bluuebunny/crossref_metadata_2025 huggingface dataset:
PSUN343 Ectopic Prolactinoma in the Bony Clivus: A Common Disease in an Uncommon Location
Authors: Eisenberg Yuval , Pradeep Pallavi
Published: November 2022

Introduction

Ectopic prolactinoma has previously been reported and may be found in various locations, including sphenoid sinus, cavernous sinus, suprasellar region, nasopharynx, and rarely the clivus. We report a case of prolactinoma without any evidence of adenoma in the pituitary, which was subsequently found to be located to be in the bony clivus, after 36 years of initial presentation.

Case Description

A 66-year-old woman was seen in the clinic for known history of hyperprolactinemia. She was first diagnosed at the age of 30 when she presented with headaches, irregular menstrual cycles, and galactorrhea. MRI Pituitary at that time was not suggestive of a pituitary adenoma. She was thought to have a microadenoma not visualized on imaging and was only treated with dopamine agonist therapy for 2-3 years at that time. Presently, she complained of mild headaches intermittently but denied any symptoms of galactorrhea. Physical examination, including visual field testing, was unremarkable. Lab tests were suggestive of elevated prolactin levels, which had increased to 171ng/ml as compared to 121 ng/ml a year ago (RR: 3.3- 26.7 ng/ml). Chemistry panel, thyroid function test were in the normal range. Given uptrending prolactin levels, MRI Pituitary was repeated, which showed normal pituitary gland for age, and an enhancing mass with intermediate T1 and T2 signal in the bony sella measuring 1.4×1.1×1.5 cm, previously measuring 1.3×1.1×1.2 cm (3y ago), with loss of the normal bony cortex abutting the pituitary gland. Pt subsequently underwent endoscopic transsphenoidal biopsy of the clival lesion. Histopathology and immunochemical staining results showed findings consistent with pituitary adenoma, prolactinoma.

Discussion

Ectopic pituitary tissue, as well as prolactinoma, have been reported at various locations along the migratory path of the pituitary gland. The craniopharyngeal canal, which provides the opening for oral ectoderm, which is also known as Rathke's pouch, to migrate superiorly into the sella, leaves a bony layer separating the intracranial sella turcica from the extracranial sinuses and nasopharynx. Growing mass in the bony sella, as seen in our patient, is concerning for several rare pathologies with malignant potential, hence requiring biopsy. Tumors of the clivus constitute less than 1% of all intracranial neoplasms- which include chordoma, lymphoma, metastatic carcinoma, chondrosarcoma, meningioma, craniopharyngioma, germ cell tumor, astrocytoma, and pituitary adenoma. Less than 15 cases of clival ectopic prolactinoma have been reported in the past.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF13 | PMON142 Long Non-coding RNAs in Pituitary Differentiation and Endocrine Function
Authors: Camper Sally , Brinkmeier Michelle L , George Akima S , Melamed Philippa , Cheung Leonard Y M
Published: November 2022

Mammalian genomes contain thousands of genes for long non-coding RNA (lncRNAs) that affect the expression of other genes through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced and polyadenylated, but they are not translated into proteins. Nuclear lncRNAs modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins. Not much is known about the role of lncRNA in pituitary gland differentiation and function, but there are several examples that provide a strong premise for investigating this class of transcripts more deeply. For example, the lncRNA MEG3 is a tumor suppressor that is silenced in non-functioning pituitary adenomas; and lncRNAs have been implicated in regulating the function of key transcription factors such as POU1F1, PITX1, and PITX2. To develop a research resource for the study of lncRNA, we used cell-type specific cre transgenes to tag individual adult pituitary cell types with fluorescent markers and enriched for thyrotropes, gonadotropes and somatotropes using fluorescence activated cell sorting. We determined the transcriptome of each cell population using RNA sequencing and mined the data for lncRNA. We detected hundreds of lncRNA in adult pituitary cells, and some were cell-type specific, and located in immediate proximity of genes that encode pituitary hormones or lineage-specific transcription factors. We discovered that the lncRNA Nr5a1os is enriched in gonadotropes, while Foxl2os is enriched in gonadotropes and thyrotropes. The lncRNA Platr9 is located on the opposite strand near Cga, which encodes the alpha subunit of thyrotropin and gonadotropin. We also mined transcriptome data from pituitary glands collected at embryonic days 12.5 and 14.5 and identified 351 unique lncRNAs, many of which are exclusively expressed during development. Among these is Six3os1, which is located upstream of Six3, a gene associated with holoprosencephaly and hypopituitarism. The location of many of these lncRNAs suggests that they may have a cis-acting regulatory role in pituitary development or physiological function. This research resource sets the foundation for examining the actions of lncRNAs on expression of nearby genes during development and in response to physiological demand. Future research will elucidate their mechanisms of action, determining whether they recruit regulatory proteins to the chromatin and/or form R-loops in these regions, and how this affects expression of the target gene(s). We expect these studies to further our understanding of pituitary biology.

Presentation: Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF25 | PMON50 Insight into Integrated Control of Pituitary Function Revealed Through Analysis of Musashi Target mRNAs
Authors: Lim Juchan , Banik Jewel , Urbaniak Alicja , Bronson Katherine , Tomlinson Sophia , Hardy Linda , Gies Allen , Byrum Stephanie , Wilczynska Ania , MacNicol Melanie , Childs Gwen , MacNicol Angus
Published: November 2022

The anterior pituitary controls growth, metabolism, reproduction and stress responses through the synthesis and secretion of specific hormones. Distinct cell lineages within the anterior pituitary generate specific hormones. Interestingly, the anterior pituitary exhibits a high level of adult cell plasticity that allows committed hormone-producing cells to alter their cell fate and produce different hormones to meet altered organismal demands. The molecular mechanisms underlying this adult cell plasticity have not been fully characterized. Our recent work has implicated the stem cell determinant and sequence-specific mRNA binding protein, Musashi, as a regulator of pituitary cell plasticity. The mechanisms by which Musashi controls pituitary cell plasticity are unknown. In this study, we have sought to identify the mRNA regulatory targets of Musashi in the adult mouse pituitary. Through the use of Musashi-RNA-immunoprecipitation we report a cohort of 1192 pituitary mRNAs that specifically interact with Musashi. mRNAs specific to each of the hormone-producing cell lineages were identified, as well as mRNAs specific to immature stem and progenitor cell lineages. The biological pathways encoded by the Musashi-enriched mRNAs include cell adhesion, cellular homeostasis, unfolded protein responses, protein trafficking, endocrine processes and female pregnancy. Functional analysis of validated mRNAs reveals both activating and inhibitory control of mRNA translation by Musashi. Together, our findings indicate a broad and complex role for Musashi in the post-transcriptional regulation of adult pituitary function.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:58 p.m. - 1:03 p.m.
PMON184 Ligand-dependent interaction between phosphatidylcholine transfer protein and PPARδ: therapeutic implications for metabolic syndrome
Authors: Druzak Samuel , Tardelli Matteo , Mays Suzanne , Bejjani Mireille , Cato Micheal , Tillman Matthew , Cohen David , Mo Xiulei , Fu Haian
Published: November 2022

Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is a soluble lipid binding protein that transports phosphatidylcholine (PC) between cellular membranes. PC-TP knockout mice are more sensitive to glucose and insulin, have increased beta oxidation and improved liver health compared to wild-type mice. To better understand the protective metabolic effects associated with PC-TP deletion, we investigated how hepatic PC-TP affects lipid metabolism, sensitivity to glucose and insulin, and energy homeostasis in a mouse model of diet-induced obesity. We generated a liver-specific PC-TP knockout mouse (L-Pctp-/-), which gains less weight and accumulates less liver fat compared to wild-type mice when challenged with a high fat diet. Hepatic deletion of PC-TP also reduces levels of triglycerides and phospholipids in skeletal muscle, suggesting that PC-TP in the liver influences lipid metabolism in the muscle. Gene expression analyses suggest that the observed metabolic changes are related to transcriptional activity of peroxisome proliferative activating receptor (PPAR) family members. An in-cell protein complementation screen between lipid transfer proteins and PPARs uncovered a novel, direct interaction between PC-TP and PPARδ that was not observed for other PPAR family members. We confirmed the PC-TP-PPARδ interaction in Huh7 hepatocytes, where it was found to repress PPARδ-mediated transactivation. Mutations of PC-TP residues implicated in PC binding and transfer combined with a reduction of exogenously supplied lipids through serum starvation relieves PC-TP mediated PPAR repression. Together our data points to a ligand sensitive PC-TP– PPARδ interaction that suppresses PPAR activity.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSUN235 Dopamine-induced polyuria
Authors: Dejhansathit Siroj , Patel Anupa
Published: November 2022

Background

Dopamine acts on dopamine-1 receptors in the renal vasculature at a low dose, resulting in natriuresis and diuresis. Polyuria is a rare condition found in patients who receive dopamine infusion. We report a young female hospitalized for ovarian torsion who underwent several surgical procedures had been infected with gram-negative bacteremia. She received a dopamine infusion for hypotension with relative bradycardia. Subsequently, she developed polyuria.

Case presentation

A 25-year-old female was referred to UMC hospital for acute diverticulitis with micro-perforation from the sigmoid colon. She presented to the outside hospital with abdominal pain, fever, nausea, and vomiting for four days. On arrival, she had a fever of 101.9F. Initial laboratory showed leukocytosis and lactic acidosis. CT abdomen at UMC revealed 16×11cm mass in the left lower quadrant, potentially originating from the left ovary. The patient was treated with IV Zosyn for acute diverticulitis. On day 5 of admission patient remained to have abdominal pain, fever, and worsening lactic acidosis. She was taken to OR for exploratory laparotomy with dissection of left salpingo-oophorectomy for torsion of adnexal mass resection. On day 91 of admission, the patient developed low-grade fever (100.7F) and hypotension (BP 63/30) with the MAP of 40. IV NS 1L was administered. CT abdomen revealed no intra-abdominal or pelvic abscess or fluid collection. For possible septic shock, the patient was started on empirical IV antibiotics. Despite IV fluid resuscitation, blood pressure remained low, vasopressin and norepinephrine were initiated. Day 92, she developed new-onset bradycardia, EKG showed third-degree AV block. IV dopamine infusion was started at the rate of 5mcg/kg/min. During dopamine infusion, the patient voided between 400-600mL/h. Over the 12-h period, the urine output was about 5L. Endocrinology was consulted for polyuria. Laboratory studies showed urine osmolality 384mOsm/kg, urine electrolytes were UNa 130mmol/L, UK 20.1mmol/L, UCl 115mmol/L, BUN/Cr 28/1.0.

Approaching polyuria, the diuresis was associated with high urine osmolality and sodium, which exhibited characteristic features of solute diuresis with natriuresis. The diuretic phase of acute renal injury could not be implicated in this patient since she has stable renal function without azotemia. There was no evidence of urinary tract obstruction to suggest post obstruction diuresis. Central or peripheral diabetes insipidus was ruled out by the lack of characteristic water diuresis. It was suspected that the diuresis was related to the dopamine infusion. Thus, dopamine infusion was discontinued. The urine output dropped within a few hours. The patient's urine output stabilized to 0.8-1.0ml/min. The striking drop in urine output after discontinuity of dopamine is consistent with the role of dopamine in this patient's diuresis.

Conclusion

This is a rare case report of dopamine-induced polyuria in septic shock patient.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBMON199 Peripheral Blood Mononuclear Cell Mitochondria Function Differs In Adolescent Transgender Males By Gnrha Use
Authors: Fuller Kelly , Nokoff Natalie , Keller Amy , Staggs Syd , Cree-Green Melanie , Moreau Kerrie
Published: November 2022

Background

About 2% of youth in the United States identify as transgender, meaning their gender identity differs from sex at birth. The Endocrine Society recommends gonadotropin-releasing hormone agonist (GnRHa) therapy for eligible individuals starting at Tanner 2 to halt endogenous pubertal progression, and later testosterone or estradiol treatment. Studies in animals and cisgender adults have shown that sex hormones influence whole-body metabolism and mitochondrial function, but most of the literature has focused on sex differences and the impact of menopause in females. Little is known about the impact of puberty blockade and gender-affirming hormone therapy on metabolic health in transgender youth.

Methods

For this pilot study, transgender males (TGM) aged 14-17 were recruited (n=16) with an assessment prior to initiation of testosterone therapy. Measures of metabolic health (body mass index [BMI], weight, exercise capacity via peak oxygen uptake [VO2 peak]) and hormone status (use of GnRHa, circulating sex hormone levels) were collected. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood via density-gradient centrifugation and mitochondrial function (maximal respiratory capacity [States 2, 3, 3s, 4, uncoupled] and respiratory control ratio [RCR]) was measured via high-resolution respirometry under carbohydrate (CHO) and lipid substrates. Participants were stratified by GnRHa use for analysis.

Results

Eight TGM were on GnRHa (average duration of use of 25.3+13.1 months). As expected, individuals taking GnRHas had significantly lower luteinizing hormone (LH; p=0. 03), follicle stimulating hormone (FSH; p<0. 01) and estradiol (p<0. 01) compared to those not on GnRHa. BMI, body weight, and VO2 peak were not different by GnRHa status. PBMC respiration differed between groups; those on GnRHa had higher ADP-stimulated State 3 respiration (p=0.11 CHO, p=0. 06 lipid) and RCR (p<0. 01 CHO, lipid) and lower basal State 4 respiration (p=0. 01 CHO, p=0. 01 lipid). Further, FSH and estradiol were negatively correlated with RCR (all p≤0. 05; Pearson's R -0.5 to -0.7), a finding consistent across both substrate experiments.

Conclusion

TGM youth on GnRHa had higher PBMC mitochondrial RCR compared to TGM not on GnRHa. These RCR data, combined with lower basal and greater ADP-stimulated respiration likely represents either an advantageous mitochondrial profile in youth using GnRHa or a compensatory increase in response to estrogen suppression. Our correlation data suggest these differences are related to the absence of estradiol and FSH rather than metabolic outcomes traditionally thought to impact respiratory capacity. Future interventional investigations are needed to evaluate the impact of GnRHa in transgender youth and should target physiological mechanisms underlying this preliminary finding.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP081 The Relationship Between Body Mass Index Changes And Bone Age Progression During Gonadotropin-releasing Hormone Agonist Treatment In Girls With Idiopathic Central Precocious Puberty
Authors: Kim Seulki , Shin Chungwoo , Choi Young J , Jang Min Jeong , Kim Sungeun , Ahn Moon Bae , Hee Kim Shin , Cho Won Kyung , Cho Kyung Soon , Jung Min H , Suh Byung-Kyu
Published: November 2022

Purpose

To analyze the relationship between body mass index change and bone age progression during gonadotropin-releasing hormone agonist(GnRHa) treatment in girls with idiopathic central precocious puberty Methods: 65 girls with idiopathic central precocious puberty who are treated with GnRHa more than 2 years were retrospectively reviewed. Height, weight, Tanner stage, bone age were measured every 6 months from the start of treatment. The degree of obesity was evaluated using the body mass index (BMI) standard deviation score (SDS), and the relationship between the change in obesity and the progression of bone age was analyzed. Overweight was defined as a BMI greater than or equal to the 85th percentile. The chronological age at the start and the end of treatment was 7. 00±0. 00 years and 10.63±0.50 years in the overweight group (16 patients), and 6.86±0.35 years and 10.71±0.54 years in the other group (49 patients), respectively.

Results

There was no difference in bone age between the normal weight group and the overweight group at the start of treatment (9.85±0.57 years vs 10. 04±0.73 years, P=0.263). Bone age was higher in the overweight group, but after 1 year of treatment, 2 years of treatment, and at the end of treatment, the overweight group had a higher bone age than the normal weight group (10.47±0.56 years vs 10.87±0.57 years, P=0. 02; 11. 06±0.47 years vs 11.46±0.51 years, P=0. 004; 11.70±0.46 years vs 12. 01±0.52 years, P=0. 03). Bone age at the end of treatment was related to overweight at the start of treatment (r=0.265, P=0. 03) and the increase in BMI SDS from normal to overweight during treatment (r=0.285, P=0. 02). There were 11 children (17%) whose BMI SDS increased from normal to overweight during treatment, compared with the other patients, there was no difference in bone age during 2 years of treatment, but bone age at the end of treatment was higher (12. 09±0.60 years vs 11.71±0.47 years, P=0. 02), and the difference in bone age before and after treatment was also greater (2.31±0.68 years vs 1.79±0.52 years, P=0. 01). Linear regression analysis demonstrated that the increase in BMI SDS from normal to overweight during treatment had a positive correlation with bone age at the end of treatment (β=0.31, R2=0. 07, P=0. 03).

Conclusion

In girls with central precocious puberty, an increase in obesity from normal to overweight during GnRHa treatment does not affect bone age progression until 2 years from the start of treatment, but might be a risk factor for bone age progression at the end of treatment.

Presentation: No date and time listed
LBODP083 Pharmacokinetics Of Metformin In Obese Non-diabetic Youth: Drug Clearance Increases With Severity Of Obesity
Authors: Halpin Kelsee , Hosey Chelsea , Paprocki Emily , De Luca Francesco , Yan Yun , Steven Leeder J
Published: November 2022

Background

Severe obesity and obesity-related conditions, such as prediabetes, are increasing in prevalence among pediatric populations. Metformin is an oral biguanide that is often used off label to treat obesity and prediabetes in youth. Despite increased prescribing in youth, there is limited knowledge about pharmacokinetics (PK) of metformin in pediatric populations, and no published data describing the effect of obesity severity on metformin PK.

Research Questions What is the variability of pharmacokinetic properties of immediate release metformin in obese, non-diabetic adolescents? Does severity of obesity impact these properties?

Methodology

Youth 12-17 years of age were included if they were obese with laboratory evidence of insulin resistance (HOMA-IR > 3) or met ADA criteria for prediabetes and had a normal renal function (GFR > 60 mL/min/1.73m2). Obesity classes were defined as class I (BMI > 95th to < 120% of the 95th percentile), class II (> 120% to < 140% of the 95th percentile), and class III (> 140% of the 95th percentile). Youth were treated with immediate release metformin dosed twice daily for at least 6 weeks. Pill diaries and pill counts were conducted to assess adherence. Youth arrived fasting and received their AM dose of metformin with a standardized meal. Blood was drawn pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose and urine collected throughout the visit. Primary outcomes included the mean, standard deviation, and range for steady state area under the plasma drug concentration-time curve adjusted for dose (AUCss_D) and apparent oral clearance at steady state (CLss/F). These outcomes were compared between obesity classes. MAJOR RESULTS There were 11 subjects (10 females), mean (SD) age was 14.3 (1.8) years. Metformin doses included: 1000mg BID (N=8), 500mg qAM 1000mg qPM (N=2), 500mg BID (N=1). Mean (SD) weight was 102.8 (19.2) kg, and mean BMI 37.5 (3.3) kg/m2. Among participants, there were N=4 with class III obesity, N=4 with class II obesity, and N=3 with class I obesity. Across all study participants, mean AUCss _D was 12.5 (SD 2.46; range 8.48-16.9) h*ng/mL/mg and mean CLss/F was 85.7 (SD 16.6; range 59. 0-118) L/h. Mean CLss/F was 76.8, 83.6, and 86.2 L/h in class I, II, and III obesity, respectively. Mean AUCss _D was 13.5, 12.17, 12.14 h*ng/mL/mg in class I, II, and III obesity, respectively. No differences were statistically significant.

Conclusions

Our pilot data suggest a 2-fold variability in apparent clearance among study participants, with apparent clearance increasing in relation to obesity severity class. Greater clearance, and thus reduced systemic exposure (AUC), may indicate a need for a larger dose of metformin in severely obese youth. Additional data is needed to further evaluate the impact of the severity of obesity on metformin clearance.

Presentation: No date and time listed
LBODP086 An Unusual Infant Case Of Gastric Volvulus Presenting With Dumping Syndrome
Authors: Lee Dahye , Choe Yunsoo , Lee Yun Jeong , Shin Choong H , Lee Young A
Published: November 2022

An 18-day female infant, born preterm small for gestational age (SGA), developed fasting hypoglycemia. A critical sample revealed an insulin level of 4.7 μIU/mL at the time of hyloglycemia (39 mg/dL) without ketoacidosis. Diazoxide therapy was started under the impression of transient neonatal hyperinsulinemia related to SGA, however, hypogycemia was developed on the 21st day of life. Targeted next generation sequencing (NGS) was performed for possible congenital hyperinuslinism. During octreotide therapy, postprandial hyperglycemia was incidentally detected at 27 days. Continuous glucose monitoring (CGM; Dexcom G6, San Diego, California) revealed postprandial hyperglycemia and subsequent hypoglycemia suggestive of dumping syndrome, although she had no prior history of surgery. An upper gastrointestinal series revealed the anomalous rotation of the stomach along the mesenteroaxial axis perpendicular to its longitudinal axis, implying gastric volvulus. The possibility of dumping syndrome caused by gastric volvulus was confirmed by stable glucose level in the euglucemic range using CGM after continuous nasojejunal feeding. She received laparoscopic gastropexy to anchor the stomach. Euglycemia was maintained after surgery and octreotide therapy was successfully discontinued. NGS identified no pathogenic variant for congenital hyperinsulinism. At 8 months of age, she exhibited catch-up growth and normal development. This is the first infant case of gastric volvulus presenting with dumping syndrome during diazoxide therapy for transient neonatal hyperinsulinism.

Presentation: No date and time listed
LBODP087 Unusual Presentation Of Salt-wasting 3-beta-hydroxysteroid Dehydrogenase-2 Deficiency
Authors: Vidal Katherine , George Anu Skaria , Morand Megan , Cooney Erin , Lee Phillip D K
Published: November 2022

Background

Biallelic pathogenic variants of HSD3B2 cause 3-beta-hydroxysteroid dehydrogenase-2 (3BHSD2) deficiency. 3BHSD2 is a rare cause of congenital adrenal hyperplasia (CAH) with two presentations in infancy including salt-wasting and a non-salt wasting with variable virilization of females and undervirilization of males (1). The salt-wasting form is usually not detected on newborn screen (NBS) and often presents with a potentially fatal adrenal crisis. We report a case of salt-wasting 3BHSD2, initially diagnosed as salt-wasting 21-hydroxylase deficiency following an abnormal newborn screen. Clinical case: A now 5.3 year old female was born at term, birthweight 3.44 kg, with no known pregnancy or neonatal problems. The first NBS at two days old was normal. The second NBS at 16 days old showed very high 17-hydroxyprogesterone (17OHP). She was clinically healthy with mild labial hyperpigmentation and rugation, and her clitoris was 1 cm in length. However, she had low sodium, elevated potassium, and elevated 17OHP with Na 127 mmol/L (RR 134-144), K 9.1 mmol/L (RR 3.5-5.2), and 17-OHP 5440 ng/dL (HPLC-MS/MS; RR 7-106). Glucocorticoid and mineralocorticoid replacement was initiated. She remained healthy with suppressed 17OHP and renin and full regression of virilization led to suspicion of the presumptive diagnosis of 21-hydroxylase deficiency. At 3 to 4 years old, CYP21A2 and CYP11B1 analyses were both resulted normal. At 4.5 years old following a two day therapeutic withdrawal test, her labs were as follows: ACTH 1940 pg/mL (RR 7-63), 17OHP 147 ng/dL (RR <299), DHEA 7240 ng/mL (RR 50-995), 17-hydroxypregnenolone 10405 ng/dL (RR ≤280) and pregnenolone 1352 ng/dL (RR 15-125). Her electrolytes were normal and all other adrenal precursors were within the normal reference range. Her diagnosis has since been revised to 3BHSD2 deficiency. At the time of submission, genetic confirmation is pending.

Conclusion

This case illustrates the variable presentation of this rare condition, and the value of genetic testing in CAH. The cause of the transient 17OHP elevation and mild virilization is uncertain; however, a possible relationship to persistent fetal adrenal is postulated. References: (1) MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2020 Jun 24]. 3-beta-hydroxysteroid dehydrogenase deficiency; [updated 2020 Jun 18; reviewed 2018 Jun 01; cited 2020 Jul 1]; [about 5 p. ]. Available from: https://medlineplus.gov/genetics/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency/.

Presentation: No date and time listed
ODP381 Changes in Perceptions of Pediatric Endocrinologists (PE) and Urologists (PU) to Infants and Children regarding care of individuals with 46,XY DSD
Authors: Lee Peter , Gardner Melissa , Kogan Barry , Khorashed Behzad Sorouri , Suorsa-Johnson Kristina , Sandberg David
Published: November 2022

Introduction

Over recent decades, controversy regarding standards of care has contributed to questioning past management recommendations for infants and children with a 46,XY DSD. Surveys conducted in 3 waves (2003, 2010, 2020) provide evidence of changes in recommendations for care have changed over this period.

Methods

Online surveys of the members of the Pediatric Endocrine Society (PE) and Societies for Pediatric Urology (PU) included case vignettes representing partial androgen insensitivity syndrome (PAIS), micropenis resulting from primary testicular failure, and penile ablation (non-DSD). Survey items included questions regarding recommended gender of rearing (GoR), genital surgery (and timing), and disclosure of diagnostic details to patient.

Results

The newborn PAIS vignette included elevated LH and FSH and a 1.2 cm. phallus that increased to 1.7 after exogenous testosterone. Male GoR was chosen by 47, 55 & 55% PE and 81, 83 & 69% of PU in waves 1 to 3, respectively; 27 PE and 28% PU chose an added "non-binary" option in 2020. The recommendation that parents, rather than patients, should decide about perineal hypospadias repair was chosen by 70, 60 & 50% of PE and 93, 90 & 79% of PU. Recommending against surgery were 25, 22 & 10% PE and 23, 13 & 8% PU. Recommending surgery be completed at <1 year of age: 56, 59, 66% PE and 69, 78, 84% PU. Recommendation against disclosure of the underlying condition to the patient 12, 17 & 28% PE and 17, 19 & 22% PU, while 35, 28 to 32% PE and 34, 43 & 30% PU recommended that disclosure occur by 11 years of age. For the penile ablation vignette, 78, 92 & 92% PE and 98, 95 & 97% PU recommended male GoR. The 2020 non-binary option was chosen by 4 and 2% PE and PU. The majority of both groups recommended male GoR for the micropenis vignette with testicular failure; 94, 94 & 89% PE and 96, 97 & 88% PU. The decline in 2020 resulted from the recommendation of the non-binary option by 9% PE and 8% PU.

Conclusions

It seems clear that a female GoR recommendation is currently rare across 46,XY vignettes with evidence of testicular function during at least some of fetal life. It is also apparent that the current emphasis/controversy regarding GoR has resulted in confusion as to how to apply this poorly understood concept. The resulting shift of delaying decisions regarding surgery until the patient can decide is inconsistent with the recommendation that hypospadias repair occur before age 1 year. Finally, lack of or delayed disclosure is inconsistent with patient centered care recommendations.

Presentation: No date and time listed
ODP385 False Negative in the Screening for Congenital Hypothyroidism in Twin Newborns
Authors: Sejas Daniela Vargas , Dorado Juan Pablo Hayes , Claros Juan Carlos Portugal , Lopez Marco Antonio Rossell , Vargas Gerben Justiniano , Zuna Jasmani Gemio Anagua
Published: November 2022

Background

In the neonatal screening for congenital hypothyroidism, false negative cases can be recorded, as evidenced in some twin newborns of the same sex, presumably due to fetal blood exchange.

Clinical Case

Neonate obtained by caesarean section indicated for twin pregnancy. The newborn and his twin, both male, presented normal TSH values (<10 mlU/L) in the neonatal screening for congenital hypothyroidism; but in the second screening, routinely performed in newborns obtained from twin or multiple pregnancies, in the second week of life, a TSH level of 27 mlU/L was evidenced in the newborn; the free T4 value was analyzed and was found to be low. With the diagnosis of congenital hypothyroidism, therapy with levothyroxine was started.

Conclusion

It is important to carry out a second neonatal screening for congenital hypothyroidism in cases of multiple pregnancy, especially twins of the same sex, in the second week of life, to avoid possible false negatives TSH values.

Presentation: No date and time listed
ODP393 Pfeiffer syndrome with growth hormone deficiency in a 4-year-old girl
Authors: Bae AHN Moon , Jeong JANG Min
Published: November 2022

Backgrounds

Craniosynostosis syndrome has a variety of causes, one of which is an autosomal dominant disorder associated with FGFR1 or FGFR2 gene mutation known as Pfeiffer syndrome (PS; OMIM 101600). It is known that PS is clinically diagnosed, not genetic judgment. PS is divided into three subtypes depending on severity of specific phenotypes. Patients with PS type 1 are broad thumbs and great toes, brachydactyly or syndactyly. They have widely spaced eyes, midface hypoplasia and dental abnormalities but short stature is not typical phenotype of PS. We report the patient who were clinically diagnosed PS with short stature because of growth hormone deficiency (GHD). Case Report: A 4 years 7 month-old girl presented with a short stature below the 3rd percentile. She was born at 40 weeks of gestation with a birth weight of 2.9 kg. Her perinatal and neonatal histories were unremarkable. Her parents are non-consanguineous and her mother had micro- pituitary adenoma. She has healthy younger brother who aged 9 months old. In physical examination, height was 91.1 cm (-3.92 SDS), weight was 15.5 kg (-1.15 SDS). Wide thumb and great toes on both sides of her are observed. At the time of admission, bone age was advanced, measured 7 years. There were no specific findings other than a decrease in IGF-1 level (108.24 ng/ml) and increase in prolactin level (27.26 ng/ml) on the basic endocrine examination. The growth hormone (GH) induced stimulation test was performed after admission. She underwent GH induced stimulation test with combinations of 2 stimulants to assess GH secretion: levodopa 150 mg and arginine 0.5 g/kg. The peak GH level was 7.41 ng/ml in levodopa test and 5.58 ng/ml after 30 minutes’ response to arginine. She was diagnosed as a partial GHD defined by peak GH between 5 and 10 ng/ml in both test. There were no findings in karyotyping and chromosomal microarray. As a result of targeted panel sequencing of 233 genes related to hereditary short stature, c.2398dupT, a pathogenic variant that had not been previously reported in the FGFR2 gene, was observed in a heterozygous form as the cause of short stature. Subsequently, recombinant human GH has been administered in units of 0.1 per day according to her weight. The height was increased from 93.6 cm (SDS) in 4 years 10 months old to 98 cm in 5 years 2 months. Any side effects or adverse reactions were not observed during the treatment period.

Conclusion

It is suggested that a growth hormone test be performed for Pfeiffer syndrome patients with short stature. GH may help growth in patients with positive in the test.

Presentation: No date and time listed
ODP397 Small-volume, Subcutaneous, 6-month Leuprolide Acetate Effectively Reduces Growth Velocity to Prepubertal Levels in Children with Central Precocious Puberty
Authors: Klein Karen O , Atkinson Stuart N , Boldt-Houle Deborah M
Published: November 2022

Introduction

Clinical signs of puberty, growth rate, rate of bone maturation, luteinizing hormone concentrations and estimates of change in predicted adult height are the common variables for assessing efficacy of central precocious puberty (CPP) therapies. (1, 2) All clinical and laboratory parameters are essential when interpreting treatment response. (3) Preservation of adult height potential is an important goal of CPP treatment and accelerated growth velocity can contribute to reduced adult height. (4) We present secondary analyses of growth velocity data from the pivotal trial of the first small-volume, long-acting, subcutaneously administered GnRH agonist for central precocious puberty (CPP), approved in 2020. (5) Methods: 62 children (60 girls, 2 boys) with treatment-naïve CPP received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals. We measured standing height with a calibrated stadiometer at Baseline and Weeks 4, 12, 20, 24, 36, 44, and 48. Growth velocity (cm/year) was calculated as a change in height (cm) between visits/((number of weeks between visits)/52).

Results

Mean growth velocity decreased throughout treatment from 10.4 cm/year for the time period from screening to baseline to 6. 0 cm/year for Week 34 to 48. The proportion of children who achieved growth velocity 4-6 cm/year increased 2.5-fold from baseline (10%) to Week 48 (25%).

Conclusions

Subcutaneous leuprolide acetate effectively decreased growth velocity to prepubertal rates in children with CPP. Mean growth velocity from Week 24 to 48 was similar to what is seen in children of the same age without CPP (5.8-6.1 cm/year, depending on sex and race). (6) These data indicate that subcutaneous leuprolide acetate may increase adult height and improve the likelihood of achieving genetic target height range. References Cited 1. Klein KO, et al. Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty. JCEM. 2020. 2. Lee HS, et al. Increased final adult height by gonadotropin-releasing hormone agonist in girls with idiopathic central precocious puberty. PLoS One. 2018. 3. Klein KO, Lee PA. Gonadotropin-releasing hormone (GnRHa) therapy for central precocious puberty (CPP): Review of nuances in assessment of height, hormonal suppression, psychosocial issues, and weight gain, with patient examples. PER. 4. Chen M, Eugster EA. Central Precocious Puberty: Update on Diagnosis and Treatment. Paediatr Drugs. 2015. 5. FENSOLVI® (leuprolide acetate) for injectable suspension, for subcutaneous use [prescribing information]. 2020. 6. Kelly A, et al. Age-based reference ranges for annual height velocity in US children. JCEM. 2014.

Presentation: No date and time listed
ODP399 Growth Hormone Peak did not predict presence of Pituitary Stalk Interruption Syndrome
Authors: Kononowicz Julia , Muhaisen Fadi A , Mitre Naim
Published: November 2022

Background

Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary gland characterized by a triad of the thin or interrupted pituitary stalk, aplasia, or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary. This can be associated with midline defects and pituitary endocrine deficiencies, ranging from isolated growth hormone deficiency to combined pituitary hormone deficiency. PSIS is a rare entity with an estimated incidence rate of 0.5/1,000,000 births. Clinical case: A 3-year-old neurodevelopmentally appropriate male was initially seen at the PCP office for growth failure. After birth, the patient appeared to have normal growth parameters, as he was in the 61st percentile for length and at the 19th percentile for weight. His growth velocity trended downwards, as he dropped to the 34th percentile at nine weeks old and the 2nd percentile by nine months old. PCP records showed that the patient was at the 10th percentile for height at one year old, but by 18-months, he had fallen below the 1st percentile. His mid-parental height was 175cm, between 25th and 50th percentile. Initial workup showed elevated TSH 9.12 mIU/ml (0.5-4.3 mIU/mL) with negative thyroid antibodies, thus started on 25 mcg of levothyroxine. The screen for systemic disease and inflammatory markers was negative. Insulin-like growth factor 1 (IGF-1) was low at <16 ng/mL (24-148 ng/mL) and insulin-like growth factor binding protein-3 (IGFBP-3) was normal at 1.2mcg/ml (0.7-3.6)A growth hormone (GH) stimulation test was obtained due to suboptimal growth, short stature, and undetectable IGF-1 level. The patient failed his GH stimulation study with a GH peak of 5.1 ng/mL (>10) after clonidine and 2ng/ml (>10) after arginine. A clinical and biochemical diagnosis of GHD was made, an MRI was ordered to evaluate for anatomic cause. Brain MRI showed an ectopic posterior pituitary gland with an absent infundibulum, suggesting PSIS. The patient was started on GH therapy with excellent response. He is currently growing well on a low dose of somatropin, around 0.234mg/kg/week.

Conclusion

PSIS is a congenital pituitary anatomical defect with a heterogeneous presentation. It is typically encountered in infancy and childhood, possibly progressing to panhypopituitarism by adulthood. Diagnosis can be delayed, as brain MRI imaging is not always obtained based on growth hormone peaks. As seen in our patient, the severity of GHD based on peak levels did not adequately predict the presence of brain anomalies. Historically, severe GHD (<5 ng/mL) is strongly associated with brain MRI abnormalities, but GH levels may not suffice to determine the severity of the disease. Based on our findings, we recommend obtaining brain MRI in all patients diagnosed with GHD to identify critical anatomical abnormalities, like PSIS, that require long-term close monitoring of pituitary function.

Presentation: No date and time listed
OR05-3 Utility of Genomic work-up for 46XY Disorder of Sex Development Patients with Severe Hypospadias
Authors: Srivastava Priya
Published: November 2022

Background

Hypospadias is a common human congenital anomaly occurring in ∼1: 200 to 1: 300 live male births in the USA, with an unexplained doubling in incidence over previous decades. Historically, 46XY Differences of Sex Development (DSD) patients, with severe hypospadias have lacked a genetic diagnosis. With the advent of commercially available DSD genomic panels, this is now changing (GeneDX. Neonatal 46 2021, In-vitae 2021). The goal of this study is to review the anatomical characteristics of severe hypospadias that can accurately define patients that have 46XY DSD and to determine the practical utility of performing a genomic workup in these rare 46XY DSD patients with severe hypospadias.Patients: 14 patients seen in disorders of sexual development clinic between 2018–2020 with severe hypospadias defined by an ectopic urethral meatus typically in the scrotum or perineum, an abnormally small glans penis size (<14 mm at maximal width in the first year of life), severe curvature and associated foreskin fusion or penoscrotal transposition were enrolled in the study.

Methods

Patients who met the criteria for 46XY disorder of sexual development and severe hypospadias were offered a genomic work-up in consultation with pediatric genetics. Patients were identified through chart review. Data extracted included karyotype, hypospadias phenotype including stretched penile length at diagnosis, age at genetic diagnosis/genomic workup, gene defect/ pathologic variant, gender identity, and clinical course.Main Outcome Measurements: The main outcome measured was the presence of a genetic mutation that can be linked to the disorder of sexual development. Secondary outcomes measured included gender identity, clinical course, and histological findings if a biopsy was obtained.

Results

Of the 14 patients that underwent genomic analysis, 8 had documented pathologic variants known to cause hypospadias. Pathologic genetic variants include defects in the AR (3), SRD5A2 (1), NR5A1 (2), WT1 (1), and ARTX (1). Five had no evidence of pathologic variants based on the Invitae and GeneDx commercial 46XY DSD panel (see Table 2 for genes tested). One had a genetic variant of unknown significance, FREM2. The patient with WT1 was consequently found to have a Wilms tumor and the patients with SRD5A2 are now undergoing adrenal insufficiency surveillance after their genetic testing.

Conclusions

Patients with 46XY DSD and severe hypospadias can benefit from genetic evaluation as their underlying disorders may unveil mutations that could have potentially life-altering consequences and change surveillance and monitoring.

Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.
OR05-5 Body Mass Index (BMI) as a Predictor of Bone Mineral Density (BMD) in Gender Diverse Youth
Authors: Rodriguez Gonzalez Adriana , Witchel Selma , Pinto Bianca
Published: November 2022

Objective

GnRH agonists (GnRHa), used to prevent development of undesired secondary sex characteristics for gender diverse youth (GDY), may impede pubertal bone mineral accrual increasing the risk for osteopenia/osteoporosis during adulthood. Based on findings of low bone mineral density (BMD) scores (relative to natal sex) prior to GnRHa [1], we hypothesized BMD might be associated with body mass index (BMI) in GDY.Method: To test our hypothesis, we reviewed medical records for 27 GDY; 16 were designated female at birth (DFAB) and 11 were designated male at birth (DMAB). Age at presentation, gender identity, ages at initiation of GnRHa and gender affirming hormone treatment (GAHT), duration of GnRHa treatment prior to GAHT initiation, auxologic parameters including BMI, and lumbar spine BMD obtained from GE lunar IDXa dual-energy X-ray absorptiometry (DEXA) were extracted. Lumbar spine BMD was used for statistical analysis. Statistical analysis was performed with Microsoft Excel Analysis ToolPak. A linear regression model was used to determine significance of BMI and GnRHa as predictors of BMD Z-score using a significance level of 0.05. Legal gender marker was used to determine BMD Z-scores.

Results

BMI ranged from 16.93 kg/m2 to 35.79 kg/m2 (5th to the 99th percentile). DEXA scan results were available for 27 GDY with age range 10-25 years; mean age (±SD) was 17±3 years. BMD of the lumbar spine was obtained from 0-61 months (mean 30 ± 21 months) following initiation of GnRHa. Length of GnRHa treatment prior to GAHT initiation ranged from 0-53 months (mean 14 ± 12 months).Individuals were at different stages of the gender affirmation process including 1) No medical treatments, 2) GnRH agonist only, 3) GAHT only, and 4) combined GnRH agonist and GAHT. Using a linear regression model, length of GnRHa therapy and length of GnRHa without GAHT were not significantly associated with lumbar spine BMD in our sample (p = 0.44 and 0.29, respectively). Using a linear regression model, BMI was a significant positive predictor of higher lumbar bone mineral density (p = 0.03).

Conclusion

Sex hormone exposure during adolescence and young adulthood is essential for bone health. While GnRH agonists lower endogenous sex hormone exposure, in our sample, lower BMD was not associated with total duration of GnRHa therapy or duration of GnRHa treatment prior to GAHT. Rather BMD was positively associated with BMI regardless of gender affirming medical therapies. Limitations include small sample size, retrospective design, and the use of legal gender marker for normative values. The next step will be larger, prospective studies to identify predictors of low BMD in GD youth. This information will guide future management regarding BMD monitoring.References: 1. Lee JY,et al., J Endocr Soc. 2020;4(9): bvaa065.

Presentation: Saturday, June 11, 2022 12:30 p.m. - 12:45 p.m.