bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-188 The Diagnostic Value of DHEAS in Subtyping Patients with Cushing Syndrome
Authors: Liu Mengsi , Zhu keying , Chen Huan , Feng Wenhuan , Zhu Dalong , Li Ping 
Published: May 2020

Abstract
Objective: Serum dehydroepiandrosterone sulfate (DHEAS) can be used to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to evaluate the clinical value of DHEAS in differentiating adrenal Cushing syndrome (ACS) from Cushing’ disease (CD). Methods: We recruited 100 patients with Cushing syndrome, 36 with CD and 64 with ACS. 72 sex-, age- and BMI-matched nonfunctional adrenal adenomas (NFAAs) were served as controls. Clinical and laboratory data were collected. DHEAS levels were measured and DHEAS ratio was calculated by dividing the measured DHEAS by the lower limit of the respective reference range (age- and sex-matched). Results: 1) No significant differences in age, sex, or BMI were detected among the NFAAs, ACS and CD groups. Compared to NFAAs group, ACS patients had lower plasma ACTH levels [1.11(1.11,1.74) vs 5.0 ± 2.9 pmol/L, P&lt;0.01], lower DHEAS levels (24.00 ± 20.72 vs 189.05 ± 82.03 ug/dL, P &lt; 0.01) and lower DHEAS ratio [0.58(0.27,0.98) vs 5.34 ± 3.0]; Plasma ACTH (22.12 ± 14.22 pmol/L), DHEAS (309.4 ± 201.1 ug/dL) and DHEAS ratio (10.51 ± 7.65) in CD patients were significantly higher compared to those in NFAAs and ACS patients (all P&lt;0.01). 2) In ACS patients, there were 53 patients with suppressed ACTH level of &lt;2.0 pmol/L, 11 patients without plasma ACTH suppression (≥2.0pmol/L). Compared to NFAAs, lower DHEAS and DHEAS ratio were detected in these two groups, and no significant differences were found in the DHEAS [15(15, 23.5) vs 23.8 ± 14.4 ug/dL, P=0.86] and DHEAS ratio [0.58(0.27, 0.80) vs 1.0(0.25,2.09) ug/dL, P=0.40] between the two groups. 3) ROC analysis showed that the area under the curve (AUC) of plasma ACTH, serum DHEAS and DHEAS ratio in diagnosing 0.954, 0.997 and 0.990 respectively. The optimal cut-off values for DHEAS and its ratio were 79.1ug/dL, and 2.09, respectively. The diagnostic sensitivity and specificity of plasma ACTH (&lt;2.0pmol/L) were 84.1 and 100%, those of DHEAS were 97.5% and 100%, and those of DHEAS ratio were 95% and 100%, respectively. Conclusions: Patients with different subtype of Cushing syndrome showed distinctive DHEAS levels and DHEAS ratio. DHEAS and DHEAS ratio are useful in differential diagnosis of Cushing syndrome. Especially, when the plasma ACTH level is not conclusive. The measurement of DHEAS may offer a supplementary test to diagnosis ACS from CD.
Keywords: Adrenal Cushing syndrome; Cushing disease; Adrenocorticotropic hormone; Dehydroepiandrosterone sulfate
SAT-273 Case of Mistaken Identity?
Authors: Pla Carlos 
Published: May 2020

Abstract
Introduction Pituitary adenomas occur in 10-15% of patients and the majority are benign. Prolactinomas are the most common form of secretory pituitary adenoma. Pituitary apoplexy, a medical emergency with resulting visual loss and hormonal hyposecretion, requires rapid surgical intervention. We present a case of pituitary macroadenoma that underwent pituitary resection for acute visual disturbance which was later discovered to be caused by undiagnosed demyelinating disease.
Clinical Case Patient is a 32-year-old male who presented initially with complain of fatigue and decreased libido. Work up revealed elevated prolactin level and low testosterone. MRI showed a 2x3cm pituitary macroadenoma. At moment of diagnosis, patient was otherwise asymptomatic. He was started on bromocriptine. During follow up visits, patient reported visual disturbance. First MRI in our clinic showed no suprasellar extension, no impingement of optic chiasm and nonspecific white matter disease. At that time, visual field testing showed left temporal defect in superior quadrant. Follow up MRI 1 year later continued to show a stable macroadenoma without impingement of the optic chiasm, but patient reported progressive left vision disturbance and new right vision loss. He was evaluated in the emergency room where he was treated for pituitary apoplexy with steroids and surgery. Vision improved the next day. Despite uncomplicated post-operative course, patient developed proximal muscle weakness and exam notable for diffuse motor deficit in bilateral lower extremities with hyperreflexia. Endocrinology workup was negative for hypercortisolism and ophthalmology diagnosed him with optic neuropathy. Neurology evaluation led to a diagnosis of multiple sclerosis (MS). Patient was started on natalizumab with complete resolution of all visual and muscle symptoms.
Clinical lesson Our patient presented with complaints of fatigue, decreased libido and work up that showed a macroprolactinoma without MRI evidence of optic chiasm impingement. During treatment, he developed acute visual deficits that were attributed to pituitary apoplexy. This visual disturbance improved after surgery and use of high dose IV steroids, with the latter likely treating what had been an MS flare. In hindsight, ophthalmologic evaluation before surgery had shown new color blindness, a sign of optic neuropathy. Despite temporary relief, patient progressed to develop new muscle weakness and recurrent visual disturbance which led to the diagnosis of MS. Since being diagnosed and treated for MS, he has had complete resolution of his symptoms. This case stresses the importance of considering other etiologies for visual defects in patients with pituitary adenomas.
MON-905 A Case of Cushing’s Disease with Glucocorticoid Positive-Feedback
Authors: Shichi Hiroki , Fukuoka Hidenori , Tsujimoto Yasutaka , Yamamoto Masaaki , Nakamura Tomoaki , Ishida Atsushi , Yamada Shozo , Takahashi Yutaka , Chihara Kazuo 
Published: May 2020

Abstract
Background: Although paradoxical response of cortisol (F) during high dose dexamethasone (Dex) suppression test (DST) is observed in a part of ectopic ACTH syndrome, few reports have been shown in Cushing’s disease (CD). It suggests a presence of glucocorticoid (GC)-driven positive-feedback loop. However, the underlying mechanism remains elusive. Here we present a case of CD showing clear clinical and pathophysiological evidences of GC positive-feedback using ex vivo 3-dimensional (D) culture method.
Case: A 62-year-old woman manifested typical Cushing’s symptoms, including moon face, central obesity, hypertension, hypokalemia, and vertebral fractures. Endocrinological data were consistent with a diagnosis of CD; morning plasma ACTH 299 pg/mL, serum F 28 μg/dL, midnight serum F 43 μg/dL, and 24hr urinary free cortisol 988 μg/day. CRH test showed a slight increase in plasma ACTH levels (1.4 fold), and pituitary MRI revealed a 14 mm macroadenoma invading into the left cavernous sinus. Interestingly, both 1 mg and 8 mg DST showed a paradoxical increase in serum cortisol levels (27.7→64.7μg/dL and 17.17→35.68μg/dL, respectively). These data indicated a presence of positive-feedback response to GC in the tumor. Indeed, after the initiation of metyrapone (1,000 mg/day) administration for the treatment of hypercortisolemia, plasma ACTH levels were decreased to 147.5 pg/mL accompanied with the decrease in serum F levels to 4.12 μg/dL. Moreover, pituitary tumor obviously shrank during the metyrapone treatment. Thereafter, we undertook transsphenoidal surgery and plasma ACTH and serum F levels decreased to 35.8 pg/mL and 7.6μg/dL, respectively.
ex vivo studies: To prove the presence of the positive feedback response and explore the underlying mechanisms, we performed a primary culture experiment using the tumor and applied 3D culture method. The resected tumor tissue was enzymatically digested, dispersed and embedded into the Matrigel. Then cells were treated with Dex (0.1-10 nM), and ACTH concentrations were measured after 72 hrs. Interestingly, ACTH levels significantly increased by 10 nM Dex treatment at 72 h (129 %, p &lt;0.01), indicating a paradoxical response to Dex in the tumor ex vivo.
Conclusions: To our knowledge, this is the first case of CD who showed clinically obvious GC positive-feedback that was proved by ex vivo 3D primary culture cell models. Notably, tumor shrinkage was observed during the metyrapone treatment, suggesting that GC positive-feedback mechanisms also involve tumor proliferation. Further investigation is required for elucidating the underlying mechanisms.
OR25-07 A Multi-Center, Open-Label, Pivotal Phase 2 Study of Azedra® (HSA I-131-MIBG) in Patients with Unresectable, Locally Advanced or Metastatic Pheochromocytoma or Paraganglioma: Updated Long-Term Survival and Safety
Authors: Jimenez Camilo , Chin Bennett B , Noto Richard B , Dillon Joseph Stephen , Solnes Lilja B , DiPippo Vincent A , Stambler Nancy , Wong Vivien , Pryma Daniel A 
Published: May 2020

Abstract
Background: Pheochromocytoma/Paraganglioma (PPGL) are rare neuroendocrine tumors with a 5-yr survival rate as low as 12%. There is a high unmet medical need for effective treatment options for patients with advanced disease. AZEDRA®, a high-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131-MIBG), is the first and only FDA-approved therapeutic radiopharmaceutical agent indicated for the treatment of adult and pediatric patients with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. Methods: Patients with advanced PPGL who were heavily pre-treated and were ineligible for curative surgery or chemotherapy received a dosimetric dose followed by up to two therapeutic doses (each at 296 MBq/kg to a max of 18.5 GBq). The primary endpoint, defined as the proportion of patients with at least 50% reduction of all antihypertensive medication(s) lasting ≥6 months, was met and previously reported. Updated secondary endpoints including overall survival (OS) and safety are reported. Results: A dosimetric dose of HSA I-131-MIBG was administered to 74 patients. Of those, 68 patients received one therapeutic dose and 50 received two doses of HSA I-131-MIBG. Clinical benefit rates (objective tumor responses defined by RECIST 1.0 and stable disease) were observed in 71.4% and 98.0% of patients receiving one and two therapeutic doses, respectively. As of October 10, 2019, median survival time for all patients was 43.2 months (95% CI 31.4, &gt;60). Median survival time was 19.3 months (95% CI 4.5, 32.4) and 49.1 months (95% CI 36.9, &gt;60) in patients receiving one and two doses, respectively. The overall survival was 73.8% at 2 yrs, 47.5% at 4 yrs and 41.5% at 5 yrs. The most common (≥50%) adverse events were nausea, fatigue, and myelosuppression. Myelosuppressive events resolved within 4-8 wks without requiring stem cell transplantation. Late radiation toxicity included 7 patients with secondary malignancies (myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), colon cancer, and lung carcinoma) of which MDS, ALL and AML were considered related to I-131 radiotherapy. Conclusions: Results from this pivotal phase 2 study suggest that HSA I-131-MIBG is an efficacious and safe treatment for advanced PPGL.
MON-241 Dome Shaped Pituitary Enlargement Warrants Detailed Endocrine Evaluation Prior to Neuro-Surgical Intervention: Case Series & Analysis
Authors: Chakraborty Satyam 
Published: May 2020

Abstract
Pituitary tumours diagnosed incidentally on imaging as sellar-suprasellar masses, often undergo unwarranted Neuro-surgical intervention, often leading to the requirement of life-long post-operative hormone supplementation. Although surgery remains the primary modality in most of the Functional (except Prolactinomas) & Non-Functional Pituitary Macro-Adenomas abutting the Optic Chiasma, Several cases are feed-back adenomas due to untreated Hypothyroidism or Drug- Induced Hyperprolactinemia which require a conservative approach.
These Pituitary enlargements may not only be Sellar but also at times extend Supra-sellar mimicking a surgically resctable one. In adolescents they come with a constellation of features like severe short stature & primary Amenorrhea in Females. Noteworthy that these symptoms appear commonly in both groups of surgically resectable masses as well as the secondary pituitary enlargements which need conservative approach, thus often resulting in inadvertent Surgical misadventures.
We report 3 cases of Adolescent females referred from peripheral centre to the Neuro-Surgical take of our Institute. Both the females had severe short stature with primary amenorrhea. The imaging characteristics in all the three patients were unique in the sense that they had uniform enlargement of the entire Pituitary extending supra-sellar without any focal hypo-intensities without any obvious mid-line shift of the Pituitary stalk & enhanced uniformly in Post-Contrast studies. We also observed that the upper margin of the masses had a uniform convexity resembling a “DOME”. Thorough Endocrine work-up revealed severe Untreated Hypothyroidism with S.TSH greater then 100micro IU/ml. The patients were treated conservatively with Levo-thyroxine supplementation. The patients had significant Height gain with menarche in the following 4-6 months of Therapy. S.TSH normalized after 2-3 months of therapy. Repeat imaging after 6 months of therapy revealed normal Pituitary architecture without the presence of any focal lesions or enlargement.
Feedback Adenomas of the Pituitary have been depicted in the literature. “DOME” shaped Pituitary enlargement seems quite unique to all Pituitary masses which can be treated with conservative means. Pituitary masses should therefore undergo thorough Endocrine intervention before any Neuro-Surgical intervention is contemplated, specifically when the incidentally discovered masses have a “DOME” shaped symmetrical upward convexity on imaging.
OR17-05 Hypospadias Is a Predictor of Adverse Cardiometabolic Risk in Adulthood - a Case-Control Study
Authors: Lucas-Herald Angela K , Padmanabhan Sandosh , Brooksbank Katriona , McCallum Linsay , Montezano Augusto C , Touyz Rhian M , Ahmed S Faisal 
Published: May 2020

Abstract
Introduction: Abnormal development of the genital tract during the first trimester can lead to hypospadias. This stage coincides with the programming window during which androgens are required for normal masculinisation of the genital tract. Since fetal development may also be associated with long-term effects on cardiometabolic outcome and testosterone is itself an important vascular hormone, we questioned whether adults with a history of hypospadias are at increased risk of long-term cardiovascular and metabolic disease. Aim: This retrospective study determined if hypospadias is associated with increased risk of cardiometabolic disease later in life. Methods: Cardiovascular and diabetes admissions data were extracted through record linkage for all males with a history of hypospadias (ICD10 Q54) from 1981 to 2019 through the NHS Scotland Information Services Division after ethics approval. Controls were matched for age, birthweight, gestation and deprivation index. Incident admissions for angina, arrhythmia, diabetes, heart failure, ischaemic heart disease, myocardial infarction, peripheral arterial disease, renal failure and stroke were obtained for each individual. Case control analysis was performed using Chi square test using R. Results: Admission data on 13,481 men with hypospadias and 9,615 matched controls were reviewed. Men with hypospadias had a 10- fold higher risk of diabetes (9.7 [8.4-11.2], p&lt;0.0001); 9- fold higher risk of ischaemic heart disease (OR [95% CI] 9.1[8.1-10.2], p&lt;0.0001); 8- fold higher risk of renal failure (7.9 [6.9-9.1], p&lt;0.0001); 6- fold higher risk of stroke (6.2 [5.2-7.2], p&lt;0.0001); 6- fold higher risk of myocardial infarction (6.4 [5.6-7.3], p&lt;0.0001); 6-fold higher risk of angina (5.9 [5.3;6.8], p&lt;0.0001); 5-fold higher risk of arrhythmia (4.8 [4.2-5.4], p&lt;0.0001) 5- fold higher risk of peripheral arterial disease (4.8 [3.7-6.1], p&lt;0.0001) and 4- fold higher risk of heart failure (3.6 [3.1-4.1], p&lt;0.0001). Conclusions: Men with a history of hypospadias are at significantly increased risk of admission for treatment for cardiovascular and metabolic conditions, especially ischaemic heart disease, diabetes and renal failure. The mechanisms underlying this observed increase are unclear and merit further evaluation.
SUN-289 Childhood-Onset, Adamantinomatous Craniopharyngioma and Successful Pregnancy: Results of Kraniopharyngeom 2000/2007
Authors: Sowithayasakul Panjarat , Boekhoff Svenja , Muller Hermann Lothar 
Published: May 2020

Abstract
Background: Hypopituitarism is associated with an increased risk of pregnancy complications, such as abortion, anemia, pregnancy-induced hypertension, placental abruption, premature birth, and postpartum hemorrhage. The advance of assisted reproductive techniques makes it possible to improve the pregnancy rate in hypopituitary patients. Data on female fertility, pregnancy, and outcome of offspring after childhood-onset, adamantinomatous craniopharyngioma (CP) are rare.
Study design: Observational study on pregnancy rate and outcome of offspring after childhood-onset CP in adult, female patients recruited in KRANIOPHARYNGEOM 2000/2007.
Patient cohorts: Since 2000, 451 CP patients (223 f / 228 m) have been recruited with high grade of completeness. 263 CP patients (128 f / 135 m) have reached adult age. 6 of 128 adult, female CP patients (5%) reported on 9 pregnancies giving birth to 10 healthy newborns.
Results: The median age at time of CP diagnosis was 14.9 years. Complete surgical CP resections were achieved in 3 patients. No patient underwent postoperative irradiation. 5 natural pregnancies occurred in 3 CP patients presenting with postoperative normal pituitary function. 4 pregnancies were achieved in 3 CP with hypopituitarism under assisted reproductive techniques (after in median 4.5 cycles, range: 3-6 cycles). Median maternal age at pregnancy was 30 years, ranging from 22 to 41 years. 6 of 10 babies were delivered by caesarean section. Gestational age at delivery was in median 38 weeks, ranging from 34 to 43 weeks; median birth weight was 2,920 gram (range: 2,270-3,520 gram), the rate of preterm delivery (&lt;38 weeks of gestation) was 33%. The rate of breastfeeding was 56%. Enlargements of CP cysts occurred in 2 women during pregnancy. Other severe complications during pregnancy, delivery and postnatal period were not observed.
Conclusions: Pregnancies after CP are rare (5%) and almost half of the patients (45%) achieved pregnancies after assisted reproductive techniques, which are effective and safe in CP patients. With regard to existing deficiencies of hypothalamic-pituitary axes, close monitoring and care by an experienced reproductive physician is necessary. Furthermore, MRI monitoring especially of CP cysts is recommended during pregnancy. Severe perinatal complications, birth defects, and postnatal morbidity of the mothers and their offspring were not observed. Most CP patients complained about their initial lack of information on potential fertility under assisted reproductive techniques.
MON-341 New Diagnosis of Hypophosphatasia in a 79-Year-Old Woman with Low Bone Density
Authors: Manavalan Anjali , Mathias Priyanka , Khoshbin Katayoun , Tabatabaie Vafa 
Published: May 2020

Abstract
Introduction: Hypophosphatasia is a rare metabolic bone disease caused by one of several mutations in the ALPL gene which encodes tissue nonspecific alkaline phosphatase (ALP). It is usually diagnosed in childhood and can have a heterogenous clinical presentation depending on the extent of enzyme deficiency. Here we report the oldest known patient with hypophosphatasia.
Clinical Case: A 79-year-old woman with a history of medullary thyroid cancer (MTC) in remission, was referred to our metabolic bone disease clinic for the evaluation and treatment of osteopenia. She had suffered from numerous musculoskeletal complaints for several years and had received a diagnosis of polymyalgia rheumatica. However, her symptoms persisted despite a six month trial of prednisone. Although she had developed dental caries at a young age, she denied premature tooth loss. Her family history was significant for arthralgias and vertebral disc disorders in multiple family members, including both her children. Her mother carried a diagnosis of rheumatoid arthritis and osteoporosis. The only pertinent physical exam finding was short stature (Height -4’6”). A DEXA scan was performed using a Hologic unit and revealed a T Score of -1.0 at the L-spine and -1.9 at the femoral neck. A FRAX score predicted a 14% risk of major osteoporotic fracture and 4% risk of hip fracture.
Laboratory data revealed: Serum Calcium 9.3 (8.5-10.5 mg/dL), Albumin 4.3 (3.5-5.0 g/dL), ALP 21 (&lt;130 U/L), Vitamin D 25OH 46.2 (&gt;30 ng/ml), Intact PTH 28.3 (15.0-65.0 pg/ml), Vitamin B6 87.7 (2-21 ng/ml).
On review of her medical record, low ALP levels ranging between 20-30 U/L were noted to be present for the last twenty years. Given her history of musculoskeletal complaints, short stature, elevated Vitamin B6 and low ALP, genetic testing for hypophosphatasia was performed. Her results confirmed a known pathogenic mutation in the ALPL gene.
Conclusion: This case highlights the importance of reviewing ALP levels and relevant patient history to rule out hypophosphatasia prior to initiating therapy for osteoporosis. This condition is often unrecognized. Bisphosphonates, which are often the first line of treatment in osteoporosis, are contraindicated in hypophosphatasia as they can increase the risk of atypical fractures.1 Teriparatide may improve bone density depending on the extent of ALP deficiency. Asfotase alfa is a new agent that is currently available for the management of certain cases of hypophosphatasia.
References:
1.”Atypical femoral fractures”during bisphosphonate exposure in adult hypophosphatasia; Sutton,RA; Mumm,S;Coburn SP; Ericson,KL; Whyte, MP; Journal of Bone and Mineral Research 2012 May;27(5):987-94.