bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT439 Euglycemic Diabetic Ketoacidosis When Combining Empagliflozin With Cocaine
Authors: Squicimari-de Cardenas Fabio Alejandro , Bosques-Lorenzo Jaymilitte , Alejandro Loyola-Velez , Rodriguez Cyndia , Carlos Cortes-Sanchez , Colon Castellano Janet Marie
Published: October 2023

Disclosure: F.A. Squicimari-de Cardenas: None. J. Bosques-Lorenzo: None. L. Alejandro: None. C. Rodriguez: None. C. Carlos: None. J.M. Colon Castellano: None.

Background: Euglycemic DKA (eu-DKA) is a life-threatening emergency that can occur in patients with either type 1 or type 2 DM, and manifests as a milder degree of hyperglycemia with glucose levels around 200mg/dL. Cocaine abuse alone has been associated with DKA and eu-DKA by inducing cortisol, epinephrine, and norepinephrine release from adrenal glands, and by its anorexigenic effects by suppressing the feeding centers in the central nervous system. Here we present a case of eu-DKA in a patient that combined SGLT2i with cocaine. Clinical Case: A 66 y/o male with past medical history significant for DM type 2 treated with empagliflozin 25mg daily, metformin 1000mg BID, glargine 45 units am and pm, and exenatide 2mg. Patient presented to the ER with general malaise, dyspnea, abdominal pain, and nauseas. On initial evaluation, vital signs were remarkable for temperature at 97.8 F, pulse at 101 bpm, blood pressure 172/113 mmHg, respiratory rate at 20 bpm. Physical examination significant for a tachypneic, restless, and acutely ill patient that was alert, oriented and able to provide medical history. He and his family members denied him using illicit drugs or alcohol. Laboratories were found with severe metabolic acidosis. Central CO2 at 3.8 mEq/L (24-32 mEq/L), central glucose 241 mg/dL (70-99 mg/dL), elevated anion gap at 29.2 mEq/L, B-hydroxybutyrate markedly elevated at >83.3 mg/dL (0.2 - 2.81 mg/dL), arterial blood gases with pH at 7.11 (7.38-7.46) and HCO3 at 3.0 mmol/L (21-29 mmol/L). Urinalysis was positive for ketones and glucosuria. Toxicology came back positive for cocaine, and negative for alcohol. Due to patients’ severe acidosis and concerns for cardiac arrest, he was intubated for airway protection and admitted to the ICU for further management. DKA protocol was initiated and treatment with IV insulin, IV 5% Dextrose, 0.45% normal saline, potassium replacement, and IV bicarbonate provided until anion gap closed and acidosis resolved. Eventually, patient was successfully extubated and transferred to ward for further management and diabetic treatment optimization. Conclusion: Cocaine use is an independent trigger for DKA and eu-DKA. Euglycemic DKA has been raising with the surge of SGLT2i. As in our patient, concomitant use of SGLT2i and cocaine can precipitate patients for development for DKA/eu-DKA. It is important to educate patients to avoid concomitant use of this two and to perform toxicology screening in patients presenting with DKA or eu-DKA.

Presentation: Saturday, June 17, 2023
SAT440 DRESS/DHIS-associated Thyroiditis And Hypophysitis
Authors: Ranasinghe Indika R , Elston Marianne Susan , Boyle Veronica
Published: October 2023

Disclosure: I.R. Ranasinghe: None. M.S. Elston: None. V. Boyle: None.

Introduction: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS/DIHS) is a severe life-threatening adverse reaction to specific drugs, including cephalosporin antibiotics (1). It is characterised by rash, fever, eosinophilia, lymphadenopathy, and inflammation of internal organs. Endocrine complications in the form of thyroid disease and Type 1 Diabetes have been reported following DRESS/DIHS (2). We report a case of thyroiditis and hypophysitis following cephalosporin-associated DRESS/DIHS. Case: A 21-year-old male farmer suffered a tractor crash accident resulting in hospitalization for bilateral compound distal femur fractures. He had no past medical history of note. One month later, he developed a maculopapular rash involving his limbs, mouth ulcers, fever, liver function derangement and eosinophilia. Punch biopsy was consistent with DRESS/DHIS. A 2- week tapering course of prednisone was initiated at 40mg daily in conjunction with a topical corticosteroid for 9 days with resolution of rash. Review of medication charts identified the most likely causative agent as cefazolin. An Endocrine consult was requested a month later due to new hypercalcemia. Investigations revealed new onset thyrotoxicosis and a decreasing morning cortisol over the following week despite having stopped all steroids one month earlier, normal ACTH, mildly elevated prolactin and secondary hypogonadism. Short Synacthen test showed suboptimal response. TRAb were negative and technetium thyroid scanning demonstrated a thyroiditis. MRI pituitary was unremarkable. He was commenced on hydrocortisone replacement for symptomatic cortisol deficiency. Biochemical abnormalities gradually normalized and his hydrocortisone ceased with symptomatic resolution. Endocrine involvement, particularly pancreas and thyroid has previously been reported in cases of DHIS/DRESS (3) (4). In this case, DHIS/DRESS-associated hypophysitis with thyroiditis may explain the clinical findings of pituitary dysfunction affecting multiple pituitary axes and the gradual recovery to normal pituitary function.

References: (1) Hama, N et al., Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis. The Journal of Allergy and Clinical Immunology: In Practice, Volume 10, Issue 5, 1155 - 1167.e5

(2) Kano, Y. et al., Visceral Involvements and Long-term Sequelae in Drug-induced Hypersensitivity Syndrome, Medical Clinics of North America, Volume 94, Issue 4,2010,

(3) Deng, M et al., Co-Occurrence of Multiple Endocrine Abnormalities Induced by the DIHS/DRESS. Int J Endocr 2019; 2019: 7959615

(4) Klimas, N et al., Drug-Induced Delayed Multi-organ Hypersensitivity Syndrome. In: Hall J, Hall B. (eds) Cutaneous Drug Eruptions. 2015. Springer, London.

Presentation: Saturday, June 17, 2023
SAT447 Gaps In Care: Endocrine-disrupting Chemicals And Metabolic Disease Management Guidelines
Authors: Obeid Michele , Majid Aaish , Sargis Robert Michael
Published: October 2023

Disclosure: M. Obeid: None. A. Majid: None. R.M. Sargis: None.

In recent decades, global rates of obesity, diabetes, and non-alcoholic fatty liver disease have increased substantially, imposing significant morbidity and mortality on patients and severe economic strain on healthcare systems. Discussions of modifiable risk factors responsible for metabolic dysfunction have classically centered upon the role of excess energy intake and insufficient energy expenditure. Consequently, clinical practice guidelines have largely focused upon these factors when addressing disease risk and treatment. In recent years, however, new metabolic risk factors have emerged, including exposure to endocrine-disrupting chemicals (EDCs). Because exposure to EDCs is potentially modifiable through individual action and/or public policy, we sought to understand how practice guidelines for metabolic disorders have incorporated this new knowledge into clinical care. To accomplish this, we searched PubMed for the years 2007 to 2022 for European, Asian, and American clinical practice guidelines related to obesity, diabetes, non-alcoholic fatty, dyslipidemia, chronic kidney disease, and cardiovascular disease. Each guideline was then searched by two reviewers for 83 terms related to environmental factors linked to metabolic dysfunction. Environment-related statements were then adjudicated by three reviewers for relevance. Select guidelines for non-metabolic disorders linked to environmental factors were similarly reviewed for comparison, including asthma, chronic obstructive pulmonary disease (COPD), and obstetrics/gynecology guidelines. In total, 68 guidelines and statements were systematically reviewed. While environmental risk reduction was partially addressed in COPD, asthma, and cardiovascular guidelines, those focused on obesity, diabetes, and non-alcoholic fatty liver disease did not address the contribution of EDCs or other ambient environmental factors. Across all guidelines only air pollution received substantive attention, leaving other EDCs nearly entirely neglected. A clear but inadequately considered component of the social and structural determinants of health, environmental exposures have emerged as modifiable risk factors for multiple metabolic disorders. While further work is needed, future clinical practice guidelines should incorporate clinical interventions, research initiatives, and policy recommendations to address the impact of poor environments on human metabolic health.

Presentation: Saturday, June 17, 2023
THU016 Hiding In Plain Sight: Florid Cushing’s Disease Presenting As A Severe Extremity Cellulitis
Authors: Godar Cassandra M , Noble Evan B , Vietor Nicole O , Knee Treyce S
Published: October 2023

Disclosure: C.M. Godar: None. E.B. Noble: None. N.O. Vietor: None. T.S. Knee: None.

Background: Cushing’s syndrome may rarely present as an emergency known as Florid Cushing’s Syndrome. Patients can exhibit severe hyperglycemia, hypertension, hypokalemia, infections, and hypercoagulability. Cushing’s syndrome is a rare disease, and the constellation of clinical features can be overlooked if clinicians are not aware of the manifestations of hypercortisolism. We present the case of a patient with Cushing’s syndrome that went unrecognized with life-threatening sequelae. Case presentation: A 52-year-old woman with well-controlled type 2 diabetes and hypertension was admitted to the hospital for severe left lower extremity cellulitis. Prior to hospitalization she had noted rapid weight gain, fatigue, weakness, mental clouding, and moodiness. She was admitted for antibiotics and surgical debridement. The infection persisted despite broad spectrum antibiotics, multiple surgical debridements, and skin grafting. She became bacteremic, and extremity amputation was considered. She additionally developed hypertensive emergency, refractory hypokalemia, and hyperglycemia to 396 mg/dL. Exam was notable for facial plethora, supraclavicular fullness, dorsocervical fat pad, and violaceous abdominal striae. Cushing’s Syndrome was suspected, and labs revealed a significantly elevated random serum cortisol of 60.5mcg/dL (Ref 6.2-19.4), significantly elevated 24H urine cortisol of 2157mcg/24H (Ref 0-50), and ACTH elevated to 81.8pg/mL (Ref 7.2-63.3) that confirmed Cushing’s Disease. MRI sella and octreotide scans did not localize a lesion. Inpatient therapy included multiple antihypertensive agents, insulin drip, aggressive potassium repletion, and initiation of ketoconazole to reduce cortisol levels. Ketoconazole was maximally dosed and she underwent surgical exploration and removal of a small pituitary microadenoma. Following surgery, she developed transient adrenal insufficiency requiring hydrocortisone and she no longer required antihypertensives, insulin, or potassium therapy. Follow up 7 years later has revealed no recurrence of Cushing’s Disease. Discussion: Cushing’s Syndrome may present with a variety of clinical features and rarely may present as a medical emergency. Delay in diagnosis can lead to Florid Cushing’s Syndrome which carries high risk for morbidity and mortality. This case illustrates the need for clinician awareness of the features of Cushing’s Syndrome: hypertension, hyperglycemia, rapid weight gain, cushingoid exam features, hypokalemia, hirsutism, virilization, infection, and/or hypercoagulable state. Severe hypercortisolism was responsible for this patient’s refractory infection, and if not controlled, she likely would have endured a lower extremity amputation. Rapid detection with elevated random serum and/or urine cortisol and treatment with a cortisol-lowering agent is critical and lifesaving.

Presentation: Thursday, June 15, 2023
THU045 WIP1 Phosphatase Is A Novel Specific Target For Epithelial GH Action
Authors: Apaydin Tugce , Zonis Svetlana , Zhou Cuiqi , Barrett Robert , Chesnokova Vera , Melmed Shlomo
Published: October 2023

Disclosure: T. Apaydin: None. S. Zonis: None. C. Zhou: None. R. Barrett: None. V. Chesnokova: None. S. Melmed: None.

Deficient DNA repair and accumulated DNA damage underlie age-associated pathological changes, tissue fragility, and neoplastic development. ATM kinase, an activator of DNA damage responses (DDR), phosphorylates DDR effectors including CHK2, p53, and γH2AX to ensure DNA repair. We have shown that GH suppresses epithelial DDR activity by suppressing ATM phosphorylation, resulting in DNA damage accumulation due to repressed DNA repair. Wip1 dephosphorylates ATM thereby attenuating DNA damage repair. We found that GH significantly induced Wip1 expression (1.6-fold) in both human normal colon cells (hNCC) and in human 3-dimensional intestinal organoids, resulting in dephosphorylated ATM, CHK2, γH2AX, and p53. Mice bearing GH-secreting tumors with high circulating GH also exhibited induced colon Wip1 expression with lower phospho-ATM, γH2AX, and p53 as well as increased DNA damage. Twofold higher Wip1 expression was observed in blood buffy coats derived from patients with GH-secreting adenoma vs patients with non-functioning pituitary adenoma. Specificity of these observations was validated by showing that in GH-treated cells, blocking GH receptor (GHR) with pegvisomant or blocking STAT5 phosphorylation with the inhibitor CAS 285986-31-4 constrained Wip1 induction and restored ATM phosphorylation, indicating that GH effects on Wip1 are GHR/STAT5-mediated concordant with the observed decreased colon Wip1 expression in GHR-/- mice devoid of GH signaling. Furthermore, Wip1 inhibition with the small molecule inhibitor (GSK2830371) reversed GH-induced DNA damage by restoring phosphorylation of ATM and other key DDR proteins. To determine a mechanism for Wip1 induction, we tested homeodomain-interacting protein kinase 2 (HIPK2) which is regulated by AMPK and potentiates Wip1 proteasomal degradation and its activity. We observed that GH increased phospho-AMPK expression, while blocking AMPK kinase activity with Compound C abrogated GH induction of Wip1. Src upregulates AMPK and triggers HIPK2 cytoplasmic relocation thereby inactivating HIPK2. We found that GH, by activating Src/AMPK phosphorylation, elicits HIPK2 cytoplasmic relocation, thus suppressing Wip1 ubiquitination and increasing its stability. Consistent with these findings, blocking Src phosphorylation with the tyrosine kinase inhibitor dasatinib abolished Wip1 upregulation and induced phosphorylation of its downstream targets. These results indicate that GH suppresses DDR by inducing Wip1 expression, and suppression of Wip1 may prevent epithelial accumulation of unrepaired DNA damage. These findings identify Wip1 as a specific novel target for GH action mediating GH-attenuation of DNA repair.

Presentation: Thursday, June 15, 2023
THU048 Determination Of Receptor Binding Affinity Of Growth Hormone Analogues To The Growth Hormone Receptor In A Drug Screening Context
Authors: Erlendsson Simon , Kulakova Alina , Poulsen Svend , Thygesen Peter
Published: October 2023

Disclosure: S. Erlendsson: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. A. Kulakova: Employee; Self; Novo Nordisk. S. Poulsen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. P. Thygesen: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk.

Growth hormone (GH) and GH analogues are characterized by their ability to bind and activate the GH receptor (GHR). Binding affinity and functional activity are pivotal parameters for development and characterization of new GH analogues for treatment of growth disorders. The GHR is a member of the class I cytokine family and obtains a tripartite structure consisting of two extracellular fibronectin type III domains (ECD), a single-pass transmembrane domain (TMD), and a disordered intracellular domain (ICD). These receptors lack intrinsic kinase activity but rely on recruitment of intracellular signalling kinases and regulatory proteins. Activation of the downstream JAK-STAT signalling cascade is initiated by formation of an asymmetric GHR dimer induced by binding of GH to the GHR ECDs via two partially overlapping binding sites designated site I and II. The structural rearrangement in the ECDs propagates through the TMD and results in a separation of the ICDs which leads to activation through cross-phosphorylation of the Janus kinases 2 (JAK2). Here we utilize isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and small angle x-ray scattering (SAXS) to characterize the binding of native GH and GH analogues including somapacitan and pegvisomant to the monomeric GHR as well as an artificial soluble stabilized dimeric GHR. The GH analogues with good binding properties were subsequently tested in vitro for biological activity using a STAT3-luciferase reporter gene assay (RGA) and a proliferation assay with BAF3 cells expressing the human GHR. Both assays were established in two formats enabling testing of both receptor agonists and antagonists. Using SPR we show that the binding of all tested compounds is preserved between the monomeric and dimeric GHR with affinities ranging from near-picomolar to lower micromolar and we are subsequently able to confirm the expected stoichiometry by utilizing a combination of ITC and SAXS. In the RGA and the proliferation assay we demonstrate that a 1:2 stoichiometry is critical for receptor activation regardless of the affinity and therefore we propose high throughput screening of receptor stoichiometry as key in discovery of new growth disorder therapeutics.

Presentation: Thursday, June 15, 2023
THU052 Serum Growth Hormone Increases At The Onset Of Lactation And Promotes Mitochondrial Activity In Human Mammary Cells
Authors: Elajnaf Taha , Rostom Hussam , Meng Xin , Fry Alexandria , Hannan Fadil
Published: October 2023

Disclosure: T. Elajnaf: None. H. Rostom: None. X. Meng: None. A. Fry: None. F. Hannan: None.

Growth hormone (GH) administration is reported to increase milk yield in breastfeeding women. However, the role of endogenous GH in human lactation is unknown. We investigated whether serum GH is associated with the initiation of lactation after child birth, and recruited n=30 pregnant women (age range 24-41 years) following informed consent (1). Serum GH was measured at 36 weeks’ gestation and during postpartum days 1-4. All women had term births and initiated lactation between postpartum days 2-4. The mean maternal serum GH value progressively increased from 0.2±0.01 mIU/L at 36 weeks’ gestation to a peak value of 0.9±0.2 mIU/L on postpartum day-3 (p<0.0001), with serum GH then decreasing to 0.2±0.03 mIU/L by postpartum day-4. We hypothesised that this early postpartum rise in serum GH may increase mammary metabolism in order to stimulate milk synthesis after child-birth. Reverse transcription-quantitative PCR (RT-qPCR) demonstrated that lactating human mammary epithelial cells (HMECs) isolated from breast milk express the GH receptor. We next assessed the effects of GH in cultured HMECs. Recombinant human GH (rhGH) caused a dose-dependent increase in the phosphorylation of Akt, which is a key signalling protein required for initiating lactation. Thus, 50ng/mL and 500ng/ml rhGH caused ∼1.5-fold and ∼2-fold increases in Akt phosphorylation, respectively (p<0.05, n=4 experiments). We further evaluated the effects of rhGH on HMECs by untargeted proteomics involving nano liquid chromatography and tandem mass spectrometry. This demonstrated that the major mammary cell biological processes induced by GH involve the mitochondria. Indeed, HMECs treated with rhGH for 8 hours showed a significant upregulation of mitochondrial proteins involved in electron transport chain assembly, namely COQ9 (>4-fold increase, p<0.05) and IBA57 (>4-fold increase, p<0.05); and upregulation of CHCHD3 (6-fold increase, p<0.05), which influences mitochondrial cristae structure. We assessed whether these mitochondrial protein changes affect mammary cell respiration. Extracellular O2, which is an indicator of oxidative phosphorylation, was measured in cultured HMECs treated with 50ng/mL rhGH for up to 5 days. Administration of 50ng/mL rhGH caused a significant increase in the rate of O2 consumed by these cells (579±28 vs. 456±14 pmol O2/min/106 cells for control HMECs, p<0.01, n=4 experiments), consistent with increased oxidative phosphorylation. In summary, these clinical and cellular studies highlight a pivotal role for GH in promoting mammary cellular metabolism at the onset of lactation.

Reference: (1) Rostom, H. et al. Protocol for an observational study investigating hormones triggering the onset of sustained lactation: the INSIGHT study. BMJ Open 12, e062478.

Presentation: Thursday, June 15, 2023
THU109 An Interesting Case Of Infiltrative Panhypopituitarism Due To Metastatic Melanoma
Authors: Arora Neha , Maxwell Carolyn , Kim Julie Minjae
Published: October 2023

Disclosure: N. Arora: None. C. Maxwell: None. J.M. Kim: None.

Introduction: Metastases to the pituitary gland are a rare phenomenon only accounting for 1% of surgically treated pituitary tumors. The majority of cases, approximately 60%, in reported literature of hypopituitarism related to metastatic malignancy are associated with metastatic breast and lung cancer. These cases typically involve loss of posterior pituitary function rather than anterior. More specifically, the reported cases of panhypopituitarism related to melanoma have been associated with treatment with check point inhibitors with resultant hypophysitis. This case illustrates an unusual presentation of panhypopituitarism from direct infiltration and destruction of the pituitary gland from metastatic melanoma. Case Description: This was a 56-year-old post-menopausal female with a past medical history of Diabetes Mellitus type II who presented with a four-week history of generalized malaise, headache, dipoplia, and right eye ptosis. On physical exam, she was found to have right periorbital swelling, proptosis, and absent extraocular movement with right cranial nerve six palsy. MRI with pituitary protocol demonstrated a destructive, infiltrative process involving the pituitary, sella turcica, and cavernous sinus suggestive of either fungal infection or malignancy. Labs were indicative of panhypopituitarism including central hypothyroidism (TSH 0.008 uIU/mL, FT4 0.82 ng/dL), hypogonadism (FSH<17 mIU/mL; LH 0.3 mIU/mL), and low prolactin (0.3 ng/ml). Labs were also notable for a random low cortisol at 11AM (1.6 ug/dL, n>2.7ug/dl) and hyponatremia (125 mmol/L, n 135-146 mmol/L). A cosyntropin stimulation test failed to stimulate appropriately and stress dose steroids were initiated. A biopsy of the mass invading the pituitary gland was performed with pathology revealing metastatic melanoma with lymphovascular invasion. The patient’s hospital course was further complicated by multiple cerebral vascular infarcts, atrial fibrillation with rapid ventricular response, and heparin induced thrombocytopenia with rapid decline in functional status and patient soon passed. Post-mortem autopsy demonstrated friable hemorrhagic tissue (6.0 x 5.0 cm) involving the sellar and parasellar regions with diffuse lymphadenopathy consistent with metastatic melanoma. Discussion: This is a rare case of infiltrative metastatic melanoma with resultant panhypopituitarism. Although rare, metastatic disease should be considered when evaluating loss of pituitary function.

Presentation: Thursday, June 15, 2023
THU110 Wrong Tissue At Wrong Place—Rare Case Of Hypopituitarism Secondary To Metastatic Renal Cell Carcinoma
Authors: Avula Sreekant , Ahmed Ammar , Salim Michael , Alameddine Hind
Published: October 2023

Disclosure: S. Avula: None. A. Ahmed: None. M. Salim: None. H. Alameddine: None.

Introduction: Metastasis to pituitary is very rare occurrence, accounting for 1-4%. Most common primary cancer that metastasis to pituitary are Breast cancer in females and Lung cancer in males. Most of the pituitary metastasis are asymptomatic with symptomatic patient account for around 7 %. Most common symptoms reported are anterior pituitary dysfunction, visual field defects, headache, diabetes insipidus. Metastasis from Renal cell carcinoma (RCC) is very rare with only 25 cases reported so far. Metastases to the pituitary from RCC cause more severe hypopituitarism and visual dysfunction in comparison to those from other primaries. We present a rare case of hypopituitarism due to metastatic RCC presenting after Clinical Case: A 59-year-old male who initially presented in 2010 with complains of abdominal pain, underwent abdominal imaging and was found to have 7 cm solid mass in the right kidney. He underwent right nephrectomy in France and pathology confirmed RCC with no lymph node involvement. Patient didn’t have any adjuvant therapy. He had 5 years of follow up surveillance scans in Palestine which didn’t show any recurrence. In 2021 patient started to notice vision changes with loss of peripheral vision loss on right side but he didn’t seek any medical attention. In 9/2022 he noticed to have excessive fatigue, low libido, low appetite, excessive thirst and worsening of his vision. He had hormonal evaluation done in Palestine which showed low testosterone, cortisol, thyroid levels and was diagnosed with panhypopituitarism and was started on Hydrocortisone, Levothyroxine, Testosterone and Desmopressin. In 9/2022 had MRI brain in Palestine and showed 2cms suprasellar enhancing mass arising in the suprasellar cistern and appears inseparable from the pituitary stalk infundibulum. In 11/2022 he came to USA for further evaluation and management. In November 2022 patient complained of hallucinations, memory loss, personality changes and bitemporal vision loss. MRI brain showed sellar and suprasellar mass, 2.1 x 2.3 x 3.8 cm, extending to the suprasellar cistern and elevates the optic chiasm with possible third ventricle involvement and had increased in size compared to previous scan. On 11/29/22 patient underwent Endoscopic Endonasal Transplanum, Transtuberculum approach for tumor removal, biopsy of sellar and suprasellar tumor which returned as metastatic RCC. Patient was discussed in tumor board and is scheduled for gamma knife. Conclusion: Metastatic RCC to pituitary is very rare and most of them are asymptomatic leading to delay in diagnosis. Treatment of pituitary metastases is not standardized and should be tailored to patients’ clinical conditions, histology, and presence of extra-pituitary metastases. We need more prospective studies to formulate guidelines for management of pituitary metastases.

Presentation: Thursday, June 15, 2023
THU111 Diffuse Large B-Cell Lymphoma Pituitary Metastasis
Authors: Martinez Cruz Maria S , Haas Christopher J , Bhat Salman Zahoor
Published: October 2023

Disclosure: M.S. Martinez Cruz: None. C.J. Haas: None. S.Z. Bhat: None.

Background: The Hypothalamus-Pituitary axis (HPA) is a rare location for metastasis of non-Hodgkin’s lymphoma. Case description: A 57-year-old woman presented to the emergency department with a one day of acute, severe fatigue, nausea, and anorexia. She reported a history of stage IIIB diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) treated with R-CHOP three months prior, complicated by a recent recurrence in the lumbar spine requiring a short dexamethasone taper and radiation therapy two weeks prior to admission. On presentation, she remained hemodynamically stable with an otherwise unremarkable exam. Diagnostics revealed severe hypotonic hyponatremia suggestive of syndrome of inappropriate antidiuretic hormone (SIADH). CT scan of the head revealed thickening of the paramedian hypothalamic structures and the pituitary infundibulum. Subsequent pituitary MRI w/wo contrast demonstrated marked thickening and enhancement of the infundibulum with restricted diffusion, as well as T2/FLAIR hyperintensity and thickening in multiple hypothalamic areas concerning for HPA metastasis. Hormonal workup demonstrated panhypopituitarism for which she was started on hydrocortisone and levothyroxine. Lumbar puncture was performed with CSF flow cytometry revealing phenotypically abnormal monoclonal B-cells consistent with DLBCL leptomeningeal metastasis. Three days prior to induction chemotherapy, she developed massive polyuria, with a rapid increase in the serum sodium and markedly low urine-specific gravity consistent with acute diabetes insipidus (DI). Management included vasopressin, as needed, followed by standing doses of desmopressin. She was initiated on methotrexate and leucovorin chemotherapy. However, three week later, she developed acute onset diplopia, headache, nausea and vomiting, urinary and bowel incontinence, and fatigue. Follow-up pituitary MRI revealed progression of her known HPA metastatic disease, and she passed away one month later. Conclusion: This is an unprecedented case of metastatic DLBCL to the leptomeninges, hypothalamus, and pituitary infundibulum confirmed by CSF cytologic analysis that presented in the context of associated panhypopituitarism that manifested initially as SIADH followed by sudden DI. Abbreviations: R-CHOP: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone

Presentation: Thursday, June 15, 2023
THU121 Dopamine Regulates Neuroendocrine Cell Expansion In The Developing Lung
Authors: Watanabe Takuya , Stupnikov Maria , Zhou Yizhuo , Ke Xiangyi , Qien Jun , Ozawa Atsushi , Horigome Mitsuaki , Yamada Masanobu , Mori Munemasa , Cardoso Wellington V
Published: October 2023

Disclosure: T. Watanabe: None. M. Stupnikov: None. Y. Zhou: None. X. Ke: None. J. Qien: None. A. Ozawa: None. M. Horigome: None. M. Yamada: None. M. Mori: None. W.V. Cardoso: None.

Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells in the lung that have function as neurosensory and endocrine cells. They arise from naive epithelial progenitor cells in mice on embryonic day (E) 12.5, migrate to branch point of proximal airway and rare found as solitary or in clusters of 5 to 20 cells termed neuroepithelial bodies (NEBs). PNECs can be aberrantly increased in a variety of human diseases, including asthma, neuroendocrine hyperplasia of infants (NEHI) and sudden infant death syndrome (SIDS). Ascl1, an Achaete-Scute family bHLH transcriptional factor is the earliest marker and master regulator of PNEC fate specification. No PNECs form in Ascl1 null mice. In an effort to identify Ascl1 downstream targets involved in PNEC specification and expansion, we performed transcriptional analysis of E14.5 lungs from Ascl1 null mouse. Gene Ontology analysis showed a number of genes associated with the catecholamine pathway downregulated in mutants, compared to WT. These included tyrosine hydroxylase (Th) dopa decarboxylase (Ddc), dopamine beta-hydroxylase (Dβh). To gain initial insights into how catecholamine signaling influence PNEC development, we cultured E12.5 lung explants with various inhibitors of the catecholamine biosynthesis pathway and examined the effects on cell differentiation and proliferation. Treatment with Metyrosine (Met) and Benserazide (Benz) which inhibits dopamine production, resulted in a striking increase in PNEC number in NEBs as seen by expansion in Ascl1+ cells, without affecting cell proliferation. By contrast, no effect was observed with Zamicastat (Zami) which inhibits norepinephrine production. To examine whether dopamine regulated PNEC differentiation, we used the D1-like receptor antagonist, SCH-23390 and the D2-like receptor antagonist, Haloperidol in lung explant cultures, as before. Only Haloperidol increased PNECs in cultured lungs. This effect was similarly observed by maternal administration of Haloperidol intraperitoneally from E9.5 to 13.5 and analysis of harvested embryos at E14.5 and 18.5. Current studies mapping expression of other components of the dopamine pathway in the developing airway epithelium suggests a complex interaction of PNECs with neighbor cells in the regulation of the proper number of NEBs and solitary NE cells. These observations may provide a link between catecholamine signaling and aberrant PNEC behavior in the pathogenesis of human conditions affecting these cells.

Presentation: Thursday, June 15, 2023
SAT674 Lipodystrophy: A Hidden Culprit In Uncontrolled Diabetes
Authors: Sayed Farah El , Banka Ajaz
Published: October 2023

Disclosure: F. El Sayed: None. A. Banka: None.

Introduction: Lipodystrophies are rare disorders with selective absence/accumulation of fat tissue. The “common” genetic forms include Congenital Generalized Lipodystrophy or Familial Partial Lipodystrophy (FPLD). Non-genetic factors like autoimmune disorders, chronic infections, or malnutrition can also contribute to a lipodystrophy phenotype. Clinical case: A 49-year-old female with diabetes mellitus, hypertriglyceridemia, gait disturbances, hypertension, hereditary hemorrhagic telangiectasias, asthma, presents with suspected lipodystrophy. She notes truncal obesity as a child, with progression as an adult and subsequent loss of volume from her arms and legs around age 30. Family history is significant for multiple family members with diabetes mellitus. On physical exam, the patient has a BMI of 22.86 kg/m2. She walks with a cane and has abdominal fat deposition, a dorsocervical fat pad, and reduced fat and muscle mass in her lower extremities. Her diabetes is poorly controlled with multiple complications including retinopathy, microalbuminuria, neuropathy, CVA, and CAD. Her medications include metformin, pioglitazone, detemir, aspart, and an insulin sliding scale for diabetes management, and rosuvastatin, fenofibrate, and omega-3-acid ethyl esters for hyperlipidemia. Her last A1C was 12.7%, and urine analysis was positive for glucosuria and ketonuria. Her lipid panel revealed high triglycerides (800s) and low HDL levels. Other pertinent labs include elevated GDF15 at 761 pg/mL. and lactate elevation at 3.4 mml/L. Given suspicion for hypercortisolism, she underwent a dexamethasone suppression test which was negative for Cushing’s disease. She subsequently underwent exome sequencing with mitochondrial deletion testing, which led to the diagnosis of FPLD. Discussion: FPLD results in loss of fat from the extremities starting around puberty, often leading to metabolic complications. Although both sexes are affected, women usually present with more severe disease. Currently, multiple genes are associated with FPLD, most commonly LMNA and PPARG which both follow autosomal dominant inheritance. Conclusion: Presently, there is no cure for lipodystrophy syndromes. However, in patients with diabetes and resistant metabolic syndrome features, a diagnosis of lipodystrophy should be considered. Further evaluation with genetic testing is warranted and has implications for family planning and medical management.

Presentation: Saturday, June 17, 2023
FRI287 Pituitary Gene Signatures Link Chronic Systemic Inflammation To Female Reproductive Physiology
Authors: Garcia Christopher , Velez Leandro , Fox Chelsea , Mark Adam , Fisch Kathleen M , Lawson Mark A , Duleba Antoni , Seldin Marcus M , Nicholas Dequina
Published: October 2023

Disclosure: C. Garcia: None. L. Velez: None. C. Fox: None. A. Mark: None. K.M. Fisch: None. M.A. Lawson: None. A. Duleba: None. M.M. Seldin: None. D. Nicholas: None.

Female reproductive function depends on a perfectly choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, LPS-induced inflammation inhibits luteinizing hormone production and secretion from the pituitary, thereby inhibiting downstream production of sex hormones. However, this outcome has only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on luteinizing hormone secretion and consequent pituitary function. An inflammatory state was induced in female mice using biweekly doses of LPS injections. Surprisingly, luteinizing hormone was not inhibited and instead we found it was increased dose-dependently with LPS treatments. This is consistent with the features of the reproductive disorder polycystic ovary syndrome (PCOS). Here, analysis of bulk RNA-sequencing of mouse pituitary and integration with genetic variation of human pituitary expression profiles revealed pathways that are highly conserved between species. These results provide insights into the impacts of LPS-induced chronic inflammation on reproductive physiology.

Presentation: Friday, June 16, 2023
FRI316 A Rare Case Of Mono-hormonal Silent Prolactinoma
Authors: Esaki Yumiko , Bheeman Chandni , Shafiq Ismat
Published: October 2023

Disclosure: Y. Esaki: None. C. Bheeman: None. I. Shafiq: None.

Introduction: Silent pituitary adenomas secrete one or more anterior pituitary hormones or express their transcriptions factors, but do not secrete hormones at a clinically relevant level. Silent lactotroph adenomas are rare and often encountered as mixed somatotroph-lactotroph adenomas. Mono-hormonal silent lactotroph adenomas are exceedingly rare with the prevalence of 0.6-1.65% with most belonging to the sparsely granulated subtype. Clinical Case: A 32-year-old male presented with right visual problem over the last 7 months. Evaluation by Ophthalmology revealed trace afferent pupil defect of the right eye and bitemporal hemianopsia. MRI head showed an enhancing mass in the sellar and suprasellar regions collectively measured 2.5 x 2.0 x 1.8 cm, which upwardly displaced and distorted the optic chiasm. Biochemical workup showed normal prolactin 8.1 ng/ml (2.6-13.1) and unremarkable other pituitary hormone levels including ACTH 26 pg/ml (7-63), cortisol 16.6 ug/dl (6.7-22.6), growth hormone 0.08 ng/ml (0.00-2.47), LH 4.1 mIU/ml (1.2-8.6), FSH 5.8 mIU/ml (1.3-19.3), estradiol 27.9 pg/ml (15.0 - 31.5), total testosterone 527 ng/dl (240-950), free testosterone 16.1 ng/dl (4.85-19.0), SHBG 23 nmol/L (10-80), TSH 3.34 uIU/ml (0.34-5.60), free T4 0.84 ng/dl (0.58-1.64). He underwent transsphenoidal hypophysectomy. Final pathology showed densely granulated lactotroph, with extensively positive PRL in tumor cells, positive Pit-1 and negative ERa. Patient did well post-operatively. Conclusion: This case illustrates a rare case of a mono-hormonal silent pituitary lactotroph adenoma. The majority of lactotroph adenomas are sparely granulated, so the densely granulated histology shown here makes this case even more rare. Unfortunately, there is no data reported in relation to the association between this histological subtype and the invasiveness of tumor. We need more cases to characterize this subtype of tumor better.

Presentation: Friday, June 16, 2023
FRI325 Pituitary Stalk Interruption Syndrome Presenting As Short Stature: A Case Report
Authors: Ravindra Shruthi , Tirupati Sunanda
Published: October 2023

Disclosure: S. Ravindra: None. S. Tirupati: None.

Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital pituitary anatomical defect that leads to a variable degree of pituitary hormone deficiency. The classic neuroimaging findings of this condition include thin or interrupted stalk, absent or ectopic posterior pituitary, and hypoplastic anterior pituitary gland. The reported incidence of PSIS is 0.5 per 1,00,000 live births. The exact pathophysiology of this syndrome is not fully understood, but chromosomal microdeletions and perinatal asphyxia have some established roles in the literature as primary miscreants. Here we report a case of an adolescent male child who presented with complaints of short stature and absent secondary sexual characters development, diagnosed with PSIS following an MRI. Clinical Case: A 16-year-old male child was referred to the endocrinology department for the evaluation of short stature and delayed secondary sexual character development. This patient was born out of a non-consanguinous marriage and delivered at term by the vaginal route, with no other significant perinatal or family history. Psychomotor milestones were attained appropriately as per age but had poor linear growth. On examination, he had short stature - height 146cms (-2.7 SDS), weight: 53.5kg BMI: 23.5 Kg/m2 with normal vitals. Head-to-toe examination revealed immature facies, deep-seated eyes, broad nasal bridge, bilateral lipomastia, high-pitched voice, Tanner stage: A1P1, SPL:4cms, the testicular volume of 3cc bilaterally, with rest of the system-wise examinations being normal. Routine laboratory investigations (CBC, RFT, LFT, Electrolytes) were within normal limits. Bone age: 13years. The hormonal assessment showed central hypothyroidism, hypocortisolemia, and GH insufficiency, with pre-pubertal gonadotropin levels- suggestive of pan-hypopituitarism (Table 1). MRI pituitary showed anterior pituitary hypoplasia with interrupted stalk, and ectopic posterior pituitary, with no other brain anomalies which is consistent with the diagnosis of PSIS. The patient was initiated on hormone replacement therapy, currently taking hydrocortisone, growth hormone, levothyroxine, and testosterone. Conclusion: PSIS is a rare condition, that can present with various spectrum of clinical features. Signs and symptoms may not be evident in the neonatal and infancy period, therefore diagnosis is often delayed. Early diagnosis and treatment are crucial for preventing adverse effects of long-term hormonal deficiencies and improving the quality of life.

Presentation: Friday, June 16, 2023
SAT680 Mounjaro: A Side Effect
Authors: Rao Kamini , Nimako Evans Kyei
Published: October 2023

Disclosure: K. Rao: None. E. Kyei Nimako: None.

Mounjaro : A Side Effect Dr K Rao, Dr Evans-Nimako, Internal Medicine, North Alabama Medical Center Introduction: Mounjaro has been heralded as a new miracle drug both in the world of diabetes management and weight loss with its pending FDA approval in the latter category. Although common contraindications are known the wider spectrum and prevalence of side effects including diabetic retinopathy, acute kidney injury and gallbladder disease are still being identified. In this case we present a patient with Mounjaro induced AKI and ileus. Case Presentation: We present the case of a 64year-old diabetic, hypertensive male presenting with a 3-day history of nausea vomiting indigestion and excessive burping one day after taking his first dose of Mounjaro. The Patient was started at a walk-in clinic on 2.5 mg subcutaneously however on the very next day he noticed the onset of cramping abdominal pain with multiple episodes of vomiting and watery diarrhea. The patient has not had any other new foods, sick contacts or preceding illnesses. He had a history of previous hernia surgery, cholecystectomy and exploratory laparotomy some 18 years ago due to concerns for nonresolving small bowel obstruction. On examination he was afebrile but tachycardic and in mild distress. His abdomen was soft and nondistended. Bowel sounds were faint but present. He had generalized tenderness without evidence of rebound or guarding. Initial investigations demonstrated a white cell count of 14.7(10E3/ul), creatinine 1.7mg/dl, potassium 4.5mmol/L, blood glucose 176mg/dl and lactate of 2mmol/L. His urine analysis showed small volume ketones, glucosuria and trace leukocyte esterase with 3-5 white blood cells. CT of the abdomen and pelvis with contrast showed distended small and large bowel loops with fluid air levels but no transition point indicative of underlying ileus. The patient was hospitalized in total for approximately six days post the onset of his symptoms and treated with supportive measures including antiemetics, IV fluids and antacids. He never had any fevers or leukocytosis during his stay. His electrolytes remained within normal limits. Conclusion: Due to the impending widespread use and increasing popularity of Mounjaro this case presentation is aimed at raising awareness of potential side effects and their severity. We also hope to contribute towards further knowledge about specific subset of patients who may be more susceptible to the gastrointestinal side effects of Mounjaro. Particularly those patients who have had previous colonic or multiple abdominal surgeries or history of bowel obstruction. In this case the patient received the medication at a walk-in clinic this also highlights the dangers of lack of established care and monitoring of Mounjaro.

Presentation: Saturday, June 17, 2023
OR17-03 Vasoinhibin Analogs Vi45-51 And Crivi45-51 Lack The Proinflammatory Properties Of Vasoinhibin In Arthritis
Authors: Ortiz Georgina , García Rodrigo José F , Martínez-Díaz Oscar F , Robles Juan P , Zamora Magdalena , Ruiz-Herrera Xarubet , de Los Ríos Ericka A , de la Escalera Gonzalo Martinez , Clapp Carmen
Published: October 2023

Disclosure: G. Ortiz: None. J.F. García Rodrigo: None. O.F. Martínez-Díaz: None. J.P. Robles: None. M. Zamora: None. X. Ruiz-Herrera: None. E.A. de Los Ríos: None. G. Martinez de la Escalera: None. C. Clapp: None.

Vasoinhibin, a fragment of prolactin, has dual actions on inflammatory arthritis. It reduces joint inflammation by the inhibition of pannus vascularization (1) but enhances arthritis by direct proinflammatory effects on synovial fibroblasts (2). Linear (Vi45-51) and cyclic (CRIVi45-51) heptapeptides comprising the 45 to 51 amino acids of vasoinhibin conserve the antiangiogenic effects and potency of whole vasoinhibin, but are easier to produce, stable, and orally active to be developed for clinical use (3). In view of their therapeutic potential in arthritis, we investigated whether Vi45-51 and CRIVi45-51 conserved the proinflammatory effects of vasoinhibin in joint tissues. Synovial fibroblasts (SF) isolated from the knee joint of male C57BL/6 mice were incubated with or without recombinant vasoinhibin of 123 amino acids (positive control), Vi45-51, or CRIVi45-51. As expected, vasoinhibin upregulated the expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) and increased the production of nitric oxide (NO) in SF. However, similar or higher concentrations of Vi45-51 and CRIVi45-51 were inactive. The lack of inflammatory properties suggested improved efficacy of antiangiogenic Vi45-51 and CRIVi45-51 in arthritis. The antigen-induced arthritis (AIA) mouse model was carried out under severe [20 μg of intra-articular administration of methylated serum albumin (mBSA) as antigen] and mild (2.5 μg mBSA) inflammatory conditions to detect the antiangiogenic and proinflammatory effects of vasoinhibin, respectively (2). Consistent with its antiangiogenic properties, intra-peritoneal injection of CRIVi45-51 reduced joint swelling and pannus formation/vascularization in male C57BL/6 mice subjected to severe AIA. Moreover, in agreement with lack of proinflammatory actions, CRIVi45-51 did not elevate joint swelling under mild AIA. We conclude that Vi45-51 and CRIVi45-51 are beneficial in arthritis due to their antiangiogenic properties and lack of proinflammatory actions. Vasoinhibin analogs may be good therapeutic alternatives in inflammatory arthritis, including rheumatoid arthritis. Supported by CONACYT (A1-S-9620B) and UNAM (DGAPA-PAPIIT IN202321).

Reference: (1) Ortiz et al., Lab Invest. 2020 Aug;100(8):1068-79. (2) Ortiz et al., Endocrinology 2022 May;163(5): bqac036. (3) Robles et al., Angiogenesis 2022 Feb;25(1):57-70.

Presentation: Saturday, June 17, 2023