bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMON122 Unveiling the Kraken- An Incidentally Found Silent Corticotroph Adenoma of the Pituitary Gland
Authors: Shteyman Sara , Azmath Misbah , Kantorovich Vitaly 
Published: November 2022

Abstract

Introduction
Silent corticotroph adenomas (SCA) are an unusual and rare variant of non- functioning pituitary adenomas (NFA) that do not produce biochemical hypercortisolism or clinical Cushing's disease (CD), yet stain strongly for ACTH on immunohistochemistry. They represent 3-19% of non-functioning adenomas and 20% of corticotroph producing adenomas. SCAs are distinguished by their late presentation, frequent cavernous sinus involvement and earlier recurrence requiring multimodal management.

Case
We present a case of a 70 year old female with a remote history of breast cancer (2002) and uterine cancer (2016) in remission who was found to have an incidental soft tissue mass in the sella turcica on CT head after a fall in 2021. An MRI brain confirmed the mass as a 1.8×2.0×1.5 cm pituitary lesion with expansion to the sella. Patient had no symptoms related to pituitary hyperfunction or mass effect. Biochemical workup including IGF-1, prolactin, LH, FSH, and AM Cortisol level were all within normal limits. Ophthalmologic evaluation was normal. Repeat pituitary MRI 2 months later showed increasing homogeneously enhancing lesion on the left petrous ridge measuring 2.8×2.8×1.3 cm. There was extension into the cavernous sinus with involvement and encasement of the carotid artery. After multi-disciplinary evaluation including neurosurgery and ENT, patient elected to undergo transnasal endoscopic resection of pituitary tumor. The tumor was only partially resected due to its close association with the carotid artery. Final pathology was significant for monotonous proliferation of tumor cells with small round nuclei and amphophilic cytoplasm, characteristic of a pituitary adenoma. The tumor cells stained strongly positive for ACTH, and negative for all other hormone receptors. Further endocrine workup showed normal morning cortisol and ACTH and marginally elevated 24 hour urine cortisol measuring 47.6 mcg/g creatinine (ULN 42.3). Her clinical presentation was consistent with a SCA. A Dotatate PET/CT was ordered to be performed 3 months postoperatively to assess for SSTR receptors for potential targeted therapy against the residual tumor.

Discussion
We present the case of an elderly female who was incidentally found to have an invasive SCA precluding its complete resection. There are multiple theories regarding the lack of biological activity of SCAs including lack of enzyme in the tumor to cleve the active ACTH from the prohormone state, dysfunctional lysosomal activity leading to destruction of ACTH before secretion, origin from POMC positive pars intermedia cells instead of true corticotropic cells. These tumors have an increased rate of tumor invasion and recurrence making them difficult to treat. A potential targeted treatment may be somatostatin receptor ligands which will be seen on the dotatate PET/CT.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON125 A Case of Hypothalamic Lipoma Causing Hyperprolactinemia in a Patient With Family History of Birt-Hogg-Dubé Syndrome
Authors: Branis Natalia , Thota Geethika 
Published: November 2022

Abstract
A 41year old female with a medical history significant for depression presented for evaluation of bilateral nipple discharge for 5 months. The patient reported that for the last 5 months she started noticing expressible nipple discharge. She reported no associated headaches, vision changes. She denied the use of vitamins, supplements, herbal remedies. No associated fatigue, changes in the shoe/ring size, heat/cold intolerance, tremors, recent weight changes. She denied neck enlargement, neck pain, dysphagia. The patient reported her menstrual cycles had always been heavy and irregular (every 33-50 days). She has never been pregnant. She has been on Sertraline for the last 4 years with no recent dose changes. Family history was significant for Birt-Hogg-Dubé (BHD) syndrome in father, brother, and sister. The patient has not been tested yet. Initial blood test revealed TSH 1.180 uiu/ml (0.45-4.5 uiu/ml), free T4 1.15 ng/dl (0.82- 1.77 ng/dl), T3 91ng/dl (71-180 ng/dl), FSH 3.8 mIU/ml, LH 3.7 mIU/ml, IGF-1 83 ng/ml (74-239 ng/ml), prolactin 107 ng/ml (4.79-23.3 ng/ml), monomeric prolactin 75.7 ng/ml, macroprolactin 23%, estradiol 16 pg/ml, AM Cortisol 6.5 ug/dl (6.2-19.4ug/dl). The urine pregnancy test was negative. Given low normal AM cortisol, a Cosyntropin stimulation test was done, which was normal. MRI Pituitary with contrast showed flattening of pituitary contour compatible with a partially empty sella turcica and an 8 mm fat intensity in hypothalamic region compatible with a lipoma, stable since last 4 years. The patient was referred to Neurosurgery for further evaluation. The patient remained asymptomatic and medical therapy was not indicated. Genetic testing for BHD was discussed. The patient will be followed in the clinic with a follow-up of prolactin levels and imaging as needed.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON129 Pituitary Adenoma Co-Secreting GH, Prolactin and ACTH
Authors: Wilson Sarah , Tucci Marissa , Lovre Dragana , Galagan Robert 
Published: November 2022

Abstract

Background
Pituitary adenomas co-secreting GH, Prolactin and ACTH are rare.

Clinical Case
A 38-year-old male with a past medical history of depression and type 2 diabetes mellitus was seen in the endocrinology clinic for an evaluation of acromegaly. In the preceding four years, the patient had experienced an enlargement of his hands and feet, hyperhidrosis, development of an underbite, snoring, daytime somnolence, erectile dysfunction, headaches, and blurry vision. His visual fields were normal.
Physical exam: BP 137/85, BMI 39 kg/m2. He had coarse facial features, acral changes of his hands and feet, and wide spacing of his teeth. There was a notable absence of facial plethora, abdominal obesity with thin extremities, proximal muscle weakness, purple abdominal striae, and galactorrhea.
Initial laboratory results: GH 16.9 ng/mL (0.05-3 ng/ml), IGF-1 1,109 ng/mL (82-242 ng/mL), Prolactin (PRL) 96.9 ng/ml (5-20 ng/ml), testosterone 34 ng/dL (200-1000 ng/dL), LH 2.3 miu/ml (1.4–12 miu/ml), FSH 4.8 miu/ml (1.5-12 miu /ml), ACTH 197.6 pg/mL (7.2- 63.3 pg/mL), 0800 cortisol 16.2 ug/dL (5-29 ug/dL), 24-hour urine free cortisol 56.84 mcg (3.5-40 mcg), HS salivary cortisol 0.242 (&lt;0.359 ug/dL), overnight 1 mg Dexamethasone suppression test cortisol 6.9 mcg/dL (&lt; 1.8 mcg/dL), normal Free T4 and TSH, and A1c 9.7%.
A pituitary MRI revealed a 3.9 cm lobulated, intra and supra-sellar mass with mass effect on the optic chiasm and 75% encasement of the left supra-clinoid internal carotid artery.
Neurosurgery performed an endoscopic, endonasal partial resection of the pituitary tumor. The histology was diagnostic of an adenoma, and immunohistochemical staining was positive for GH and PRL, but not ACTH.
Post-op lab results: GH 1.07 ng/ml, IGF-1 353 ng/ml, PRL 9.6 ng/ml, testosterone 41 ng/dL, ACTH 68.2 pg/ml, cortisol 4.5 ug/dL, 24-hr urine free cortisol 8 mcg, HbA1c 5.7%.

Discussion
The intent of this case presentation is to report the rare finding of a pituitary tumor co-secreting GH, ACTH, and Prolactin. The diagnosis of acromegaly was confirmed by significant elevations of GH and IGF-1. The diagnosis of subclinical Cushing's disease was confirmed by elevated ACTH level, 24-hr urine free cortisol, and failed dexamethasone suppression test. The elevated PRL may have been due to tumor PRL secretion or stalk effect. The reduction of these parameters after surgery corroborated the presence of pleurihormonal secretion. This patient's findings support screening for co-secretion of multiple pituitary hormones in patients with acromegaly.

Reference
Pleurihormonal ACTH-GH Adenoma: Case Report and Systematic Literature Review World Neurosurg 2018 114: 158-164
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON132 Biochemical and Radiologic Discordance in the Post-operative Surveillance of a Filipino Patient With Acromegaly
Authors: Enverga Mariel C , Isidro Jocelyn C , Po Rainer Wandrew Y , Sarigumba Marion B 
Published: November 2022

Abstract

Background
Trans-sphenoidal surgery is the recommended initial therapy in patients with acromegaly. Early cure rate is 80-90% for microadenomas and &lt;50% for macroadenomas. The goal is a serum IGF-1 that is normal for age and gender with GH &lt;1mcg/L by immunoradiometric or chemiluminescent assays.

Clinical Case
A 71-year old male who consulted for diabetes management was eventually worked up for acromegaly He presented with coarsened facial features, hoarse voice, frontal bossing and enlarged hands and feet. Medical history includes hypertension, hepatosplenomegaly, colonic polyposis, obstructive sleep apnea and nasal septal deviation post-repair.
Laboratory tests showed elevated IGF-1 (566.15, n: 91-282 ng/ml) and non suppressed GH after 75g OGTT (50.1, n&lt;2.47 ng/mL). Pituitary hormonal profile showed normal prolactin (98.13, n: 86-324 mIU/L), TSH (1.63, n: 0.27-4.2 uIU/ml), FT4 (17.78, n: 12-22 pmol/L), ACTH (35, n: 7.2-63.3 pg/mL), Cortisol (387.4, n: 172-497 nmol/L), LH (4.56, n: 1.7-8.6 mIU/mL) and FSH (15.4, n: 1.5-12.4 mIU/mL). Contrast-enhanced pituitary MRI revealed a 1.5×2.0×1.9 cm pituitary macroadenoma with compression of the optic chiasm.
Patient underwent trans-phenoidal surgery and excision of the tumor. Histopathology revealed a homogenous cells in sheets, acidophilic, densely granular and consistent with sommatotrophs, mammotrophs and sommatomammotrophs.
Post-procedure GH was normal (2.731 ng/mL). Two months post-operatively, there was a significant decrease in both GH (1.84 ng/mL) and IGF-1 levels (258.59 ng/mL) while other pituitary hormones all within reference range. Contrast-enhanced pituitary MRI at 2 months showed interval surgical removal of the mass, with decompression of the optic chiasm. Clinically, there was softening of facial features and improvement in his voice. His cranial did not show pituitary mass. However, repeat GH after 75g OGTT (0.37 ng/mL, 2.3 ng/mL) and IGF-1 (361 ng/mL, 523,6 ng/mL) at 9 and 12 months post-surgery, respectively, were found above the reference range.

Conclusion
Discordance between anatomic and biochemical testing must be investigated thoroughly considering pulsatile hormone secretion, comorbidities and possible microscopic residual disease. Testing with the same assay is important to avoid inter-assay variability. Post-operative monitoring should be done at 12 weeks as it may take time for IGF-1 to normalize. If IGF-1 remains elevated, medical, surgical, radiotherapy, or combination may be considered especially in the presence of an identifiable focus.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON161 Decreased serum Wnt antagonist levels in patients with active acromegaly
Authors: Chen Huan , Huang Hong , Wang Yijie , Zhang Yan , Liu Mengsi , Yuan Lou , Zhang ZiWei , Zhu Dalong , Li Ping 
Published: November 2022

Abstract

Objectives
The Wnt signalling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients.

Methods
We recruited 77 patients newly diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. Wnt antagonists [sclerostin (SOST), dickkopf-related protein 1 (DKK-1), and Wnt inhibitory factor 1 (WIF-1)], bone turnover markers [osteocalcin, procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX)] and the bone remodelling index were investigated at baseline and posttreatment.

Results
Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodelling index than controls (all P &lt; 0.01). Serum SOST, DKK-1 and WIF-1 levels were significantly decreased in acromegalic patients compared to controls (all P &lt; 0.01). Serum SOST and WIF-1 levels correlated negatively with growth hormone levels; SOST levels were positively correlated with WIF-1. Posttreatment, serum bone turnover markers and the bone remodelling index decreased, while SOST and WIF-1 significantly increased (P &lt; 0.05). DKK-1 levels did not change compared to baseline (P &gt; 0.05). In biochemically controlled patients, SOST, WIF-1 and bone turnover markers almost reached normal levels (all P &gt; 0.05).

Conclusion
Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists might be involved in the compensatory mechanism of increased bone fragility in active acromegaly.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON182 PACAP Receptor Expression in Sympathetic Ganglia of the Autonomic Nervous System
Authors: Pandher Parleen , Rahim Yamna , Duong Katrina , Gray Sarah 
Published: November 2022

Abstract

In obesity, energy intake exceeds energy expenditure and concomitantly increases risk of chronic diseases, including metabolic diseases such as diabetes. Therapeutics to correct dysregulations in energy balance are needed and one notable neuropeptide being studied is pituitary adenylate cyclase-activating polypeptide (PACAP), an overarching regulator of the stress response1,2. In the context of metabolism, PACAP has been shown to regulate adaptive thermogenesis, an energy burning process regulated by the sympathetic nervous system (SNS) in response to cold stress and overfeeding. While research suggests PACAP acts centrally at the level of the hypothalamus to regulate energy balance3-5, PACAP is also known to be expressed in the SNS. In preganglionic neurons innervating the adrenal medulla6, PACAP is co-localized with acetylcholine and regulates catecholamine synthesis and release. Recent neuronal tracing studies have shown that postganglionic fibres of the stellate ganglia innervate intrascapular brown adipose tissue (BAT), the main thermogenic tissue in mammals7. However, PACAP's role within the sympathetic nerves innervating and regulating energy metabolism in adipose tissues is not known. As such, our group is interested in characterizing PACAP and PACAP receptor expression in sympathetic nerves innervating and regulating energy metabolism in BAT (via the stellate ganglia) in response to metabolic stressors, such as cold stress. We hypothesize that PACAP is released from preganglionic nerves which binds PACAP receptors (PAC1, VPAC1, VPAC2) expressed in postganglionic nerves of the stellate ganglia. Here we report, for the first time, PAC1 and VPAC1 expression in the stellate ganglia with sex-specific differential gene expression based on housing temperature. Analysis of PAC1 splice variant expression identified at least two variants in tissues of the SNS (adrenal gland, superior cervical ganglia and the stellate ganglia). These results will support future functional studies characterizing PACAP regulation of catecholamine production in peripheral ganglia which will contribute to assessing G-protein coupled receptors (GPCRs) as potential therapeutic targets for obesity and metabolic disease.

References
1. Gray SL, Cline DL. 2019. Fink G, Ed. Elsevier: London UK. p.279-91. 2. Mustafa T. 2013. Adv Pharmacol. San Diego, Calif. p.445-57. 3. Banki E, Pakai E, Gaszner B, et al. 2014. J Mol Neurosci 54(3): 543-54. 4. Contreras C, Gonzalez F, Fernø J et al. 2015. Ann Med. 47(2): 150-68. 5. Resch JM, Maunze B, Gerhardt AK, et al. 2013. Am J Physiol-Endoc M. 305(12): E1452-E1463. 6. Eiden LE, Emery AC, Zhang L, et al. 2018. Pflügers Arch. 470(1): 79-88. 7.François M, Torres H, Huesing C, et al. 2019. Ann N T Acad Sci. 1454(1): 3-13.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON37 Diabetes and Hypopituitarism Secondary to Iron Overload in a Patient with Pure Red Cell Aplasia
Authors: Jo Inha , Mora Guido , Robinson Sylvia , Minutti Carla 
Published: November 2022

Abstract

Background
Pure red cell aplasia is a rare bone marrow disorder that results in decline in red blood cell production by the bone marrow. Treatment involves multiple blood transfusions to keep up the red blood cell count, which can lead to iron overload. Hypopituitarism is a condition, where two or more pituitary hormones are deficient. Here we present a case of diabetes and hypopituitarism secondary to iron overload from blood transfusions.

Clinical Case
A 19 year male with pure red cell aplasia was admitted for anemia and was noted to have short stature with growth percentile at 0.36% with predicted MPH estimated to be 180.5 cm. He was Tanner stage 2 on exam and work-up showed IGF1 128 (n 281-510 ng/mL), Testosterone of &lt;1 (n 250-1100 ng/dL), LH 1.1 (n 1-10 mIU/mL), FSH 1.5 (n 1-10 mIU/mL), delayed bone age of 15 years consistent with delayed puberty and hypogonadotropic hypogonadism so he was initiated on 50 mg IM Testosterone monthly. After 1 month, he presented to the hospital again for mild DKA secondary to high dose steroids as part of treatment for his underlying medical condition and also pancreatic dysfunction given history of regular transfusions and iron overload. Initial Fructosamine level was 438 equivalent to HgbA1c of ∼10-11%. He was started on SQ insulin regimen with both long- and short-acting insulin and 50 mcg Levothyroxine as thyroid levels checked during admission showed hypothyroid state, thus, meeting diagnostic criteria for hypopituitarism. Brain MRI was obtained which was negative for mass or lesions, however abdominal MRI showed very high level iron overload on liver, spleen and pancreas. Steroids were weaned and insulin regimen was adjusted on a regular interval according to his blood glucose levels, however, he was not able to wean off insulin even after steroids were discontinued and was transitioned to 70/30 regimen for ease of management with normalization of Fructosamine levels. His testosterone was eventually increased up to 200 mg and was transitioned to daily topical Androgel and currently increasing dose gradually. His most recent testosterone level was 38 ng/dL with goal range of 400-600 ng/dL. His thyroid levels continued to be stable on current dose. He had passed the ACTH stimulation test ∼4-6 weeks after discontinuation of steroids and decided not to pursue growth hormone therapy.

Conclusion
Patients who receive regular blood transfusions are at risk of iron overload, which can affect multiple organs including the pancreas and pituitary gland. This can subsequently lead to insulin-dependent diabetes and hypopituitarism, which should bring awareness of regular assessment of diabetes and pituitary function starting early in life.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP034 Circulating Protein Biomarkers for Discriminating Malignant from Benign Adrenal Tumors Using Mass Spectrometry-Based Proteomic Analysis
Authors: Park Seung Shin , Moon Sun Joon , Jang Han N , Han Dohyun , Kim Jung Hee 
Published: November 2022

Abstract

Backgrounds
Adrenal cortical carcinoma (ACC) is a rare malignant tumor derived from the adrenal gland with a poor prognosis. Since there is no effective medical treatment, early diagnosis and surgical resection are the only way to cure ACC completely. However, early diagnosis of ACC is sometimes tricky because there are no useful diagnostic biomarkers to differentiate ACC from benign adrenal tumors. Therefore, we aimed to identify circulating protein biomarkers to distinguish malignant from benign adrenal tumors using mass spectrometry-based proteomic analysis.

Methods
Plasma samples were obtained from 27 patients with ACC and 69 age- and sex-matched patients with adrenal adenoma. We performed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a data-independent acquisition (DIA) method in plasma samples. Among the quantified 381 proteins, differentially expressed proteins (DEPs) were selected using Student's t-tests for pairwise comparison with a false discovery rate &lt; 0. 05 and |fold-change|&gt; 1.5. In addition, we performed machine learning algorithms such as random forest and XGBoost to select featured DEPs to discriminate ACC.

Results
The mean age of patients was 52 years, and 38 (39.6%) patients were male. Among 19 DEPs, 8 proteins were overexpressed and 11 were underexpressed in ACC patients. In a further analysis using machine learning algorithms, random forest identified 4 proteins as important features for establishing the classifier. The panels with these four proteins showed a good discrimination performance with an area under the curve (AUC) of 0.94 and an accuracy of 0.96. Eight proteins were identified in the XGBoost algorithm. Four proteins in plasma samples were common DEPs from the traditional methods and machine learning algorithms.

Conclusions
High plasma levels of two proteins (One is involved in the migration, attachment and organization of cells into tissues. The other is V region of the variable domain of immunoglobulin light chains), and low plasma levels of two proteins (One is involved in cell-cell adhesion and recognition. The other is V region of the variable domain of immunoglobulin heavy chain) might be circulating protein biomarkers of ACCs compared with benign adrenal adenomas.
Presentation: No date and time listed
PMON49 Checkpoint Inhibitor Induced Hypophysitis with Growth Hormone Deficiency and Implications for the Treatment of ACTH Deficiency
Authors: DeCherney Stephen , Favoreto Natalia , Fiacco Nicholas , Ishizawar Rumey , Saxena-Beem Shruti 
Published: November 2022

Abstract

Background/Purpose
Hypophysitis is a known complication of immune checkpoint inhibitor (ICI) therapies used in the treatment of malignant cancers. In general, central adrenal insufficiency (AI) and hypothyroidism are the most recognized deficiencies following a diagnosis of ICI induced hypophysitis. As a result, other hypothalamic-pituitary axes (HPAs) are either incompletely evaluated or are disregarded from a therapeutic standpoint. Of particular importance is the growth hormone axis which is well established to affect tissue level metabolism of cortisol and cortisone through its effect on 11 beta hydroxysteroid dehydrogenase in target tissues. Our hypothesis is that growth hormone deficiency is also present in ICI induced hypophysitis.

Methods
We queried current and legacy electronic medical records of patients who received ICI for clinical notes mentioning adrenal insufficiency and concern for hypophysitis using the EMERSE tool. Patients with ICI exposure were included if they had 2 of the following 3 criteria; new onset central AI as defined by a low ACTH and cortisol, pituitary imaging suggestive of hypophysitis, or clinical presentation concerning hypophysitis. Patients were excludedfrom the analysis if there was a history of brain irradiation or in whom the diagnosis was not clear due to high dose steroid exposure prior to biochemical evaluation.

Results
Twenty-nine patients met inclusion criteria. Out of 29 patients, 16 underwent testing of the growth hormone axis with IGF-1 (11) and/or random growth hormone level (5). Seventeen patients (59%) had biochemical evidence of deficiency of 3 or more HPAs. Twenty-six patients (90%) had biochemical evidence of 2 or more PHAs. Two patients only underwent evaluation of 2 pituitary axes so it is unknown if they indeed suffered from panhypopituitarism. Most patients (28/29) were prescribed hydrocortisone for AI with an average dose of 20 mg per day.

Conclusions
Our findings are suggestive that growth hormone deficiency may be present in ICI induced hypophysitis. This finding holds implications for cortisol replacement therapy for coexisting AI. When one considers the average adrenal cortisol production is 5.7–7.4 mg/m2/day or 9.5–9.9 mg/day, 20 mg of daily cortisol replacementmay be too high in the face of concomitant growth hormone deficiency. Practice changes may include lower doses ofhydrocortisone replacement or adjustment to cortisone acetate which has been shown to have more favorable effectson tissue level metabolic effects.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.