bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-291 Presence of Aberrant Adrenocorticotropic Hormone Precursors in Two Cases of McCune- Albright Syndrome
Authors: Yamagata Satoshi , Takayasu Shinobu , Makita Koshi , Kageyama Kazunori , Okawa Yuta , Oki Yutaka , Asari Yuko , Terui Ken , Daimon Makoto 
Published: May 2020

Abstract
Background: McCune-Albright syndrome (MAS) is a rare disorder. MAS is caused by an activating postzygotic somatic mutation in the GNAS, and, is classically defined by the occurrence of fibrous dysplasia (FD), café-au-lait skin macules, and precocious puberty. Autonomous GH and/or PRL production in MAS has been reported. However, there have been no reports of ACTH excess in MAS. Method: Plasma ACTH and serum cortisol (F) levels were assessed using electrochemiluminescence immunoassays (Eclusys ACTHTM and Eclusys Cortisol IITM, respectively; Roche Diagnostics K.K., Tokyo, Japan).Clinical Cases: Case1; 42-year-old man showed craniofacial deformities and suffered from multiple bone fractures. He was diagnosed with FD at the age of 23 years. Café-au-lait macules were found on his back. He had slightly acromegaloid features. He showed no cushingoid features. Pituitary adenoma or hyperplasia was not detected by MRI. The diagnosis of GH excess was confirmed by no suppression of serum GH levels by a 75-g oral glucose tolerance test (nadir GH: 2.34 ng/mL) and an elevated serum IGF-I level (307 ng/mL; normal range: 92-257 ng/mL). The patient was treated with monthly subcutaneous lanreotide injection and then GH excess was well controlled. Basal ACTH and F levels in blood were 40.6-63.4 pg/mL and 8.0-10.5 μg/dL, respectively. The urinary free cortisol (UFC) level was 53 μg/day. Autonomous F excess was excluded by the level of midnight F (1.2 μg/dL) and the level of F (0.2 μg/dL) after a low-dose (1 mg) dexamethasone suppression test (DST). Case2; A 32-year-old man was diagnosed with MAS and gigantism at the Pediatrics Department at the age of 5 years. Treatment of GH excess was well controlled by monthly octreotide depot. He had no acromegaloid features and no cushingoid features. Café-au-lait macules were observed from the left flank to the back. Pituitary adenoma or hyperplasia was not detected by MRI. Basal ACTH and F levels in blood were 35.5-73.1 pg/mL and 7.0-11.7 μg/dL, respectively. The UFC level was 61 μg/day. Autonomous F excess was excluded by the level of F (&lt;0.2 μg/dL) after a low-dose (0.5 mg) DST.Possibility of primary adrenal insufficiency was excluded by ACTH stimulation test and/or insulin tolerance test in both cases. The involvement of 11β-HSD1 by GH excess and PC1/3 deficiency were also excluded. Gel exclusion chromatography was then performed. POMC and pro-ACTH were detected and the aberrant ACTH/normal ACTH ratio was 42% in both cases. Conclusion: This is the first report of the presence of aberrant ACTH precursors, particularly POMC, in MAS. A high ratio of circulating ACTH to F may suggest secretion of inactive ACTH precursors in MAS. Further investigations are required to determine whether GNAS mutations or other mechanisms are involved in the presence of aberrant ACTH precursors in MAS.
SUN-274 Pituitary Macroadenoma Treated with Peptide Receptor Radionuclide Therapy in a Patient with Common Variable Immunodeficiency - Case Report
Authors: Brodowska-Kania Dorota , Saracyn Marek , Kolodziej Maciej , Kowalski Lukasz , Kaminski Grzegorz 
Published: May 2020

Abstract
Background: Nonfunctional adenomas comprise 25-35% of all pituitary tumors, 70-90% of these are gonadatroph cell adenomas. While ‘silent’ adenoma is the most common type of pituitary macroadenoma. The incidence of silent adenomas is estimated at 22/100000. Common Variable Immune Deficiency (CVID) is the most common primary immune disorder which is associated with neoplasia, mostly of the lymphatic or digestive system. We present probably the first case report of gonadotropinoma in a patient with CVID, treated with PRRT.
Clinical Case:
A 45-year-old man has been a patient at the Endocrinology Clinic for 12 years. Aged 33 years, he was diagnosed with a common variable immunodeficiency. The human immunoglobulin treatment was included. He also suffered from severe, spreading headaches. MRI of the head was performed. A 45mm tumor was found in the sella turcica, spreading to the sphenoid sinus. The tumor was slipped into the epidural reservois and both cavernous sinuses, causing compression of the internal carotid arteries and compressed the optic chiasm. Laboratory tests were as follows: TSH 2.18uIU/ml, LH 4.26mIU/ml, FSH 9.76 mIU/ml, ACTH 25.88pg/ml, PRL 18.34 ng/ml, HGH 3.9uU/ml, normal plasma and urine osmolality. So, the silent pituitary macroadenoma was diagnosed. Endoscopic transsphenoidal incomplete tumor resection was performed. The operation was complicated by massive parenchymal bleeding. Histopatological examination confirmed presence of pituitary adenoma, and immunohistochemical positive staining also of FSH (+), subunit alpha (+), TSH (+/-). A Ki67 proliferation index was 1%. After 12 months endoscopic reoperation was performed. The extent of operation was larger but not total. After 12 month the tumor mass increased (50x50x45mm). Imaging of somatostatin receptors by SPECT-CT was performed. It showed a heterogeneous radiolabel accumulation in the pituitary tumor. In 2010, 2 doses of 200mCi 90-Y-DOTATATE were administered with good effect. Tumor size was reduced to 20x23x25mm. The patient has had no headache for that time. Since 2011 he has also been treated with octreotide30 mg/month, with good therapy tolerance.
Conclusion:
This is probably the first description of a 12-year history of complicated but successful treatment of pituitary silent macroadenoma. It was also probably the first use of PRRT in the pituitary tumor with excellent effect. The patient remains in a very good condition, without neurological symptoms and no disorders of pituitary function.
MON-240 Histologically Proven Lymphocytic Hypophysitis with Marked Improvement on Glucocorticoid Therapy
Authors: Mathias Priyanka , Tabatabaie Vafa 
Published: May 2020

Abstract
Background: Lymphocytic hypophysitis (LH) is a rare autoimmune disorder characterized by lymphocytic infiltration of the pituitary gland. The disease predominantly affects women, with &gt;50% of cases presenting during pregnancy or postpartum.1 LH is often associated with other autoimmune conditions, primarily thyroiditis, and adrenalitis.2
Clinical case: A 27-year-old female presented with secondary amenorrhea for eight months. Workup revealed hyperprolactinemia (PRL 65 ng/mL) and a heterogenous pituitary mass measuring 3.3 cm in the largest dimension. Cabergoline was initiated for a presumed prolactinoma. Laboratory evaluation was significant for hypogonadotropic hypogonadism (estradiol &lt;50 pg/mL, progesterone &lt;1 ng/mL, FSH 2.9 mIU/mL, LH 0.45 mIU/mL) despite normalization in prolactin. She was also found to have Hashimoto’s thyroiditis (FT4 0.7 ng/dL, TSH 8.2 uU/mL with positive TPO antibodies) and was started on levothyroxine.
Repeat imaging demonstrated a 2.4 cm heterogenous expanding sellar mass with soft tissue extension to the dorsum sella concerning for a meningioma. Visual field testing was intact without evidence of chiasmal compression. She underwent trans-sphenoidal pituitary decompression surgery which was terminated prematurely due to the presence of extensive fibrous tissue in the sella. Pathology was consistent with LH. Immunohistochemical staining was positive for lymphocytic markers CD3 and CD20, confirming marked infiltration of inflammatory B-cells and T-cells. Her postoperative course was notable for panhypopituitarism. In view of the pathological findings of LH, she was started on a high dose of 40mg of prednisone daily. Within two months, sellar magnetic resonance imaging revealed a homogenous normal-appearing pituitary with a reduction in soft tissue mass in the sellar and suprasellar region. Oral contraceptive therapy was initiated for sex hormone replacement with the resumption of menses. Prednisone was gradually tapered to 5mg/day, and she was subsequently transitioned to maintenance hydrocortisone for central adrenal insufficiency.
Discussion: LH is a rare chronic inflammatory disease that should be considered in the differential diagnosis of a non-secreting pituitary mass, especially if occurring in young women presenting during pregnancy or postpartum. The condition is associated with preferential destruction of corticotroph and thyrotroph cells.3 Appropriate management remains controversial. High dose glucocorticoid therapy, to which our patient responded to dramatically, has been shown to be beneficial in reducing mass effect. Optimal treatment involves surgical resection of the pituitary mass to decompress surrounding structures.3
References:
1. JCEM, Volume 100, Issue 10, October 2015, Pages 3841-3849
2. JCEM, Volume 80, Issue 8, August 1995, Pages 2302-2311
3. Horm Res, 2007;68 Supplement 5:145-50
SUN-185 Severe Hyponatremia and Type 4 Renal Tubular Acidosis (Functional Hypoaldosteronism) Secondary to Trimethoprim
Authors: Koh Yun Qing , Hoe Kian Ming Jeremy , Quek Timothy Peng Lim 
Published: May 2020

Abstract
Introduction:
Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. We present a case of severe hyponatremia and Type 4 renal tubular acidosis (functional hypoaldosteronism) in a patient treated with TMP-SMX.
Clinical Case:
A 62 year old gentleman with hypertension, dyslipidemia and a surgically repaired abdominal aortic aneurysm developed an aortic graft infection. He was admitted to hospital for acute right lower limb ischemia with embolic phenomena, and underwent surgical graft explantation. He required multiple courses of antibiotics post operatively.
He was initially referred to Endocrinology for severe hyponatremia, deemed likely to be from a salt losing nephropathy secondary to polymyxin. Thyroid function and morning cortisol levels were normal. He was managed with intravenous hypertonic saline and oral salt tablets. The hyponatraemia resolved a week after polymyxin was stopped.
Intravenous TMP-SMX was commenced the next day at 240 mg BD. A week later, the hyponatremia recurred, with concomitant hyperkalemia and a normal anion gap metabolic acidosis.
The serum sodium was 126 mmol/L (reference interval (RI) 135-145) and the serum osmolality 275 mmol/kg (RI 275- 305). Urine studies showed a high urinary sodium (154 mmol/L) and osmolality (481 mmol/kg), consistent with renal salt wasting. The serum potassium rose to a peak of 6.1 mmol/L (RI 3.5 - 5.0), with a normal anion gap metabolic acidosis (bicarbonate 17 mmol/L (RI 21 – 31)). A paired urine pH of 8 pointed to an inability to acidify the urine.
Given the clinical course and laboratory investigations, the diagnosis of TMP-associated hyponatremia and Type 4 RTA was made. Oral resonium was started to correct hyperkalemia, with a combination of oral sodium chloride and sodium bicarbonate used to treat the hyponatremia and metabolic acidosis. Fludrocortisone was not used given the concerns of causing hypertension in a patient with a diseased aortic graft.
The dose of TMP-SMX was gradually reduced with improvement of the acid-base and electrolyte abnormalities, lending weight to our diagnosis. After the dose of the TMP-SMX was reduced to 80 mg BD, the hyperkalemia and metabolic acidosis resolved. The oral sodium chloride and sodium bicarbonate were gradually tailed off and stopped after cessation of the TMP-SMX.
Clinical Lesson:
Trimethoprim blocks the epithelial sodium channel (ENaC) of the principal cells in the terminal portion of the nephron, similar to potassium sparing diuretics like amiloride and triampterene. The resulting hyponatremia, hyperkalemia and metabolic acidosis can be life threatening. Therefore, monitoring of electrolytes and acid base status is important, particularly in susceptible patients or in those where a high dose of trimethoprim is required.
OR33-04 The Effect of Adiposity on the Fasting Serum Proteome in Normal Weight and Obese Men
Authors: Harshman Stephanie Geris , McCormack Shana Erin , Zhang Zhe , Maso Ana Aulinas , Lawson Elizabeth Austen 
Published: May 2020

Abstract
In many individuals with obesity, adipose tissue is not only increased in mass but also exhibits altered function. Disordered adipokine secretion contributes to a pro-inflammatory milieu that may lead to obesity-related co-morbidities. Hypothesis-generating, high-throughput techniques can generate novel insights. Our objective was to identify proteome-wide alterations in serum proteins related to adiposity. We evaluated the fasting serum proteome in 25 men [13 normal weight (mean±SD body mass index (BMI 21.2±1.4 kg/m2) and 12 with obesity (BMI 31.5±4.8 kg/m2)]. Blood was drawn at 0, 15, 30, and 55 minutes for proteomic analysis after an overnight fast (SOMAScan, SomaLogic, Inc.). The number of proteins and pathways that significantly differed between the two groups was determined across all time points during the fasting period. Normalized protein levels were compared between adiposity groups using rank product testing. Overrepresentation of protein constituents of established biological pathways was evaluated by hypergeometric test. P-values were adjusted using the Benjamini-Hockberg method, and those with an associated false discovery rate (FDR) of &lt;0.05 were considered statistically significant. A total of 4,785 protein isoforms were robustly identified in serum of normal weight and men with obesity, of which 226 protein isoforms were significantly higher in obesity (vs. normal weight), and 178 were significantly lower in obesity (vs. normal weight). Higher levels of leptin and lower levels of IGFBP1 and IGFBP2 were observed in individuals with obesity during fasting (all FDR &lt; 0.019). Functional annotation using Gene Ontology indicated that the following pathways differed most between obese vs. normal weight men: complement and coagulation cascade activation, amine metabolism, phosphatase activity, cellular response to nutrients (lipids, alcohol, and vitamin D), organic acid catabolism, and regulation of inflammatory responses. The protein isoforms identified in serum likely reflect systemic tissue-level changes in metabolism that may yield insights into the pathogenesis of obesity-related comorbidities and rational targets for intervention.
SUN-012 Role of Leptin-Receptor Expressing Cells in the Pathogenesis of Polycystic Ovary Syndrome (PCOS)
Authors: Cara Alexandra , Burger Laura Lynn , Myers Martin Grosvenor , Gendt Karel De , Moenter Sue , Elias Carol F 
Published: May 2020

Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, and is characterized by hyperandrogenism, oligo/anovulation, and/or polycystic ovaries. Many women with PCOS also suffer from adverse metabolic phenotypes, including central adiposity, insulin resistance, and glucose intolerance, which can exacerbate reproductive dysfunction. Androgens can act upon androgen receptors (AR), which are expressed in many reproductive and metabolic tissues, and contribute to the pathogenesis of PCOS. AR are highly expressed in the neuroendocrine hypothalamus in areas which regulate the hypothalamic-pituitary-gonadal axis and contribute to the central regulation of metabolism. Many phenotypes of PCOS can be modelled in rodents by administration of the non-aromatizable androgen dihydrotestosterone (DHT) during critical periods of development. Neuronal AR is key in the development of PCOS, as female mice with neuronal AR deletion who are exposed to androgen excess are protected against development of anovulation, polycystic ovaries, and metabolic abnormalities. Yet it is not known which populations of neurons confers this protection. We hypothesize that leptin-receptor (LepR) neurons participate in the pathogenesis of PCOS, as sub-populations of LepR neurons co-express AR in the hypothalamus, and LepR neurons are critical in the central regulation of energy homeostasis, and exert permissive actions on puberty and fertility. We have pre-natally androgenized (PNA) a mouse model of AR deletion specifically in LepR cells (LepRΔAR) and are conducting reproductive and metabolic phenotyping. As previously demonstrated, control PNA females show long periods of acyclicity, whereas LepRΔAR PNA female mice show a similar number of days in each stage of the estrous cycle, number of cycles, and cycle length as vehicle treated LepRΔAR females. Our findings indicate that a subpopulation of AR/LepR cells mediate the effects of prenatal androgen excess on female estrous cycles in a mouse model of PCOS-like phenotype.
MON-081 Mathematical Modeling of Residual Endogenous FT4 Synthesis and Exogenous L-Thyroxine Administration over the First 2 Years of Life in Infants with Congenital Hypothyroidism
Authors: Leroux Stéphanie , Marc Pfister , Welzel Tatjana , Gächter Pascal , Konrad Daniel , L’Allemand Dagmar , Szinnai Gabor , Koch Gilbert 
Published: May 2020

Abstract
L-Thyroxine (L-T4) is the treatment of choice of congenital hypothyroidism (CH). Longitudinal measurements of free T4 (FT4) serum concentrations were collected over the first two years of life with oral L-T4 treatment in infants with CH. Purpose of this study was to develop an integrated mathematical model to characterize the kinetics of exogenous L-Thyroxine (L-T4) after multiple dosing in infants with CH, and the dynamics of residual endogenous FT4 synthesis under treatment in the context of severe, moderate and mild disease.
A total of 200 FT4 concentrations from 30 patients were available for analysis. At start of treatment, mean (standard deviation [SD]) postnatal age and weight of the population were 11 (8) days and 3.9 (1.3) kg. Mean (SD) pretreatment FT4 concentration was 11.3 (7.4) pmol/L. Measured FT4 concentrations were modelled as sum of residual endogenous FT4 and exogenously administered FT4 (L-T4). The integrated mathematical model consists of an absorption compartment for the exogenous FT4 administration, and a central compartment for measured FT4 with linear elimination. Hence, for residual endogenous and exogenous FT4 the same elimination rate constant was assumed. For the residual endogenous synthesis, different approaches were tested: a constant production and typical time-dependent production functions. FT4 data were analyzed using nonlinear mixed-effects modeling.
The integrated mathematical model with a time-dependent non-linear Emax function describing a decreasing residual endogenous FT4 synthesis for increasing time provided the best data fit in terms of Akaike value and various goodness-of-fit plots. This is in line with the expected progressive suppression of the thyroid stimulating hormone by the exogenous FT4, and the subsequent decrease of residual FT4 endogenous synthesis. The developed mathematical model allows simulation of FT4 pharmacokinetic profiles for different disease severities and different dosing regimens.
SUN-677 The Warburg Effect: A Case of Persistent Hypoglycemia and Lactic Acidosis
Authors: Majety Priyanka , Erenler Feyza , Castillo Ma Dolores Del , Siegel Richard D 
Published: May 2020

Abstract
Background: It is well established that malignant cells are able to metabolize glucose to lactate in the presence of oxygen, known as the Warburg effect (WE) - a rare metabolic complication of malignancies, presenting with lactic acidosis & hypoglycemia. It signifies a poor prognosis with high mortality rates. We present the case of a woman with malignancy who presented with persistent hypoglycemia requiring a dextrose drip and type B lactic acidosis. Clinical case: A 63-year-old female was referred to our institution for persistent hypoglycemia and lactic acidosis after being admitted to another hospital for a urinary tract infection. Her history was notable for generalized fatigue & weight loss. She had lactic acidosis (18-25mEq/L; Normal: 0.5–2.2mEq/L) despite stable hemodynamics that did not improve with resuscitation & antibiotics. Her hospital course was complicated by worsening mental status & non- hypoxic respiratory distress due to profound acidosis, requiring intubation. She required a dextrose infusion of up to 40g/hour to maintain normoglycemia and with the infusion, an increase in lactate level was noted. Workup to rule out insulin-dependent hypoglycemia, adrenal insufficiency, GH deficiency, MELAS, mesenteric ischemia & drug-related lactic acidosis was unremarkable. EEG was not suggestive of seizure activity. Initial labs were notable for elevated levels of CA-19-9 408U/mL (normal: 0–34), & CA 125 430U/mL (normal: 0–34) which were attributed to her newly diagnosed cirrhosis. However, the degree of her liver dysfunction was felt to be not severe enough to cause hypoglycemia. Imaging studies looking for tumors were unrevealing. A bone marrow biopsy done to rule out occult malignancy showed metastatic carcinoma with neuroendocrine features. Further treatment was not pursued by her family. Based on the diagnosis of metastatic cancer, it was felt that her persistent hypoglycemia was due to the Warburg effect. Conclusion: The Warburg effect (WE) is observed in cancers when the malignant cells utilize glycolysis over oxidative phosphorylation, regardless of oxygen content, for energy production. This involves aerobic glycolysis & lactic acid is its by-product. Cancer cells use more glucose via the glycolysis pathway to meet their demands leading to hypoglycemia & concurrent lactic acidosis despite normal oxygen levels. WE is a rare but severe complication of malignancies that signifies a poor prognosis. Patients with this complication need to be monitored closely until definitive treatment can be implemented. This case highlights the importance of maintaining a high clinical index of suspicion for diagnosing WE. Reference Elhomsy G. C., Eranki V., Albert S. G., et al. “Hyper-warburgism,” a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin’s lymphoma. The Journal of Clinical Endocrinology & Metabolism. 2012;97(12):4311–4316.