bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI257 Adrenal Insufficiency Secundary Due Immune Checkpoint Inhibitors Therapy
Authors: Rivera Sandra Rocio , Valencia Javiera , Figueroa Elizabeth , Calisto Javiera 
Published: October 2023

Abstract
Disclosure: S.R. Rivera: None. J. Valencia: None. E. Figueroa: None. J. Calisto: None.
Background: Immune checkpoint inhibitors (ICIs) are new anticancer immunotherapies that can trigger a variety of immune related adverse events (irAEs) in different organs, including the endocrine system. Adrenal insufficiency is uncommon with a nonspecific clinical presentation that must be recognized in time due to its potential mortality. Clinical Case: 41 year old man diagnosed with papillary renal cell carcinoma. He underwent surgery, performing a ​​right radical nephrectomy plus bilateral lymphadenectomy. He started chemotherapy in March 2022 with ICIs, Nivolumab and Ipilimumab. Three months later he presents with myalgias, fatigue and 6 kilogram weight loss. Physical exam: in regular conditions, vital signs with blood pressure 70/40 mmHg, heart rate 84 bpm, with no signs of hyperpigmentation or dehydration. No evidence of clinical hyperthyroidism. Lab results: low ACTH levels: 6.4 pg/ml (9 - 69 pg/ml), low cortisol: 0.06 µg/dl ( 6.02-18.4 µg/dl), low TSH: 0.1 µU/ml ( 0.4- 4.2 µU/ml) and normal free T4: 1.01 ng/dl ( 0.93-1.7 ng/dl). Antibody tests were negative: anti thyroglobulin, anti TPO and TRAB. Normal thyroglobulin levels. Sellar MRI was requested: normal, metastasis were ruled out. Thyroid ultrasound: normal thyroid gland. Exclusion of exogenous use of corticosteroids and levothyroxine was done. Case was interpreted as an adrenal insufficiency due to hypophysitis with associated thyrotoxicosis. Treatment with hydrocortisone was started, while thyroid function progression was observed. In the following lab control, elevation of TSH was noted. Two months later, we documented elevation of TSH levels: 5 µU/ml and decline of free T4 levels: 0.58 ng/dl, starting levothyroxine supplementation. Patient had a favorable clinical evolution. Conclusion: Adrenal insufficiency due to hypophysitis is uncommon and is mostly linked to Ipilimumab use. In those cases pituitary gland MRI is often normal most of the time. Thyroid involvement, which is frequently seen with Nivolumab therapy, varies from thyrotoxicosis, hyperthyroidism and hypothyroidism. Usually produces chronic damage and needs permanent treatment. The potentially lethal nature of these events makes it essential for oncologists and endocrinologists to be aware of these manifestations in order to achieve early treatment.
Presentation: Friday, June 16, 2023
FRI258 A Diagnostic Journey To Autoimmune Polyendocrine Syndrome Type 2
Authors: Amankwah Samuel , Driscoll Henry Keane , Muojieje Chukwudi , Sanati Milad 
Published: October 2023

Abstract
Disclosure: S. Amankwah: None. H.K. Driscoll: None. C. Muojieje: None. M. Sanati: None.
Background: Approximately 50-65% of patients with autoimmune adrenal insufficiency have one or more autoimmune endocrine disorders. This case demonstrates the importance of considering autoimmune polyendocrine syndrome (APS) when a patient presents with more than one autoimmune endocrine disorder. Case: A 29-year-old woman with history of idiopathic intracranial hypertension, hypothyroidism on levothyroxine 50 mcg daily, endometriosis, and chronic migraines complained of fatigue, word finding difficulty, misspeaking of words, and staring spells. An MRI of the brain w+wo IV contrast revealed hypo-enhancing appearance of the pituitary gland. The patient was referred to endocrinology by neurology. Hormonal work up was performed checking for prolactin, ACTH, morning cortisol, TSH, Free T4, FSH, LH, IGF-1 and a serum chemistry panel. Thyroid antibodies were also ordered to help understand the etiology of her hypothyroidism. Pituitary hormones were normal except elevated TSH and borderline low serum cortisol. Subsequently a co-syntropin stimulation test resulted in inadequate cortisol rise. ACTH level measured inappropriately low normal. The patient then started steroid replacement therapy. Thereafter, 21-hydroxylase antibodies, serum renin and aldosterone were checked to screen for Addison Disease. Her 21-hydroxylase antibody was positive, aldosterone level low, and renin elevated pointing to autoimmune adrenalitis etiology. Her thyroid antibodies were also positive indicating autoimmune thyroid disease. Considering these results, the condition of APS came into question. Hence, the patient was screened for type 1 diabetes mellitus which was positive for glutamic acid decarboxylase 65 antibody but negative for insulin and pancreatic islet cell antibodies. Her hemoglobin A1c was 5.0%. Due to her history of gluten intolerance, she was screened for celiac disease which was negative for t-Transglutaminase antibody. The patient’s fatigue improved on steroid replacement therapy. She became euthyroid after increasing her levothyroxine dose to 75 mcg daily, and repeated MRI a year later did not show pituitary abnormalities. Discussion: APS type 2 is a polygenic inherited disorder associated with HLA-DR3 and DR4 that affects adult females more than males. The syndrome is characterized by type 1 diabetes mellitus, autoimmune thyroid disease and Addison disease. Associated nonendocrine autoimmune syndromes include celiac disease, pernicious anemia, and atrophic gastritis. These characteristics overlap with APS type 1 except for autoimmune thyroid disease that presents with type 2. It should be noted that thyroxine therapy can precipitate a life-threatening Addison crisis in a patient with untreated adrenal insufficiency and hypothyroidism. Therefore, it is necessary to evaluate adrenal function in all hypothyroid patients in whom APS is suspected.
Presentation: Friday, June 16, 2023
FRI259 Antiphospholipid Syndrome And Adrenal Insufficiency: An Underrated Association
Authors: Khalid Sualeha , Arumugam Minni Shreya , Passarella Pasquale 
Published: October 2023

Abstract
Disclosure: S. Khalid: None. M. Arumugam: None. P. Passarella: None.
Introduction: Catastrophic Antiphospholipid Syndrome (CAPS) is a rare and life-threatening subtype of Antiphospholipid Syndrome (APS) that causes widespread vascular thrombi. Endocrine complications of APS are very rare, however the most common is Adrenal Insufficiency (AI). Overt AI is only found in 0.4% of patients with APS while only 0.5% of patients with AI are diagnosed with APS. Either thrombosis leading to infarction or hemorrhage can cause AI in patients with APS. Sometimes, adrenal insufficiency or crisis can be the primary presentation of APS. Here, we present a case of AI in the setting of CAPS. Case Presentation: A 17-year-old woman with past medical history of chronic immune thrombocytopenia was admitted to the intensive care unit due to cardiogenic and distributive shock. One week prior to her presentation she had developed a sore throat followed by progressive lethargy that eventually evolved into a state of unconsciousness and she was brought to the emergency department. Her presenting vital signs included temperature of 40.7 C and blood pressure of 89/36 mmHg. On physical exam, she appeared somnolent and pale, and had cool extremities. Labs on admission (11 pm) revealed cortisol level of 3.6 UG/DL (reference range 3.8-19.4 UG/DL), TSH 4.61 UIU/ml (reference range 0.45-4.5 UIU/ml), free T4 1.3 ng/dl (reference range 0.6-1.3 ng/dl), aldosterone 11.3 ng/dl (reference range supine &lt; 3-39.2 ng/dl), sodium 135 MEQ/L (reference range 135-145 MEQ/L), and potassium 4.7 MEQ/L (reference range 3.5-5.2 MEQ/L). Echocardiogram was remarkable for new onset reduced ejection fraction of 25-30% and left ventricular thrombi. Additionally, brain MRI showed acute infarcts. Due to concern for an underlying rheumatological disease, extensive autoimmune work up was initiated, and she was started empirically on methylprednisolone 30 mg intravenous twice daily. To further evaluate thrombi, CT scan of the abdomen and pelvis was performed, revealing bilaterally enlarged and hypoenhancing adrenal glands likely related to ischemia or infarction along with left renal vein thrombosis. Laboratory work-up returned positive for anti-cardiolipin IgM and IgG antibodies. In the setting of multiple vascular thrombi and positive antibodies, she was diagnosed with CAPS. The diagnosis of AI was made due to a low cortisol level in a state of shock and was deemed secondary to CAPS. For the treatment of CAPS she was continued on methylprednisolone with a plan for a slow taper. To ensure mineralocorticoid replacement was adequate fludrocortisone was also added at a dose of 0.1 mg with close monitoring of electrolytes and vital signs. Conclusion: Our case illustrates a rare though potentially fatal endocrine complication of CAPS and highlights the importance of its awareness. Undiagnosed and untreated adrenal insufficiency can lead to extremely poor outcomes, including death.
Presentation: Friday, June 16, 2023
FRI271 A Case Of Autoimmune Polyglandular Syndrome Type 2 Presenting With Cardiac Symptoms
Authors: Lin Joanne , Lee Christopher , Crawford Andrew Robert , Taub Cynthia 
Published: October 2023

Abstract
Disclosure: J. Lin: None. C. Lee: None. A.R. Crawford: None. C. Taub: None.
Autoimmune polyglandular syndrome type 2 (APS 2) is characterized by the combination of autoimmune adrenal insufficiency with autoimmune primary hypothyroidism, and/or type 1 diabetes mellitus, as well as other autoimmune conditions. The estimated prevalence is reported to be 1.4-4.5 cases per 100,000 persons. Presenting symptoms are often nonspecific, leading to delayed diagnosis; however, manifestations can sometimes become rapidly life-threatening. Cardiac symptoms, rare but clinically significant, can be the first presentation for APS 2.
34 year old male with history of asthma presents with nausea and chest pain, found to have pericarditis that was complicated by pericardial tamponade and cardiogenic shock requiring emergent pericardiocentesis and mechanical support with veno-arterial extracorporeal membrane oxygenation. Stress dose steroids were given due to concern for fulminant myocarditis. His condition improved with glucocorticoid treatment, but the etiology of his acute decompensation was unclear. He completed the prednisone taper before discharge and was started on amiodarone for atrial flutter. He presented with recurrent symptoms a week later. Cardiac MRI showed pericarditis without myocarditis. PET scan showed pericardial inflammation without evidence of malignancy or vasculitis. Broad infectious workup including viral studies was negative. An extensive biochemical workup showed low serum aldosterone and high renin activity while on prednisone. Autoimmune workup was positive for 21-hydroxylase antibody, thyroid peroxidase antibody, and homozygous for celiac HLA DQ8, suggestive of APS 2. Patient was started on levothyroxine for subclinical hypothyroidism with TSH &gt;20. Interleukin blockade with anakinra was initiated, and patient was discharged with 25mg of daily prednisone pending insurance authorization for anakinra. A month later, patient re-presented with pericarditis. Patient received stress dose steroids, and was started on fludrocortisone. Levothyroxine was stopped because of amiodarone induced thyrotoxicosis. Patient was discharged on a prednisone taper regimen, and anakinra was approved a month later.
Few case reports have described the association between APS 2 with pericardial tamponade. In healthy patients presenting with unexplained pericarditis, autoimmunity should be considered as a differential diagnosis as it can rapidly become life-threatening requiring urgent intervention. It is important to recognize for these patients, they are at risk for recurrent pericarditis and cardiac tamponade.
Presentation: Friday, June 16, 2023
SAT263 Osteocalcin Promotes Cortisol Production In Human Adrenal Cells
Authors: Scheske Rachel , van Rooyen Desmaré , Rainey William E 
Published: October 2023

Abstract
Disclosure: R. Scheske: None. D. van Rooyen: None. W.E. Rainey: None.
Background: Osteocalcin (OCN) is a peptide exclusively produced by osteoblasts in bone. In an uncarboxylated form, OCN has been shown to function as a hormone affecting physiological processes such as reproduction and energy metabolism in mice and humans. Murine studies have shown that uncarboxylated OCN upregulates fetal mouse glucocorticoid production through a unique regulatory axis between osteoblasts and adrenal cortex cells. The increase in adrenal steroid production has been attributed to OCN heightening adrenocorticotropic hormone (ACTH). The influence of adrenal glucocorticoids on glucose metabolism and bone composition is well studied but the effect of OCN on human adrenal steroidogenesis remains unknown. Herein, we hypothesized OCN would stimulate cortisol production in human adrenal cells. Methods: OCN’s effect on adrenal glucocorticoid production was investigated using primary cultures of human adrenal cells (PAC). Cells were treated for 24h with 1000 nM OCN with/without cAMP/protein kinase A (PKA) signaling pathway agonists (ACTH, forskolin, 8-bromo cAMP (8Br-cAMP), and dibutyryl cyclic AMP (dbcAMP)). Cortisol levels were quantified using an enzyme-linked immunosorbent assay. RNA was isolated and assessed by quantitative real-time PCR (RT-qPCR) to identify changes in transcript levels of enzymes catalyzing glucocorticoid production: cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase/17,20-lyase (CYP17A1), and 11β-hydroxylase (CYP11B1). Results: Cortisol production in PAC were significantly induced by all tested agonists; ACTH (22-fold), forskolin (27-fold), 8Br-cAMP (26-fold), and dbcAMP (30-fold) relative to basal. Although OCN, alone, did not significantly increase cortisol in this cell model, co-treatment with ACTH increased cortisol levels 1.4-fold (40.1 ng/mL; p&lt;0.0001) compared to ACTH (28.2 ng/mL). Similarly, co-treatment with forskolin or 8Br-cAMP increased cortisol, relative to the respective agonists, by 1.3-fold (p&lt;0.001) and dbcAMP by 1.2-fold (p&lt;0.01). RT-qPCR analysis showed no changes in CYP11A1 or CYP17A1 transcript levels in co-treatments with OCN and ACTH relative to ACTH. However, CYP11B1 mRNA levels, relative to the respective controls, were increased in samples co-treated with OCN and ACTH/-agonist. OCN co-treatments with ACTH, forskolin, 8Br-cAMP and dbcAMP increased CYP11B1 levels by 1.8-, 1.4-, 1.3-, and 1.2-fold, respectively. Conclusion: Data presented in this study show stimulatory effect of OCN on human adrenal cells. OCN, in the presence of ACTH and other PKA agonists, increased cortisol production via upregulating CYP11B1 transcript levels. Defining the mechanism and receptor interaction through which OCN functions in human adrenal cells remain to be determined.
Presentation: Saturday, June 17, 2023
SAT270 Parity Increases Corticosterone Response To Restraint-induced Stress After Mild Blast Traumatic Brain Injury In Mice
Authors: Anisowicz Sarah , Loayza Careaga Mariella Bodemeier , John Wu T 
Published: October 2023

Abstract
Disclosure: S. Anisowicz: None. M. Bodemeier Loayza Careaga: None. T. Wu: None.
Background: Traumatic brain injury (TBI) is a common problem worldwide, with an estimated incidence of 69 million injuries per year. In the US military, one of the most common forms of TBI during operational deployments after Sep 11, 2001 was the blast TBI, thought to be responsible for over 80% of TBI sustained in theater. One consequence of TBI is dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. HPA axis dysregulation is linked to increased risk for psychiatric disorders. Furthermore, prior research has shown that TBI may dysregulate the HPA axis in a sex-dependent manner. Throughout a female’s life span, there are several sentinel events of hormonal consequence, including pubarche, menopause, and parity, which are known to be times of changes in risks for psychiatric disorders. Objectives: The role of parity on TBI response has not yet been studied, though parity has been shown to decrease fear-related behaviors and decreased corticosterone load in multiparous mice when compared to nulliparous (NP) controls. Our objective is to determine if parity alters corticosterone (CORT) response to restraint, a mild psychological stressor, in mice exposed to mild blast TBI (mbTBI). Methods: One hundred thirteen NP or primiparous (PP) C57Bl6/J mice were randomly assigned to receive sham or mbTBI. Among those that received mbTBI (19.2 ± 0.12 psi), 32 were NP and 24 were PP. Among sham mice, 32 were NP and 26 were PP. All mice received isoflurane anesthesia prior to sham or mbTBI treatment. At 7-8 days after mbTBI, half the mice within each treatment group were subjected to a mild 20-min restraint before being anesthetized by CO2 followed by collection of trunk blood. Serum was harvested and analyzed for CORT concentrations by ELISA (Enzo Life Sciences). Results: All mice that received mbTBI had a longer (p&lt;0.05) righting time compared to those that did not. There was no main effect of parity in the righting time (p&gt;0.1). PP mice who experienced mbTBI demonstrated a greater (p&lt;0.05) CORT response to restraint (157.3 ± 21 pg/mL) when compared to NP mice (95.9 ± 7.2 pg/mL). CORT response to restraint did not differ (p&gt;0.1) between NP and PP mice who did not experience mbTBI (96.1 ± 7.6 vs 109.2 ± 16 pg/mL). Conclusions: Our data indicates that mbTBI alters HPA axis reactivity in PP mice compared to NP mice, increasing the CORT response to restraint induced stress. Parity alone did not alter CORT response to restraint stress or baseline CORT levels. The results of our finding highlight the importance of parity as a factor in an individual’s lifespan.
Presentation: Saturday, June 17, 2023
SAT278 Thyroid Hormones Regulate 11bhsd Enzymes: A Novel Function In Glucocorticoid Hormone Metabolism
Authors: Bessiene Laura , Perrot Julie , Hescot Segolene , Bourdin-Pintueles Alexandra , Vitellius Geraldine , Sachs Laurent M , Kamenicky Peter , Lombes Marc , Pussard Eric , Viengchareun Say , Martinerie Laetitia 
Published: October 2023

Abstract
Disclosure: L. Bessiene: None. J. Perrot: None. S. Hescot: None. A. Bourdin-Pintueles: None. G. Vitellius: None. L.M. Sachs: None. P. Kamenicky: None. M. Lombes: None. E. Pussard: None. S. Viengchareun: None. L. Martinerie: None.
Glucocorticoid hormone metabolism is regulated by 11-beta hydroxysteroid dehydrogenase enzymes: 11βHSD2, mostly expressed in the distal nephron, converts corticosterone into 11-dehydrocorticosterone in rodents, while 11βHSD1 catalyzes the opposite reaction in liver. Glucocorticoid hormone metabolism may be altered under pathophysiological conditions of hypothyroidism. However, direct functional relationship between glucocorticoid and thyroid hormones (T3) signaling pathways remains elusive. Identification of putative Thyroid Response Elements (TRE) in the promoter regions of hsd11b2 and hsd11b1 genes suggested that T3 might directly regulate expression and/or activity of these enzymes.We used human translational studies, a mouse model of hyperthyroidism and murine renal and hepatic cell lines to investigate the role of thyroid hormones in glucocorticoid hormone metabolism.In hypothyroid patients, the urinary [E]/[F] ratio measured by LC-MS/MS technology, showed a 60% decrease (P&lt;0.05), compared to age- and sex- matched euthyroid controls, suggesting a regulation of glucocorticoid metabolism by T3. Similarly, a significant positive correlation was observed between the urinary [E]/[F] ratio and serum T4L concentration in hyperthyroid patients before and after normalization of T4L levels.Administration of T3 in drinking water, mimicking a mouse model of hyperthyroidism, led to significant increase in renal 11βHSD2 mRNA (P&lt;0.05) and decrease in liver 11βHSD1 mRNA and protein levels (P&lt;0.01), compared to control mice.Finally, T3 induced an increase in 11βHSD2 transcript levels in renal KC3AC1 cells (P&lt;0.01) and a decrease in 11βHSD1 mRNA levels in hepatic HepG2 cells (P&lt;0.01). 11βHSD2 activity increased by 20% (P&lt;0.05). In HEK 293T cells, T3 transactivated hsd11b2 promoter via the Thyroid Receptor α1 (TRα1). ChIP experiments further demonstrated a T3-dependent specific recruitment of TRα1 onto hsd11b2 promoter. Altogether, these findings demonstrate that T3 directly regulate expression and activity of 11βHSD enzymes, thereby controlling glucocorticoid hormone metabolism and action.
Presentation: Saturday, June 17, 2023
SAT281 Screening For Adrenocortical Insufficiency In Patients With X-linked Adrenoleukodystrophy
Authors: Berquist John , Kiani Rabia Nadeem , Wahl Matthew Patrick 
Published: October 2023

Abstract
Disclosure: J. Berquist: None. R.N. Kiani: None. M.P. Wahl: None.
Background: A 41-year-old male initially presented to neurology clinic for complaints of poor balance, lower extremity weakness, and numbness. He previously had exam findings of lower extremity spasticity and hyperreflexia, distal vibratory loss, positive Romberg, and difficulty with Tandem gait. His symptoms had been progressive following an ankle sprain 8 years earlier and he was treated with physical therapy and baclofen. He is highly active otherwise and enjoys rock climbing, which was difficult to do given his symptoms. Clinical Case: Genetic screening was performed to evaluate for hereditary spastic paraparesis, which resulted positive for a mutation in the ABCD1 gene with a p.Lys336Glu mutation of uncertain significance. Interestingly, this ABDC1 variant was not detected in submitted maternal sample, hence patient’s mutation likely occurred de novo. This variant is not established in population databases (gnomAD no frequency) but has been observed in at least one individual with clinical features of adrenomyeloneuropathy. X-linked adrenoleukodystrophy causes impairment of beta oxidation that leads to accumulation of saturated very long chain fatty acids (VFLA) in multiple tissues. There are many clinical phenotypes, but they are hallmarked by neurologic signs and symptoms. Although neurologic symptoms can often develop in childhood, they can be delayed and present in adulthood, as can adrenal insufficiency (AI). However, males are overwhelmingly likely to develop adrenocortical insufficiency compared to females. Our patient presented with a BMI of 22.94, HR 50 bpm, and blood pressure 120/76; reflecting his active lifestyle. Recent electrolytes were within normal limits, AM cortisol was 13.0, and ACTH 544.0 Given the elevated ACTH and known cause of adrenal insufficiency, we proceeded with ACTH stimulation test. Peak cortisol resulted at 13.1 (at 60 minutes) and he was started on replacement glucocorticoid therapy per body-surface area. Upon further literature review, patients can also develop loss of mineralocorticoid production. Renin and aldosterone were ordered and were both within normal limits. Conclusion: Males with adrenoleukodystrophy are at a much higher risk of developing adrenal insufficiency (AI) compared to females. Additionally, AI will often develop later in life, so a low threshold for screening should be present for the endocrinologist. Mineralocorticoid deficiency can also develop, although not as commonly. Loss of adrenal function can lead to patient demise, and therefore adrenal function needs to be closely evaluated in people with leukodystrophy.
Presentation: Saturday, June 17, 2023