bluuebunny/crossref_metadata_2025 huggingface dataset:
6686 Age-Associated Local GH Adversely Impacts the Microenvironmental Epithelial Landscape
Authors: Chesnokova V M , Zonis S , Apaydin T , Wang Valencia C , Ainsworth R , Barrett R , Kettenbach A , Melmed S
Published: October 2024

Disclosure: V.M. Chesnokova: None. S. Zonis: None. T. Apaydin: None. C. Wang Valencia: None. R. Ainsworth: None. R. Barrett: None. A. Kettenbach: None. S. Melmed: None.

The tissue microenvironmental homeostasis is disrupted with age-related changes. Knowledge of mechanisms enabling the age-associated tissue landscape is limited. Senescent cells increase with age, and the secretome released from senescence cells (SASP) affects neighboring cells, often creating a milieu favoring neoplasia. We previously showed that local non-pituitary epithelial growth hormone (GH) is induced and secreted from senescent cells, accumulates with age, and suppresses DNA repair, leading to abundant DNA damage. To examine SASP-derived autocrine GH actions, we analyzed normal human colon cells (hNCC) infected with lentivirus expressing hGH (lentiGH) or vector (lentiV). Mass spectrometry revealed significant changes in the Rho signaling pathway reflecting cell cytoskeletal rearrangements. To examine paracrine GH action, we co-cultured intact human 3D intestinal organoids with organoids infected with lentiGH for 5 weeks. Using whole-exome sequencing we found that local paracrine GH emanating from lentiGH organoids increases neighboring intact organoid cell chromosomal instability, inducing somatic mutations, including deletions, breakends, duplications, and insertions. Mechanisms for observed chromosomal instability include sequelae of GH-mediated suppressed DNA damage repair proteins including pATM, pATR, and pBRCA2, leading to DNA damage accumulation and favoring cell transformation over the long term. Furthermore, enriched gene ontology and KEGG pathway analysis of intact organoids exposed to paracrine GH identified distorted extracellular matrix (ECM) gene expression and focal adhesion pathways. We confirmed these genomic changes with Western blotting showing altered proteins associated with ECM and those responsible for cell structural rearrangements. Moreover, phospho-omics of GH-exposed cells revealed significant phosphorylation changes in proteins associated with cell skeletal rearrangement and cell migration pathways. We found that GH triggers these changes by EMT activation as shown by suppressing E-cadherin and inducing Twist2 and Snai1 transcription factors. Together, all these changes are consistent with observed increased migration, invasion, and anchorage-independent growth of hNCC infected with lentiGH or co-cultured with GH-secreting hNCC or with GH-secreting normal colon fibroblasts. As paracrine GH also facilitates metastases after intra-splenic injection of senescent cells in nude mice carrying xenografts secreting GH, our results indicate that accumulated and locally secreted GH in aging tissue enables a microenvironmental landscape favoring epithelial cell transformation.

Presentation: 6/1/2024
12404 Aging-Associated Decline in the Pituitary Gland Using Single-Cell Transcriptomes
Authors: Kim Ye bin , Lee Soohyun , Kim Na-Yeong , Lee Eun Jig , Oh Ju Hun , Oh Chang-Myung , Ku Cheol Ryong
Published: October 2024

Disclosure: Y. Kim: None.

Introduction: Age-related decline in endocrine function has been associated with multiple physiological changes. However, aging-associated molecular shifts in the pituitary gland have not yet been systematically investigated. This study aimed to investigate the mechanism underlying these age-related molecular changes in young and old mice model using single cell transcriptomics. Method: Single-cell RNA sequencing (scRNA-seq) were conducted in young (2-month) and old (20-month) mouse. We used systems biology techniques to build a specific protein interaction network for somatotrophs, integrating validated interactions and gene expression data. By simulating drug effects on this network, we predicted changes in transcription factor activities due to aging. We identified potential therapeutic targets for preventing aging in somatotrophs by assessing the anti-aging effects of chemical perturbations, similar to methods used in the Connectivity Map project. Results: We identified 14 distinct cell types including follicular stellate cells (FSCs), somatotrophs, corticotrophs, gonadotrophs, lactotrophs, and melanotrophs. We found that the effect of aging on transcription was cell type dependent. FSC subtypes are heterogeneously regulated by aging at the transcriptomic level. However, somatotroph subtypes shared functional alterations with aging in terms of mRNA surveillance and spliceosome pathways. Our systems biology approach identified SENP1(Sentrin specific peptidase gene), as a critical node in the regulatory network affecting somatotroph aging. The senescence-associated beta-galactosidase staining (SAbgal) showed that Momordin (Mc), a SENP1 inhibitor, had anti-aging effects on somatotrophs, regardless of age-promoting doxorubicin. Western blot analysis indicated a two-fold increase in growth hormone levels in aged GH3 cells treated with Mc compared to vehicle. Conclusion: Our data and analysis provide promising resources to better understand the molecular shifts of pituitary aging at the transcriptomic level and help the community generate interesting hypotheses to develop anti-aging strategies for the pituitary gland. We suggest that SENP1 inhibitors may represent potential anti-aging targets in somatotroph.

Presentation: 6/3/2024
7741 Artri King As A Cause Of Adrenal Insufficiency
Authors: Aziz Qurrat-ul-ain , Fatima Sanna , Laurel Amber , Mrkaic Ana , Izuora Kenneth E
Published: October 2024

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

IntroductionDietary supplements are highly unregulated and may have substance that can be harmful. Due to its easy availability, more patients may have access to these supplements which can cause detrimental health outcomes, such as adrenal insufficiency. Clinical Case Patient is a 46 year old female with past medical history of hypertension and obesity presents to the hospital for worsening left hip pain, which started 2 weeks ago. She heard a crack in her left hip and denied any trauma or injury prior. She was found to have subtrochanteric fracture. Nine months ago, she had right hip pain and was unable to bear weight. Physical exam was notable for alopecia in frontal and temporal region, dorsocervical fat pad, multiple bruises, round facies, and multiple purple straie. She also reported a 50 pound weight gain in the last year. She stated that she took an over the counter “pain medication”, but denied any supplements. Due to the non-traumatic fracture and physical features, AM cortisol was ordered for suspicion of Cushing’s Syndrome by primary team and was low at 2.4. Endocrinology team was consulted. Cosyntropin stimulation test showed baseline AM cortisol level 1.4 and 1 hour after cosyntropin, cortisol was 8.3. ACTH 3.4, testosterone undetectable, androstendione undetectable, Aldosterone 42.2, DHEA undetectable. It was found later that patient was taking an over the counter supplement called Artri King, up to 4 tablets a day. Artri King has been advertised as a supplement for joint and muscle pain and contains unknown amount of dexamethasone and diclofenac. She was soon placed on hydrocortisone for adrenal insufficiency and was titrated down. The hypothalamic-pituitary-adrenal (HPA) axis can be suppressed with as low as 5 mg prednisone equivalent a day. This can lead to inadequate adrenal response to stress. If a patient has prolonged exposure to exogenous steroids, insufficient ACTH secretion can lead to atrophy of the zona fasciculata and reticularis, resulting in reduced ability to secrete cortisol. Therefore, it is important to help withdraw patient from glucocorticoids. When initiating glucocorticoid withdrawal, hydrocortisone may be helpful due to short half life, allowing HPA axis more opportunity to recover. Adrenal atrophy may be slowly reversible, but 4 years after diagnosis of glucocorticoid induced adrenal insufficiency, recovery of adrenal function is unlikely to occur. ConclusionsIt is important to obtain a thorough history, especially for supplements. Many supplements are not regulated and can pose harm to our patients. Adrenal insufficiency due to glucocorticoids may not only occur from steroid injections, long course of prescription glucocorticoids, but can include supplements if it is hidden from the ingredient list.

Presentation: 6/3/2024
7013 An Inpatient Perspective: Hyperprolactinemia and Granulomatous Mastitis
Authors: Le Andy , Wade Jarrett , Martz Kevin , Girgis Daniel , Shahlapour Mahmood , Horani Mohamad Hosam
Published: October 2024

Disclosure: A. Le: None. J. Wade: None. K. Martz: None. D. Girgis: None. M. Shahlapour: None. M.H. Horani: None.

Introduction: Mastitis is a highly prevalent condition impacting thousands of women every year. Most commonly associated with lactation, mastitis is estimated to impact 2-20% of lactating women particularly in the first 4-6 weeks of breastfeeding (Wilson et al., 2020). The majority of cases are associated with bacterial infection with Staphylococcus aureus precipitated by nipple trauma and hyperlactation in the setting of genetic predispositions and disturbances to the human milk microbiota (Fernández et al., 2020). In rare cases, mastitis is seen outside of the context of lactation. One cause of non-lactational mastitis is idiopathic granulomatous mastitis (IGM). The pathogenesis of IGM is poorly understood, but there has been a rare association between IGM and hyperprolactinemia reported in the literature (Nikolaev et al., 2016). Case Presentation: In January 2022, A 20 year old female with past medical history of type 2 diabetes mellitus and hypertension, initially presented to the emergency department with complaints of headache. Patient’s history is notable for two years of amenorrhea and periodic nipple discharge. MRI scan of the head revealed a 1.6 cm pituitary macroadenoma which correlated with a markedly elevated prolactin level at 533.3. She was discharged with a prescription for Cabergoline 0.5 mg BID. In July 2022, the patient presented to the ED complaining of severe left breast pain with associated discharge for 4 days. She admitted to being non-adherent to Cabergoline treatment since April 2022 due to lack of endocrine follow-up. CT of the breast at that time showed a 3.8 cm subareolar abscess. Aspiration of the abscess revealed non-purulent fluid and cultures of the aspirate were negative. In February 2023, patient presented for right breast pain with a similar workup to previous hospitalization. MRI of the brain revealed a 1.6 cm sellar mass is unchanged since January 2022. Prolactin level was elevated at 652.4. Patient stated she has been off Cabergoline for the prior 5 months. She was subsequently seen for right and left mastitis 3 times over the next 12 months. Upon endocrine consultation, the patient was counseled on the importance of Cabergoline treatment in regression of future mastitis episodes, and the patient has subsequently not returned to our service. Conclusion: This case demonstrates the rare association between prolactin secreting pituitary adenomas and granulomatous mastitis that clinicians need to consider in order to avert delays in treatment and unnecessary hospitalizations. Specifically, when working up a patient with a history of IGM and prolactinemia, it is imperative to monitor prolactin levels periodically over an extended course of time with appropriate MRI imaging of the pituitary gland to assess for regression of prolactinoma and episodes of IGM.

Presentation: 6/1/2024
8264 An Interesting Case of Hypophysitis in a Young Woman
Authors: Garcia Alejandro , Sharma Rajeev , Knight Colette M
Published: October 2024

Disclosure: A. Garcia: None. R. Sharma: None. C.M. Knight: None.

Background Hypophysitis is an uncommon disorder and presents with clinical signs and symptoms along with biochemical abnormalities. Herein, we present a case of hypophysitis that responded well to high dose steroids. Case An 18 y.o black, adopted woman presented to hospital with complaints of headache and vision disturbances. Endocrinology was consulted for pituitary macroadenoma. Symptoms started a month prior. She had extensive work-up at an outside hospital including brain imaging, CSF analysis, and bloodwork. No definitive diagnosis was made and she was sent home on topiramate. Her symptoms continued to worsen prompting her to seek another opinion. No family history as she is adopted. She has a history of depression controlled with medication. MRI Brain showed 1.8x1.1x1.6 cm T2-enhancing mass with suprasellar extension deforming the midline optic chiasm. Initially, a diagnosis of macroadenoma was made and Endocrinology and Neurosurgery services consulted. Patient denied galactorrhea, menstrual abnormality, polyuria, polydipsia, cold intolerance, orthostasis, or weight gain. Bloodwork was significant for low TSH (0.045 uIU/ml; normal 0.35-4.94), low free T4 (0.58 ng/dl; normal 0.76-1.79). Thyroid functions were normal approximately one year prior. Cortisol was very low at 1.8 mcg/dL and ACTH inappropriately low-normal at 12 pg/ml (normal 6-50). LH and estradiol were low, while FSH was low normal. Prolactin, GH, IGF-1, sodium, glucose and creatinine were normal. Endocrine reviewed the previous MRI brain done four weeks ago that was reported as normal. Discussion with previous outside hospital radiologist suggested that pituitary was indeed not normal but was fuller with convexity towards chiasm although no definitive adenoma was found. Since it is unlikely that such adenoma would develop over 4 weeks, Endocrinology reached out to our radiologist who assessed this as pituitary enlargement due to likely hypophysitis, especially when compared to imaging 4 weeks ago. Further work up showed mildly-elevated ESR, and normal ACE, dsDNA, ANA, and Sjogren’s antibody levels. Tests for pregnancy, Lyme disease, tuberculosis, EBV and syphilis were negative. SARS-CoV-2 was negative for COVID. IgG4 levels were normal. CSF analysis was normal. She was started on levothyroxine and high-dose corticosteroids with improvement in her symptoms. Repeat imaging after 5 days of corticosteroids showed about 30% decrease in pituitary size. A diagnosis of likely lymphocytic hypophysitis was made and pituitary surgery averted for time being. Conclusion We present a case of possible lymphocytic hypophysitis in a young woman who avoided pituitary surgery due to diligent history and examination, in addition to a multidisciplinary team approach. It is very important to have prompt multidisciplinary approach if there is any doubt about a diagnosis as in this case.

Presentation: 6/3/2024
6589 Antisense Oligonucleotides for Reducing ACTH Secretion in a Model of Cushing's Disease
Authors: Varughese Maria Susan , Eltumi Hanan , Kemp Elizabeth Helen , Newell-Price John D C
Published: October 2024

Disclosure: M.S. Varughese: None. H. Eltumi: None. E.H. Kemp: None. J.D. Newell-Price: None.

Antisense Oligonucleotides for Reducing ACTH Secretion in a Model of Cushing’s Disease Background: Cushing’s disease (CD) is a multi-system disorder with high morbidity and mortality characterised by pathologically raised serum cortisol due excess expression of proopiomelanocortin (Pomc) and overproduction of ACTH by a pituitary corticotroph adenoma. Trans-sphenoidal adenomectomy is the treatment of choice, but there is a 30% recurrence rate over time. Advances in medical therapy are needed. Antisense oligonucleotides (ASOs) can silence mRNA translation by specific base-pairing. Locked nucleic acid (LNA) and 2’-O-methyl (OMe) ribose terminals make ASOs more effective by improving affinity and resistance to nuclease degradation. Aims: To investigate the effectiveness of LNA- and OMe-modified anti-Pomc ASOs at reducing ACTH secretion from murine adrenotropic tumour (AtT20) cells. To analyse the nuclease resistance of Pomc ASOs and their ability to drive an immune response. Methods: Two ASOs (ASO2 and ASO3) were designed against Pomc with phosphorothioate backbones modified with either LNA or OMe ribose terminals. These were used in lipofectamine-mediated cell transfections of AtT20 cells and ACTH in the culture medium measured by immunoassay. ASO stability was assessed by nuclease degradation assays and immunogenicity by cytokine ELISAs. Results: When compared with untreated AtT20 cells, LNA- and OMe-modified Pomc ASOs at 1 nM significantly suppressed ACTH secretion for up to 120 h and 96 h, respectively (n = 4; Unpaired t tests, all P values < 0.05). In contrast, control treatments, including scrambled and mismatched ASOs, did not cause a significant reduction. For comparison, 1 nM of ASO2-OMe, ASO2-LNA, ASO3-OMe and ASO3-LNA lowered ACTH at 24 h by 62%, 71%, 63% and 79%, respectively. Modified Pomc ASOs showed 14-31% degradation over a 120-min incubation period with 3’- and 5’-exonucleases, whilst equivalent unmodified Pomc ASOs were completely degraded. No secretion of IFN-α, IFN-β, TNF-α, IL-6 or IL-1β was detected following transfection of AtT20 cells with Pomc ASOs. Conclusions:Pomc ASOs caused significant reduction of ACTH secretion from AtT-20 cells. LNA-modified Pomc ASOs were more effective than those with OMe modifications, with neither stimulating a detectable immune response. These ASOs hold promise as a systemic therapy for Cushing’s disease.

Presentation: 6/3/2024
12578 Assessment Of Sarcopenic Obesity in Patients with Acromegaly
Authors: Rocha Claudia Pinheiro Sanches , Hupalowski Natália Nachbar , Fidalski Solena Ziemer Kusma , Boguszewski Cesar Luiz , Borba Victoria Z C
Published: October 2024

Disclosure: C.P. Rocha: None. N.N. Hupalowski: None. S.Z. Fidalski: None. C.L. Boguszewski: Consulting Fee; Self; Recordati. Research Investigator; Self; Crinetics. Speaker; Self; Ipsen, Novo Nordisk. V.Z. Borba: None.

Introduction: Patients with acromegaly in activity exhibit modifications in body composition with increased skeletal muscle mass and decreased body fat. The effects of growth hormone on muscle strength and performance are uncertain, suggesting possible changes in physical performance due to compromised strength and functioning of skeletal muscle not correlated with total lean body mass. Sarcopenia is a progressive disorder of skeletal muscle, associated with risk of falls, fractures, loss of autonomy, and increased mortality, sarcopenic obesity is defined as the coexistence of both comorbidities. Objective: To assess sarcopenic obesity in patients with acromegaly compared to controls. Patients and Methods: observational, case-control study, matched 1:1 by age and sex with a control group. The study was approved by the ethics committee and individuals included after formal consent. The study group patients under clinical follow-up at a reference service in southern Brazil. All individuals underwent clinical evaluation through questionnaires; muscle strength [sit-to-stand test (STST5x) and hand grip strength (HGS)]; muscle mass quantification by dual-energy X-ray absorptiometry (DXA) and physical performance [Gait Speed, the Short Physical Performance Battery (SPPB), and the Timed-Up and Go test (TUG)]. Sarcopenic obesity was calculated following the ESPEN and EASO consensus. Results: The study population included matched 48 patients with acromegaly and 48 controls matched 1:1 by age and sex. The population was predominantly female (54.1%), mean age of 56.31 ± 11.60 years, with 79.1% below 65 years of age, and 64.58% (31) were in inactive acromegaly. The mean weight was 87.88 ± 18.02 kg, and the mean BMI was 31.25 ± 4.95. Mean muscle lean mass was higher in the patient group, and the diagnosis of sarcopenic obesity was similar between groups. However, all performance tests were worst in patients than controls with altered tests: TSL5X in 24 (50%) vs 2 (4,3%) controls; gait speed test in 14 (29.2%) vs. 3 (6,4%) controls and in the SPPB in 15 (31.37%) vs 0 (0%) controls, p<0.005 for all. The investigation of sarcopenia in patients with active or inactive disease did not show significant differences. Conclusion: We identified in a population of patients with acromegaly a low performance despite of a preserved lean mass and similar diagnosis of sarcopenic obesity. This study highlights the impairment of physical performance and functionality, not reflecting the adequate muscular amount in patients with acromegaly.

Presentation: 6/2/2024
7497 Association between Plasma Prolactin Levels and Menopausal Vasomotor Symptoms
Authors: Galbiati Francesca , Kang Jae Hee , Cote David J , Manson JoAnn E , Kaiser Ursula B
Published: October 2024

Disclosure: F. Galbiati: None. J. Kang: None. D.J. Cote: None. J.E. Manson: None. U.B. Kaiser: None.

Background: High prolactin (PRL) levels inhibit gonadotropin-releasing hormone (GnRH), causing hypogonadism. GnRH release is regulated by neurokinin B (NKB) and kisspeptin. NKB antagonists are used in treatment of menopausal hot flashes and vasomotor symptoms (VMS). In mice and humans with hyperprolactinemic anovulation, kisspeptin restored ovarian cyclicity and LH pulsatility. However, the interplay between kisspeptin and PRL is not fully understood. In two menopausal women with hyperprolactinemia and central hypogonadism, treatment with bromocriptine led to PRL normalization and new-onset VMS, suggesting that hyperprolactinemia inhibited VMS associated with hypogonadism. We aimed to investigate the association between PRL and menopausal VMS in women from the Nurses’ Health Study I and II (NHS, NHSII). We hypothesized that women with higher PRL levels would have a lower frequency/severity of menopausal VMS. Methods: We conducted a cohort study of 2618 females enrolled in NHS (n=1692) and NHSII (n=926) in whom blood samples were collected between 1989-99, were not pregnant or on hormonal therapy, and were either pre or post-menopausal as of blood draw. Subjects were free of breast, ovarian and other cancers, and provided complete data on VMS at menopause as well as in the past 4 weeks (assessed in 2008 in NHS and 2009, 2013, 2017 in NHSII). Plasma PRL was measured as part of 28 case-control studies of various health outcomes. We evaluated the presence and severity of VMS at menopause and 4 weeks prior to the questionnaire, as well as duration (in years) of VMS. We used multiple logistic regression, adjusting for covariates to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). Results: Women were aged 33-65 years at blood draw; range for years from blood draw to menopause was -10 to 10 (median=1.8) years; range for years from blood draw to report of VMS (both at menopause and current VMS) was 9.8 to 22 years. Mean PRL (SD; range) was 14.7ng/mL (10.1; 0.08-246). Women with the highest PRL levels were likely to be younger and less likely to be current smokers or obese. 77.4% of women reported VMS at menopause and 47.6% in recent 4 weeks; 52.3% reported moderate-to-severe VMS at menopause and 32.0% reported VMS in recent 4 weeks. Overall, PRL was not associated with duration of VMS or moderate-to-severe VMS at menopause or in the past 4 weeks; compared to the lowest quintile (≤8.0ng/mL), those in the highest PRL quintile (≥18.2ng/mL) had MVRR of 1.23(95%CI=0.94,1.60) for moderate-to-severe menopausal VMS and 1.03(95%CI=0.67,1.59) for recent VMS. Menopausal status did not affect the association between prolactin levels and VMS. Conclusion: PRL levels were not associated with occurrence, severity, or duration of menopausal VMS in a large cohort of women.

Presentation: 6/1/2024
8427 Association of Circulating Prolactin Levels with Degree of Glycemic Control as Determined by Glycated Hemoglobin
Authors: Hashim Ibrahim A , Abraham Elizabeth
Published: October 2024

Disclosure: I.A. Hashim: None. E. Abraham: None.

Background: Prolactin is suggested to stimulate pancreatic β cells and may thus play a role in glucose metabolism. This retrospective study examined the relationship between circulating prolactin levels and glycated hemoglobin (A1c) levels among diabetics and patients being investigated for glucose intolerance. Methods: A1c values and their corresponding prolactin levels performed over 15 months (July 2021 to October 2022) were retrieved from the electronic medical records and subjected to statistical analysis. Patients’ glycemic status was characterized as normal (A1c ≤5.7%), prediabetic or in control (A1c >5.7 to <6.4 %), diabetic in control (A1c >6.5% to <9.0%), and poorly controlled (A1c >9.0%). Results: A total of 276 patients were included in the study, ages ranged from 12 to 84 (median 37 years) among females (n=229) and from 14 to 75 (median 38 years) among male patients (n=47). In patients with A1c ≤5.7 (n=152, 55.1% of patients) A1c ranged from 4.1 to 5.6 (median 5.3%) and prolactin levels ranged from 14 to 84 (median 36 ng/dL). Patients with A1c levels >5.7 to <6.4 % (n=71, 25.7%) A1c ranged from 5.7 to 6.4 (median 5.9%) and prolactin levels ranged from 1 to 1152 (median 11.9 ng/dL). Patients with A1c levels >6.5 to <9.0 (n=33, 11.9%) A1c ranged from 6.6 to 9.0 (median 7.1%) and prolactin levels from 1.1 to 154.5 (median 11.9 ng/dL). Patients with A1c >9.0% (n=19, 6.9%) A1c ranged from 9.2 to 14.5 (median 10.5%) and prolactin levels ranged from 2.7 to 41.2 (median 14.6 ng/dL). Overall, there was no correlation between A1c and prolactin levels for all study patients (r = -0.03, p= 0.6). There was no significant difference in prolactin levels among patients with normal A1c and those in control (p= 0.57 and 0.33 respectively). However, prolactin levels were lower in patients with poor control (A1c >9%) (p=0.02).Discussion: Markedly elevated but not significantly different prolactin levels were observed in prediabetic patients and those with good control. However, significantly lower prolactin levels were observed in poorly controlled diabetic patients. The study findings suggest a possible role for prolactin in glycemic control and that further studies are required to further investigate pathophysiology and possible mechanism.

Presentation: 6/2/2024
8067 AVP Gene Mutation: A Rare Cause of Diabetes Insipidus
Authors: Navrange Nishika , Williams Maeve , Madhavan Parvathy
Published: October 2024

Disclosure: N. Navrange: None. M. Williams: None. P. Madhavan: None.

Introduction: Arginine vasopressin deficiency (AVP-D), also known as neurohypophyseal or central diabetes insipidus (DI), is marked by a reduced secretion of arginine vasopressin (AVP), resulting in polyuria and polydipsia. AVP-D is a rare disorder, with a prevalence of 1 in 25,000. Typically, the disorder is acquired. However, in less than 5% of cases, it has a genetic etiology. The majority of mutations in the AVP gene are autosomal dominant. Normally, AVP encodes vasopressin, also known as antidiuretic hormone (ADH). It plays a key role in the reabsorption of water in the kidney, the regulation of blood pressure, and controlling the body’s osmotic balance. However, a mutation in this gene leads to a deficient release of ADH, leading to reduced reabsorption of water in the collecting duct and decreased ability to concentrate urine. This results in increased urine output and excessive thirst. The onset and severity of symptoms varies between individuals. Case Report: In this report, we discuss the case of a 40-year-old Caucasian female with familial neurohypophyseal diabetes insipidus. The patient presented to the clinic for follow-up care of DI and hyponatremia. She received her DI diagnosis before the age of 5 and has multiple family members with the condition including her maternal grandfather, mother, and 2 siblings. Additionally, she suspected one of her children was exhibiting excessive urination. Past medical history is also significant for seizure disorder, postpartum cardiomyopathy, Chiari malformation type I and remote history of substance abuse. Vitals were stable with blood pressure of 122/86 mmHg, heart rate of 93 bpm, body mass index of 31.8. Physical exam was unremarkable except for obesity. She is currently managed with DDAVP 0.05 mg twice daily. Previously, imaging was performed to rule out pituitary abnormalities. The patient was referred for genetic testing due to her family history and was found to have a previously described rare autosomal dominant mutation of the AVP protein. The single nucleotide polymorphism in exon 1 results in a missense mutation substituting an alanine nucleotide for threonine (c.55G>A). The patient was counseled to share these results with her children’s pediatrician, as they could benefit from testing for the mutation. Discussion: Our patient has a pathogenic variant in AVP, specifically a missense mutation from Alanine to Threonine at codon 19 of the AVP protein. This mutation is associated with autosomal dominant neurohypophyseal diabetes insipidus. This case provides an example of a rare cause of neurohypophyseal diabetes insipidus and emphasizes the necessity of obtaining detailed family history in patients who have DI and considering genetic testing for patients with suspicion for familial involvement.

Presentation: 6/2/2024
6555 Cabergoline-induced psychiatric symptoms in a patient with a pituitary macroadenoma
Authors: Patel Goonja S , Prater Janna
Published: October 2024

Disclosure: G.S. Patel: None. J. Prater: None.

Cabergoline is a long-acting dopamine agonist that is used for the treatment of hyperprolactinemia, especially in pituitary macroadenomas. It reduces the levels of prolactin (PRL) but is also effective in reducing the tumor size and allows patients to avoid undergoing surgical resection of the mass. It commonly causes side effects such as abdominal pain, bloating, dizziness, and headaches. It rarely can cause new onset psychological side effects or an exacerbation of pre-existing mood and behavioral disorders. We present the case of a male on cabergoline therapy who had new-onset psychiatric symptoms that persisted even after treatment was discontinued. The patient is a 40-year-old male who was found to have a pituitary macroadenoma measuring 2.2 x 1.8 x 1.6 cm on brain MRI after a one-year history of headaches, dizziness, and hearing loss. His vital signs and physical examination were unremarkable. Laboratory investigations revealed a PRL of 1,072 ng/mL. He was started on cabergoline 0.25 mg twice a week which reduced levels of PRL to 465.3 ng/dL. Throughout the next year, his PRL levels remained persistently elevated to >100 ng/dL and the cabergoline dose was steadily increased to 1 mg three times per week. About a year into treatment he began experiencing significant emotional lability, a tendency to cry, and bursts of temper which required the addition of multiple psychiatric medications. After two years of continued psychiatric symptoms, there was an attempt to both reduce cabergoline doses and switch to escalating doses of bromocriptine, both of which resulted in a reduction of psychiatric symptoms but also significant increases in PRL levels. The patient’s mood symptoms returned shortly after switching back to cabergoline, especially with increased doses. He eventually underwent trans-sphenoidal resection for his treatment-resistant pituitary macroadenoma. He was taken off cabergoline before surgery with a significant reduction in his mood symptoms but continues to require psychiatric medications for lasting emotional lability. Although rare, psychiatric side effects of cabergoline have been documented and must be addressed if a patient develops them while receiving treatment. Our patient had a severe presentation of mood symptoms from cabergoline therapy that required multiple psychiatric medications in escalating doses to control. It not only affected his quality of life but also resulted in long-term consequences. It is recommended that patients with similar presentations should be continued on cabergoline with the addition of clozapine as it has less of an effect on PRL levels. Other treatment options also include aripiprazole and quetiapine. However, when patients have treatment resistant macroprolactinomas and are unable to tolerate cabergoline, one would have to consider surgical treatment options for the treatment of hyperprolactinemia from pituitary macroadenomas.

Presentation: 6/1/2024
12343 Cardiac Function Recovery Following Left Adrenalectomy For A Pheochromocytoma With Ectopic ACTH Syndrome
Authors: Williams Tyler D , Lovre Dragana , Galagan Robert C
Published: October 2024

Disclosure: T.D. Williams: None. D. Lovre: None. R.C. Galagan: None.

Background: Pheochromocytoma and Cushing’s Syndrome are implicated in Non-ischemic Cardiomyopathy/Heart Failure with reduced Ejection Fraction (NICM/HfrEF) due to catecholamine induced hypertension and cardiomyocyte toxicity. Subsequent hypoxia and calcium overload in cardiomyocytes results in oxidative stress and cell death. Excess cortisol secretion increases angiotensin II, causing hypertrophy. Subsequent increases in atrogin I lead to myo-fibrinolysis and fibrosis. We present a patient with NICM/HFrEF due to both catecholamine excess and ectopic ACTH syndrome from an adrenal pheochromocytoma. Following adrenalectomy, systolic cardiac function returned to normal. Clinical Case A 42-year-old female was referred to endocrinology after a hypertensive emergency concurrent with NSTEMI, NICM, and HFrEF (EF 45%). Initial work up revealed: Troponin I 0.49 ng/ml; (0 - 0.04 ng/ml), Na+ 140 mmol/L; (136 - 144 mmol/L), K+ 2.3 mmol/L; ​​(3.7 - 5.2 mmol/L), CO2 41 mmol/L; (23 - 29 mmol/L), Glucose 53 mg/dL; (64 - 100 mg/dL), Cortisol 57.2 ug/dL; (5 - 25 ug/dL), ACTH 363.7 pg/mL; (7.2 - 63.3 pg/mL). She failed both 1 mg and 8 mg overnight dexamethasone suppression tests: 0800 cortisol 48.5 ug/dL (< 1.8 ug/dL) & 56.8 ug/dL (> 50% decrease in baseline cortisol level of 57.2 ug/dL) consistent with ectopic ACTH syndrome. Elevated plasma normetanephrine 0.98 nmol/L; (0 - 0.89 nmol/L) and chromogranin A 250 ng/mL; (0 - 103 ng/mL) suggested a neuroendocrine tumor. Pituitary MRI revealed a normal pituitary gland. Abdominal MRI detected a 3.6 x 2.5 cm left adrenal nodule and PET/CT CU-64 showed increased activity (Krenning 4) consistent with a pheochromocytoma. Notwithstanding Ketoconazole (200 mg/day) for 7 months, her EF fell to a low of 15-20%. A left adrenalectomy was performed and post-op 0800 cortisol was 12.3 ug/dL (6.0 - 26.0 ug/dL). Oral hydrocortisone was initiated at 20 mg QAM/10 mg QPM for steroid withdrawal syndrome, tapered over 8 months and withdrawn when a cosyntropin stimulation test 60-min cortisol was 19.3 ug/dL; (>18.0 ug/dL). Eleven months post op, her 0800 cortisol was 8.8 ug/dL and ACTH 27.4 pg/mL. One month post-op, TTE showed EF: 15-20%, six months post-op EF: 25-30%, eight months post-op EF: 35-40% and 15 months post-op EF was normal at 50%. Her heart failure symptoms resolved, and her activity returned to normal. Conclusion This case illustrates a remarkable restoration of cardiac function following resection of a pheochromocytoma. Our patient's case is unique due to the restoration of cardiac function despite the dual impact of excessive catecholamines and cortisol. Our patient’s clinical course contributes to an evolving understanding of cardiomyopathy associated with pheochromocytoma and ectopic ACTH syndrome and highlights the potential for cardiomyopathy reversal with targeted endocrine surgical and medical interventions.

Presentation: 6/1/2024
8081 Case report of sympathetic paraganglioma presenting as chronic catecholamine induced cardiomyopathy
Authors: Tan Zi , Taiwo Adeyinka
Published: October 2024

Disclosure: Z. Tan: None. A. Taiwo: None.

Background: Sympathetic paragangliomas are rare neuroendocrine tumors (<1/100,000) arising from extra-adrenal autonomic paraganglia, generally in the thorax, abdomen, and pelvis. They secrete catecholamines predominantly norepinephrine, which can cause a rare complication of catecholamine-induced cardiomyopathy. Clinical Case: A 33-year-old male, with history of obesity and borderline hypertension not on medication, presented with dyspnea on exertion, worsening paroxysmal nocturia dyspnea of 1 month duration and sudden onset of severe right flank pain. Work up for his chronic shortness of breath revealed: Troponin negative. EKG showed sinus tachycardia. Echocardiogram revealed enlarged left ventricle, severely decreased LV systolic function of 25-30%. Given the absence of angina symptoms, negative troponin, and EKG findings, his new-onset cardiomyopathy was presumed to be non-ischemic. CT chest, abdomen and pelvis was performed for the new onset right flank pain, which revealed a 4.1 cm x 4.0 cm centrally necrotic aortocaval soft tissue mass. This raise a concern about malignancy. A CT-guided Fine-Needle Aspiration of the retroperitoneal mass suggested paraganglioma. Further investigation showed plasma normetanephrine at 5.56 nmol/L (Reference range: 0-0.89 nmol/L), 24 hour urine normetanephrine at 2411 ug/d (Reference range: 114-865 ug/d), and 24 hour urine norepinephrine at 179 ug/d (Reference range: 14-20 ug/d). Plasma metanephrines and plasma dopamine were within the normal range. A gallium DOTATE PET/CT revealed a necrotic aortocaval mass with peripheral uptake, consistent with the known paraganglioma. He was diagnosed with sympathetic paraganglioma complicated with chronic catecholamine-induced cardiomyopathy and had exploratory laparotomy excision of his paraganglioma. Preoperatively, he was treated with phenoxybenzamine and carvedilol. However, his post-surgical course was complicated by acute on chronic heart failure and pneumonia, and he subsequently passed away from a pulseless electrical activity arrest. Conclusion: Although sympathetic paragangliomas rarely presents as catecholamine-induced cardiomyopathy, this case emphasizes the importance of considering hormonal abnormalities in patients who present with non-ischemic cardiomyopathy without high risk factors. Reference: 1. Alessandra Giavarini, Antoine Chedid et al. Acute catecholamine cardiomyopathy in patients with phaechromocytoma or functional paraganglioma. Heart 2013; 99: 1438-1444.

Presentation: 6/2/2024
8252 Central Adrenal Insufficiency Masquerading as Syndrome of Inappropriate Antidiuretic Hormone (SIADH): A Case Report
Authors: Sazon J G , Reyes J L , Chua J V , Kho S A
Published: October 2024

Disclosure: J.G. Sazon: None. J.L. Reyes: None. J.V. Chua: None. S.A. Kho: None.

Hyponatremia, the most common electrolyte imbalance encountered in clinical practice, has various causes and presentation. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is a frequent hospital-related cause, potentially leading to misdiagnosis with adrenal insufficiency due to shared clinical features which may cause potential deleterious effect. We present a case of a 41-year-old male hyponatremic patient with a two-month history of progressive generalized body weakness and lightheadedness, initially managed as SIADH. Upon admission, the patient persistently showed low serum sodium level (122mmol/L) (NV: 135-145mmol/L), exhibited signs of euvolemic hyponatremia despite fluid restriction, intravenous furosemide, and sodium chloride tablets. Further work-up revealed normocytic normochromic anemia (Hgb 107 g/L) (NV: 120-160g/L), elevated ESR of (31mm/hr) (NV: 0-15mm/hr), low Ft4 (2.97 pmol/L) (NV: 12-22 pmol/L) and normal TSH (2.2 uIU/mL) (NV: 0.27-4.20 uIU/mL). During hospital stay, he experienced an episode of hypotension at 80/50mmHg and hypoglycemia at 65 mg/dL. Investigation revealed adrenal insufficiency secondary to pituitary macroadenoma with apoplexy as showed in magnetic resonance imaging. Patient was started on Prednisone. Pre-operatively, hydrocortisone 100mg IV every 8 hours preoperatively. He underwent transsphenoidal surgery; excising a 2.5cm soft and grayish suprasellar mass. Post-operatively, he was given Prednisone and Levothyroxine resulting in symptom improvement and normal sodium levels.The occurrence of hyponatremia due to adrenal insufficiency is relatively uncommon, emphasizing the need for heightened suspicion when assessing patients with prolonged or recurring hyponatremia. This paper highlight the need to replace glucocorticoid prior supplementation of thyroid hormone in such cases, averting the occurrence of adrenal crisis. This case indicated a mechanism of persistent hyponatremia attributed to secondary adrenal insufficiency, with added therapeutic benefits observed through the use of glucocorticoids and transsphenoidal surgery.

Presentation: 6/1/2024
8147 Central Diabetes Insipidus Following COVID-19 Infection: An Unusual Complication
Authors: Rivera Luisa Bernacet , Inzucchi Silvio E
Published: October 2024

Disclosure: L. Bernacet Rivera: None. S.E. Inzucchi: None.

SARS-CoV 2 infection has been associated with organ-specific complications since the 2020 pandemic, including several endocrinopathies. This has been mostly theorized to be related to high expression of angiotensin-receptor enzyme 2 (ACE-2) receptors in the endocrine system. Since the virus’ main mechanism of entry to host cells is via these receptors, endocrine glands may thus be susceptible for injury. A rarely described complication is isolated central diabetes insipidus (DI). We present a woman who developed spontaneous central DI soon SARS-CoV infection, without other cause. A 41-year-old woman with medical history of gastroesophageal reflux presented to the clinic for evaluation of polydipsia and polyuria. She contracted COVID 19 infection about 3 months prior to presentation. She had mild symptoms and did not require hospitalization or any pharmacological treatment. Approximately 3 weeks following infection she noticed the sudden development of increased urination and thirst. She reported urinating approximately every 2 hours (including 3-4 times overnight) and drinking 1-1.5 gallons of fluid daily, much more than her baseline. Given persistence of symptoms she sought medical attention at a local emergency room (ER) for further evaluation. There was no history of prior pituitary disease, brain masses, head trauma, granulomatous conditions. Workup was significant for serum sodium of 142 mmol/L and urine specific gravity <1.005. She was discharged from the ER to follow with her primary care provider. Patient had a 24-hour urine collection which yielded 6.1 L, with an osmolality of 93 mOsm/kg, while her serum sodium concentration was 141 mmol/L. Pituitary hormonal workup had normal levels of morning cortisol , free T4, TSH, prolactin, LH, FSH, and IGF-1. Due to normal serum osmolality at the time of the urine collection, the patient underwent an overnight water deprivation test of 12 hours to determine etiology of her polyuria. This resulted in a serum sodium of 148 mmol/L, serum osmolality of 300 mOsm/kg, urine osmolality of 159 mOsm/kg, and low serum copeptin level 2 pmol/L confirming the diagnosis of central DI. Patient was initiated on oral DDAVP with improvement in symptoms. A pituitary MRI revealed thickening of the pituitary infundibulum to 4 mm. The presence of central DI and thickening of pituitary stalk were suggestive of infundibuloneurohypophysitis. Other laboratory testing was negative and there was no other explanation for her condition. Follow-up pituitary MRI has shown no change in the pituitary stalk over a one-year period. The relationship between SARS-CoV 2 infection and this patient’s DI remains unclear but the temporal association and lack of other systemic related conditions makes it as strong possibility. They have been case reports with isolated central DI following COVID-19 infection. The pathogenesis remains unclear, but likely involves immune activation.

Presentation: 6/2/2024
6549 Central Diabetes Insipidus, A Puzzling Path to Diagnosing Infundibuloneurohypophysitis
Authors: Foo Francine F , Naronowicz Gabriela , Akula Monika Soujanya , Holland Soemiwati W , Cheng Jennifer , Ong Raquel Kristin , Hu Katherine , Chalasani Krishna
Published: October 2024

Disclosure: F.F. Foo: None. G. Naronowicz: None. M.S. Akula: None. S.W. Holland: None. J. Cheng: None. R. Ong: None. K. Hu: None. K. Chalasani: None.

Background: Autoimmune lymphocytic infundibuloneurohypophysitis (LINH) is a potential cause of panhypopituitarism with biopsy being the gold standard for diagnosis. This report illustrates a unique case of LINH, detailing the methods employed in diagnosis and treatment. Case Presentation: A 77-year-old man with a history of myelofibrosis, type 1 diabetes mellitus, and history of Nocardia meningitis requiring craniotomy over 20 years ago presented to the hospital for evaluation of neutropenic fever. On arrival, he was also found to be in diabetic ketoacidosis and was admitted to ICU for intravenous insulin infusion and antibiotics. Over the course of his stay, the patient reported increased urine output which was initially attributed to his hyperglycemia, however his symptoms continued to worsen even when euglycemic. Lab studies revealed serum Na 153 mmol/L, urine osmolarity 215 mOsm/Kg, urine specific gravity <=1.005 and a net fluid balance of -6,756 mL over three consecutive shifts, which was consistent with diabetes insipidus. MRI revealed thickening of the infundibular stalk with central hypoenhancement, abnormal increased T2 hyperintense signal, and loss of the normal posterior pituitary bright spot. While LINH was strongly suspected, various alternative diagnoses, including bacterial invasion and chemotherapy-induced effects, were considered and excluded. Due to the abnormal MRI findings, further testing was done to evaluate for other endocrinopathies. These tests resulted in Cortisol: 11.63 ug/dL, ACTH: 41 pg/mL, TSH: 0.07 ng/dL, FT4: 0.74 uIu/mL. The patient was started on levothyroxine for central hypothyroidism in addition to continuing desmopressin. Additionally, copeptin and vasopressin-cell autoantibody were checked as they have been recorded to be potential biomarkers for LINH. The Copeptin and vasopressin-cell autoantibody testing were both negative and unfortunately we were unable to check for the additional biomarker Rabphilin-3A due to laboratory limitations. However, after ruling out other causes, the patient was given a diagnosis of LINH based on imaging and his development of central diabetes insipidus and central hypothyroidism. Conclusion: LINH is a potential cause of central diabetes insipidus. Acknowledging the significance of LINH, despite its rarity, underlines the importance of continued monitoring as other endocrinopathies can develop later on. While biopsy remains the gold standard for diagnosis, alternative approaches such as imaging and biomarkers can facilitate confirmation.

Presentation: 6/2/2024