Elevated Thyroid-stimulating Hormone Research Articles

Challenges in Thyroid Function Testing: Interferences and Clinical Implications

In recent decades, significant advancements have been made in the methodologies used for evaluating thyroid dysfunctions. These advancements include the development of radioimmunoassays, immunometric assays, and liquid chromatography coupled with mass spectrometry. The main thyroid function tests include thyroid-stimulating hormone (TSH) and the measurement of triiodothyronine (T3) and thyroxine (T4), including their total and free fractions. Over time, different generations of TSH tests have been developed, starting from radioimmunoassays to immunometric assays, and more recently, tests utilizing fluorophores and chemiluminescent molecules. The third-generation tests are currently the most widely used due to their high sensitivity and specificity. Thyroid-stimulating hormone is preferred as the initial test for evaluating thyroid function since it has a log-linear relationship with free T4 levels, enabling the identification of subclinical hypothyroidism and subclinical hyperthyroidism. The reference range for normal TSH levels is typically between 0.45 and 4.5 mIU/L. However, there can be variations in TSH levels based on factors such as sex, age, and ethnicity. Specific reference values may be required for certain populations, such as the elderly, pregnancy, and neonates. In the elderly, an increase in TSH levels is expected. In the neonatal period, TSH levels are high after birth and take a few weeks to normalize. During pregnancy, various physiological changes occur, leading to alterations in thyroid hormones to meet fetal demands. Laboratory interferences in thyroid hormone assays must be considered to ensure accurate results. Biotin interference can lead to falsely low TSH and falsely high free T3 and T4 levels. Macro-thyrotropin can cause elevated TSH levels with normal thyroid hormone levels. Heterophilic antibodies can also cause false results. Additionally, the evaluation of autoantibodies and markers used in thyroid cancer follow-up needs special attention. Patients experiencing conditions like trauma, particularly in severe cases, may undergo changes in thyroid hormone levels, even without having a specific thyroid disease, which is called low triiodothyronine syndrome. In conclusion, it is essential to be aware of potential laboratory interferences and consider individual variations to ensure accurate interpretation and appropriate management of patients.

Exploring biomarkers of osteosarcopenia in older adults attending a frailty clinic

Osteosarcopenia is a new definitional approach that can increase the risk of falls and fractures in elderly compared with that of osteoporosis and sarcopenia alone. However, biomarkers for osteosarcopenia have not been well identified. Thus, we aimed to explore the biomarkers of osteosarcopenia, including bone, muscle, and geriatric markers. Outpatients attending a frailty clinic were enrolled in the study. Osteosarcopenia was defined as the coexistence of osteoporosis and sarcopenia. Osteoporosis was defined according to the criteria of the Japan Osteoporosis Society. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus (2019). We selected 35 blood/serum pathological parameters, including bone, inflammation, nutritional, and aging markers for the study. Logistic regression analysis for osteosarcopenia was performed to explore the biomarkers of osteosarcopenia. Of the total 600 patients with a mean age of 76.6 years, 595 were enrolled in the registry during the study period. Logistic regression analysis for osteosarcopenia showed that elevated thyroid-stimulating hormone (TSH) (odds ratio [OR]:1.375; 95 % confidence interval [CI]: 1.092–1.731), bone-specific alkaline phosphatase (BAP) (OR: 1.059; 95 % CI: 1.002–1.120), and estimated glomerular filtration rate (eGFR) (OR: 1.029; 95 % CI: 1.007–1.053) increased the likelihood of osteosarcopenia. On the other hand, elevated 25-hydroxyvitamin D (25OHD) (OR: 0.905; 95 % CI: 0.841–0.974), blood urea nitrogen (BUN) (OR: 0.895; 95 % CI: 0.829–0.966) and K (OR: 0.241; 95 % CI: 0.081–0.717) decreased the likelihood of osteosarcopenia. It is worthwhile to examine these biomarkers for older adult outpatients attending a frailty clinic for screening osteosarcopenia. Further studies are needed to investigate the effects of other markers of bone metabolism.

Age-specific serum thyrotropin reference range for the diagnosis of subclinical hypothyroidism and its association with lipid profiles in the elderly population

The overdiagnosis of subclinical hypothyroidism (SCH) in the elderly has driven researchers to establish age-specific thyroid stimulating hormone (TSH) intervals to precisely evaluate the prevalence of SCH. Moreover, abnormal lipid profiles, an insidious manifestation of SCH, show various impacts on different age groups. This study aimed to establish an age-specific TSH reference range to clarify the spectrum of SCH in the elderly. The prevalence of dyslipidemia and the age-specific association between TSH and lipid profiles were analyzed to elucidate the relationship between SCH and dyslipidemia. This cross-sectional study enrolled 2460 participants aged ≥ 65 years via cluster sampling. All participants received physical, laboratory tests and thyroid ultrasound examination and completed the questionnaire. The chi-square test was used to analyze variations of dyslipidemia prevalence among different groups. The Cochran-Armitage trend test was applied for testing the linear trends of age-specific prevalence of dyslipidemia among different TSH intervals in each age group. After adjusting for confounding factors, the age-specific association between TSH and lipid profiles was identified using multi-variate linear regression analysis. The TSH reference ranges in the 65–70 age group, 71–80 age group and > 80 age group were 0.65–5.51 mIU/L, 0.85–5.89 mIU/L and 0.78–6.70 mIU/L, respectively. Using these age-specific reference ranges, the prevalence of SCH in the whole population was 3.74%, which was significantly lower than the prevalence based on the laboratory reference range (10.28%). In the 65–70 age group, only the prevalence of high total cholesterol (TC) increased significantly with the age-specific TSH intervals, and TSH was positively associated with TC and low-density lipoprotein cholesterol (LDL-C). In the 71–80 and > 80 age groups, the prevalence of high TC, high triglycerides (TGs), and high LDL-C increased significantly with elevated TSH reference ranges. The levels of TC, TGs, and LDL-C were also positively associated with TSH level in 71–80 age group. However, such an association disappeared in > 80 age group. An age-specific reference range for TSH can effectively prevent the overdiagnosis of SCH in the elderly. Aging could somewhat attenuate the impact of TSH on lipid profiles.

The association between serum concentration of thyroid hormones and thyroid cancer: a cohort study.

The impact of serum thyroid hormone levels on thyroid cancer risk is unclear. Some studies reported that elevated thyroid-stimulating hormone (TSH) is associated with higher risk for incidence of thyroid cancer, but other studies reported no relationship. We conducted a large cohort study in 164,596 South Korean men and women who were free of thyroid cancer at baseline and underwent health examination with hormone levels of thyroid function. A parametric proportional hazard model was used to evaluate the adjusted hazard ratio (HR) and 95% CI. During 2,277,749.78 person-years of follow-up, 1280 incident thyroid cancers were identified (men = 593, women = 687). Among men, the multivariable-adjusted HR (95% CI) for thyroid cancer comparing low levels of TSH with normal levels of TSH was 2.95 (1.67-5.23), whereas the corresponding HR (95% CI) in women was 1.5 (0.88-2.55). High levels of free T4 and free T3 were also associated with incident thyroid cancer in both men and women. In clinical implication, overt hyperthyroidism is associated with thyroid cancer in both men and women. Within the euthyroid range, the highest tertile of TSH was associated with a lower risk of thyroid cancer than the lowest TSH tertile and the highest FT4 tertile was associated with a higher risk of thyroid cancer than the lowest FT4 tertile in both men and women. Our finding indicates that low levels of TSH and high levels of FT4, even within the normal range, were associated with an increased risk of incident thyroid cancer.

Thyroid Function in 509 Premature Newborns Below 31 Weeks of Gestational Age: Evaluation and Follow-up

Preterm and low birth weight (LBW) neonates may present with thyroid dysfunction during a critical period for neurodevelopment. These alterations can be missed on routine congenital hypothyroidism (CH) screening which only measures thyroid stimulating hormone (TSH). The objective of this study was to evaluate a protocol for thyroid function screening (TFS) six years after national implementation. Serum TSH and free thyroxine (fT4) were measured during the second week of life in neonates below 31 weeks. Patients with abnormal TFS (fT4 <0.8 ng/dL and/or TSH >5 mU/L) were followed up with repeated tests until normal levels were reported. Patients who were still on levothyroxine (LT4) at three years of age were re-evaluated. Five-hundred and nine neonates were included. Thyroid dysfunction was detected in 170 neonates (33%); CH n=20 (3.9%) including typical CH n=1; delayed TSH elevation CH n=19; hypothyroxinemia of prematurity (HOP) n=15 (2.9%); and transient hyperthyrotropinemia n=135 (26.5%). Twenty-one neonates (4.1%) were treated (20 for CH and 1 for HOP). At 3-year follow-up only three patients were diagnosed with permanent CH and still need treatment. LBW infants tended to have TSH levels higher than those with adequate weight. This protocol was able to detect thyroid dysfunction in preterm neonates who were not identified by the current program based on TSH determination in whole-blood. This thyroid dysfunction seems to resolve spontaneously in a few months in the great majority of neonates, but in some cases LT4 could be needed. There is a critical need for specific guidelines regarding the follow-up and re-evaluation of transient CH in preterm neonates.

Abstract 11878: Two Life-Threatening Conditions: Myxedema Coma and Type A Aortic Dissection

Case Presentation: A 59-year-old female with a history of hypertension was brought to a local hospital after being found unresponsive at home. Computed tomography angiography (CTA) of the chest showed type A aortic dissection (TAAD) with maximal aortic dimension of 9.0 cm. She was transferred to our center for escalation of care. She had poor neurological status but stable hemodynamic status, without malperfusion or acute cerebrovascular accident. Lab studies showed severely elevated thyroid-stimulating hormone of 80.4 mIU/ML and free thyroxine 4 (T4) less than 0.2 ng/dL, indicating severe hypothyroidism consistent with myxedema coma. Due to her low functional baseline status, surgical repair was deferred. Anti-impulse therapy was initiated with short acting beta blocker and calcium channel blocker infusion to maintain control of heart rate (HR) and blood pressure (BP). Her clinical course was complicated by pulseless electrical arrest and acute renal failure. After 100 mcg of intravenous levothyroxine, she was extubated and regained renal function. After 40 days, she was discharged to an acute rehabilitation center. 6 weeks later, she showed marked improvement in her frailty index, and medications were optimized. She underwent elective aortic repair, coronary bypass surgery, and was discharged to home. Discussion: Due to the patient’s initial neurological status, repair of her TAAD with aneurysmal degeneration was deferred. She was later diagnosed with myxedema coma and her TAAD was deemed chronic rather than acute . Surgical repair of both acute and chronic TAAD remains the gold standard; however, medical therapy with strict control of HR and BP parameters may stabilize the patient for future surgical repair. 1,2 In this case, by treating the patient’s underlying hypothyroidism and managing risk factors, her surgical risk was reduced, and she underwent successful aortic repair, reporting drastically improved functional status and quality of life.

Abstract 14091: Severe Hypothyroidism Revealing Hidden Tracts

Discussion: Atrioventricular reciprocating tachycardia (AVRT) is a type of Supraventricular tachycardia (SVT) caused by an accessory pathway can result in symptomatic and also life-threatening arrhythmias. Supraventricular tachycardias are less commonly seen in hypothyroidism than hyperthyroidism. We present a case of a 41 year old gentleman who presented with chest pain and SVT was found to have severe hypothyroidism with pre-excitation pattern on his EKG. Case: 41-year-old Caucasian gentleman with history of untreated Hashimoto’s thyroiditis presented with palpitations and acute onset left-sided chest pain. His symptoms were aggravated with movement and improved with rest. When EMS found him, his vitals were significant for tachycardia with a heart rate (HR) of 200 beats per minute (bpm). EKG showed supraventricular tachycardia. Vagal maneuvers were attempted followed by adenosine. This resulted in conversion to sinus rhythm and improvement in HR to 88 bpm. His chest pain completely resolved. He was then brought to the emergency room where he had normal vitals. Examination revealed thyroid gland was palpable and noted to be diffusely enlarged. Laboratory data was significant for an elevated thyroid-stimulating hormone (TSH) of 373 mIU/ml and undetectable free thyroxine (fT4) levels. His creatinine kinase (CK) was high at 16260, and troponin was elevated at 0.220 ng/ml (reference:&lt;0.04 ng/ml). TPO antibodies were &gt;600 IU/ml. EKG demonstrated sinus rhythm with pre-excitation and incomplete left bundle-branch block. He had normal chest x-ray. An echocardiogram showed an ejection fraction of 55% with mild LV diastolic dysfunction. He later underwent a stress myocardial perfusion scan which showed no definite evidence of inducible ischemia. Follow up: He was started on thyroxine replacement therapy. He is due for an EP study to evaluate for an accessory pathway causing pre-excitation with repolarization pattern on his ECG. Conclusion: This case suggests that severe hypothyroidism can also cause supraventricular tachycardias (SVT) by metabolic and conduction derangements revealing concealed bypass tracts in patients with accessory pathways. In most cases these arrhythmias are reversible once the underlying thyroid disorder is treated.

Radiation-Induced Hypothyroidism in Patients with Breast Cancer after Hypofractionated Radiotherapy: A Prospective Cohort Study

<h3>Purpose/Objective(s)</h3> To assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiotherapy (RT) in patients with breast cancer, and identify the dose constraint for the thyroid gland. The trends of RHT over time were also evaluated to determine the optimal timing of screening for RHT in breast cancer patients treated with hypofractionated RT. <h3>Materials/Methods</h3> Consecutive eligible breast cancer patients who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times following RT (every 3-4 months during the first two years, then every six months until five years). RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT. The incidence of RHT was calculated from the end of RT using the Kaplan–Meier method, and the differences between groups were compared with the log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. A multivariate Cox proportional hazards regression model with penalized spline (P-spline) was used to examine the relationship between thyroid mean dose (Dmean) and RHT. A two-sided test of P < 0.05 was considered statistically significant. <h3>Results</h3> A total of 500 patients treated between 2017 and 2020 were analyzed. All patients underwent chest wall/breast ± regional nodal irradiation with a prescription dose of 43.5Gy in 15 fractions. Among them, 369 (73.8%) patients received supraclavicular nodal radiation (SCRT). Eighty-two (16.4%) patients had elevated TSH before RT. At a median follow-up of 21.9 months, 131 (26.2%) patients developed RHT, and 59 (11.8%) patients received thyroid hormone-replacement therapy. The 2-year cumulative incidence of RHT was 26.0%. Patients with SCRT had a significantly increased 2-year cumulative incidence of RHT compared with patients without SCRT (31.5% and 11.4%, p<0.001). The median time to the onset of RHT was 9.3 months (range, 1.0-42.4) after RT. The peak incidence of RHT occurred around 6-12 months after RT. Multivariate analysis revealed that elevated baseline TSH and increased thyroid Dmean as a continuous variable were independent risk factors for developing RHT. After adjusted for baseline TSH, there was a nonlinear relationship between Dmean and the risk of RHT. Dmean > 21 Gy was identified as the threshold value for predicting RHT (HR=2.2, p<0.001). Dmean > 21 Gy compared with Dmean ≤ 21 Gy was associated with a significantly higher incidence of RHT at two years after RT (17.0% vs. 32.2%, P<0.001). <h3>Conclusion</h3> The incidence of RHT was high in breast cancer patients. Thyroid function test should be started no later than six months following RT. We recommend that the Dmean of the thyroid should be kept lower than 21Gy for hypofractionated RT.

LBSAT367 Association Of Thyroid Functioning With Depression: A Population-based Historical Cohort Study

Abstract Background Despite the abundance of literature, the relationship between hypothyroidism and depression is not clearly defined. We conducted this study to investigate the association of thyroid functioning [measured by serum Thyroid Stimulating Hormone (TSH) level] with depression [measured by Patient Health Questionnaire-9 (PHQ-9)] in a population-based study. Method: This is a cross-sectional and longitudinal study, which included all adult patient who received care at the Marshfield Clinical Health System from 2015 through 2020 and had one or more TSH and PHQ-9 measurement pair within 6 months. Logistic regression was used to estimate the effect of TSH level on depression in patients without or with thyroid diseases (untreated thyroid disease- not on any thyroid medications and treated thyroid disease - on thyroid medications). Candidate models included depression regressed on (1) TSH, (2) log-transformed TSH, (3) TSH level: normal (0.5-4.9), elevated (5. 0-9.9), very elevated (≥10), and model fit statistics were used to select the TSH-level model. Patient characteristics that were significantly associated with TSH level were included as covariates including Charlson Score. Results 127,587 unique patients with 236,799 pairs of PHQ-9 and TSH were identified from Electronic Medical Record (EMR) data base. The average age was 53.6 (19.1) years, 90.4% were Caucasians, and 66.2% were females. 87.8% had no depression, 4.4% had minimal depression, and 3.6% had moderate depression, while rest had severe depression. 5.4% had low TSH, 85.8% had normal TSH, 6.8% had elevated and 2. 0% had very elevated TSH. 38.6% had thyroid disease, off which 32.6% were treated In adjusted model, patients without thyroid disorder did not have an increased risk of depression with elevated and very elevated TSH. However, patients with untreated thyroid disorder had increased risk of depression with very elevated TSH (OR=2. 08, 95% CI: 1.39-3.12), while patients with treated thyroid disorder had increased risk of depression with elevated (OR=1.15, 95% CI: 1. 03-1.27) and very elevated TSH (OR=1.26, 95% CI: 1.11-1.42) Conclusions: This large cohort study suggests that there is no association between TSH and depression in patients without any thyroid disorders. However patients with thyroid disorders do have higher risk of depression with elevated TSH level. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT366 Liquid L-thyroxine (L-T4) Formulation Normalizes TSH in Hypothyroid Patients Treated with Tablets L-T4

Abstract The absorption of L-thyroxine (L-T4) can be affected by different factors, such as the manner of L-T4 assumption (during breakfast, or with food), the age of the patient, the interference with other drugs, absorption kinetics, adherence to therapy, and others. L-T4 tablets malabsorption can occur due to the increased gastric pH in patients in treatment with proton pump inhibitors (PPI; omeprazole, pantoprazole, lansoprazole) for gastritis, gastric ulcer, etc. We enrolled 25 patients in treatment with L-T4 in the tablet formulation, and with elevated serum thyroid-stimulating hormone (TSH) levels; they were switched to the same dose of an oral liquid L-T4 preparation. A normalization, or reduction, of circulating TSH levels occurred after the switch from L-T4 in tablet formulation to the liquid one (at the same dose). Eleven of these subjects who, for different reasons, were switched back again to assume L-T4 in tablets (with the same dosage), had a worsening of TSH levels, reaching the hypothyroid range. Our results show that the pH alteration issue due to PPI could be overcome by the assumption of the oral L-T4 liquid formulation. Other future studies are needed to investigate liquid L-T4 formulation also in other conditions of altered L-T4 absorption. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP529 Update on the Prevalence and Pathogenesis of Central Hypothyroidism

Abstract Background Central hypothyroidism (CH) is a rare form of hypothyroidism characterized by insufficient stimulation of a normal thyroid gland by the thyroid-stimulating hormone (TSH). It can be of pituitary origin (secondary hypothyroidism) or hypothalamic origin (tertiary hypothyroidism). The diagnosis is suspected by the finding of low serum free thyroxine associated with low, normal, or slightly elevated serum TSH, in the absence of goiter. This review presents an update on the prevalence and pathogenesis of different types of CH. Methods A systematic search of literature was conducted using the search terms hypothyroidism, central hypothyroidism, congenital central hypothyroidism, acquired central hypothyroidism, TSH deficiency, prevalence, and pathogenesis. Results The prevalence of overt hypothyroidism in the US population is at least 0.3% and the prevalence of subclinical hypothyroidism ranges from 4% to 10%. Primary hypothyroidism is more prevalent in females. The prevalence of CH ranges from 1: 13,000 to 1: 120,000. CH is observed in less than 1% of hypothyroid subjects, with no evidence of sex predominance. Itcan occur prenatally (congenital CH) or after birth (acquired CH). Congenital CH, which is a rare cause of CH (prevalence around 1: 13,000), may result from genetic/malformative causes [e. g., pituitary-specific transcription factor defects, TSH-beta subunit gene mutations, isolated TSH-releasing hormone (TRH) deficiency, TRH receptor gene mutation, immunoglobulin superfamily member 1 deficiency, De Morsier syndrome, Prader Willi syndrome]. In 60% of the cases, congenital CH is associated with other pituitary hormone deficiencies and in 40% of the cases, congenital CH is due to isolated TSH deficiency. Acquired CH, which is the most common cause of CH andusually associated with other pituitary hormone deficiencies, results from the destruction or inhibition of the pituitary and/or hypothalamus. In decreasing order of frequency, acquired CH can be secondary to invasive and/or compressive lesions (e. g., pituitary macroadenomas, craniopharyngiomas, pituitary metastases, carotid aneurysm), iatrogenic factors (e. g., surgery or irradiation, glucocorticoids, dopaminergic drugs, somatostatin analogs, immune checkpoint inhibitors), trauma (e. g., brain injury), vascular causes (e. g., pituitary apoplexy, postpartum pituitary necrosis, hemorrhage), autoimmunity (e. g., lymphocytic hypophysitis), infiltrative lesions (e. g., hemochromatosis, sarcoidosis), and infections (e. g., tuberculosis, syphilis). Conclusion CH is a rare cause of hypothyroidism resulting from a variety of congenital or acquired causes. Acquired CH is the most common cause of CH. In many cases, both congenital and acquired CH are associated with multiple pituitary hormone deficiencies. Isolated TSH deficiency is rare and usually of congenital origin. Presentation: No date and time listed

PSUN39 A rare presentation of autoimmune thyroid diseases and myasthenia gravis: A clinical case report

Abstract We report a case of a 37-years-old female that presented with a three-week history of diplopia, ptosis, muscle weakness, difficulty chewing, tachycardia, and fatigue; these clinical symptoms were concerning for acute myasthenia gravis crisis. The diagnosis of Myasthenia gravis was further confirmed by a positive immunology workup. Chest CT imaging during her assessment showed anterior mediastinal mass/enlarged thymus indicative of thymic hyperplasia. Medical therapy with intravenous immune globulin, pyridostigmine and further treatment with high-dose steroid. She had a positive response to treatment but still reported persistent symptoms of fatigue, tachycardia, and intermittent diplopia, raising suspicions for underlying Graves’ thyrotoxicosis. Thyroid function testing was performed which showed a very suppressed thyroid-stimulating hormone (TSH) and elevated Free t4 levels. Further workup for Graves thyroid autoimmune antibodies indicative of extremely elevated thyroid stimulating hormone receptor autoantibodies consistent with Graves’ disease. We initiated medical therapy for Graves’ disease with a beta-blocker and thioamide (methimazole). She endorsed progressive improvement in her symptoms following treatment for Grave's disease. She was discharged with high dose steroids, pyridostigmine, and appropriate therapy for Graves’ disease. She did well after her discharge from the hospital and six months afterwards she returned to the hospital for a robot-assisted right thymectomy. Final pathology report indicative of non-thymomatous myasthenia gravis. She continued to follow up with us in the endocrinology outpatient clinic. Her steroid therapy was tapered off and medical therapy for Graves’ disease was continued accordingly. She demonstrated a positive response to medical therapy with remarkable improvement in the remaining of her symptoms, especially her neurological and ocular symptoms after initiation of treatment for Graves’ disease. Conclusion we report two rare concomitant autoimmune diseases, myasthenia gravis, and Graves’ disease. Both conditions have similar overlapping clinical features making diagnosis and treatment challenging in clinical practice. It is well reported in clinical literature and studies that hyperthyroidism may worsen symptoms of MG and management of hyperthyroidism in the setting of MG may lead to worsening of myasthenia symptoms; hence, certain precautions should be taken to avoid worsening symptoms of myasthenia gravis. Therefore, we call for more case-control, case series and clinical trials to explore more clinical knowledge about the association between the two conditions and formulate better management strategies. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP635 A rare case of metastatic papillary thyroid carcinoma on NTRK inhibitor with thyrotoxicosis

Abstract We present a case of 26-year-old Hispanic female with neck enlargement and worsening dyspnea. She was noted to have enlarged thyroid nodules; biopsy revealed papillary thyroid carcinoma (PTC) with ETV6-NTRK fusion by next-generation sequencing (NGS). Further work up revealed extensive bilateral milliary pulmonary metastases and Graves’ disease with elevated thyrotropin receptor antibodies and thyroid-stimulating immunoglobulin titers. Tuberculosis work up was negative and bronchoalveolar lavage revealed metastatic PTC. The patient was initiated on larotrectinib (100mg administered twice daily) as well as block-and-replace regimen with levothyroxine and methimazole. Her dyspnea improved and she successfully underwent total thyroidectomy as well as bilateral neck dissections; methimazole and thyroid hormones were discontinued thereafter. Interestingly, patient developed thyrotoxicosis post-surgery even without being on levothyroxine with elevated free T3 at 18 pg/mL (normal range 2.3–4.2), compared to 5.8 pg/mL prior to surgery. Despite discontinuation of levothyroxine, patient continued to be biochemically and clinically hyperthyroid. She was treated with methimazole for 4 months after surgery, and subsequently underwent radioactive iodine (RAI) ablation with 30 mCi of I-131 of sodium iodide. After RAI, thyroid function started to improve, prompting re-initiation of very low dose levothyroxine about 5 months after surgery. Since then, she has remained clinically stable. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Changes in the content of hormones of hypothalamic-pituitary-thyroid axis in growth of single and multiple primary tumors in the presence of comorbidity

Introduction. Thyroid dysfunction is known to be associated with higher risks of cancer development. The purpose of this study was to analyze levels of thyroid axis hormones in the hypothalamus, pituitary gland, thyroid, and blood serum of male and female Balb/c nude mice with B16/F10 melanoma and/or lewis lung carcinoma. Material and methods. Male and female Balb/c nude mice were divided into groups: 1 – intact mice (n=7), 2 – mice with b16/f10 melanoma (n=7), 3 – mice with lewis lung carcinoma (LLC) (n=7), 4 – mice with melanoma and LLC (n=7). Levels of thyroid-stimulating hormone (TSH), triiodothyronine (fT3), and thyroxine (fT4) were measured by ria in homogenates of the hypothalamus, pituitary gland, thyroid and blood serum of all animals, and TH-releasing was measured by ELISA. Statistical processing of results was performed using the Statistica 10.0 program. Results. TH-releasing was reduced in the hypothalamus of all tumor-bearing mice, compared to initial values. TSH levels in the pituitary gland and thyroid were changed only in males with the combination of tumors (increased by 2.8 and 1.5 times, respectively). Levels of free forms of hormones in the thyroid in animals of both genders sharply increased, together with the elevation of TSH in the blood serum and, as a result, the decrease of fТ3 and fТ4 levels. Conclusion. Female and male Balb/c nude mice of the studied groups demonstrated hypothalamic dysfunction manifested by the absence of regulation in the hypothalamus-pituitary-thyroid relationship, and by the hypothyroid status of animals.

Clinical and genetic characteristics for 4 patients with Type Ib pseudohypoparathyroidism.

Pseudohypoparayhyroidism (PHP) is a rare autosomal dominant or recessive genetic disorder characterized by low calcium, high phosphorus, and target organ resistance to parathyroid. The clinical characteristics and genetic features in 4 patients with Type Ib PHP in the Third Xiangya Hospital, Central South University, have been reviewed. All 4 patients had low calcium, high phosphorus, and parathyroid resistance. Among them, 2 patients had slightly elevated thyroid stimulating hormone and mild features of Albright's hereditary osteodystrophy, and one patient had hypokalemia. No guanine nucleotide-binding protein alpha-stimulating activity polypeptide 1 (GNAS) and gene variant associated with hypokalemia were identified using the whole exome sequencing. The results of the methylation-specific multiple ligation-dependent probe amplification showed that there were abnormal methylation of the upstream differentially methylated regions of GNAS in the 4 patients. There were phenotype overlap among the various subtypes of PHP. Detection of GNAS gene methylation in patients with clinical suspicion of Type Ib PHP is helpful for the diagnosis and treatment of PHP.

Radiation-Induced Hypothyroidism in Patients With Breast Cancer After Hypofractionated Radiation Therapy: A Prospective Cohort Study

Our objective was to assess the incidence and risk factors of radiation-induced hypothyroidism (RHT) after adjuvant hypofractionated radiation therapy (RT) in patients with breast cancer. Eligible patients with breast cancer who were treated with hypofractionated RT were prospectively evaluated. Thyroid function tests were performed before and at regular times after RT. RHT was defined as twice elevated serum thyroid-stimulating hormone (TSH) with decreased or normal free thyroxin after RT. The patient, tumor, and treatment factors were evaluated for possible associations with the risk of RHT. Five hundred patients were analyzed. All patients underwent chest wall/breast with or without regional nodal irradiation. Among them, 369 (73.8%) patients received supraclavicular nodal radiation (SCRT). Eighty-two (16.4%) patients had elevated TSH before RT. At a median follow-up of 21.9 months, 131 (26.2%) patients developed RHT, and 59 (11.8%) patients received thyroid hormone-replacement therapy. Patients with SCRT had a significantly increased 2-year cumulative incidence of RHT compared with patients without SCRT (31.5% and 11.4%, P<.001). The peak incidence of RHT occurred around 6 to 12 months after RT. Multivariate analysis revealed that elevated baseline TSH and increased thyroid mean dose (Dmean) were independent risk factors for developing RHT. After adjusted for baseline TSH, there was a nonlinear relationship between thyroid Dmean and the risk of RHT. Dmean >21 Gy was the threshold value for predicting RHT (hazard ratio, 2.2; P<.001). The incidence of RHT was high in patients with breast cancer. Thyroid function test should be started no later than 6 months after RT. We recommend that the Dmean of the thyroid should be kept lower than 21 Gy for hypofractionated RT.

Sustained remission of psychotic symptoms secondary to hypothyroidism (myxedema psychosis) after 6 months of treatment primarily with levothyroxine: a case report

BackgroundPsychotic symptoms associated with hypothyroidism, also known as “myxedema psychosis,” are a treatable cause of psychosis often associated with complete recovery. While most cases receive both thyroxine and a short course of antipsychotics, some reports indicate that symptoms can resolve without antipsychotic treatment, though follow-up in these cases has often been short or not reported. This is one of the first case reports demonstrating sustained remission of psychotic symptoms at 6 months in a case of myxedema psychosis treated with minimal antipsychotic medication.Case presentationWe describe the case of a 40-year-old Caucasian woman who was brought to hospital with a 7-day history of anxiety and decreased sleep and 1 day of disorganized speech, paranoid delusions, and auditory hallucinations. After being admitted to psychiatry for management, screening blood work revealed elevated thyroid-stimulating hormone. The patient was initiated on treatment with levothyroxine and low doses of antipsychotics. Her symptoms resolved on the third day of her admission with ongoing symptomatic remission at 6 months follow-up.ConclusionsThe identification of myxedema psychosis is important owing to the implications on treatment and prognosis of the disorder. Our case suggests that sustained symptom resolution may occur with little to no antipsychotic treatment, though these findings are preliminary and additional study is needed before definitive conclusions on the optimal approach can be made.

Hashimoto’s encephalopathy masquerading as affective illness: a case report

BackgroundHashimoto’s encephalopathy (HE) is a rare but controversial syndrome showing a variety of neurological and psychiatric manifestations associated with autoimmune thyroiditis.Case presentationWe present a case of 46-year-old hypertensive female who developed acute onset of behavioral symptoms mimicking affective disorder (mania). Investigations revealed high levels of anti-thyroid peroxidase antibodies with elevated thyroid-stimulating hormone. EEG and MRI findings were consistent with those seen in Hashimoto’s encephalopathy. She showed excellent response to high dose corticosteroids that helped in making the diagnosis of Hashimoto’s encephalopathy.ConclusionsHashimoto’s encephalopathy is an extremely important, though rare, diagnosis. It should be suspected and screened for in patients with encephalopathy of unknown origin because responses to treatment are usually excellent.

Elevated thyroid-stimulating hormone (TSH) is associated with atrial fibrillation and directly modulates electrophysiological properties of atrial cardiomyocytes

Abstract Background Thyroid dysfunction has a strong association with cardiac arrhythmias. However, subclinical hypothyroidism (SH) is often neglected in studies. SH is characterized by increased values of TSH and normal values of T3/T4. Recent studies indicate that high TSH levels are related to an increased incidence of cardiac electrical abnormalities, especially atrial fibrillation (AF). Purpose The present work aims to investigate direct effects of TSH on ion channel remodelling in cardiomyocytes and a possible causative role in the increased occurrence of arrhythmia in SH. Methods A retrospective monocentric study analysed medical records, ECGs and echocardiographies of 3134 patients between 2007 to 2020. Inclusion criteria comprised patient age ≥18 years, normal fT4, TSH values 4–75 mU/l and available ECGs. The patient cohort was divided into two groups based on current treatment recommendations for SH (TSH level 4–9.9 mU/l; 10–75 mU/l). Direct effects on ion channel remodelling were analysed in HL-1 and neonatal cardiomyocytes with confirmed expression of TSH receptors. TSH concentrations of 15, 30, and 60 mU/l simulated different degrees of hypothyroidism. RT-qPCR analyses, western blots and immunofluorescence stainings were performed after incubation with respective TSH concentrations for 24h. In vitro video analyses of automatism in NRCM before and after TSH incubation were performed. Statistical comparisons were calculated using student's t-tests and the chi-square test. In addition, a multivariate analysis of factors affecting the occurrence of AF in patients with SH was carried out. Results Elevated TSH levels were associated with higher prevalence of AF. In the group of patients with a TSH value of 10–75 mU/l, AF was observed in 42.8% of cases compared to 31.7% in patients with lower TSH levels (p&amp;lt;0.0001). In vitro, TSH application to cardiomyocytes led to significant changes in mRNA and protein expression of key ion channels and regulatory proteins. Incubation of HL-1 cells with 15 mU/l TSH showed a decrease in Kcne1 protein, while 60 mU/l TSH caused an upregulation of K2P3.1 (TASK-1), Kv7.1, and KCa2.1 expression. To further elucidate the TSH signaling cascade in cardiomyocytes, we investigated TSH effects on PKAα, CaMKIIδ and CaMKIIγ. PKAα was upregulated after 24h incubation with 60 mU/l TSH and exhibited an increase of the phosphorylated state. Finally, neonatal cardiomyocytes showed an increased beating rate after incubation with TSH. Conclusion The prevalence of atrial fibrillation is significantly increased in patients with SH. Our findings further reveal a direct effect of TSH on ion channel expression in cardiomyocytes as potential proarrhythmic mechanism. TSH induced changes in the expression of ion channels that determine action potential duration. Subclinical hypothyroidism contributes to the development of atrial fibrillation. Underlying mechanisms and therapeutic implications require further research. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Heidelberg University Medical School - Olympia Morata

ASSESSING THE UTILITY OF SIMULTANEOUS CO-TESTING APPROACH WITH THYROID STIMULATING HORMONE (TSH) AND THYROID PEROXIDASE (TPO) ANTIBODY TESTING IN INFERTILE WOMEN

Thyroid stimulating hormone (TSH) levels >2.5 mIU/L in the presence of thyroid peroxidase (TPO) antibodies have been associated with adverse pregnancy outcomes but treatment with levothyroxine has been shown to improve outcomes. Many fertility centers initiate treatment when TSH is >2.5 without evaluating TPO antibodies though benefits are unclear when TPO antibodies are negative. By forgoing TPO antibody testing, patients with elevated TSH but negative TPO antibodies are not identified. Therefore, we sought to identify the number of patients needing to undergo co-testing (NNT) with TSH and TPO antibodies to identify 1 patient with TSH >2.5 and negative TPO antibodies.