bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMON144 FOXO1 is required for glucocorticoid induced somatotrope maturation
Authors: Das Pratyusa , Ellsworth Buffy Sue 
Published: November 2022

Abstract
The pituitary somatotrope is responsible for the secretion of growth hormone (GH). GH deficiency (GHD) affects 1 in 4000 to 1 in 10,000 live births and can manifest as a partial or complete insufficiency of GH from the pituitary gland. Evidence shows that GH secretion can be directed by several transcription factors (TF) and some hormones such as glucocorticoids that play the main role not only in somatotrope maturation but also maintenance of function. We found that FOXO1 is required in glucocorticoid induction of important somatotrope genes. Inducing somatotrope-derived MtT/S cells, with glucocorticoid for 96 hours, showed upregulation of Gh1, Ghrhr, Foxo1, and the calcium binding protein, C2cd4a. Deletion of Foxo1 from MtT/S cells using CRISPR/Cas-9 impairs basal and glucocorticoid-induced expression of Gh1 and C2cd4a, but does not impair expression of Ghrhr. GH protein is also reduced in Foxo1 deleted clones compared to control. In mice, we find that dexamethasone, a synthetic glucocorticoid, can stimulate premature somatotrope maturation at e15.75. Evidence of premature maturation includes presence of GH protein and increased expression of Gh1. To sum up, these data demonstrate that FOXO1 may be an important factor mediating glucocorticoid induction of somatotrope maturation.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON166 Safety Comparison of 40- vs 60-mg/day Doses of Oral Octreotide Capsules for Treatment of Acromegaly in the CHIASMA OPTIMAL Trial
Authors: Elenkova Atanaska , Jensterle Mojca , Kennedy Laurence , Manning Patrick , Melmed Shlomo , Strasburger Christian J , Samson Susan , Nachtigall Lisa , Fleseriu Maria , Molitch Mark E , Giustina Andrea , Haviv Asi , Biermasz Nienke 
Published: November 2022

Abstract

Background
Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States who have previously responded to injectable somatostatin receptor ligands (iSRLs, octreotide or lanreotide). In previous phase 3 studies, the safety of OOC was shown to be consistent with iSRLs, without dose-dependent adverse reactions. In the double-blind, placebo-controlled period (DPC) of the CHIASMA OPTIMAL trial (NCT03252353), patients were randomized to twice-daily OOC at 40-mg/day, with the option for up-titration to 80-mg/day. In contrast, patients entered the open-label extension (OLE) at a 60-mg/day dose.

Objective
Examine the safety of 40-mg/day versus 60-mg/day OOC doses.

Methods
Eligible patients had the option to enroll in the OLE following the core trial. All patients received OOC 60-mg/day upon entering the OLE regardless of prior treatment in the DPC, including patients who received placebo in the DPC. OOC doses were up- or down-titrated based on insulin-like growth factor I (IGF-I) level and/or acromegaly signs or symptoms. The current analysis compared the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAE-related study drug discontinuation, and acromegaly-related TEAEs (defined as new or worsening signs or symptoms of acromegaly).

Results
Twenty-eight patients randomized to OOC in the DPC (40-mg/day dose) and 19 who were originally randomized to placebo and continued into the OLE (60-mg/day dose) were included in the analysis. Biochemical control was similar in both groups as demonstrated by mean IGF-I levels over the respective periods. Ninety-six percent of patients on 40-mg/day and 57.9% on 60-mg/day experienced ≥1 TEAEs. Two patients on 60-mg/day reported a total of 2 SAEs, both deemed unrelated to study drug. Two patients on 40-mg/day experienced TEAEs leading to study drug discontinuation (headache and gastrointestinal symptoms). The incidence of acromegaly-related TEAEs was generally lower in those on 60-mg/day versus 40-mg/day.

Conclusions
This is the first analysis exploring differences in OOC doses. The nature and incidence of TEAEs occurring with an OOC dose of 60-mg/day versus 40-mg/day were similar, though this analysis was limited by differences in TEAE reporting across sequential phases of a lengthy trial. A trend was observed for decreased incidence of acromegaly-related TEAEs with the 60-mg/day dose. This finding is in line with previous analyses showing no dose-related TEAEs with OOC.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON35 An Unusual Case of Sporadic Congenital Hypopituitarism Presenting With Micropenis and Infantile Adrenal Crisis
Authors: Wojeck Brian , Peter Patricia 
Published: November 2022

Abstract

Introduction
Congenital hypopituitarism is a rare and potentially devastating disorder occurring in 1 in 4000 to 1 in 10,000 live births. Congenital hypopituitarism can occur due to mutations in transcription factors and signaling molecules involved in the embryologic development of the pituitary. In a small number of cases there is a family history of the disorder. In these cases, multiple genes have been implicated including HESX1, PROP1, POU1F1, LHX3, LHX4, SOX2, SOX3, OTX2, PAX6, FGFR1, GLI2, and FGF8 with different forms of inheritance. However, the majority (80-90%) of these cases are sporadic, and patients do not have an identifiable genetic mutation. We present a case of sporadic congenital hypopituitarism to bring awareness to this unusual disorder.

Case
At birth, the patient's pediatrician noted that he had a micropenis on physical exam. Six weeks later he became hypotonic in his mother's arms and was rushed to a local hospital where he was found to a blood glucose of 18 mg/dL. As part of this evaluation, a head CT was performed which revealed an empty sella. Endocrinology was consulted and found that he was adrenally insufficient and hypothyroid. He was started on hormone replacement, improved and was discharged. At 18 months old, he had a grand mal seizure in the setting of an infection during which he required stress dosing of steroids. Since that time, he has remained seizure-free and without any episodes of adrenal crisis. At age 12, he was started on testosterone injections for the initiation of puberty and remained on this therapy for 2 years. He was also briefly on growth hormone supplementation during this time. He had mood swings with this formulation and so was converted topical testosterone though has had intermittent adherence to this. He had some excess urination in the past and was trialed on DDAVP, but this was eventually discontinued as laboratory evaluation was not consistent with diabetes insipidus. On presentation to adult endocrinology, his hormone replacement was adequate aside from low testosterone levels related to intermittent adherence and a low IGF-1 level.

Conclusion
Congenital hypopituitarism is a rare, potentially life-threatening disorder that can be difficult to diagnose. Patients that present at birth with hypoglycemia and micropenis should be evaluated for this condition early in their course. These patients require a complete pituitary evaluation and prompt treatment for pituitary hormone abnormalities. Ophthalmic evaluation is also indicated as many patients have abnormal development of optic nerves. We present this case to bring awareness to this unusual disorder.

References
[1] Bosch I Ara L, Katugampola H, Dattani MT. Congenital Hypopituitarism During the Neonatal Period: Epidemiology, Pathogenesis, Therapeutic Options, and Outcome. Front Pediatr. 2021;8: 600962. Published 2021 Feb 2. doi: 10.3389/fped.2020.600962
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON97 Pituitary Abscess: Long-term follow up
Authors: Hoang Thanh , Brown Kevin , Leimbach Robert , Hatfield Jennifer , Shakir Mohamed 
Published: November 2022

Abstract

Introduction
In spite of recent advances in radiological evaluation, preoperative diagnosis of pituitary abscess is often difficult and the diagnosis is established at the time of surgery. Most patients present with a chronic and indolent course with few infective manifestations, thus mimicking a pituitary tumor. Although there are several case reports in literature, long term follow-up of these patients have not been reported previously. We report long-term follow-up of two patients with pituitary abscess who underwent trans-sphenoidal surgery (TSS).

Case 1
A 45-year-old female was seen in endocrine clinic for follow-up of a pituitary abscess diagnosed 22 years earlier. At the age of 23, the patient had severe headaches and bitemporal visual field defects. Workup included a pituitary MRI which revealed a 2.3 cm mass with compression of the optic chiasma. She denied any fever or chills. Detailed pituitary function confirmed secondary hypogonadism and secondary adrenal insufficiency. Because of the visual defects she underwent TSS which revealed the diagnosis of pituitary abscess. Additionally, the pituitary abscess was confirmed by histological examination and cultures from the abscess grew coagulase negative staphylococcus. Anaerobic and fungal cultures were negative. The patient was successfully treated with vancomycin, ceftazidime and metronidazole. After the TSS, she required treatment for diabetes insipidus, central hypothyroidism, adrenal insufficiency and hypogonadism. For the last 22 years she has had no further major illnesses and continues to require treatment for diabetes insipidus and hypopituitarism.

Case 2
A 37-year-old female underwent evaluation for migraines 7 years ago. During workup, a pituitary MRI showed a 6×5 mm lesion suggestive of a partially cystic microadenoma. The patient had worsening of her headaches and a follow-up MRI 6 weeks later showed an enlarging heterogeneous pituitary macroadenoma now 1.9×2.1×1.5cm, with marked effect on the optic chiasm. The patient underwent TSS and intraoperatively a diagnosis of pituitary abscess was made. Although cultures were negative for any pathogens, the patient received empiric antibiotic treatment with cefotaxime and metronidazole for 4 weeks. After the TSS, she developed central diabetes insipidus and hypopituitarism. Since surgery she has had no significant illness and has been leading an active life for the last 7 years.

Conclusion
Both of these patients underwent treatment with TSS with an intraoperative diagnosis of pituitary abscess and were able to recover with no long-term sequelae or evidence of recurrent abscesses. They did however develop the common side effects of TSS surgery including diabetes insipidus and hypopituitarism, but are able to live a normal life on medical therapy.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF13 | PMON92 Chance or Pedigree?: A Rare Case of Familial ACTH Producing Pituitary Tumor
Authors: Gordon Ashley , Azmath Misbah , Kantorovich Vitaly 
Published: November 2022

Abstract

Background
ACTH secreting pituitary adenomas are rare accounting for only 5-10% of pituitary adenomas. Most often these are sporadic, however there are rare associated familial disorders and genetic mutations. This case highlights a 41-year-old male with an ACTH secreting macroadenoma similar to one found in his brother previously.

Case
A 41-year-old male with no significant medical history presented to the hospital with headaches and visual changes for the past week and decreased libido, weight gain, and cold intolerance for the past year. Physical exam demonstrated left eye ptosis, proptosis, and pupillary dilation with intact visual fields, as well as Cushingoid features including BMI 35.1, abdominal obesity with striae, enlarged breasts and tanned skin. Family history revealed a brother diagnosed with an ACTH producing pituitary microadenoma requiring surgical resection 18 years prior.Brain MRI revealed a 2.6×2.5×3.7 cm sellar mass with optic chiasm compression and pituitary apoplexy. Labs revealed elevated ACTH 708 pg/mL (7.2–63 pg/mL) suggesting a functional macroadenoma, as well as signs of early hypopituitarism with TSH 0.37 uIU/mL (0.35-5.50 uIU/mL), free T4 0.5 ng/dL (0.5-1.3 ng/dL), free T3 2.6 pg/mL (2.3–4.2 pg/mL), prolactin 2.0 ng/mL (2.6-13.1 ng/mL), GH 0.2 ng/mL (&lt;/= 7.1 ng/mL).
He received Dexamethasone and Levothyroxine before undergoing transsphenoidal resection which confirmed an ACTH-secreting macroadenoma resulting in Cushing's disease. Given his family history, he underwent evaluation for MEN (multiple endocrine neoplasia) which revealed normal gastrin, calcium, calcitonin, PTH and chromogranin A. Furthermore, the patient and his brother underwent genetic testing which was negative for mutations associated with isolated familial pituitary adenomas (including MEN1, CDKN1A, PRKAR1A, AIP). After discharge, he was started on testosterone and transitioned to hydrocortisone with plans for ACTH stimulation test and steroid taper as tolerated.

Conclusion
Pituitary adenomas are fairly common, and most tend to be sporadic. ACTH secreting pituitary adenomas are rare and in rarer instances can be inherited as isolated tumors or as part of multiple endocrine neoplasia syndrome [1]. Early identification of genetic predisposition can allow for screening of associated comorbidities and early screening in family members. The patient and his brother both had rare ACTH-secreting adenomas, however genetic testing for genes associated with familial disorders was unrevealing in this case. While it is possible that the ACTH secreting tumors in both brothers were sporadic or due to environmental exposure, it is also possible that they share a genetic mutation not yet identified.

References
[1] Dworakowska D, et al. The pathophysiology of pituitary adenomas. Best Practice & Research Clinical Endocrinology & Metabolism. 2009;23(5): 525-541.
Presentation: Sunday, June 12, 2022 1:24 p.m. - 1:30 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF25 | PMON76 Kissing carotid arteries: An unusual cause of male hypogonadotropic hypogonadism.
Authors: Bushman Jordan , Esfandiari Nazanene , Bapuraj Jayapalli , Shlensky David 
Published: November 2022

Abstract

Background
Aneurysms of the internal carotid arteries are a rare cause of pituitary dysfunction1. While there are reports of primary amenorrhea in females due to ectatic internal carotid arteries2, hypogonadism in a male due to "kissing internal carotid arteries" causing compression of the pituitary gland has not previously been reported.

Clinical Case
A 27-year-old male with history of Crohn's disease, obesity, depression and sleep apnea on CPAP presented to endocrinology clinic for evaluation of low testosterone levels diagnosed 9 months prior to his initial visit. At the time of initial evaluation patient was using intramuscular testosterone cypionate 120mg weekly with total testosterone of 2.43 ng/mL (2.50-9.50 ng/mL). Testosterone replacement therapy was discontinued at that time to assess the hypothalamic-pituitary-gonadal (HPG) axis. After 9 months without testosterone treatment, repeat labs demonstrated total testosterone 0.91 ng/mL, bioavailable testosterone 0.69 ng/mL (1.10-4.0 ng/mL), SHBG 8 nmol/L (10-89 nmol/L), LH 3.1 mIU/mL (2-12 mIU/mL), FSH 2.7 mIU/mL (1.5-10 mIU/mL), estradiol 23 pg/mL (6-44 pg/mL), IGF-1 193 ng/mL (85-310 ng/mL), prolactin 10 ng/mL (3-23 ng/mL), TSH 1.03 mIU/L (0.3-5.5 mIU/L), FT4 1.15 ng/dL (0.76-1.70 ng/dL), 8 AM cortisol 13.5 ug/dL (5.3-22.5 ug/dL) and ACTH 37 pg/mL (5-52 pg/mL). Semen analysis was also performed which was unremarkable. Pituitary MRI revealed symmetric ectatic cavernous portions of the internal carotid arteries compressing and distorting the normal anatomy of the anterior pituitary gland consistent with "kissing carotid arteries." MRA was performed which did not demonstrate aneurysm or malformation of the cavernous internal carotid arteries. Patient was started on subcutaneous semaglutide 0.25mg weekly which was titrated to 1mg weekly for treatment of obesity. Testosterone replacement therapy was not re-initiated given future fertility goals and normal semen analysis.

Conclusion
To our knowledge, this is the first reported case of kissing internal carotid arteries causing isolated hypogonadotropic hypogonadism in a male patient.

References
1) Heshmati HM, Fatourechi V, Dagam SA, Piepgras DG. Hypopituitarism caused by intrasellar aneurysms. Mayo Clin Proc. 2001 Aug;76(8): 789-93. doi: 10.1016/S0025-6196(11)63222-9. PMID: 11499817 2) Sahin M, Dilli A, Karbek B, Unsal IO, Gungunes A, Colak N, Uçan B, Cakal E, Ozbek M, Delibasi T. Unusual cause of primary amenorrhea due to kissing internal carotid arteries. Pituitary. 2012 Jun;15(2): 258-9. doi: 10.1007/s11102-012-0393-9. PMID: 22492265.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:44 p.m. - 12:49 p.m.
LBMON196 A Randomized Controlled Trial Of Vosoritide In Infants And Toddlers With Achondroplasia
Authors: Savarirayan Ravi , Wilcox William W , Harmatz Paul , III John Phillips , Polgreen Lynda E , Tofts Louise , Ozono Keiichi , Arundel Paul , Irving Melita , Bacino Carlos A , Basel Donald , Bober Michael B , Charrow Joel , Mochizuki Hiroshi , Kotani Yumiko , Saal Howard M , Jeha George , Han Lynn , Fisheleva Elena , Huntsman-Labed Alice , Day Jonathan 
Published: November 2022

Abstract

Background
Vosoritide increases annualized growth velocity (AGV) in children with achondroplasia aged 5 to 18 years. This global, phase 2, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of vosoritide on growth in children with achondroplasia aged 3 months to &lt;5 years.

Methods
This study compared once-daily subcutaneous administration of vosoritide, at doses of 15 or 30 μg/kg of body weight, with placebo. Eligible patients had participated, for up to 6 months, in an observational growth study to calculate their baseline AGV. The primary objective was to evaluate the safety and tolerability of vosoritide in children with achondroplasia. The primary efficacy evaluation was the change from baseline in height Z-score versus placebo at week 52 using an ANCOVA model. Secondary efficacy analyses included change from baseline in AGV and upper-to-lower body segment ratio versus placebo at Week 52 using an ANCOVA model.

Results
A total of 75 patients were enrolled, with 11 sentinel subjects who received vosoritide to establish PK and safety. A further 32 were randomized to receive vosoritide and 32 to receive placebo. A total of 73 patients completed the 52-week trial. All patients reported at least one adverse event. Four serious adverse events occurred with vosoritide and 8 with placebo, none were treatment-related. Two participants discontinued, one on vosoritide with pre-existing respiratory morbidity who had a fatal respiratory arrest and one on placebo who withdrew consent. In the full analysis population, vosoritide (n=43) compared to placebo (n=32), increased height Z-score by 0.30 SD (95% CI 0. 07, 0.54); increased AGV by 0.92cm/year (95% CI 0.24, 1.59); and did not worsen upper-to-lower body segment ratio which changed by -0. 06 (95% CI -0.15, 0. 03).

Conclusions
Daily, subcutaneous administration of vosoritide to young children with achondroplasia was safe and resulted in increases in height Z-score and AGV. (Funded by BioMarin; ClinicalTrials.gov NCT03583697)
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON198 Improving Knowledge And Implementation Of Healthcare Transition (HCT) Policy And Procedure For Transgender And Gender Diverse (TGD) Youth At The UCSF Child And Adolescent Gender Center (CAGC)
Authors: Walch Abby , Pennella Sophia , Russell Meredith R , Lee Janet Y 
Published: November 2022

Abstract

Introduction
The UCSF CAGC has served TGD youth since 2009. Increased referrals coupled with an expanding young adult patient population has resulted in longer wait times and an increased need for transition to adult care services. As part of an ongoing quality improvement initiative to develop an equitable HCT program tailored to the unique needs of TGD youth at the UCSF CAGC, we developed and aimed to improve provider knowledge of a standardized policy and procedure for HCT from pediatric to adult gender care.

Methods
CAGC providers received training in 11/2021 on the HCT policy and procedure, including a standardized method to identify patients with whom to initiate HCT discussions. Providers completed pre- and post-training surveys evaluating knowledge and confidence regarding HCT practices. Knowledge was assessed with yes/no questions and confidence with 5-point Likert scales (1 = lowest, 5 = highest). Pre- and post-survey results were compared using proportions tests for dichotomous outcomes and Wilcoxon rank-sum tests for confidence levels. To evaluate effectiveness, baseline data on % of eligible TGD youth seen in the UCSF CAGC in 1-2/2021 with "Counseling for transition from pediatric to adult care provider" (Z71.89) added to their problem list in the electronic medical record were collected and compared to % of eligible TGD youth with Z71.89 added to their list the 4 consecutive months following the training session.

Results
Nine and 7 CAGC providers completed the pre- and post-training surveys, respectively. Knowledge increased in all areas although not all were statistically significant: Age limit for new patient referrals (78% to 100%, p = 0.18), upper age limit at which patients must transition to an adult provider (56% to 100%, p = 0. 04), standardized method to track patients with whom HCT discussions have been initiated (0% to 100%, p = 0. 0001), and list of criteria for assessing HCT readiness (11% to 100%, p = 0. 0004). Confidence increased in identifying patients with whom HCT has been initiated (median 2 to 4, p = 0. 02) but not in identifying patients ready to initiate the HCT process (median 4 to 4, p = 0.43). The % of eligible TGD youth seen in the UCSF CAGC with Z71.89 added to their problem list increased from 0% at baseline to 72%, 82%, 86%, and 90% in the 4 months consecutively following the training session.

Conclusions
Our findings indicate that standardized training led to increased provider knowledge, participation, patient identification, and implementation of HCT program policy and procedure tailored to our TGD youth population. Future initiatives will include collaboration with adult gender centers to transition TGD youth to adult care services and to evaluate the experiences of TGD youth and providers who receive them.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP082 Thresholds For Normal In Low Dose Cortrosyn Stimulation Depends On Assay Type
Authors: Lutz Natalie Linn Larson , Barger Katie , Newbern Dorothee , Oatman Oliver , Wilson Rochelle , Shaibi Gabriel Q , Beauregard Susan , Velasquez Amy , Kapadia Chirag R 
Published: November 2022

Abstract
Stimulation testing is used to diagnose adrenal insufficiency. The low dose stimulation test uses Cosyntropin 1 mcg to measure cortisol when pituitary disease is suspected. Protocols call for cortisol levels at baseline, 30, and 60 minutes post-administration. A passing peak cortisol threshold of 18 mcg/dl is often used. In 2019, most cortisol assays in our area shifted to more sensitive methods; these are reported to require a lower pass threshold of 12 -14 mcg/dl. We did a retrospective review on 186 consecutive patients in whom newer assays were used, to describe pass/fail rates by timepoint/threshold. Using newer assays, and cortisol cut-off of 14 mcg/dl, a significantly higher percentage pass than if one used newer assays with the older cut-off of 18 mcg/dl (84.9% vs 72%.). When a cut-off of 14 is used, a 60 min assay adds little (pass rate including only 0 and 30 min values =83.3%; pass rate if include 0, 30, and 60 min values = 84.9%). We suggest that with newer assays, interpreting with a 14 mcg/dl cut-off shows higher pass rate than with 18 mcg/dl cut-off. We also suggest that when using newer assays and cut-off of 14 mcg/dl, 60 min assays add little.
Presentation: No date and time listed