bluuebunny/crossref_metadata_2025_split huggingface dataset:
6426 Pregnancy-induced ACTH-independent Cushing Syndrome: A Rare Phenomenon Secondary To Aberrant Receptors On Adrenal Glands
Authors: Manglani Kajol , Sharma Susmeeta T 
Published: October 2024

Abstract
Disclosure: K. Manglani: None. S.T. Sharma: None.
Pregnancy-induced hypercortisolism is a rare phenomenon with very few cases reported in the literature. The pathogenesis is thought to be secondary to the expression of aberrant LH/hCG receptors on the adrenal gland that stimulate cortisol production in pregnancy. We present a case of a 31-year-old female with no past comorbidities until her first pregnancy in 2017 when she gained around 50lbs, developed violaceous striae, acne, hirsutism, depression with suicidal ideation for which she was hospitalized twice, and underwent emergent C-section at 34 weeks’ gestation due to pre-eclampsia. She was referred to the Endocrinology clinic post-delivery, and screening for Cushing syndrome was negative at that time: 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC) and 1-mg dexamethasone (dex) suppression test (DST) were normal. She presented again in 2020 during her second pregnancy at 14 weeks gestation, with 20lb weight gain in the first trimester, acne, hirsutism, and easy bruising. Labs showed cortisol of 22.4 mcg/dL (6.2-19.4), ACTH &lt;1.5 pg/mL, total testosterone 168 ng/dL (8-48), androstenedione 751 ng/dL (41-262), DHEAS 91.2 mcg/dL (84.8-378), 24-hour UFC 277 mcg/day (6-42), LNSC 0.671 mcg/dL, 1mg DST with post-dex cortisol 24 mcg/dL (dex level 58 ng/dL), and 8-mg DST with post-dex cortisol level of 28.2 mcg/dL (dex level 457 ng/dL). Testing was consistent with ACTH-independent Cushing syndrome. Ultrasound and MRI of the abdomen/pelvis showed normal adrenal glands with no hyperplasia or mass. Given worsening hypercortisolism and her course during a prior pregnancy, medical treatment with metyrapone was initiated. We started at a dose of 500 mg daily and gradually increased to 1500 mg with close monitoring of her blood pressure and cortisol levels. She underwent vaginal delivery at 38 weeks’ gestation, and the baby required a brief stay in the NICU for respiratory distress but was otherwise doing well. The patient developed secondary adrenal insufficiency post-delivery requiring hydrocortisone, with recovery of her HPA axis in around 10 weeks. Since then, she has been off hydrocortisone with normal UFC, ACTH, and cortisol levels. This case enables discussion regarding the underlying etiology, diagnostic difficulties, and management of this rare condition. Although the exact etiology is unknown, the postulated mechanism is aberrant LH/hCG receptor expression given the patient’s presentation during each pregnancy, normal cortisol levels between both pregnancies, and a brief period of adrenal insufficiency post-delivery. Management of hypercortisolism during pregnancy remains challenging. Metyrapone, a steroidogenesis inhibitor, can be considered for control of hypercortisolemia during pregnancy (off-label) in select cases to prevent maternal and fetal complications.
Presentation: 6/1/2024
9313 Prevalence And Incidence Of Fragility Fractures In Patients With Nonfunctioning Adrenal Incidentalomas
Authors: Favero Vittoria , Cairoli Elisa , Eller-Vainicher Cristina , Morelli Valentina , Stefano Salcuni Antonio , Della Casa Silvia , Muscogiuri Giovanna , Columbu Carla , Pugliese Flavia , Corbetta Sabrina , Persani Luca , Scillitani Alfredo , Chiodini Iacopo 
Published: October 2024

Abstract
Disclosure: V. Favero: None. E. Cairoli: None. C. Eller-Vainicher: None. V. Morelli: None. A.S. Salcuni: None. S. Della Casa: None. G. Muscogiuri: None. C. Columbu: None. F. Pugliese: None. S. Corbetta: None. L. Persani: None. A. Scillitani: None. I. Chiodini: None.
Context: The risk of vertebral fractures (VFx) in patients with non-functioning adrenal incidentalomas (NFAI) is unknown. Objective: To evaluate the VFx prevalence and incidence in NFAI patients. Design. Cross-sectional and longitudinal study on retrospective data. Setting. Four Italian endocrinology units. Patients. 306 NFAI patients (cross-sectional arm) and 213 matched control subjects to evaluate VFx prevalence; 85 NFAI patients (longitudinal arm, follow-up 30.3±17.5 months) to evaluate VFx incidence. Main outcome measures: serum cortisol after 1 mg-dexamethasone test (F-1mgDST), bone mineral density (BMD) at spine (LS) and femur (FN), and VFx presence by x-ray. Results:. Cross-sectional arm: prevalent VFx was associated with F-1mgDST with the cut-off set at 1.2 µg/dL (33 nmol/L, area under the curve 0.620±0.39, p=0.002). As compared with controls and with NFAI patients with F-1mgDST &lt;1.2 µg/dL (33 nmol/L, Group NFAI-A), NFAI patients with F-1mgDST ≥1.2 µg/dL (33 nmol/L, Group NFAI-B) showed higher VFx prevalence (10.8%, 12.6% and 29.5%, respectively, p&lt;0.001 for all comparisons), which was independently associated with F-1mgDST ≥1.2 µg/dL (33 nmol/L, odds ratio 3.02, 95% confidence interval 1.63-5.58, p&lt;0.001) regardless for influencing factors including BMD. Longitudinal arm: the VFx incidence was higher in Group NFAI-B than in Group NFAI-A (19.3% vs 3.6%, p=0.05). In NFAI-B group, all incident VFx occurred in patients without low BMD. The F-1mgDST cut-off for predicting an incident VFx was 1.2 µg/dL (33 nmol/L), but the incident VFx was not independently predicted by F-1mgDST ≥1.2 µg/dL (33 nmol/L) after adjusting for possible influencing factors, including BMD and presence of prevalent VFx. Conclusions: In NFAI patients, F-1mgDST levels ≥1.2 µg/L (33 nmol/L) are associated with prevalent VFx and may identify NFAI patients at higher risk of incident VFx
Presentation: 6/3/2024
8204 Rare Asymptomatic Presentation Of A Large Pheochromocytoma
Authors: Lorin Arkadiy , Kamini Persaud Christine , Kemm Matthew H 
Published: October 2024

Abstract
Disclosure: A. Lorin: None. C.K. Persaud: None. M.H. Kemm: None.
Background: Pheochromocytoma is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal medulla. It is associated with excessive release of catecholamines causing symptoms of hypertension, palpitations, diaphoresis, and headaches. These symptoms are particularly prominent with larger pheochromocytomas. We present the case of a large 13 cm pheochromocytoma (PCC) without the typical associated symptoms. Clinical Case: A 45-year-old male with medical history of osteoarthritis and gastroesophageal reflux presented to his primary care doctor with 2 months of intermittent right upper quadrant abdominal pain associated with nausea. Work up with CT abdomen/pelvis found a 9.3 cm heterogeneous right adrenal mass with mass effect on the right liver lobe, superior pole of the right kidney, duodenum, and pancreatic head. Hormonal testing was notable for plasma metanephrine 257.8 pg/mL (0-88), plasma normetanephrine 12063.7 pg/mL (0.0-218.9), 24 hr urine metanephrine 159 mcg/24 hr (58-276), 24 hr urine normetanephrine 22575 mcg/24 hr (156-729), and chromogranin A 5387 mg/mL (0-101.8). Given lab evaluation, diagnosis was made of pheochromocytoma, and patient was initiated on alpha blockade with doxazosin. Patient’s blood pressure and heart rate were at goal prior to doxazosin initiation and patient needed to be decreased from 1 mg daily to 0.5 mg daily due to side effects of low blood pressure and orthostatic hypotension. Patient had an uncomplicated open right adrenalectomy with pathology showing a 13 cm pheochromocytoma with invasion through the capsule into the periadrenal adipose tissue. Genetic testing revealed no known mutation variants associated with PCC. Labs drawn two weeks postoperatively showed resolution of elevated plasma metanephrine, normetanephrine, and chromogranin A. Conclusion: While the patient had an elevated plasma metanephrine, the normetanephrine was predominantly elevated. Such a hormone profile is more common in extra-adrenal PCCs, consistent with cluster 1 associated genes. This noradrenergic phenotype is likely a reason the patient did not have typical symptoms, despite the size of his pheochromocytoma. A proposed pathophysiologic mechanism for this is the dissociation of renal medulla from the cortex given the large size of the tumor. This would lead to lower local availability of corticosteroid to potentiate the conversion of norepinephrine to epinephrine, thus decreasing likelihood of classical PCC symptoms. Despite lack of expected symptoms and an imaging initially concerning for adrenocortical carcinoma, we should recognize the potential for a large adrenal tumor to represent PCC and evaluate accordingly.
Presentation: 6/1/2024
8275 Recurrent Retroperitoneal Paraganglioma
Authors: Kang Jannat , Gupta Vishaal , Subauste Jose S 
Published: October 2024

Abstract
Disclosure: J. Kang: None. V. Gupta: None. J.S. Subauste: None.
Paragangliomas are rare, highly vascular neuroendocrine neoplasms that may originate from sympathetic or parasympathetic paraganglia and may secrete catecholamines. They are closely related to pheochromocytomas which are considered to be their intra-adrenal counterparts. A 65-year-old African American male with type 2 diabetes and tobacco use presented to his primary care physician with night sweats and unintentional weight loss of about 30 pounds in 3 months. Review of systems and laboratory workup was unremarkable. CT Chest/Abdomen/Pelvis with contrast showed a homogenous, well-circumscribed 4.6cm retroperitoneal mass causing mass effect on portal vein, Inferior vena cava, and right renal artery. Interventional radiology performed fine needle aspiration with intra-procedural blood pressure rising to 201/70 mmHg. Pathology showed paraganglioma, staining positive for synaptophysin, chromogranin A, CD 56 and S-100 protein. Plasma metanephrines were elevated at 2818 pg/mL, plasma normetanephrines at 1247 pg/mL with consistent 24-hour urine results. Workup for other adrenal hormones was negative. No family history of pheochromocytoma/paraganglioma or any clinical manifestations of Von-Hippel-Lindau syndrome or Neurofibromatosis were present. He was started on alpha blockade followed by beta blocker and surgical resection was planned. In the interim, escalating requirements of insulin were noted. Intra-operative course was complicated by systolic blood pressure rising to 290s which resolved after mass was removed. Immunohistochemical studies sent to Mayo, Rochester showed retained cytoplasmic SDHB expression in tumor cells. Hence, no further genetic testing was performed. Post excision, plasma-free metanephrines normalized with significant improvement in blood pressure and diabetes. He was followed with yearly plasma-free metanephrines for surveillance. Although asymptomatic, a three-fold rise of plasma metanephrines was noted five years later. CT Abdomen was concerning for recurrence. Dotate/PET scan showed dotate-avid para-aortic soft tissue lesion measuring 2.3 cm between the celiac artery and the superior mesenteric artery which was surgically excised with pathology consistent with paraganglioma (Ki67&lt;1%). Diagnosis of paragangliomas is often in 3rd - 5th decade. About 30% are hereditary and associated with Von-Hippel-Lindau, Neurofibromatosis-1, MEN2A/B among other syndromes. They are mostly benign but SDHB pathogenic variants are likely to be malignant. Genetic testing should be considered in all paraganglioma patients to screen for germline pathogenic variants in SDH and other genes. Diagnosis of secretory paraganglioma is by urinary and/or plasma fractionated metanephrines and catecholamines. Treatment of choice is surgery when amenable to resection with preoperative medical blockade to prevent perioperative complications.
Presentation: 6/1/2024
12383 Salivary Cortisone Measurement In Mild Autonomous Cortisol Secretion: Retrospective Single-center Cohort Study
Authors: Villavicencio Torres Camila A , Chai Yubo , Grebe Stefan K , Maus Tony D , Bancos Irina 
Published: October 2024

Abstract
Disclosure: C.A. Villavicencio Torres: None. Y. Chai: None. S.K. Grebe: None. T.D. Maus: None. I. Bancos: None.
Background: Mild autonomous cortisol secretion (MACS) is diagnosed based on abnormal post-dexamethasone cortisol &gt;1.8 mcg/dL. Late-night salivary cortisol (SalF) measurements in MACS are usually within normal ranges, and as such are not recommended by the adrenal incidentaloma guidelines. Late-night salivary cortisone (SalE) measurement may have a higher accuracy than SalF in diagnosing MACS. Objectives: To determine associations between SalF and SalE and post-dexamethasone cortisol concentrations in patients with MACS. Methods: We conducted a single-center retrospective cohort study of data between 2020-2023 that included patients with MACS who had concomitant SalF and SalE measurements at the time of diagnosis. Electronic medical records were reviewed for clinical, imaging, biochemical characteristics, and outcome data. Results: In 45 patients with MACS (31, 69% women) evaluated at a median age of 62 years (IQR 54-70), median post-dexamethasone cortisol was 3 mcg/dL (IQR 2.5-5.7), median corticotropin (ACTH) was 11 pg/mL (IQR 5.2-30), and median dehydroepiandrosterone sulfate (DHEAS) was 47.5 mcg/dL (IQR 27.8-98.8). In 36 patients, 24h-urine cortisol was also available, with a median cortisol of 14 mcg/dL (IQR 11.3-18), normal ranges &lt;45 mcg/24h. Median adrenal adenoma size was 2.2 cm (IQR 1.6-3.0), and median unenhanced HU was 10 (IQR -5 to 22).Median SalF was 52 ng/dL (IQR 23.9-97.5), and median SalE was 332 ng/dL (IQR 222.5-607.0), with a median SalE/SalF ratio of 6.6 (IQR 5.7-9.0). SalF was normal (&lt;50 ng/dL) in 22 (49%) patients with MACS, without differences in the post-dexamethasone cortisol concentrations between those with normal and abnormal SalF (median of 3 mcg/dL vs 3 mcg/dL, P=0.94). SalF correlated with SalE (R2=0.83, P&lt;0.0001). However, only SalE was associated with post-dexamethasone cortisol (R2=0.09, P=0.04). Conclusion: SalE is associated with post-dexamethasone cortisol in patients with MACS and, after an appropriate validation, may provide additional value in support of diagnosis of MACS.
Presentation: 6/3/2024
7362 Single-Cell Analysis Of Cortisol-Producing Adrenal Adenomas
Authors: Kono Takashi , Fujimoto Masanori , Taki Yuki , Tanaka Tomoaki 
Published: October 2024

Abstract
Disclosure: T. Kono: None. M. Fujimoto: None. Y. Taki: None. T. Tanaka: None.
Introduction: Cortisol-producing adenoma (CPA) is a common adrenal tumor. Although the contribution of mutations to the pathogenesis of CPA is well-established, mutations alone cannot explain all the diverse clinical manifestations. Therefore, it is important to observe the nature of the tumor from a different perspective, based on the clinical features, and understand the pathogenesis of the disease. Recently, single-cell analysis techniques have been developed to accurately define and analyze diverse cell populations, such as tumor cells, immune cells, and stromal cells, in tumor tissues. It is expected that these techniques will reveal the nature of tumor cells that were not visible in the averaged analysis of the entire tumor. Method: We performed genetic mutation analysis and single-cell RNA sequencing on 58 samples of normal adrenal tissue and 13 cases of CPA. Result: The results showed that both normal adrenal tissue and CPA tumor tissue were composed of various cells, including adrenal cortical cells, immune cells dominated by macrophages and T cells, endothelial cells, and fibroblasts. The genetic mutations of CPA are mainly divided into two groups: (1) mutations in PRKACA and GNAS that contribute to the activation of the cAMP pathway and (2) mutations in CTNNB1 that contribute to the activation of the Wnt pathway. Based on the patterns of genetic mutations, we divided the tumor cells into four groups: PRKACA, GNAS, CTNNB1, and N.D. (Not detected). We then used single-cell analysis of tumor cells to observe the differences in their nature using consensus clustering and module analysis. The results showed that the cluster with the most cells with PRKACA mutations was the largest, and the steroidogenesis gene cluster showed correlated changes. Conclusion: Single-cell analysis revealed that the adrenal tissue is composed of diverse cell populations, and it was possible to identify and analyze specific cell populations. In the future, it is necessary to clarify the relationship between tumor cell origin and zonation, as well as to develop new disease phenotypes and classifications based on the interactions between diverse cells that construct the tissue.
Presentation: 6/1/2024
5179 Uncommon Benign Mimics Of Suspicious Adrenal Nodules
Authors: Zhu L , Loh L M , Gan V , Kek P 
Published: October 2024

Abstract
Disclosure: L. Zhu: None. L. Loh: None. V. Gan: None. P. Kek: None.
Introduction: Adrenal incidentaloma is often detected in imaging studies. In addition to biochemical testing, imaging plays a key role in guiding the management of such lesions. We describe two uncommon cases of benign lesions masquerading as suspicious adrenal nodules. Case 1. A 54-year-old man with hypertension, diabetes, dyslipidaemia, ischaemic heart disease and atrial fibrillation (on warfarin) underwent CT scan to exclude malignancy when he presented with thigh DVT, and was found to have a right 3.2cm adrenal nodule. Adrenal hormone profile was unremarkable. CT contrast characterization showed attenuation of 30, 35, and 32 HU on pre-contrast, venous and 10-minute delayed phase respectively. Given the minimal enhancement in high density areas, possible haemorrhage was considered and he was put on imaging surveillance. CT scans over the following 5 years showed stability of the lesion, resolution of high-density areas, and pre-contrast attenuation of -35HU, suggestive of myelolipoma. Further follow-up over the next 2 years then revealed tumour enlargement to 8.5cm, progressive predominance of dense areas (58 HU), and development of compressive symptoms. In view of mass effect, growing heterogeneity and possibility of a collision tumour, right adrenalectomy was performed. Histopathology revealed myelolipoma with extensive haemorrhage and no evidence of malignancy. Case 2. A 65-year-old woman had hypertension, ischaemic heart disease, dialysis-dependent end-stage renal disease secondary to glomerulonephritis, and oncological history of left renal cell carcinoma (RCC) and low-grade papillary urothelial carcinoma, both surgically resected 10 years ago. A new 1.6cm right adrenal nodule was seen on her surveillance CT scan for RCC. It was not present in a CT scan 7 years ago. The nodule displayed suspicious features such as nodular avid rim enhancement, persistent enhancement on delayed phase of contrast washout and central cystic change. Biochemical screening revealed plasma free metanephrine of 0.33 nmol/L (NR: &lt;0.33) and plasma free normetanephrine of 0.99 nmol/L (NR: &lt;0.71). Other adrenal hormone profiles were unremarkable. Cystic phaeochromocytoma was suspected and she underwent right adrenalectomy and nephrectomy following alpha blockade. Histopathology revealed a well-circumscribed nodule in the supra-renal adipose tissue, with vascular proliferation and features of anastomosing haemangioma. The right kidney was reported to have acquired cystic disease associated RCC. She was well post-operatively and remained on follow-up with the urologist for her RCC. Discussion: Haemorrhagic adrenal myelolipoma and supra-renal anatomosing haemangioma are benign lesions that may have CT characteristics similar to those of sinister lesions. Pre-operative diagnosis can be challenging. Surgical excision may be required to confirm diagnosis and exclude malignancy.
Presentation: 6/3/2024
6485 Unilateral Adrenal Metastasis From Unknown Primary Carcinoma Mimicking Primary Adrenocortical Carcinoma
Authors: Watanabe Suzuka , Suzuki Sawako , Ishiwata Kazuki , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro 
Published: October 2024

Abstract
Disclosure: S. Watanabe: None. S. Suzuki: None. K. Ishiwata: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None.
Background: Adrenal metastasis from carcinomas of the lung, breast, and melanoma are observed. However, isolated adrenal metastasis with unknown primary carcinoma origin has been rare, and the diagnosis is challenging. We encountered a case of unilateral adrenal tumor clinically diagnosed as non-functional primary adrenocortical carcinoma, but found to be a metastatic tumor on postoperative pathology. Clinical Case: A 68-year-old man was referred to our hospital for examination of an 8mm right adrenal incidentaloma. He underwent hormone therapy for prostate cancer four years ago, and the condition is in remission with no recurrence signs. Follow-up CT revealed that the adrenal tumor rapidly enlarged from 8 mm to 36 mm within six months, and its mean attenuation value was 38 HU. MRI showed that the adrenal tumor had a low signal intensity on T1 and a high signal on T2. At the same time, there is mediastinal lymphadenopathy and a 9-mm nodule in the lower lobe of the right lung, which was considered benign from the stable condition. FDG-PET/CT showed FDG uptake only in the right adrenal tumor (maximum standardized uptake value of 21.39). [1]23I-MIBG scintigraphy did not show any accumulations. The serum and urinary adrenal hormones were all within normal limits. Notably, tumor markers such as prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and cancer antigen 19-9 (CA 19-9) were all within normal ranges. Therefore, we clinically suspected non-functional primary adrenocortical carcinoma, and the laparoscopic right adrenalectomy was performed. The resected right adrenal lesion was encapsulated and measured 79×54×22 mm. On histological analysis, the nodule comprised tumor cells with eosinophilic cytoplasm, and abundant tissue infiltrating lymphocytes. Immunohistochemical studies revealed that the tumor was not of adrenal origin due to negative steroidogenic factor-1 (SF-1) and inhibin alpha staining. From these results, the adrenal tumor was diagnosed as adrenal metastasis from unknown primary carcinoma. The tumor cells were positive for cytokeratin19, CEA, and thyroid transcription factor-1 but negative for PSA, p63, cytokeratin 5/6, insulinoma-associated protein-1, and synaptophysin. Genetically, the adrenal tumor harbored genomic abnormalities in CDKN2A, TP53, NF1, PBRM1, and KEAP1 genes. Conclusion: Isolated adrenal metastasis without a detectable primary tumor is rare but should be considered a differential diagnosis in the case of an enlarged, non-functioning adrenal tumor. Adrenalectomy or tumor biopsy may be actively considered to diagnose and determine the optimal course of treatment.
Presentation: 6/3/2024