bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP362 An Unexpected Finding of Adamantinomatous Type Craniopharyngioma in the Late Seventh Decade of Life: a case report
Authors: Ahmed Ammar , Biswas Suman , Tan Zi , Jahshan Bishara , Meedani Hassan E
Published: November 2022

Background

Craniopharyngioma is a rare solid, mixed solid, and benign cystic neoplasm derived from remnants of Rathke's pouch from the sellar region and its surroundings parasellar area. It mainly has two major histopathological subtypes, Adamantinomatous and Papillary. The adamantinomatous subtype is more common in children, and the papillary subtype is more common in adults. Clinical case: A 66-year-old male with no known endocrinological disorder presented with progressive fatigue, decreased oral intake, lightheadedness, nausea, visual changes, low libido, myalgia, nausea, vomiting, polyurea, headache, visual field defects, and seizure-like activities requiring hospital admission. The endocrinological workup revealed a deranged HPA axis (panhypopituitarism). MRI revealed 3 cm macroadenoma within the pituitary gland. An endonasal transsphenoidal resection of pituitary mass resection with abdominal fat graft was done as definitive treatment along with correction of the multiple endocrinological derangements. The surgical tissue biopsy revealed a rare with adamantinomatous type Craniopharyngioma WHO Grade I. He was discharged on testosterone supplements, hydrocortisone, levothyroxine, and Desmopressin with significant improvement in his symptoms.

Conclusion

Craniopharyngioma (CP) is a rare benign intracranial mass (incidence 0.5-2/100000) that can present with extensive endocrinological dysfunction. However, due to the lack of patient-level data and reporting of adult-onset craniopharyngiomas, it can be easily missed during the initial presentation. Not considering craniopharyngioma in differential diagnoses may result in delayed diagnosis and adverse outcomes. Although the papillary CP type is more common among adults, occasionally, adamantinomatous type CP may occur in this group of patients.

Presentation: No date and time listed
ODP618 The profile of patients with ACTH-secreting pituitary adenomas and subclinical pituitary apoplexy
Authors: Tatsi Christina , Saidkhodjaeva Lola , Flippo Chelsi , Stratakis Constantine
Published: November 2022

Background

Subclinical hemorrhage or necrosis of pituitary adenomas (PAs), often defined as subclinical pituitary apoplexy (SPA), presents in up to 20% of all PAs and is more common in large prolactinomas. SPA in corticotropinomas in patients with Cushing disease (CD) is not common and the clinical and biochemical characteristics of patients with CD and SPA are not known. Subjects and methods: Pediatric patients with confirmed CD diagnosed between 2005-2021 with available MRI images before any surgical intervention were included in the study (n= 171). SPA diagnosis was based on MRI findings. Although MRI sequences and machines were not same for all patients and varied over time, the results were based on possible signs of hemorrhage on the available images, but smaller areas of bleeding or necrosis may have been missed. Statistical analyses were performed with Wilcoxon signed-rank test, chi-square or Fisher's exact test, and Cox proportional hazard as appropriate. Results are shown as median [Q1, Q3], count (percentage) and odds ratio (OR) (95% confidence intervals, 95%CI).

Results

Out of 171 patients, 12 patients (7%) were found to have imaging characteristics of possible hemorrhage or intratumor infarct. Patients with and without SPA were similar in age (median age: 12.5 years [10.6, 15.6] in SPA group vs 13.1 years [10.6, 15.4] in non-SPA group, p= 0.95) and gender distribution (n of female= 5 (41.7%) in SPA group vs 89 (56%) in non-SPA group, p= 0.51). Patients with SPA had shorter duration of disease as noted by changes in their growth chart parameters (median duration: 1. 0 year [1. 0, 2. 0] in SPA group vs 2.5 years [1.5, 3. 0] in non-SPA group, p= 0. 014). Morning and midnight cortisol and 24hour urinary cortisol levels were similar in both groups, but patients with SPA had higher levels of morning ACTH (60.8 pg/mL [43.5, 80.3]) compared to patients without SPA (39.8 pg/mL [28.5, 53.4], p=0. 017). Change of cortisol and ACTH levels during CRH stimulation test were similar between the two groups, but patients with SPA had lower suppression of cortisol after overnight high dose (8mg or weight-based equivalent) dexamethasone suppression test (58. 0% [-85.4, -49.7]) compared to patients without SPA (85.8 [-90.5, -76.8], p= 0. 035). Specifically, patients with SPA had lower chance of passing the threshold of 69% that it suggestive of pituitary source of hypercortisolemia compared to patients without SPA (OR: 0.18, 95%CI: 0. 03-0.95). The odds of remission after surgery and the risk of recurrence after initial remission did not differ based on the presence of SPA.

Conclusion

Patients with CD and sings of hemorrhage or necrosis in their tumor may present with different characteristics on their biochemical evaluation which should be considered during their diagnostic workup, especially in the setting of a discordant dexamethasone suppression test.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON107 Pineal Germinoma with Pituitary Involvement: Long-Term Survival following Treatment with Whole Ventricular Radiation
Authors: Khoury Brandon , Shin Terry , Vietor Nicole , Hoang Thanh , Shakir Mohamed
Published: November 2022

Introduction

Intracranial germinomas usually arise from midline structures such as the pineal gland or suprasellar region. Involvement of both structures occur in 6% of cases. We are reporting long-term follow up of a patient with pineal germinoma with pituitary involvement treated successfully with whole ventricular radiation.

Clinical Case

A 36-year-old man presented with polydipsia and polyuria 12 years ago. He also reported fatigue and cold intolerance. Vital signs: BP 130/75 mmHg, HR 69 bpm. Physical examination demonstrated moist mucous membranes and the rest of the examination was unremarkable. Labs: serum albumin 4.9 g/dL, calcium 9.8 mg/dL, glucose 91 mg/dL, potassium 4.2 mEq/L, sodium 145 mEq/L, and serum osmolality 294 mOsm/kg (reference 275-295). The patient also had multiple urinalyses showing a specific gravity of 1.005. Results of a water deprivation test: urine osmolality 114 mOsm/kg (50-1350) at 0805, 87 mOsm/kg at 0858, 73 mOsm/kg at 0955, 80 mOsm/kg at 1045, 88 mOsm/kg at 1150, and 102 mOsm/kg at 1253. His serum antidiuretic hormone during the water deprivation test was <0.8 pg/mL (ref 0.0-4.7). Since these labs suggested central diabetes insipidus, a pituitary MRI was performed that demonstrated two mass lesions in the region of the cephalad portion of the pituitary stalk, hypothalamus, and optic chiasm as well as in the pituitary gland region. Biopsy of the mass lesions was consistent with germinoma. MRI of the spine revealed no evidence of disseminated disease. Additional labs: TSH 1.88 mIU/L, free thyroxine 0.46 ng/dL, IGF-1 62 ng/mL (109-284), prolactin 25 ng/mL, FSH 1.9 mIU/mL, LH 2.5 mIU/mL, total testosterone 183 ng/dL, and cortisol 3.2 ug/dL. An ACTH stimulation test confirmed central adrenal insufficiency. The patient was treated with radiation therapy to the whole ventricles with for a total dose of 45 Gray per cycle. Follow-up MRI in our patient following treatment demonstrated no evidence of persistent or recurrent disease. However, he continues desmopressin for diabetes insipidus and levothyroxine 88 mcg daily for central hypothyroidism whereas the adrenal insufficiency has completely resolved. The patient has been without disease recurrence for the last 12 years and is doing well with a good quality of life. Radiation therapy alone has been highly effective in the management of intracranial germinomas with an overall survival of up to 85%. However, recent studies have shown that chemotherapy followed by lower dose of complete ventricular radiation is as effective as high dose ventricular radiation for local or bifocal germinomas with lower risk of long-term consequences.

Conclusion

This case illustrates that long-term survival can be achieved in patients with germinomas following appropriate treatments.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON118 Cerebral Palsy Resulting in Hypothalamus Volume Loss and Temperature Dysregulation
Authors: Phan Van , Erenler Feyzer , Lechan Ronald
Published: November 2022

Background

Cerebral palsy is a syndrome caused by a non-progressive brain injury or malformation during early brain development, which can lead to severe physical disability. However, there is limited data on the consequences of cerebral palsy on other crucial brain functions such as hypothalamus and pituitary gland. We report a case of hypothalamic-pituitary involvement in a cerebral palsy patient.

Clinical case

A 28-year-old man with history of quadriplegic cerebral palsy, severe cognitive delay and seizure disorder presented to our clinic with temperature dysregulation for 2 years. He is wheel-chair-bound and non-verbal. His core temperature generally ranges from 96.8o to 97.2oF but occasionally he has had fluctuations as high as 102oF and as low as 88oF associated with extremes in surrounding temperature. At the time of initial evaluation, his temperature was 96.8oF (36°C) and his skin was cool and mottled. He was on levothyroxine replacement for hypothyroidism and thyroid hormone levels were within the normal range (Free T4 of 1.33 ng/dL and Total T3 of 153 ng/dL). Head CT revealed extensive encephalomalacia involving the frontal and temporal lobes, diffuse thinning of the parenchyma of the parietal and occipital lobes with secondary lateral ventricle enlargement, and volume loss in the deep gray nuclei including the hypothalamus. Further evaluation revealed a borderline response to Cortrosyn (16.9 ug/dL at 60 min) but associated with an adequate baseline cortisol of 13.7 ug/dL. IGF-1 and prolactin levels were normal (IGF-1 of 117 ng/mL and prolactin of 7.9 ng/mL), but testosterone was 175 ng/dL associated with an LH of 3.1 mIU/mL and FSH of 10.7 mIU/mL consistent with central hypogonadism. The family was advised to carefully regulate and monitor ambient temperature, and maintain dress appropriate for the surrounding temperature.

Conclusion

Although periventricular white matter lesions are most commonly associated with cerebral palsy resulting in motor dysfunction, deep gray matter lesions are also occasionally documented. These lesions should be recognized, as they could be detrimental to the body. The hypothalamus, with the preoptic area as its main thermoregulatory locus, plays an important role in temperature regulation. It integrates all information from the surface thermoreceptors and local brain temperature then initiates heat production or heat loss mechanisms to help maintain homeostasis. Therefore, volume loss of the hypothalamus can lead to serious consequences such as poikilothermia that can lead to life-threatening hypothermia or hyperthermia.

Keywords: Cerebral palsy, hypothalamus, temperature dysregulation, poikilothermia

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON40 A Rare Etiology of Chronic Diarrhea: Zollinger-Ellison Syndrome
Authors: Rashid Hytham , McKinney Nathan , Jernigan Grant , Rhodes Alexander , Nix Emily , Morrissette Charles
Published: November 2022

Introduction

Zollinger-Ellison Syndrome (ZES) is a rare etiology of chronic diarrhea caused by a gastrin-secreting neuroendocrine tumor. Early suspicion can prevent multiple readmissions for recurrent diarrhea thus improving clinical outcomes through prompt diagnosis and treatment, as the following case highlights.

Case presentation

A 74-year-old African-American female with hypertension and chronic atrial fibrillation presented to the ED complaining of watery, non-bloody diarrhea for the past 3 weeks. She reports her symptoms worsened after completing a course of amoxicillin for pharyngitis one week prior. On further questioning, she reported intermittent diarrhea for over 20 years lasting approximately two days per episode. She denied recent travel, sick contacts, pet reptiles, and recent ingestion of undercooked meat. On arrival, she was afebrile and hemodynamically stable. She was admitted for an acute kidney injury with an elevated creatinine of 3.23 mg/dL (N: 0.6-1.1 mg/dL) due to dehydration. Her renal function improved with fluids, but she developed bloody diarrhea for which gastroenterology was consulted. Stool studies were negative for Shiga-toxin, C. difficile, lactoferrin, and parasites. Computed Tomography of the abdomen showed enteritis with fluid noted throughout the colon consistent with colitis. Unprepped colonoscopy revealed blood throughout the length of the colon, suggestive of an upper gastrointestinal bleed. Esophagogastroduodenoscopy (EGD) revealed multiple bleeding duodenal ulcers controlled with hemostasis. Her symptoms improved and she was discharged home on oral pantoprazole, and told to follow up outpatient. Two weeks later, she denied any new episodes of diarrhea, and a random serum gastrin level was elevated at 413 pg/mL (N: <180 pg/mL). Repeat gastrin level off pantoprazole for 7 days was also elevated at 678 pg/mL, and a serum Chromogranin A level was elevated at 629 pg/mL (N: <390 pg/mL). Repeat EGD found her Gastric pH to be 1 with multiple non-bleeding duodenal ulcers. Somatostatin receptor scintigraphy revealed a high intensity signal consistent with a duodenal gastrinoma causing ZES. She elected for surgical resection, and was discharged home on high dose pantoprazole. Three months later, she stated that her diarrhea had completely resolved.

Conclusion

This case confirms ZES as a rare cause of chronic diarrhea in the setting of multiple duodenal ulcers refractory to proton pump inhibitors. Diagnosis can be made with a fasting serum gastrin level >1000 pg/mL or >400 pg/mL with a gastric pH <1. A Secretin Stimulation Testing can also be used. Treatment starts with high dose proton pump inhibitors, octreotide for hormonal regulation, and surgical resection if necessary.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON63 The Impact of Protein-Energy Malnutrition on Outcomes of Adult Hospitalizations for SIADH: A Nationwide Analysis
Authors: Ojemolon Pius , Olafimihan Ayobami , Awoyomi Moyosoluwa , Kwei-Nsoro Robert , Shaka Hafeez
Published: November 2022

Introduction

Protein-energy malnutrition (PEM) is a leading cause of morbidity and mortality, particularly in developing countries. Via multiple mechanisms, there is an association between PEM and hyponatremia, but not much is known about concomitant PEM and the syndrome of inappropriate anti-diuretic hormone secretion (SIADH) or the effect of PEM on the outcomes of patients admitted with SIADH.

Methods

We extracted data from the US Nationwide Inpatient Sample (NIS) for 2019. The NIS contains hospital discharge information estimating yearly US hospitalizations. We included hospitalizations with a principal discharge diagnostic code for SIADH using the ICD-10-CM code (E22.2). Hospitalizations of patients less than 18 years of age were excluded from the study. This cohort was divided based on the secondary diagnosis of PEM.

Outcomes analyzed included comparing inpatient mortality rates, mean length of hospital stay (LOS), mean hospitalization cost (THC), and rates of septic shock, acute myocardial infarction (AMI), acute respiratory failure (ARF), acute renal failure (AKI), acute pulmonary edema (PE) between the subgroups. Adjustments were made for age, sex, race, primary payer, median household income by zip code, Charlson Comorbidity Index (CCI), hospital location, bed-size, and teaching status using multivariate regression analysis. Statistical significance was set at a p-value < 0.05.

Results

There were 39,110 hospitalizations involving patients with SIADH as the reason for the admission in 2019, and 13.2% of them had comorbid PEM. While both cohorts had a higher proportion of females, the subgroup with comorbid PEM had a lower proportion of females comparatively (57.8 vs 62.3%, p=0.006). There was no significant difference in mean age (72.7±13.6 vs 72.1±12.2 years, p=0.113), but the cohort with PEM had a higher proportion of CCI >2 and more ethnic minorities.

In patients with SIADH, PEM was associated with higher adjusted odds ratio (aOR) for mortality (2.53 vs 0.9%, aOR: 2.1, p=0.004), increased LOS (6.6 vs 4.7 days, p<0.001) increased THC (13,884 vs 10,223 US$, p <0.001), and higher odds of comorbid septic shock (8.7 vs 2.8%, aOR: 2.69, p=0.014), CVA (14.6 vs 6.5%, aOR: 2.02, p=0.042), PE (8.7 vs 2.5%, aOR: 2.8, p=0.023) and ARF (13 vs 6.5%, aOR: 1.97, p<0.001), with no significant difference in AKI or AMI odds.

Conclusions

Comorbid PEM was associated with increased odds of mortality, LOS, THC, septic shock, CVA, PE, and ARF in hospitalizations for SIADH. The mechanism of this association is unclear, but further studies are necessary to better understand this potentially important relationship.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON79 Supraphysiologic Vasopressin-Induced Receptor Desensitization: A Case Report
Authors: Rabiei Samaneh , Jaffa Matthew , Kantorovich Vitaly
Published: November 2022

Background

Arginine vasopressin (AVP) is a nonapeptide released from the neurohypophysis in response to increases in plasma osmolality, hypovolemia, hypotension, and angiotensin II. V2 receptors, expressed on the basolateral membrane of the renal collecting ducts coupled to the adenylyl cyclase-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. PKA increases the synthesis and shuttling of aquaporin 2 water channel containing vesicles (AQMCV) from cytoplasmic vesicles to the luminal surface of the renal collecting ducts (and inhibits the endocytosis of the vesicles), where they are inserted into the apical cell membrane. As a result, AVP increases free water reabsorption from the filtrate and decreases serum osmolality. There are different protocols for CDI management in post neurosurgical patient, including IV or SQ injections as well as continuous vasopressin drip. Here we discussed a case where prolonged IV drip could probably have caused loss of response to IV DDAVP injections.

Case

Patient is a 46-year-old male admitted with AMS with imaging revealed ruptured anterior communicating artery aneurysm associated with subarachnoid and intra parenchymal hemorrhage. The patient underwent emergent aneurysm coiling and EVD placed. The patient was subsequently started on heparin infusion due to a large frontal lobe clot which was found on cerebral angiogram. The next day, the patient developed acute diabetes insipidus with hypernatremia and polyuria. Repeat head CT demonstrated increased cerebral edema around the frontal clot. The patient underwent right frontal craniotomy for clot evacuation. He patient was subsequently started on vasopressin infusion (ranging from 0.5-6 units/hour) by neurosurgery team for urinary output less than 200 mL/hour. ​Urinary output and sodium level improved and remained stable on infusion. When endocrinology attempted transition to DDAVP IV injections patient responded with severe polyuria to initial 0.5 mcg injection. Eventually patient required 1 mcg IV every 4 hours dosing to maintain normal urine output and required a slow wean off to the standard dose of 0.5 mcg every 8 hours over 14 days.

Discussion

we are presenting a case of CDI associated to SAH who was started on IV infusion of vasopressin, required slow weaning. phenomenon called for slow re-sensitization of the receptors with gradual decreasing of DDAVP dosing. Animal studies have shown that V1 and V2 receptors levels are sensitive to hormone-induced downregulation of hormone receptors. Hypervasopressinemia in rats whose blood vasopressin concentration was experimentally elevated by IV infusion to extraphysiologic levels caused significant desensitization of kidney vasopressin receptors. In another study, IM injection of DDAVP to rats led to a total loss of kidney V receptors. Thus, it is likely that administration of high dose DDAVP IV in this patient induced downregulation of kidney V2 receptors.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON88 A Rare Case of Composite Paraganglioma in the Bladder
Authors: Kreit Helen , Chary Priyanka Kesavan , Bright Tamis , Rehman Aziz U
Published: November 2022

Background

Paragangliomas are neuroendocrine tumors that arise from embryonic neural crest cells; they are essentially extra-adrenal pheochromocytomas most frequently found in the head and neck. Composite tumors are rare and consist of the presence of two histologically distinct tissues within a single tumor. Additionally rare is the presence of a composite paraganglioma in the retroperitoneum and urinary bladder, of which there are few reported cases.

Case Report

We present a case of a 57 year old female who was found to have an incidental pelvic mass noted to progressively increase in size over the years on subsequent imaging. The patient had a cystoscopy and retrograde pyelogram that were both unremarkable. MRI Pelvis showed a 1.8×1.8×1.9 cm rounded, well-circumscribed lesion at the left posterior lateral bladder extending exophytically from the serosa at the ureterovesicular junction. As she had associated hypertension, palpitations, and anxiety, the patient was evaluated for pheochromocytoma.Laboratory workup showed elevated plasma levels of free Metanephrines at 130 (<57 pg/mL), free Normetanephrines at 247 (<148 pg/mL), and a free Total level at 377 (<205 pg/mL). 24-hour urine collection was consistent with mild elevation of Metanephrines at 330 (90-315 mcg/24 h), normal levels of Normetanephrines at 469 (122-676 mcg/24 h), and normal levels of Total urine Metanephrines of 799 (224-832 mcg/24 h). 24-hour urine free Catecholamines showed: Epinephrine of 6 (2-24 mcg/24 h), Norepinephrine of 77 (15-100 mcg/24 h), and a Total (Epi+NE) of 83 (26-121 mcg/24 h), with Dopamine of 220 (52-480 mcg/24 h).Due to mildly elevated metanephrine levels, the patient was started on the alpha-blocker doxazosin. She ultimately underwent a laparoscopic removal of the bladder mass, with pathology reports confirming presence of a composite paraganglioma with atypical features. Additionally, further immunohistochemistry was negative for the SDHB gene mutation in the tissue samples obtained.

Conclusion

Composite paragangliomas of the urinary bladder are very rare. Certain genetic pathologic variants carry an increased risk for malignancy and possible metastasis; therefore, these neuroendocrine tumors usually require targeted mutation testing. At this time, the pathogenesis of composite paragangliomas is still largely unknown, with little information available about treatment options and clinical outcomes.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF01 | PMON44 Absence of Kisspeptin in KNDy Neurons of Mice Causes Sexually Dimorphic Metabolic Dysfunction on a High-Fat Diet
Authors: Nandankar Nimisha , Negrón Ariel , Al-Samerria Sarmed , Levine Jon , Radovick Sally
Published: November 2022

Kisspeptin neurons in the arcuate nucleus (ARC) of the hypothalamus are considered as the gonadotropin-releasing hormone (GnRH) pulse generator to control the cascade of hormone secretions that constitute the reproductive axis. These neurons typically co-express Neurokinin B and Dynorphin and are thus dubbed KNDy neurons. In addition, KNDy neuron kisspeptin is hypothesized to be a major sensor and regulator of metabolic homeostasis while relaying energy status to the hypothalamic-pituitary-gonad (HPG) axis. However, the direct metabolic impact of KNDy neuron kisspeptin has not been well-characterized. To explore this role, we examined the metabolic profile of our previously established KNDy neuron-specific kisspeptin knock-out mouse model (Pdyn-Cre/Kissfl/fl, or KO). To do so, we performed glucose tolerance tests, EchoMRI body composition analysis, and measured body weight in wild type (WT) control or KO mice fed with either regular chow or a high-fat diet (HFD, 60% kcal fat, Research Diets, New Brunswick, NJ) for 12 weeks post-weaning. At 4 weeks on the HFD, KO females weighed significantly more than HFD WT females, which continued through the remaining 8 weeks. Additionally, we found significantly decreased glucose tolerance and increased fat mass in HFD KO females compared to HFD WT females. However, KO males exhibited no significant differences in body weight, body composition, or glucose tolerance between the genotypes on either diet. This data suggests that KNDy neuron kisspeptin is critical for metabolic homeostasis and preventing metabolic dysfunction when challenged with a high-fat diet. Our findings further suggest a sexual dimorphism whereby KNDy neuron kisspeptin performs this action predominantly in females.

Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF01 | PMON45 Urocortin 3 Interaction with GABA and Glutamate in the Posterodorsal Subnucleus of The Medial Amygdala Mediates Suppression of GnRH Pulse Generator Frequency in Female Mice
Authors: Ivanova Deyana , Li Xiao-Feng , McIntyre Caitlin , Xu HongBei , O’Byrne Kevin
Published: November 2022

Stress exerts a profound impact on reproductive function and disrupts pulsatile luteinizing hormone (LH) secretion. The posterodorsal subnucleus of the medial amygdala (MePD) is an upstream modulator of the hypothalamus pituitary gonadal axis. Stress alters neuronal activity within the MePD, increasing the expression of Urocortin3 (Ucn3) while enhancing the inhibitory output from the MePD to key hypothalamic reproductive centres. Designer receptor exclusively activated by designer drugs (DREADDs) inhibition of MePD Ucn3 neurons prevents psychological stress-induced suppression of LH pulses in female mice. The neurochemical pathways in the MePD responsible for regulating the GnRH pulse generator in the presence of stress remain unknown. We investigate the neurotransmission involved in the neural circuitry responsible for the suppression of GnRH pulse generator activity by MePD Ucn3 neuronal activation. Ucn3-Cre-tdTomato female ovariectomised (OVX) mice were unilaterally injected with AAV-ChR2 and implanted with optofluid cannulae targeting the MePD. Firstly, we optically stimulated MePD Ucn3 neurons with blue light at 10 Hz, 10 mW and monitored the effect on LH pulses. Next, we combined optogenetic activation of MePD Ucn3 neurons with pharmacological antagonism of GABAA or GABAB receptors with bicuculline or CGP, respectively, and observed the effect on LH pulsatility. Finally, during optical activation of MePD Ucn3 neurons we administered a combination of NMDA and AMPA receptor antagonists, AP5 and CNQX respectively, and monitored the effect on pulsatile LH secretion. Optogenetic stimulation of MePD Ucn3 neurons suppressed pulsatile LH secretion compared to controls and administration of aCSF had no effect on LH pulse interval (MePD Ucn3 activation: 36.04 ± 2.49 vs. pre-treatment control period: 17.50 ± 0.67 vs control virus: 21.67 ± 1.67 min; mean ± SEM; p<0.0001; n=12). Intra-MePD infusion of bicuculline (BIC) or CGP during optogenetic stimulation of MePD Ucn3 neurons completely blocked the suppressive effect of MePD Ucn3 neuronal activation on LH pulsatility (MePD Ucn3 activation and BIC: 20.50 ± 2.03 vs. pre-treatment control period: 17.58 ± 0.75 min; MePD Ucn3 activation and CGP: 16.30 ± 0.63 vs. pre-treatment control period: 17.50 ± 0.77 min; n=7-10). Intra-MePD infusion of AP5 + CNQX during optogenetic stimulation of MePD Ucn3 neurons similarly completely blocked the suppressive effect of MePD Ucn3 neuronal activation on LH pulsatility (MePD Ucn3 activation and AP5 + CNQX: 19.58 ± 1.42 min; n=6). Our findings show for the first time that optogenetic stimulation of MePD Ucn3 neurons inhibits GnRH pulse generator activity via GABA and glutamate signalling within the MePD.

Presentation: Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF01 | PMON46 Regulation of the Pituitary Cell Lineage Regulator Prop1 by the Stem Cell Determinant Musashi
Authors: Banik Jewel , Childs Gwen V , Hardy Linda L , Lim Juchan , MacNicol Angus M , MacNicol Melanie C , Tomlinson Sophia , Urbaniak Alicja
Published: November 2022

The pituitary gland controls responses to changing physiological requirements during growth, pregnancy, puberty, and stress. Synthesis and secretion of appropriate pituitary hormones in response to changing organismal demands is mediated through a remarkable capacity for cellular plasticity of the distinct hormone-producing cells. The mechanisms governing pituitary cellular plasticity are not fully understood. We hypothesize that plasticity in the adult tissue is mediated through similar mechanisms to those that occur during embryonic and postnatal pituitary development. The Prophet of Pit1(Prop1), a paired-like homeodomain transcription factor, is the earliest pituitary-specific transcription factor and is highly expressed in pituitary progenitor cells where it controls lineage commitment to the distinct hormone-producing cell types. Our recent work has identified post-transcriptional regulation of pituitary gene expression in the adult tissue via the stem cell determinant, mRNA binding protein, Musashi. The full-length mouse Prop1 (mProp1) mRNA 3' untranslated region (UTR) contains 24 consensus binding elements for Musashi (MBEs) and demonstrates Musashi1-dependent translational activation in vitro. Specifically, the terminal mProp1 3' UTR MBE directs 40% of Musashi1-mediated translation activation, and mutational disruption of this terminal MBE abolishes all Musashi1-dependent translational activation. Immunoprecipitation of Musashi-mRNA complexes from adult mouse pituitaries confirmed Musashi1-mProp1 mRNA association in adult tissue. The gene sequence data for the human Prop1 (hPROP1) mRNA 3' UTR is incomplete in the Ensembl and RefSeq databases. Using published RNA sequencing datasets, we identified an expressed full-length hPROP1 mRNA 3' UTR of 6996 nucleotides with 54 predicted consensus MBEs, suggesting that the human PROP1 mRNA, like the murine Prop1 mRNA, may be subject to Musashi-dependent translational control. Our findings are consistent with the hypothesis that the Musashi protein exerts evolutionarily conserved control of Prop1 mRNA translation to facilitate plasticity of anterior pituitary function.

Presentation: Saturday, June 11, 2022 1:31 p.m. - 1:36 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON186 Beta-agonist Profiling Reveals Novel Biased Signaling Phenotypes For The Beta 2-adrenergic Receptor With Implications In The Treatment Of Asthma
Authors: Pascali Francesco D , Ippolito Michael , Wolfe Emily , Komolov Konstantin E , Hopfinger Nathan , Lemenze Douglas , Kim Nicholas , Armen Roger S , An Steven S , Scott Charles P , Benovic Jeffrey L
Published: November 2022

Asthma involves chronic airway inflammation and airway smooth muscle (ASM) cell contraction. Treatment include agonists of the beta 2-AR, a GPCR that induces the Gs/cAMP pathway leading to ASM relaxation. These agonists can also promote severe side effects which have been correlated with beta-arrestins (barr) activation. Therefore, biased ligands selective for the Gs/cAMP pathway over the barr-induced side effects should be beneficial. To test this, we have used high-throughput screening to identify Gs-biased agonists. The initial lead candidates were further analyzed for their ability to modulate Gs and Gi interaction, cAMP production, and barr interaction. We identified three compounds which showed minimal barr recruitment as well as decreased barr-mediated outputs including receptor internalization and ERK activation. They also showed reduced GRK-mediated phosphorylation of the receptor as well as decreased agonist-promoted receptor desensitization in human ASM cells. These Gs-biased agonists may contribute to develop more effective drugs for asthma and may help to determine the structure determinants of receptor mediated biased signaling.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBSMON194 Diagnosing Adrenal Insufficiency In Children: A Survey Among Pediatric Endocrinologists In North America
Authors: Silva Carolina , Patel Trisha , Lam Carol
Published: November 2022

Accurately diagnosing adrenal insufficiency (AI) is of vital importance, but it can be challenging, particularly in children. While the ACTH stimulation test remains the gold standard test for diagnosing AI, its protocols and interpretation of results remain controversial. There are no international recommendations specific for the pediatric age group.

Objective

to understand current practices of North American pediatric endocrinologists, regarding the diagnosis of AI in children, with focus in interpreting results of ACTH stimulation tests.

Methods

an anonymous, electronic survey was sent to members of the Pediatric Endocrine Society in February of 2022. Email reminders were sent over the following month, and the survey was closed after 6 weeks. RedCap was used to administer the survey and store data.

Results

221 survey responses were included. 52% of participants had more than 10 years of clinical experience, and 78% practiced in academic centers. All respondents ordered ACTH stimulation tests for the diagnosis of AI; 82% also used morning cortisol levels, 77% used cortisol levels during stress, and 14% used random cortisol. For the diagnosis of primary AI, 85% chose high-dose ACTH stimulation tests (HDST). For secondary AI, 62% ordered low-dose ACTH stimulation tests (LDST), 22% HDST, and the remainder used both. The most frequently used time points for the HDST were 0 and 60 minutes, and for the LDST, 0, 30 and 60 minutes. For interpretation of ACTH stimulation test results, 95% considered peak cortisol levels, 70% also took into context the clinical picture, and 48% considered the relative increase in cortisol levels from baseline. 17% of respondents used different cutoff values for LDST vs. HDST; 18% used specific cutoffs for newborns. Median (IQR) cortisol levels after ACTH stimulation tests for diagnosing AI was 18 (15.5-18) ug/L; 54% of participants used 18 ug/dL, 40% considered levels between 10 and 18 ug/L, and 7% used cutoffs between 18 and 20 ug/L. Finally, 43% of providers did not know what type of cortisol assay was used in their laboratory.

Discussion

In North America, pediatric endocrinology providers use ACTH stimulation protocols variably, including decisions about HDST vs. LDST, time points for cortisol measurement, and interpretation of results. Notably, there was a wide distribution of responses concerning cortisol cutoffs. Also, a significant proportion of providers who ordered and interpreted results of ACTH stimulation tests did not know which biochemical assay was employed. These exploratory results highlight the need for pediatric-specific recommendations on ACTH stimulation protocols, based on the best available evidence.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP374 Abdominal Distention as a Unique Sign of Congenital Hypothyroidism
Authors: Antezana Vania Lizzeth Escobar , Dorado Juan Pablo Hayes , Justiniano Walter Montero , Colque Doris Maribel Totola , Parada Valeria Urizar , Arias Paola Andrea Colque
Published: November 2022

Background

Most neonates with congenital hypothyroidism have a normal appearance at birth. Infrequent clinical presentations have been reported, including abdominal distention as the only sign, which remit with the initiation of levothyroxine therapy.

Clinical Case

Female newborn, full-term, appropriate weight for gestational age, six days old, who presented abdominal distension, without vomiting and with normal meconium elimination. No visceromegaly or abdominal masses were palpated. With the diagnosis of sepsis, treatment was started with ampicillin and amikacin, decompressive nasogastric tube and intravenous fluids. Abdominal X-ray showed intestinal distension. The requested cultures were negative. On the seventh day of life a TSH level of 89 mlU/L was reported; the free T4 value was analyzed and was found to be low. With the diagnosis of congenital hypothyroidism, levothyroxine therapy was indicated, and the abdominal distension remitted one week after initiation of therapy.

Conclusion

Most cases of congenital hypothyroidism are asymptomatic; abdominal distension, as the only sign of congenital hypothyroidism, is caused by the lower intestinal motility frequently observed in congenital hypothyroidism.

Presentation: No date and time listed
ODP386 Growth Velocity and Growth Hormone Deficiency During Puberty
Authors: Currais Carolina , Seeherunvong Tossaporn
Published: November 2022

Background

A subnormal growth velocity (GV) is a characteristic feature of growth hormone deficiency (GHD). During puberty growth hormone (GH) levels increase markedly in response to sex hormone secretion. The normal range for GV declines during childhood, increases during puberty with peak levels at mid-puberty. Hence, pubertal status rather than age alone must be considered in the evaluation of GV in children and adolescents. In most cases, a diagnosis of GHD is established by a subnormal response in GH levels following a stimulation with two pharmacological agents.

Objective

We determined the reliability of GV as a predictor of GHD during puberty.

Methods

We conducted a retrospective study of pubertal children and adolescents who underwent a GH stimulation test in our pediatric endocrinology clinic. Seventy-nine subjects (57 boys and 22 girls) were included in this study. Bone age was determined for all patients. Serum levels of insulin like growth factor-1 (IGF-1) were obtained prior to GH stimulation test. Serum IGF-1 levels, expressed as a standard deviation score were compared to the IGF-1 levels expected chronological age (CA), height age (HA), and bone age (BA). Serum GH levels were determined following the administration of arginine and levodopa. GHD was established by a peak GH level <10 ng/mL. IBM SPSS Statistics software version 28. 0. 0. 0 (190) was used for data analysis.

Results

Subjects ranged in age from 7.3-17.9 years. Thirty-nine patients (49.4%) had GV < 10 th percentile for CA; Forty patients (50.6%) had GV <10 th percentile for BA. Sixty percent of patients with GV <10 th percentile for CA had GHD. A similar number (59%) of patients with normal GV for CA also had GHD. Among patients with GV <10 th percentile for BA, 72.5% of subjects had GHD. By contrast, the percentage of patients who had normal GV for bone age and GHD (46.2%) was significantly less than that of subjects with GV <10 th percentile for BA (p = 0. 015). Positive predictive value, negative predictive value, sensitivity and specificity for GV <10 th percentile for BA in the diagnosis of GHD were 72.5%, 53.8%, 61.7%, and 65.6%, respectively. With respect to the diagnostic value of serum IGF-1, when the area under the ROC curve was used to measure how well the serum IGF-1 standard deviation score distinguished between GHD and normal, serum IGF-1 standard deviation score for CA, HA, and BA were not predictive of GHD (p = 0.1, 0.47, and 0.27, respectively).

Conclusions

During puberty, slow growth velocity for bone age (but not slow growth velocity for chronological age) was useful to predict a diagnosis of growth hormone deficiency.

Presentation: No date and time listed
ODP389 Lipid Peroxidation System Reactivity in Adolescents During Constitutional Obesity Non-drug Therapy
Authors: Darenskaya Marina , Rychkova Lyubov , Kolesnikov Sergey , Kravtsova Olga , Semenova Natalya , Nikitina Olga , Kolesnikova Lyubov
Published: November 2022

Background

In recent years, there has been a worldwide trend toward preventing and controlling childhood obesity by non-drug therapy. The success of this trend largely depends on better understanding the various metabolic and regulatory systems functions. Lipid peroxidation (LPO) - antioxidant defense (AOD) nonspecific system reactivity should be of special attention. The aim of the study was to reveal the lipid peroxidation and antioxidant defense parameters changes in different sex's adolescents during constitutional obesity non-drug therapy.

Materials and methods

Adolescents of 12-17 years old with constitutional obesity (CO) (22 boys and 24 girls) before and after constitutional obesity non-drug therapy were examined. The therapy included routine recommendations for food consumption modification, motivational education in the School of Rational Eating, a steady diet, a low-calorie diet, aerobic physical exercises (running track), impulse physiotherapy on the rectus abdominis. Healthy teenager's data (20 boys and 16 girls) were used as a control. We analyzed the content of LPO products - diene conjugates (DC), ketodienes and conjugated trienes (KD and CT), TBA-active products and AOD factors activity: total antioxidant activity (TAA), α-tocopherol, retinol, reduced (GSH) and oxidized (GSSG) glutathione, superoxide dismutase activity (SOD). Spectrophotometric and fluorometric methods were used.

Results

The boys with CO had decreased values of primary LPO products – DC (by 1.35 times lower, p=0. 001) and AOD factors: TAA (by 1.16 times lower, p=0. 036) and SOD activity (by 1.49 times lower, p<0. 0001), against the increased background values of secondary products - KD and CT (by 1.42 times higher, p=0. 046) in comparison with control results. Boys with CO therapy did not lead to normalization of the studied parameters. The girls with CO had decreased values of TAA values (by 1.4 times lower, p=0. 0001), SOD (by 1.42 times lower, p<0. 0001) and α-tocopherol (by 1.33 times lower, p=0. 012) compared to the control group. After the course of therapy, there was an increase in GSSG levels (by 1.14 times higher, p=0. 029).

Conclusions

This study showed the presence of negative changes in the pro- and antioxidant status in adolescents with CO, which did not normalize after a course of non-drug therapy. Additional pharmacological correction by prescription of antioxidant drugs becomes relevant in addition to the course of non-drug therapy.

Presentation: No date and time listed
ODP391 Neurodevelopmental and Growth Outcome of Congenital Hypothyroidism: A National Investigation of Birth Cohort Study
Authors: Jung Mo Kyung , Cha Hye Ryeong , Lee Seung Won , Ha Eun Kyo , Kim Ju Hee , Yoo Eun-Gyong , Han Man Yong
Published: November 2022

Objectives

The purpose was to investigate the neurodevelopmental and growth status of Congenital hypothyroidism (CH) patients compared to normal children using population-based cohort study.

Methods

The National Investigation of Birth Cohort in Korea study 2008 (NICKs-2008) consisted of the Korean National Health Insurance System (NHIS) and the National Health Screening Program for Infants and Children (NHSPIC) databases comprising children born in 2008 (n=469,248) and 2009 (n=448,459). The CH patients were enrolled with International Classifications of Diseases-10 codes and drug classification (levothyroxine over 5 years) codes. We investigated their developmental outcomes using the Korean-Ages and Stages Questionnaire (K-ASQ), and serial changes of BMI (BMI-z) and height (height -z) were compared in children with and without CH. Risk ratios were obtained using a modified Poisson regression and weighted risk differences using binomial regression.

Results

Of the 919,707 newborns, 433 children (boys, 47.7%) were diagnosed as CH (1: 2,124 of prevalence). The risk ratio (RR) for delayed development based on the results from the 5th–7th K-ASQ was higher for the total developmental area (adjusted RR = 2.77, 95% CI: 1.507-5.118) in CH patients. There was significant difference between patients with CH and controls in the assessment of gross motor, fine motor and problem-solving areas (P < . 0001). At 66-71 months of age, short stature (height-z < -1.63) were increased in the CH group compared with normal children (adjusted RR 2.27, 95% CI 1.328-3.865). Obese children (BMI-z > 1.63) were not increased.

Conclusions

The adequate large cohort data showed that prevalence of developmental delay and short stature were higher in CH patients than normal. Careful and early intervention is needed.

Presentation: No date and time listed
OR05-1 Testicular Magnetic Resonance Imaging (MRI) Findings and Predictive Factors of Gonadal Neoplasia in Complete Androgen Insensitivity Syndrome
Authors: Carvalho Filomena Marino , Coelho Fernando Morbeck Almeida , Costa Elaine Maria Frade , Craveiro Flora Ladeira , Dantas Patricia Perola , Domenice Sorahia , Mendonca Berenice Bilharinho , Viana Publio Cesar Cavalcante , Batista Rafael Loch
Published: November 2022

Introduction

Complete Androgen Insensitivity Syndrome (CAIS) is characterized by a complete external genitalia appearance and testicular development in 46,XY individuals carrying inactivating mutations in the AR gene. Prophylactic gonadectomy versus saving gonads has been debatable in CAIS management, mainly due to the absence of an accurate biomarker for testicular germ cell tumors (GCT).

Objective

to cross the preoperative pelvic MRI data with the histological gonadal findings from CAIS patients who underwent prophylactic gonadectomy to identify predictive factors of GCT development.

Methods

We evaluated 30 gonads from 15 CAIS patients with proven AR mutation. All performed pelvic MRI before gonadectomy through the same MRI machine and were included in the MRI data analysis. Three blinded radiologists specialized in urology performed image analysis. The immunohistochemical markers PLAP, c-KIT, OCT3/4, SALL4, ER, alpha-inhibin, CD99, and calretinin were performed.

Results

Nine (60%) performed gonadectomy after puberty (>16 years old). We identified one case of classical seminoma and one case of Sertoli cell neoplasia (at 18 and 19 years of age, respectively). Overall, the prevalence of neoplasia was 13.3%. No case of premalignant intratubular germ cell neoplasia was detected.Histological data revealed a high prevalence of benign lesions (n=12; 80%). Leydig Cell Hyperplasia (67%), stromal fibrosis (53%), Sertoli Cell nodules (47%), hamartomatoums nodules (40%) and paratesticular cysts (67%) which are more frequent after puberty (p<.01). MRI detected heterogeneity in all cases harboring hamartomatoums nodules, Sertoli cell nodules, and testicular neoplasia. Benign lesions were bilateral in all cases. Regarding the MRI data, the presence of testicular cystic mass (by tumoral necrosis) on MRI and tumor size (higher among malignancies) correlated with malignancy (p=.008 and p=.03, respectively), whereas gonadal location (inguinal/abdominal), presence of solid nodules, T2WI and postcontrast features, nodule diffusion restriction, and presence of perigonadal cysts did not. Chronological age >16 years was associated with malignancy with a 4.3 OR (1.6–11.69).

Conclusion

Pelvic MRI is sensitive to detect gonadal nodules in CAIS patients, regardless of the gonad position, but most nodules are benign. Testicular malignancy should be suspicious in the presence of testicular cystic mass and large testis size in CAIS patients >16 years old.

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