bluuebunny/crossref_metadata_2025 huggingface dataset:
OR27-1 11-Oxygenated C19 Steroids Are the Predominant Androgens Responsible for Hyperandrogenemia in Cushing's Disease
Authors: Adaway Jo , Auer Matthias , Bidlingmaier Martin , Braun Leah , Hawley James , Keevil Brian , Lottspeich Christian , Reincke Martin , Reisch Nicole , Schilbach Katharina , Tschaidse Lea , Vogel Frederick , Nowotny Hanna
Published: November 2022

Background

Symptoms of hyperandrogenism are common in patients with Cushing's disease (CD), but they cannot be sufficiently explained by measured concentrations of circulating androgens. In this study we analyzed the contribution of 11-oxygenated (11oxC19) androgens to hyperandrogenemia in female patients with CD as well as the influence of treatment with steroidogenesis inhibitors osilodrostat and metyrapone on 11oxC19 and classic androgens.

Methods

In this single-center study, we assessed saliva day profiles of 23 females with treatment naïve CD, 26 female controls, 5 females with CD treated with metyrapone and 5 treated with osilodrostat for cortisol, cortisone, androstenedione (A4), 11-hydroxyandrostenedione (11OHA4), testosterone (T), 11-ketotestosterone (11KT) by by liquid chromatography tandem mass spectrometry as well as morning baseline levels of gonadotropins and estradiol, sex hormone-binding globulin, cortisol anddehydroepiandrosterone sulfate (DHEAS) in serum and adrenocorticotropic hormone in plasma.

Results

Treatment naïve females with CD showed significantly elevated area under the curve (AUC) of 11OHA4 and 11KT throughout the day compared to controls (11OHA4 mean rank difference (mrd) 18.13, p = 0.0002; 11KT mrd 17.42; p = 0.0005) whereas A4, T and DHEAS were comparable to controls. Patients with more symptoms of hyperandrogenism displayed higher concentrations of 11oxC19 androgens and had significantly lower SHBG concentrations. Gonadotropin levels were normal in all patients with CD (LH 7.18 U/l (SD 14.28 U/l); FSH 7.68 U/l (SD 12.0 U/l)) and did not correlate with any other parameters. Treatment with osilodrostat and metyrapone efficaciously blocked 11oxC19 synthesis. In metyrapone but not in osilodrostat treatment a trend towards increased concentrations of T and significantly increased A4-concentrations were observed (A4 mrd 23.07, p = 0.0119).

Conclusion

Hyperandrogenemia in CD is predominantly caused by excess of 11oxC19 androgens. Due to lower compensatory increase of A4 and T, osilodrostat seems to be more suitable for treatment of females with CD and hyperandrogenism than metyrapone.

Presentation: Tuesday, June 14, 2022 9:45 a.m. - 10:00 a.m.
PMON100 IgG4 hypophysitis with granulomatous histopathology
Authors: Gultekin Sakir , Kargi Atil Y , Barrera Francisco
Published: November 2022

Background

IgG4-related disease is characterized by a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells that may be accompanied by elevated serum IgG4 levels, presence of granulomatous histopathology with multinucleated giant cells has not been reported in patients with IgG4 related hypophysitis.Clinical case: A 39-year-old female with no significant past medical history until April of 2021, when she developed gradual onset of headaches. MRI brain showed a mass in the sella, she was treated for over a month with glucocorticoids by ENT and her headaches improved. She finished the course of glucocorticoids, and soon after, she had a recurrence of her symptoms. Repeat brain MRI revealed a large pituitary mass and she had her first endoscopic endonasal transsphenoidal resection on 8/2021 at an outside hospital. Pathology report of the surgery suggested that she had a colloid cyst of the pituitary and cultures grew actinomyces and streptococcus oralis, likely, as a consequence of contamination from an ethmoid sinus infection/surgical infection, she was treated with antibiotics. Surgery was also complicated by diabetes insipidus for which she is taking desmopressin tablets.She presented to our hospital in November 2021, with persistent symptoms (headaches and worsening vision), and a postoperative brain MRI showing an expansion of the lesion with compression of the optic chiasm, she was evaluated by neurosurgery who recommended repeat revision endoscopic endonasal transsphenoidal resection of this lesion.The patient underwent a second transsphenoidal surgery on 11/29/2021 at our institution. During admission TSH was 0.123 mcIU/ml (0.27-4.2mcIU/ml) with Free T4 0.52ng/dL (0.93-1.7ng/dL). She was discharged on hydrocortisone, desmopressin tablets, and levothyroxine.The pathology report of the second surgery revealed mixed chronic and acute inflammation with granulomatous components containing histiocytic clusters and multinucleated giant cells. Many plasma cells, rare eosinophils, and foci of neutrophils are present. The ratio of IgG4 to IgG is over 70%, with more than 10 IgG4 (+) cells per 10HPF. GMS and AFB were negative for fungi and mycobacteria.Patient's outpatient labs were consistent with panhypopituitarism with AM cortisol of 1.9mcg/dL, ACTH 19pg/mL (6-50 pg/ml), FSH 6.5 mIU/ml, LH 2.4 mIU/ml and estradiol <15pg/ml. TSH was 1.26 mcIU/ml (0.27-4.2mcIU/ml) with Free T4 0.8ng/dL (0.8-1.8ng/dL). IGF-1 level was 72ng/ml (79-259ng/ml). Prolactin was 7.0 ng/ml (3.0-30.0ng/ml). IgG4 serum level was 100.2mg/dL (4.0-86.0mg/dL), IgG1 serum level was 446mg/dL (382-929mg/dL).

Conclusion

This is a unique patient with panhypopituitarism that meets the criteria for IgG4 related hypophysitis but also has secondary granulomatous components developed after the rupture of the colloid cyst during the first surgery. The implications of these findings are unknown in terms of management and prognosis.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON109 A Case of Non-functioning Pituitary Adenoma With Unexpectedly High Prolactin Level
Authors: Mahali Lakshmi Priyanka , Tariq Sana , Abraham Smita
Published: November 2022

Introduction

Lactotroph or prolactin (PRL)-secreting adenomas account for approximately 45% of all pituitary adenomas. They are classified by size as microprolactinomas (<10 mm) and macroprolactinomas (≥10 mm). A giant prolactinoma is arbitrarily defined as an adenoma > 4 cm. PRL levels are often proportional to the size of tumor ranging from <200 ng/mL in adenomas smaller than 1 cm, 200 ng/mL to 1000 ng/mL in 1 cm to 2 cm adenomas and more than 1000 ng/ml in tumors larger than 2 cm. Nonfunctioning pituitary adenomas (NFPA) can cause mild increases in PRL levels due to pituitary stalk compression, however, levels more than 6 times the upper limit of normal have not been reported. We present a rare case of NFPA with significantly elevated prolactin levels Case: 42 yo female presented with headache and left eye blurry vision worsening over 2 years. MRI revealed a pituitary macroadenoma measuring 4.1×4.7×3cm with supra-sellar extension, mass effect including severe compression and displacement of the optic apparatus, and potential cavernous sinus invasion. Initial biochemical profile: TSH 1.01 (0.30–4.20 uU/mL), FT4 0.9 (0.6–1.5 ng/dL), AM ACTH of 20 (7.2-20 pg/ml), peak cortisol 18.8 mg/dl after cosyntropin stimulation, FSH 14.6 mIU/mL, LH 2.4 mIU/mL, IGF-1 71 (52-328 ng/mL) and prolactin 452 (<25.0 ng/mL), confirmed by dilution. PRL levels were concerning for prolactinoma but did not correlate with tumor size making giant prolactinoma an unlikely diagnosis. Yet, levels were higher than those expected from stalk compression. An interdisciplinary decision was made to proceed with operative management. The patient underwent trans-sphenoidal pituitary resection (TSPR). Tumor pathology showed sparsely granulated gonadotroph adenoma with weak LH expression and negative PRL staining, confirming NFPA. PRL level one-month post op was 33.2 ng/mL and vision is improved.

Conclusion

Medical treatment with dopamine agonists is first line treatment for any size prolactinoma with a high remission rate of 90% and prescribed before TSPR even in those with vision disturbance or neurologic symptoms. Giant NFPAs with compressive symptoms are best surgically managed.To our knowledge, this is the first report of significant PRL elevation due to stalk compression. Not only was the PRL higher than that previously associated with stalk compression, but also well above 250 ng/mL, which is typically diagnostic of prolactinoma. This case also highlights the importance of assessing the relationship between PRL level and tumor size to determine the correct course of management.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON112 Primary Pituitary Lymphoma Presenting as Apoplexy
Authors: Abdelaziz Sara , Abrahamson Martin , Mottalib Adham
Published: November 2022

Background

Primary pituitary lymphoma (PPL) in immunocompetent individuals represents a distinct and rare clinical entity.

Clinical Case

A 49-year-old menopausal woman with past medical history of hypertension and obesity who presented to the emergency room with sudden onset loss of vision in her right eye with blurriness on the left. She had been having intermittent headaches and flu-like symptoms over the 2 days preceding her presentation. Her BP was 179/116 mmHg, initial basic metabolic profile was normal, and head CT showed hemorrhage into a bilobed sellar and suprasellar mass measuring 2.2×2.2×3.3 cm. On ophthalmic exam, the right eye showed near-complete visual field loss with some residual island of vision superotemporally while left eye showed temporal hemianopsia. Initial endocrine workup was notable for a normal cortisol 15.9 (ref 2-20) ug/dL and normal prolactin; low-normal TSH 0.73 (ref 0.2-4.2) uIU/mL; low free T4 0.3 (ref 0.9-1.7) ng/dL; low FSH, LH, and IGF-1. She received a pituitary MRI showing hemorrhagic pituitary macroadenoma with significant upward bowing of the optic chiasm and infiltration into the cavernous sinuses. The patient developed diabetes insipidus (DI) before being taken to the operating room for transsphenoidal surgery with debulking and biopsy. Postoperatively and while waiting for pathology results, she developed panhypopituitarism and was being treated with hydrocortisone, levothyroxine, and desmopressin. Her pathology was consistent with diffuse large B-cell lymphoma (DLBCL) of non-germinal center type. She had a complete hematologic workup including whole body PET-CT showing sellar and suprasellar fluorodeoxyglucose avid disease without evidence of disease elsewhere in the head, neck, and torso which confirmed the diagnosis of PPL. The patient was started on chemotherapy using R-CHOP (rituximab, cyclophosphamide, hydroxyadriamycine, vincristine, and prednisone) with high-dose methotrexate. Following the first chemotherapy treatment cycle, she had a modest improvement in her vision; however, her DI was permanent.

Conclusion

This case demonstrates that PPL can present with pituitary apoplexy and can result in panhypopituitarism and permanent DI. Individuals with this condition require a multidisciplinary care team including endocrinology, neurosurgery, hematology, and ophthalmology.

References

A Giustina, M Gola, M Doga, E A Rosei. Primary Lymphoma of the Pituitary: An Emerging Clinical Entity. JCEM. 2001 Oct;86(10): 4567-75.A Tarabay, G Cossu, M Berhouma, M Levivier, R T Daniel, M Messerer. Primary pituitary lymphoma: an update of the literature. J Neurooncol. 2016 Dec;130(3): 383-395.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON127 Neuroendocrine Tumor of the Spinal Cord- A Case Report of Rare Endocrine Tumor Presentation
Authors: Varghese Diana Grace , Yoldy Dorisca , Raygada Margarita , Sedlack Andrew , Anaraki Kimia Saleh , Reilly Karlyne , Widemann Brigitte , del Rivero Jaydira
Published: November 2022

Introduction

Neuroendocrine tumors (NETs) are heterogeneous group of malignant neoplasms arising from neuroendocrine cells distributed throughout the body. The most common sites of NETs are the gastrointestinal tract, pancreas and lungs which account for 82% of all NET cases. Other NET sites are those arising in the parathyroid, thyroid, adrenal, and pituitary glands. Rare NET sites include biliary, prostate, breast, head, and neck. Only a few cases report have been documented in the spinal cord as primary site of origin. Here we present a neuroendocrine tumor case arising from the cervical spinal cord.

Clinical Case

A 60-year-old male presented with posterior cervicalgia and left side facial, neck and shoulder paresthesia. A magnetic resonance imaging (MRI) of the head and cervical spine was performed and demonstrated an heterogenous, non-enhancing mass in the lower brain stem/upper cervical cord. An intramedullary 1.2×1.3×3.4 cm mass was identified with edema surrounding the mass. An MRI of the thoracic and lumbar spine was unremarkable. A fluorodeoxyglucose (FDG)-positron emission tomography (PET)- PET/CT scan only demonstrated a hypermetabolic lesion at the upper cervical spine. A posterior craniotomy and C1 laminectomy was performed with resection of the mass. Surgical pathology revealed a Grade 2 well-differentiated NET with Ki67 proliferation rate approaching 20%. A 68Ga-DOTATATE PET/CT post-surgery only showed a small focus of uptake within the left side of the upper cervical cord, with an SUV max of 3.9. Patient was subsequently treated with 45 Gy of external beam radiation therapy in 25 fractions. Molecular profile was performed on the patient's tumor (TSO 500; TruSight Oncology, Illumina); pathogenic variants were identified in EPHA3 and Tp53, and a copy number gain was found on CCND1. No further therapy was indicated, and patient continued active surveillance.

Conclusion

NETs constitute approximately 2% of all cancer diagnosed in the western world. The incidence has increased sixfold in the past four decades affecting approximately 170000 patients in USA. NETs (primary/ metastatic) are a rare occurrence in the Central Nervous System (CNS), and very few case reports of this condition are described in the literature. Surgery remains the mainstay treatment modality, with the goal of complete resection of the tumor. For residual tumors, somatostatin analogs, targeted molecular therapy (mTOR inhibitors and tyrosine kinase inhibitors) and chemotherapy (capecitabine /temozolomide) are indicated. No consensus guidelines exist for the treatment of spinal NETs and majority of the tumors are treated with surgery and radiation. Further studies are warranted for the diagnosis and management of spinal NETs.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON144 FOXO1 is required for glucocorticoid induced somatotrope maturation
Authors: Das Pratyusa , Ellsworth Buffy Sue
Published: November 2022

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

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

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

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

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 (</= 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

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

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 <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

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

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
LBODP085 Effects Of Elexacaftor-tezacaftor-ivacaftor On Glucose Tolerance And Other Metabolic Parameters In Children With Cystic Fibrosis
Authors: Choudhari Pooja , Ham Melissa Rebecca
Published: November 2022

Cystic fibrosis related diabetes (CFRD) occurs in up to 20% of teenagers and has detrimental effects on lung function and nutritional status. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have had positive and mixed effects on glucose tolerance in children. Our study aimed to investigate the effect of elexacaftor-tezacaftor-ivacaftor (ETI) on glucose tolerance, as well as on anthropometric measures and lipids, in children. We hypothesized that glucose tolerance and BMI would improve. We completed a retrospective study of children at a Pediatric Cystic Fibrosis (CF) Center who were started on ETI after December 2019. Our inclusion criteria were children 12 years and older who were on ETI for at least one year. We did not include children on long-term corticosteroids, with type 1, type 2, or other secondary diabetes, or who were post-transplant. Blood glucose at 2 hours after an oral glucose tolerance test (2-hour BG), Hemoglobin A1c (HgbA1c), lipids, and weight and BMI z-scores were assessed after at least one year on ETI. For patients with CFRD, only HgbA1c was performed for monitoring glycemic control. These measures were compared to corresponding measures in control groups of children older than or at 12 years old, heterozygous or homozygous for F508d, who were seen at the CF Center 4 years prior, and therefore were not receiving ETI. Patients with normal and impaired glucose tolerance (NGT/IGT) were compared to controls with similar glucose tolerance and separated by age. Patients with CFRD were compared to controls with CFRD only. Average length of time on ETI was 18.7 months. CFRD was diagnosed in 8.6% of patients and impaired glucose tolerance in 13.8% of patients. Previous CFTR modulators were used in 31.6% of patients. Average 2-hour BG increased by 3.2 mg/dl (n=44, p=0.6) and average HgbA1c decreased by 0. 05% (n=53, p=0.18) after the use of ETI. Weight z-score increased by 0. 07 (n=54, p=0.38) and BMI z-score increased by 0.13 (n=58, p=0.31). Total cholesterol increased significantly by 17.6 mg/dl (n=56, p<0. 0001), but in contrast, triglycerides only increased by 4.75 mg/dl (p=0.46). Change in average 2-hour BG for children in the NGT/IGT control group (total n=30) were similar to children receiving ETI: 12-13 years: 3.6 versus 3.2 mg/dl, 13-14 years: -9. 0 versus -3.5 mg/dl, and 14-18 years: 18.5 versus 8.6 mg/dl (all p>0. 05). In children with CFRD, the control (n=7) and ETI (n=5) groups had similar changes in HgbA1c (-0.56% versus -0.5%, p=0.94). In a retrospective analysis of children, 2-hour BG and HgbA1c changed minimally after at least one year on ETI and did not differ significantly when compared to controls. Minimal changes were also seen for BMI, weight, and triglycerides after use of ETI. However, total cholesterol increased significantly with the use of ETI.

Presentation: No date and time listed
ODP373 A Tale of Two Syndromes: Coexistence of Russell-Silver and Klinefelter Syndrome
Authors: Pillai Chanthu
Published: November 2022

Background/Aims

Klinefelter syndrome is a common condition characterized by an extra X chromosome, tall stature, gynecomastia, and hypogonadism. Russell-Silver syndrome is a rare disorder characterized by intrauterine growth restriction, poor growth after birth, and triangular facies. The coexistence of Russell-Silver and Klinefelter syndrome has so far not been reported in the literature. This study aimed to characterize the phenotype of such an individual.

Methods

Clinical and endocrinal investigations were performed and followed by pathogenic variant screening of candidate genes.

Results

An 8-year-old boy was evaluated for short stature. He was a former 27-week preemie who had postnatal growth failure. His mean parental height was5'6" (66 inches). His growth chart showed that he was below the 0. 01% percentile in both height and weight for age. He had behavioral issues. On physical exam, he had high riding prepubertal testes and proportional limbs. He was evaluated by both genetics and endocrine. His bone age was delayed by 4 years. He passed his growth hormone stimulation test. He had a nondiagnostic bone survey. His chromosomal microarray showed an XXY karyotype. Further testing was collected because it did not explain his short stature. He was found to have maternal uniparental disomy of 7q32.2. He was started on growth hormone and his most recent growth velocity was 4 cm a year. He continues to be below the 0. 01% percentile in both height and weight for age Conclusion: This is the first report on a patient with the coexistence of Russell-Silver and Klinefelter syndrome. It shows that the short stature and postnatal growth of Russell-Silver syndrome is the prevailing phenotype in this rare combination.

Presentation: No date and time listed
ODP376 Accuracy of Doppler Assessment of the Uterine Arteries for the Diagnosis of Pubertal Onset in Girls: A Scoping Review
Authors: Cheuiche Amanda , de Paula Leila , Lucena Iara , Moro Candice , Silveiro Sandra
Published: November 2022

Introduction

The uterine artery pulsatility index (PI) assessed by Doppler ultrasonography (US) reflects the blood flow impedance in the vessel distal to the sampling point and tends to decrease with the onset of puberty, being suggested as a parameter to define pubertal development.

Objective

To evaluate the accuracy of the uterine artery PI for the diagnosis of puberty in girls.

Methods

A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with "puberty" and "Doppler ultrasonography" as search terms. Studies that included girls aged 0-18 years who underwent pelvic US with Doppler of the uterine arteries and calculation of the PI were considered eligible.

Results

Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies were published between 1996 and 2021 and included participants from five countries (Italy, Brazil, Iran, Belgium and Denmark). Six studies included girls who were referred for evaluation of pubertal disorders, mainly thelarche or early-onset pubarche, while four studies selected only healthy girls. Nine studies found a significant difference in Doppler and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of onset of puberty, with a sensitivity of 77-94%, specificity of 85-100% and accuracy of 79-98%.

Conclusion

Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of onset of secondary sexual characteristics in girls.

Presentation: No date and time listed
ODP392 Persistence with daily growth hormone treatment among pediatric patients with growth hormone deficiency in the UK
Authors: Loftus Jane , Wogen Jen , Oliveri David , Benjumea Darrin , Jhingran Priti , Chen Yong , Alvir Jose , Sanz Elena Rivero , Kowalik Jack Charles
Published: November 2022

Background

Suboptimal adherence to, and persistence with, daily somatropin therapy to treat children with growth hormone deficiency (GHD) has been documented previously, and has also been shown to have negative effects on the growth response.

Objectives

To describe discontinuation of, and persistence to, daily somatropin treatment among pediatric patients with GHD in the UK.

Methods

This was a retrospective cohort study of pediatric patients (≥3 and <16 years) with >1 medication prescription for daily injectable somatropin from 1 st July 2000 to 31 st December 2020 in the IQVIA Medical Research DATA (IMRD) database. Patients were required to have >1 diagnostic code for GHD during the 6 months preceding and including the first somatropin prescription date ("index date"), and to be continuously enrolled in the database >6 months preceding and >3 months following index date. Patients with >1 somatropin prescription during the 6 months prior to index date, or with diagnoses for other causes of short stature were excluded. Patients were followed for up to 48 months post-index. Early persistence was defined as the proportion of patients prescribed ≥1 somatropin refill subsequent to the initial prescription. Discontinuation was defined as the first date at which a medication gap (defined as either >60 days or >90 days between prescriptions) for somatropin occurred. Persistence (non-discontinuation) over time was evaluated using Kaplan-Meier methods to assess time to first discontinuation event. The relationship of patient characteristics with time to medication discontinuation was evaluated using Cox proportional hazards models.

Results

Among pediatric patients included in this study (n=117), the majority (n=84, 71.8%) had 48 months of available follow-up; 56.4% were male and mean (median) age was 8.6 (8. 0) years. About 98% of patients exhibited early persistence. Persistence over the follow-up period decreased with follow-up duration. Using a 60-day gap definition, persistence at 12, 24, 36, and 48 months was estimated among 48.3%, 35.4%, 26.7%, 16.5% of patients; using a more conservative 90-day definition, an estimated 72.4%, 58.6%, 52.8%, and 43.3% were persistent at the same time periods. No significant patient predictors of time to discontinuation were identified.

Conclusions

Despite high early persistence with somatropin, a sizable proportion of patients were increasingly non-persistent over time. In this UK-based study more than 1 in 4 patients were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months. These results suggest that strategies to support improved medication-taking behavior among pediatric patients with GHD in the UK are warranted.

Presentation: No date and time listed