bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT601 The Role Of The Melanocortin System In Ovine Puberty
Authors: Aerts Eliana G , Griesgraber Max J , Thomson Ashleigh , Brown Malori , Seman Andrew , Bowdridge Elizabeth , Hardy Steven L , Goodman Robert L , Nestor Casey , Hileman Stanley M
Published: October 2023

Disclosure: E.G. Aerts: None. M.J. Griesgraber: None. A. Thomson: None. M. Brown: None. A. Seman: None. S.L. Hardy: None. R.L. Goodman: None. C. Nestor: None. S.M. Hileman: None.

The neural mechanisms that regulate the timing of puberty onset are not completely known. In several species, including sheep, puberty onset relies on an increase in gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion as a result of decreased sensitivity to estradiol (E2) inhibition. Additionally, it is unclear how E2 acts in the hypothalamus to inhibit GnRH/LH secretion, as GnRH neurons do not contain estrogen receptor alpha (ERα). Neurons within the arcuate nucleus (ARC) of the hypothalamus that contain kisspeptin, neurokinin B, and dynorphin (KNDy neurons) are critical for the generation of GnRH pulses and contain ERα. Data from our laboratory suggests that KNDy neurons, while critical, may be responding to other inputs that time puberty onset. Proopiomelanocortin (POMC) and Agouti-related peptide (AgRP) neurons in the ARC have been shown to contain ERα and provide input to KNDy neurons, which contain the melanocortin 3 and 4 receptor (MC3R, MC4R). The goal of this work was to assess POMC- and AgRP-positive cell numbers, input onto KNDy neurons, and neuronal activity changes in a puberty-specific manner. Female sheep were ovariectomized and given subcutaneous E2 implants at 5 months (prepubertal, n=4), 8 months (peripubertal, n=5), and 10 months (postpubertal, n=5) of age. Two weeks after surgery, blood samples were collected via jugular venipuncture every 12 minutes for 4 hours and assessed for LH. The sheep were then sacrificed and hypothalamic tissue was perfused, collected, and prepared for staining. The tissue was assessed via immunohistochemistry for POMC, AgRP, kisspeptin, NKB, and c-Fos, a known marker of neuronal activity. Pulsatile LH secretion was, as expected, reduced at 5 months and highest at 10 months. ARC POMC cell numbers did not significantly change over development (p>0.10). The number of ARC POMC close contacts onto ARC kisspeptin neurons increased significantly with development (p<0.05), as well as the percentage of ARC POMC neurons expressing c-Fos (p<0.05). ARC AgRP cell numbers and the percentage of AgRP cells colocalized with c-Fos decreased significantly over time (p<0.05). The number of AgRP close contacts onto ARC NKB cells is currently being analyzed. The percentage of NKB cells colocalizing c-Fos throughout pubertal development also increased significantly (p<0.05). This data supports the hypothesis that the ARC melanocortin system impacts KNDy neurons to regulate GnRH/LH secretion throughout pubertal development.

Presentation: Saturday, June 17, 2023
SAT620 Dopamine Challenge: Treatment Of Pituitary Macroadenoma/Prolactinoma In Patient On Antipsychotic Medication
Authors: Bazhenov Aleksei , Alpertunga Ipek
Published: October 2023

Disclosure: A. Bazhenov: None. I. Alpertunga: None.

Background When hyperprolactinemia is a well-known side effect of antipsychotic medications1, the link between prolonged treatment with dopamine antagonist and the development of lactotroph adenomas is still unclear4. Treating a patient with prolactinoma and psychotic disorder may pose a challenge. Antipsychotic agents can cause increases in prolactin levels. Additionally, treatment of prolactinoma with dopamine agonists may worsen psychotic symptoms. Case presentation We present a case of 56 yo male with a PMH of bipolar disorder with psychotic features who was found to have a macroprolactinoma after 18 years of treatment with antipsychotic medications. At age 30, the patient was diagnosed with Bipolar Disorder with psychotic features. The course of the disease was complicated by numerous hospitalizations and frequent changes to the treatment plan, with different combination of second-generation antipsychotic, haloperidol and antiseizure medications. The patient’s prolactin level was 50 ng/ml at the time. 18 years after the diagnosis, the patient developed severe headaches. An MRI revealed a pituitary macroadenoma measuring 1.3 cm, and a repeat prolactin level resulted in 729 ng/ml. He was started on cabergoline 0.5 mg twice a week. As a result, the prolactin level dropped to 32 ng/ml and the macroprolactinoma size decreased to 1.1 cm. Unfortunately, the patient was lost to follow up. Once he re-established his care, he was started on Olanzapine 15 mg daily, Lamotrigine 200 mg daily and cabergoline 0.5 mg twice a week. After reinitiating cabergoline, the patient developed three maniac episodes, two of which required hospitalization. The dose of the cabergoline was decreased to avoid future maniac episodes. Neurosurgery will be consulted for possible surgery treatment. Discussion The treatment of a patient with prolactinoma and a psychotic disorder poses a particular challenge. We believe that care of these patients requires a multidisciplinary approach, and surgical treatment should be considered for those who cannot tolerate dopamine-agonist therapy. Literature 1. Bostwick JR, et al. Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009;29(1):64-73. 2. Lertxundi U et al. Antipsychotics and pituitary tumors. Int Clin Psychopharmacol. 2019;34(2)89. 3. Andrade EH, et al. Insights in the management of antipsychotics. Case Rep Med. 2010;2010. 4. McCarren M,et al. Follow-up study of a pharmacovigilance signal. J Clin Psychopharmacol. 2012;32(6)743. 5. Bakker IC, et al. Successful treatment of a prolactinoma on antipsychotic drug. Endocrinol Diabetes Metab Case Rep. 2016. 6. The challenges in managing prolactinomas SFEBES2009 Accessed April 11 2023. https://endocrine-abstracts.org 7. Howes OD et al. The role of dopamine in schizophrenia. Biol Psychiatry. 2017;81(1)9. 8.Bamarinejad A, et al. Schizophrenia and Macroprolactinoma: Adv Biomed Res. 2020;9(1)38.

Presentation: Saturday, June 17, 2023
SAT621 Hemorrhage After Treatment: A Case Of Pituitary Apoplexy In Metastatic Prostate Cancer After Leuprolide
Authors: Dillon Martha , Shteyman Sara , Rashid Waleeja , Ramchandani Bhanvi Prakash , Samat Aashish G
Published: October 2023

Disclosure: M. Dillon: None. S. Shteyman: None. W. Rashid: None. B.P. Ramchandani: None. A.G. Samat: None.

Introduction: Hormone-sensitive cancers, including prostate and breast cancer, and some gynecological conditions can be treated with GnRH agonists, including leuprolide. However, pituitary apoplexy is a rare potential complication after administration. Case Description: 71-year-old gentleman with metastatic hormone-sensitive prostate cancer presented with an acute headache after receiving a dose of leuprolide. This was his first GnRH agonist dose after prior Degarelix treatment. After two hours, the patient developed a constant throbbing headache, palpitations, left eye tearing and non-bilious non-bloody vomiting. Vitals were within normal ranges, and initial lab work showed low serum cortisol of 4.6. CT scan of the head showed exophthalmos and a mildly enlarged sella. Subsequent MRI demonstrated pituitary hemorrhage and optic chiasm impingement from resulting swelling. Hormone levels remained normal. Since the patient did not develop visual field defects or other ocular complaints, the decision was to manage the patient medically rather than with surgery. The day after admission, he developed hypotension requiring high dose steroids. After discharge, outpatient repeat MRI showed interval resolution of hemorrhage into a predominantly cystic pituitary macroadenoma. Discussion: With continued stimulation, GnRH agonists desensitize the pituitary and cause a downregulation of hormonal induced cancer growth. However, there is an initial transient burst of stimulation that can induce pituitary apoplexy in patients who already have a large adenoma. The hemorrhage and subsequent swelling cause a sudden severe headache and possible visual loss or hypopituitarism. This is life-threatening due to hypotension from catecholamine insensitive blood vessels in the absence of cortisol. Treatment involves high dose steroids, frequent sodium checks and possible emergency neurosurgery for decompression. It is important with GnRH agonists to watch out for this rare complication, whether the hormonal axis is being suppressed for metastatic cancer treatment or for hormonally driven gynecological conditions. Sources: Briet C, Salenave S, Bonneville JF, Laws ER, Chanson P. Pituitary Apoplexy. Endocr Rev. 2015 Dec;36(6):622-45. doi: 10.1210/er.2015-1042. Epub 2015 Sep 28. PMID: 26414232. Tanios G, Mungo NA, Kapila A, Bajaj K. Pituitary apoplexy: a rare complication of leuprolide therapy in prostate cancer treatment. BMJ Case Rep. 2017 Jul 14; 2017:bcr2016218514. doi: 10.1136/bcr-2016-218514. PMID: 28710301; PMCID: PMC5534692.

Presentation: Saturday, June 17, 2023
SAT623 Everolimus For Treatment-refractory Prolactinomas
Authors: Lin Andrew L , Geer Eliza Brevoort , Page-Wilson Gabrielle , Magge Rajiv S , Young Robert J , Tabar Viviane
Published: October 2023

Disclosure: A.L. Lin: Grant Recipient; Self; Bristol-Myers Squibb. E.B. Geer: None. G. Page-Wilson: None. R.S. Magge: None. R.J. Young: Consulting Fee; Self; Olea Sphere, ICON plc. V. Tabar: None.

Introduction: Treatment-refractory prolactinomas are life-limiting tumors without a standard of care treatment option after the oral alkylator, temozolomide, fails to provide tumor control. Methods: We reviewed an institutional database of pituitary tumors for patients with aggressive prolactinomas who progressed following treatment with a dopamine agonist, radiotherapy and temozolomide. In this cohort of patients with aggressive prolactinomas, we identified 4 patients who were treated with everolimus and we report their response to this therapy. Treatment response was determined by a neuroradiologist, who manually performed volumetric assessment and determined treatment response by Response Assessments in Neuro-Oncology (RANO) criteria. Results: 3 of 4 patients who were treated with everolimus had a biochemical response to therapy and all patients derived a clinically meaningful benefit based upon suppression of tumor growth. While the best overall response as assessed by RANO criteria was stable disease for the 4 patients, a minor regression in tumor size was appreciated in 2 of the 4 patients. Conclusion: Everolimus is an active agent in the treatment of prolactinomas that warrants further investigation.

Presentation: Saturday, June 17, 2023
SAT624 Neurosarcoidosis Presenting With Panhypopituitarism
Authors: Niedzialkowska Ewelina Marta , Blazin Tatjana , Strubchevska Kateryna , Kozyk Marko , Saini Nidhi
Published: October 2023

Disclosure: E.M. Niedzialkowska: None. T. Blazin: None. K. Strubchevska: None. M. Kozyk: None. N. Saini: None.

Introduction: Neurosarcoidosis is estimated to occur in approximately 5-15% patients with sarcoidosis. Pituitary involvement may be present in up to 5% of those cases and can manifest as hypothalamus, adenohypophysis dysfunction or arginine vasopressin deficiency (AVP-D) in isolated fashion or variedly combined. Clinical case: 32 year old male presented with chief complaint of worsening bilateral lower extremity weakness, urinary incontinence, polyuria and polydipsia. 9 months prior to admission the patient was diagnosed with neurosarcoidosis. At that time brain MRI showed diffuse leptomeningeal enhancement, chest CT showed hilar lymphadenopathy, lumbar puncture with CSF analysis showed protein 227 mg/dl (N<38), ACE 6 U/l (N <2.5), WBC 10 (N<5) with 88% lymphocytes. Hilar lymph node biopsy was consistent with non-caseating granuloma. The patient was diagnosed with neurosarcoidosis and started on prednisone and methotrexate. The patient was referred to our institution for further evaluation. On examination gait ataxia and gynecomastia were noted. Laboratory results showed urine specific gravity of 1.001, LH 0.4 mIU/ml (N 0.6-1.2), FSH 1.1 mIU/ml (N 1-12), ACTH <5 pg/ml (N 6-46), cortisol 2.1 ug/dl (N 2.9-19.4), prolactin 10.5 ng/ml (N 2-18), total testosterone 4 ng/dl (N 240-1080), free testosterone 0.1 ng/dl (N 4.8-19), TSH 0.58 uIU/ml (N 0.4-4.5), free ft3 1.5 pg/ml (N 1.7-3.7), free ft4 0.6 ng/dl (N 0.7-1.5), IGF-1 52 ng/ml (N 71-234), Copeptin proAVP of <2.8 pmol/l( N>13.2), urine osmolality of 72 mOsmol/kg, blood osmolality of 297 mOsmol/kg (N <295), vit D 25-OH 9 ng/ml (N 30-100), vit D 1,25-OH 57.3 pg/ml (N 19.9-79.3). MRI of the spine showed extensive nodular enhancement of the leptomeninges of the cervical, thoracic spine and lumbar cauda equina nerve roots. Brain MRI was positive for numerous small nodular enhancement involving leptomeninges and pituitary stalk. The patient was started on desmopressin with significant improvement of symptoms and increase in urine osmolality to 709 mOsmol/kg. Due to risk of hypercalcemia and normal vit D 1,25-OH vitamin D supplementation was not initiated. For neurosarcoidosis the patient was started on pulse dose methylprednisolone and infliximab infusion. Upon discharge he was transitioned to oral hydrocortisone and started on levothyroxine and testosterone replacement therapy. Conclusion: We present a case of pituitary neurosarcoidosis presenting with AVP-D, secondary hypothyroidism, secondary adrenal insufficiency, hypogonadism and growth hormone deficiency. Panhypopituitarism with complete anterior and posterior pituitary dysfunction is extremely rare and might be found in up to 13% cases of pituitary sarcoidosis. The diagnosis should be considered in patients with sarcoidosis and endocrine dysfunctions.

Presentation: Saturday, June 17, 2023
SAT629 Do Antipsychotic Medications Cause Prolactinoma Growth? A Systematic Review Of Imaging And Serum Findings
Authors: Durrani Umar Safwaan
Published: October 2023

Disclosure: U.S. Durrani: None.

Between 2013 and 2018 approximately 4 million adults in the U.S. were reported to be taking antipsychotics. Since increased dopamine levels in the brain are a known etiology for psychosis, antipsychotics function by reducing dopamine levels; dopamine is also a neurotransmitter involved in the regulation of prolactin, a hormone secreted by the pituitary gland which plays a role in lactation and mammary gland development. Prolactinomas are pituitary tumors in which excess prolactin is secreted and their treatment often involves dopamine agonists, which function to decrease prolactin production. Understanding that dopamine agonism decreases prolactin production, our project seeks to examine if dopamine antagonism can cause prolactinoma growth. We aim to answer this question by conducting a PubMed literature review focusing on prolactinoma patients who are concurrently prescribed antipsychotics. Our search yielded 32 studies representing a total of 40 patients. Although imaging data was limited, we used serum prolactin levels as a surrogate marker for prolactinoma growth. Preliminary results uncovered two major themes from our search: the use of certain antipsychotics (risperidone, haloperidol, thioridazine, thiothixene, and amisulpride) was associated with an increase in prolactin levels, and discontinuation led to a decrease in prolactin as well as normalization of the pituitary gland when imaging was provided. However, there were also some exceptions where antipsychotic use had minimal or no effect on prolactinomas. There were 4 patients who took antipsychotics (risperidone, thioridazine) and did not have prolactinoma symptoms until they used other drugs in combination. There were 2 patients taking risperidone without any worsening of their existing prolactinoma when taking the drug in small doses with cabergoline or when using a long acting form. In conclusion, while the relationship between antipsychotic use and prolactinoma growth may not be fully clear, it is known that ceasing medication use can help with treatment of the tumor. We recommend that providers be aware of the potential relationship between these drugs and this tumor and adjust treatment plans accordingly.

Presentation: Saturday, June 17, 2023
FRI352 Diabetes Insipidus With Hypokalemia In A 30 Week Pregnant Female
Authors: Stanfield Caleb Benjamin
Published: October 2023

Disclosure: C.B. Stanfield: None.

In this case, we will discuss a 29 year old G4P0121 African American female at 30 weeks gestation presented to women’s urgent care for nausea, vomiting and diarrhea after starting magnesium supplementation for incidentally diagnosed hypokalemia around 4 weeks prior. Vitals were significant for a BP of 133/60 and HR 110. Laboratory studies were significant for potassium of 3 mmol/L, sodium 155 mmol/L, magnesium 2.2mmol/L, AST 104, ALT 62 and UA with 2+ proteinuria. Patient admitted to the OBGYN service for preeclampsia with severe features. Patient was noted to have over 16L UOP over the first 24 hours of admission; 4.5L intake. Further labs obtained showed hemoglobin A1C of 4.9, serum osmolality of 308 mOsm/kg, urine osmolality 77 mOsm/kg and urine specific gravity 1.002. DDAVP was given with urine osmolality increasing from 77 to 137 mmol/L. Working differential diagnoses included gestational diabetes insipidus (DI), central DI or nephrogenic DI due to hypokalemia. Co-peptin assay was drawn; is a send out at our institution. Of note, the patient had no known history of brain injury, surgery, radiation or Sheehan Syndrome. However her previous pregnancies had been complicated by hypokalemia, hypertension and pre-eclampsia with emergent cesarean-section. She subsequently underwent emergency cesarean-section on hospital day 2 for non-reassuring fetal activity with delivery of viable 1230g male. After delivery, the patients hypokalemia resolved. Post-op, DDAVP for 3 days was continued per hospital DI protocol with appropriate response. Co-peptin resulted at 22.3, excluding central DI as a diagnosis. On time of discharge, patient had gone without DDAVP for >48 hours with intact thirst mechanism. Given improvement/resolution of DI and persistently low urine osmolality even after DDAVP administration prior to delivery, the DI was believed to be gestational with a component of nephrogenic DI as well due to hypokalemia. Gestational DI occurs due to increased placental vasopressinase which degrades the antidiuretic hormone (ADH). It is associated with pre-eclampsia, acute fatty liver of pregnancy and HELLP syndrome. DDAVP is a modified synthetic analog of endogenous ADH and is resistant to breakdown by placental vasopressinase and can be used to treat gestational DI. Definitive management is achieved with delivery of the fetus and can last up to six weeks after delivery.

Presentation: Friday, June 16, 2023
THU161 The Characteristics Of DNA Methylation Pattern In Children Born Small For Gestational Age Who Failed To Catch-up Growth
Authors: Kang Min Jae , Kwon Eun Byul , Hwang Il Tae
Published: October 2023

Disclosure: M. Kang: None. E. Kwon: None. I. Hwang: None.

Introduction: DNA methylation is one of major mechanisms of epigenetic mutation. Differentially methylated regions (DMRs) are found in various imprinting disorders. In this pilot study, we aimed to analyze DNA methylation pattern of short stature children born small for gestational age (SGA-SS). Method: SGA-SS subjects were included when all the following criteria were met: birth weight ≤ 3 percentile; height z-score after age 4 ≤ -1.881 (3 percentile); both parental heights > -1.881 (3 percentile). When the age of subjects were 4.0-7.5 years, they were sorted into SGA-SS group 1 (n=17). Normal control (NC) was age- and sex-matched to SGA-SS group 1 (n=11). NC subjects were normal birth weight (>10 percentile) and normal stature (> 10 percentile). When the height z-score after age 4<-2.5, they were sorted into SGA-SS group 2. DNA methylation patterns of IGF2, H19, PLAG1, MEG3, MEST, SGCE-PEG10, KvDMR genes were performed by pyrosequencing. Result: Mean birth weight and height z-score of NC was 3.3 kg and 0.60, respectively. Mean birth weight SDS and height z-score of SGA-SS group 1 was -2.37 and -2.08, respectively. Mean birth weight SDS and height z-score of SGA-SS group 2 was -2.60 and -2.98, respectively and birth weight was not significantly different compared to that of SGA-SS group 1. Mean DNA methylation levels of IGF2/H19/PLAG1/MEG3/MEST/SGCE-PEG10/KvDMR gene were 58.0/46.8/44.4/55.0/53.2/45.4/48.7%, 55.1/38.2/45.6/53.1/50.6/42.8/47.1%, and 54.4/42.7/45.0/53.6/51.8/44.7/46.3 % in NC, SGA-SS group 1, and SGA-SS group 2, respectively. DNA methylation levels of SGA-SS group 1 were decreased in IGF2 (P=0.027), MEST (P<0.001) compared to those of NC. There was difference of DNA methylation levels of MEST between SGA-SS group 1 and SGA-SS group 2 (P=0.013). Conclusion: DNA methylation levels of SGA-SS groups were different in several candidate genes related to fetal growth compared to those of NC. Although the mechanism of epigenetic mutation is diverse, DNA methylation pattern may have the role in pathophysiology and heterogeneity in SGA children.

Presentation: Thursday, June 15, 2023
THU186 A Case Of 3beta-hydroxysteroid Dehydrogenase Type2 Deficiency Diagnosed By Whole Genome Sequencing In A Patient With Congenital Adrenal Hyperplasia
Authors: Chang Seong Hwan , Kim Chan Jong
Published: October 2023

Disclosure: S. Chang: None. C. Kim: None.

3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare type of congenital adrenal hyperplasia (CAH) caused by HSD3B2 gene mutations. The estimated prevalence is less than 0.5% of all CAH and less than 1/1,000,000 at birth. It is a disorder of impaired steroidogenesis and sex steroid deficiency characterized by variable degrees of salt wasting, hypoglycemia, male incomplete masculinization and female virilization. Some newborns with 3βHSD2D have increased level of 17-hydroxyprogesterone (17OHP) that clinicians misdiagnose them as having classic 21-hydroxylase deficiency. A male newborn was referred to our hospital for generalized hyperpigmentation. Laboratory test showed hyponatremia, hyperkalemia and hypoglycemia. Hormonal study showed high level of adrenocorticotropic hormone, 17OHP, progesterone, renin activity, dehydroepiandrosterone (DHEA), androstenedione and low level of aldosterone. Clinically diagnosing with CAH, we administered glucocorticoid and mineralocorticoid replacement. We performed PCR sequencing for CYP21A2 gene mutation to confirm 21 hydroxylase deficiency but revealed normal result. After follow-up for 17 years with replacement treatment, he happened to have the opportunity to perform whole genome sequencing. Whole genome sequencing allowed to detect two pathogenic mutations in the HSD3B2 gene, described in compound heterozygosity (p.Arg249Ter and c.-149_143-1766del). One mutation (c.-149_143-1766del) is inherited from his father and the mother was not done for gene study. While there have been less than 100 cases of 3βHSD2D reported worldwide, in our best knowledge, this is the first case of genetically confirmed 3βHSD2D in Korea.

Presentation: Thursday, June 15, 2023
THU197 Peripheral Precocious Puberty In A 6-year-old Girl With Extreme Estradiol Elevation With Rapid Normalization: A Case Report
Authors: Meller Leo , Marinkovic Maja , Elizabeth Mary
Published: October 2023

Disclosure: L. Meller: None. M. Marinkovic: None. M.E. Patterson: None.

Background: Peripheral precocious puberty (PPP) in girls is typically associated with ovarian or adrenal tumors, ovarian cysts, McCune-Albright syndrome (MAS), or exogenous hormone exposure. We present an unusual case of PPP with extreme estradiol elevation and rapid normalization. Clinical Case: A 6.5-year-old previously healthy girl presented with two-month history of bilateral breast growth and tenderness, associated with daily cramping. Subsequently, she developed clear, odorless vaginal discharge. Two days prior to the visit she started light vaginal bleeding. Parents denied any medication intake or use of lavender or essential oils. She had no family history of early puberty. On the exam, she was tall for her age (95%) with a recent growth spurt. She had breast buds (Tanner 2) and vaginal bleeding without pubic hair (Tanner 1) or signs of hyperandrogenemia. There were no skin lesions or gross bone abnormalities. Bone age was equal to chronological age. She had an extreme elevation of estradiol of 156pg/mL and 170pg/mL (reference range<=16pg/mL) measured two weeks apart with prepubertal LH/FSH. Thyroid tests were normal. Pelvic ultrasound and abdomen/pelvis CT showed no abnormalities of ovaries and adrenal glands. Nine days after the onset, vaginal bleeding and cramping spontaneously resolved. Estradiol levels measured two days after cessation of vaginal bleeding normalized (7pg/mL) while LH/FSH remained prepubertal. Interestingly, two weeks after the bleeding stopped her pelvic ultrasound showed significantly enlarged ovaries (R 4.1mL, L 4.3mL), while her estradiol remained normal (5pg/mL). Conclusion: We describe an unusual presentation of PPP in a young girl with extreme estradiol elevation causing simultaneous premature breast development and vaginal bleeding. We suspect PPP was secondary to ruptured ovarian cyst that was not captured by imaging. Other differentials include MAS, exogenous hormone exposure, adrenal or ovarian tumors. These were unlikely due to lack of abnormal skin or bone findings, environmental hormone exposure and normal imaging. Her ovarian enlargement could be secondary to high endogenous estrogen exposure, and she may be at risk of developing central precocious puberty. This unique case emphasizes the importance of prompt assessment of children with precocious puberty and discusses the differential diagnosis process for PPP with markedly elevated estradiol with rapid normalization.

Presentation: Thursday, June 15, 2023
THU198 Peripheral Precocious Puberty In Girls Due To Ovarian Cyst
Authors: Lee Hae Sang , Hwang Jin Soon , Shim Young Suk , Heo Seung
Published: October 2023

Disclosure: H. Lee: None. J. Hwang: None. Y. Shim: None. S. Heo: None.

Objective: Peripheral precocious puberty (PPP) is precocious development of secondary sexual characteristics caused by mechanisms that do not involve activation of pulsatile GnRH secretion. PPP in girl is less frequent than central precocious puberty (CPP). it is caused by various disease such as gonadal and adrenal tumors, ovarian cysts, hypothyroidism and exposure to exogenous sex steroids. In particular, discordant pubertal development with vaginal bleeding within one year of breast development suggests hyperestrogenic state, and may be caused by autonomous ovarian cysts, McCune-Albright syndrome (MAS) and hypothyroidism. We aimed to investigate clinical characteristics and long-term clinical course of PPP in girls with ovarian cyst. Methods: This study was conducted through a retrospective medical record analysis. We studied 12 patients who were diagnosed with PPP due to ovarian cyst after pelvic sonography from January 2003 to May 2022. Patients were examined for pelvic sonography when there was vaginal bleeding and/or nipple pigmentation in PPP. pelvic sonography findings, clinical characteristics, management and prognosis of patients with ovarian cysts were investigated. Results: Ten out of 12 cases had vaginal bleeding and the 3 cases had nipple pigmentation. E2 was elevated to median value 36 pg/mL ([IQR], 19-61). There was a total of 18 episodes of ovarian cyst including recurrence. The median size of cyst was 28 mm ([IQR], 24- 34). Surgical management was performed in one patient with large cyst of 70 mm. Aromatase inhibitor was used in three cases. Follow-up pelvic sonography was performed to confirm regression of ovarian cyst. Median time to regression of ovarian cyst was 6 months ([IQR], 3-9). Five cases were diagnosed with MAS. Later, In 4 out of 12 cases were progressed to CPP and cyst was recurred more than 2 episodes in 3 cases. Median total follow-up duration of cases was 2.5 years ([IQR], 0.9-5.3). Conclusion: Most of ovarian cysts in PPP disappear spontaneously. However, It may appear as a one of findings with MAS or can progress to CPP in recurrent case. Therefore, careful follow-up is necessary in ovarian cysts of PPP.

Presentation: Thursday, June 15, 2023
THU216 The Influence Of Age At Diagnosis On Clinical Presentation And Prognosis Of Childhood-onset Craniopharyngioma
Authors: Beckhaus Julia , Friedrich Carsten , Boekhoff Svenja , Calaminus Gabriele , Bison Brigitte , Eveslage Maria , Timmermann Beate , Flitsch Joerg , Muller Hermann Lothar
Published: October 2023

Disclosure: J. Beckhaus: None. C. Friedrich: None. S. Boekhoff: None. G. Calaminus: None. B. Bison: None. M. Eveslage: None. B. Timmermann: None. J. Flitsch: None. H.L. Muller: None.

The association between age at diagnosis (AaD) and clinical presentation and prognosis of pediatric patients with craniopharyngioma (CP) is not clear. Seven hundred and nine patients diagnosed with adamantinomatous CP have been recruited between 1999 and 2021 in HIT-ENDO, KRANIOPHARYNGEOM 2000/2007, KRANIOPHARYNGEOM Registry 2019 and prospectively observed. In our cohort study, we analyzed clinical presentation and outcome in these CP patients with regard to different AaD: Infants and toddlers (under 2 years), early childhood (2-6 years), middle childhood (6-12 years), and early adolescence (12-18 years). Following a median follow-up of 8.4 years, functional capacity (FMH), overall and event-free survival (EFS), and quality of life (QoL) (PEDQOL) were evaluated. 45.4% of the patients presented with severe obesity (BMI > 3SDS) at last visit. Children with AaD <6y showed lower EFS but higher QoL than children with AaD >6y. Reduced functional capacity (FMH) percentiles were linked to higher BMI-SDS at last visit (rho=-0.125, 95% CI [-0.21; -0.04]). Posterior hypothalamic involvement and surgical lesion were independent risk factors for both, severe obesity at last visit (OR=2.94, 95% CI [1.73;5.08]) and events (HR=1.59, 95% CI [1.12;2.26]). In the PEDQOL body image domain, patients with posterior hypothalamic involvement and lesion report lower scores. Nearly half of all patients suffer from sequelae of severe obesity and the hypothalamic syndrome. A diagnosis of CP before the age of 6 years may enable patients to adjust to their limitations earlier, but it may also increase the risk of relapse. The cause of severe obesity and a lower QoL is not AaD but posterior hypothalamic involvement of CP.

Presentation: Thursday, June 15, 2023
THU221 Measurements Of Head Circumference During Developmental Monitoring Visits Before Diagnosis Of Pediatric Craniopharyngioma
Authors: Beckhaus Julia , Boekhoff Svenja , Krieger Leonie , Peng Junxiang , Friedrich Carsten , Muller Hermann Lothar
Published: October 2023

Disclosure: J. Beckhaus: None. S. Boekhoff: None. L. Krieger: None. J. Peng: None. C. Friedrich: None. H.L. Muller: None.

Craniopharyngiomas (CP) are congenital, benign, embryonic malformations which arise from ectoblastic remnants of Rathke’s pouch and are located in the (supra-)sellar region. Many patients show a reduced growth rate and an increased BMI early before the diagnosis of CP. However, it is unknown whether patients with CP present with increased head circumference before diagnosis. A cohort of 83 patients was screened for medical records of their developmental monitoring visits. We observed, that CP patients with hypothalamic involvement of their tumor tend to have an increased head circumference SDS before CP diagnosis. When comparing head circumference SDS before diagnosis at defined time points between birth and four years of age, all head circumferences were in the upper normal range. However, no statistically noticeable differences were found between hypothalamic involvement and no hypothalamic involvement of the tumor. Congenital embryonic malformations such as CP located in the parasellar area can have impact on cerebrospinal fluid circulation and lead higher head circumferences due to hydrocephalus early before diagnosis. Our results show, that head circumference SDS could be an effective early-indicator for CP. A standardized procedure for head circumference measurements during developmental monitoring visits should be implemented in clinical care. We anticipate that our study is the starting point for prospective studies with larger sample size to assess the potential predictive value of head circumference measurements for an early CP diagnosis.

Presentation: Thursday, June 15, 2023
THU224 Is Chronic Lymphocytic Thyroiditis Associated With Aggressive Differentiated Thyroid Cancer In A Predominantly Hispanic Pediatric Population?
Authors: Solano Natalia , Baboun Daniela , Martinez-Sanchez Andrea , Diaz Alejandro , Carrillo-Iregui Adriana , Alkhoury Fuad
Published: October 2023

Disclosure: N. Solano: None. D. Baboun: None. A. Martinez-Sanchez: None. A. Diaz: None. A. Carrillo-Iregui: None. F. Alkhoury: None.

Background: The risk of developing papillary thyroid carcinoma (PTC) appears to be increased among patients with chronic lymphocytic thyroiditis (CLT). Studies in adults have shown that the presence of CLT is associated with less aggressive PTC; however, this correlation is unclear in pediatric patients. Objective: The purpose of this study is to determine a possible correlation between CLT and markers of aggression severity using histopathological findings, tumor size, and lymph node involvement among patients with differentiated thyroid carcinoma (DTC) in a free-standing children’s hospital with a predominantly Hispanic population. Methods: Upon Institutional Review Board approval, we performed a retrospective chart review from 2012-2022 of 55 patients with a final diagnosis of DTC. We analyzed the correlation between CLT and histopathological findings. Statistical analysis was performed by using t-tests and chi-squared tests. Results: The patients reviewed were between 8-20 years of age. Forty-nine (89.1%) patients identified as Hispanic, and 41 (74.6%) were females. Twenty-five (45.5%) patients had a diagnosis of CLT; 19 (76.0%) of these patients had classic PTC, 3 (12.0%) had the follicular variant of PTC, and 3 (12.00%) had another variant of PTC. Of the 30 (54.5%) patients who did not have CLT, 13 (43.3%) had the classic variant of PTC, 10 (33.3%) had the follicular variant of PTC, and 7 (23.3%) had another variant of PTC. The distribution of the histopathological findings was significant (p=.048). Patients with CLT had significantly smaller tumor sizes (1.8 vs. 2.5 cm, respectively [p=.048]). Of the 36 patients with lymph node involvement, 20 (55.6%) had CLT. Of the 19 patients without lymph node involvement, 5 (26.3%) had CLT. The association between the presence of CLT and lymph node involvement was significant (p=.038). Conclusions: In our population, patients with CLT had a significantly higher presence of the classic variant of PTC. Studies in adults have shown a tendency of these lesions to have a higher risk of disease than those with the follicular variant. Patients with CLT had a smaller tumor size, likely as a result of earlier detection of thyroid nodules due to frequent clinical evaluations and thyroid ultrasounds. However, patients with CLT tended to have a higher frequency of lymph node involvement. More studies with pediatric populations are needed to clarify the possible association between CLT and DTC.

Presentation: Thursday, June 15, 2023
THU227 Isosexual Peudo-precocious Puberty Due To Leydig Cell Tumor In A Prepubertal Child
Authors: Baby Merilyn , Xu Alex , Shacham Nitsan , Shapiro Ellen , Shah Bina Cherryl
Published: October 2023

Disclosure: M. Baby: None. A. Xu: None. N. Shacham: None. E. Shapiro: None. B.C. Shah: None.

Background: Testicular tumors account for 2-4% of all childhood cancers. Leydig cell tumors are the most common form of sex cord stromal tumors and represent 1-3% of all testicular tumors. In the pediatric population, testicular Leydig cell tumors present with signs of precocious puberty. Workup reveals low gonadotropins with elevated testosterone and testicular mass on ultrasound. Treatment involves surgical enucleation (partial orchiectomy) in most cases. Clinical case: We present the case of a 4 year 10 month old male who presented to endocrine clinic for precocious puberty. He developed pubic hair three months prior with body odor. He did not have any CNS symptoms including headaches or visual changes. There was no use of exogenous androgens at home. He was born full term, small for gestational age with an uncomplicated postnatal course. There was no family history of precocious puberty. Height was at the 99th percentile (z-score 2.7), weight 98th percentile (z-score 2.07), and BMI 86th percentile (z-score 1.09). On exam, he was lean and appeared muscular. His testes were asymmetrical with the right testicle measuring 3 ml and the left testicle 2 ml. Scrotal hair was curly and sparse, Tanner III. Stretched penile length was 7 cm (90th percentile), width was 3.2 cm. Results: Bone age was advanced to 10 year 0 months with height age of 7 year 3 months. Serum gonadotropins were low, testosterone was pubertal at 115 ng/dl (Electrochemiluminescence Immunoassay). Serum 17-hydroxyprogesterone (221 ng/dl, ref range 0-90 ng/dl) androstenedione (163 ng/dl, ref range = < 51 ng/dl), and IGF-1 (368 ng/ml, ref range 108 – 293 ng/ml) were elevated. ACTH, cortisol, thyroid profile, and prolactin were normal. Beta-HCG and AFP were negative. ACTH stimulation test showed normal response. Testicular ultrasound with doppler was performed; right testicle measured 1.82 x 1.06 x 1.36 cm, volume of 1.4 ml, while left measured 1.27 x 0.72 x 0.87 cm, 0.4 ml. Within the right testicle, there was a mass that was hypoechoic, vascular (with a testicular artery feeding branch in the periphery), multinodular and measured 1.2 x 0.8 x 1.10 cm (0.53 ml). He was referred to urology and underwent enucleation of the right testicular mass through an inguinal approach. Grossly, the mass appeared tan and lobulated and surgical pathology confirmed a benign Leydig cell tumor. The patient recovered well and post-operative serum testosterone level at 2 weeks was <2.5 ng/dl. Conclusion: We present a case of a testicular Leydig cell tumor that presented as peripheral precocious puberty marked by low gonadotropins and elevated testosterone with ultrasound findings of a vascular mass with testicular artery feeding branch in the periphery. Early detection of a Leydig cell tumor is crucial as it can be treated by enucleation thus salvaging the testes.

Presentation: Thursday, June 15, 2023
THU231 Thyroid Function And Childhood Bone Mineral Density: Abnormal Thyrotropin Concentration May Be Another Predictor Of Pediatric Low Bone Mass
Authors: Ahn Moon Bae
Published: October 2023

Disclosure: M. Ahn: None.

Backgrounds: Thyroid hormone (TH) whose synthesis and secretion are mainly regulated by thyrotropin (TSH) play a critical role in the metabolism, growth, and development of human body. While TH is responsible for normal growth and differentiation of various organs, bone is known to be one of the major endocrine organs affected by the regulation of TH. Low bone mass or osteoporosis of child and adolescents can occur in numerous chronic conditions, however the influence of abnormal TH and TSH on low bone mineral density (BMD) of children and adolescents remains controversial. Investigating the effect of excessive or deficient TH and TSH on childhood BMD may unveil a better understanding of uncertain role of thyroid function in bone density of pediatric population. Objective: To elucidate the connection between thyroid function and childhood low bone mass. Methods: Serum T3, FT4 and TSH of 619 children aged between 10 to 18 years and previously diagnosed with hemato-oncologic, rheumatoid, gastrointestinal, endocrine conditions whose treatment was completed were assessed simultaneously with mineral density of lumbar spine and femur measured by dual energy x-ray absorptiometry. Serum T3, FT4, and TSH were subcategorized as either high/normal/low or normal/abnormal group with respect to age-matched reference range, then LSBMD data were compared. Comparison, correlation and regression analyses were performed to examine the association between the abnormality of thyroid function and low BMD. Results: Mean LSBMD z-scores of 619 children and adolescents were 0.49±1.28 and those who were less than -1.0 accounted for 37.7 % while serum T3, FT4, and TSH levels were 1.25±0.29 ng/mL, 1.28±0.19 ng/dL, and 2.76±1.87 µU/mL, respectively. Both lumbar and femoral BMD z-scores were not significantly different in between subjects with either abnormal or normal serum T3 and FT4, however were lower in children with abnormal serum TSH. LSBMD (g/cm2) was negatively correlated with serum T3 whereas its z-scores showed no correlation with any of serum T3, FT4 and TSH. In linear regression, BMI z-scores were positively associated whereas serum T3, FT4, TSH were not directly associated with LSMBD z-scores. When the abnormality of T3, FT4, and TSH was considered as determinants for decreasing LSBMD z-scores, TSH abnormality was a significant risk factor having highest odds ratio as LSBMD z-scores decreased. Conclusion: Although serum T3, FT4, and TSH did not show a direct correlation with childhood LSBMD z-scores, abnormal TSH concentration could predict low LSBMD z-scores, therefore indicate low bone mass of children with various underlying conditions.

Presentation: Thursday, June 15, 2023
THU239 Tolvaptan For SIADH Management In Children
Authors: Igarashi Mizuho , Kashima Takemoto , Doi Hibiki , Yoshii Keisuke , Naiki Yasuhiro , Horikawa Reiko
Published: October 2023

Disclosure: M. Igarashi: None. T. Kashima: None. H. Doi: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None.

[Background] Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is common after brain surgery and its’ management is difficult. In Japan, tolvaptan was approved for SIADH management in adults, but there are limited reports on the use of tolvaptan for SIADH in children.We presented two cases which showed triphasic response after neurosurgery and was treated with tolvaptan for SIADH phase. We will also summarize other cases which were treated with tolvaptan for SIADH phase after neurosurgery in discussion. [Case] Case1 is a 5-month-old boy with choroid plexus papilloma.A tumor resection was performed after chemotherapy. After tumor resection, serum sodium level went up to 171 mEq/L with diluted polyuria. So he was diagnosed as diabetes insipidus and treated with vasopressin. The dose of vasopressin was decreased and it was stopped on postoperative day (POD) 6, but serum sodium level further decreased and he was diagnosed as SIADH. Water restriction and hypertonic saline administration were performed. Tolvaptan at a dose of 0.1mg/kg was administered and sodium level improved from 123 mEq/L to 137 mEq/L.However, urine volume was decreased again and sodium level went down to 132 mEq/L, so tolvaptan was administered again. After second administration of tolvaptan, polyuria lasted and sodium level went up to 145 mEq/L, which was managed with temporary use of vasopressin. Case 2 is a 6-year-old girl with craniopharyngioma. After tumor resection, polyuria was observed and she was diagnosed as diabetes insipidus, which was treated with vasopressin.On POD 4, she was diagnosed as SIADH. Since water restriction was not effective, tolvaptan was administered twice (0.1mg/kg and 0.4mg/kg respectively). After second administration of tolvaptan, due to polyuria and diluted urine sodium level went up to 161 mEq/L, which was treated with vasopressin. Diluted urine and polyuria lasted, so finally she was diagnosed as diabetes insipidus. [Discussion] Tolvaptan was used for the management of SIADH that was resistant to water restriction or salt supplementation and it was useful for improving or maintaining sodium level. However, in some case, hypernatremia due to excessive free water excretion was caused after the dose of tolvaptan was increased. The appropriate dosage of tolvaptan has not yet been established. The risk of rapid sodium elevation should be considered and monitoring of water balance and sodium level was needed after using tolvaptan. [Conclusion] Tolvaptan could be an effective option for the management of SIADH, but frequent monitoring of sodium level is needed.

Presentation: Thursday, June 15, 2023
FRI590 Predictors Of Metabolically (Un)Healthy Obesity In Children
Authors: der Veken Lotte Van , Chestermann Xavier , Casteels Kristina , Helsen Jan , Rochtus Anne Maria
Published: October 2023

Disclosure: L. Van der Veken: None. X. Chestermann: None. K. Casteels: None. J. Helsen: None. A.M. Rochtus: None.

Childhood obesity is a growing problem worldwide and can lead to type 2 diabetes, hypertension, dyslipidemia, and carotid-artery atherosclerosis. This is known as “metabolically unhealthy obesity” (MUO). However, a subgroup of children who are obese have been described as “metabolically healthy” (MHO) due to the absence of these cardiometabolic risk factors. The current definition of MHO only includes cardiometabolic criteria (MHO-CR) such as systolic blood pressure, diastolic blood pressure, triglycerides, HDL-cholesterol and a measure of fasting plasma glucose. The aim of this review is to compare the current definition based on cardiometabolic risk factors with a definition that includes insulin resistance (MHO-IR). We investigated the differences between these definitions in terms of prevalence, characteristics, predictors, and the recommended way of measuring insulin and its respective cut-off value. We searched Pubmed, Embase, Web of Science and Cochrane Library for studies on prevalence and predictors of insulin resistance in pediatric MHO. The prevalence of MHO-CR, MHO-IR, MUO-CR, MUO-IR and MHO, based on combined criteria from both MHO-CR and MHO-IR, were compared and the mean-values for each group were calculated. A meta-analysis study was designed to investigate the characteristics of MHO-CR and MHO-IR. Summary effects were calculated using random effects models. The standardized mean differences (SMD) are presented together with their confidence intervals (5% significance level). The recommended way of measuring insulin resistance was investigated by a frequency-based representation of used units and cut-off values in the included studies. Eight full text articles met the eligibility criteria for inclusion. Out of 4036 participants, the mean prevalence of different groups was MHO-CR (35%), MHO-IR (44%), MUO-CR (61%) and MUO-IR (56%). After combining the cardiometabolic criteria with the factor insulin resistance, prevalence of MHO and MUO were respectively 11% and 54%. The characteristics found to be significantly different between MHO-CR and MHO-IR were fasting insulin [SMD 1.7406; CI (0.0198-3.4614); P=0.0481] and HOMA-IR [SMD 0.7202; CI (0.4414-0.9989); P=0.0007]. HOMA-IR was also significantly higher in MUO-IR than MUO-CR [SMD -0.3940; CI (-0.7471- -0.0409); P=0.0342]. Several predictors for MHO-CR and MHO-IR were defined. The most frequently used unit and cut-off value of MHO was HOMA-IR<3.16.The implementation of insulin resistance in the definition of pediatric MHO could provide a stricter way of categorizing patients as MHO and MUO, and allow earlier treatment interventions.

Presentation: Friday, June 16, 2023