have documentation of hypothyroidism or developed it prior to immunotherapy were excluded. The proportion of patients who were eligible for, and who received weight-based repletion is summarized in the table. The proportion of patients who received guideline-recommended thyroid repletion was: 6/17 (35%) SITC-guideline recommended dose, 18/27 (67%) NCCN-guideline recommended dose and 6/22 (28%) ASCO-guideline recommended dose. The median time to free T4 normalization was 9 weeks (IQR 6-15 weeks) and TSH normalization was 13 weeks (IQR 9-30 weeks). Conclusions: At an urban comprehensive cancer center, the incidence of hypothyroidism in ICI-treated cancer patients is 10%. The compliance with guideline recommended weight-based dosing is low, with 33-72% of patients not receiving appropriate therapy, translating into prolonged time to thyroid function normalization. We aim to develop a quality improvement intervention to improve thyroid dosing in this patient population. Proportion of patients receiving guideline-recommended thyroid repletion. Criteria Per SITC Guidelines Per NCCN Guidelines (if lower end of dosing range) Per ASCO Guidelines Patients eligible for weight-based dosing 17 27 22 # of patients who received appropriate initial dosing 6 (35%) 18 (67%) 6 (28%) Average initial dose prescribed 81 mcg 78 mcg 76 mcg Average initial dose per guidelines (based on ideal body weight) 107 mcg 71 mcg 109 mcg

Early life air pollution exposures and thyroid function in children: a prospective cohort study

Studies on early life ambient air pollution exposures and childhood thyroid function are scarce. This study aimed to evaluate the relationships between early life fine particulate matter (≤ 2.5 μm; PM2.5) and nitrogen dioxide (NO2) exposures and thyroid function in children. We measured the levels of thyrotropin, triiodothyronine, and free thyroxine in children (n = 684) residing in a rural Korean area at age 2, 4, 6, or 8 years from 2012 to 2020 in the Environment and Development of Children cohort. The relationship between residential average exposure levels of PM2.5 and NO2 during pregnancy and 1-year average levels before visit and thyroid function during childhood were analyzed. Inverse association between increases of 10 μg/m3 in PM2.5 during the first trimester and thyrotropin levels at aged 4 (β, -0.12; 95% CI: -0.22, -0.02) and 6 years (β, -0.16; 95% CI: -0.26, -0.06) were observed. No association was found between PM2.5 exposure during the second and third trimester and childhood TSH levels. Childhood PM2.5 exposure was positively associated with thyrotropin rise at aged 4 (β, 0.2; 95% CI: 0.06, 0.35) and 6 years (β, 0.16; 95% CI: 0.02, 0.29) and inversely related with free thyroxine levels at aged 8 years (β, -0.04; 95% CI: -0.07, -0.01). No relationship between NO2 exposure and thyroid function was found. In conclusion, association between PM2exposure and childhood thyrotropin levels varied depending on exposure timing. Early gestational exposure showed an inverse relationship, whereas childhood exposures were positively associated with childhood thyrotropin levels. The long-term effects of early life air pollution exposure and underlying mechanisms should be investigated in future studies.

Prevalence of physiological and perceptual markers of low energy availability in male academy football players: a study protocol for a cross-sectional study

Low energy availability (LEA) is a core feature of the female athlete triad and relative energy deficiency in sport (REDs). LEA underpins multiple adverse health and performance outcomes in various...

Energy availability and its association with health-related outcomes among national athletes at risk of relative energy deficiency in sports (REDs)

BackgroundLow energy availability (LEA) occurs when athletes’ energy intake fails to match the energy expended during exercise, resulting in insufficient energy to support essential functions for optimal health, a condition...

8423 Pattern of Thyroid Function Tests Variation Among an Elderly Population

8423 Pattern of Thyroid Function Tests Variation Among an Elderly Population

Dynamic analysis of Hashimoto’s Thyroiditis bio-mathematical model using artificial neural network

This article establishes an efficient solution scheme for a mathematical model of Hashimoto’s Thyroiditis (HT) employing artificial neural networks. HT is an auto-immune disorder hostile to the thyroid follicle cells, effectuating hypothyroid or hyperthyroidism. Under this condition, the thyroid-stimulating hormone (TSH) alters incomparably to the free thyroxine (FT4) interrupts the functioning of the hypothalamus-pituitary-thyroid (HPT) axis, implicating the thyroid follicle cells getting destroyed. We primarily focus on utilizing artificial neural network (ANN) to perform numerical simulations for the system of ordinary differential equations describing the dynamics of an existing 4D model of HT. The presented model comprises four time-dependent variables: TSH, FT4, anti-thyroid antibodies (Ab), and size of the thyroid gland (T). We utilize ND-Solver and ANN scheme in the Mathematica software to acquire the computational data and illustrate thus retrieved results with essential performance plots. Further, mean square error has been considered in validating the proposed ANN-based approach accurately. The plot for training and validation loss exhibits the effectiveness of the proposed methodology, and substantiate that the suggested ANN approach is a good fit for the solving the mathematical model of HT.

Comparative Analysis of Oxidative Metabolism in Liver in Different Experimental Models of Hypothyroidism: Low Iodine Diet and Anti-Thyroid drug (Methimazole)

Objectives: On the concept of oxidative stress in hypothyroidism, which still remains ambiguous and controversial, the article emphasizes the issue of the impact of the experimental conditions on the validity of the data obtained in different methods of modeling thyroid dysfunction. Materials and Methods: Experiments were conducted on 112 white nonlinear male rats. Thyroid hormones and biomarkers of oxidative metabolism in the liver tissue were determined in rats kept for 3 months on a low-iodine diet (LID) and in rats with methimazole (MMI)-induced hypothyroidism (2,5 mg/100 g of body weight for 3 weeks). Results: In LID-rats (n=96) total serum T4 amounted 43, total T3 in liver tissue - 73% of the level found in euthyroid animal, p=0.0121 and p=0.0051, respectively), whereas in MMI-rats (n=96) both total and free serum T4 were 67% of control (p=0.0002 for both total and free T4). In LID-rats cytochrome oxidase (CcOX) activity in liver tissue was 68.5, concentration of malondialdehyde (MDA) - 58% of euthyroids (p value - 0.0202 and 0.0127, respectively), while protein carbonyls (PC) level was 116% of the control (p=0.0411). In MMI-rats liver malate dehydrogenase (MDH) activity decreased up to 70.9, but succinate dehydrogenase (SDH) activity and MDA concentration increased up to 163.6 and 154% of the level in euthyroid animals respectively (p˂0.05). Conclusion: LID-model led to the more pronounced inhibition of thyroid function, than that the MMI-hypothyroidism model used. LID-model was accompanied by a decrease in the intensity of oxidative metabolism in liver tissue, whereas MMI-hypothyroidism - by activation of the succinate oxidation pathway and an increase in the concentration of secondary lipid peroxidation products in the liver of experimental animals. The results suggest that the conflicting data obtained from studies of oxidative metabolism in hypothyroidism, among other assumptions, may be due to the different approaches used by researchers to model thyroid dysfunction.

Thyroxine Replacement Therapy during Ramadan Fasting: A Narrative Review

Abstract Introduction Ramadan fasting-induced changes in eating and sleeping patterns pose a risk of influencing thyroid hormone levels. There is a recognition of the potential impact of fasting and feasting on levothyroxine (L-T4) absorption. Materials and Methods A narrative, nonsystematic literature review from two major medical online databases (PubMed and Google Scholar) from their inception to the search day (February 22, 2024). A relevant combined search term was used. The retrieved literature is narrated in a concise account. Results There is a relationship between metabolism and thyroid-stimulating hormone (TSH). This relationship contributes to transient metabolic disturbances that influence the pharmacodynamics and pharmacokinetics of various drugs, adding complexity to the management of hypothyroidism during Ramadan fasting. Several observational studies have studied the changes in thyroid function levels during unmodified L-T4 regimens. Experimental trials explored the impact on body weight, well-being, and thyroid functions when the timing of L-T4 administration changes. Findings are far from homogeneous due to different study protocols. A recent meta-analysis demonstrated a significant post-Ramadan increase in TSH levels among euthyroid patients. L-T4 timing points, encompassing pre-Iftar, post-Iftar, and pre-Suhoor, are associated with elevated TSH levels after Ramadan fasting. The emphasis on individualized L-T4 regimens during Ramadan fasting is underscored, with recommendations for patients to refrain from food for at least 3 hours before and 30 minutes after L-T4 intake to ensure optimal compliance by most experts. The association between adherence to L-T4 during Ramadan fasting and maintaining euthyroid status is highlighted, encouraging patients to follow prescribed regimens diligently. Modified dosing frequencies, such as weekly regimens, exhibit promising results, especially in patients grappling with compliance issues. Proactive consultations with physicians before Ramadan are needed to review the latest thyroid function test and make possible dose adjustments. Conclusion Managing hypothyroidism during Ramadan necessitates an understanding of medication timing, food-drug interactions, and prior regimens. Adherence, facilitated by flexibility, plays a critical role in achieving euthyroid status.

Combined Levothyroxine and Propylthiouracil Treatment in Children with Monocarboxylate Transporter 8 Deficiency: A Multicenter Case Series of 12 Patients.

Objective: To evaluate the combined administration of propylthiouracil (PTU) and levothyroxine (LT4) in managing monocarboxylate transporter 8 (MCT8) deficiency and identify optimal therapeutic dosages. Methods: This multicenter case series involved 12 male patients with MCT8 deficiency whose parents/guardians consented to PTU and LT4 treatment. Data were collected from January 2008 to June 24, 2024. The study focused on treatment safety and outcomes, analyzing baseline and last encounter biochemical, metabolic, and anthropometric parameters. Statistical analyses included Wilcoxon signed ranks tests and generalized estimated equations to assess effects on thyroid and metabolic markers, and receiver operating characteristics curves to predict optimal dose. Results: Patients showed a significant reduction in serum total triiodothyronine (TT3) concentration and TT3/TT4 ratio, with increased serum TT4 and free T4 (fT4) concentrations. The use of PTU effectively reduced TT3 concentration by 25% at an average dose of 6.8 mg/kg/day, while LT4 increased fT4 concentration by 40% from baseline at an average dose of 4.3 µg/kg/day. Thyrotropin concentration was undetectable on treatment. No statistical differences were observed in metabolic and physical parameters between baseline and last encounter overall for the group, but six of eight patients for whom these data were available had an increase in weight (z-score). There were no adverse effects on liver function or granulocyte numbers noted throughout the period of observation. Conclusion: Combined treatment with PTU and LT4 normalized serum T3, fT4, and TT4 in patients with MCT8 deficiency. Individualized dose adjustments were crucial for achieving therapeutic goals, indicating the need for personalized treatment plans.

Seasonal and Sexual Variations in Corticosterone and Total Triiodothyronine: A Pilot Study in Mediterranean Tortoises (Testudo hermanni)

The Mediterranean tortoise Testudo hermanni inhabits different regions bordering the northwestern Mediterranean. This species is vulnerable, protected by legislation, and involved in various breeding and reintroduction programs. Wild populations face numerous environmental and anthropogenic stressors that can potentially interfere with their conservation. While seasonal changes in stress-response biomarkers, such as glucocorticoids and thyroid hormones, have been widely studised in mammals and birds, there is a paucity of research in reptile species. Therefore, the present study aimed to evaluate the seasonal fluctuations in corticosterone and total triiodothyronine levels in adult and juvenile Hermann’s tortoises (Testudo hermanni) as a measure of the physiological stress response. Blood samples were collected seasonally (winter, spring, summer, and autumn) and posteriorly analyzed by using a specific and validated enzyme immunoassay for both hormones, respectively. The results showed that corticosterone levels varied seasonally and differed between sexes, whereas total triiodothyronine levels changed seasonally but did not differ between sexes. Notably, juveniles exhibited no seasonal changes in either corticosterone or total triiodothyronine levels. Additionally, no correlation between blood extraction duration and hormonal concentrations was observed. This study is pioneering in its comprehensive evaluation of corticosterone and total triiodothyronine changes across all four seasons, including winter, and its focus on juvenile Hermann’s tortoises.