bluuebunny/crossref_metadata_2025 huggingface dataset:
LBODP010 A Case of Glucocorticoid Resistance Syndrome
Authors: Sudhakar Shwetha Mallesara , Story Shannon Ellen
Published: November 2022

Case presentation

A 55 yr old female presented with persistent mild elevation of cortisol for the previous 7 years. Four years prior to presentation, she was incidentally noted to have a small left sided adrenal nodule on CT scan of the abdomen. Biochemical evaluation of the nodule showed 24 hour urine cortisol of 176(0-50), morning cortisol of 36 ug/dl(6.2-19.4), ACTH 18 pg/ml(7.3-66.3), two out of three salivary samples with elevated cortisol. High dose dexamethasone suppressed ACTH to <1.1 from 13.8, cortisol from 30 to 3.3. She did not have signs and symptoms of Cushing's syndrome, mineralocorticoid excess nor androgen excess. Serum testosterone and DHEA were normal. DEXA revealed normal bone density. MRI brain demonstrated normal pituitary . She had no family history of pituitary or adrenal tumors nor endocrine syndromes. She underwent laparoscopic left adrenalectomy with pathology demonstrating benign adrenal adenoma, although the pathologist was unable to exclude nodular hyperplasia due to fragmented specimen. Elevation of 24 hour urine cortisol, serum cortisol and ACTH have persisted after surgery, without any clinical features of Cushing's. Gene sequencing with copy number analysis revealed heterozygous variant in the NR3C1 gene c.2239A>T(p. Ile747Phe), suspicious for autosomal dominant hereditary primary glucocorticoid resistance syndrome also known as Chrousos syndrome.

Discussion

Glucocorticoid resistance syndrome is rare, may be familial or sporadic, and is characterized by end organ insensitivity to glucocorticoids. Glucocorticoids are steroid hormones synthesized and secreted by adrenal cortex. The actions of glucocorticoids are mediated by the glucocorticoid receptor, which belongs to nuclear receptor family of ligand-dependent transcription factors. Affected individuals have elevations in circulating cortisol and ACTH, but no clinical evidence of hypercortisolism. Excess ACTH can result in increased mineralocorticoid and/or androgenic activity resulting in HTN and/or hypokalemic alkalosis and acne/hirsutism/infertility/male pattern hair loss. Asymptomatic, normotensive patients with primary glucocorticoid resistance do not require any treatment. Aim of treatment is to suppress excess ACTH to decrease mineralocorticoid and androgen effects. Treatment involves high doses of dexamethasone(1-3 mg/day), which activate the mutated and/or wild type hGR alpha and suppresses endogenous secretion of ACTH.

Conclusion

Mutations in human GR gene impair one or more molecular mechanisms of glucocorticoid action affecting signal transduction and altering tissue sensitivity to these hormones. Recognition of this condition avoids unnecessary adrenal surgery and informs appropriate treatment and long term follow up of patients and family members.

Presentation: No date and time listed
LBSAT56 Adrenal And Juxta-adrenal Schwannomas: A Single Center Study
Authors: Rolak Stacey , Dogra Prerna , McKenzie Travis , Young William F , Bancos Irina
Published: November 2022

Objectives

Adrenal schwannomas and juxta-adrenal schwannomas are rare tumors with limited data on clinical and radiologic features. We aimed to summarize the clinical, biochemical, and imaging characteristics of adrenal and juxta-adrenal schwannomas.

Methods

We performed a single-center retrospective study of patients with a histopathologic diagnosis of adrenal or juxta-adrenal schwannoma between 1995-2022.

Results

A total of 24 patients (18, 75% women) were diagnosed with either primary adrenal schwannoma (8, 33%) or a juxta-adrenal schwannoma (16, 67%) at a median age of 57 years (range, 27 - 77 years). Most tumors (21, 88%) were discovered incidentally on imaging, while 2 were diagnosed because of symptoms of mass effect, and 1 diagnosed incidentally on pathology during nephrectomy performed for renal cell carcinoma. None of the patients had a known genetic syndrome. The median time from identification of schwannoma on imaging to hormonal evaluation was 62 days (range, 0–2076 days). All tumors were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumor size was 4 cm (range, 2 - 13 cm). Adrenal schwannomas were smaller when compared to juxta-adrenal schwannomas (median of 3.1 cm [range, 2 - 9 cm] vs 4.6 cm [range, 2.3 - 13.3 cm]) (P=0. 037). On imaging, the tumors were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid-cystic in 7 (32%), heterogeneous in 14 (61%), and homogeneous in 9 (39%). Scattered or peripheral calcifications were seen in 2 cases. In 9 patients with available contrast-enhanced CT, all of the schwannomas demonstrated enhancement. The median unenhanced CT attenuation was 30 Hounsfield units (HU) (range, 12 - 38 HU). In 6 patients with available follow-up imaging of at least 6 months, median growth per year was 0.27 cm (range, 0 - 0.8 cm). Of the 20 patients who underwent complete hormonal testing, all had non-functioning tumors. Biopsy was performed in 5 (20%) patients and all were diagnostic of schwannoma. Adrenalectomy was performed in in 23 (96%) patients (laparoscopic in 16 [70%] and open in 7 [30%]). Open adrenalectomy was more common in patients with larger tumors (median size 7.5 cm; range, 2–13.3 cm) when compared to patients treated laparoscopically (median size 4 cm; range, 2.3–5.4 cm) (P=0. 041). Postoperatively, patients were followed clinically for a median of 1.7 years (range, 0-19 years) or radiographically (n=11) for a median of 2 years (range, 0. 01-11 years), without recurrence or new tumor development.

Conclusions

Adrenal and juxta-adrenal schwannomas are nonfunctioning benign tumors that present with indeterminate radiographic features, including large tumor size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumor is based on biopsy or resection.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP015 "Malignant" Hypertension in an Older Male
Authors: Naha Sowjanya , Gardner Michael
Published: November 2022

Background

Malignant hypertension connotates extreme elevation of blood pressure with associated acute target organ injury. Secondary causes of hypertension should always be considered in patients presenting with acute organ dysfunction especially when the hypertension is also resistant. Clinical case: A 66-year-old male was transferred to our hospital after two successive admissions to a local hospital with acute confusion. Importantly, he was noted to have acute kidney injury and hypokalemia in the course of those admissions. On review of his records, it was noted that he had been evaluated recently for chest pain with a contrast enhanced chest CT which incidentally detected a left adrenal mass. Biopsy of the mass had been performed and returned positive for adrenocortical carcinoma. Past history was also notable for chronic hypertension, type 2 diabetes and hypothyroidism for which he was on appropriate therapy. On physical examination, the patient was noted to be hypertensive. Other pertinent findings included facial plethora, extensive bruising and supraclavicular fat pad fullness. Abdominal striae were not seen. Laboratory investigations showed hyperglycemia (glucose: 201 mg/dL), hypokalemia (potassium: 3. 0 mmol/L) and metabolic alkalosis (bicarbonate: 30 mmol/L). Endocrine work up showed suppressed aldosterone (<4. 0 ng/dL, n: <21 ng/dL), total testosterone (31 ng/dL, n: 240-950 ng/dL) and ACTH (<5. 0 pg/mL, n: 7.2-63 pg/mL). Dehydroepiandrosterone (474 mcg/dL, n: 12-227 mcg/dL) and androstenedione (219 ng/dL, n: 40-150 ng/dL) levels were elevated. Cortisol levels did not suppress with overnight dexamethasone suppression test (29.8 mcg/dL). A diagnosis of Cushing's syndrome secondary to adrenocortical carcinoma was made. The patient was initiated on chemotherapy with carboplatin and etoposide. He was planned for mitotane therapy but passed away unexpectedly before the drug could be arranged.

Conclusion

Adrenocortical carcinoma can present with rapid onset of Cushingoid symptoms as well as sudden decompensation of previously controlled chronic hypertension, both of which were seen in this case. Although relatively uncommon, it remains a treatable and yet deadly cause for secondary hypertension, and should be considered in the appropriate clinical and biochemical settings.

Presentation: No date and time listed
ODP294 An Unusual Case of Endocrine Disruption as an Early Expression of Low Grade Intra Sellar Chordoma
Authors: Babu Vedesh Kumar , Suravajjala Devi , Kolli Swapna , Eranki Madhuri , Eranki Vijay
Published: November 2022

A 53y/o male patient presented to his PCP with fatigue and diagnosed with low testosterone and was started on testosterone. P ituitary labs were not checked then. After 6-8 weeks he was referred to neurology for new onset vision problems, diplopia, and daily headaches. MRI brain then showed a sellar mass of 2.4×2.6×2.7 cm with sphenoid sinus extension and bony thinning alongthe margins of the sella turcica which was nearly imperceptible. On testosterone replacement, biochemical assessment of anterior pituitary function showed total testosterone: 836 (264–916 ng/dl), Free Testosterone: 32.6 (2.5-9.5 ng/ml), LH<0.1 (1.2-8.6 IU/L), FSH 0.2 (1.5-12.4 IU/L), Prolactin 18 (4-26 ng/ml), TSH 0. 03(0.4-4.1 UIU/ml), FT4 0.63 (0.8-1.9ng/dl), IGF 188 (55-186 ng/ml), ACTH<5 (10-65 pg/ml), Cortisol<1 (4.8-19.5 ug/dl). Endoscopic endonasal surgery was performed with complete removal of the tumorand abdominal fat graft harvest. Histopathological findings confirmed well differentiated low grade chordoma. Post operatively he improved, and headaches and visual disturbances resolved. Patient was sent home on Hydrocortisone 10mg am/5mg pm. Then, he presented to our endocrine clinic for initial hormonal evaluation. On steroid replacement, endocrine testing was repeated four weeks post-surgery. Labs showedTSH 2. 070 (0.4-4.1 UIU/ml), FT4 1.16 (0.8-1.9ng/dl), FSH<0.3(1.5-12.4 IU/L), LH<0.3(1.2-8.6 IU/L), Prolactin 26 (4 -26), ACTH 19.6 (10-65 pg/ml), Cortisol 7 (4.8-19.5 ug/dl), IGF-1 129 (55-186 ng/ml). Four months after the surgery, patient passed the cosyntropin stimulation test and was able to wean off the hydrocortisone replacement. Post-op repeat MRI brain showed complete resolution of the clivial mass. Current, he remains stable with regular follow ups. The most common presenting symptoms of a sellar chordoma include visual problems and uncommonly hypopituitarism. Our case shows that non-adenomatous tumors can still challenge us with the original presentation as an endocrine deficit. In a case series, only one of nine cases had presented with pituitary dysfunction. Our patient was noted to have hypogonadism and started on testosterone supplementation without further investigation. It is important to evaluate hormonal status in all pituitary masses and recognize that some cases of sellar chordoma can present with endocrine dysfunction as the initial manifestation. In our case, endocrine function of the patient returned to normal once the pituitary compression from chordoma was eliminated.

Presentation: No date and time listed
ODP301 Corticotroph Macroadenomas with Extensions to Third Ventricle: Four Case Reports
Authors: Suzuki Yasuhiro , Igarashi Katsushi , Fujimoto Masanori , Suzuki Sawako , Koide Hisashi , Horiguchi Kentaro , Yokote Koutaro
Published: November 2022

Background

Pathophysiology of corticotroph macroadenomas has not been elucidated. In this study, we present four cases of adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas with extensions to the third ventricle (TV) and investigate their clinical and pathological characteristics.

Case 1

A male in his seventies went to a hospital because of a fall. Upon performing computed tomography, a tumor was incidentally noted. Pituitary MRI revealed a macroadenoma with extension to TV. He presented with Cushingoid features (CF). His basal ACTH level was 112 pg/mL, and urinary free cortisol (UFC) was 129.1 μg/day. Cortisol was not suppressed in the 0.5 mg dexamethasone suppression test (0.5 mg DST). ACTH level increased in the corticotropin-releasing hormone (CRH) stimulation test and the desmopressin (DDAVP) stimulation test. He was diagnosed with Cushing's disease (CD), and endoscopic transsphenoidal surgery (ETSS) was performed. Pathological findings showed densely granulated corticotroph adenoma (DGCA). Somatostatin receptor type 5 (SSTR5) was negative, and ubiquitin-specific protease 8 (USP8) was not mutated.

Case 2

A female in her fifties had a visual field defect and pigmentation of the face. MRI revealed a macroadenoma with extension to TV. She presented with CF. Her basal ACTH level was 57.9 pg/mL, and UFC was 259.7 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH level increased in the CRH test and the DDAVP test. She was diagnosed with CD. Pathological findings showed DGCA. SSTR5 was moderate positive, and USP8 was suspected to be mutated.

Case 3

A female in her fifties had a throbbing headache. MRI showed a macroadenoma with extension to TV. She did not present with CF. Her basal ACTH level was 71.8 pg/mL, and UFC was 134.3 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH showed response to the CRH test and the DDAVP test. She was diagnosed with subclinical Cushing's disease (SCD) and sparsely granulated corticotroph adenoma (SGCA). SSTR5 was slightly positive, and USP8 was not mutated.

Case 4

A male in his fifties had general malaise and polyuria. MRI showed a macroadenoma with extension to TV. He did not present with CF. His basal ACTH level was 179 pg/mL, and UFC was 187.4 μg/day. Cortisol was not suppressed in the 0.5 mg DST. ACTH did not show response to the CRH test and the DDAVP test. He was diagnosed with SCD, and the tumor had oncocytic changes. SSTR5 was negative, and USP8 was not mutated.

Conclusion

The findings from these case reports suggest that phenotypes of CD and SCD are associated with the differences between SGCA and DGCA. Moreover, it is also suggested that USP8 mutations correlate with SSTR5 expression in macroadenomas that extend to the TV.

Presentation: No date and time listed
ODP306 Diplopia as Presenting Manifestation of Acromegaly
Authors: Rjoob Hani , VanUum Stan , Alexander Fraser J , Ohorodnyk Pavalo , Bursztyn Lulu , Mcinnis Rachel Lang
Published: November 2022

Introduction

Acromegaly is a chronic disorder characterized by excess growth hormone production, withclinical manifestations ranging from subtle signs to significant systemic complications. We describe a patient who presented with diplopia as initial symptom of acromegaly. Clinical case: A 72-year-old female patient was referred for diplopia. Upon questioning, she reported headache, muscle aches and heavy sweating. On physical assessment, she had coarse facial features, thickened tongue and hand enlargement. Orbital CT images revealed a mild to moderate symmetric enlargement of the extraocular muscle which spared myotendinous junction. MRI sella showed a 12 mm pituitary adenoma. The diagnosis of acromegaly was confirmed with high IGF-1 and oral glucose tolerance test. The patient underwent endoscopic debulking of the pituitary tumor and pathology showed a densely granulated GH producing adenoma. Upon follow up, she reported improvement of the diplopia which was completely corrected with prism glasses. Remission of acromegaly was confirmed biochemically and repeated MRI sella showed no residual tumor.

Conclusion

Acromegaly is the most likely cause of extraocular muscle enlargement with subsequent diplopia in this patient. Ocular manifestations in patients with acromegaly include visual field defect, excessive lacrimation, proptosis and double vision. This case adds to previous literature that diplopia could be the presenting manifestation of acromegaly. This is the first case reporting of improvement of diplopia following remission of acromegaly. Comprehensive ophthalmic assessment of patients presenting with eye symptoms and features suggestive of acromegaly is of value as it helps with early diagnosis as well as improving the outcome of this condition.

Presentation: No date and time listed
ODP308 Does This Patient Have Sheehan's Syndrome Due to Thrombosis?
Authors: Dawahir Wafa , Gilden Janice
Published: November 2022

Background

Sheehan syndrome (SS) is the necrosis of the anterior pituitary cells due to ischemia. The most common etiology is the result of postpartum hemorrhage, causing hypovolemia and decreased blood supply to an already enlarged pituitary gland, which occurs during pregnancy. Other less common causes are thrombosis, vasospasm, or compression on hypophysial arteries.

Clinical Case

A 35-year-old lady G1P1 was referred to Endocrinology Clinic for evaluation of secondary amenorrhea and infertility, and a desire for a second child. Prior to birth of her daughter, she had irregular menses every 30-90 days. She did not have excessive bleeding with delivery. However, she developed postpartum deep vein thrombosis, and was treated with enoxaparin for 1 year after delivery. Although she had no symptoms of hypopituitarism, she has not had a menstrual period since delivery of her child and does not exercise vigorously. She did not have symptoms or signs of PCOS. Upon evaluation, Factor V Leiden showed a heterozygous mutation, Estradiol14.98L[19.5-144.2 pg/mL], LH 2.3[ 1.9 - 26.2 mIU/mL], FSH 7.4[2.3 - 12.6 mIU/mL], FT4 1.3 [0.76 - 1.46 ng/dL],TSH 1.10[ 0.358 - 3.74uIU/mL], IGFI 182[ 53 - 331ng/mL], ACTH 12[ 0–47 pg/mL], am Cortisol 15.2[5.3 - 22.5 ug/dL],Testosterone18 [ 2–45 ng/dL],DHEA Sulfate58[35-430mcg/dL] Prolactin 5.7[<25 ng/ml],with normal fallopian tubes on HSG. Pituitary MRI was done due to low estradiol with inappropriately normal FSH and LH and was normal. The patient was diagnosed with Hypogonadotropic deficiency leading to secondary amenorrhea, of unclear etiology, in the setting of possible hereditary caused thrombosis. The concern for hormonal therapy for a second pregnancy was whether this is safe and effective, given her history of DVT and factor V Leiden mutation.

Discussion and Conclusion

Previous studies have found that 82% of cases with SS were due to postpartum hemorrhage, but also suggests that there are other etiologies for SS. In addition, failure of lactation occurs in 67% of patients and secondary amenorrhea in 73% of patients, as in our case. However, the extent of pituitary involvement can vary, with abnormal GH and prolactin in 90-100% of cases, while abnormal TSH, Cortisol and GnRH in 50-100%. Although anti-phospholipid syndrome has been described as a possible etiology for hypopituitarism, related to formation of thrombi, our case suggests that other coagulopathies should be considered as a cause of partial pituitary dysfunction leading to hypogonadotropic hypogonadism, due to thrombus formation.

Presentation: No date and time listed
ODP316 Hyponatremia as a Prognostic Factor for Mortality in COVID-19 at The National Hospital "Dos de Mayo", Lima Peru.
Authors: Miranda Gonzalo , Uriarte Manuel Angel Jiménez , Velasquez Anggi July Tadeo
Published: November 2022

Introduction

Hyponatremia is the most common electrolyte disorder in hospitalized patients. It's more common in patients who were hospitalized with a diagnosed of pneumonia, which worsen the prognosis of the general condition. The infection in patients with SARS-CoV-2, can present hyponatremia, which would affect in a negativity way the recovery of them with mild, moderate or severe respiratory symptoms.

Objective

Establish if hyponatremia is a prognostic factor of mortality in patients with covid-19 diagnosis.Material and methods: The sample consisted of 185 medical records of patients with a COVID-19 diagnosis, which has been seen between June 2020 and February 2021 an observational, cohort and retrospective study. We recorded epidemiological, demographic, clinical, biochemical and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis during hospitalization. Descriptive analysis was used for main variables, Chi square tests, OR calculation and confidence interval were used to assess the statistical association of the variables. Finally, a logistic regression analysis was performed to evaluate confusing variables.

Results

160 patients have hyponatremia (34.9% mild, 26.7% moderate and 40% severe) and none of them had a previous diagnosis of SIHAD (Syndrome of inappropriate antidiuretic hormone secretion) consigned in their clinical histories. The increase of mortality was consigned (viewed) in patients with severe hyponatremia compared with moderate and mild hyponatremia diagnosed at hospital admission (20.8% mild hyponatremia, 21.6% moderate and 46.4% severe, p=0. 03)

Conclusion

Severe hyponatremia at hospital admission was associated with elevated mortality in SARSCoV-2 patients.

Presentation: No date and time listed
ODP317 Hypophysitis or No? A Rare Case of Bipolaris Fungal Sinusitis Causing Severe Pituitary Inflammation.
Authors: Aleman Lorianna , Burks James , Malik Sonika
Published: November 2022

Clinical case: A 28 year old male with uncontrolled diabetes mellitus presented to the hospital with severe, worsening holo-cephalic headache associated with fevers, light sensitivity which was unresponsive to pain medications. Initial CT of the brain showed severe paranasal sinus disease. Lumbar puncture was significant for elevated protein and cell count with neutrophilic predominance and negative CSF culture. Patient was empirically treated for meningitis. Due to no improvement in his symptoms, MRI brain with contrast was done that showed complete opacification of the left sphenoid sinus with partial opacification of the ethmoid sinus. Of note, heterogeneous enlargement and enhancement of pituitary gland including portion of distal infundibulum was seen with mild compression of optic chiasm. High dose dexamethasone was initiated. Pituitary workup revealed preservation of all axes including AM cortisol 36.5 mcg/dL (6.6mcg/dl- 33 mcg/dl), prolactin 2.9 ng/ml (2.1ng/ml-17.7ng/ml), TSH 1.4 uIU/mL (0.34-5.6 uIU/mL), FT4 0.99 uIU/mL (0.80-1.80 uIU/mL) with normal serum chemistry and hemodynamics. Repeat MRI brain showed sphenoid pyomucocele with infection extending to the sella, cavernous sinuses and anterior/middle cranial fossas. ENT surgery was emergently performed with surgical debridement of the sphenoid and ethmoid sinuses revealing green cement like debris causing posterior septal perforation from the pressure. Interestingly, ethmoid sinus fluid culture grew Bipolaris fungal species. Patient's condition gradually improved and he was discharged on oral itraconazole with steroid taper. The patient did not develop signs or symptoms of hypophysitis during his hospital course.

Presentation: No date and time listed
ODP323 Increased Serum High-Sensitivity C-Reactive Protein Levels in Adult Growth Hormone Deficient Patients with Non-Functioning Pituitary Tumors
Authors: Seki Yasufumi , Takano Noriyoshi , Yamashita Kaoru , Bokuda Kanako , Sasaki Nobukazu , Ishikawa Toru , Kimura Miwa , Watanabe Satoshi , Watanabe Daisuke , Morimoto Satoshi , Ichihara Atsuhiro
Published: November 2022

Background

Growth hormone (GH) deficiency, a common endocrine deficit in non-functioning pituitary tumors, causes visceral obesity and fatty liver and increases cardiovascular event risks. High-sensitivity C-reactive protein (hs-CRP) has been used as a useful marker to estimate cardiovascular event risks. Because GH supplementation therapy was reported to decrease serum hs-CRP levels in GH deficient patients, inflammatory processes might be activated in GH deficient state, however, the underlying mechanism has been still unknown.

Patients and Methods

We retrospectively reviewed charts of 134 patients with non-functioning pituitary adenoma and Rathke's cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests and investigated the association between serum hs-CRP levels and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases or received GH supplementation therapy were excluded. GH secretion was determined by GHRP-2 tests.

Results

Among 134 patients (94 NFPA and 40 Rathke's cysts), 46 (34%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (723 [299-1285] vs 278 [124-561] ng/mL, P < 0. 001). Serum hs-CRP levels were significantly higher in men (P = 0. 003) and in patients with diabetes mellitus (P = 0. 040) and were significantly correlated with age (r s = 0.19, P = 0. 039), body mass index (r s = 0.37, P < 0. 001), serum levels ofgamma-glutamyl transpeptidase(r s = 0.28, P = 0. 001), creatinine (r s = 0.30, P < 0. 001), low-density lipoprotein cholesterol (r s = 0.21, P = 0. 013), triglyceride (r s = 0.38, P < 0. 001) and free thyroxine (r s = -0.30, P= 0. 001), blood hemoglobin A1c levels (r s = 0.20, P = 0. 018), peak GH response to GHRP-2 (r s = -0.47, P < 0. 001) and IGF-1 SD score (r s = -0.18, P = 0. 040). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0. 003) after adjustment with age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, serum levels ofgamma-glutamyl transpeptidase, creatinine,triglyceride and free thyroxine and adrenal function.

Conclusion

We observed a significant association between GH deficiency and increased serum hs-CRP levels independent to BMI and liver dysfunction. GH deficient state might cause inflammation independent to development of visceral obesity and fatty liver.

Presentation: No date and time listed
ODP324 Internal Carotid aneurysm inside a pituitary macroadenoma: case study and literature review
Authors: Rabiei-Flori Elham , Farhad Hasan
Published: November 2022

BACKGROUND: Coexisting pituitary adenoma (PA) and intracranial aneurysms (IA) is relatively frequent. However, the finding of an aneurysm inside a PA is extremely rare. We report a patient with pituitary macroadenoma with an embedded internal carotid artery (ICA) aneurysm, who presented with anterior hypopituitarism. CLINICAL CASE: 73 y. o. black female presented after a fall secondary to orthostastic hypotension. In the ER her BP was 78/50 mmHg, HR 76/min sinus rhythm. She reported fatigue, presyncope, and 20 lbs weight loss in the preceding 3 months. CT head without contrast showed a sellar mass. Pituitary MRI confirmed a 20×24×29 mm sellar mass consistent with a macroadenoma extending laterally to both cavernous sinuses with bilateral encasement of ICAs, superiorly elevating optic chiasm, and mild extension to the left Meckel's cave. The study also incidentally showed a > 5 mm ICA aneurysm embedded within the macroadenoma. Diagnostic cerebral angiogram demonstrates a medially directed left superior hypophyseal ICA aneurysm measuring 5.4×4. 0 mm with a 3.5 mm neck. The patient denied headaches, peripheral vision loss, or polyuria. On examination her weight was 154 lbs, height 5'6", normal visual field testing, and no neurologic deficits. Endocrine testing was consistent with anterior hypopituitarism: ACTH 17 pg/mL (10-48), Cortisol 4.7 mcg/dL (6-18.4), TSH 1.4 mIU/L (0.4- 4. 0), FT4 0.7 (0.7-1.9 ng/dL), IGF1 7 ng/mL (55-162), Prolactin 38.3 ng/mL (4.8- 23.3), and FSH 6.6 IU/mL (20-138). Clinical improvement followed hydrocortisone and levothyroxine replacement. Patient was discharged home with a plan for outpatient endocrine follow up and subsequent endovascular intervention. Unfortunately, she presented a few weeks later with pulmonary embolism, for which she was treated with Eliquis. Given high risk of bleeding, the plan for endovascular embolization was postponed. Patient was educated about sick day rules and is set for routine endocrine visit and periodic MRI surveillance of the macroadenoma. DISCUSSION: intracranial aneurysms appear to occur more frequently in association with PAs than among the general patient population. In 2 cohort of patients with PA, 5.4-7.3% had coexisting IAs, the majority of which are outside the pituitary region. However, the presence of an aneurysm embedded within a PA, as in our case, is very rare, and most are discovered by accident. In such cases, although spontaneous aneurysm rupture or pituitary apoplexy is extremely rare, misdiagnosis of the embedded aneurysm can potentially result in catastrophic outcomes if it is not appropriately recognized and addressed prior to pituitary surgery. Cerebral angiography with embolization or coiling of the aneurysm prior to hypophysectomy can decrease the risk of perioperative rupture or bleeding. In our case, given the risk of bleeding while on anticoagulation therapy, the plan for endovascular intervention was postponed.

Presentation: No date and time listed
ODP330 Long-term Effects of Prenatal Undernutrition on Hypothalamic KNDy Gene Expression in Female Rats
Authors: Minabe Shiori , Iwata Kinuyo , Watanabe Youki , Ozawa Hitoshi
Published: November 2022

Accumulating evidence suggested that the nutritional environment during development periods induces metabolic programming, leading to metabolic disorders and detrimental influences on human reproductive health. The purpose of this study was to determine whether intrauterine malnutrition has a long-term adverse effect on a reproductive center, kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) of the female offspring. In female offspring from 50% undernutrition (UN) dams, first virginal estrus tended to be advanced, and hypothalamic neurokinin B gene (Tac3) expression was increased in adolescents. Conversely, the UN caused the significant suppression of ARC kisspeptin (Kiss1) and Tac3 gene expression after 29 weeks of age. These results suggested that intrauterine undernutrition stress caused developmental programming in KNDy neurons, which changed in their gene expression depending on life stages. Furthermore, our data showed obesogenic effects of prenatal undernutrition in the female rats; UN offspring showed low birth weight, rapid catch-up growth at four weeks of age, visceral fat accumulation, and an increase in calorie intake and plasma triglyceride levels at adulthood. The current study demonstrated that intrauterine undernutrition affected hypothalamic developmental programming in female rats, which induced long-term effects on hypothalamic KNDy gene expression and could influence metabolism and reproductive function later in life.

Presentation: No date and time listed
ODP339 Nonfunctioning Giant Adenomas
Authors: Oliveira Miriam C , Nesello Alberto C , Pereira-Lima Ana Paula S , Rech Carolina GSL , Pereira-Lima Julia Fernanda S , Corso Eduardo Raul B
Published: November 2022

Introduction

Giant pituitary tumors (GA), those with 4 cm or more on the largest axis, exhibit extension beyond the sella turcica and invade structures adjacent to it.

Objectives

To evaluate demographic, clinical, and imaging variables in a cohort of nonfunctioning GA(NGA) patients.

Methods

We conducted a retrospective and observational study of patients with NGA followed in our tertiary center between 2005 and 2021. We evaluated variables related to diagnosis, treatment, and follow-up.

Results

We found 48 patients diagnosed with NGA. Most patients were men (n=35, 73%), and meanage at diagnosis 55.5 ± 11.8 years (35-83). Symptoms such as headache and visual alteration were present within 13 years of diagnosis. The BMI was higher than 30 in 10 cases, two with morbid obesity. Among the comorbidities, 10 patients had diabetes mellitus and one glucose intolerance; hypertension was present in 20 cases and depression in 7. Polymedication was verified in 20 patients. Pituitary MRI revealed the largest tumor axis between 4-4.9 cm in 33 patients, 5-5.9 cm in 9, and equal or greater than 6 cm in 6. In 14 cases, there was intraventricular extension, invasion of the sphenoid sinus in 11, cavernous sinus in 21, frontal lobe in 1, temporal region in 6, clivus in 3, retroclivus in 3, and rhinopharynx in one. Hyperprolactinemia was detected in 17 cases (maximum value: 70.8 ng/mL). Only three patients presented all hormonal axes intact. Respectively, 9, 15, 11, and 8 patients presented 1, 2, 3, or 4 deficient axes. Hypocortisolism was present in 18 cases, GH deficiency in 16, hypothyroidism in 32, hypogonadism in 35, and hypoprolactinemia in 3. Four patients had diabetes insipidus. Ten cases of the 44 who underwent surgery underwent two interventions and 4 cases, 3. Nine patients underwent radiotherapy. After the first surgery, 26 patients had follow-up greater than 12 months (13 to 214 months). The last image showed a giant lesion in 7 cases, macroadenoma with a larger axis less than 4 cm in 15 cases, a lesion restricted to the sella in 3 cases, and 1 case without lesion.

Conclusion

In our cohort, the results show the handling difficulty of NGA, determined by the complex removal of the lesion, high degree of invasion to adjacent structures, and tumor regrowth. Sequential therapeutic decisions in this group of patients require a qualified multidisciplinary team to maximize the patients’ life expectancy and quality of life while working on sharing experiences and investing in the tumor molecular characterization and new molecules that add to the poor therapeutic arsenal available.

Presentation: No date and time listed
ODP340 NOVEL THERAPY OSILODROSTAT AS AN OPTION FOR RECURRENT CUSHING'S DISEASE
Authors: Marin Luis Madera , Nieves Yadiel Rivera , Rivera Monica Ortiz , Burgos Alexandra Rosado , Cordero Nicole Hernandez , Ortega Nydia Burgos , Vick Margarita Ramirez , Rodriguez Loida Gonzalez , Alvarado Milliete
Published: November 2022

Introduction

Cushing's Disease (CD) denotes a pathologic endogenous hypercortisolism secondary to excessive adrenocorticotropic hormone (ACTH) production. Cushing Disease is a rare condition with an estimated incidence of approximately 1.2-1.4 new cases / 1. 000. 000 per year. Although surgical intervention is the gold standard in the management of CD, many patients may present persistence or recurrence of disease despite surgical intervention, resulting in significant deterioration of their quality of life (QoL). For those in whom pituitary surgery is not an option or has not been curative, medical therapies have been developed. One of these newer treatments is the drug Osilodrostat, an inhibitor of the enzyme 11-beta-hydroxylase, responsible for the final step of cortisol biosynthesis in the adrenal glands.

Case Discussion

Case of a 21 year-old female patient with history of Cushing's Disease status post-transsphenoidal surgery (TSS) in 2017, obesity and oligomenorrhea who presented to our clinics showing signs and symptoms of hypercortisolism despite previously documented post-surgical remission in 2017. Patient reported recent development of acne, weight gain, round face, elevated blood pressure and mood changes. At the moment of evaluation, her most recent MRI showed post-surgical changes without a discrete lesion. Work-up was compatible with recurrence of Cushing's with an ACTH at 75pg/mL (nl, 10-60pg/mL), urinary free cortisol (UFC) at 1,122mcg/24h (nl, 4-50mcg/24h) and serum morning cortisol at 24. 0mcg/dL (nl, 5-20mcg/dL). In view of a negative MRI for a pituitary lesion, a Bilateral Inferior Petrosal Sinus Sampling (BIPSS) was performed. The BIPSS procedure revealed a pituitary source with a right pituitary lateralization suggestive of a right ACTH-producing tumor. The patient was consulted to Neurosurgery Service, but while waiting for repeat surgery, control of hypercortisolism was needed. The patient was started on Osilodrostat 2mg twice a day and was able to achieve normalization of UFC to 4mcg/24h, serum morning cortisol 5mcg/dL and late-night salivary cortisol (LNSC) of 30ng/dl (<90ng/dL) with significant improvement in her QoL, depression and clinical manifestations. The patient tolerated therapy well.

Conclusion

Cushing's Disease is a complex condition with potential serious complications if untreated. Even though TSS is the first line therapy, approximately 25% of patients show persistence of disease, and a similar proportion may experience recurrence. When surgery fails, medical treatment such as Osilodrostat, can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations improving patients’ QoL while more definitive therapy is established.

Presentation: No date and time listed
ODP021 A Feminizing Adrenocortical Carcinoma Presenting with Marie-Antoinette Syndrome
Authors: Alnuaimi Abdulla , Alameri Majid , Marco Aimee D , Wernig Florian
Published: November 2022

Introduction

Adrenocortical carcinomas (ACCs) are rare and aggressive malignant tumors often with an unfavorable prognosis accounting for 0. 05-0.2% of all cancers. ACCs can be separated into 2 groups: Functioning (hormone-producing) and non-functioning tumors. About 60% of ACCs synthesize hormones. Hormone-secreting ACCs most commonly cause virilization or Cushing's syndrome. On very rare occasions, ACCs can lead to feminization in male subjects. Clinical manifestations are gynecomastia and/or hypogonadism. Here, we present a case of an estradiol-secreting adrenal cortical carcinoma.

Case presentation

A 58-year-old male presented with patchy hair loss, change in hair colour to white, loss of body hair and eyebrows, and breast tenderness. Hormone testing revealed significantly elevated estradiol came 582 pmol/L [NR<190] with a very low testosterone of 1.6 nmol/L [NR10-30], low FSH 0.1 mIU/mL [NR 0.95-11.5] and LH of 0.6 mIU/mL [NR1.14-8.75]. A testicular ultrasound was unremarkable. An adrenal MRI revealed an 11 cm heterogeneous right adrenal mass invading the inferior vena cava. FDG PET-CT revealed an intensely metabolically active tumor without any evidence of metastatic disease. The tumor was successfully removed via an open procedure. Histology confirmed an adrenocortical carcinoma with a Weiss score of 8 with a mitotic account of 10/50 HPF and Ki-67 labelling index of 20-25%. There was vascular invasion with large areas of necrosis, ENSAT (European Network for the Study of Adrenal Tumours) stage II. Postoperatively, he made a good clinical recovery and was offered adjuvant Mitotane and EDP (Doxorubicin, Etoposide and Cisplatin) chemotherapy. Due to a significant rise in GGT and platelets, Mitotane had to be stopped temporarily. During the course of his treatment, he developed a hoarse voice and CT neck revealed abnormal thickening of the lateral aspects of the aortic arch suggesting possible tumor recurrence or aortitis. A biopsy was not diagnostic, but did not show any features of malignancy. He completed his five cycles of EDP chemotherapy. Estradiol has remained normal and his hoarse voice improved.

Conclusion

We describe a rare case of an estradiol-secreting ACC presenting with feminization and Marie-Antoinette syndrome as well as possible paraneoplastic aortitis. Targeted molecular tumor analysis may guide further treatment options and enrolment in clinical trials should be considered.

Presentation: No date and time listed
ODP343 Phoenixin as a Novel Autocrine/Paracrine Factor Stimulating Prolactin Secretion and Gene Expression at the Pituitary Level in Fish Model
Authors: Wong Anderson O L , Li Dongliang , Ye Cheng , He Mulan , Ko Wendy K W
Published: November 2022

Phoenixin (PNX), a new peptide first identified by bioinformatics, is widely expressed at tissue level and confirmed to be the ligand for the orphan receptor GPR173. Its mature peptide PNX 20 is highly conserved across species and emerged as a novel regulator for reproductive, appetite control, memory retention, plain perception and cardiovascular protection. However, not much is known for the comparative aspects of PNX and the post-receptor signaling mediating PNX action is still unclear. Using grass carp as a model for bony fish/teleost, carp PNX and its receptor GPR173 were cloned and confirmed to be single-copy genes in the carp genome. Using RT-PCR, transcript signals of PNX and GPR173 were found to be widely expressed in different tissues, including the brain-pituitary axis. As revealed by LC/MS/MS and ICC staining, protein signals of PNX and GPR173 could be detected in the pituitary and co-localized in immuno-identified lactotrophs. In primary culture of carp pituitary cells, static incubation with the synthetic peptide of carp PNX 20 was effective in increasing prolactin (PRL) release, PRL cell content and total production of PRL with a parallel rise in PRL mRNA level. The opposite was true for PRL secretion and transcript expression in parallel experiment with removal of endogenous PNX by immunoneutralization using PNX antiserum. Besides the stimulation on PRL signals, similar treatment with PNX 20 could also elevate cAMP and intracellular Ca 2+ levels with rapid phosphorylation of PI3K, Akt, MEK 1/2 and ERK 1/2 in carp pituitary cells. In the same model, except for a lack of effect with PKC blockade, co-treatment with the pharmacological inhibitors for different signalling components of the cAMP/PKA, PLC/IP 3, PI3K/Akt and MAPK cascades was effective in reducing/causing a total blockade of PNX 20 -induced PRL release and gene expression. Our results, as a whole, suggest that (i) PNX produced locally within the carp pituitary, presumably via activation of GPR173, could act as an autocrine/paracrine signal to stimulate PRL secretion and gene expression in carp lactotrophs, and (ii) the stimulatory effects on PRL regulation caused by the local actions of PNX probably are mediated by the cAMP/PKA-, PLC/IP 3 -, PI3K/Akt- and MAPK-dependent signaling mechanisms.

Presentation: No date and time listed
ODP348 Regional disparities in functional impairment due to arthropathy in patients with acromegaly.
Authors: Ahmad Syed , Chen Kevin , Chik Constance , Clarke David , Ibrahim Aisha , Imran Syed , Ladouceur Michel , Steeves Keillor , Title Michaela , Tramble Lisa , VanUum Stan , Wang Yuqi
Published: November 2022

Objective

While arthropathy is common in acromegaly (ACRO), its impact on the physical function of patients is not well understood. We sought to compare physical function between patients with a history of ACRO or with a nonfunctioning pituitary adenomas (NFA) who had previously undergone pituitary surgery.

Methods

Sex- and age-matched participants (n=34 for both groups) were recruited from the Halifax Neuropituitary Program. All ACRO patients were in remission with or without medical therapy. All patients completed validated questionnaires related to musculoskeletal disability and symptoms of the upper extremity (QuickDASH), functional impact of arthropathy in the weight-bearing joints (hips: HOOS-JR, knees: KOOS-JR, ankles: Quick-FAAM), and balance (ABC-6). We also assessed the number of falls in the past 12 months. HOOS-JR and KOOS-JR scores were compared using paired t-tests, whereas the Wilcoxon signed-rank test was used to compare DASH, DASH-Work, DASH-Instrument, Quick-FAAM, and ABC-6 scores between the two groups.

Results

ACRO compared with NFA patients, respectively, had higher upper-limb musculoskeletal disability and symptoms scores [17. 04 (0-70.45) vs. 4.55 (0-50. 00); p=0. 009]. However, there were no significant differences between the DASH-Work score or DASH-Instrument score between the two groups (p=0.317 and 0.18, respectively). ACRO patients had poorer functional scores for the hip compared with NFA (73.43±22.41 vs 86.45±15.43, p=0. 014) and knee (72.69±22.15 vs. 83.30±17.67, p=0. 056). However, there were no differences in ankle scores (p=0. 097). The number of falls within the last 12 months did not differ between the two groups (p=0.424), but there was a trend towards lower levels of self-confidence to maintain balance in ACRO patients compared with NFA patients (75% (8.33-100% vs90% (28.33-100%, p=0. 051).

Conclusion

ACRO patients showed significantly lower functionality of upper extremities and hips and a trend to greater functional impairment in the knee joints. Even though the number of falls was not different between the two groups, we did note a trend towards reduced levels of self-confidence to maintain balance in ACRO patients.

Presentation: No date and time listed
ODP354 Telomeres Length and Wnt/beta-catenin Pathway in Adamantinomatous Craniopharyngiomas
Authors: Ítalo S. Mota José , Silva-Júnior Rui M Patrício , Martins Clarissa Silva , Bueno Ana Carolina , Eduardo Wildemberg Luiz Eduardo Luiz , da Silva Antunes Ximene L , Okanobo Ozaki Jorge G , Coeli-Lacchin Fernanda B , Garcia-Peral Carlos , Oliveira Antonio Edson R , dos Santos Antonio Carlos , Moreira Ayrton C , Machado Helio Rubens , dos Santos Marcelo V , Colli Leandro M , Gadelha Mônica R , Antonini Sonir R , de Castro Margaret
Published: November 2022

Objectives

To evaluate how telomeres length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design: Retrospective cross-sectional study enrolling 42 aCPpatients from two tertiary institutions.

Methods

Clinicopathological features were retrieved from patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths.

Results

Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; p=0. 04) and a trend to recurrent disease (76% vs 24%; p=0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597 vs 0.607, IQR: 0.445-0.778; p=0. 04) but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomere and CTNNB1-mutated aCPs.

Conclusions

CTNNB1 mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres. This is the first evidence for a relationship between the Wnt/beta-catenin pathway and telomere biology in the pathogenesis of aCPs.

Presentation: No date and time listed
ODP602 A Rare Case of Nonfunctional Metastatic Pancreatic Neuroendocrine Tumor Transformation into an Insulin-secreting Tumor: A Management Dilemma
Authors: Azmath Misbath , Faisal Sobia , Kantorovich Vitaly , Guruli Marie
Published: November 2022

Pancreatic neuroendocrine tumors (PNETs) although rare, have recently increased in incidence . Clinically they can be classified as functional or nonfunctional depending on presence or absence of active hormone symptomatology and this has a bearing on prognosis and management . Rarely nonfunctioning tumors can undergo biological transformation into a hormone-secreting tumor. We present a rare clinical scenario of a young male with widely metastatic nonfunctional PNET who later presented with profound hypoglycemia with concerns for transformation into an insulin secreting tumor.

Presentation: No date and time listed