bluuebunny/crossref_metadata_2025 huggingface dataset:
6393 Prolactinoma with Concomitant Moyamoya Disease
Authors: Davis Adam N , Elshimy Ghada
Published: October 2024

Disclosure: A.N. Davis: None. G. Elshimy: None.

Introduction: Moyamoya disease is a cerebrovascular condition associated with stenosis of the intracranial internal carotid arteries and their proximal branches. Moyamoya is rare and has been reported to have an incidence of 0.086 cases per 100,000 persons. Only a few cases had reported concomitant prolactinoma with Moyamoya disease. We present a rare case of Moyamoya disease accompanied by a prolactin-secreting pituitary adenoma. Case: A 38-year-old female with history of prior CVA in 2019, 2022, and 2023 and prolactin-secreting pituitary macroadenoma diagnosed 2019 presented February 2023 to establish care in the Endocrine clinic for management of hyperprolactinemia. She reported history of hyperprolactinemia diagnosed 2019 and was treated with cabergoline in the past. She had CTA head January 2023 during admission for left sided weakness showing high-grade stenosis of the proximal M1 segment of the right MCA concerning for vasospasm versus occlusion with collateralization. Moreover, in January 2023 she had an angiogram performed demonstrating critical right MCA stenosis with Moyamoya changes with distal collaterals from the right ACA and PCA. When seen in clinic, she complained of galactorrhea with breast soreness and oligomenorrhea. Labs at this time were significant for prolactin level of 122.89ng/mL, estradiol 74pg/mL, LH 1.75mIU/mL, FSH 2.50mIU/mL. She was restarted on cabergoline 0.5mg twice weekly. Repeat prolactin level 8/16/23 was improved to 2.71ng/mL with improvement in her symptoms. Discussion: Moyamoya refers to the angiographic changes involving the occlusion of the arteries near the circle of Willis with arterial collateral development. Moyamoya disease refers to patients with Moyamoya findings potentially from a genetic predisposition, whereas Moyamoya syndrome refers to the presence of Moyamoya findings with associated medical conditions (history of radiation therapy, trauma, brain tumors, atherosclerosis, meningitis, hypercoagulability etc.) which may explain the occlusion. There have been several sellar and suprasellar masses reported in conjunction with Moyamoya disease including craniopharyngioma and other hormone-producing pituitary adenomas. It has been postulated that hypothalamic disturbances owing to reduced perfusion may lead to hyperprolactinemia via reduced downregulation of lactotrophs. Interestingly, our patient had unilateral rather than bilateral arterial stenosis which have been reported in other cases in the literature. Initial management is like other patients with prolactinomas and includes medical management with dopamine agonists. Conclusion: We report a rare case of Moyamoya disease with concomitant prolactinoma. This disease has been also reported with other hormone-producing pituitary adenomas and hypopituitarism. Hence, endocrinologists should be aware of these rare cases.

Presentation: 6/1/2024
8514 Rapid Improvement of Visual Field Defect with Medical Treatment in Giant Prolactinoma with Optic Nerve Compression
Authors: Sharma S , Acharya M , Sherpa C
Published: October 2024

Disclosure: S. Sharma: None. M. Acharya: None. C. Sherpa: None.

Introduction: Prolactinomas are the most common form of pituitary adenomas of which micro-prolactinomas comprise of 90% and measure less than 1 cm and occur mostly in women. Giant prolactinoma, defined as a prolactinoma >4 cm, serum prolactin concentration higher than 1000 ng/mL, and invasive tumor growth pattern with mass effects occur mostly in men. Giant prolactinomas have an estimated prevalence of 0.5-4.4% of all pituitary tumors. We report a case of giant prolactinoma causing optic nerve compression that responded well to Cabergoline. Case description: 47-year-old male with no significant past medical history was having vision disturbances for 6 months which included blurry vision and was seen by ophthalmologist. Visual field testing was done and was found to have bitemporal visual field defect/heteronymous hemianopia which prompted an emergent MRI of brain which showed 4.1x3.1x3.1 cm pituitary macroadenoma with suprasellar extension compressing the optic chiasm and optic nerves as well as the inferior anterior portion of the third ventricle and adjacent cerebrum. He was referred to neurosurgery and endocrinology. He reported intermittent headaches occurring 3-4 times a week. Denied any weakness, bowel/bladder incontinence. He denied any significant weight gain or weight loss, no palpitations, or severe fatigue. Hormonal work up showed: Elevated Prolactin level 9226 ng/ml (Reference range 2-18 ng/ml), Low Total testosterone was 213 ng/dL (Reference range 250-1100 ng/dL), low free testosterone 31.3 pg/ml (Reference range 35-155 pg/ml), with inappropriately normal luteinizing hormone and follicle stimulating hormone consistent with central hypogonadism. Thyroid stimulating hormone, free thyroxine, adrenocorticotropic hormone, am cortisol, Insulin like growth factor-1, and serum sodium were normal. He was seen in endocrinology clinic and started on cabergoline 0.5 mg twice a week. Repeat prolactin level in 3 weeks decreased to 285 ng/ml. Repeat visual field testing in 2 weeks after starting cabergoline showed that the bitemporal visual field defect had improved. His headache has improved and has intermittent episodes of dizziness. Discussion: There are few case reports describing giant prolactinoma, however there are no clear guidelines for management of giant prolactinomas causing optic nerve compression leading to visual field defects. Medical management of prolactinomas include dopamine agonists like Cabergoline, bromocriptine which are first line. The dilemma between choosing medical versus surgical management occurs in cases where there is worsening of visual field defects. Our case report highlights the drastic improvement in visual field defect and prolactin level after starting cabergoline within 3 weeks.

Presentation: 6/2/2024
8782 Rare presentation of a rapidly progressive metastatic paraganglioma in an elderly man
Authors: Haddad Joseph , Acosta Gonzalo
Published: October 2024

Disclosure: J. Haddad: None. G. Acosta: None.

Background: Pheochromocytomas and paragangliomas (PPGLs) are endocrine tumors originating from neural crest-derived cells of the adrenal medulla or from the sympathetic or parasympathetic paraganglia. According to the World Health Organization classification, all PPGLs are considered to have metastatic potential. Treatment is challenging and a multidisciplinary approach is needed to manage such complex cases.Case: A 73-year-old male with a history of melanoma s/p resection, obstructive sleep apnea, left neck vagal paraganglioma s/p radiation therapy in 2011 and hypogonadism presents for evaluation of progressive hoarseness. Associated symptoms included vertigo, left facial numbness/tingling and left sided hearing loss. Physical examination revealed a red mass visible behind the tympanic membrane and a leftward tongue deviation. MRI showed rapid tumor growth in the jugular fossa with transcranial extension to the left cerebellar hemisphere concerning for tumor progression; of note, tumor size had been stable on serial neck imaging, last done one year prior. Plasma free metanephrines and 24-hour urine fractionated metanephrines were normal. The patient underwent intracranial tumor resection by neurosurgery, pathology consistent with paraganglioma; immunohistochemical staining showed loss of SDHB and next generation sequencing revealed a pathogenic variant of SDHC gene (SDHC p.M1V). At 6 months post-op, MRI scan showed stable size of residual tumor and evolving post-op changes. However, six months later, brain MRI showed growth of both intracranial and extracranial tumor components, compatible with disease progression. Ga-DOTATATE PET/CT scan showed avid uptake in left skull base (primary tumor) with extensive bony involvement in the spine, hips, sternum, ribs and left shoulder. Chromogranin A level was slightly elevated at 134.7 ng/mL (0.0 - 101.8 ng/mL) and repeat 24-hour urine fractionated metanephrines remained negative.The patient was initially prescribed octreotide and sunitinib; however, due to insurance issues, he was only able to receive one dose of octreotide. After multidisciplinary discussion between neuro-oncology, neurosurgery and endocrinology, decision was made to start systemic therapy with temozolomide and zoledronic acid. Given potential risk of catecholamine surge, alpha blockade therapy with doxazosin was recommended. Plan to monitor treatment response with Ga-DOTATATE PET/CT every 2 months. Conclusion: Metastatic paragangliomas pose diagnostic and therapeutic challenges, especially when exhibiting an aggressive behavior. A multidisciplinary approach is paramount in managing metastatic paragangliomas given the complex nature of this disease.

Presentation: 6/3/2024
7379 Shining Light on the Teleost Pituitary: Generating a Zebrafish Prop1 Reporter
Authors: Mayer Julián Jorge Martínez , Balakrishnan Mridula , Stainier Didier , Perez-Millan Maria Ines
Published: October 2024

Disclosure: J.J. Martínez Mayer: None. M. Balakrishnan: None. D. Stainier: None. M. Perez-Millan: None.

Anterior pituitary gland development is conserved across vertebrates, with zebrafish possessing all hormone-producing cell populations found in mammals. The transcription factor PROP1 is the primary transcription factor defining the anterior pituitary hormone-producing lineages, and PROP1 mutations in mammals cause congenital hypopituitarism. Here, we aimed to establish a transgenic zebrafish line to study pituitary development by tracking prop1+ cells in vivo. We first decided to use Tol2 mediated transgenesis to express EGFP under a prop1 promoter region. To define which sequences drive prop1 expression, we looked for open chromatin marks (H3K4me1) and interspecies conservation using the UCSC Genome Browser Zv9/danRer7. We found a conserved element 6 kb upstream of the promoter as well as a conserved sequence in the first intron, with a putative GLI2 binding site. Because these two regions were separated by a highly repetitive sequence and extended over 10kb, three different constructs were tested separately: 1) 2kb upstream conserved sequence (construct 1); 2) upstream promoter region up to 6 kb upstream (construct 2 - which includes construct 1) and 3) a minimal promoter (500 bp) plus exon 1 and intron 1 (construct 3). After microinjection we observed transient EGFP expression in pituitary cells at 30 and 48 hpf in transgenic animals for constructs 1 and 3, respectively. Transgenic zebrafish for construct 2 displayed no EGFP expression. These results suggest that the repetitive region in the prop1 promoter may act as a silencer and that prop1 expression relies on several genetic elements that can not be easily captured in a single construct. These observations led us to opt for a knock-in approach, which would recapitulate prop1 expression more faithfully. Using CRISPR-Cas9 coupled with modified double stranded DNA donors, a P2A-GAL4-VP16 construct was inserted into exon 2 of prop1. After founder screening by PCR, positive fish were crossed with UAS:mCherry-CAAX to enable live imaging of early pituitary development. The fluorescent signal was detectable from 26 hpf and persisted until day five, which was the final time point assessed. We performed live-imaging of early anterior pituitary development in prop1 reporter zebrafish at high resolution. Interestingly, we found a previously undescribed population of prop1 expressing cells that resides outside the pituitary gland. This population is likely to represent a unique feature of teleost development and is currently under investigation.

Presentation: 6/2/2024
8574 Single-Cell Assessment of Gene Expression of the Tuberal Hypothalamus and Preoptic Area From Birth to Puberty in Male and Female Mice
Authors: Ruiz Daniel , Corces Victor
Published: October 2024

Disclosure: D. Ruiz: None. V. Corces: None.

The hypothalamus houses numerous cell types that control essential physiological functions and behaviors. Early postnatal life is a critical period of development where hypothalamic cells mature in function, hypothalamic circuits are refined, and sex differences in cell populations are established. Nonetheless, we have a limited understanding of the cell-specific changes in gene expression that occur throughout hypothalamic postnatal development. Having a detailed understanding of transcriptomic dynamics during this critical period of development will help our understanding of metabolic, reproductive, and behavioral disorders whose pathogenesis has been linked to insults during early postnatal life. Here, we perform single-cell RNA seq separately in microdissected tuberal hypothalamus and preoptic area (POA) from C57Bl6/J male and female mice at multiple time points throughout postnatal development, including within an hour after birth, during minipuberty and puberty. We identify changes in gene expression in cells that control reproduction including GnRH and GnIH neurons, as well as Kisspeptin neurons from the Arcuate nucleus and the Anteroventral Periventricular nucleus. We also identify changes in cell types that control appetite, including POMC and AgRP neurons, as well as SF-1 neurons of the Ventromedial Hypothalamus. Subclustering of neurons allows us to identify extensive transcriptomic heterogeneity in some well-known hypothalamic neurons that can help us understand previously unrecognized functions. Additionally, we find extensive transcriptomic changes in non-neuronal cells, including microglia, astrocytes, ependymal cells, and cells from the pars tuberalis throughout postnatal development. Current work aims to understand the function and physiological relevance of these extensive temporal and sex-driven changes in gene expression.

Presentation: 6/2/2024
12471 Spasms, Salt And Stroke; A Sequelae Of Post-operative Complications Of Pituitary Adenoma Resection
Authors: Jamshed Irha , Bhandari Shreya , Rastogi Natasha
Published: October 2024

Disclosure: I. Jamshed: None. S. Bhandari: None. N. Rastogi: None.

Introduction: Pituitary adenomas are neoplasms of pituitary adenonophyseal lineage accounting for approximately 15% of all intracranial tumors. Surgical resection is considered first-line therapy for all adenoma subtypes except prolactinomas. Multiple medical and surgical complications can occur following trans-sphenoidal resection of adenomas. Clinical presentation: A 73-year-old male with history of previously resected pituitary adenoma 6 years ago, presented for elective endoscopic trans-sphenoidal surgery due to recurrence. Postoperatively, the patient exhibited worsening mental status, left-sided hemiparesis and urine output of 8 liters in 2 hours, leading to a severe free water deficit of 1.7 liters. Labs revealed sodium 155(n 136-145 mmol/l) from 149 pre-operatively, serum osmolality 322(275-300 mOsm/ kg) and urine osmolality 768(n 50-1200 mmol/kg), in keeping with diagnosis of Central Diabetes Insipidus. Subsequent CTH showed bilateral cerebral subarachnoid and intraventricular hemorrhage and a central midbrain infarct with accompanying edema. Patient was commenced on intravenous DDAVP and D5W infusion. However, his condition deteriorated, culminating in unresponsiveness. Repeat imaging revealed new bilateral watershed infarctions, likely attributed to diffuse multivessel vasospasm, as seen on CTA head. No clinical improvement was noted with Nimodipine. Hence, the family opted for comfort care measures and the patient expired shortly after. Surgical resection of pituitary tumors, while considered safe, is not without risks, including diabetes insipidus, cerebral hemorrhage, infarction, and vasospasm. Important markers for predicting the onset of DI include serum sodium levels after surgery, the shift in sodium levels from before to after the procedure, and the volume of urine produced prior to administering DDAVP. Subarachnoid hemorrhage and hemiparesis shortly after surgery could be linked to vasospasm that has shown to be responsive to nimodipine. However, nimodipine treatment has proved to be beneficial in those patients who incurred full recovery neurologically (1). Conclusion: The case underscores the inherent risks associated with trans-sphenoidal resection of pituitary tumors. While the procedure is predominantly safe, it can occasionally lead to severe complications contributing to morbidity and mortality. It is imperative that patients are fully briefed on these potential outcomes before undergoing surgery. References: 1.EseonuCI,ReFaeyK,GeocadinRG,Quinones HinojosaA.PostoperativeCerebral Vasospasm Following Transsphenoidal Pituitary Adenoma Surgery. World Neurosurg. 2016 Aug;92:7-14. doi: 10.1016/j.wneu.2016.04.099. Epub 2016 May 4. PMID: 27155378.

Presentation: 6/1/2024
8801 Towards Safe and Efficacious Medical Therapy for Patients with Clinically Non-Functioning Pituitary Tumors
Authors: Zhang D , Bergsneider M , Kim W , Wang M B , Vinters H , Heaney A P
Published: October 2024

Disclosure: D. Zhang: None. M. Bergsneider: None. W. Kim: None. M.B. Wang: None. H. Vinters: None. A.P. Heaney: None.

Clinically non-functioning pituitary tumors (CNFTs) account for one-third of all pituitary adenomas. They do not cause clinical and/or biochemical evidence of tumor-related hormone hypersecretion, grow insidiously and typically present with mass effect symptoms such as headache and visual field deficits. Surgical resection is the current standard of care for CNFTs but complete resection is infrequently achieved due to their size and invariable invasion of locally adjacent structures. CNFT remnant tumor regrowth rates approach 50% and these patients may need repeat surgery and/or radiotherapy (RT). The latter is quite effective in achieving tumor control, but carries a risk of hypopituitarism of ∼ 40% at 10 years. Although dopamine agonists and somatostatin receptor ligands have been explored as medical therapy, there are currently no consistently effective medical treatments for CNFTs. There is a clear unmet need for novel safe and effective medical therapies for these comparatively common tumors. In a highly innovative approach we have used patient-derived ex vivo 3D tumoroid human CNFTs in an automated high throughput compound screen (HTS) to identify novel tumoricidal and growth inhibitory compounds for CNFTs. To date, we have screened ∼4,000 compounds and have identified 13 potential hits that inhibited tumor cell proliferation (a reduction of 76±15%) and induced apoptosis (induction rate of 8.2 ± 6.6) in the CNFT tumoroids respectively. The hit compounds to date fall into 3 categories based on their targets, namely Na+/K+-ATPase inhibitors (n=6), reactive oxygen species (ROS) regulators (n=4), and cell cycle inhibitors (n=3). Representative “hit” compounds from each group identified in our primary screen were rescreened in triplicate in 20 concentrations from 25µM to 50pM at 2-fold dilutions. Dose-response curves characterized compound doses that inhibited cell viability by 50% (IC50) and ranged from 13nM to 103nM. Two of these 3 compounds also induced 2-3-fold apoptosis at 0.1uM with the final compound displaying a potent 5-10-fold pro-apoptotic effect at 0.15uM concentration. In parallel, we used single cell RNA sequencing to validate targets that emerged from our HTS and to characterize the mechanism of action (MOA) of these hit compounds. As proof of concept, several of the known drug targets were noted to be amongst the highest differentially expressed genes in the CNFT tumor cell population. This approach validating a candidate target in conjunction with demonstrable activity of a drug for that same target in CNFTs may simultaneously provide us with a back-bone molecule to further develop with structural activity relationship analysis and/or allow us to individualize drug choice in patients based on immunocytochemical tumor target expression.

Presentation: 6/1/2024
5034 Characterizing the Physiological Side-Effects of Over-the-Counter Arthritis Supplements
Authors: Wei K S , De La Torre M O , Flores A , Chiu C E , Angell T E
Published: October 2024

Disclosure: K.S. Wei: None. M.O. De La Torre: None. A. Flores: None. C.E. Chiu: None. T.E. Angell: None.

Introduction: Over the counter (OTC) health supplements are commonly used by patients for a variety of ailments but may contain active ingredients that are not stated, such as glucocorticoids. Here, we present a case series of 12 patients seen by the Endocrinology Consult service at an urban safety net hospital during 2022-2023 and determined to have iatrogenic adrenal insufficiency (AI) from specific OTC supplements that surreptitiously contained glucocorticoids. Clinical Cases:12 patients using OTC arthritis supplements [Artri King (n=8), Ardosons (n=3), and Ajo Rey (n=1)] were identified. Median age was 52 years and 33.3% were female. All started using the supplements because of joint pain. Median length of use prior to cessation was 6 months. The most common presenting symptoms were nausea/vomiting (42%), fatigue (42%), abdominal pain (33%), and dizziness (17%). The most common physical exam findings of steroid excess included moon facies (66%), central adiposity (66%), abdominal striae (50%), dorsocervical fat pad (33%), and bruising (33%). 3/12 patients required ICU admission. Cortisol assessment was performed in 11/12 patients, which showed normal cortisol level in 1 patient (cortisol ≥16 mcg/dL), AI in 3 patients (cortisol ≤3 mcg/dL), and an equivocal level (cortisol 3-16 mcg/dL) in 7 patients. Cosyntropin stimulation testing in 6/7 patients with equivocal cortisol levels suggested AI in 4 (cortisol level <16 mcg/dL at 60 minutes after ACTH stimulation), whereas 2 showed lower but normal response (cortisol levels 18.2 mcg/dL and 18.4 mcg/dL). In total, 10/12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis. The most common regimens were hydrocortisone 20mg qAM/10mg qPM (33%) and hydrocortisone 5mg qAM/5mg qPM (17%). To date, 2/10 patients have successfully discontinued steroid replacement. Conclusion: These cases demonstrate possible Cushing’s syndrome and/or adrenal insufficiency after unintentional exposure to glucocorticoids in these OTC arthritis supplements, which has only previously been reported in a small number of case reports (1). This series collected over a 2-year period offers important clinical insights: Because patients may not identify or recall a supplement, possible use of OTC medications for arthritis or other anti-inflammatory purposes should be specifically assessed in patients presenting with adrenal insufficiency (especially with concomitant findings suggesting Cushing’s syndrome). For patients on such supplements, immediate discontinuation may not be possible without cortisol replacement and should be done with caution. 1) Boncompagni A.C. et al. A case of iatrogenic Cushing syndrome and subsequent adrenal insufficiency from a hidden ingredient in the supplement Artri Ajo King. J Am Coll Emerg Physicians Open. 2023;4(4):e13007.

Presentation: 6/1/2024
12506 Vagal Glp-1 Receptors Are Essential In The Efficacy Of Orally Administered Exendin-4
Authors: Bethea M M , da Silva Teixeira S , Cook T M , Hendrix J , Sandoval D
Published: October 2024

Disclosure: M.M. Bethea: None. S. da Silva Teixeira: None. T.M. Cook: None. J. Hendrix: None. D. Sandoval: None.

Oral formulations, such as the first and only FDA-approved oral GLP-1 analog (semaglutide), have the advantage of improving patient adherence and quality of life. Yet, how these oral GLP-1 receptor (GLP-1R) agonists mediate their glucose-lowering effects is unknown. Because systemic administration of GLP-1R analogs likely targets different GLP-1R populations than that of oral administration, it is imperative that we advance our understanding of the key GLP-1Rs needed for the metabolic benefits of orally administered GLP-1 therapies. We have preliminary data demonstrating that the oral administration of free Ex-4 significantly enhances glucose tolerance in fasted non-diabetic mice, strongly suggesting that oral Ex-4 is bioactive after transit through the GI system. Importantly, we have additional evidence that shows the oral administration of either Ex-4 or GLP-1 does not lead to detectable circulating levels of either peptide, suggesting that a local source is mediating this effect. Furthermore, using a GLP-1R Cre mouse crossed with a tdTomato reporter mouse, we see that the GLP-1R is expressed on epithelial cells within the intestine, yet oral Ex-4 administration in mice lacking GLP-1R in intestinal enterocytes elicited glycemic improvements. We hypothesized that neuronal GLP-1R populations within the gastrointestinal tract mediate the glycemic improvements of orally administered GLP-1 agonists. To test this hypothesis, we used various genetic mouse models lacking GLP-1Rs subjected to an oral gavage of Exendin-4, a GLP-1RA. We found that vagal GLP-1Rs are necessary for the glucose-lowering effects of orally administered Exendin-4. These findings will ultimately facilitate the development of more efficacious tailored compounds for the treatment of T2D and enhance our knowledge of GLP-1 biology.

Presentation: 6/1/2024
8656 A Case of Wolfram Syndrome Accompanied by Growth Hormone Deficiency
Authors: Jung Hyeon Jun , Kim Goo Lyeon , Park Yooyeon , Yu Jeesuk
Published: October 2024

Disclosure: H. Jung: None. G. Kim: None. Y. Park: None. J. Yu: None.

Background: This case report explores the presentation, diagnosis, and multidisciplinary management of an 11-year-old female patient with Wolfram syndrome, a rare and progressive genetic disorder. Wolfram syndrome is a rare genetic disorder characterized by early-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration. The prevalence of this syndrome is very low, affecting approximately 1 in 770,000 individuals. Prompt diagnosis is essential as early intervention and comprehensive management can improve the patient's quality of life and prognosis. Clinical Case: A female patient aged 9 years and 2 months was brought to our Pediatric Endocrinology Clinic because an elevated blood sugar level (520 mg/dL) was detected during a routine health checkup. She was born at 40 weeks, weighing 3kg, and had no remarkable perinatal history except for cleft lip. At the time of admission due to diabetes mellitus, the patient showed symptoms of developmental delay, language impairment, short stature, and strabismus. During follow-up over 1 year with management of diabetes mellitus, she showed persistent short stature and poor growth velocity. She underwent a growth hormone (GH) stimulation test, which confirmed GH deficiency. Further investigation found optic atrophy through ophthalmological examination and genetic investigation based on whole exome sequencing revealed a homozygous mutation in WFS1 (c.1475C>T, p.Pro492Leu), suggesting Wolfram syndrome. Pure tone audiometry did not reveal specific abnormality but there were some limitations in the interpretation of the study result due to language and communication difficulties. She also showed nocturia, and in the absence of glycosuria, the urine specific gravity was less than 1.005, suggesting diabetes insipidus. She is currently receiving multidisciplinary treatment including pediatrics, otolaryngology, and ophthalmology. Conclusion: This case underscores the importance of increasing clinical awareness regarding Wolfram syndrome, as early intervention through timely diagnosis may lead to improved patient outcomes. This case also suggests that although GH deficiency is uncommon in Wolfram syndrome, growth assessment is important in patients with Wolfram syndrome in addition to managing diabetes mellitus and diabetes insipidus.

Presentation: 6/2/2024
7634 Delayed Diagnosis of Classical Congenital Adrenal Hyperplasia: Case Series and Literature Review
Authors: Jafar B , Kilberg M , Vogiatzi M G
Published: October 2024

Disclosure: B. Jafar: None. M. Kilberg: None. M.G. Vogiatzi: Other; Self; Consultant for Spruce, Crinetics and Eton. Research support from Neurocrine, Spruce and Adrenas.

Congenital adrenal hyperplasia affects (CAH) 1 in 15,000 newborns and is the most common adrenal insufficiency. Newborn screening (NBS) for CAH began with the development of a radioimmunoassay, measuring 17 α-hydroxyprogesterone (17OHP) using blood on microfilter paper. 17OHP screening due 21-hydroxylase deficiency is now part of the NBS in many countries. Although this has revolutionized CAH diagnosis for both simple virilizing (SV) and salt wasting (SW) CAH, NBS was developed to prevent salt wasting crises, especially in 46,XY CAH where neonates may be otherwise asymptomatic. Additional pitfalls to testing include improper sampling, steroid use perinatally and postnatally and a sex driven discrepancy. We present 7 cases of CAH who presented later in life, all with a normal NBS. Patient A presented as a 2-week-old 46,XX presenting with clitoromegaly. NBS 17OHP was 14.7ng/mL (normal <30ng/mL), serum testing was concordant with 17OHP 221 ng/dL (normal 1-5-day infant = <460ng/dL), and pelvic ultrasound showed a uterus. High dose ACTH stimulation testing was ultimately obtained at 7 months of life, showing adrenal insufficiency with a cortisol peak of 6 mcg/dL. 17OHP baseline was 6,632 ng/dL and peaked at 24,115 ng/dL.Patients B, C and D were 46,XY, presenting between ages 4-8 YO with advanced bone age (BA) and premature adrenarche. Their laboratory evaluations showcased elevated 17OHP, low peak in cortisol level.Patients E, F and G were 46,XY, presenting between ages 3-6 YO with central precocious puberty, and advanced BA. Their laboratory evaluations showcased elevated 17OHP, pubertal gonadotropins and low peak in cortisol level.All patients were initiated on hydrocortisone replacement given the diagnosis of SV CAH and associated adrenal insufficiency. 3 patients elected to pursue treatment for central precocious puberty. 2 patients were started on an aromatase inhibitor for advanced BA.Of the 7 cases we present, all were simple virilizing. While the goal of the NBS (preventing salt wasting crises) may have been satisfied, it is plausible that these patients may have been remained undiagnosed entirely due to reports of normal screening tests. These cases highlight the importance for providers to pursue the diagnosis of classical CAH in spite of normal screening - detecting CAH and initiating hydrocortisone therapy prior to adrenal crisis is imperative while the other noted impacts of growth and puberty deserve discussions of management options, education and counseling for future implications.

Presentation: 6/3/2024
8210 Reversible Proximal Myopathy Due to Severe Vitamin D Deficiency in a Child With Autism
Authors: Ozcan Ozan , Subedi Sonika , Velasquez Sara , Dave-Sharma Swati
Published: October 2024

Disclosure: O. Ozcan: None. S. Subedi: None. S. Velasquez: None. S. Dave-Sharma: None.

Introduction: Severe Vitamin D(Vit.D) deficiency can present dramatically and mimic other illnesses. Autism Spectrum Disorder(ASD) is one of the conditions that pose a risk for nutritional deficiency due to the severely restricted diet. Symptoms can be masked and unclear in a child with ASD due to limited verbal communication. Case Presentation: We report an African-American male with ASD, initially presented at 9 years of age with complaints of back pain after a fall and difficulty in walking.Diet history was significant for severely restricted to instant noodles and french fries.Evaluated by peds neurology, the exam showed Grover’s sign, mildly decreased DTRs, and downgoing plantar response. The upper extremity couldn’t be assessed because the patient was not cooperative. CBC, CRP, LFT, ESR, and CPK were sent for possible myopathy and inflammatory conditions. Lab values reported within normal limits other than CPK 462 U/L(reference range 20-200 U/L) and ALK P 1511 U/L(Reference range: 40-130 U/L). Peds neurology suspected progressive muscle disorder. X-rays, electromyography, and MRIs of the spine and hip were within normal limits. Referred to Genetics, basic genetic panels were within normal limits. The patient followed for two years without improvement with the concerns of limb-girdle muscular dystrophy. The patient later presented with persistent shoulder and neck pain to ED. Labs showed CK(elevated 510), LFT (ALK P 1700), BMP (Ca 5.3mg/dl reference range: 8.4 – 10.5mg/dl), Ionized Ca: 2.92 mg/dl (Ref range: 4.8-5.5 mg/dl). The endocrinologist was consulted, and further investigations included PTH 562.5 pg/ml (Ref range: 15-65 pg/ml), Phosphorus: 4.3 mg/dl (3-5 mg/dl), 25 OH Vit.D levels < 4 ng/ml(reference range 30-80ng/ml). X-rays were significant for demineralization. The muscular dystrophy panel resulted negative. The patient was admitted to the inpatient unit and started on calcitriol, CaCO3, and ergocalciferol. After initial stabilization, the patient was discharged home. During the discharge, the patient was still demonstrating problems with walking. The patient was sent home on calcitriol 0.25mcg, CaCO3 tablets, and Ergocalciferol 50 000 units weekly , weekly physical therapy and follow-up by ped. endocrinlogist. As Vit.D levels improved, CPK decreased . With close follow-up, supplements, and physical therapy, myopathy entirely resolved in following 2 years. Conclusion: Vit. D deficiency is an uncommon cause of myopathy and should be in a differential diagnosis for myopathy as the condition is reversible and can be treated. Due to restrictive eating patterns and limited social interactions, patients with ASD are at increased risk for developing nutritional deficiencies. Physicians should maintain a high index of suspicion in patients with restrictive eating.

Presentation: 6/2/2024
7006 Transient Adrenal Suppression in Pediatric Patients following Propofol Infusion: A Case Report
Authors: Salama Mostafa , Nadim Aida
Published: October 2024

Disclosure: M. Salama: None. A.N. Lteif: None.

Introduction: Intravenous propofol is widely employed for procedural sedation, monitored anesthesia care, and induction of general anesthesia. It can be administered as a bolus or an infusion. While extensively used, reports in adults and animal studies suggest potential implications of propofol on adrenal steroidogenesis. In this study, we present findings detailing transient adrenal suppression in two pediatric patients following propofol infusion. Case: The first case involves a 5-year-old boy diagnosed with left cerebellar high-grade glioma, having undergone tumor resection and proton beam irradiation. Morning cortisol levels measured twice post-propofol sedation (20 mg bolus followed by infusion at a rate of 275 mcg/kg/min prior to radiation therapy were 3.1 and 1.2 mcg/dl (ref range: 2.4-15 mcg/dl), accompanied by an undetectable ACTH level. Subsequent non sedated cortisol testing done four days later revealed a robust reading of 24 mcg/dl, with an ACTH level of 46 pg/ml.The second case is a 4-year-old boy diagnosed with right cerebellar high-grade astrocytoma glioma, who underwent total resection two months before his initial cortisol assessment. Following proton beam irradiation and propofol sedation (20 mg bolus followed by propofol infusion at a rate of 300 mcg/kg/min) for therapy, his morning cortisol obtained 45 minutes after starting propofol infusion was low at 2 mcg/dL (ref range: 2.4-15 mcg/dl). A repeat cortisol test eight days later showed an increase to 5.6 mcg/dL. Notably, neither patient was on exogenous steroids or medications impacting the adrenal axis. Discussion: The transient decline in cortisol and ACTH observed in these cases gains significance as the patients were not on any medication known to potentially induce adrenal suppression. Additionally, the gliomas were not parasellar in location and radiation had just begun. These findings align with prior reports linking propofol administration with the suppression of the hypothalamic-pituitary-adrenal axis. The impact of propofol on adrenal function needs to be considered especially in pediatric patients undergoing procedures or treatments. Conclusion: Our cases shed light on the potential transient influence of propofol on adrenal function in pediatric patients. Further studies are warranted to comprehensively evaluate the effects of propofol injections and infusions on adrenal function in pediatric cohorts.

Presentation: 6/3/2024
8561 Association Of Alopecia And Hirsutism With Severity Of Depression In A Sample Of Hispanic Women With Polycystic Ovary Syndrome
Authors: Loyola Cristina Marie Casas , Rivera-Rodriguez Yanni Gabriel , Rodriguez Brenda Marin , Roque Torres Jose A , Gonzalez Rodriguez Loida A , Romaguera Josefina
Published: October 2024

Disclosure: C.M. Casas Loyola: None. Y.G. Rivera-Rodriguez: None. B. Marin Rodriguez: None. J.A. Roque Torres: None. L.A. Gonzalez Rodriguez: Research Investigator; Self; Lilly USA, LLC. J. Romaguera: None.

Purpose: Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder in females has been associated with several chronic diseases. Females with PCOS have been found with a higher prevalence of mental disorders. Depression and its severity have been associated with the development and progression of cardiovascular disease. We aimed to assess depression severity and its association with PCOS related comorbidities such as alopecia and hirsutism. Methods: A cross sectional study of females aged 21-45 years was conducted in the endocrinology clinics at the RCM-Clinics. PCOS was diagnosed using the Rotterdam criteria, hirsutism was defined by modified Ferriman-Gallwey score (mFG ≥ 9), alopecia was defined using the Ludwig scale and Depression using the Patient Health Questionnaire (PHQ9). Severity of depression and presence of alopecia and hirsutism were compared among groups. Results: A total of 112 patients were included in this study (85 patients PCOS+ and 27 patients PCOS-). Mean age was 32 ± 6 years. Severity of depression in PCOS- patients was: 44% none to minimal, 30% mild and 27% moderate to severe. Severity of depression in PCOS+ patients was: 28% none to minimal, 35% mild and 36% moderate to severe. Participants with alopecia and PCOS+ had a greater percentage of moderate to severe depression (58%) compared to the control group without alopecia (30%) (p value<0.05). No differences were observed between hirsutism and severity of depression among groups. Conclusion: Our study showed an association between alopecia and severity of depression in patients with PCOS+. The presence of hirsutism was not associated to severity of depression. Currently, there are more available treatments for hirsutism than for alopecia. For this reason, patients with hirsutism have more opportunities to manage their condition than patients with alopecia, which often require more invasive procedures. The presence of alopecia can be considered a risk factor for developing major depressive disorder in patients with PCOS. Treatment of PCOS-related abnormalities should be emphasized soon after diagnosis. Evaluation of mental health is imperative in our PCOS patients.

Presentation: 6/3/2024
7848 Characterization of vasomotor symptoms-like temperature changes in a mouse model of menopause
Authors: Torres Jimenez E , Silva M , Zdon S T , Navarro V M
Published: October 2024

Disclosure: E. Torres Jimenez: None. M. Silva: None. S.T. Zdon: None. V.M. Navarro: None.

Most menopausal women suffer vasomotor symptoms (VMS), also known as hot flashes(HFs), induced by the decline in estrogen levels towards the menopausal period. HFs aredescribed as a sudden-onset sensation of extreme warmth, cutaneous vasodilation, sweatingand cold-seeking behavior as part of an inappropriate heat dissipation response to a drop incore temperature. HFs vary in frequency, duration and severity, and can impair the quality oflife of the women affected. These variables change within the same individual throughout theday, indicating that HFs are under the control of yet unknown circadian and ultradian cues.Unfortunately, the field is lacking an experimental mouse model that recapitulates the onsetand progression of VMS during menopause to investigate the neuroendocrine mechanismscontrolling this phenomenon. Here, we used the mouse model of menopause based on theshort-term bilateral removal of the ovaries (ovariectomy, OVX). To monitor core- and skintemperatures (Tc and Tskin, respectively) in response to estrogen loss, we placed temperaturedata loggers (DST-nano probes) in the abdomen of 3-mo female C57BL/6 mice (n=5) for Tcrecordings, and in the ventral surface of the tail for Tskin recordings in the same mouse. Tcand Tskin were recorded simultaneously every 10 min to provide a complete sequence of HFs-like events in the transition from gonad intact (pre-menopause) to short-term OVX (menopause). We observed a continuous fluctuation in Tc and Tskin throughout the dark (ZT12– ZT0) and light (ZT0 – ZT12) phases. Basal, maximum, amplitude and mean temperaturewere monitored on each phase for all mice. Interestingly, temperature changes were observedduring the dark phase, with an increase in the heat loss index (HLI, indirect measurement oftail skin vasodilatation) during week 1 post-OVX. Additionally, during the first week post-OVX,maximum Tskin increased during both dark and light phases. Interestingly, mean Tc decreasedthroughout the two weeks post OVX, leading to a significant shortening of Tc amplitude (i.e.range) post OVX. This decrease in mean Tc in response to OVX was directly correlated withan increase in the mean and amplitude of Tskin (increased heat dissipation), thus replicatinga human VMS. These changes in Tc and Tskin were more evident during the dark phase.Overall, this study supports the use of OVX mice as a model of human VMS. This modelpresents an exacerbation of the temperature fluctuations (VMS) during the dark phase which,despite the species differences in dark/light activity, correlates with the worsening of VMS insome women at night. Finally, the increase in basal temperature during the first week postOVX, but not the second, suggests that the mouse window for menopause-like symptoms isrelatively short post-OVX and by the second week they may resemble a post-menopausalmodel where VMS are less severe.

Presentation: 6/2/2024
7701 Comparative Analysis of Dried Blood Spot and Serum ELISAs for AMH, FSH, and LH in Patients Seeking IVF Treatment
Authors: Kumar Tanya , Chauhan Rahul , Kalra Bhanu , Patel Amita S , Chauhan Subodhsingh , Kumar Ajay
Published: October 2024

Disclosure: T. Kumar: None. R. Chauhan: None. B. Kalra: None. A.S. Patel: None. S. Chauhan: None. A. Kumar: None.

Relevance: Dried Blood Spot (DBS) technology has not been widely implemented in the diagnostic industry due to its limitations in obtaining reliable, quantitative data from small blood samples. However, recent advancements in methods, i.e., sensitive antibodies, homogeneous and reproducible paper quality, and painless needles have renewed the interest in the DBS collection technique. Objective: The aim of the study is to validate the hormone measurements using DBS technology and compare the correlation matrix between AMH, LH, FSH, inhibin B, Antral Follicle Counts (AFC), age, and BMI in patients seeking infertility workup. Materials and Methods: Matched serum and DBS samples from thirty-nine patients between the ages of 18 and 45 years were collected on day 3 of the cycle. The subjects were visiting the clinic for initial fertility workup and subjects on medications for ovarian suppression were excluded. The samples were tested on Ansh Labs DBS AMH (AL-129), FSH (AL-187), and LH (AL-190), PCOCheck AMH (N-N terminus, AL-196), picoAMH (C-N terminus, AL-124-r), US Inhibin B (AL-195) ELISAs. Baseline AFC obtained via transvaginal ultrasound, BMI, and age were collected. Spearman’s correlations, and regression analysis using Passing and Bablok were calculated to examine the relationship between AFC, AMH, inhibin B, FSH LH, age, and BMI. Results: DBS samples were highly correlated to their matched serum specimens. The slope and Spearman’s rank correlation (rs) between matched serum and DBS specimens for AMH, FSH, and LH were 1.17x, 1.07x, 1.07x, and 0.98, 0.93, and 0.97, respectively. DBS AMH strongly correlated with AFC. The Spearman’s rank correlation (rs) between AFC and DBS AMH, DBS LH, and DBS FSH were 0.80, -0.11, and -0.31, respectively. A strong correlation was observed between age and AMH, LH and FSH. A weak correlation was observed between BMI and AMH, LH and FSH. The Spearman’s rank correlation (rs) between age and DBS AMH, LH, and FSH were -0.34, 0.28, and 0.25, respectively. DBS AMH, LH, and FSH correlation with BMI were -0.06, 0.05, and 0.09, respectively. Inhibin B had a strong correlation to age (rs -0.33), BMI (rs -0.67), AFC (rs 0.44), DBS AMH (rs 0.40), DBS FSH (rs -0.19), DBS LH (rs-0.11), respectively. AMH method comparison between N-N and N-C terminal ELISA using 39 serum samples yielded slopes of 0.85x and Spearman’s rank correlation of 0.97. Conclusions: DBS and serum measurements for AMH, LH, and FSH are very accurate and precise. They can be used interchangeably. The strong relationship between BMI and Inhibin B will require further investigation and may open new avenues in obesity and reproductive endocrinology.

Presentation: 6/1/2024
12257 Diagnosis Of Pheochromocytoma With Atypical Imaging Characteristics
Authors: Park Sanghwa E , Duc Hoang Thanh , Shakir Mohamed K M , Joseph Spiro Andrew
Published: October 2024

Disclosure: S.E. Park: None. T.D. Hoang: None. M.K. Shakir: None. A.J. Spiro: None.

Background: Diagnosis of pheochromocytoma is based on characteristic findings on imaging and lab studies. CT and MRI are the primary imaging modalities used when evaluating adrenal lesions. Gadolinium-68(68Ga)-DOTATATE PET/CT is somatostatin receptor based form of imaging used in the evaluation of patients with neuroendocrine tumors, including pheochromocytomas and paragangliomas (PPGLs). 68Ga-DOTATATE PET/CT is reported to have high sensitivity for the detection of PPGLs. Clinical Case: A 50-year-old man was evaluated for a 1.7cm right adrenal nodule, incidentally found on spinal MRI. He had no significant medical history and was not taking medications. He was asymptomatic without paroxysms of headache, palpitations, or diaphoresis. He had no notable family history. His physical exam was unremarkable. A low-dose dexamethasone suppression test showed appropriate cortisol suppression. Aldosterone and renin were in the normal range. Plasma fractionated metanephrines showed normal metanephrine level with mildly elevated normetanephrines, 194 pg/mL (ref. 0-145 pg/mL). 24hr-fractionated urine metanephrines showed normal metanephrine and normetanephrine levels. Adrenal CT showed a 1.9 x 1.4 x 1.9cm right adrenal lesion with 38 HU on noncontrast imaging. 15-minute washout showed absolute and relative washout of -27.1% and -11.1% respectively. Adrenal MRI showed a T2-hyperintense/T1-hypointense lesion. Due to concern for an asymptomatic pheochromocytoma, 68Ga-DOTATATE PET/CT was performed, and the right-side nodule showed relative absence of uptake compared to the rest of the adrenal gland. The results were interpreted as reassuring that the lesion was unlikely to represent a pheochromocytoma. During follow-up, two years later, a repeat adrenal CT showed an increase in size of the lesion to 2.0 x 1.9 x 2.6cm, with similar HU and washout. Plasma fractionated metanephrines increased to 420 pg/mL (ref. 0-145 pg/mL) and urine fractionated metanephrines were elevated 822 mcg/24hr (ref. 156-729). A clonidine suppression test was performed. During the test, the normetanephrine levels did not suppress, consistent with a pheochromocytoma. He underwent laparoscopic adrenalectomy, with pathology confirming a 2.3cm pheochromocytoma. Labs checked one month after surgery showed normalization of serum and urine normetanephrines. Conclusion: 68Ga-DOTATATE PET/CT is reported to have high sensitivity for the detection of PPGLs. In our patient, 68Ga-DOTATATE PET/CT showed relative absence of uptake in the adrenal lesion, which led to decreased suspicion for pheochromocytoma. Diagnosis was eventually made during follow-up, based on CT imaging, biochemical testing, and clonidine suppression test. More research is needed to determine the utility of 68Ga-DOTATATE PET/CT in the evaluation of adrenal pheochromocytomas.

Presentation: 6/1/2024