bluuebunny/crossref_metadata_2025_split huggingface dataset:
8230 Adrenal Crisis, Unrevealing the Impact of Immigration on Central Adrenal Insufficiency
Authors: Sacoto Daniel Hernan , Madani Kulsum , Patel Dhara , De Rosairo Anne , Rai Gur Kiratt , Belokovskaya Regina , Franco-Akel Alberto A 
Published: October 2024

Abstract
Disclosure: D.H. Sacoto: None. K. Madani: None. D. Patel: None. A. De Rosairo: None. G. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel: None.
Introduction: Even though patients with secondary adrenal insufficiency (AI) may go through life without an episode of adrenal crisis, there is a 50% chance of developing it. Around 90% have a known precipitating, with infections and surgery being frequent causes. However, emotional stress is unrecognized. With the recent increase in worldwide immigration, it is important to recognize these as potential triggers in those with AI. Here, we present a case of adrenal crisis triggered by immigration. Case presentation: A 41-year-old female diagnosed eighteen years ago with Sheehan syndrome, with unknown replacement therapy status, is brought to ED for altered mental status. One week before, she crossed the Mexican-US border as an illegal immigrant and was hospitalized in Arizona after developing mutism and mood lability. She was initiated and discharged on hormone replacement therapy. She arrived in New York confused with flat affect and impaired recent memory. She was hypotensive (BP: 92/64 mmHg), hyponatremic (Na: 133 mEq/L), and anemic (Hb: 10.6 g/dL). She had an inappropriate normal ACTH of 25 pg/mL (7.2-63.3 pg/mL). MRI findings confirmed empty sella, suggestive of central AI. Additional studies revealed central hypothyroidism (low normal TSH (1.36 uIU/mL), low-normal Free T4 (1.4 ng/dL), gonadotroph dysfunction with low FSH (2.7 IU/L), and low estrogen levels (20 pg/mL) for her age, and low normal prolactin (4.6 ng/mL). After initiating a stress dose of IV hydrocortisone and IV levothyroxine, her affect, memory, mental status, and vital signs (BP: 128/80 mmHg) improved. She was educated regarding the need for maintenance doses as an outpatient. At the one-month follow-up, she continued with a positive response. Discussion: Patients with chronic AI are unable to produce sufficient cortisol and are at risk of acute adrenal crisis when under stress. Stressful situations, including accidents, job interviews, or death in the family, have been described. However, with almost doubling the number of people entering the US without prior authorization between 2022 and 2023, immigration, which poses physical and emotional stress, certainty will become a matter of importance for those with AI. Guidelines to manage cortisol replacement in times of fever, infections, trauma, surgery, or severe pain are available. However, it is more difficult to define how emotional and psychological challenges affect the stress response, mainly because each challenge is unique. Therefore, it is important to advocate for policies to provide medical alert bracelets to immigrants with known AI in addition to providing education about emergency injection kits in cases of impending crisis.
Presentation: 6/3/2024
7839 Assess Management of Adrenal Insufficiency in Melanoma Patients Treated with Cancer Immunotherapy
Authors: Lin W , Min L 
Published: October 2024

Abstract
Disclosure: W. Lin: None. L. Min: None.
Despite high prevalent of adrenal insufficiency in melanoma patients treated with cancer immunotherapy, no study has examined the management of adrenal insufficiency in these patients. We performed this retrospective, longitudinal cohort study at Mass General Brigham, Boston, aims to characterize the management of adrenal insufficiency in melanoma patients. Patients were identified through our RPDR search tool, and medical record reviews were conducted. Three patient groups were analyzed: Melanoma with secondary adrenal insufficiency group (Mel_SAI, n=74), Melanoma matched control group (Mel_Con, n=69), and Pituitary macroadenoma-related adrenal insufficiency matched control group (Pit_Con, n=37). We compared self-perceived quality of life, glucocorticoid replacement dose, and clinic visit. Mel_SAI patients exhibited significantly higher incidences of anxiety (43.1%, 95%CI: 32.3-54.6), fatigue (73.6%, 95%CI: 62.4-82.4), pain (58.3%, 95%CI: 46.8-69.0), and insomnia (36.1%, 95%CI: 26.0-47.6), as compared to Pit_Con group (21.6%, 11.4-37.2; 24.3, 13.4-40.1; 29.7%, 17.5-45.8; 5.4%, 1.5-17.7, respectively). The initial hydrocortisone dose was higher for Mel_SAI (30mg qd, 95%CI: 20.5-25.1) compared to Pit_Con (15mg qd, 95%CI: 12.8-18.3). Additionally, the Mel_SAI group had fewer endocrinology clinic visits (3, 95%CI: 3.40-5.04) than the Pit_Con group (9, 95%CI: 7.35-10.9). Subgroup analysis indicated a higher mortality risk (HR 2.61, 95% CI 1.11-6.13) in Mel_SAI patients with fewer than three endocrinology visits over five years. Compared to the Mel_Con group, Mel_SAI patients also showed higher incidences of fatigue (71.6%, 95%CI: 60.5-80.6; Mel_Con: 55.1%, 95%CI: 43.4%-66.2%), but lower rates of depression (25.7%, 95%CI: 17.1-36.7; Mel_Con: 43.5%, 95%CI: 32.4-55.2) and appetite loss (24.3%, 95%CI: 16.0-35.2; Mel_Con: 47.8%, 95%CI: 36.4-59.4). No significant difference in other self-perspective symptoms. Furthermore, Mel-SAI patients had more oncological clinic visits (71, 95%CI: 74.0-109.2) than those in the Mel_Con group (41, 95%CI: 42.1-64.1). Our study suggests that most self-perceived quality of life in the Mel_SAI group is related to melanoma rather than adrenal insufficiency. Therefore, a higher initiating dose of hydrocortisone in melanoma patients with adrenal insufficiency may not be necessary. However, increasing endocrine clinic visits in cancer patients with cancer immunotherapy-related adrenal insufficiency may improve their survival outcomes.
Presentation: 6/3/2024
8589 Case Report of Metastatic NET in a Middle-Aged African American Female
Authors: Anaraki Kimia Saleh , Tsou Han Chen Tom , Ahmed Elham Ahmed , Birhane Tekabe N , Wang Xiaoyan 
Published: October 2024

Abstract
Disclosure: K. Saleh Anaraki: None. H. Tsou: None. E. Ahmed: None. T.N. Birhane: None. X. Wang: None.
Neuroendocrine neoplasms (NEN) is an umbrella term characterizing cancers of both neural and endocrine cells. In addition, depending on the speed of proliferation; Ki-67 levels, they are then classed as either low grade; neuroendocrine tumor (NET), or high grade; neuroendocrine carcinoma (NEC). With more than 12,000 new occurrences detected in the United States year, Neuroendocrine tumors make up approximately 0.5% of all newly diagnosed malignancies with approximately 175,000 people concurrently with this condition hinting at an increase in both prevalence, incidence, but most importantly, survival outcomes. Here we present a case of a well differentiated NET in a 59 year old female with an PMH of HTN, HLD, Osteoarthritis, vitamin D deficiency, who presented to the ED with left sided atypical chest pain lasting for 20 hours. She reports a 5/10 dull to sharp chest pain lasting 5 to 10 seconds localizing to the sternal area with no radiation and episodes of complete pain resolution. She also reports no aggravating or relieving factors or other accompanying symptoms. Workup for cardiac causes was negative but a CT scan to rule out PE revealed incidental findings of liver masses and spine lesions suggestive of metastasis. Liver core biopsy discovered a low grade metastatic well differentiated neuroendocrine tumor with immunohistochemical staining favoring colorectal as the primary origin. In addition, tumor cells were positive for chromogranin, synaptophysin, AE1/AE3 and CDX2, with Ki-67 showing a low proliferative index. CEA and AFP were negative. FDG-PET showed multiple hypodense lesions throughout the liver in both lobes, with a few hypermetabolic soft tissue masses in the root of the mesentery which was consistent with the suggestive finding of metastatic disease. NETs from either the gastroenteropancreatic or respiratory structures account for approximately 65% and 25% of total NETs respectively and are usually the most common sites of origin. It is also important to note the differing incidences of origins among different races as well; such as caucasian patients having more midgut NETs, whereas rectal NETs occur more commonly in other races. It is also important to distinguish that most NENs are NETs which have a slower progression rate, whereas NECs; which have a rapid disease progression, make up approximately 15% of all cases. With most neuroendocrine tumors being asymptomatic, it is often hard to come to a clinical diagnosis at time of presentation due to the various hormone secretions that these tumors produce which can result in unique clinical syndromes. Therefore it is important for clinicians to be aware of the diverse manifestations of this disease as the key step to the management of these rare tumors as well as safeguarding patients who may have a more sinister pathology.
Presentation: 6/2/2024
12432 Chronic Intermittent Hypoxia Impairs Calpain And Caspase-3 Activity In The Hippocampus
Authors: Mabry Steve , Bradshaw Jessica L , Gardner Jennifer J , Wilson Elizabeth Nicole , Yeung Hannah , Cunningham Rebecca L 
Published: October 2024

Abstract
Disclosure: S. Mabry: None. J.L. Bradshaw: None. J.J. Gardner: None. E.N. Wilson: None. H. Yeung: None. R.L. Cunningham: None.
Background: Obstructive sleep apnea (OSA) is a highly prevalent sleeping disorder in the USA with known sex differences in incidence and severity. OSA is associated with memory impairments. However, the mechanisms by which OSA disrupts memory are not fully understood. Calpain and caspase-3 are proteases which regulate synaptic function and memory formation and have been observed to be sensitive to gonadal hormone levels (testosterone, estradiol). OSA has been observed to decrease gonadal hormones. This study examined whether chronic intermittent hypoxia (CIH), a rat model of OSA: (1) induced dysregulation in calpain and caspase-3 activity in the dorsal hippocampus; (2) if these proteases were dependent on circulating gonadal hormones; and (3) if these effects were dependent on sex. Methods: Adult Sprague-Dawley male and female rats were exposed to CIH or normoxic room-air for 14 days. At the conclusion of CIH, rats were sacrificed, and tissues were collected. Plasma was collected to measure circulating gonadal hormones (testosterone, estradiol). Gonadal hormones were extracted from the plasma and analyzed by high throughput multiplex. Brains were flash frozen and dissected for hippocampal subregion isolation. We quantified calpain and caspase-3 cleavage activity by measuring cleaved spectrin within CA1 and CA3 subregions of the dorsal hippocampus. Results: CIH impaired calpain cleavage activity in the CA1 of males, with no effect on calpain activity in the CA1 of females. No effects of CIH or sex on caspase-3 cleavage activity were observed in the CA1. In contrast, caspase-3 cleavage activity was reduced by CIH in the CA3 in females but not males. No effects of CIH or sex were observed on calpain cleavage activity in the CA3. No effects of CIH were observed on gonadal hormones. We observed expected sex differences in testosterone (males higher than females) and estradiol (no sex difference between males and females). Conclusions: Our results indicate that CIH impairs calpain and caspase-3 cleavage activity in a hippocampal subregion- and sex-specific manner. These effects were independent of circulating gonadal hormones. Since the CA1 and CA3 subregions of the dorsal hippocampus are involved in memory consolidation, these cellular changes in calpain and caspase-3 activity could mediate CIH-induced memory impairments, such as impaired recollective memory. These findings could have clinical implications for memory impairments in patients with OSA.
Presentation: 6/2/2024
8037 Ciliopathy Genes are Expressed in the Developing Pituitary Gland and Mature Hormone-Producing Cells
Authors: Athul Sandria W , Jaramillo Natalie , Ellsworth Buffy S 
Published: October 2024

Abstract
Disclosure: S.W. Athul: None. N. Jaramillo: None. B.S. Ellsworth: None.
Primary cilia play critical roles in several signaling pathways including sonic hedgehog and Wnt to help regulate cell differentiation and proliferation. Ciliopathies are a group of disorders associated with genetic mutations resulting in an abnormal formation or structure of the primary cilium. Recently, congenital hypopituitarism was identified in some patients with ciliopathies. To begin to evaluate the role of these genes in pituitary gland function, we used the International Mouse Phenotyping Consortium (IMPC) database to identify several ciliopathy genes that, when mutated, cause pituitary hypoplasia in mice. To determine if primary cilia are present in the somatotrope-like GHFT1-5 cells, ARL13B, a regulatory GTPase protein that is localized to the ciliary membrane, was identified. In the absence of serum, it was seen that the number of cilia present was relatively high, likely as a result of the lower rate of cell division. Gene expression of the ciliopathy genes, Cc2d2a, Mks1, and Pibf1 was detected via RT-qPCR in GHFT1-5 cells. While Mks1 and Pibf1 were expressed at low levels, Cc2d2a was more robustly expressed. Expression of Cc2d2a, Mks1, Pibf1, and Rpgrip1l was observed on adult pituitary glands of C57BL/6 mice. Consistent with active SHH signaling during early pituitary organogenesis we see the expression of Rpgrip1l and Pibf1 in Rathke’s pouch at e10.5, 11.5, and e12.5. ARL13B and α-Tubulin, markers of primary cilia, were used to determine which hormone-producing cell types contain primary cilia in adult and e18.5 C57BL/6 mice. Primary cilia are present in a fraction of all hormone-producing cell types. These studies suggest that primary cilia are present in the pituitary gland during early organogenesis and may also be involved in the function of mature hormone-producing cells. Understanding the function of ciliopathy genes is important for expanding our understanding of congenital hypopituitarism.
Presentation: 6/3/2024
6701 Bilateral Adrenal Hematomas As Initial Presenting Sign Of Lung Adenocarcinoma
Authors: Gumireddy S , Panta R , Shaikh Y 
Published: October 2024

Abstract
Disclosure: S. Gumireddy: None. R. Panta: None. Y. Shaikh: None.
Introduction: Lung cancer typically presents with dyspnea, chest pain, hemoptysis, weight loss, or recurrent pulmonary infections. This case illustrates primary lung adenocarcinoma presenting with abdominal pain and bilateral adrenal hematomas. Clinical Case: 51-year-old male presented to the emergency department with left sided abdominal pain persisting for one week. CT abdomen showed a left suprarenal mass measuring 4.5 x 5 x 4.3cm indicating an acute adrenal hematoma. An MRI showed a partially solid left adrenal lesion that had hemorrhaged and a 1.3cm hemorrhagic nodule in the right adrenal gland. The patient remained hemodynamically stable. Hormonal evaluation done while patient was in the hospital showed renin level 0.417ng/mL/hr, aldosterone level &lt;1.0ng/dL, epinephrine level 312pg/mL, norepinephrine level 333pg/mL, cortisol 11.3, ACTH level 13, plasma metanephrine levels 93pg/mL, plasma normetanephrine levels 111.7pg/mL, DHEA-S 151mcg/dL, potassium 4.1mmol/L, raising concern for hypersecretion. Patient was discharged with plans for outpatient follow-up but was readmitted in two months due to worsening abdominal pain. Repeat imaging revealed an increase in size of adrenal lesions, measuring 3.3 x 3.6 cm within the right adrenal gland and a 6.7 x 6.3 cm heterogeneously enhancing lesion within the left adrenal gland concerning for metastatic disease to bilateral adrenals and to the ileum causing small bowel obstruction. Chest imaging showed a 2.2cm irregular right apical nodule. Subsequent hormonal evaluation showed normalization of plasma metanephrine levels at 15.8pg/mL, renin level 3.314ng/mL/hr, aldosterone level 4.3ng/dL, deoxycorticosterone level 4.8ng/dL, androstenedione level 40ng/dL, plasma normetanephrines 146.4pg/mL. The patient underwent left adrenal gland mass biopsy which showed metastatic poorly differentiated adenocarcinoma of pulmonary origin. Tumor cells were positive for keratin cocktail, TTF1 and synaptophysin supporting the morphologic interpretation. Patient is currently receiving treatment with carboplatin, pemetrexed, and pembrolizumab. Conclusion: Adrenal masses can be unilateral (85%) or bilateral (15%). While most unilateral adrenal masses are benign and nonfunctional, bilateral adrenal masses are likely to be metastatic disease, hemorrhage, infiltrative disease, congenital adrenal hyperplasia, macronodular Cushing’s syndrome, or bilateral cortical adenomas. Although uncommon, our case highlights the importance of considering metastatic disease to the adrenal glands as a potential initial manifestation of primary cancers. The most likely primary cancers to metastasize to the adrenal glands are breast, lung, colon, kidney, and esophagus.
Presentation: 6/1/2024
8014 Cushing’s Syndrome: Two Sides of The Spectrum
Authors: Aguilera M , VU A , Shakil J , Al-Ward R 
Published: October 2024

Abstract
Disclosure: M. Aguilera: None. A. Vu: None. J. Shakil: None. R. Al-Ward: None.
Introduction: Cushing’s syndrome (CS) is a rare condition with an annual incidence of 2-8 per million. Endogenous CS is mainly due to corticotroph adenoma of the pituitary followed by excessive glucocorticoid production from adrenal and ectopic sources. CS has significant morbidity and mortality hence the need for timely diagnosis. The varied presentations often pose great challenges in identifying the source of hypercortisolism. We present two unusual cases of CS with distinct clinical presentations and atypical laboratory profiles. Case 1: 25-year-old male with no medical history presented with 9 months of facial puffiness, weight gain, fluid retention, hypertension and blurred vision. Physical examination revealed round facies, bilateral supraclavicular fat pads and wide abdominal striae. Laboratory workup showed markedly elevated ACTH 537 pg/mL [7.2-63 pg/mL], serum cortisol 8.5 ug/dL [6.2-19.4 ug/dl], 24-hour urine free cortisol (UFC) 30 [5-62 ug/24H] and normal late-night salivary cortisol (LNSC). Repeat workup a month later showed serum cortisol of 56ug/dL, ACTH 874 pg/dL, 24-hour UFC of 11880ug/24H and elevated LNSC. Pituitary MRI showed a large heterogenous 3.1 cm partially cystic sellar mass with suprasellar extension. Due to significantly elevated ACTH and short duration of symptoms, we suspected an ectopic source. Due to initial negative testing, except for high ACTH level, a silent corticotroph adenoma was also considered. The patient underwent transsphenoidal resection resulting in significant decrease of cortisol and ACTH postoperatively. Pathology showed a corticotroph adenoma with Ki-67 index of &lt;1%. Case 2: 47-year-old woman with medical history of obesity, polycystic ovary syndrome and a stable 1 cm lung nodule since 2020, presented with fluid retention, worsening acne and resistant hypertension over a 1-year period. She required hospitalization for hypertensive emergency and hypokalemia. Laboratory data showed morning serum cortisol 28 ug/dL, ACTH of 90.1 pg/mL, 24-hour UFC 346 ug/24H, elevated LNSC on two occasions and cortisol 24.3 ug/dl after a 1mg dexamethasone suppression. MRI did not show a pituitary mass. PET dotatate scan revealed a tracer avid 1 cm right upper lobe pulmonary nodule. She underwent a right upper lobe lobectomy, resulting in a significant decrease in cortisol and ACTH levels on postoperative day 1. Pathology confirmed a typical carcinoid tumor. Discussion: High ACTH levels and a short symptom duration often point to ectopic production, paraneoplastic syndromes or corticotroph carcinomas. Cushing's disease typically exhibits mildly elevated ACTH levels, but our cases deviate from this norm, complicating source identification. This atypical presentation highlights the complexity of Cushing's syndrome, challenging conventional diagnostic paradigms.
Presentation: 6/1/2024
8295 Development of Type 1 Diabetes and Primary Adrenal Insufficiency Secondary to Immunotherapy Treatment for Chordoma in a Patient With Hypopituitarism
Authors: Kesavan Chary P , Silverstein J M 
Published: October 2024

Abstract
Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None.
Background: Cranio-cervical chordomas are rare locally aggressive, invasive, and slow-growing bone neoplasms. Treatment involves a combination of excision and radiation therapy, and sometimes immunotherapy for recurrent disease. Endocrine-related toxicities from immune checkpoint inhibitors are well recognized and include autoimmune thyroid disease, hypophysitis, and less commonly, type 1 diabetes mellitus (T1DM) and primary adrenal insufficiency (PAI). We present a case of a patient with hypopituitarism secondary to a recurrent and aggressive skull base chordoma with leptomeningeal spread who developed T1DM and PAI after treatment with nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody. Diagnosis of PAI was delayed because patient was on hydrocortisone replacement for secondary adrenal insufficiency. Case Report: A 38 year old male with history of primary hypothyroidism underwent endoscopic endonasal transsphenoidal resection and adjuvant proton beam radiation therapy for a sellar chordoma after presenting with diplopia. Testing was consistent with hypopituitarism and the patient was started on hydrocortisone, levothyroxine, and testosterone replacement. Due to recurrent disease and leptomeningeal spread, he subsequently underwent three additional surgeries and two courses of gamma knife radiosurgery. Five months after starting systemic therapy with nivolumab, the patient developed insulin dependent diabetes presumed to be T1DM secondary to immunotherapy. He was continued on nivolumab, and six months into treatment developed hyperkalemia and hyponatremia requiring inpatient admission. He was treated with diuretics and fluid restriction initially without improvement in his electrolyte abnormalities although he remained relatively asymptomatic. Laboratory evaluation showed a renin activity of 66 ng/mL/H and aldosterone &lt; 4.0 ng/dL (&lt;= 21) with sodium of 128 mmol/L (135-145) and potassium 5.8 mml/L (3.3-4.9). Due to suspicion for PAI secondary to checkpoint-inhibitor induced adrenalitis, 21-hydroxylase antibody was checked and was positive. It was felt that the patient had not had other signs or symptoms classic for PAI such as nausea and/or vomiting because he had already been on glucocorticoid replacement for his hypopituitarism. Ultimately, the patient was started on fludrocortisone, with resolution of his hyponatremia and hyperkalemia. Conclusion: Adrenal insufficiency from immunotherapy is most commonly caused by hypophysitis. T1DM and PAI due to adrenalitis are less common. In patients on steroid replacement for hypopituitarism, the development of electrolyte abnormalities with or without symptoms in a patient on immunotherapy should raise the suspicion for rarer endocrine side effects such as primary adrenal insufficiency.
Presentation: 6/3/2024