bluuebunny/crossref_metadata_2025 huggingface dataset:
THU146 Triglyceride Glucose Index Is Superior To The Homeostasis Model Assessment Of Insulin Resistance For Predicting Severity Of Nonalcoholic Fatty Liver Disease In Korean Children And Adolescents
Authors: Yoon Jong Seo , Kim Eun Young
Published: October 2023

Disclosure: J. Yoon: None. E. Kim: None.

Background: Triglyceride glucose (TyG) index is known as a reliable insulin resistance surrogate marker to identify non-alcoholic fatty liver disease (NAFLD). Ultrasonographic fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting hepatitis in patients with NAFLD and accurately identifies histological severity. Few studies have compared the TyG index to homeostasis model assessment of insulin resistance (HOMA-IR) in the detection of NAFLD in children and adolescents. Additionally, there were no studies comparing the ability of TyG index and HOMA-IR to assess the severity of NAFLD. Objects: Therefore, we investigated the relationship between TyG index and NAFLD compared to HOMA-IR in identifying and assessing the severity of NAFLD in children and adolescents. Methods: Alanine aminotransferase (ALT) was used as the screening method for NAFLD (>26IU/L in boys and >22IU/L in girls), and US-FLI was performed on children who met these criteria. The US-FLI is a scoring system ranging 2-8 that evaluates based on intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. TyG index was calculated as ln(fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. The US-FLI was significantly correlated with TyG index (r=0.264, p=0.003) but not with HOMA-IR after controlling for sex, age, and BMI. Multiple linear regression analysis showed that TyG index were significantly associated with US-FLI (β=0.202, p=0.002) not with HOMA-IR after controlling for sex, age, and BMI. The TyG index was superior to HOMA-IR in its ability to detect the severity of NAFLD in US-FLI ≥4, ≥5, and ≥6. Conclusions: Both TyG index and HOMA-IR were useful for detecting pediatric NAFLD. However, the TyG index was useful for detecting the severity of NAFLD, whereas HOMA-IR was not. Therefore, we propose to use the TyG index to predict and evaluate the severity of NAFLD in children.

Presentation: Thursday, June 15, 2023
THU153 Deep Vein Thrombosis As The Presenting Symptom In An Adolescent With New-Onset Type 2 Diabetes
Authors: Cooper Felicia Ilyssa , Gurnurkar Shilpa , Carakushansky Mauri
Published: October 2023

Disclosure: F.I. Cooper: None. S. Gurnurkar: None. M. Carakushansky: None.

Introduction The prothrombin G20210A mutation occurs in a small portion of the population, but usually does not become apparent unless the individual exhibits another risk factor for clotting (such as diabetes in adulthood). In this case report, we discuss a 15-year-old male with extensive deep vein thrombosis (DVT) in the setting of hyperglycemia and a newly-discovered prothrombin G20210A mutation. Case Presentation A previously healthy, obese 15-year-old male presented to the emergency department with two days of left hip pain radiating down to the left calf, and one day of left calf swelling. The patient denied prolonged immobility, recent infections, or recent vaccinations. There was strong maternal family history of diabetes but no history of thrombosis. D-dimer was 2013 ng/mL (0-500 ng/mL). A Computed Tomography of the abdomen and pelvis with contrast revealed thrombi in the inferior vena cava, left common iliac, left external iliac, left internal iliac and left common femoral veins. Initial labs were remarkable for unexpected significant hyperglycemia-- random serum glucose 317 mg/dl (<140 mg/dl).He was started on unfractionated heparin infusion as well as Lantus and Humalog insulins. An echocardiogram did not reveal pulmonary embolism or right heart strain. Hemoglobin A1C was 11.8% (3.4-5.6%) and C-peptide was detectable at 1.2 ng/mL (1.1-4.4 ng/mL), suggesting type 2 diabetes (in addition to negative anti-GAD 65 and islet cell antibody titers, in this child with a BMI of 34 kg/m2). The patient underwent image-guided thrombolysis and thrombectomy from the popliteal vein to the left iliac vessels and received continuous infusion of heparin and tissue plasminogen activator (TPA). As the clot improved over the subsequent days, he underwent image-guided angioplasty and removal of the popliteal sheath. He was then transitioned to enoxaparin and discharged on day 10 of hospitalization. His blood sugars responded well to insulin therapy (85-308 mg/dl). The patient received a staged thrombophilia workup. A heterozygous mutation was found in factor II (prothrombin G20210A) gene which is associated with a 2-4 fold increased risk of venous thromboembolism. The patient was discharged on enoxaparin, as well as Lantus and Humalog. He is followed by the Hematology and Endocrinology departments. Conclusion In this case, we presented the first written occurrence of DVT in a pediatric patient with type 2 diabetes. Our patient’s hyperglycemia caused by his new onset type 2 diabetes may have led to onset of an extensive DVT thrombosis at an usually young age, since he had an underlying prothrombin G20210A mutation. Our case also illustrates the need for a multidisciplinary approach (involving endocrinology, hematology, pediatric intensive care, and interventional radiology) for successful outcomes in these patients.

Presentation: Thursday, June 15, 2023
THU154 The Effects Of Combined Arginine And Sinemet Stimulation On Copeptin Levels In The Pediatric Population
Authors: Sastry Shruti , March Christine , Garibaldi Luigi , McPhaul Michael John , Wheeler Sarah
Published: October 2023

Disclosure: S. Sastry: None. C. March: None. L. Garibaldi: None. M.J. McPhaul: None. S. Wheeler: None.

Introduction: Most agents that stimulate the secretion of growth hormone (GH) also induce secretion of copeptin (COP), a stable surrogate of AVP. For the evaluation of the polyuria-polydipsia syndrome (PPS), COP stimulation by intravenous (IV) arginine (ARG) has been proposed as a less invasive test than those based on osmotic stimulation of the posterior pituitary, though it provides a weaker stimulus in children than in adults (∼30% vs. 50% increase). After having observed a robust COP response to combined ARG and insulin stimulation (March C, Horm Res Pediatr 2023, PMID: 36513057), we explored the effect of combined IV ARG and oral L-Dopa/carbidopa (LDc, 10:1 ratio), another known stimulus for GH secretion, on COP secretion in non-AVP deficient children. Subjects and Methods: We enrolled 30 healthy subjects with short stature (73% male, mean age ± SD 10.5±3.0 years) undergoing fasting GH stimulation testing in a prospective, single-arm study to assess their COP response. At 0 minutes (min), ARG (500 mg/kg) was infused over 30 min IV and LDc (200 mg/m2 BSA of L-Dopa) was given orally. Serum COP (B.R.A.H.M.S Kryptor assay, Quest Diagnostics) was measured at 0, 60, 90 and 120 min. Results: Median (interquartile range (IQR)) COP values (pmol/L) were 8 (5-10) at 0 min, 17 (13-44) at 60 min, 24 (13-41) at 90 min, and 30 (16-56) at 120 min. Peak COP concentrations at 60, 90, and 120 min all increased significantly from baseline (p<0.001, Wilcoxon sign rank test), but were highly variable in both value (range 10-449) and the timing of the peak (60 min in 33%, 90 min in 17%, 120 min in 50%). Except for 1 subject whose COP values did not change, all subjects had a robust COP peak, ranging from 1.6 to ∼90x the baseline value. The median (IQR) copeptin peak value [50 (41-129) pmol/L] was higher in subjects experiencing nausea/vomiting than in those who did not show this known side effect of LDc [25 (16-44), p=0.03 by Wilcoxon test]. Conclusions: Combined ARG and LDc appear to induce intense stimulation of COP secretion, with widely variable stimulated COP responses. The lowest COP peak value and the median response in this series were much greater than those previously reported to ARG alone in our previous study and the literature. Side effects were well tolerated. The data suggest that this test should be piloted for the differential diagnosis PPS as an alternative to ARG stimulation alone and/or the water deprivation test.

Presentation: Thursday, June 15, 2023
THU168 PRMT7 Gene Mutation—A Rare Genetic Syndrome With Novel Endocrine Associations
Authors: Nutakki Krishna Veni , Nalla Smitha , Deb Prasun , Vulpala Alekya
Published: October 2023

Disclosure: K. Nutakki: None. S. Nalla: None. P. Deb: None. A. Vulpala: None.

Background: Causes of short stature in children include pathologic causes (genetic diseases, underlying systemic disease, or growth hormone deficiency) and non-pathological variants such as familial and constitutional short stature. Genetic causes include Turner’s syndrome, SHOX mutations, Noonan’s syndrome and Silver- Russel syndrome besides others. Homozygous/compound heterozygous mutations in Protein Arginine Methyltransferase 7 (PRMT7) can result in Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS) . Here, we report a child with SBIDDS syndrome who has associated endocrine manifestations of growth hormone deficiency and primary hypothyroidism. Case report: A 9-year-old male child, twin A of dichorionic diamniotic gestation, presented to the Endocrine OPD with short stature. There was a history of developmental delay, seizure disorder and mild intellectual deficit. Excessive weight gain was observed since 4 years of age. On examination, he was short with abdominal obesity, brachydactyly, simian crease and macroglossia. Height was below 3rd centile and weight at the 97th percentile. SMR was pre-pubertal. Investigations confirmed primary hypothyroidism.GH deficiency (peak GH after clonidine stimulation was less than 4 microgram/L) and reduced IGF-I levels were also found. Twin B was noted to have a normal height percentile. In both, skeletal maturation was consistent with chronological age. Twin A was treated with rGH and levothyroxine and responded well to rGH treatment. Whole exome sequencing revealed homozygosity for PRMT7 mutation in twin A with both parents heterozygous for the same gene mutation. His twin sibling, twin B was also found to be homozygous for the mutation, but he did not display any characteristics of the syndrome. Discussion: To the best of our knowledge, this is only the second reported case of SBIDDS syndrome (PRMT7 mutation) with documented growth hormone deficiency and only case with documented primary hypothyroidism. Height gain observed over the period of rGH treatment is suggestive of a possible role of GH/IGF-I axis alterations as contributors of growth impairment in these children. PRMT7 encodes for an arginine methyltransferase, involved in several biological processes, such as DNA transcription and repairing, RNA splicing, cell differentiation. We would like to propose that children with SBIDDS syndrome may be tested for GH deficiency as part of their overall assessment. Likewise, it should be further explored if PRMT7 gene mutation testing should be recommended in a child presenting with short stature and one or more manifestations of SBIDDS syndrome.

Presentation: Thursday, June 15, 2023
THU612 SDHx Pheochromocytoma/Paraganglioma Has Elevation Of Arginine And Lysine Metabolites
Authors: Ghayee Hans Kumar , Richter Susan , Bechmann Nicole , Kalavalapalli Srilaxmi , Joy Guingab-Cagmat , Xu Yiling , Cusi Kenneth , Tischler Arthur , Powers James F , Beuschlein Felix , Robledo Mercedes , Fliedner Steffi , Quinkler Marcus , Fassnacht Martin , Timmers Henri , Pacak Karel , Eisenhofer Graeme , Garrett Timothy J
Published: October 2023

Disclosure: H.K. Ghayee: None. S. Richter: None. N. Bechmann: None. S. Kalavalapalli: None. G. Joy: None. Y. Xu: None. K. Cusi: None. A. Tischler: None. J.F. Powers: None. F. Beuschlein: None. M. Robledo: None. S. Fliedner: None. M. Quinkler: None. M. Fassnacht: None. H. Timmers: None. K. Pacak: None. G. Eisenhofer: None. T.J. Garrett: None.

Background: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that arise from the chromaffin cells of the adrenal medulla or sympathetic/parasympathetic paraganglia respectively. There are more than 25 genetic drivers identified in these tumors. These genetic mutations are categorized into the three main clusters. However, cluster 1 and cluster 2 comprise most of the known genes. Within cluster 1, SDHx mutations are associated with aggressive disease. To better understand the metabolic signature of these tumors, our group performed untargeted metabolomics of over 200 pheochromocytomas and paraganglioma tissue samples. Methods: Frozen tissues were processed and sent to the University of Florida and analyzed in 2 batches. Analysis was conducted using liquid chromatography high-resolution mass spectrometry with full blinding and randomization. Raw data were converted to mzXML and then processed using MZmine to identify features. Blank feature filtering was conducted to filter noise and very low abundant features. Metabolite identification was first conducted with reference to an in-house retention time library of 1200 metabolites and further identification was conducted by searching the human metabolome database. Statistical analysis was performed in R. Results: Comparing cluster 1 vs cluster 2, we observed an overall increase in purine metabolites specifically adenine, AMP, GMP, UMP, CMP, cytidine, and dihydrothymine in cluster 2. Arginine metabolism was lower in cluster 2, specifically dimethylarginine, citrulline, and N-methyl-L-arginine. Comparing SDHx vs cluster 1, we observed an overall increase in arginine metabolism with ornithine, citrulline, N-acetyl-ornithine, proline and hydroxy-proline. We also observed an increase in lysine metabolism in SDHx vs cluster 1 with lysine, N-acetyl-lysine, cadaverine, glutarate, 2-hydroxyglutarte, 2-oxoglutarate, succinate and trimethyllysine all being elevated. A decrease in serotonin in SDHx compared to cluster 1 was seen. Conclusion: Global metabolomic analysis of pheochromocytomas and paragangliomas has uncovered important pathways that drive the metabolic functions depending on the gene cluster. Most notably, arginine and lysine metabolites were increased in SDHx tumors.

Presentation: Thursday, June 15, 2023
THU184 Varying Presentations Of 46XX OTD
Authors: Mishra Ipsita , Sahoo Subhendu Kumar , Baliarsinha Anoj Kumar
Published: October 2023

Disclosure: I. Mishra: None. S.K. Sahoo: None. A.K. Baliarsinha: None.

Ovotesticular disorder of sex development (OT-DSD) is a condition associated with presence of both testicular and ovarian tissue in same individual, in which these tissues may co-exist either in the same gonad or independently. 46 XXOTD are most common. We describe 3 cases of 46 XXOTD presenting in their post pubertal years with varied presentation. Case 1: 19 year old reared as male presented with peripubertal gynaecomastia and cyclical pain abdomen. On examination there was symmetrical genitalia, non palpable gonads, microphallus, single genital opening below phallus (Prader 3), pubic hair stage 4, axillary hair stage 3 and breast stage 5. Biochemical evaluation revealed serum testosterone (19 ng/dl), 17-hydroxy progesterone (1.7ng/ml), LH (2.6IU/L), FSH (8.6IU/L) and E2(112pg/ml). Karyotype 46XX, FISH SRY negative. USG abdomen s/o uterus like structure with absent wollfian remnants. Post laproscopy histopathology s/o bilateral ovotestis, normal ovarian stroma with hyalinized seminiferous tubule, sertoli cells and leydig cells. Case 2: 18 year old reared as male presented with peripubertal gynaecomastia and genital ambiguity. On examination there was asymmetrical genitalia, palpable right scrotal gonads, phallus, single genital opening at base of phallus, pubic hair stage 4, axillary hair stage 3 and breast stage 5. Biochemical evaluation revealed serum testosterone (110ng/dl), LH (4.6IU/L), FSH (11.2IU/L) and E2(46pg/ml). Karyotype 46XX.USG abdomen s/o hypoplastic uterus like structure with possible ovary in left side of pelvis, hypoplastic testis in right scrotal sac. Post laproscopy histopathology was s/o left dysgenetic ovary, and hypoplastic uterus. Case 3: 17 year old reared as male presented with peripubertal gynaecomastia. On examination there was symmetrical genitalia, non palpable gonads, microphallus, single genital opening at the base of phallus (Prader 4), pubic hair stage 4, axillary hair stage 2 and breast stage 4. Biochemical evaluation revealed serum testosterone (98ng/dl), 17-hydroxyprogesterone (0.58ng/ml), LH (4.05IU/L), FSH (7.12IU/L) and E2 (96 pg/ml). Karyotype 46XX, FISH SRY positive. USG abdomen s/o uterus like structure with apparent left ovary and non visualization of right gonads. Post laproscopy histopathology s/o rudimentary uterus, left ovary with follicles and right gonads showing semineferous tubules with sertoli cells and few hyperplastic leydig cells. 46 XX OTDSD presents with wide phenotypic variability, which influences decisions about gender assignment and need of surgery. Conservative therapy, whenever feasible, is desirable to achieve fertility. Multidisciplinary team approach is required for healthy physical and psychological well-beings of these individuals.

Presentation: Thursday, June 15, 2023
THU185 Molecular Etiologic Spectrum Of Patients With 46,XY And 46,XX Disorders Of Sex Development
Authors: Kim Ja Hye , Park Soyoung , Hwang Soojin , Yoon Ji-Hee , Kim Gu-Hwan , Yoo Han-Wook , Choi Jin-Ho
Published: October 2023

Disclosure: J. Kim: None. S. Park: None. S. Hwang: None. J. Yoon: None. G. Kim: None. H. Yoo: None. J. Choi: None.

Background: Disorders of sexual development (DSDs) is a group of congenital conditions associated with discordant development of chromosomal, gonadal, and anatomical sex. Sex development is a complex process with a precise synergistic temporal-spatial transcriptional regulation of multiple genes. Advances in next-generation sequencing (NGS) techniques have achieved genetic diagnosis for up to 40 % of 46,XY DSDs. This study investigated the etiological distribution of DSDs identified by NGS. Methods: This study included 70 patients with DSDs (56 patients with 46,XY DSD and 14 patients with 46,XX DSD). Molecular genetic analysis was performed using targeted gene panel sequencing (n = 43) and whole-exome sequencing (WES, n = 26), including 25 patients for the first-line test and one without sequence variants by targeted gene panel sequencing. Whole-genome sequencing (WGS) was performed on 7 patients, including two patients for the first-line test and five patients without sequence variants by targeted gene panel sequencing or WES. Results: Patients with DSDs presented in infancy with ambiguous genitalia and at older children with aberrant pubertal development or discordance between karyotype and external genitalia. Twenty-four of 56 patients (42.9%) with 46,XY DSD were reared female, and 5 of 14 patients (35.7%) with 46,XX DSD were raised as a male. Pathogenic or likely pathogenic variants were identified in 21 of 56 patients with 46,XY DSD (37.5%); however, no rare sequence variants were found in patients with 46,XX DSD. The AR variants were the most common (8/70, 11.4%), followed by CYP17A1 (4/70, 5.7%), SRD5A2 (4/70, 5.7%), NR5A1 (2/70, 2.8%), GATA4 (1/70, 1.4%), MYRF (1/70, 1.4%), and deletion of DMRT1/2 (1/70, 1.4%). Mutation-positive patients with 46, XY DSD were assigned as female more frequently than mutation-negative patients (19/21 vs. 6/35, P-value <0.001). The lower diagnostic yield was observed in patients with a less severe phenotype, such as hypospadias or micropenis. Conclusions: This study demonstrated that genetic etiologies could be identified in 37.5% of patients with 46,XY DSD, whereas there were no genetic variants in patients with 46,XX DSD. Patients with a more severe phenotype were more likely to have a conclusive genetic diagnosis. NGS is a helpful technique to improve diagnostic efficiency in patients with DSD because of phenotypic and genetic heterogeneity.

Presentation: Thursday, June 15, 2023
THU188 Clinical Conundrum: Salt Wasting Congenital Adrenal Hyperplasia With Paradoxical High Cortisol
Authors: Pillai Chanthu
Published: October 2023

Disclosure: C. Pillai: None.

Background: Salt wasting congenital adrenal hyperplasia (CAH) is a severe life-threatening condition and thus a cannot miss diagnosis. In salt wasting CAH, cortisol is generally very low. An ACTH stimulation test is often used to diagnose adrenal insufficiency and initiate life-saving hydrocortisone therapy. Clinical Case: I present a case of a male infant who was found to have salt-wasting CAH crisis despite a paradoxically high serum cortisol. He had an abnormal newborn screen for CAH. He was sent to the ER for reportedly high 17-hydroxyprogesterone (17-OHP). Endocrine was consulted and a serum 17-OHP, ACTH and cortisol level was requested. He was an incredibly difficult patient to collect blood work and after multiple attempts only a serum cortisol was collected. He was admitted for an ACTH stimulation test to rule out salt wasting CAH. His physical exam was unremarkable with male external genitalia with descended prepubertal testes. His cortisol from the ER resulted at 36.5 mcg/dL without any steroid administration in the morning. Family refused to do any additional blood work in the morning. Even anesthesiology was not able to collect the requested labs. The ACTH stimulation test was canceled, and he was discharged with close follow-up in 1 week. The state newborn screen department called and reported his initial 17-OHP was undetectably high. He was seen the same day and his BMP showed clear signs of salt wasting. His serum sodium was 131 mmol/L and potassium was 7.2 mmol/L. He was admitted for a salt wasting crisis and responded well to hydrocortisone and fludrocortisone. Serum sodium and potassium normalized. Blood draw issues continued and only BMP were collected during the hospitalization. 17-OHP after several days of therapy was 3270 ng/dl. 17-OHP, sodium and potassium have normalized on therapy. Genetic testing is pending. Conclusions: By reporting this case, I draw attention to the possibility that high levels of cortisol do not definitely rule out salt-wasting CAH.

Reference Ranges: NA 132 - 145 mmol/L K 3.0 - 6.0 mmol/L Cortisol: 1.7 - 14.0 ug/dL 17 OHP:INTERPRETIVE INFORMATION for 17-Hydroxyprogesterone in premature and normal male infants: Premature (26 to 28 weeks) 124 to 841 ng/dL Premature (29 to 35 weeks) 26 to 568 ng/dL Full term Day 3 7 to 77 ng/dL 4 days to 2 months Less than 200 ng/dL.

Presentation: Thursday, June 15, 2023
THU615 Rhabdomyolysis: A Rare Presentation Of Extra-adrenal Neuroendocrine Tumor
Authors: Saleem Marwa , Harman Sherman Mitchell , Targovnik Jerome
Published: October 2023

Disclosure: M. Saleem: None. S.M. Harman: None. J. Targovnik: None.

Introduction:Paraganglioma is a rare neuroendocrine tumor (NET) arising from neural crest progenitors located outside of the adrenal gland and predominantly produce norepinephrine if functional. Here, we present a case of epinephrine producing extra-adrenal sympathetic neuroendocrine tumor. Case: A 66-year-old male with history of resistant hypertension (on amlodipine, lisinopril & metoprolol), hyperlipidemia & obesity presented for evaluation of possible pheochromocytoma/paraganglioma. He reported paroxysmal episodes of muscle spasm & paresthesia accompanied by hypertension (up to 200 mm Hg), palpitation, sweating & tremor lasting about 30-60 minutes. His CPK was elevated up to 428 U/L (NR 30-170 U/L) during those episodes. He reported 7 "major episodes" beginning ∼15 years prior to diagnosis, of which 3 occurred after major surgery with "small episodes" occurring monthly, exacerbated by sun & heat. Family history was remarkable for sister with recurrent rhabdomyolysis. Labs showed elevated epinephrine 181 pg/ml (normal <57), Dopamin 67 pg/ml (normal <10) and normal norepinephrine, significantly elevated 24h urine metanephrine 855 mcg/24h (normal 90-315), normal normetanephrine & dopamine levels. CT showed a 2.2 x 2.2 x 2.1 cm retroperitoneal mass with 84% absolute concerning for possible paraganglioma. FDG-PET and DOTATATE showed hypermetabolic activity (SUV max 6.63) and DOTATATE avid left retroperitoneal mass respectively. After discontinuing beta blocker and optimizing alpha blockage with doxazosin, the patient was referred to endocrine surgery and had a successful resection of this mass and left adrenalectomy. Pathology was consistent with chromaffin cell neoplasm and normal left adrenal gland. Patient had clinical and biochemical resolution of his symptoms post-op. Genetic counseling was done with pending results.

Discussion: Pheochromocytomas & paragangliomas (PPGLs) are rare NET arising from chromaffin cells of the adrenal medulla or neural crest progenitors located outside of the adrenal gland, and predominantly produce epinephrine and norepinephrine respectively. Adrenal medullary tissue secretes epinephrine due to the activity of PNMT, induced by high local levels of cortisol from the adrenal cortex, which attaches a methyl radical to the catechol amino group. Extramedullary sympathetic secretory cells normally lack this enzyme and secrete norepinephrine. Thus, it is likely that the neoplasm we report had ectopic expression of this enzyme. PPGLs have variable signs and symptoms which mainly reflect the hemodynamic and metabolic actions of the catecholamines produced and secreted by the tumors with hypertension being the most common sign. Rhabdomyolysis is an unusual manifestation. This case is unique in that it presented as an extra-adrenal NET predominantly produced epinephrine and presented with rhabdomyolysis.

Presentation: Thursday, June 15, 2023
THU200 Three Cases Of Prepubertal Vaginal Bleeding
Authors: Doi Hibiki , Igarashi Mizuho , Kashima Takemoto , Ujita Nagisa , Konno Hiroaki , Fujioka Akiko , Miyagi Hajime , Yoshii Keisuke , Naiki Yasuhiro , Horikawa Reiko
Published: October 2023

Disclosure: H. Doi: None. M. Igarashi: None. T. Kashima: None. N. Ujita: None. H. Konno: None. A. Fujioka: None. H. Miyagi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None.

Introduction: Children with prepubertal vaginal bleeding (PVB) are usually referred to pediatric endocrinologists, because precocious puberty is one of the important causes of PVB. However, the diagnosis remains challenging due to a wide variety of causative diseases beyond endocrinological disorders. We present three illustrative cases of children with PVB in our institution. Case presentations: Case 1. A 2-year-old girl had suppressed serum LH and FSH levels and elevated estradiol level. She had café-au-lait spots with jagged “coast of Maine” borders on her left chest and back. Her bone X ray showed multiple fibrous dysplasia. The diagnosis of McCune-Albright syndrome was made by a triad of skin, bone and hyperfunctioning endocrinopathy. Case 2. A 5-year-old girl had low serum LH, FSH, and estradiol levels. Her pelvic MRI showed a mass in her vagina and contrast enhancement of the vaginal membrane. Although some malignant tumor had been suspected, vaginal observation using cystoscopy revealed a foreign body of a sponge that seemed to be part of a toy. Her vaginal bleeding disappeared after removal. Our multidisciplinary team concluded that this case was not child abuse. Case 3. A 4-year-old girl had been misdiagnosed as central precocious puberty due to slightly elevated gonadotropin levels. She was referred to our hospital because gonadal suppression therapy with leuprorelin didn’t stop her PVB. Although the observation of her urethra, bladder, vagina, and uterus using cystoscopy revealed no abnormal findings, a small fistula on the membrane of her vaginal opening was noted. Finally, the diagnosis of von Willebrand’s disease type I was made by low level of von Willebrand factor. We speculated that her repeated bleeding was triggered by minor trauma with the background of bleeding tendency. When severe bleeding occurs or is expected to occur, factor VIII containing von Willebrand factor should be administered. Discussion: There are various etiologies of PVB. Detailed history taking and physical examination are quite important, but might be difficult for young pediatric patients. Neoplasms and sexual abuse must be ruled out. In case of suspicion of abuse, the patient’s safety should be guaranteed. Inspection using cystoscopy under general anesthesia is a useful option in recurrent PVB cases. It is critical to make the correct diagnosis because the treatments can be totally different. Conclusion: In PVB cases we need to perform detailed assessments including careful history taking, physical examination and necessary testing considering a broad range of possible diseases.

Presentation: Thursday, June 15, 2023
THU202 Peripheral Precocious Puberty In A 7-year-old Female As A Result Of Exposure To Bath Bombs
Authors: Gordner Chelsea C
Published: October 2023

Disclosure: C.C. Gordner: None.

Introduction: Recent studies have demonstrated a progressive decrease in the age of onset of puberty in children. Endocrine disrupters are increasingly being identified as an important contributing factor to this shift in pubertal timing. We present here a case of peripheral precocious puberty in a 7-year-old female after a brief intense exposure to bath bombs. Clinical Case: A healthy pre-pubertal 7-year-old female used daily bath bombs for 7 days. She developed tender Tanner II breast buds the following week with no other pubertal or adrenarchal signs. Growth chart review revealed stable linear growth without growth acceleration. Bone age x-ray was consistent with chronologic age (CA 7y0m, BA 6y10m). LH, ECL, was 0.058 miU/mL (ref: 0.02-0.3), Estradiol, LCMS, was 2.0 pg/mL (ref < 15), DHEA-Sulfate, LCMS, was 45 mcg/dL (ref: 6-7y: < 72). The breast buds started to resolve after 2 months and were completely gone after 3 months from the initial exposure. Clinical Lessons: Endocrine-disrupting chemicals are found in pesticides, plasticizers, lavender, fennel, and tea tree oils and can lead to precocious puberty, delayed puberty, and/or impact sexual differentiation. Consumer products are often not well labeled to identify these chemicals and often use confusing terminology like “all-natural” and “organic” which can be misleading. Conclusions: Bath bombs should now be added to the growing list of consumer products associated with precocious puberty. Leaders should advocate for better labeling of consumer products to help identify potentially harmful products.

Presentation: Thursday, June 15, 2023
THU205 A Case Of Infant With Familial-Male Limited Precocious Puberty (FMPP) Inherited From Father Due To An Activating Mutation Of The Luteinizing Hormone/Chorionic Gonadotropin Receptor Gene
Authors: Yoo Han-Wook , Ha Jihyun , Jung Mo Kyung , Choi Yunha , Yoo Eun-Gyong
Published: October 2023

Disclosure: H. Yoo: None. J. Ha: None. M. Jung: None. Y. Choi: None. E. Yoo: None.

We present an extremely rare case of FMPP with an activating mutation of the LHCGR gene in a Korean infant. A 16-month-old-boy was brought to the out-patient clinic with complaints of pubic hair, acne and rapid growth acceleration. His father had become aware of the symptoms 4 month before. His grandfather and father had a family history of precocious puberty and profound short stature (Height of grandfather and father: 148 cm and 158 cm respectively). At physical examination, his height was 83 cm (+1.2 SDS) and his weight was 14.3 kg (+2.8 SDS). The testicular volume was 2 mL and pubic hair was appropriate for Tanner stage 2. Stretched penile length was 7 cm (>2 SDS). He did not have any café au lait spots or hyperpigmentation. His bone age was significantly advanced to that of a 4 year old. Laboratory findings showed abnormally elevated serum testosterone (5.74 ng/mL) and slightly elevated α-fetoprotein (14.1 ng/ml; reference 0-10 ng/mL) with suppressed LH level (<0.07 mIU/mL). Serum levels of β-human chorionic gonadotropin, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone sulfate were within normal range. A gonadotropin releasing hormone (GnRH) stimulation test revealed a prepubertal response(peak LH 0.52). Brain magnetic resonance imaging study was reported to be normal. Ultrasound of the scrotum and adrenal gland were both normal. Due to the patient’s classic presentation and his family history of male-limited precocious puberty, a genetic analysis for LHCGR gene was performed. Molecular genetic analysis identified a pathogenic variant of LHCGR (c.1730 C>T, p.Thr577Ileu), which was previously reported in a FMPP patient. His father and paternal grand father also carry the same mutation. Anti-androgen treatment with bicalutamide (25mg/day) and aromatase inhibition with anastrozole (1mg/day) were initiated. After treatment, there was improvement in pubertal progression, accelerated growth velocity and rate of skeletal maturation without any specific side effects.

Presentation: Thursday, June 15, 2023
THU220 Legal Degree Of Disability In Childhood-Craniopharyngioma Survivors After Follow-up - Results Of The Hit-Endo Study
Authors: Boekhoff Svenja , Eveslage Maria , Beckhaus Julia , Friedrich Carsten , Muller Hermann Lothar
Published: October 2023

Disclosure: S. Boekhoff: None. M. Eveslage: None. J. Beckhaus: None. C. Friedrich: None. H.L. Muller: None.

Craniopharyngiomas are rare low-grade embryonic malformational tumors of the sellar/parasellar area. After a diagnosis during childhood and adolescence, endocrine and hypothalamic long-term sequalae affect the prognosis. Financial resources for psychological rehabilitation and involvement of craniopharyngioma survivors are made available by a legal status of the degree of disability (GdB), according to the German Social Code Book V. This study analyzed the relationship between clinical/psychosocial traits and quality of life (QoL) measures and the resulting GdB. The HIT-Endo study included pediatric craniopharyngioma patients (%lt;18 years of age at the time of diagnosis) and diagnosed before the year 2000. The GdB was evaluated in a cohort of 108 patients following a median follow-up time of 16 years. The GdB at follow-up was evaluated in relation to endocrine, ophthalmological, neuropsychological, and psychosocial factors. 44 patients (41%) did not receive a GdB, three patients (3%) received a GdB of 30-40, 43 patients (40%) a GdB of 50-90 and 18 patients (17%) the maximal GdB of 100. Higher GdB was associated with lower levels education, higher body mass index (BMI SDS), more severe visual impairment, and hypothalamic involvement of the tumor. Patients with a GdB of 100 reported impairments in social and occupational settings, as well as loss of physical and cognitive function, fatigue, dyspnea, and pain problems. In addition, they performed worse on the German Daily Life Ability Scale (FMH) than individuals with lower GdBs. The GdB reflects the long-term effects of craniopharyngioma during childhood and adolescence and is linked to physical and psychosocial problems. A low functional capacity, as measured by FMH scale, may indicate the eligibility for a higher GdB of craniopharyngioma survivors.

Presentation: Thursday, June 15, 2023
THU226 Pituitary Hyperplasia With Optic Chiasm Compression Secondary To Levothyroxine Non-adherence In An Adolescent Patient
Authors: Hawco Cassandra , Bursztyn Lulu , Gallego Patricia , Van Uum Stan
Published: October 2023

Disclosure: C. Hawco: None. L. Bursztyn: None. P. Gallego: None. S. Van Uum: None.

Background: Pituitary hyperplasia is a rare complication of primary hypothyroidism in pediatric patients. There have been multiple reports of unnecessary surgical procedures for this medically treatable condition. Clinical Case: A 16-year-old female was referred for pituitary enlargement. She had presented to a community hospital following an unwitnessed syncopal event, complicated by retrograde amnesia and headache. At the age of 2 she was diagnosed with primary hypothyroidism during work up for similar syncopal episodes. Past medical and developmental history was otherwise non-contributory. She had a long-standing history of medication non-compliance, and had not taken Levothyroxine during the previous 11 months. On her presentation to hospital, a CT scan revealed pituitary enlargement with a hypodensity suspicious for hemorrhage. Pituitary panel was significant for TSH greater than 1000 (0.51-4.30) mIU/L, free T4 of 4 (13-21) pmol/L and Prolactin 98 ng/mL (<25) ng/mL. She was subsequently transferred to our tertiary care pediatric hospital for admission and ongoing care. An MRI of the sella identified a 1.0 x 2.3 x 1.7 cm pituitary mass with suprasellar extension and mass effect on the optic chiasm and nerves. There was no associated hemorrhage. The thyroid gland was diffusely enlarged. Visual acuity was 20/60 in both eyes at the time of hospital admission, compared to 20/20 the previous week at her optometrist. Formal visual field testing was abnormal, but unreliable with no clear defects. She was initiated on Levothyroxine 100 mcg daily and closely monitored for adherence and symptom resolution. After two months on this dose, repeat MRI sella showed a decrease of the pituitary mass to 0.8 x 2.1 x 1.0 cm in size, consistent with a diagnosis of pituitary hyperplasia secondary to untreated primary hypothyroidism. After treatment for 3 months, her visual acuity returned to 20/20 in both eyes with normal visual fields. With ongoing adherence to medical therapy, she remained clinically euthyroid with further decrease in her pituitary size, and normalization of both thyroid indices and prolactin[SV1]. Conclusion: This case is a rare presentation of pituitary hyperplasia in the setting of treatment nonadherence in primary hypothyroidism. It emphasizes the importance of monitoring for signs and symptoms of pituitary enlargement when low or non-adherence for levothyroxine treatment is suspected. The resolution of pituitary enlargement with Levothyroxine treatment also reinforces that this condition is best managed medically, avoiding unnecessary surgical procedures.

Reference: (1) Sapkota, S., Karn, M., Sapkota, S. Pituitary hyperplasia in childhood primary hypothyroidism: a review. Childs Nerv Syst. 2021;37;749-762. [SV1]

Presentation: Thursday, June 15, 2023
THU228 Thyrotoxic Periodic Paralysis In Three Adolescent Males
Authors: Ra Esther , Austin Juliana
Published: October 2023

Disclosure: E. Ra: None. J. Austin: None.

Thyrotoxic periodic paralysis (TPP) is a rare but potentially fatal complication of hyperthyroidism associated with Graves disease. Paralysis is due to hypokalemia caused by overactivation of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase). TPP is usually seen in males between 20 - 40 years of age who are of Asian descent. We report 3 Hispanic American adolescent males, as young as 13 years old, who presented with TPP without an existing diagnosis of Graves disease. All three presented with leg weakness and were found to be hypokalemic and ultimately diagnosed with hyperthyroidism. Each patient was supplemented with potassium, either intravenously or orally, with their symptoms resolving within 24 hours. Although TPP is most prevalent in Asian adult males, theorized to be due to an underlying genetic preposition related to a variant of the KCNJ18 gene, there are increasing reports of non - Asian adolescents presenting in TPP. Therefore, pediatric care providers should consider TPP in their differential if a patient presents with weakness and hypokalemia, even without a pre-existing diagnose of hyperthyroidism.

Presentation: Thursday, June 15, 2023
THU236 Mild Asymptomatic Hypercalcemia Secondary To A Novel Calcium-sensing Receptor Mutation
Authors: Tarkoff Joshua
Published: October 2023

Disclosure: J. Tarkoff: None.

Background: Familial hypocalciuric hypercalcemia (FHH) is a rare cause of mild hypercalcemia that is usually secondary to heterozygous mutations of the calcium-sensing receptor (CaSR) with autosomal dominant inheritance. The distinction between this entity and primary hyperparathyroidism can be difficult. Clinical Case: A 15-year-old female presented to the endocrinology clinic for an incidentally found elevated total calcium of 10.9 mg/dl (8.9-10.4) and elevated ionized calcium 5.5 mg/dl (4.8-5.3 mg/dl). Her labs at that time also showed a PTH of 29 pg/mL (12-71) and phosphorus 3.5 mg/dl (2.5-4.5 mg/dl). She denied any symptoms of hypercalcemia and there is no reported family history of mineral disorders or fractures. She does not take any medications. Her physical exam was unremarkable. Our evaluation showed calcium 10.5 mg/dl, phosphorus 4 mg/dl, magnesium 2.2 mg/dl (1.5-2.5 mg/dl) 25-hydroxyvitamin D 32 ng/ml (30-100 ng/ml), fractional excretion of calcium (FeCa) based upon spot urine sample = 0.0104, TSH 1.29 mIU/L (0.5-4.3 mIU/L), alkaline phosphatase 79 U/L (45-150 U/L), and normal renal function. Given her spot FeCa being <0.02, sequencing of the CASR gene was offered to the family because of potential overlap of her FeCa with primary hyperparathyroidism for which the treatment would be surgical (1). Commercial genetic testing was notable for a previously unreported heterozygous nonsense mutation, c.3001C>T (p.Gln1001X). It is expected to disrupt the final 78 amino acids of the protein in its intracellular domain and may play a role in preventing downstream signaling. At follow-up without treatment, her calcium has ranged between 10-10.9 mg/dl and she remains asymptomatic. Clinical lesson/conclusion: Hypocalciuria in the setting of hypercalcemia should raise the suspicion of FHH even without family history. Genetic testing of the CaSR is a crucial step in facilitating the diagnosis of FHH, especially given the importance of distinguishing it from primary hyperparathyroidism.

Reference: (1) Christensen, S.E., Nissen, P.H., Vestergaard, P., Heickendorff, L., Brixen, K. and Mosekilde, L. (2008), Discriminative power of three indices of renal calcium excretion for the distinction between familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a follow-up study on methods. Clinical Endocrinology, 69: 713-720.

Presentation: Thursday, June 15, 2023
THU238 Experience In Transition From Pediatric To Adult Care In Chronic Endocrinological Pathology
Authors: Tormo Silvina , Kastelic María Sofía , Forclaz Maria Veronica , Varela Silvana Anabella , Giacoia Evangelina
Published: October 2023

Disclosure: S. Tormo: None. M.S. Kastelic: None. M.V. Forclaz: None. S.A. Varela: None. E. Giacoia: None.

Introduction: Advances in medicine in recent decades have increased the survival of pediatric patients with complex chronic pathologies who reach adulthood. Transition refers to the process followed by young persons with chronic conditions to transfer health care, in our case from the pediatric endocrinologist to the adult endocrinologist. It is a dynamic, complex process and must be planned considering medical, psychosocial and educational needs of the adolescent in the change of care that implies an increase in autonomy. ObjectivesPrimary: describe the demographic characteristics of the population that attended the transitional endocrinology clinic. Secondary: evaluate the result of the TRAQ.5.0 survey (Transition readiness assessment questionnaire) in this population. Material and methods Design: observational, cross-sectional and analytical study. The medical records of 155 patients over 15 years old in follow-up for chronic endocrinological diseases in the transition clinic from November 2018 to August 2022, were analyzed. The patients underwent the TRAQ questionnaire validated in Argentina. Statistical Analysis: Quantitative variables are presented with medians and range and qualitative variables with absolute and relative frequencies. The comparisons between the subgroups were made through the Mann Whitney test, considering a p value <0.05 as statistically significant. Results: 155 patients with a median age of 20 years (r:15-30 years) were included. Most were women (61%). 75 % were derived from pediatrics at our hospital. 81% of them attended accompanied. 98% of the patients completed the Questionnaire (TRAQ). No statistically significant changes were found in the TRAQ score according to sex, age and whether the patients were accompanied or not. 79.8 % of the patients stated that they were studying at the time of follow-up, 11% of patients work. 15% (24 patients) were transferred to adult clinics, of which 87% continue follow-up. 80% of non-transferred patients continue follow up. When comparing the TRAQ questionnaire between the transferred patients and those who continue in follow-up, we found significant differences in medication management with a median of 3.6 in the referred group and 3.1 in the follow-up group p: <0.03, and appointment attendance: with a median of 3 in the referred group, 2.3 in the follow-up group (p < 0.01) Conclusions: The goal of the transition is to reduce loss of follow-up and improve the quality of life of patients through an orderly process. We highlight the usefulness of certain tools, such as the TRAQ questionnaire to assess the preparation of patients for the transition.

Presentation: Thursday, June 15, 2023