bluuebunny/crossref_metadata_2025 huggingface dataset:
6572 Acute Adrenal Crisis Secondary To Undiagnosed Addison's Disease
Authors: Deirmenjian Jacqueline M , Nickowitz Harris , Kavafyan Talar
Published: October 2024

Disclosure: J.M. Deirmenjian: None. H. Nickowitz: None. T. Kavafyan: None.

Addison’s disease, also known as primary adrenal insufficiency, is when the adrenal gland has a defect in making cortisol. Signs and symptoms of Addison’s disease include nausea, vomiting, diarrhea, fatigue, dizziness, hyperpigmentation, and mood changes. Acute Adrenal Crisis can occur as a result of Addison’s disease when patients experience acute physiologic stress such as acute illness. Patient is a 35- year-old woman with a PMHx of iron deficiency anemia presenting with intractable nausea and vomiting for 10 days and a single witnessed syncopal episode two days prior to presentation. She was also had intermittent dizziness. Patient initially presented to urgent care where she was found to be hyponatremic and then was sent to the ED. She had no seizure like activity or rashes prior to admission. On initial physical exam, her skin was warm and dry with skin discoloration and hyperpigmentation. She was awake, alert, and oriented to person, place, time, and situation. Patient had no neurological deficits and no lateral or vertical nystagmus on initial assessment. On admission, patient was hyponatremic to 114 mEq/L, potassium was 5.0 mEq/L, and glucose level was 79 mg/dL. Despite receiving a 500 cc NS bolus, 1L NS bolus, 25 grams of albumin, and D5-0.45 NS at 50 cc/hr, the hyponatremia was difficult to correct. Her sodium initially corrected to 120 mEq/L but the sodium later decreased to 117 mEq/L. The morning after admission, patient became hypotensive and hypoglycemic. Random cortisol was measured and found to be 2.2 mcg/dL, raising concern for acute adrenal crisis as a result of undiagnosed Addison’s Disease. ACTH level was 17 pg/mL. Endocrinology was consulted and she was treated with IV 100 mg Hydrocortisone in addition to IV hydrocortisone 50 mg IV q6h. Patient was able to be transitioned to PO hydrocortisone 15 mg qAM and 5 mg qPM and was started on PO fludrocortisone 0.1 mg daily. On day of discharge, sodium improved to 127 mEq/L. CT Abdomen with contrast was completed to evaluate the adrenal glands and it showed a normal appearance of the adrenal glands. The etiology of the patient’s acute adrenal crisis was secondary to undiagnosed Addison’s Disease. It is interesting to note that patient was not hypoglycemic on admission but later became hypoglycemic during her hospital course. Adrenal crisis is a possible fatal complication of undiagnosed Addison’s disease. Therefore, a possible Addison’s Disease diagnosis is important to consider when patients are presenting with symptoms such as nausea, vomiting, dizziness, and electrolyte derangements including hyponatremia. If patient’s present with hyponatremia, ruling out possible adrenal insufficiency by checking a cortisol level may change the course of patient’s care. After discharge, she was able to establish care with Endocrinology and remain stable on treatment with PO hydrocortisone and PO fludrocortisone.

Presentation: 6/3/2024
12207 A Two-hit Model Of Pcb Exposure And Immune Challenge, And Effects On Behaviors In Rats
Authors: Khoury S E , Hynes A , Davis L K , Thompson L , Sanchez K , Fonken L , Gore A C
Published: October 2024

Disclosure: S.E. Khoury: None. A. Hynes: None. L.K. Davis: None. L. Thompson: None. K. Sanchez: None. L. Fonken: None. A.C. Gore: None.

This study evaluated how two common life experiences: exposures to environmental endocrine-disrupting chemicals (EDCs), and immune challenges, can act independently or in combination to affect social and anxiety-like behaviors in rats. The class of endocrine-disrupting chemical (EDC) used was polychlorinated biphenyls (PCBs), a family of industrial chemicals that, despite their ban in the 1970s, are detectable in the body tissues of virtually all humans and animals today due to their persistence. Exposures to PCBs were given prenatally and in early postnatal life through feeding of rat dams, during hormone sensitive periods of brain development in the offspring. The immune challenge was given postnatally during adolescence through injection of lipopolysaccharide, to induce neuroinflammation. These challenges are individually associated with increased behavioral disorders in humans and rodent models, but how they interact is unknown. In this 2x2 design, rats received either PCBs or oil in early life, and LPS or saline in adolescence. The animals were then tested in a series of behavioral assays to assess for social and anxiety-like behaviors, including Open Field (OF), Juvenile Social Exploration (JSE), Three Chamber Social Test (TCST), Light Dark Box (LD), and Elevated Plus Maze (EPM). An effect of PCB was observed in OF center time. Interactions of EDC and LPS were found in aspects of EP, and TCST. Further work examining protein and gene expression in the hippocampus and hypothalamus is in progress and will help to elucidate the underlying biological mechanism of the observed behavioral changes.

Presentation: 6/3/2024
8812 Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center Retrospective Study
Authors: Luna N B , Mendoza E , Kho S A
Published: October 2024

Disclosure: N.B. Luna: None. E. Mendoza: None. S.A. Kho: None.

Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center, Retrospective Study Immune checkpoint inhibitors (ICIs) serve as immunomodulatory antibodies, which enhance the immune system and substantially improve the prognosis for patients with advanced malignancies [1]. Referral to endocrinology have been increasing because ICIs were associated with endocrine-related adverse effects including hypothyroidism, hyperthyroidism, diabetes, hypophysitis and adrenalitis. Hence, the study aimed to retrospectively determine the local prevalence and profile of Filipino patients who developed endocrinopathies during ICI therapy at the University of Santo Tomas Hospital (USTH), Manila, Philippines from 2013-2019. A single-center retrospective study of ICI-treated cancer patients with serial biochemical and/or radiologic monitoring of endocrine adverse effects was done upon approval by the Research Ethics Committee. A total of 27 subjects were included with a median age of 60 years and male predominance. Pembrolizumab consisted 93% of the ICIs given. The incidence of thyroid dysfunction was 36% (18% overt hypothyroidism, 9% subclinical hypothyroidism, and 9% subclinical hyperthyroidism). The median time at risk for development of overt hypothyroidism is 4 weeks with median TSH level of 9.05 uIU/mL from baseline level of 3.77 uIU/mL. All patients who had baseline hypothyroidism worsened with increase from baseline levothyroxine dose by 50 to 230% in order to achieve euthyroidism (p 0.037). Serial monitoring was done every 2 weeks until euthyroidism. ICIs were temporarily put on hold in 75%. Diabetes (p 0.05), renal carcinoma (p 0.001) and dose of 200mg (p 0.42) were associated to developing overt hypothyroidism. Checking of glycemic levels was not routine among non-diabetic patients. Fifteen percent of diabetic patients had worsening of control (median HbA1c 8.5% [8-9] and 23% were newly diagnosed pre-diabetes (median fasting glucose 114mg/dL [104-120]). With the available imaging results, there were no abnormal adrenal metabolic uptake on PET scan and no evidence of hypophysitis in pituitary MRI. In conclusion, overt hypothyroidism is a common occurrence during ICI therapy (18%). Worsening occurred among all patients with hypothyroidism at baseline. New-onset pre-diabetes and worsening of glycemic control were seen in 15 and 23%, respectively. Serial clinical and biochemical monitoring is important and referral to endocrinology should be made if deemed necessary. [1] L Agrawal, A Bacal, S Jain, V Singh, N Emanuele, Ma Emanuele & F Meah (2020) Immune checkpoint inhibitors and endocrine side effects, a narrative review, Postgraduate Medicine, 132:2, 206-214, DOI: 10.1080/00325481. 2019. 1709344

Presentation: 6/1/2024
5074 Licorice Root Supplement As A Cause Of Hypokalemic Hypertension
Authors: Gill Gurbir , Harman Sherman Mitchell , Robles Lydia Alejandra
Published: October 2024

Disclosure: G. Gill: None. S.M. Harman: None. L.A. Robles: None.

A 67-year-old female Veteran presented to an emergency room with a one-day history of high blood pressure, chest tightness, and exertional dyspnea. Her blood pressure was 162/90 mm Hg, pulse regular at 71 BPM, and pain level 5/10. She had a history of hypertension, stable on hydrochlorothiazide alone, hyperlipidemia, anxiety, and depression. Physical exam was benign. EKG revealed normal sinus rhythm at 60 BPM, normal axis, a prolonged QT interval of 510 ms, and no ST changes. Lab evaluation showed a low potassium of 2.4 mEq/L, sodium 145 mEq/L. Other lab measurements (CBC, liver function tests and cardiac enzymes) were within laboratory reference ranges. Medications included topiramate for migraine and over-the-counter supplements for constipation, “thyroid health,” and a topical “testosterone booster” prescribed by a non-allopathic practitioner. Her hypokalemia was attributed to hydrochlorothiazide and topiramate and both were discontinued. She was started on nifedipine for blood pressure control and 40 mEq/day of potassium for hypokalemia. Within 2 weeks of discharge, she presented again with elevated blood pressure and a plasma potassium of 4.0 mMol/L. Further history revealed that her constipation supplement consisted of licorice root (glycyrrhiza glabra) extract 900 mg per capsule, of which she took 3 to 4 capsules daily. The patient was advised to discontinue all supplements. Thyroid function tests were within normal limits. Due to a suspicion of hyperaldosteronism, the ED physician requested an abdominal CT scan which showed a 1 cm, -17.5 Hounsfield unit, right adrenal nodule. Also consistent with hyperaldosteronism, plasma renin activity (PRA) was suppressed at 0.07 ng/mL/hr. However, a serum aldosterone level was less than 1 ng/dL. Her 24-hour urinary metanephrines were normal and a 24-hour urine free cortisol was 31.6 mcg/dL. Morning plasma cortisol was 5.1 mcg/dL. A tentative diagnosis of licorice-induced hyperaldosteronism was made and the patient was treated with a taper of spironolactone. After discontinuing spironolactone, blood pressure was 116/70mmHg and serum potassium was 4.5 mMol/L with a PRA of 0.66 ng/mL/hr and serum aldosterone of <5.0 ng/dL. The syndrome of factitious hyperaldosteronism due to licorice consumption has been well described. The mechanism, inhibition of renal (type 2) 11-beta-hydroxysteroid dehydrogenase by glycyrrhizic acid, allowing cortisol to exercise its considerable mineralocorticoid action, is well understood. Most prior reports have been in patients habitually consuming licorice candy, usually imported, since conventional licorice sold in the U.S. is artificially flavored. Our report illustrates the importance of obtaining a history of use of over-the-counter supplements and assessing their ingredients and the fact that presence of an adrenal nodule and a low PRA does not always indicate endogenous hyperaldosteronism.

Presentation: 6/2/2024
7115 Long-Term Exposure To Air Pollution And Precocious Puberty In Korea
Authors: Choi Jung Eun , Oh Jongmin , Lee Ro Sie , Mun Eunju , Kim Kyung Hee , Ha Eunhee , Kim Hae Soon
Published: October 2024

Disclosure: J. Choi: None. J. Oh: None. R. Lee: None. E. Mun: None. K. Kim: None. E. Ha: None. H. Kim: None.

Backgrounds and Aims The increasing prevalence of precocious puberty is emerging as a significant medical and social problem worldwide. However, limited research has investigated the relationship between long-term air pollution exposure and precocious puberty. We aimed to investigate the association between long-term air pollution exposure and first onset of precocious puberty in South Korea, nationwide. Methods: We investiagted a retrospective cohort using Korea National Health Insurance Database. Children born from 2007 to 2009 were followed-up from the age of six (2013 to 2015). We included boys aged ≤10 years and girls aged ≤ 9 years who visited hospitals for early pubertal development and were diagnosed with precocious puberty according to the ICD-10 (E228, E301,and E309) and gonadotropin-releasing hormone agonist (GnRHa) treatment. We conducted the association between long-term air pollution exposure and first onset of precocious puberty using a Cox proportional hazard model. We estimated the hazard ratios (HR) and 95% confidence intervals (CI) per 1 μg/m3 increase for fine particulate matter (PM2.5) and particulate matter (PM10) and per 1 ppb increase for sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3). Results: A total of 1,205,784 childrens aged six years old were included during 2013­-2015. A positive association was found that the association between 48-month moving average PM2.5 (HR: 1.019, 95% CI: 1.012, 1.027), PM10 (HR: 1.009, 95% CI: 1.006, 1.013), SO2 (HR: 1.037, 95% CI: 1.018, 1.055), O3 (HR: 1.006, 95% CI: 1.001, 1.010) exposure and precocious puberty in girls. In contrast, no association was found in boys. Conclusions Our findings supported that long-term exposure to air pollution is associated with an increased risk of precocious puberty. The study provides valuable insights into the harmful effects of air pollution during childhood and adolescence, emphasizing that air pollution is a modifiable risk factor that can be managed and improved.

Presentation: 6/1/2024
7849 The EDC Mixture “NeuroMix” Has Developmental, Anxiolytic, And Obesogenic Effects In Rats
Authors: Morales-Grahl Elena , Thompson Lindsay M , Hilz Emily N , Gore Andrea C
Published: October 2024

Disclosure: E. Morales-Grahl: None. L. M. Thompson: None. E.N. Hilz: None. A.C. Gore: None.

Humans are exposed to a variety of endocrine disrupting chemicals (EDCs) on a daily basis through drinking water, food, and contact with everyday objects. Safety guidelines aim to keep exposure to individual EDCs below certain levels but don’t take into account the potentially unpredictable effects of simultaneous exposure to multiple EDCs. Furthermore, EDCs may exhibit non-monotonic dose responses. The present study assessed the effect of an EDC mixture at three different doses on two sets of behaviors implicated in EDC research: anxiety, and high fat and sugar consumption. Beginning in early pregnancy and until pups were weaned at day 21, Sprague Dawley rats were fed daily with NeuroMix, our lab’s EDC mixture containing 9 common industrial chemicals, at three doses (0.1x, 1x, 10x). The base dose (1x) contained EDCs below the no observed adverse effect level in humans (NOAEL). In adulthood, the female and male offspring were then subjected to an open field and light/dark test, followed by a high fat and high sucrose preference test. 0.1x NeuroMix exposure advanced the timing of vaginal opening in female offspring, while all doses increased anogenital distance in males, marking differences in sexual development. 1x NeuroMix exposure in male rats increased their time in the open field corners and their time immobile in the corners, indicating higher anxiety. No difference was seen in sucrose preference. Female rats exposed to 1x NeuroMix showed a higher preference for a high-fat diet, and gained more weight compared to the controls while on this diet. These findings demonstrate that a mixture of human-relevant chemicals, when administered perinatally to rats, have developmental, anxiogenic and obesogenic effects in a sexually dimorphic manner. We also show a non-monotonic response to our chemical mixture, with the 1x dose showing greater effects than the 10x dose. Overall, we provide evidence that even at levels considered safe for individual EDCs, there are adverse developmental and behavioral effects of EDCs when combined. Grant support: R35 ES035024, F32 ES034257.

Presentation: 6/1/2024
7282 Arginine-Vasopressin Deficiency And Long COVID: A Causal Or A Coincident Relationship?
Authors: Medeiros Regina Saudade , Pereira Bernardo , Pataco Andreia , Senra Catarina , Ponte Maria João , Anselmo João , Sousa Isabel
Published: October 2024

Disclosure: R.S. Medeiros: None.

Introduction: Arginine-vasopressin deficiency (AVP-D) has been reported in few case reports as a very rare complication of COVID-19 and SARS-COV2 immunization. Long COVID is defined as signs, symptoms, and conditions that develop after COVID-19, and it can affect several organs and systems. Autopsy studies showed SARS-COV2 genetic sequence in degenerated neurons of hypothalamus, and expression of angiotensin-converting enzyme type 2 in median eminence capillaries and paraventricular nucleus have also been demonstrated. Clinical Case: A 47-year-old male presented with polydipsia (8 L/day) and polyuria 8 weeks after non-severe COVID-19. Past medical history was relevant for untreated dyslipidemia. He denied past head trauma, surgery or radiotherapy. Family history was unremarkable. Biochemical evaluation revealed normal glucose, serum electrolytes, renal and hepatic parameters; urine osmolality was 160 mOs/Kg and 24h urinary volume was 10350 mL. Basal pituitary surveys were also normal. A water deprivation test was performed but stopped after 2 hours due to development of hypernatremia (Na+ 146 mEq/L), serum osmolality of 311 mOs/Kg (reference: 280-300) and urine osmolality of 105 mOsm/Kg. After 20 ug intranasal desmopressin urine osmolality increased to 357 mOsm/Kg. A contrast-enhanced MRI revealed an absent posterior pituitary bright spot and thickening of the pituitary stalk suggesting infundibulo-neurohypophysitis. Further biochemical and imaging surveys excluded infectious and infiltrative causes of AVP-D; however, due to elevated serum iron (204.0 ug/dL; reference: 65-175) and transferrin saturation (68%; reference: 15-45%), genetic screening of hemochromatosis by next-generation sequencing of all hemochromatosis-associated genes (HFE, HJV, HAMP, TFR2 and SLC40A1) revealed a heterozygotic variant c.187C>G p.(His63Asp) in HFE, a genotype not associated with iron overload. He started oral desmopressin 0.2 mg/day, to which he showed a prompt response, titrated to 0.8 mg/day (in 3 divided doses). Conclusion: Although molecular and histologic confirmation of SARS-COV2 infundibulo-neurohypophysitis could not be investigated, a strong temporal relationship and the absence of an alternative diagnosis renders plausible the inclusion of AVP-D in the myriad of manifestations of long COVID. Further studies with patients recovered from COVID-19 are necessary to gain a better understanding on the epidemiology, pathophysiology and clinical course of this very rare endocrine association of SARS-COV2 infection with infundibulo-neurohypophysitis.

Presentation: 6/3/2024
12255 Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue And Cognitive Impairment In Mice
Authors: Dantzer R
Published: October 2024

Disclosure: R. Dantzer: None.

Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue and Cognitive Impairment in Mice Brandon Chelette, PhD, Anand Singh, PhD, Robert Dantzer, DVM, PhDDept. of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Fatigue and cognitive impairments are commonly reported by cancer patients undergoing chemotherapy. The mechanisms of these neurotoxicities are still obscure. We hypothesize that they are mediated by mitokines that are released by cells undergoing mitochondrial stress in response to chemotherapy. For the present study, we have focused on growth differentiation factor 15 (GDF15) which acts in the brain by activating its receptor, GDNF family receptor alpha-like (GFRAL). Chemotherapy-induced fatigue was assessed by reduced voluntary wheel running. Cognitive impairment was assessed by altered performance in the Puzzle Box Test that measures executive function. We first checked whether commonly used chemotherapeutic drugs can induce GDF15. Mice were injected with cisplatin, paclitaxel, or bortezomib, and their effects on plasma levels of GDF15 were measured 24 h after (ELISA). Cisplatin was used in the following experiments in the form of one or two cycles of daily injections for five days with a rest of five days between cycles. To determine whether GFRAL mediates the effects of cisplatin on wheel running and performance in the puzzle box, mice were injected with a neutralizing antibody targeted to GFRAL (GFRALna) during or after cisplatin treatment. All studies were carried out in male and female C57BL/6 J mice using a 2 (+ chemotherapy) x 2 (+ GFRALna) factorial design with a minimum of 6 mice/group. Mitochondrial dysfunction was measured via Seahorse XF Analyzer Mito Stress Test. To determine whether activation of the GDF15/GFRAL axis recruits a central GDF15 compartment, Gdf15 mRNA was measured by qRT-PCR in the brain parenchyma, meninges, and choroid plexus. All the chemotherapeutic agents we tested induced statistically significant increases in circulating GDF15. GFRALna administered during cisplatin treatment (prevention) or after completion of cisplatin treatment (cure) abrogated cisplatin-induced decrease in wheel running and the deficit displayed by cisplatin-treated mice in the first hard trial run in the puzzle box. GFRALna also blocked the decrease in maximal oxygen consumption rate of mitochondrial in synaptosomes from cisplatin-treated mice. Cisplatin did not induce Gdf15 mRNA in the brain parenchyma but increased its expression in the meninges and choroid plexus. Although the role of this GDF15 brain compartment in the neurotoxicity of cisplatin remains to be determined, the present findings can be interpreted to suggest that GDF15-GFRAL signaling represents a new target for the treatment of chemotherapy-induced fatigue and cognitive impairment. Count: 2,246 characters

Presentation: 6/1/2024
8156 Exploring Gender-Specific Characteristics Of Diabetes Among Young Adults In Korea: The Korea National Health And Nutrition Examination Survey 2011-2012 And 2019-2020
Authors: Chung C
Published: October 2024

Disclosure: C. Chung: None.

Background: The escalating global incidence of diabetes among young adults could be linked to dynamic socio-environmental changes including pandemic and climate shifts. In this investigation, we aimed to discern the distinct features of diabetes among young adults in Korea. Methods: This cross-sectional study included 63,489,047 Korean young adults (32,173,248 male, 31,315,799 female) aged 20-39 years who participated in the Korean National Health and Nutrition Examination Survey 2011-2012 and 2020-2021. Diabetes cases were identified through hospital diagnoses or the prescription of insulin or non-insulinemic anti-diabetic medications. The significant insulin resistance was defined as HOMA-IR above 2.9. Complex sampling design and cross-tabulation analyses were used to examine both socioeconomic and laboratory factors. Results: The prevalence of diabetes was higher in men in both 2011-2012 and 2020-2021 (Men vs. Women, 2011-2012: 2.2 ± 0.5 vs. 1.2 ± 0.3 %, p<0.001; 2020-2021: 3.0 ± 0.5 vs. 1.6 ± 0.3 %, p<0.001). The use of insulin and oral hypoglycemic agent (OHA) was comparable between men and women in 2011-2012 (Insulin: 18.1 ± 8.2 vs. 5.2 ± 5.1 %, p=0.305; OHA, 18.2 ± 6.3 vs. 19.5 ± 6.5 %, p=0.239), but more women used insulin and more men used OHA in 2020-2021 (Insulin: 5.3 ± 3.7 vs. 28.7 ± 9.4 %, p=0.016; OHA: 31.4 ± 7.7 vs. 19.6 ± 7.3 %, p=0.009). Execution of fundus exam (25.7 ± 10.6 vs. 68.5 ± 14.1 %, p=0.021) and diagnosis of diabetic retinopathy (0 vs. 8.9 ± 3.3 %, p=0.001) was higher in women in 2020-2021. HbA1c was higher in men in 2020-2021 (8.1 ± 0.4 vs. 7.3 ± 0.3 %, p <0.001), but was similar between men and women in 2011-2012 (8.4 ± 0.6 vs. 8.1 ± 0.6 %, p=0.697). Obesity, one of the most common comorbidities of diabetes, was higher in women in 2011-2012 (24.8 ± 4.8 vs. 79.4 ± 9.3 %, p<0.001), but was higher in men in 2020-2021 (94.4 ± 2.9 vs. 67.8 ± 11.0 %, p<0.001). The factors associated with increase in HOMA-IR in 2020-2021 was different between men and women. Unexpectedly, men with low mental stress showed positive correlation with HOMA-IR (B = 3.9, 95% CI 0.1-7.7, p=0.047). For women, mental stress did not affect HOMA-IR, but those with regular anaerobic exercise (B = -10.5, 95% CI -18.3 - -2.6, p=0.011) and stable employment status (B = -11.9, 95% CI -19.4 - -4.8, p=0.002) presented negative correlation with HOMA-IR. Conclusion: In comparison to before the COVID-19 pandemic, men diabetic patients showed more obese tendency after COVID-19, and there was also a statistically significant difference in HbA1c disparity with women. The higher prevalence of diabetic retinopathy despite of lower HbA1c in women during pandemic era needs to be further investigated in well-designed cohort study.

Presentation: 6/3/2024
7492 Fibroblast Growth Factor 21 In The Diagnosis And Treatment Of Metabolic Disorders
Authors: Heshmati Hassan M , Abu-Lebdeh Haitham S
Published: October 2024

Disclosure: H.M. Heshmati: None. H.S. Abu-Lebdeh: None.

Background: Fibroblast growth factor 21 (FGF21), a member of the human FGF superfamily, is a 181 amino acid peptide hormone primarily produced by the liver. The gene of FGF21, located on chromosome 19, was cloned in 2000. FGF21 is involved in the maintenance of metabolic homeostasis. This review presents an update on the relevance of FGF21 in the diagnosis and treatment of metabolic disorders including obesity, nonalcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes. Methods: A systematic search of literature was conducted using the search terms fibroblast growth factor 21, obesity, nonalcoholic fatty liver disease, dyslipidemia, and type 2 diabetes. Results: FGF21 is a stress hormone with effects on energy expenditure and metabolism of lipids and glucose. FGF21 exerts its endocrine action in the central nervous system and adipose tissue. The serum FGF21 levels in normal subjects increase with aging. Stressful conditions (e.g., fasting status, protein restriction, exercise, metabolic disorders, kidney diseases, cardiovascular diseases, and sepsis) increase FGF21 secretion. Serum FGF21 levels are increased in obesity, NAFLD, dyslipidemia, and type 2 diabetes. Some of these patients may have a state of FGF21 resistance. The resistance to FGF21 is related, at least in part, to the presence of high circulating levels of fibroblast activation protein, a protease that inactivates FGF21. It has been suggested that the exercise-induced weight loss can be due to increased FGF21 secretion and decreased FGF21 resistance in adipose tissue. Serum FGF21 level has the potential to be used as a biomarker for early diagnosis of metabolic disorders (e.g., NAFLD and type 2 diabetes). Based on different metabolic properties of FGF21, FGF21-based therapy has been considered as an attractive approach for the treatment of metabolic disorders. Since native FGF21 has poor pharmacodynamic properties (e.g., short half-life and proteolytic cleavage by proteases), long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been synthesized and tested in clinical trials for the treatment of obesity, NAFLD, dyslipidemia, and type 2 diabetes. The available results show that FGF21 analogs can reduce body weight, liver fat, blood lipids, and fasting insulin/insulin resistance. Overall, the treatment with these analogs is safe and well tolerated. Conclusion: FGF21 is a predominantly liver-derived peptide hormone regulating energy expenditure and metabolism of lipids and glucose. Serum FGF21 levels are increased in several metabolic disorders including obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is an attractive target for the treatment of these metabolic disorders. Despite some promising results observed with the use of FGF21 analogs, more clinical studies are needed before recommending FGF21-based therapies in metabolic disorders.

Presentation: 6/2/2024
7902 Improvement In Follow-Up Of Post-Hospital Discharge Patients After Targeted Approach
Authors: Ward S , Aziz Q u , Champion A L , Izuora K E
Published: October 2024

Disclosure: S. Ward: None. Q. Aziz: None. A.L. Champion: None. K.E. Izuora: None.

Improvement in Follow-up of Post-hospital Discharge Patients after Targeted Approach Introduction: Outpatient follow up after discharge from the hospital is a well-established factor affecting health outcomes in patients with chronic medical conditions. A prior QI project at our institution utilizing a Plan-Do-Study-Act (PDSA) cycle showed that overall follow up rate was 24% in patient expected to follow up in our outpatient clinic. The aim of this QI project was to identify and implement a targeted approach to improve outpatient follow up at our clinic. Methods: This study was a second round of a PDSA cycle with the goal of improving outpatient follow up. Analysis of prior data identified 54 patients referred for outpatient follow up in our endocrinology clinic after hospital discharge (non-targeted approach). Of these 54 only 13 patients had established follow up care (24%). We looked closer at the 39 patients who did not follow up to identify areas we could act on to improve follow up; 38% of these patients did not follow due to one of the following: did not know they needed to follow up, lack of knowledge of how to contact office, unable to reach office by phone. To overcome these obstacles, we developed a targeted approach for all patients seen in the hospital who were expected to follow up in the outpatient setting. This approach included the following: clinic business card with contact information given to patient, follow up instructions included in discharge instructions including how and when to contact office, message sent from physician to outpatient clinic staff requesting staff contact patient and schedule follow up appointment. This targeted approach was implemented for all patients requiring outpatient follow up seen by the UNLV Endocrinology consult service from August 1, 2023 to September 30, 2023. Results: During the two months of recruitment we identified 34 patients who needed outpatient follow up. All 34 of these patients had the targeted approach implemented. Of the 34 patients 12 have successfully followed up and one patient has a future appointment scheduled. This is a follow up rate of 35%, an increase of 11% compared with the prior QI data that did not use a targeted approach. If all future appointments are kept the follow up rate will be 38%. Five patients who had scheduled appointments did not show up to their appointment and are not counted in the successful follow group . Conclusions: Our targeted approach showed an improvement in outpatient follow up from 24% to 35% compared to a non-targeted approach. Five patients that scheduled appointments did not keep those appointments. Future steps would include evaluating reasons for no-show and identifying approaches to improve our no-show rate. .

Presentation: 6/2/2024
6848 Improvement Of Free Thyroxine Measurement Quality Through The CDC Clinical Standardization Programs
Authors: Ribera Ashley , Vazquez Norma , Knoblock Samantha , Sugahara Otoe , Buchannan Tatiana , Collins Lynn , Spector David , Zhang Li , Danilenko Uliana , Vesper Hubert W
Published: October 2024

Disclosure: A. Ribera: None. N. Vazquez: None. S. Knoblock: None. O. Sugahara: None. T. Buchannan: None. L. Collins: None. D. Spector: None. L. Zhang: None. U. Danilenko: None. H.W. Vesper: None.

Thyroid function tests are among the most requested tests in patient care, and reliability of these measurements are crucial for appropriate diagnosis and management of thyroid disorders. In response to concerns from the clinical and research community about the quality of thyroid function tests, the CDC Clinical Standardization Programs (CSP) has created the hormone standardization (HoSt) program for free thyroxine (FT4) in partnership with the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC). As a first step, CDC CSP has completed an interlaboratory comparison study of commercial immunoassays (IA) and lab-developed tests (LDT) to determine the current agreement among assays. Participants received 40 blinded, high quality individual donor serum samples with FT4 reference values assigned by the CDC FT4 reference measurement procedure (RMP). FT4 concentrations ranged between 11-32 pmol/L. Samples were analyzed in duplicate over 2 days and results were compared to the CDC FT4 RMP. To assess the potential impact of standardizing measurements to the CDC HoSt FT4 program, reported results were normalized to the CDC RMP results (recalibrated in silico using linear regression). Mean percent bias to the reference value was evaluated pre- and post-recalibration. In addition, inter-assay agreement of classification (assignment of hypo-, eu- or hyperthyroid status according to FT4 reference intervals) were assessed pre- and post-recalibration using the assay-specific and CDC RMP reference intervals, respectively. A total of 19 methods participated, consisting of 15 IA and 4 LDT. All participants showed a negative mean bias to the RMP, with IA showing a higher magnitude of bias (average: -20.7 ± 0.9%) than LDT (average: -4.7 ± 1.1%). Of the 40 samples measured, only 53% were classified uniformly by all 19 participants. Post-recalibration, mean percent bias improved profoundly (IA average: 0.0 ± 0.8%, LDT average: 0.1 ± 1.1%), and classification agreement improved by 33% to 86% of samples with consistent classification. The CDC CSP interlaboratory comparison among FT4 assays highlights the critical need for measurement standardization to improve accuracy of FT4 measurements and increase consistency in result interpretation. This study demonstrates that it is possible to develop common FT4 reference intervals via measurement standardization, which would allow for universal evidence-based clinical guidelines to be used in patient care.

Presentation: 6/3/2024
7845 Machine Learning Methods In Differential Diagnosis Of Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Its Phenocopies
Authors: Trukhina Diana , Voronov Kirill , Mamedova Elizaveta , Solodovnikov Alexander , Belaya Zhanna
Published: October 2024

Disclosure: D. Trukhina: None. K. Voronov: None. E. Mamedova: None. A. Solodovnikov: None. Z. Belaya: None.

Background. MEN-1 is a rare autosomal dominant disorder caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterised by the occurrence of parathyroid tumours, gastroenteropancreatic neuroendocrine tumours, pituitary adenomas, and other endocrine and non-endocrine neoplasms. If a patient with the MEN-1 phenotype does not have any mutation in the MEN1 gene, the condition is considered a phenocopy of the syndrome (phMEN1).The goal of this study was to develop a machine learning algorithm to estimate the probability of gMEN-1 vs phMEN-1 based on easily available clinical features at first line differential diagnostics. Materials and methods. A single-center, one-stage, cohort, retrospective study was carried out. Patients were randomly stratified into 2 cohorts: training (80%) and test (20%). Eight machine learning algorithms were used to develop predictive models: Logistic Regression, k-nearest neighbors (kNN), Naive Bayes, binary decision tree (CART), C5.0 decision tree algorithms, Bagged CART, Random Forest, Gradient Boosting (Stochastic Gradient Boosting, GBM). Results. The study included 95 patients with genetically confirmed gMEN-1 syndrome and 60 patients with its phenocopies. As a result of preliminary data processing and selection for the most informative features, the final variables for the classification and prediction of gMEN-1 syndrome were identified: the number of affected parathyroid glands, age at diagnostics, pancreatic tumour existence, heredity, type of pituitary adenoma secretion, and gender. The kNN algorithm demonstrated the best diagnostic performance in a training sample (ROC-AUC - 0.96, sensitivity - 84%, specificity - 100%), which was confirmed in a test sample (ROC-AUC - 1.0; sensitivity - 94.4%, specificity - 100%) to determine genetically confirmed MEN-1 syndrome. Conclusion. The k-nearest neighbours (kNN) algorithm may be used as a first-line differential diagnostics method to select patients to be refered for genetic testing for gMEN-1.

Presentation: 6/1/2024
8278 Myxedema Coma With COVID-19 Infection
Authors: Kalas R , Manohar V , Bapat N S , Kim Y
Published: October 2024

Disclosure: R. Kalas: None. V. Manohar: None. N.S. Bapat: None. Y. Kim: None.

Myxedema coma is a rare medical emergency that occurs in severe hypothyroidism with a mortality rate reaching 60%. The hallmarks include depressed mental status and hypothermia, but hypotension, hyponatremia, bradycardia, and hypoventilation can also occur. This complication can occur in patients with a longstanding history of severe hypothyroidism especially when precipitated by an acute event such as infection, myocardial infarction, or surgery. Prompt recognition and treatment of the condition is important to prevent fatal outcomes. We present a case of myxedema coma in the setting of COVID-19 infection and nonadherence to medication. A 91-year-old woman with history of hypothyroidism, hypertension, coronary artery disease, cardiomyopathy, and chronic obstructive pulmonary disease presented with dyspnea. Her home medications included levothyroxine 75 mcg daily, which she reported not taking for at least 3 weeks. Vital signs revealed a normal heart rate and blood pressure of 84 beats/min and 137/78 mmHg, but the patient was hypothermic to 35.7 °C. On exam, she was somnolent. Labs were notable for markedly elevated TSH level of 111 (0.380 - 4.700 uIU/mL), low free T4 level of 0.57 (0.93 - 1.70 ng/dL), random cortisol level of 25.5 (6.2-18.4 ug/dL), and positive SARS-COV-2 PCR test. Chest x-ray revealed bilateral lower lung parenchymal consolidations and arterial blood gas revealed a pH of 7.29 and pCO2 of 52.5 (35-45 mm Hg), indicating hypercapnia. She was treated for COVID pneumonia and given concern for COVID induced myxedema coma she was given IV levothyroxine 100 mcg for 2 days, after which the patient’s hypothermia and somnolence improved, with an improved repeat free T4 level 0.87 ng/dL. She was subsequently transitioned to oral levothyroxine 112 mcg daily and discharged after improvement of her COVID symptoms. Myxedema coma is a rare complication of decompensated hypothyroidism, frequently triggered by an infection. Thyroid hormone plays an important role in regulating both the innate and adaptive immune systems. As a result, individuals with hypothyroidism are at increased risk of acquiring infections, which can further lead to myxedema coma. COVID-19 infection has been associated with thyrotoxicosis, thyroiditis and hypothyroidism. Given the associated high mortality rate, regardless of the underlying precipitant, prompt diagnosis and early administration of thyroid hormone replacement therapy is crucial to improve outcomes.

Presentation: 6/3/2024
6855 Nationwide Analysis Of Mentorship In Endocrinology Fellowship
Authors: Toro-Tobon David , Billings Heather , Bancos Irina
Published: October 2024

Disclosure: D. Toro-Tobon: None. H. Billings: None. I. Bancos: None.

Background: Mentorship is crucial for training physicians' career development, yet evidence of its impact on endocrinology trainees is lacking. We assessed the current state of mentorship in endocrine fellowship training in the United States. Methods: We conducted a cross-sectional study between June and September 2023. Endocrine fellows were invited to complete an online questionnaire describing their mentorship experience and its influence on burnout, satisfaction, and scholarly productivity. Results: Of 153 participants (mean age 34, 69% women, 47% White, 20% Hispanic/Latino), 73% had a mentor. Having a mentor was not associated with age, gender identity, race, or ethnicity. Those without mentors were more commonly in two-year fellowships (63% vs. 81%, p=0.04), had less access to formal mentorship programs (48% vs. 21%, p<0.01), cited insufficient faculty availability for mentoring (11% vs. 26%, p=0.01), and encountered more challenges finding mentors in their training programs (11% vs. 38%, p<0.001). Mentored participants exhibited increased post-fellowship interest in academic practice (69% vs. 50%, p<0.01), higher involvement in clinical research (65% vs. 49%, p=0.01), more fellowship-dedicated scholarly time (36% vs. 22%, <0.001), a greater median number of publications (4.6 vs. 1.8, p<0.01) and abstracts (7 vs. 3.7, p<0.01), were more likely to have submitted a grant (29% vs. 5%, p=0.03) and had higher satisfaction with training (92% vs. 64%, p<0.001). Mentors were mostly chosen by mentees (70%) and shared gender identity (61%) but often had a different race or ethnicity (71.8%). The majority found mentorship relationships satisfactory (87%), contributing to increased academic productivity (84%) and reduced mentee burnout and stress levels (60%). In bivariate analysis, all mentor attributes significantly influenced higher academic productivity and mentee satisfaction. The most divergent for academic productivity were improved communication, alignment with expectations, inspiration for goal attainment, and effective networking. For mentorship satisfaction, distinctions were found in communication enhancement, goal-oriented assistance, knowledge/skill enrichment, and personalized career path development. Traits like active listening and adapting communication styles were not linked to decreased burnout, but actively supporting work-life balance independently correlated with reduced burnout. Conclusion: Mentorship positively affects endocrine fellows' scholarly productivity and career development. Yet, a significant number lack mentors or access to programs. Mentor attributes, like effective communication, goal alignment, and networking support boost productivity and satisfaction. However, reducing mentee burnout hinges on actively fostering work-life balance.

Presentation: 6/3/2024
7759 Undetectable PTHrP and Elevated Il-6 in a 517759 Year Old Male With Clear Cell Renal Carcinoma, Complicated by Paraneoplastic Hypercalcemia
Authors: Cedeno Evangelina , Patel Toral Aminbhai , Zacharia Christine
Published: October 2024

Disclosure: E. Cedeno: None. T. Patel: None. C. Zacharia: None.

Title Undetectable PTHrP and elevated IL-6 in a 51-year-old male with clear cell renal carcinoma, complicated by paraneoplastic hypercalcemia. Introduction: Malignant hypercalcemia as a paraneoplastic syndrome is very common in lung and kidney cancers. Traditionally, humoral hypercalcemia of malignancy (HHM) is linked to excess PTHrP production, but other possible contributors, such as interleukin-6 (IL-6), have been identified. We present a case of HHM with undetectable PTHrP and elevated levels of IL-6. Case A 51-year-old male with RCC presented with symptomatic hypercalcemia (polyuria and polydipsia), found during a pre-op visit. Initial tests were consistent with non parathyroid-mediated hypercalcemia: adjusted Ca 13.2 (9.1-11.2 mg/dL), iCal 1.69 (0.95-1.32 mmol/L), iPTH <4.0 (8.0-85.0 pg/mL), 25-OH-Vit D 41(30-80 ng/mL), 1,25-OH D 64.7 (24.8- 81.5pg/mL), PTHrP undetectable (<2.0 pmol/L), SPEP and UPEP without abnormalities. A CT showed a large 15x12x14 cm partially necrotic mass arising from the right kidney, consistent with malignancy. The patient was treated with isotonic IV fluids and underwent a right nephrectomy on day 6 of hospitalization with subsequent complete resolution of hypercalcemia 24 hours post-surgery. Adjusted Ca and iCal normalized. iPTH from initial 4 improved to 30.1 (8.0-85.0 pg/mL), and IL-6 was found to be high to 62.5 (0.0-13.0 pg/mL). Final pathology was consistent with clear cell RCC. The patient was discharged, with normal laboratory values on follow-up. Conclusion: Hypercalcemia is the most common paraneoplastic complication of RCC, and approximately 17% of all patients with RCC will develop hypercalcemia. Although usually mediated by PTHrP, evidence points towards other possible contributors. IL-6 has been hypothesized to be a possible mediator of malignant hypercalcemia in paraneoplastic syndromes¹. This is evidenced by our case, where our patient had undetectable levels of PTHrP in the setting of RCC, and was later found to have elevated IL-6, pointing to the latter as a possible culprit. In conclusion, our case supports IL-6 as a possible contributor to the pathogenesis of malignant hypercalcemia in RCC patients, literature is sparse on PTHrP-independent HHM and rare case reports demonstrated this phenomenon not just in RCC but also in other malignancies like ALL. There are some hypotheses implicating IL-6 influencing tumor growth as well as bone metastasis. Our case adds a valuable contribution to this limited database. Further studies are warranted to understand the role of IL-6 in HHM as well as anti-IL6 agents as a potential therapeutic option for treatment-resistant hypercalcemia. Reference: Max G. Weissglas, The Role of Interleukin-6 in the Induction of Hypercalcemia in RCC Transplanted into Nude Mice, Endocrinology, Volume 138, Issue 5, May 1997, Pages 1879-1885.

Presentation: 6/2/2024
7715 A Case of Cerebral Infarction Resulting From Pituitary Apoplexy
Authors: Jenkins William Evan , Elmaaz Ahmed , Makdissi Antoine
Published: October 2024

Disclosure: W.E. Jenkins: None. A. Elmaaz: None. A. Makdissi: None.

Background: Acute cerebral infarction as a sequela of pituitary adenoma and apoplexy is a rare phenomenon with poor outcomes. The mechanism is typically direct mechanical compression of the internal carotid artery secondary to hemorrhage. There is a very small number of reported cases of non-hemorrhagic compression. We report a case of a pituitary adenoma causing tandem internal carotid-middle cerebral artery occlusion with resultant infarction, most likely due to non-hemorrhagic pituitary apoplexy. Clinical Case: A 76-year-old male with hypertension and type II diabetes mellitus presented to the emergency department with a sudden onset severe headache, left facial droop, and left-sided weakness. CT stroke study revealed a right-sided cavernous ICA occlusion and a tandem MCA occlusion with a large sellar mass extending into the right sphenoid and cavernous sinus. Ophthalmologic evaluation revealed right pupillary dilation and ophthalmoplegia concerning for orbital apex syndrome. Emergent thrombectomy, angioplasty, and stenting of the occlusion in the supraclinoid segment of the ICA were performed, and treatment with dual antiplatelet therapy was initiated. MRI confirmed a large 25x20x20 mm right paramedian sellar/suprasellar mass with encasement of the ICA, however there was no evidence of sellar hemorrhage. Given recent stenting and the patient's hemodynamic stability, the neurosurgical team opted for delayed surgical intervention. The patient was discharged with marked improvement in left-sided weakness, although his right pupil remained minimally reactive with visual perception only to light. Based on biochemical evaluation, the mass was deemed non-functional, as prolactin and IGF-1 were within normal limits. There was evidence of secondary hypothyroidism and hypogonadism. Transsphenoidal surgery was pursued, occurring 114 days from symptom presentation. Histopathology revealed foci of devitalized anterior pituitary consistent with infarction of a pituitary adenoma. He was started on IV hydrocortisone on the day of surgery and tapered to a daily replacement dose. Visual acuity in the right eye remained severely reduced after the operation. Conclusion: Our case displays that, while extremely rare, clinicians should be aware that pituitary adenomas can result in cerebral infarction secondary to mechanical compression of the internal carotid artery, typically caused by an apoplexy event, hemorrhagic or ischemic. Emergent medical and endovascular treatment of the infarction should take precedence, and if clinical stability allows, a delayed surgical approach to resect the pituitary mass may be appropriate.

Presentation: 6/2/2024