bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &lt;=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
8750 Characterization of 11βHSD1-Like Protein: A Novel Species-Restricted Member of the 11βHSD Enzyme Family
Authors: Valbe E , Ng J , Fuller P J , Cole T J 
Published: October 2024

Abstract
Disclosure: E. Valbe: None. J. Ng: None. P.J. Fuller: None. T.J. Cole: None.
The 11β-hydroxysteroid dehydrogenases (11bHSD) are a subfamily of short-chain dehydrogenase/reductase enzymes, which regulate cortisol metabolism and their physiological actions in vivo. Although much is known about the biology and function of 11bHSD1 and 11bHSD2, little is known of a recently discovered third member of the 11bHSD family, 11bHSD1L, which is expressed in primates, fish, plants, and other mammals, but is absent in most rodent species. Current expression profiling in human, sheep and marmoset tissues suggest that 11bHSD1L may be linked to the regulation of reproduction through the hypothalamic-pituitary-gonadal (HPG) axis and/or to an unknown regulatory role in the central nervous system. The definitive physiological substrate for 11bHSD1L is unknown. We have assessed the expression of 11bHSD1L in the non-human primate marmoset and show that 11bHSD1L mRNA and protein levels are highest in regions of the brain and reproductive organs, which parallels expression patterns in human tissues. Localization of 11bHSD1L protein in marmoset tissue sections by immunohistochemistry identified several cell populations previously unreported for 11bHSD1L, that included the Sertoli cells in the testis, prostate epithelial cells and theca cells in the ovary, further implicating 11bHSD1L as a potential novel regulator of the HPG Axis. Furthermore, we have measured expression of 11bHSD1L in sub-regions of the foetal sheep brain and other tissues, where mRNA levels were elevated in neural-derived tissues. There is some evidence that 11bHSD1L has a functional role in cortisol turnover, as a cortisol oxidase. Using a dual-luciferase based reporter system and a quantitative LC-MS/MS technique with HSD1L overexpressing cells, we show that cortisol is unlikely to be a substrate of 11bHSD1L. We have also demonstrated via CRISPR-CAS9 mediated gene knockout that 11bHSD1L may play a role in cell proliferation or survival in the human neuroblastoma cell line SH-SY5Y, which expresses very high levels of HSD1L. Upon knockout of both 11bHSD1L alleles, SH-SY5Y cells become unviable. This may further implicate 11bHSD1L as a relevant gene in cancer cell growth, particularly considering its increased expression in many tumour cell lines. Finally, we discuss our progress in purifying 11bHSD1L as a recombinant protein for in vitro substrate and structural studies.
Presentation: 6/3/2024
12612 Chiasmal Herniation - A Rare Complication Of Prolactinoma Treatment
Authors: Syeda A , Kantorovich V 
Published: October 2024

Abstract
Disclosure: A. Syeda: None. V. Kantorovich: None.
Introduction: Primary treatment of symptomatic prolactinomas is medical therapy with dopamine agonists (DA). Herniation of optic chiasm is a rare complication of tumor shrinkage induced by DA therapy which causes secondary deterioration in visual fields. Case:A 26-year-old man presented to our hospital after a syncopal episode. He had headaches and blurry vision in the left eye for the past 4 months. He was diagnosed with a 4 cm x 3.6 cm x 2.6 cm pituitary macroprolactinoma compressing the optic chiasm, his prolactin (PRL) was 4700 ng/mL (N: 4.0-15.2 ng/mL) and testosterone was suppressed to 10 ng/dL (N: 249-836 ng/dL). Other hormonal workup was unremarkable. Ophthalmologic evaluation was consistent with left optic nerve pallor and neural rim thinning suggestive of a guarded prognosis. Immediate neurosurgical intervention was deemed unnecessary. Cabergoline 0.25 mg twice a week was initiated. Subsequently, the PRL levels improved but remained elevated to 414.2 ng/mL and cabergoline dose was increased to 0.5 mg twice a week. MRI Brain after 10 months revealed significant tumor reduction to 2.1 cm x 2.1cm x 1.2 cm. He was inconsistent with his endocrinology follow up appointments and was also non-adherent to cabergoline intermittently. After 14 months of starting DA therapy, he presented with worsening blurriness in his left eye. A repeat brain MRI showed stable appearance of the large pituitary macroadenoma with inferior bowing of the optic chiasm. Significant distortion, tented appearance, and attenuation of the left prechiasmatic optic nerve was also noted. He was evaluated by neuro ophthalmology and a diagnosis of secondary visual deterioration due to optic chiasmal herniation was made. Cabergoline therapy was promptly discontinued. Two weeks post-cabergoline cessation, he underwent trans-sphenoidal resection reporting vision improvement pre-surgery. Post-operative MRI depicted changes with no residual tumor and improved optic chiasm position. Discussion:Various theories explain chiasmal herniation with dopamine agonist (DA) treatment for prolactinomas. Pre-existing chiasm-tumor tethering may exacerbate downward pull during tumor reduction caused by DA therapy. Some case series have suggested that not all patients with chiasmal herniation have visual field defects and that despite improvement in visual fields with decrease in DA dosage, there are no appreciable radiographic changes/reversal of chiasmal herniation. One of the explanations for this lack of correlation is that visual impairment is rather a consequence of vascular compression. This case underscores the need for regular perimetry in macroprolactinoma patients on medical treatment. Adjusting dopamine agonist dosage to allow controlled tumor regrowth, monitored closely with frequent visual field and prolactin assessments, is crucial for relieving optic chiasm tension.
Presentation: 6/3/2024
6616 Copeptin Use To Reduce Hospital Stay In A Complicated DI Case
Authors: Kowsika Sree S , Moran Heberth , Yuksel Simge , Bleich David 
Published: October 2024

Abstract
Disclosure: S.S. Kowsika: None. H. Moran: None.
Introduction: While there is literature describing the use of copeptin for the diagnosis of polyuria-polydipsia syndrome, its utilization remains very limited in many hospitals. We present a case where the patient, initially misdiagnosed with central diabetes insipidus (DI), was appropriately diagnosed with partial nephrogenic DI through the use of copeptin. Case: A 48-year old female with a history of cardiac arrest, anoxic brain injury and diabetes insidious (DI) presented to the emergency department with hypernatremia (Na 154 mmol/L). The patient had been initiated on desmopresin (DDAVP) at an outside facility prior to her current admission. Despite receiving high doses of DDAVP, her sodium levels remained elevated, prompting further investigation. DDAVP administration was discontinued. A water deprivation test was subsequently performed, followed by IV administration of 2 mcg of DDAVP, which resulted in an increase in urine osmolality from 191 to 331 mosm/kg, which was less than the expected 50% increase observed in central DI. Additionally, a baseline copeptin level was obtained and noted to be 31 pmol/L, confirming the diagnosis of partial nephrogenic DI. The patient was started on Amiloride, leading to normalization of sodium levels. Discussion: Many patients with polyuria-polydipsia syndrome are frequently misdiagnosed and receive incorrect treatment, potentially worsening their clinical condition. Copeptin (Carboxy-Terminal-Pro-vasopressin) is the C-terminal peptide of pro-vasopressin, co-secreted with arginine vasopressin (AVP). It has been proposed as a direct test for diagnosing polyuria-polydipsia syndrome. Baseline Copeptin testing without stimulation can accurately diagnose nephrogenic DI if elevated (&gt;21.4, pmol/L). To differentiate between central DI and chronic polyuria, prior thirsting with hypertonic saline or glucagon stimulation is necessary, with stimulated copeptin &lt;4.9 pmol/L diagnosing central DI. Despite its diagnostic potential, Copeptin is underutilized in many settings. In this case, using Copeptin to accurately diagnose our patient led to appropriate treatment and the resolution of hypernatremia.
Presentation: 6/1/2024
6630 Crooke Cell Pituitary Adenoma Without a Cushingoid Appearance
Authors: Hodge Jordesha , Idriss Setana , Jamal Issra , Panta Raju 
Published: October 2024

Abstract
Disclosure: J. Hodge: None. S. Idriss: None. I. Jamal: None. R. Panta: None.
Background: Crooke cell pituitary adenomas are corticotroph adenomas with Crooke’s cell changes, which are cytoplasmic accumulation of cytokeratin filaments in response to glucocorticoid excess. They are aggressive, invasive tumors, typically macroadenomas, with a high rate of Cushing’s disease and post -treatment (surgery and/or radiotherapy) recurrence. We present a case of Crooke cell pituitary adenoma without a Cushingoid appearance. Clinical Case: A 66-year-old Hispanic male with a 16-year history type II diabetes mellitus with retinopathy, presented with a pituitary macroadenoma at age 60. This was found incidentally when he had a brain CT for evaluation of vertigo. Subsequent brain MRI demonstrated a large 2.4 x 2.0 x 1.7 cm pituitary macroadenoma with extension into the suprasellar cistern and the left cavernous sinus. He was asymptomatic, without Cushingoid features. Hormonal evaluation revealed central hypogonadism and hypothyroidism, mildly elevated prolactin of 39.3 (4-15.2 ng/mL) and morning cortisol level of 12.7 (6-18.4 ug/dL). A 24-hour urine cortisol was normal. He was started on testosterone and thyroid hormone replacement therapy. His diabetes mellitus became progressively difficult to control with a peak HbA1C of 10.1%, about 7 years prior the macroadenoma finding. His HbA1C remained persistently elevated in the 8.1-9.5% range despite being on 6 anti-hyperglycemic agents, including basal insulin. A morning ACTH level 4 years after the initial visit, was 115 (6-50 pg/mL) with a cortisol level of 13.7 (6-18.4 ug/dL). Repeat morning ACTH and cortisol levels 7 months later were very similar. 5 years after the macroadenoma finding, he was noted to have worsening glaucoma, which was believed to be due to optic nerve compression. Therefore, he underwent endoscopic transphenoidal resection for tumor debulking. Pathology supported the diagnosis of Crooke cell corticotroph pituitary adenoma. Repeat brain MRI 3-months post-surgery demonstrated residual tumor, but normal optic chiasm and optic tracts. He had an abnormal dexamethasone suppression test prior to surgery (cortisol 6.4 ug/dL) and continued to do so post-operatively (cortisol 3.7 ug/dL with persistently elevated ACTH). Just prior to his surgery, testosterone replacement therapy was held. Total testosterone level after surgery was normal 309.6 (280-800 ng/dL) and free testosterone 7 (5-21 ng/dL); he remained off replacement therapy. Conclusion: Crooke cell pituitary adenomas are rare with limited data on prognosis and guidance for clinical management. Some patients may have subtle features of hypercortisolism, such as difficult to control diabetes mellitus, without an overt Cushingoid appearance.
Presentation: 6/1/2024
6743 Decline in IGF-1 after surgery of the nonfunctioning pituitary neuroendocrine tumor
Authors: Sugata J , Fujio S , Makino R , Hanada T , Hanaya R 
Published: October 2024

Abstract
Disclosure: J. Sugata: None. S. Fujio: None. R. Makino: None. T. Hanada: None. R. Hanaya: None.
Background: Patients undergoing surgical treatment for nonfunctioning pituitary neuroendocrine tumors (PitNET) may experience impaired secretion of growth hormone (GH). The optimal timing for assessing GH secretory function postoperatively remains unclear. In our department, we typically conduct hormone-loading tests three months after surgery. However, even in some cases without a diagnosis of growth hormone deficiency (GHD) at that point, there might be a gradual decline in Insulin-like growth factor-1 (IGF-1). Methods: We studied patients who exhibited peak GH levels &gt; 1.8ng/ml in an insulin tolerance test (ITT) three months after undergoing surgery for nonfunctioning PitNET. We evaluated the levels of IGF-1 during the last observation, excluding cases where reoperation or radiosurgery was performed. Results: We identified 67 cases (29 males, 38 females) meeting the study criteria, with a median age of 54 years. The median follow-up time spanned 6 years (range 1-13 years). The median standard deviation (SD) scores of IGF-1 three months after surgery were -0.96, with 14 cases (21%) below -2.0 SD. At the end of the follow-up period, the median SD scores of IGF-1 were -1.31. This was significantly lower than the three-month time point (p&lt;0.01), and 21 cases (31%) recorded were below -2.0 SD. In 6 cases suspected of severe GHD due to subjective symptoms or decreased IGF-1, ITT, or GH-releasing peptide-2 were retested. Among these, 2 cases were diagnosed with severe GHD, while the remaining demonstrated normal secretion of GH despite the low concentration of IGF-1. The IGF-1 SD scores at the end of follow-up and the three-month time-point exhibited a significant correlation (R2=0.74, p&lt;0.01). However, no correlation was found between IGF-1 scores and peak GH concentration, age, tumor size, pituitary apoplexy, or preoperative IGF-1 SD scores. Conclusions: IGF-1 exhibited a progressive decrease in the majority of cases without severe GHD, with some cases showing reductions greater than -2.0 SD. Our findings emphasize the importance of cases with long-term clinical follow-up low IGF-1 after PitNET surgery, even when GH secretion appears normal.
Presentation: 6/1/2024
7464 Delayed Diagnosis of Cushing’s Disease after Five Year History of Hirsutism
Authors: McBride Erin , Davis Adam N , Elshimy Ghada , Vender John 
Published: October 2024

Abstract
Disclosure: E. McBride: None. A.N. Davis: None. G. Elshimy: None. J. Vender: None.
Introduction: Women may experience hirsutism for years before seeing a physician or before undergoing diagnostic testing. This case demonstrates that delayed workup of hirsutism can lead to delayed diagnosis and treatment of aggressive Cushing’s disease. Case: A 40-year-old African American female presented for initial evaluation with a 5-year history of hirsutism, which had never been evaluated, and a high cortisol level in the setting of type 2 diabetes mellitus and hypertension. She had a 60lb weight gain over 5 years, progressive hirsutism, easy bruising, and purple striae. Labs were significant for cortisol 23.86mcg/dL, ACTH 67pg/mL, HbA1c 8.9%, DHEAS 347mcg/dL, 17-OH progesterone 102ng/dL. A 1mg dexamethasone suppression test resulted in a non-suppressed cortisol of 12.64mcg/dL. She had an elevated 24 hour urine free cortisol level of 78mcg and an elevated midnight salivary cortisol with values of 474ng/dL and 396ng/dL. An 8mg dexamethasone suppression test resulted in a cortisol of 5.55mcg/dL. MRI brain pituitary protocol revealed a 6x4mm microadenoma of the pituitary gland. This is consistent with an ACTH producing pituitary adenoma (Cushing’s disease). The microadenoma was surgically removed by transsphenoidal approach. The pathology of the tumor revealed an elevated Ki-67 of 5%. Patient required hydrocortisone replacement for a couple of months that was later discontinued. Moreover, she is no longer on any medications for her diabetes, and her hypertension significantly improved postoperatively. Discussion: Hirsutism and androgen excess in women are most commonly caused by polycystic ovarian syndrome (PCOS). However, non-PCOS diagnoses, such as Cushing’s disease, should be considered as they are commonly missed due to lack of a pragmatic screening approach. Pituitary microadenomas are often benign, but 30-40% of cases are invasive and considered aggressive. Aggressiveness can be evaluated by using the tumor marker Ki67, which is a nuclear marker that reflects cell proliferation. While controversial, one proposed cutoff for aggressive pituitary adenomas is Ki67 ≥3%. The pathology of the tumor in this patient was aggressive with Ki67 of 5% This case demonstrates the importance of identifying hirsutism early in order to exclude the more dangerous causes of hirsutism such as Cushing’s disease. By early diagnosis and surgery, we may limit the progression of associated comorbidities such as diabetes mellitus and limit the growth of a potentially aggressive adenoma.
Presentation: 6/1/2024
7594 Diagnostic utility of 11C-Methionine PET-CT imaging in persistent or recurrent Cushing’s disease after transsphenoidal surgery
Authors: Furnica R , Devuyst F , Mathey C , Constantinescu S , De Herdt C , Renaud L , Maiter D M 
Published: October 2024

Abstract
Disclosure: R. Furnica: None. F. Devuyst: None. C. Mathey: None. S. Constantinescu: None. C. De Herdt: None. L. Renaud: None. D.M. Maiter: None.
Introduction: Equivocal or negative pituitary magnetic resonance imaging (MRI) findings pose a significant challenge in the management of persistent or recurrent Cushing’s disease (CD), compromising the chances of success of a further transsphenoidal surgery (TSS). The aim of our study was to determine the diagnostic utility of [1][1]C-methionine (MET) positron emission tomography coupled with computerized tomography (PET-CT) in localizing the residual corticotroph adenoma. Methods: We retrospectively analyzed the results of all MET-PET-CT performed between May 2002 and November 2023 in patients with a CD persisting or relapsing after TSS, and equivocal (n=14) or negative pituitary MRI findings (n=8). In 15 cases, images obtained from MET-PET were also co-registered with a high-resolution 3D pituitary MRI. All patients had a pathologically confirmed corticotroph tumor, and/or biochemical evidence of early postoperative remission after the first TSS, and/or proven ACTH-dependent Cushing’s syndrome with positive bilateral inferior petrosal sinus sampling. Results: Twenty-two patients were included (18 females and 4 males), with a mean age of 35.5 years at diagnosis. Initial tumors were mostly microadenomas with a mean tumor volume of 15 mm3. Thirteen out of the 22 patients had a suspect anomaly on conventional MRI that could however not be clearly distinguished from postsurgical changes, while the remaining 9 had a negative MRI. A significant MET standardized uptake value (SUV) in the suspected area of the tumor residue was defined as a ratio ≥ 1.80 relative to cerebellum SUV and was found in 12/22 patients (55%; 4 patients with negative pituitary MRI and 8 with equivocal findings). On the basis of positive imaging, repeat TSS was performed in 10 patients and was successful in 6, while Gamma Knife radiosurgery (GKRS) was performed in 2 patients allowing remission in both (total remission rate: 8/12). Among the 4 patients not cured by TSS, the presence of corticotroph adenoma in the resected tissue was found in 3 cases. Exploratory TSS was performed in 4 of the 10 PET negative patients, with no remission. Two patients were treated with GKRS, with remission in 1 case. Among the 4 other patients, bilateral adrenalectomy was performed in one case and adrenal steroidogenesis inhibitors were used in the remaining patients. Conclusions: [1][1]C-Methionine PET-CT imaging can provide valuable diagnostic information to detect a residual active corticotroph adenoma in about half of patients with a persistent or recurrent CD and equivocal or negative MRI results, thereby allowing targeted TSS or radiosurgery with a global success rate of 67% in this selected subpopulation.
Presentation: 6/1/2024