bluuebunny/crossref_metadata_2025 huggingface dataset:
PMON210 Ovariectomy of Middle-Aged Female Mice Leads to Decreased Fat Oxidation and Energy Expenditure Accompanied by Weight Gain and Dysregulated Blood Glucose
Authors: Stokar Joshua , Gurt Irina , Lishinsky Natan , Offir Neta , Dresner-Pollak Rivka
Published: November 2022

Introduction

In humans, menopause brings upon total body weight gain with increased visceral adiposity and a resulting increase in cardiometabolic risk profile. Although well described, the specific sequence and underlying mechanisms for this remain elusive. Rodent ovariectomy (OVX) is routinely used as an animal model for the study of human menopause but is often performed in young reproducing specimen, failing to replicate the complex interaction of concomitant chronological aging with the loss of sex hormones observed in humans. In this study we used middle-aged ovariectomized mice to explore the effect of concomitant estrogen deficiency with chronological aging on key aspects of cardiometabolic health and energy expenditure.

Methods

10-month-old C57BLj/6 female mice, were subjected to a SHAM or OVX procedure and followed for 6 weeks post-surgery (n=5 per group). Non-fasting blood glucose (BG) and body weight were measured weekly. Prior to sacrifice mice were observed in metabolic cages using the Promethion Metabolic Phenotyping System (Sable Systems International). Body composition including total body fat and lean mass were evaluated by EchoMRI. A Reduction in uterine weight was used to confirm successful OVX.

Results

Relative to baseline weight, OVX mice weighed 13% more than SHAM mice 6-weeks after surgery (p= 0.04; t-test) with no significant change in body composition. Non-fasting BG was consistently higher throughout the study period in OVX vs SHAM mice (p<0.01; ANOVA). OVX mice exhibited an increased respiratory quotient (0.84 vs 0.81; p<0.01; t-test) driven by a reduction in fat oxidation (24 vs 34 g/d/kgeff. mass p<0.000; t-test). OVX mice showed a 17% percent decrease in total energy expenditure in both the light and dark phases (p<0.01), driven by a 38% percent decrease in ambulatory activity (p=0.04) and close to a 3-fold decrease in wheel running (p<0.001). No significant change was observed in overall food or water intake between the groups.

Discussion

It is difficult to detangle the complex web of causes and effects relating to the deranged metabolic phenotype induced by menopause. Here we show that even without additional insults such as a high-fat-diet or genetic manipulation, the combination of chronological aging at middle-age with the sex hormone deficiency resulting from OVX, led to an increase in total body weight, a dysregulated glucose profile and a deranged energy expenditure pattern. Additional studies are warranted using similar animal models to tease out cause and effect as well explore novel therapeutics and biomarkers for the rapidly increasing population of post-menopausal women at risk for cardiometabolic disease.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON211 Energy metabolism hormones irisin and leptin affect steroidogenesis in human granulosa cells: in vitro studies
Authors: Avtanski Dimiter , Poretsky Leonid , Singer Tomer , Stojchevski Radoslav , Ziskovich Karina
Published: November 2022

Energy metabolism and reproduction are closely linked; however, the role of the individual energy metabolism hormones in this association is still poorly understood. Irisin is a hormone produced mostly by skeletal muscle cells during exercise or shivering, and leptin is a satiety adipokine synthesized by the white adipose tissue. The aim of this study was to investigate the in vitro effects of irisin and leptin on steroidogenesis in cultured human granulosa cells. The cells were purified from follicular fluid samples from patients undergoing in vitro fertilization (IVF). Primary cell cultures were treated with increasing concentrations of irisin (0, 125, 250, 500, 1,000, and 2,000 ng/ml) or leptin (0, 25, 50, 100, 200, and 400 ng/ml) for 24 hours and subjected to qRT-PCR analysis for the expression of key steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A1, HSD3B1, and HSD17B3). Concentrations of progesterone, testosterone and estradiol in the conditioned cell culture medium were measured using ELISA. Results demonstrated that both irisin and leptin significantly upregulated CYP19A1 mRNA expression. Leptin also increased the expression of HSD3B1 mRNA levels. Although not statistically significant, leptin produced a trend of increasing estradiol production after 24 hours of treatment. Taken together, these data support the hypothesis that irisin and leptin may affect steroid hormone metabolism in the ovary by modulating the expression of key steroidogenic enzymes.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON244 Alterations in Nonesterified Free Fatty Acids (NEFA) Trafficking Rather Than Hyperandrogenism Contribute to Variations in Insulin Sensitivity Among Obese Women with Polycystic Ovary Syndrome
Authors: Azziz Ricardo , Chen Ida Y , Ezeh Uche
Published: November 2022

Objectives

To compare the metabolic and hormonal features of metabolically unhealthy obese PCOS women (MU-PCOS) vs. metabolically healthy obese PCOS women (MH-PCOS) and determine whether alterations in non-esterified free fatty acids (NEFA) response to hyperinsulinemia contribute to variations in insulin sensitivity between MU-PCOS and MH-PCOS.

Design

Prospective cross-sectional study.

Setting

Tertiary-care academic center.

Methods

Insulin resistance (IR) in the basal state was assessed by HOMA-IR in 125 consecutive obese oligo-ovulatory PCOS women (BMI≥ 30 kg/m2; NIH 1990 or Rotterdam 2003 Phenotype A/B) undergoing an oral glucose tolerance test (oGTT); and IR in the dynamic state assessed by the modified frequently sampled intravenous glucose tolerance test (mFSIVGTT) in a subgroup of 16 non-diabetic obese PCOS women.

Main Outcome Measures: Primary outcome measures were: 1) IR in AT was assessed in the basal state by the Adipose Insulin Resistance Index [Adipo-IR]) and dynamically by the mFSIVGTT-derived indices of insulin-mediated NEFA suppression [NEFAnadir, TIMEnadir, and %NEFAsupp]); 2) peak lipolysis rate [SNEFA]; and 3) peak NEFA uptake rate [KNEFA]. Secondary outcome measures were levels of insulin and glucose during oGTT, HOMA-β%, and degree of hyperandrogenism (i.e. mF-G score, free testosterone [T], total T, DHEAS).

Results

Eighty-five obese PCOS participants undergoing oGTT had a HOMA-IR index of ≥2.5 (MU-PCOS) and 40 had a HOMA-IR of <2.5 (MH-PCOS). MU-PCOS had higher mean HOMA-β%, levels of fasting, 1-hr and 2-hr. glucose and insulin, and peak insulin during the oGTT, and higher prevalence of prediabetes and elevated 1-hr. glucose and a trend towards higher prevalence of type 2 diabetes mellitus (T2DM), than MH-PCOS. Alternatively, measures of HA were similar between the groups. Assessing IR dynamically, subjects were subdivided into MU-PCOS by an insulin sensitivity index [Si] ≤1.7 [mU/L]−1·min−1 (n=8) or MH-PCOS by an Si ≥5.6 [mU/L]−1·min−1 (n=8), matched for age and BMI. MU-PCOS had lower Si and KNEFA, smaller %NEFAsupp, longer TIMEnidar, and higher NEFAnidar and Adipo-IR than MH-PCOS, although fasting plasma NEFA levels and SNEFA were similar. In bivalent analysis, Si correlated strongly and negatively with NEFAnadir, weakly and negatively with TIMEnadir, and positively and strongly with KNEFA and NEFAsupp, in MUO-PCOS only.

Conclusion

Independent of age and BMI, metabolically unhealthy obese PCOS women, compared with metabolically healthy obese PCOS women, had lower rates of NEFA uptake and altered insulin-mediated plasma NEFA suppression in response to mFSIVGTT-determined endogenous insulin secretion, rather than disparities in HA and rate of lipolysis, mechanism that may contribute to variations in insulin sensitivity among obese PCOS women.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON248 Predictive value of markers of hyperandrogenism in 1610 women with PCOS
Authors: VanHise Katherine , Wertheimer Sahar , Handelsman Roy , Clark Ekaterina , Buttle Rae , Chan Jessica , Wang Erica , Azziz Ricardo , Pisarska Margareta
Published: November 2022

Polycystic ovary syndrome (PCOS), an endocrine disorder that affects 10% of women worldwide. In 1990, the NIH established the first consensus on diagnostic criteria for PCOS which included chronic anovulation with clinical and/or biochemical hyperandrogenism, after the exclusion of related disorders. Traditionally the assessment of hyperandrogenism included serum studies of total testosterone (TT), free testosterone (FT), and dehydroepiandrosterone sulfate (DHEA-S), and physical exam assessing hirsutism using the modified Ferriman-Gallwey (mFG) score. The most recent 2018 International Guidelines suggest the measurement of DHEA-S can be considered if TT or FT are not elevated, but probably provide limited diagnostic value. We evaluated the diagnostic utility of TT, FT, DHEA-S and hirsutism in a large prospective cohort of PCOS women.

Subjects presented to tertiary-care specialty clinics with symptoms of androgen excess in Birmingham, Alabama and Los Angeles, California from 1987-2010. Clinical hyperandrogenism was assessed using the mFG score, and hirsutism was defined as mFG >4. Participants underwent serum studies to assess for hyperandrogenemia and exclude other causes of hyperandrogenism. Fasting blood samples were obtained on cycle days 3 through 8 of a spontaneous or progesterone-induced vaginal bleed for measurement of TT, FT and DHEA-S. Elevated serum androgens were defined as values exceeding the laboratory reference range or greater than the 95th percentile of reported values. Subjects were considered to have oligomenorrhea if they reported >35 day cycles, <10 bleeds per year or reported being eumenorrheic but were confirmed non-ovulatory with a luteal phase progesterone <4 ng/mL. One thousand six hundred and ten women and adolescents (n=1610), aged > 14 years, were diagnosed with PCOS by NIH Criteria and included.

Of these 1610 subjects, 39.3% (n=643) were diagnosed with PCOS based upon an elevated TT and FT with oligomenorrhea; 23.9% (n=384) based upon an elevated TT, normal FT and oligomenorrhea; 11.3% (n=182) based upon an elevated FT, normal TT and oligomenorrhea; 1.1% (n=17) based upon oligomenorrhea with normal TT, normal FT and elevated DHEA-S; and 23.9% (n=384) based upon normal serum androgens, oligomenorrhea, and hirsutism (mFG>4).

Results suggest that the diagnosis of PCOS is rarely made based upon elevated DHEA-S in the setting of normal TT and FT. Most women had elevated TT and/or FT values, but still a significant proportion (23.9%) of women were diagnosed with PCOS based upon hirsutism in the context of normal serum androgens. Thus, an assessment of hirsutism, which is both timely and inexpensive, is a strong predictor and valuable tool in diagnosing PCOS, reserving DHEAS when better measures of hyperandrogenism are not diagnostic.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP065 Impact of Comorbid Adrenal Insufficiency on Outcomes During Hospitalization For Cardiogenic Shock
Authors: Kumi Dennis D , Ramirez Marcelo , Nissan Ninos , Patel Birju , Soon-shiong Raquel , Shrestha Prajwal , Karki Sadicchya
Published: November 2022

Background

The catabolic stress associated with cardiogenic shock requires a robust metabolic, neuroendocrine, and immunologic response to mitigate, and adrenocortical hormones play a huge role in this process. On the other hand, excessive aldosterone production is known to play a key part in the long-term progression of myocardial insufficiency through myocyte remodeling. It is thus intriguing to understand how adrenocortical insufficiency impacts the outcomes of patients admitted for cardiogenic shock. Method: A retrospective cohort study was designed using data obtained from the 2016 to 2018 combined National Inpatient Sample (NIS) database. Adult patients (age >18) with principal admission diagnosis of cardiogenic shock were identified using the international diseases classification code, tenth revision (ICD 10), and separated into two cohorts based on the presence of a secondary diagnosis of adrenal insufficiency. Primary outcomes assessed were, mortality, length of stay (LOS) and total hospital charge. Secondary outcomes evaluated included rate of mechanical ventilation, mechanical circulatory support device use and cardiac arrest. Multivariate linear and logistic regressions were used to adjust for confounders.

Results

There was a total of 477,695 adult hospitalizations for cardiogenic shock, out of which 1.28% had associated secondary diagnosis of adrenal insufficiency. There was a statistically insignificant increased odds of mortality among patients with adrenal insufficiency (33.42% vs 33.35%, AOR: 1. 05, 95% CI: 0.93 to 1.19, p: 0.462). There was also an increased length of stay (18.91 days vs 11.35 days, adjusted mean difference: 6.5 days, 95%CI: 5.22 days to 7.78 days, p < 0. 001) and an increased total charge (364,864.5 vs 238,591.9 USD, adjusted mean difference: 105,491.9 USD, 95%CI: 78,252.2USD to 132,731.3 USD, p < 0. 001) among patients with adrenal insufficiency compared with the counterpart cohort group and these were statistically significant. Patients with adrenal insufficiency also had 42% increased odds of being mechanically ventilated during cardiogenic shock admission compared to patients without (55.67% vs 46.61%, AOR: 1.42, 95%CI: 1.26 to 1.60, p < 0. 001). Other secondary clinical outcomes assessed, including mechanical circulatory support devices use and cardiac arrest were not statistically different between the two groups.

Conclusion

Adrenal insufficiency as a comorbid diagnosis among patients admitted with cardiogenic shock was associated with increased odds of requiring mechanical ventilation, prolonged length of stay and higher total hospital charges. There was a trend towards increased mortality, but this was not statistically significant. There was no difference in other clinical outcomes including mechanical circulatory support devices and cardiac arrest rate.

Presentation: No date and time listed
PMON284 Triamcinolone Cream-Induced Cushing Syndrome
Authors: Sacco Susana Barreiro , Francisco Barrera Echegoyen Francisco , Ferri-Guerra Juliana , Hannoush Zeina
Published: November 2022

Introduction

Iatrogenic Cushing syndrome (CS) is typically due to systemic corticosteroids. Less frequently, it can be caused by inhaled, ocular, intra-articular, and topical glucocorticoids.

There are multiple reported cases of pediatric CS due to topical corticosteroids, this is partly due to this patient's population thinner dermis which allows for higher absorption. In adults, there are few reported cases of iatrogenic CS secondary to Clobetasol, one of the highest potency topical steroids available. We present a unique case of severe Iatrogenic CS secondary to topical Triamcinolone in a patient with no medications that could interfere with glucocorticoid metabolism.

Case

A 30-year-old-female with Type 2 Diabetes Mellitus and psoriatic arthritis was admitted with generalized psoriatic lesions affecting 70% of her body surface area (BSA) and non-healing open wounds affecting two thirds of her upper legs. The leg wounds had failed to improve after seven washouts and three skin grafts in the course of four months. Additionally, she reported recent weight gain and a new diagnosis of hypertension. Pertinent physical exam findings included moon facies, dorsocervical fat pad, acanthosis nigricans, and open wounds in 67% of bilateral upper legs. Subsequently, her cortisol was found to be 1.2 mg/dL (6.2-19.4 mg/dL) with an ACTH level of 1.2 pg/mL (7.2-63.3 pg/mL). ACTH stimulation test confirmed adrenal insufficiency.

The only medication she was prescribed for psoriasis at the time of admission was 0.1% Triamcinolone cream. She had been applying the steroid to over 50% of her BSA, including open wounds, for the past four months. Upon admission, Triamcinolone was discontinued, and she was started on cyclosporine and a TNF inhibitor for psoriasis management as well as oral hydrocortisone for adrenal insufficiency. Three months later, during her last office visit, her facial rounding and plethora, dorsocervical fat pad and hypertension had moderately improved.

Discussion

To the best of our knowledge, this is the first reported case of adult iatrogenic CS secondary to topical Triamcinolone in the absence of any drug-drug interaction. Purser et al reported Triamcinolone induced CS in an HIV patient taking Ritonavir, a cytochrome P450 inhibitor that increases the amount of active steroid. Our patient had increased absorption due to the application of the cream to a large BSA and to open wounds. The two main factors that determine the development of iatrogenic CS are the potency of the glucocorticoids and the duration of exposure. The pathophysiology of wound healing in CS has been well studied and reported, therefore, the objective of this report is to understand how a relatively benign topical medication can have detrimental systemic effects.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBSAT290 Papillary Thyroid Cancer Discovered After Benign Afirma Gene Testing, A Case Report
Authors: Ahmad Mobeen , Thelmo Franklin , Ucciferro Peter
Published: November 2022

Introduction

Grave's disease is an autoimmune form of hyperthyroidism characterized by antibody stimulation of the thyrotropin receptor. Although there are conflicting study results, patients suffering from Grave's disease appear to have an increased incidence of thyroid cancer. Fine needle aspiration helps detect potential carcinoma, however, it is indeterminate in 15-30% of cases. In cases where fine needle aspiration of a thyroid nodule returns Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS), next-generation sequencing, including Afirma gene testing (created by Veracyte inc) provides guidance for therapy. However, like any screening test, the chance for false negatives still exists. We describe the case of a 41-year-old man suffering from Grave's disease with a solitary thyroid nodule which was found to be papillary thyroid carcinoma despite benign Afirma gene testing.

Case description

A 41-year-old male with no past medical history presented to his primary care provider with no active complaints but was found to have a blood pressure of 142/92 mmHg. He notably had a diffusely enlarged thyroid gland on examination. The patient was sent for thyroid function testing which demonstrated TSH: < 0. 01 uIU/ml and a free T4: 1.1 ng/dL. The patient was sent for a thyroid ultrasound which demonstrated a right-sided nodule measuring: 3.5 cm×2.4 cm×3.2 cm (TI-RADS 4). Radioactive idodine uptake scan revealed this was a cold nodule and the patient underwent fine-needle aspiration biopsy and Afirma gene testing. The patient's biopsy demonstrated AUS while Afirma gene testing was benign. After discussing treatment options for Grave's disease with his endocrinologist, the patient underwent total thyroidectomy. Post-surgical biopsy of the patient's thyroid demonstrated follicular variant papillary thyroid carcinoma with capsular invasion. The patient is currently being followed closely by endocrinology with regular TFT and thyroglobulin testing.

Discussion

Grave's disease is postulated to increase patients’ risk of developing papillary thyroid cancer. Many of the proposed hypotheses explaining this higher risk center around thyroid-stimulating antibodies promoting tumor invasion and angiogenesis. When these patients demonstrate suspicious thyroid nodules on imaging, they undergo fine-needle aspiration, however, these biopsies are indeterminate in 15-30% of cases. Afirma gene testing has been proposed as a sensitive test to rule out carcinoma in these indeterminate cases. We describe a case where, despite benign Afirma gene testing, the patient was found to have papillary thyroid cancer after thyroidectomy. We propose that Grave's disease patients with suspicious nodules with indeterminate biopsy and benign Afirma testing still be considered for total thyroidectomy given their increased risk of thyroid cancer.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP467 CDC Clinical Standardization Programs (CSP) for Free Thyroxine (FT4) to improve the accuracy and reliability of FT4 measurements in patient care and clinical research
Authors: Sugahara Otoe , Ribera Ashley , Danilenko Uliana , Collins Lynn , Buchannan Tatiana , Coffman Clark , Vazquez Norma , Pokuah Fidelia , Zhang Li , Lyle Alicia N , Hubert Vesper , Thonkulpitak Janet
Published: November 2022

Concerns about the accuracy and reliability of thyroid function tests, especially free thyroxine (FT4), have been stated by the clinical laboratory community for many years. Thyroid function tests are the most used tests in the U. S. and are the only means to detect and treat diseases of the thyroid. The consequences of inadequate thyroid hormone levels can be severe and are easily preventable and treatable with early detection. In response to these concerns, the CDC CSP has partnered with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and created a standardization program for FT4 based on the IFCC reference system. The CDC program aims to improve the accuracy, reliability, and comparability of current methods and, thus, improve the diagnosis, treatment, and prevention of thyroidal illnesses. There were no commutable, certified serum-based FT4 reference materials (RMs) available to assess the accuracy and reliability of FT4 assays. CDC has developed an accurate and sensitive reference measurement procedure (RMP) to assign reference values to individual donor sera. Assay manufacturers and research and clinical laboratories can use these sera to assess the analytical performance of their measurements, and monitor performance over time. In addition, the CDC's FT4 RMP is used to assign reference values to materials used in EQA/PT programs to verify that standardization efforts at the developer level translate to the end-user level. The CDC FT4 RMP uses equilibrium dialysis (ED), based on an internationally recognized ED procedure, followed by solid-phase and solvent extractions before analysis by LC-MS/MS. Certified primary RM IRMM468 is used as calibrators. The intra- and inter-day imprecision of the CDC RMP are 3. 0% and 1.1%, respectively. The CDC RMP measurement range is 3. 02–258 pmol/L, which is suitable for analysis of hypo- and hyperthyroid patients. Based on an IFCC comparison study between four FT4 RMPs, the CDC RMP's bias was within 2.5% of the all-labs mean. CDC CSP is currently conducting a comparison to further define the differences among various types of commercially available FT4 assays. A set of 40 serum RMs value assigned with the FT4 RMP are now available via the Phase 1 of the Hormone Standardization (HoSt) Program. These materials can be used for calibration and verification by assay developers. CDC CSP is currently working to develop a Phase 2 of the HoSt Program for FT4 to assist developers with certification of FT4 assays. Based on the needs and requests from the clinical community, programs for new biomarkers, such as thyroid-stimulating hormone, are also being developed.

Presentation: No date and time listed
ODP504 PERICARDIAL EFFUSION AS A LIKELY CONSEQUENCE OF NON-COMPLIANT MANAGEMENT OF HYPOTHYROIDISM
Authors: Rimal Priya , Zbarsky Dmitri , Musurakis Clio , Havrylyan Andriy , Barsano Charles
Published: November 2022

Hypothyroidism is a well-known cause of pericardial effusion with an incidence of about 3-27%. If not diagnosed in time it can lead to potentially serious complications, such as cardiac tamponade leading to hemodynamic instability. It should be considered as a causative or exacerbating agent in any patient presenting with pericardial effusion and known, suspected or laboratory evidence of hypothyroidism, e. g., elevated TSH or reduced serum free T4. We present a case of a 50-year-old woman with a Past Medical Hx of hypertension, intermittently insulin-treated type 2 diabetes for 20 years, coronary artery disease, and hypothyroidism with medical non-compliance, and s/p right BKA. She initially presented to an outside hospital for altered mental status (specifically, inability to follow simple commands and orientation only to self). She was transferred to this facility for evaluation of limb ischemia. She was agoitrous with no reported palpable thyroid abnormalities. Her admission chest x-ray exhibitedan enlarged cardiac silhouette. Her initial serology was significant for a serum TSH of 178 uIU/mL (NL: 0.45-5.33 uIU/mL), FreeT4 <0.25 ng/dl (NL: 0.58-1.64 ng/dl),Free T3 1.65 pg/mL (NL: 2.5-3.9 pg/mL), andhighly elevated anti-thyroglobulin and anti-peroxidase antibodies. She was diagnosed as having primary hypothyroidism secondary to Hashimoto's thyroiditis. She was re-started on levothyroxine (L-T4) at a dose of 150 mcg on day 1, which was reduced to 100 mcg daily on days 2-4 but readjusted to 125 mcg daily on days 5-8 and 150 mcg daily thereafter. During the 25 th day of admission in the Rehabilitation unither serum TSH showed a gradual decline from 178 to 22 prior to discharge. Her Free T4 increased to 1.18 and her Free T3 increased to 2.24 by discharge. Her pericardial effusion was managed by placement of a pericardial window. Pericardiocentesis yielded over 600 ml of clear serous fluid (protein content 5.1 gm/dl) without evidence of malignancy, infection or inflammation. This case highlights the importance of not only recognizing the diagnosis of hypothyroidism but of assessing the duration and adequacy of its management. Likewise, an enlarged cardiac silhouette in this setting should be considered as possibly representing a pericardial effusion and impending source of a cardiac tamponade.

Presentation: No date and time listed
ODP508 PRIMARY DIFFUSE LARGE B-CELL THYROID LYMPHOMA: A CASE REPORT
Authors: Tan Margarita Katrina Amor , Ty Wilson , Uy Melissa Claire
Published: November 2022

Background

Primary thyroid lymphoma (PTL) is a rare disease, accounting for <5% of all thyroid malignancies. Diffuse B-cell lymphoma (DBCL) is the most common type of PTL. The diagnosis and management of PTL depends on the histopathologic results.

Clinical Case

A 77-year-old female (with T2DM, Hypertension and CAD) had sudden onset of rapidly enlarging neck mass associated with compressive symptoms such as dyspnea, dysphagia and hoarseness of voice. She underwent neck CT scan with contrast revealing a heterogenous mass on right thyroid lobe 9.7×6.9×5.5 cm, with encasement and invasion of adjacent portions of trachea and right common carotid artery . Thyroid function tests were normal and anti-TPO was elevated at 1891.76 IU/ml (NV: < 5.6 IU/mL). Patient underwent tracheostomy and excision biopsy of the mass. Histopathologic report showed atypical lymphoid proliferation and Hashimoto's thyroiditis. Immunohistochemical staining of the neoplastic cells were reactive to CD20, CD3; and Ki67 was positive in 70-90%. Fluorescence in situ hybridization test for c-myc, BCL 6 rearrangement and IGH/BCL 2 fusion for ruling out aggressive double-hit lymphomas came out negative, hence the final diagnosis of Non-Hodgkin's Diffuse Large B-cell Lymphoma. Most PTL originate from B cells, especially DBCL, which accounts for 50–80%. A standard management in PTL is controversial due to limited clinical trials and due to its heterogenous nature. A multidisciplinary approach is the best management technique for PTL. Chemotherapy can cause remission but recent studies showed better response with chemoradiotherapy. The patient was started on R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone). One year after, FDG-PET showed resolution of right thyroid lobe mass with mild diffuse metabolic activity in the rest of thyroid gland, and absence of hypermetabolic lymph nodes.

Conclusion

In older patients presenting with a rapidly enlarging goiter, especially in a setting of Hashimoto's thyroiditis, the diagnosis of PTL should be considered and differentiated from other types of thyroid disease. The prognosis and management of PTL differ from secondary thyroid lymphoma and other types of neoplasm. It can have a good outcome when recognized in earlier stages and if with less aggressive histopathologic type.

Presentation: No date and time listed
ODP526 Thyrotoxic Periodic Paralysis in Graves’ Disease: A rare presentation in an African American male
Authors: Ghoweba Mohamed , Jain Sidharth , Patel Nisargi
Published: November 2022

INTRODUCTION: Thyrotoxic Periodic Paralysis is a rare but life-threatening manifestation of hyperthyroidism characterized by hypokalemia, acute flaccid paralysis, and signs of hyperthyroidism. Despite being commonly seen in East Asian males, TPP has been increasingly reported in other parts of the world including western countries. Early recognition and prompt treatment of TPP is essential in preventing its grave and potentially life-threatening consequences. CASE PRESENTATIONA 21-year-old African American male patient with past medical history significant for hypertension and untreated hyperthyroidism presented to the emergency department with sudden onset bilateral lower extremity weakness and difficulty walking for one day. Upon arrival to the emergency department, vitals were unremarkable. On examination, patient had a decreased muscle tone in bilateral lower extremities with depressed deep tendon reflexes. The thyroid gland was diffusely enlarged. The remainder of physical exam was normal. Electrolyte abnormalities were also present with decreased serum potassium level of 1.2 mEq/L (3.6-5.1 mEq/L) and magnesium of 1.7 mg/dL (1.8-2.5 mg/dL). A low TSH level of <0. 010 mIU/mL (0.350-4.940 mIU/mL) with elevated free T4 levels of 4.30 ng/dL (0.70-1.48 ng/dL) were noted. CT Head/ Brain without contrast and Chest X ray were unremarkable. Potassium replacement was initiated with oral and intravenous potassium chloride. He was also started on oral atenolol (25 mg daily) and methimazole (10 mg daily). The patient's symptoms resolved in few hours after the treatment was started. An ultrasound of the thyroid gland showed diffuse heterogeneity of the gland most consistent with thyroiditis or similar abnormality. No definite focal abnormalities were noted. TSH receptor antibodies were also elevated with levels at 10.70 IU/L (≤1.75 IU/L) making Graves’ disease the most likely diagnosis. The patient's condition significantly improved along his hospitalization with complete resolution of symptoms and electrolyte abnormalities. He was subsequently discharged on atenolol and methimazole with outpatient follow up at the endocrinology clinic. DISCUSSION TPP is an underreported yet possibly fatal medical complication of hyperthyroidism. Prevalence is higher in Asia, however, incidence in Western countries has been increasing. While the underlying pathophysiology is poorly understood, h ypokalemia in TPP results from an intracellular shift of potassium induced by an increased adrenergic sensitization of Na + /K + –ATPase pump. Genetic and environmental factors may possibly play a role. Treatment of TPP entails beta-blockade to prevent intracellular shift of potassium, replenishing potassium stores, as well as correcting the underlying hyperthyroid state. Immediate diagnosis and initiation of treatment prevents serious cardiopulmonary complications and increases the probability of full recovery of muscle weakness.

Presentation: No date and time listed
ODP527 To Treat or Not to Treat Pembrolizumab-Induced Thyroiditis: Using Common Terminology Criteria for Adverse Events as a Decision-Making Aid
Authors: Alatrash Batool , Arnouk Nelly , Cheikh Malek , Mohebtash Mahsa , Schroeder Pamela
Published: November 2022

Introduction

Programmed cell death-1 (PD-1) checkpoint inhibitors are immunotherapeutic agents that are used to treat advanced malignancies including breast cancer. The adverse effects of these medications include thyroid and pituitary dysfunction and may be treated with glucocorticoids, which may cause steroid-induced effects such as hyperglycemia, osteoporosis, and adrenal suppression. The Common Terminology Criteria for Adverse Events (CTCAE) widely used by oncologists for management can support treatment decisions by endocrinologists in patients undergoing treatment with PD-1 checkpoint inhibitors.

Case Description

A 42-year-old female with stage IIIc high-grade triple negative left breast invasive ductal carcinoma was started on pembrolizumab immunotherapy (PD-1 inhibitor). Prior to starting treatment, the patient's thyroid function tests were normal: free T4 0.93 ng/dL (normal range [NR] 0.89-1.76 ng/dL) and thyroid-stimulating hormone (TSH) 1.42 uIU/mL (NR 0.55-4.78 uIU/mL). Two weeks later, she developed heat intolerance, diarrhea, weight loss, and dysphagia. At that time, thyroid tests were consistent with thyrotoxicosis with elevated total T3 644.6 ng/dL (NR 60-180 ng/dL) and totalT4 >12. 00 ng/dL with suppressed TSH 0. 01 uIU/mL. Despite negative TSH receptor antibody and thyroid-stimulating immunoglobulin, CT scan of the neck showed diffuse enlargement of the thyroid gland and thickening of the extraocular muscles. On physical examination she had mild exophthalmos. The etiology of thyrotoxicosis was initially thought to be Graves’ disease, but thyroiditis could not be ruled out. Treatment with methimazole and beta blockers was initiated. Three weeks after methimazole was started, her symptoms improved significantly, with repeat thyroid function tests: TSH 3.64 uIU/mL and free T4 1.29 ng/dL. Methimazole was held. Four weeks later, the second dose of pembrolizumab was administered. Later that day, repeat thyroid function tests showed high TSH 53.12 uIU/ml, and low T4 0.55 ng/dL with negative thyroid-stimulating immunoglobulin and thyroid peroxidase antibodies, consistent with thyroiditis. Endocrinology and Oncology teams discussed the CTCAE determining that the severity of thyroiditis was grade 2 (moderate symptoms, able to perform activities of daily living, TSH persistently above 10 uIU/L). Pembrolizumab was continued and hypothyroidism was treated with levothyroxine.

Discussion

CTCAE is used by oncologists to aid in treatment decisions in patients treated with PD-1 inhibitors. Endocrinologists should consider using the CTCAE grading (severity) scale for each adverse event. Adoption and utilization of the CTACE severity scale by endocrinologists may lead to a more standardized and systematic approach for treatment of thyroid disorders associated with PD-1 inhibitor immunotherapy

Presentation: No date and time listed
ODP570 Immunotherapy and its Implications for the Future of Endocrinology: A Case Discussion of Pembrolizumab Induced Myxedema Coma
Authors: Coppinger Anna , Meek Jessica A , Demoranville Beatriz , Al Dulaimi Ahmed
Published: November 2022

Introduction

Immunotherapy is a relatively new type of cancer treatment that has been successful in prolonging survival time and improving quality of life for patients with a wide variety of cancers.1 While these therapies do not usually have the same systemic toxicities seen in traditional chemotherapies, they can lead to significant autoimmune disorders due to their method of action.2 We present a case of pembrolizumab induced Hashimoto's thyroiditis leading to myxedema coma. Case A 67-year-old male presented to the hospital ED via EMS after being found unconscious in his car by his neighbor. On arrival, he was confused, lethargic, unable to answer questions, and had a Glasgow Coma Scale of 12. He was hypotensive 87/55 mmHg, bradycardic 55 bpm, respirations 12 breaths/min, SpO2 99% on room air, temperature 37 °C. Past medical history included type 2 diabetes mellitus on insulin and non-small cell lung cancer metastatic to bone and brain treated with pembrolizumab, denosumab, steroids, and radiation therapy. Initial labs revealed elevated TSH of 47. 01 with undetectable T3 and T4, glucose 514 mg/dL and elevated beta hydroxybutyrate 1.61, WBCs 3.9, hemoglobin 11.7, platelets 105. TPO antibodies were elevated 44.5IU/ml. Patient was treated with IV levothyroxine, hydrocortisone, insulin, and fluids and his condition improved rapidly. Patient was transitioned to oral levothyroxine with plans for outpatient endocrinology follow upon discharge. Thyroid tests done during a prior hospitalization following the initiation of pembrolizumab six months earlier demonstrated a low TSH of <0. 003 and an elevated free T4 of 2. 09. The diagnosis of autoimmune thyroiditis induced by immunotherapy was made.

Discussion

Pembrolizumab is one of several immune-checkpoint inhibitors (ICIs) used to treat cancer by blocking the programmed-death (PD-1) receptor, allowing T-cells to detect malignant cells and mount an immune response. ICIs are part of a larger therapeutic class known as immunotherapy which acts to enhance the body's own detection and elimination of cancerous cells.1 As a result, approximately 10% of patients treated with immunotherapy develop autoimmune reactions.2 In this case, the patient had positive thyroid autoantibodies for Hashimoto's thyroiditis, that eventually lead to his profound hypothyroid state and myxedema coma. As these therapies become more widely utilized, the incidence and prevalence of autoimmune induced endocrine disorders will naturally increase. Awareness of the mechanisms and implications of immunotherapy in patients presenting with endocrine disorders will led to early recognition, treatment and improved patient outcomes.

Waldman AD, et al Nat Rev Immunol. 2020;20(11): 651-668.

Barroso-Sousa R, et al. . JAMA Oncol. 2018;4(2): 173-182.

Presentation: No date and time listed
OR11-4 Teprotumumab Markedly Improves Disease-related Quality of Life: Lessons From Two Randomized, Placebo-controlled Trials
Authors: Douglas Raymond S , Holt Robert , Qashqai Anahita , Sile Saba , Smith Terry J , Vesel Claudia , Kahaly George J
Published: November 2022

Background

Thyroid eye disease (TED) can result in eye-bulging (proptosis) and double-vision (diplopia) and inflammation, which frequently impacts quality of life (QoL). Teprotumumab, an insulin like growth factor-1 receptor inhibitory antibody, improves TED outcomes and QoL1 as measured by the Graves Ophthalmopathy-Quality of Life (GO-QoL) questionnaire and its appearance (AP) and visual function (VF) subscales. The primary factors driving QoL improvement in TED are unknown; therefore, we examined outcomes associated with improvement as observed in 2 placebo-controlled trials.

Methods

Data from Phase 2/3 placebo-controlled trials of teprotumumab were examined with a mixed-effect model with change in overall GO-QoL, AP, and VF scores as dependent variables to explain within-patient variability. Independent variables included demographics, visits, treatment, symptoms (Gorman diplopia scores [0-3], proptosis change (mm), spontaneous orbital pain, gaze-evoked orbital pain). Variability between subjects was tested over the 24-week study.

Results

Teprotumumab treatment significantly correlated with improved overall GO-QoL, VF and AP scores. Improvements in diplopia, proptosis, gaze-evoked and spontaneous orbital pain were associated with those in overall GO-QoL score (coefficient -4.01, -1.00, -31.21 and -4.37, respectively, all p<0.001). Improvements in diplopia scores and spontaneous orbital pain were significantly correlated with higher VF scores (coefficients -5.51 and -6.66, respectively, both p<0.001). Improvements in diplopia and proptosis correlated significantly with higher AP scores (coefficients -2.98, -1.62, both p<0.001). Patients with pain had lower AP scores (coefficient -38.21, p<0.001). Increasing age was positively correlated with higher GO-QoL AP scores (coefficient 0.41, p<0.001), but negatively correlated with GO-QoL VF scores (coefficient -0.29, p<0.001). Variability between subjects was considerable, accounting for >60% of random variance.

Conclusions

Improvements in diplopia, proptosis, and pain drove improvements in QoL. In older patients, changes in AP impacted QoL to a lesser degree, while reduced VF had a greater negative impact on QoL.

References

Kahaly et al, Lancet Diabetes and Endocrinol 2021; 9(6): 360-372

Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.
PSAT235 The Role of Systemic Immune Activation in the Development of Thyroid Dysfunction in COVID-19
Authors: Kolpakova Evgenia , Elfimova Alina , Nikankina Larisa , Troshina Ekaterina
Published: November 2022

Background

The research of cytokine-induced thyropathies in the midst of continuing COVID-19 pandemic is a very important and urgent problem. This work is based on the hypothesis that the hyperactivation of the immune system during COVID-19 is accompanied by a massive production of proinflammatory cytokines, and this could lead to thyroid gland disruption.

Aim

The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (T3f), and free thyroxine (T4f) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, T3f, T4f values, and patient survival.

Materials and Methods

This retrospective, single-center study included 122 patients hospitalized at the National Endocrinology Research Centre with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, T3f, T4f, AT-TPO, and AT-recTSH. Additionally, the markers of the inflammatory process were assessed in all patients, including: interleukin-6 (IL-6).

Results

Five patients (4%) were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with IL-6 (r: -0.221; p = 0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p = 0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]. Based on the hypothesis that the immunosuppressive effect of genetically engineered biological therapy may have a protective role against thyroid damage in the development of cytokine storm, a comparative analysis of TSH values in two groups of patients with cytokine storm was performed (p=0.080).

Conclusion

Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. In addition to the pathophysiological aspects of thyrotoxicosis, this study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate. The results obtained indicate a high risk of developing cytokine-induced thyropathies in patients with COVID-19. In support of the hypothesis of thyroid tissue damage being caused by pro-inflammatory cytokines, the differences in detected TSH values rose to the level of a statistical trend in 2 groups of patients with cytokine storm (i.e., patients who received tocilizumab therapy, and patients who received symptomatic therapy).

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT241 Variation in the Diagnosis of Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP) in the United States
Authors: Chen Debbie , Rob Farizah , Mukherjee Rik , Giordano Thomas , Haymart Megan , Banerjee Mousumi
Published: November 2022

Background

The North American Association of Central Cancer Registries (NAACCR) develops and promotes uniform data standards for cancer registries, such as uniform cancer coding, and is used by all central cancer registries in the United States (US) and Canada, including Surveillance, Epidemiology and End Results (SEER). Effective January 1, 2017, the NAACCR modified its coding scheme and noninvasive encapsulated follicular variant of papillary thyroid cancer (EFVPTC) was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to reflect the indolent nature and very low risk of adverse outcomes of this thyroid tumor. The diagnostic use of NIFTP was anticipated to impact tens of thousands of patients in the US. Since NIFTP is no longer considered a cancer, as of January 1, 2021, it was no longer a reportable diagnosis in SEER. However, little is known about how the diagnosis of NIFTP was utilized across different regions and patient populations in the US when it was a reportable diagnosis.

Methods

Data was extracted from the US SEER-21 cancer registry (2000-2018). The study cohort comprised of individuals diagnosed with papillary or follicular thyroid cancer (2000-2018), or NIFTP (2017-2018). We examined the annual incidence of thyroid cancer by subtypes and NIFTP. Using data for 2018, we determined the rates of NIFTP for each of the 16 sites included in SEER-21. In addition, we compared the demographics of patients diagnosed with NIFTP to that of patients diagnosed with papillary and follicular thyroid cancer using Chi-square test.

Results

Between 2010 and 2018, we identified a total of 191,107 cases (182,893 PTC, 7,445 FTC, and 769 NIFTP). Incidence of FVPTC sharply declined from 2015 to 2018, with observed increases in NIFTP and encapsulated PTC/ invasive EFVPTC each accounting for 17% and 10% of the decline in FVPTC, respectively. High heterogeneity was observed in the regional incidence of NIFTP in 2018, with incidence rates ranging from 0.0% (Alaska) to 5.8% (Seattle-Puget Sound). Based on 2018 data, a diagnosis of NIFTP (2.2% of total thyroid cancer cases) was significantly associated with female sex (P=0.001), Black race (P<0.001), and non-Hispanic ethnicity (P<0.001) compared to diagnosis of papillary and follicular thyroid cancer.

Conclusion

There is marked variation in the use of the NIFTP diagnoses. The recent NAACCR coding change that resulted in NIFTP, a tumor with uncertain malignant potential and for which there is no long-term outcome data available, no longer being a reportable diagnosis will disproportionately affect women and Black patients, and patients who reside in regions with higher rates of NIFTP diagnoses.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.