bluuebunny/crossref_metadata_2025_split huggingface dataset:
7534 Characterizing The Presentation Of Non-Classical Congenital Adrenal Hyperplasia
Authors: Patel Sruti , Skamagas Maria , Levine Alice C , Yau Mabel 
Published: October 2024

Abstract
Disclosure: S. Patel: None. M. Skamagas: None. A.C. Levine: None. M. Yau: None.
Introduction: 21-hydroxylase deficiency, due to CYP21A2 gene mutations, is the most common steroidogenic enzymatic defect causing congenital adrenal hyperplasia (CAH). Disease severity is categorized into the classical and milder, non-classical (NCAH) form. Many patients go undiagnosed due to variable presentation and delayed onset. We aim to investigate the specific presenting concerns, age of onset, and genotypes associated with NCAH. Methods: A retrospective chart review of 285 patients with CAH seen over the past 2 years at our academic pediatric and adult endocrine clinics was performed. Records were reviewed for presenting concerns and age of symptom onset. CYP21A2 gene analysis was performed commercially via multiplex ligation-dependent probe amplification or next generation sequencing. Results: Of the 165 patients classified with NCAH, genotypes were available for 124 patients. Of the patients with a V281L allele, 43 were homozygous and 49 were heterozygous. 7 patients had the P30L allele and 7 had other allele combinations. The overall most common presenting concerns were early pubarche (29%), hirsutism (28%), and irregular menses (26%). In V281L homozygotes, family history most commonly led to diagnosis (30%). In patients with V281L heterozygosity or the P30L allele, the predominant concern was early pubarche (37% and 43% respectively). 15% of patients were screened prenatally or only due to family history and were asymptomatic at diagnosis. Patients’ age at diagnosis ranged from 0-40 years, with the mean age at diagnosis for the total group being 13.3 ± 8.9 years. Mean age of onset in symptomatic V281L homozygotes (15.4 ± 7.9 years) trended toward an older age compared to symptomatic V281L heterozygotes (15.1 ± 10.5 years) (P value = 0.90). Those who were heterozygous for V281L/P30L or undetermined whether homozygous for V281L or heterozygous with a deletion were excluded from age of onset comparisons. Discussion: The mean age of symptom onset was in adolescence and did not differ significantly between V281L homozygotes and heterozygotes. Early pubarche is a frequent presenting symptom in children with NCAH, and our data support this finding. P30L has been associated with a more severe phenotype than V281L, and in our cohort, the only patient presenting in adrenal crisis had a genotype with a P30L mutation. As NCAH is one of the most common autosomal recessive disorders in humans and there is an allelic predominance of V281L in NCAH patients, it is not surprising that a large percentage of V281L homozygotes were diagnosed due to family history prior to developing symptoms. Such patients need to be followed clinically and our data describing symptom onset could be useful in counseling these families and those with prenatal diagnoses.
Presentation: 6/1/2024
6640 Utility of bilateral inferior petrosal sinus sampling for diagnosis and management of Cushing's disease in children ; a case report
Authors: Leal V , Socha L , Awadalla S S 
Published: October 2024

Abstract
Disclosure: V. leal: None. L. Socha: None. S.S. Awadalla: None.
The causes of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) are Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis of CS and the localization of lesions in CD and EAS are often challenging. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children.A 16-year-old girl was referred for evaluation and treatment of Cushing syndrome she experienced weight gain, secondary amenorrhea, and back pain. 24-hour urinary free cortisol and low-dose dexamethasone suppression tests suggested Cushing syndrome. Adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance reported a microadenoma. To rule ectopic ACTH syndrome, and localize the pituitary tumor, bilateral inferior petrosal sinus sampling (BIPSS) was performed with desmopressin to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to right ACTH-secreting pituitary microadenoma and underwent endoscopic endo-nasal transsphenoidal surgery.In conclusion , BIPSS can be a valuable tool not only for discriminating between pituitary origin and ectopic ACTH-secreting Cushing syndrome, but also for providing precise localization of pituitary adenomas, thereby facilitating appropriate treatment.
Presentation: 6/1/2024
6545 Weekly Somapacitan Reduces Serum C-reactive Protein Levels in Adult Patients with Growth Hormone Deficiency
Authors: Seki Y , Morimoto S , Ikemoto M , Takano N , Yamashita K , Bokuda K , Watanabe D , Ichihara A 
Published: October 2024

Abstract
Disclosure: Y. Seki: None. S. Morimoto: None. M. Ikemoto: None. N. Takano: None. K. Yamashita: None. K. Bokuda: None. D. Watanabe: None. A. Ichihara: None.
Background: Adult growth hormone deficiency (GHD) is known to be associated with increased inflammation. Our previous research revealed a significant association between GHD and elevated serum C-reactive protein (CRP) levels. Limited studies have demonstrated a significant association between GH replacement therapies and CRP levels; only two reports showed a significant reduction in serum CRP levels with daily somatropin. This study aimed to investigate the effects of weekly somapacitan on serum CRP levels in adult patients with GHD. Methods: We prospectively observed serum CRP levels as the primary outcome before and 6 months after somapacitan treatment in adult patients with GHD with no history of GH supplementation therapy within the past 6 months. Secondary outcomes included anthropometric data, IGF-1 levels, and kidney and liver functions. The somapacitan dose was titrated based on IGF-1 levels during the 6-month treatment period. Results: Eight adult patients (mean age 50±17, male 4 [50%]) with GHD received weekly somapacitan treatment. Of the patients, 2 (25%) had ACTH deficiency, 2 (25%) had TSH deficiency, and 2 (25%) had gonadotropin deficiency. Two patients (25%) were on glucocorticoid replacement. The somapacitan dose at 6 months was 1.9 (1.5-2.6) mg/week. Weekly somapacitan significantly increased serum IGF-1 level (48 [29-122] to 125 [63-205] ng/mL, P = 0.001) and IGF-1 SD score (-3.3 [-5.3-0.9] to -0.7 [-3.0-0.8], P = 0.008) and significantly decreased serum CRP level (0.243 [0.056-0.464] to 0.093 [0.036-0.290] ng/mL, P = 0.008). However, it did not affect body weight (80.6±11.6 to 79.8±10.5 kg, P = 0.67) or serum creatinine (0.74±0.13 to 0.68±0.21 mg/dL, P = 0.35) and alanine aminotransferase (60 [20-99] to 48 [21-85] U/L, P = 0.23) levels. Changes in CRP levels were significantly correlated with changes in IGF-1 levels (rs = -0.83, P = 0.010) and IGF-1 SD scores (rs = -0.79, P = 0.021). Conclusion: GH supplementation therapy with weekly somapacitan reduced serum CRP levels in adult patients with GHD without affecting body composition or kidney and liver functions.
Presentation: 6/3/2024
7418 Xanthoma Disseminatum - A Rare cause of Diabetes Insipidus
Authors: Balasubramanian Priyadarshini , Cohen Jeffrey , Corbin Zachary , Panse Gauri , Inzucchi Silvio E 
Published: October 2024

Abstract
Disclosure: P. Balasubramanian: None. J. Cohen: None. Z. Corbin: None. G. Panse: None. S.E. Inzucchi: None.
Background: Xanthoma disseminatum is a rare non-Langerhans cell-derived benign histiocytosis of unknown etiology, characterized by mucocutaneous xanthomatosis. Systemic involvement occurs in a subset of patients, the most common manifestation being central diabetes insipidus in the setting of hypothalamic-pituitary- infundibulum infiltration, occurring in about 30-50% of the patients. We present the case of a man with biopsy proven cutaneous xanthoma disseminatum who developed central diabetes insipidus due to pituitary stalk involvement. Case Presentation: A 69-year-old male presented with a 2-year history of symmetrically distributed, erythematous to hyperpigmented macules and papules in the axillae and inguinal folds. He did not have any mucosal lesions. Skin biopsy revealed histiocytic infiltrate consistent with non-Langerhans cell histiocytosis, likely xanthoma disseminatum. He developed symptoms of polyuria and nocturia around the same time of the eruption, resulting in a large daily fluid intake of 100-120 ounces/day for several months. Laboratory evaluation revealed normal electrolytes. After an overnight water deprivation test, serum osmolality was 299mOsm/kg, serum sodium was 144mmol/L and urine osmolality was 280mOsm/kg, consistent with partial central diabetes insipidus. MRI pituitary with and without IV contrast showed thickening and hyperenhancement of the pituitary stalk. Anterior pituitary function was intact except for mild hypogonadotropic hypogonadism. He was started on DDAVP with good response and resolution of symptoms. Conclusion: Xanthoma disseminatum is characterized by extensive mucocutaneous xanthomatosis with occasional systemic involvement. The natural history of xanthoma disseminatum is usually benign, indolent, and slowly progressive with spontaneous regression described in a few cases. Hypothalamic and pituitary involvement may cause hyperprolactinemia, central diabetes insipidus, and variable degrees of hypopituitarism. Diabetes insipidus is often mild and sometimes transient. Occasionally, central diabetes insipidus can precede the skin lesions. Prognosis is generally good. Central nervous system involvement outside the hypothalamus/pituitary carries a poor prognosis.
Presentation: 6/2/2024
9293 Do Obesity-Associated MRAP2 Variants Modulate MC4R and GHSR Signaling?
Authors: Rondon Alejandra Virginia Rodriguez , Volker Femke , Welling Mila Sofie , de Groot Corjan , van Haelst Mieke M , van den Akker Erica L T , van Rossum Elisabeth F C , Delhanty Patric John , Visser Jenny A 
Published: October 2024

Abstract
Disclosure: A.V. Rodriguez Rondon: None. F. Volker: None. M.S. Welling: None. C. de Groot: None. M.M. van Haelst: None. E.L. van den Akker: None. E.F. van Rossum: None. P.J. Delhanty: None. J.A. Visser: None.
Melanocortin 2 receptor accessory protein 2 (MRAP2) is a membrane-bound protein expressed on hypothalamic neurons that modulate the function of appetite-regulating receptors, including melanocortin-4 receptor (MC4R) and growth hormone secretagogue receptor (GHSR). While pathogenic variants in the MRAP2 gene are associated with obesity, the mechanism for this remains unclear. The aim of this study is to investigate the functional impact of wildtype (WT) MRAP2 and MRAP2 variants on MC4R and GHSR signaling. Four MRAP2 variants (S80F, R125C, P167A and Q174X) were identified in patients with obesity by obesity gene panel analysis. The functional effects of these variants were analyzed by co-transfecting HEK293 cells with expression plasmids encoding WT or variant MRAP2 and WT MC4R or WT GHSR. Endpoint analyses included cell surface expression, and ligand-induced second messenger responses (α-MSH-induced cAMP response for MC4R and ghrelin-induced Ca2+ mobilization for GHSR), β-arrestin-2 recruitment, and internalization. WT MRAP2 significantly decreased basal MC4R cell surface expression by 68.1±4.3% (p&lt;0.001). In the absence of MRAP2, α-MSH induced MC4R internalization. However, in the presence of WT MRAP2, MC4R cell surface expression was increased by 89.4±6.9% upon α-MSH stimulation (p&lt;0.001). GHSR cell surface expression and ghrelin-induced internalization were not affected by WT MRAP2. Furthermore, in the cells expressing MC4R with WT MRAP2, the maximal α-MSH-induced cAMP and β-arrestin-2 recruitment responses were increased by 29.8±5.2% and 81.3±4.2% respectively (p&lt;0.001), compared with those lacking MRAP2. We also investigated GHSR ghrelin-induced Ca2+ mobilization and found that, in the presence of WT MRAP2, this increased significantly by 95.37±21.9%, (p&lt;0.0003). However, ghrelin-induced β-arrestin-2 recruitment was suppressed by 69.8±7.6%, (p&lt;0.001). Using these endpoints we found no effect of the variants on the ability of MRAP2 to modulate ligand-induced signaling by MC4R and GHSR. Our results indicate that WT MRAP2 enhances the cAMP response by increasing MC4R cell membrane expression upon α-MSH stimulation, and enhances GHSR Ca2+ mobilization by decreasing β-arrestin-2 recruitment upon ghrelin stimulation. The MRAP2 variants assessed in this study behaved as WT MRAP2 in α-MSH-induced MC4R and ghrelin-induced GHSR signaling, suggesting that these may be benign variants. However, since MRAP2 can modulate multiple receptors, we cannot rule out that these MRAP2 variants affect other appetite-regulating receptors and thereby influence body weight regulation via other pathways.
Presentation: 6/3/2024
7354 A Case of Continuous Glucose Monitoring in Children with Glutamate Dehydrogenase Hyperinsulinism
Authors: Kim Kyung Hee , Mun Eunji , Eun Choi Jung , Lee Rosie , Soon Kim Hae 
Published: October 2024

Abstract
Disclosure: K. Kim: None. E. Mun: None. C. Jung Eun: None. R. Lee: None. K. Hae Soon: None.
A Case of Continuous Glucose Monitoring in Children with Glutamate Dehydrogenase(GLUD1) Hyperinsulinism Background: Continuous glucose monitoring (CGM) is increasingly being used in pediatric patients with diabetes. CGM can help prevent hypoglycemia and support the management of hypoglycemic problems. Congenital hyperinsulinism is a rare condition in which hypoglycemia occurs due to hyperinsulinemia caused by the dysregulation of insulin secretion, and it can lead to complications such as developmental delay and seizures. Case presentation: A 14 months years old, male infant was referred to the pediatric emergency room representing symptoms of GTC type seizure during 2-3 minutes and hypoglycemia. He had no perinatal problems with no significant family history. During seizure, He was found to have a blood glucose of 39mg/dL, ammonia of 183μmol/L, insulin of 28.3 mcg/mL and ketone 203.4μmol/L. C-peptide was 1.4 ng/mL (≥ 0.5ng/mL) and free fatty acid was 0.492mmol/L (&lt;1.7mmol/L) for evaluation. He was thought to have GDH hyperinsulinism. Blood glucose level was followed up with feeding frequency and protein restricted diet. Congenital hyperinsulinism genetic test was requested. Brain CT showed normal. EEG revealed no focal abnormalities, no persistent asymmetries. CGM was used in patient. Diazoxide was started with 5mg/kg/day in 2 divided doses and then blood glucose level was observed below 60mg/dL 3-4 times for day. Complete blood counts and uric acid levels were measured at baseline and 5 days after starting diazoxide therapy, and thereafter increase to 6.25mg/kg/day Conclusions: In children with GDH hyperinsulinism, the utilization of CGM can serve as a tool to assess the impact of treatment before and after medication therapy, as well as also aiding in hypoglycemia prevention.
Presentation: 6/2/2024
9296 A Novel LC-MS/MS Salivary Fludrocortisone Method With Potential for Monitoring in Adrenal Insufficiency Patients
Authors: Dolan Megan , Marshall David , Hawley James , Reisch Nicole , Keevil Brian G 
Published: October 2024

Abstract
Disclosure: M. Dolan: None. D. Marshall: None. J. Hawley: None. N. Reisch: None. B.G. Keevil: None.
Fludrocortisone (FC) is a fluorinated exogenous mineralocorticoid used to treat conditions associated with adrenal insufficiency including Addison’s disease and classic congenital adrenal hyperplasia (CAH). The mineralocorticoid action of FC allows the drug to compensate for aldosterone deficiency, thus helping to maintain blood pressure and other homeostatic mechanisms. Optimising FC replacement is vital as under-replacement can cause dizziness and hypotension, whereas over-replacement can lead to cardiometabolic disturbances. Treatment in classic CAH patients, who are typically diagnosed as new-borns, is even more complex as the requirement for mineralocorticoid replacement decreases with age. Endocrine Society guidelines recommend that FC monitoring should involve the clinical assessment of symptoms, which can be non-specific, and regular blood pressure measurements. Plasma renin activity (PRA) should be measured if clinical changes occur, aiming towards the upper end of the reference range. The utility of PRA is debated due to methodological issues and the inherent variability of the analyte itself, which may not always represent FC replacement status. Therefore, investigation into alternative biochemical markers of FC replacement is required. Here we aimed to facilitate this by developing an LC-MS/MS method for the measurement of salivary FC. Method: A salivary FC LC-MS/MS assay has been developed and validated for use according to FDA and EMA guidelines. Passive drool samples from 10 clinical trial patients with classic CAH were collected on two separate occasions at select time points throughout the day (0800, 1200, 1600, 2000 and 2300h). In most patients the 0800h sample was taken pre-FC dose. Once in the laboratory the patient samples were extracted and analysed using the FC method to produce a FC concentration day curve. Results: The method analysis time was 2.1 minutes, with a mean recovery of 102% and limit of quantification of 5 pmol/L (2.1 pg/mL). No analytical interference was identified. Analysis of patient samples using the method showed the presence of FC allowing the production of day curves. In most patients, the pre-dose sample contained no FC, with the subsequent samples showing a peak FC concentration corresponding to the Cmax. After this the FC concentration gradually tapered off throughout the remainder of the day. Conclusions: We have developed a novel assay for the measurement of salivary FC, which may allow the calculation of the area under the curve. As an optimal FC dose has yet to be determined this method may facilitate more in-depth pharmacokinetic studies into FC metabolism and blood pressure control. Thereby identifying patients that are fast metabolisers or poor absorbers of the medication, enabling a non-invasive strategy to optimise patient care.
Presentation: 6/1/2024
12212 A Rare Case Of Central Precocious Puberty In A Male Infant With Adrenal Hypoplasia Congenita
Authors: Mastoropoulou Aikaterini , Lane Andrew Harry 
Published: October 2024

Abstract
Disclosure: A. Mastoropoulou: None. A.H. Lane: None.
Introduction: We describe a male with Adrenal Hypoplasia Congenita (AHC) caused by a novel mutation in NR0B1, who was noted at 9 months of age to have central precocious puberty (CPP). Clinical case: A 3 week-old full-term male presented with hypothermia and lethargy, and a 0.3 kg weight loss since birth. Labs were consistent with adrenal crisis: Na 109 mmol/L, K 10.4 mmol/L, Ca 12.2 mg/dL, glucose 43 mg/dL. He was stabilized with stress dose hydrocortisone (HC), insulin and antibiotics, and was admitted. Subsequent labs revealed cortisol 3.5 ug/dL (4.6-23), ACTH 1,123 pg/mL (7.2-63), 17OHP 181 ng/dL (&lt;199), and a renin of 180 ng/mL/h (1.7-11.2) with aldosterone 14.9 ng/dL (6-179). Abdominal ultrasound was remarkable for non-visualization of the adrenal glands. The patient was discharged with HC, fludrocortisone and sodium supplementation with good tolerance and interval weight gain and normal electrolytes. Genetic testing identified a novel pathogenic c.707G&gt;A [p.Trp236Ter] nonsense variant in the DNA-binding domain of NR0B1 (DAX-1). At 9 months of age, penile enlargement with prepubertal testes was noted. Testosterone was 318 ng/dL (Tanner stage I: 0-18), LH 3.2 mIU/mL (prepubertal: 0-0.3), DHEA-S 2 ug/dL (0-33), FSH 1.1 mIU/mL (prepubertal: 0-1), consistent with hypothalamic pituitary gonadal (HPG) axis activation. Given previous reports of prolonged but self-resolving “mini-puberty of infancy” in AHC, observation was initially chosen. At 12 months of age the bone age was consistent with the Greulich and Pyle 17 months standard. At 13 months of age testosterone remained elevated, therefore based on others’ reported experiences we increased HC from 8 to 15 mg/m2/day and noted a decrease in testosterone to 104 ng/dL within 5 days. HC was further increased to 18 mg/m2/day for 15 days, however testosterone increased to 270 ng/dL, therefore decision was made to treat with Lupron Depot. Conclusions: Historically, hypogonadotropic hypogonadism has been observed in 76% of adolescent patients with AHC who have alterations in NR0B1. CPP has been infrequently described in AHC, and the natural history and management of CPP in this setting is not established. CPP in AHC does not seem to correlate with any particular functional domain of DAX1, because previously reported NR0B1 variants associated with CPP, and this case’s, are dispersed across the gene. The course of our patient suggests multiple underlying mechanisms, including early HPG axis activation as well as the possibility of ACTH dependent precocious puberty. Our observations may contribute to the understanding of factors influencing normal and abnormal puberty in infants. Increased awareness of the possibility of CPP in AHC will aid clinicians in the earlier clinical and laboratory detection of this complication.
Presentation: 6/1/2024