bluuebunny/crossref_metadata_2025_split huggingface dataset:
8130 A Case of Cushing’s Disease Presenting with Posterior Reversible Encephalopathy Syndrome
Authors: Chincholi A H , Goldberg M D 
Published: October 2024

Abstract
Disclosure: A.H. Chincholi: None. M.D. Goldberg: None.
Introduction: Posterior reversible encephalopathy syndrome (PRES) is characterized by headaches, altered mental status, vision changes, and seizures, along with characteristic imaging findings of bilateral white matteredema in the posterior cerebral hemispheres. The syndrome often occurs in the context of severe hypertension, and has previously been reported in 6 patients with Cushing’s syndrome (CS) - 4 with ectopic sources of ACTH, 1 with micronodular adrenal hyperplasia and 1 pediatric case with Cushing’s disease. Clinical Case: An 18-year-old-man was admitted to our hospital after experiencing a second seizure at home. His presentation was significant for lethargy, hypertension, facial plethora, acne, proximal muscle weakness,central obesity, extensive purple striae, hyperglycemia, and hypokalemia. Two months prior, a diagnosis of ACTH-dependent CS had been made at an outside facility when he presented with a hypertensive emergency and new-onset diabetes. One month prior, he had been hospitalized with pneumonia complicated by acute kidney injury requiring temporary hemodialysis, and his first seizure. Brain MRI had shown extensive T2/FLAIR hyperintensities in the temporal lobes and cerebellum,consistent with PRES. On this admission, morning serum cortisol was 56.1 mcg/dL, and then 57.9 mcg/dL following 10 mg dexamethasone at night; ACTH was 120 pg/mL, and 24-hour UFC was 2,204 mcg. Ketoconazole and spironolactone were added, with no appreciable improvement in his cortisol levels but normalization of blood pressure. He required up to 150 units of insulin per day to manage his hyperglycemia. PituitaryMRI revealed a 0.6 cm adenoma, along with the T2/FLAIR hyperintensities. Chest CT showed no masses. A 10 mcg IV desmopressin stimulation test resulted in a 248% increase in ACTH and 32% increase in cortisol, and a second MRI with a 3T scanner measured the pituitary adenoma to be 1.0 cm. It was concluded that he had Cushing’s disease, and he underwent transsphenoidal resection of the pituitary adenoma. The surgery was curative, as reflected by postoperative central adrenal insufficiency. The patient was discharged on postoperative day 3 with oral hydrocortisone. Two weeks later, he was euglycemic off insulin and his blood pressure had normalized off spironolactone. Three months later, his muscle weakness and his headaches had completely resolved. Brain MRI showed complete resection of the pituitary adenoma and resolution of the white matter changes. Conclusion: To our knowledge, this is the first report of PRES associated with CS due to an ACTH-secreting pituitary adenoma in an adult. We suspect that this patient’s marked secondary hypertension triggered the reversible encephalopathy. Providers should be aware of this potential complication of hypercortisolism. This case also highlights the utility of desmopressin stimulation test in defining the cause of ACTH-dependent CS.
Presentation: 6/3/2024
8129 A Case of Pituitary Stalk Interruption Syndrome Presenting With Panhypopituitarism
Authors: Salvat Aleida , Sevilla Marla 
Published: October 2024

Abstract
Disclosure: A. Salvat: None. M. Sevilla: None.
Background: Pituitary stalk interruption syndrome (PSIS) is a rare congenital abnormality characterized by the classic triad of a thinned or interrupted pituitary stalk, an ectopic or absent neurohypophysis, and a hypoplastic or absent anterior pituitary gland. Clinical manifestations vary and can include neonatal hypoglycemia, short stature, cryptorchidism, and delayed puberty. Symptoms can present at birth or later in life with variable degrees of hormone deficiency. Clinical case: A 25-year-old male with hypothyroidism (on levothyroxine since age 13) presented for evaluation of hypogonadotropic hypogonadism. At birth, he was diagnosed with bilateral cryptorchidism and had frequent hypoglycemic episodes. During his childhood and early teenage years, his growth paralleled of his peers. However, at age 18, he experienced a growth spurt with unusually long arms and legs. He never developed secondary sexual characteristics. Physical examination showed blood pressure of 109/62 mmHg, height 193 cm, weight 76 kg, Tanner stage 1 pubic hair, microphallus, and nonpalpable testicles. The initial labs were consistent with panhypopituitarism: FSH 0.14 mIU/mL (0.95–11.95 mIU/mL), luteinizing hormone &lt;0.09 mIU/mL (0.57–12.07 mIU/mL), total testosterone &lt;4 ng/dL (240–871 ng/dL), prolactin 30.31 ng/dL (3.46–19.40 ng/dL), AM cortisol &lt;1 ug/dL (3.7–19.4 ug/dL), ACTH 14 pg/mL (6–50 pg/mL ), cortisol levels 60 minutes after consyntropin stimulation test of 3.6 ug/dL (3.7–19.4 ug/dL), IFG-1 &lt;16 ng/mL (63–373 ng/mL), TSH 7.24 uIU/mL (0.35–4.94 uIU/mL), free T4 0.53 ng/dL (0.70–1.48 ng/dL). Karyotype 46, XY, inv (9) (p12q13). The whole exome sequencing testing was negative. Pituitary magnetic resonance imaging showed hypoplasia of the anterior pituitary gland, ectopic location of the posterior pituitary gland at the expected base of the pituitary infundibulum anterior to the mammary bodies, and hypoplastic or absent pituitary infundibulum, findings suggestive of pituitary stalk interruption syndrome. Scrotal ultrasound showed no testicular or epididymal tissue within the scrotum. DEXA scan showed osteoporosis associated with a long history of non-treated testosterone deficiency. The levothyroxine was adjusted, and the patient was started on intramuscular testosterone, calcium, and vitamin D to manage the hypogonadism and improve the bone mineral density. Conclusion: Diagnosis of PSIS is often delayed due to its variable presentation and age of onset. Although this condition is considered rare, it should be in the differential diagnosis of patients presenting with panhypopituitarism. Early identification of deficient hormones, as well as prompt initialization of hormone replacement therapy, is essential to prevent serious complications associated with these deficiencies, such as adrenal crisis, osteoporosis, diminished quality of life, delayed puberty, and infertility.
Presentation: 6/3/2024
8024 A Case of Smoldering Clinically Silent Cushing’s Disease
Authors: Bheeman Chandni , Shafiq Ismat 
Published: October 2024

Abstract
Disclosure: C. Bheeman: None. I. Shafiq: None.
Aggressive pituitary adenomas account for about 10% of all pituitary adenomas. These aggressive tumors are noted to have unusually rapid tumor growth rate despite optimal standard therapies including surgery, medical therapy and radiotherapy. We present a case of a 39-year-old female with no prior past medical history who initially presented with complaint of amenorrhea. She had reported she had not menstruated for the past 6 months. She also endorsed galactorrhea with nipple stimulation. A pituitary dedicated MRI revealed a pituitary adenoma measuring 2.5 x 1.7 x 1.7 cm. Hormonal work-up showed salivary cortisol on two consecutive nights that was 66 ng/dL and 52 ng/dL (reference range: 0 - 99 ng/dL) and a prolactin that was slightly elevated at 44.9 ng/mL (reference range: 4.8-23.3 ng/mL). This elevation in prolactin was thought to be due stalk effect and since her hypothalamus-pituitary-gonadal axis was suppressed, patient had a transsphenoidal resection of what was thought to be a nonfunctioning adenoma. However, the pathology of her tumor was significant for extensive ACTH staining and a Ki-67 of 11 - 15%. Her clinical course proved to be challenging as her tumor reoccurred multiple times and she eventually developed biochemical and clinical evidence of Cushing’s disease and had visual defects due to compression of the tumor on the optic nerves. This tumor was refractory to multiple surgeries, radiation treatment and chemotherapy. Through the presentation of this case, we aim to highlight the factors associated with aggressive pituitary adenomas, the current treatment guidelines and emerging medical therapies.
Presentation: 6/1/2024
6459 A Novel Long-Acting GH Receptor Antagonist Optimizing Therapeutic Efficacy and Duration
Authors: Ku Cheol Ryong , Kang Chan Woo , Hun OH Ju , Wang Eunkyung , Song Hyung Nam , Park Ki Bum , Kim Bum Joon , Kim Kyuwan , You Sun-Ah , Park Soon-Jae , Lee Eun Jig 
Published: October 2024

Abstract
Disclosure: C. Ku: None. C. Kang: None. J. Oh: None. E. Wang: None. H. Song: None. K. Park: None. B. Kim: None. K. Kim: None. S. You: None. S. Park: None. E. Lee: None.
Background: Forty to sixty percent of acromegalic patients undergo medical treatment, utilizing somatostatin analogues, dopamine agonists, and GH receptor (GHR) antagonists. The GHR antagonist, pegvisomant exhibits the most robust efficacy in reducing IGF-1 levels in acromegalic patients. However, pegvisomant faces several clinical limitations, such as poor compliance due to the necessity of daily injections. This study aimed to develop a novel, long-acting fusion GHR antagonist with optimized therapeutic efficacy and duration. Method: Twelve mutant proteins with alterations in the C-terminal and N-terminal regions of GHR were generated to confirm the GHR binding affinity and inhibitory potency compared with pegvisomant, which was evaluated with STAT5b luciferase reporter assay. Several carriers were engineered into selected mutant GHRs to increase the therapeutic duration. For in vivo experiments, single or repetitive injection of GHR antagonists were applied to acromegalic mouse model (somatotroph specific Aip knock out (sAIPKO) mice). Pharmacokinetics (PK) and pharmacodynamics (PD) were evaluated in New Zealand White (NZW) rabbits. Result: Four out of the 12 GHR mutants exhibited higher affinity and stronger inhibitory potency toward human GHR when compared to pegvisomant. Specifically, three GHR mutants significantly reduced serum IGF-1 levels in sAIPKO mice following daily injections of 20 mg/kg for 7 days (52.3±6.0 to 5.9±1.3, 50.3±3.5 to 32.3±2.3, and 49.8±3.7 to 13.9±4.3 ng/mL; all p &lt; 0.05). Among them, S4020N exhibited the lowest EC50 value for GHR binding affinity in in vitro analysis containing human GHR (0.594 nM) and mouse GHR (0.891 nM). Following fusion with each long-acting carrier, S4020N with the Fc carrier protein (ALT-B5) demonstrated the highest binding affinity and the strongest inhibitory potency toward human GHR, surpassing pegvisomant by 14 and 25 times, respectively. Administration of ALT-B5 (80 mg/kg) and pegvisomant (24 mg/kg) at a 3-day interval revealed the superior efficacy of ALT-B5 over pegvisomant (1879±219.4 vs. 3800±355.9 ng*hr/mL IGF-1 AUC for 5 days in ALT-B5 and pegvisomant, respectively; p &lt; 0.01). In PK/PD studies, ALT-B5 was administered at doses of 3 mg/kg and 10 mg/kg in NZW rabbits, and PK/PD parameters were compared with the same molar concentration of pegvisomant. ALT-B5 exhibited the longest therapeutic duration and the highest efficacy compared to pegvisomant. Conclusion: ALT-B5 exhibited the longest duration and highest effectiveness in lowering IGF-1 levels. ALT-B5 emerges as a potential novel therapeutic option for acromegaly.
Presentation: 6/1/2024
8301 A Rare Case of IgG4-Related Hypophysitis
Authors: Kesavan Chary P , Silverstein J M 
Published: October 2024

Abstract
Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None.
Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (&lt;2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of &gt;10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up.
Presentation: 6/2/2024
7420 A Role for Glycoprotein Hormone Subunit Alpha 2 in Pituitary Development
Authors: Raetzman Lori Therese , Ge Xiyu , Weis Karen 
Published: October 2024

Abstract
Disclosure: L.T. Raetzman: None. X. Ge: None. K. Weis: None.
Hypopituitarism results when the pituitary gland is not able to make one or more of its hormones. It is estimated that up to 80% of hypopituitarism detected at or near birth has no identifiable cause. We have created a mouse model of congenital hypopituitarism by conditionally deleting the gene Notch2 in the developing pituitary. NOTCH2 is expressed in pituitary stem cells and is necessary for stem cell maintenance, proliferation, and differentiation. However, the pathways NOTCH2 engages to affect pituitary development remain unclear. It is important to determine the mechanism of NOTCH2 action in the pituitary because it might help to reveal novel causes of hypopituitarism. In this study, we hypothesized that glycoprotein hormone subunit A2 (GPHA2), a corneal stem cell factor, is downstream of NOTCH2 signaling in the mouse pituitary. We found Gpha2 is expressed in a subset of quiescent Sox2-expressing pituitary stem cells by RNAscope in situ hybridization and scRNA seq analysis. A scRNA seq study in rats has also localized Gpha2 to Sox2-expressing folliculostellate cells. In Notch2 conditional knockout pituitaries, Gpha2 mRNA is reduced over 75% compared with control littermates. We then investigated the possible functions of GPHA2, hypothesizing it might have a role in stem cell maintenance and quiescence. However, pituitaries treated with a GPHA2 peptide do not have a change in proliferation or stem cell-related gene expression. Another role of GPHA2 may be as a paracrine signal to control lineage restricted cell fate. GPHA2 has been demonstrated to be a ligand for the thyroid stimulating hormone receptor (TSHR) and part of the hormone thyrostimulin. We demonstrated that, in dissociated adult pituitary cells, GPHA2 increased pCREB expression and this induction was reversed by co-treatment with a TSHR inhibitor. Our data show that TSHR is expressed in the rostral tip thyrotropes of the pars tuberalis and in isolated cells in the anterior lobe. These data suggest GPHA2 is a NOTCH2 related stem cell factor that activates TSHR signaling, potentially impacting pituitary development and maintenance as a paracrine signaling molecule.
Presentation: 6/3/2024
8203 A Solitary Fibrous Tumor Mimicking a Non-functional Pituitary Macroadenoma
Authors: Rivera Luisa Bernacet , Omay Sacit , Huttner Anita , Inzucchi Silvio E 
Published: October 2024

Abstract
Disclosure: L. Bernacet Rivera: None. S. Omay: None. A. Huttner: None. S.E. Inzucchi: None.
Background: A solitary fibrous tumor (SFT), also known as hemangiopericytoma (HPC), is a rare subset of soft tissue tumors of mesenchymal origin. This type of tumor tends to have aggressive behavior and a high risk of recurrence. Approximately less than 1% of central nervous system (CNS) tumors have been identified as part of this subtype. Case Presentation: A 73-year-old female with medical history of primary hypothyroidism, myelodysplastic syndrome (MDS), and IgM kappa MGUS initially presented to her primary care physician for evaluation of progressive visual loss over several weeks, accompanied by worsening headaches. Ophthalmologic exam revealed bitemporal hemianopsia which prompted urgent imaging. Pituitary MRI with IV contrast revealed a solid sellar mass with suprasellar extension measuring 1.8 x 1.3 x 1.9 cm. The lesion was noted to superiorly displace the optic chiasm as well as to cause mild impingement of the anterior cerebral arteries. Patient was urgently referred to neurosurgery and endocrinology for further evaluation. Initial neuroendocrine laboratory assessment, performed at 8 am, revealed a cortisol 16.5 ug/dL, free T4 1.2 ng/dL, TSH 0.77 mIU/L, prolactin 9.9 ng/mL, IGF-1 17 ng/mL, the latter value consistent with adult growth hormone deficiency. Her LH and FSH were 4.3 mIU/mL and 12.6 mIU/mL, respectively, lower than expected for a post-menopausal woman. She underwent a transnasal transsphenoidal resection of the sellar lesion. Surgery was difficult due to the fibrous nature of the tumor, for which complete resection was not achieved. Post-operative course was complicated by thrombocytopenia due to MDS. Hormonal workup following surgery was consistent with central adrenal insufficiency, hypogonadotropic hypogonadism, and central hypothyroidism. Pathology showed densely cellular spindle cell neoplasm with a collagenous background consistent with hemangiopericytoma. She underwent fractionated radiotherapy and tumor has since remained stable in size. Her visual symptoms resolved quickly following surgery. Discussion: SFT is an aggressive mesenchymal tumor which rarely appears in the sellar region. There are no identified brain MRI findings that would suggest the nature of this tumor. As a result, endocrinologists should be aware of this rare condition while evaluating pituitary neoplasms.
Presentation: 6/3/2024
12526 Acromegaly Secondary to Sparsely Granulated Adenoma
Authors: John D , Kinaan M , Titus J , Lamar K 
Published: October 2024

Abstract
Disclosure: D. John: None. M. Kinaan: None. J. Titus: None. K. Lamar: None.
The most common pathological finding in acromegaly is a densely granulated adenoma which is composed of large round eosinophilic cells with prominent nucleoli and spherical nuclei that closely resemble a somatotroph cell. Less common finding is a sparsely granulated adenoma that is composed of sheets of poorly cohesive, pleiomorphic nuclei, chromophobic cells. We present a case of a 58-year-old gentleman presenting to our endocrine clinic for evaluation of a pituitary macroadenoma. The patient was hospitalized for nausea, vertigo, headaches, and blurring of vision. CT brain at that time showed a pituitary mass measuring 2.4 x 1.6 x 1.7 cm centered in the right cavernous sinus and inseparable from the pituitary gland. Hormonal work-up in the hospital was remarkable for high GH level. IGF-1 level was not done. Patient was advised to follow-up with neurosurgery as outpatient and no emergent surgery was planned. In the clinic, patient denied symptoms of DI, adrenal insufficiency or hypothyroidism. He has history of hypogonadotropic hypogonadism and was on testosterone therapy, but he stopped it since his hospitalization. On physical examination, he was noted to have macroglossia, deep voice, prominent jawbone, and soft tissue swelling in the hands and feet. Patient did not have any visible joint swelling. He stated he did not notice these changes personally and that he’s always been a “big guy” and always had a deep voice since he was a teenager. Repeat hormonal workup (done at 8 AM) showed: normal CMP, ACTH, cortisol, prolactin, TSH, T4, and T3. Testosterone was low with LH and FSH inappropriately within the normal reference range consistent withhypogonadotropic hypogonadism. IGF-I was elevated at 628ng/mL with a Z score of 3.9. These findings were consistent with acromegaly. He underwent surgery for tumor resection and pathology report showed that about 40% of the cells demonstrated weak immunoreactivity for GH, and rare (less than 1%) prolactin-positive cells were present within the tumor. The specimen was negative for TSH, ACTH, FH, and LH immunostains. Immunostain for CAM5.2 showed predominantly perinuclear dot-like immunoreactivity. The *MIB1 proliferation index is about 1%. The findings were consistent with a sparsely granulated gonadotrophic adenoma, which may demonstrate aggressive behavior. Postoperative MRI showed postoperative changes with residual pituitary tissue (normal gland vs. residual tumor). Postoperative cortisol &gt;16. Postoperative GH dropped from 4.39 to 2.69 after 1 month. After 3 months, patient was doing well with no symptoms. However, IGF1 level (&gt;400) showing that surgery was not curative. Currently he is awaiting gamma knife radiation therapy with possible medical therapy afterwards. Our case will provide an overview of the specific management considerations for these tumor and how they differ from densely-granulated tumors.
Presentation: 6/3/2024