bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT273 Characterizing The Diurnal Rhythm And Duration Of Adrenal Suppression Following Weeklong Corticosterone Treatment And Withdrawal
Authors: Snyder Christen N , Spencer-Segal Joanna L 
Published: October 2023

Abstract
Disclosure: C.N. Snyder: None. J.L. Spencer-Segal: None.
Exogenous or endogenous glucocorticoid can create a dependence on glucocorticoid excess that manifests as a withdrawal syndrome during attempted taper. The etiology of this syndrome is unclear, and mechanistic understanding is hampered by the lack of a suitable mouse model. Here we present results from one attempt to define a suitable mouse model of chronic glucocorticoid excess and withdrawal. Male mice were treated with corticosterone (45μg/mL) in 1% ethanol in the drinking water for one week prior to withdrawal to a lower dose (10μg/mL) or complete withdrawal (vehicle). Control groups received vehicle or corticosterone 45μg/mL without withdrawal. Tail vein blood samples were collected from mice numerous times during the withdrawal and plasma levels of corticosterone were measured using an Enzyme Immunoassay (Arbor Assays) to determine circulating levels of corticosterone achieved at the diurnal peak and trough during treatment and withdrawal. There were three main goals of this study: (1) measure the circulating levels of corticosterone achieved at the peak and trough using this treatment paradigm (2) determine if 10μg/mL was a physiologic dose during the withdrawal period, and (3) to determine the duration of HPA axis suppression. Results showed that the diurnal rhythm of corticosterone in the treated mice was the opposite of control such that corticosterone levels were high in the morning and low in the evening. Corticosterone levels returned to control levels within 24 hours of withdrawal to 10μg/mL. When withdrawn completely, corticosterone levels decrease below control levels twenty-four hours into the withdrawal but begin to return to baseline by seventy-two hours post-withdrawal indicating rapid recovery of the endogenous HPA axis. This shows that providing corticosterone to mice in the drinking water alters the diurnal peak and trough of circulating corticosterone without continuous corticosterone elevation or prolonged HPA axis suppression. This disruption of the diurnal peak and trough should be considered in the interpretation of studies using chronic corticosterone in the drinking water. Further, this model may not be suitable for studying glucocorticoid withdrawal from chronic excess as the level of corticosterone drops below control at time points in this treatment model.
Presentation: Saturday, June 17, 2023
SAT320 Cyclic Cushing Syndrome Caused By An ACTH-Producing Pheochromocytoma
Authors: Omotosho Yetunde Bernice , Wierman Margaret E , Bukhari Khulood , Pacak Karel , McGlotten Raven , Nieman Lynnette K 
Published: October 2023

Abstract
Disclosure: Y.B. Omotosho: None. M.E. Wierman: None. K. Bukhari: None. K. Pacak: None. R. McGlotten: None. L.K. Nieman: None.
Background: Although pheochromocytomas (Pheo) predominantly produce catecholamines, they also rarely produce Adrenocorticotropin (ACTH) and present with Cushing syndrome (CS). Cyclic CS is an uncommon presentation of hypercortisolism. We here report a unique case of cyclic ectopic ACTH secretion from a Pheo. Clinical case: A 72-year-old female was referred to the NIH with a five-year history of intermittent episodes of unintentional weight gain, hair loss, skin thinning, striae, tremors, labile emotions, glucose intolerance, and a sense of impending doom, interspersed with anorexia, weight loss, normal glucose levels, headaches, and fatigue. The external evaluation documented ACTH-dependent CS with episodes of hypercortisolism, thought to be occult ectopic ACTH secretion. On admission, blood pressure ranged from 122/75 to 171/78 mmHg, and she had a Cushingoid habitus. The biochemical investigation showed basal ACTH 219 pg/ml (NL 5- 46 pg/ml); serum cortisol of 76.9 mcg/dl after 1mg dexamethasone (Dex) suppression test (NL &lt;1.8 mcg/dl), with Dex level of 903; cortisol increased from 13.3 mcg/dl to 15.5 mcg/dl after 8mg Dex, Dex level 4680 ng/ml; plasma normetanephrine 1.8 nmol/L, (NL &lt; 0.9 nmol/L); metanephrine 0.6 nmol/L (NL &lt;0.5 nmol/L); norepinephrine 1493 pg/mL (NL 70-750 pg/mL); epinephrine 298 pg/mL (NL &lt;111 pg/mL); chromogranin A 1314 ng/mL (NL &lt;93 ng/mL). MRI pituitary was normal and bilateral inferior petrosal sinus sampling did not show a central: peripheral gradient before or after desmopressin administration. CT abdomen showed a right adrenal nodule measuring 2.3 cm x 1.8 cm, with pre-and post-contrast Hounsfield units of 30 and 106, and 54% washout. The adrenal mass showed intense activity on 68Ga-DOTATATE and 18F-DOPA PET/CT scans. The patient underwent a right adrenalectomy; the 2.7 x 2.3 x 1.5 cm mass was a Pheo with immunohistochemical staining for ACTH, chromogranin A, and synaptophysin. Post-operatively, blood pressure normalized, and medications were reduced from preoperative metoprolol, lisinopril, and doxazosin to low-dose metoprolol at discharge. Morning cortisol and ACTH levels were &lt;1 mcg/dl and &lt;5 pg/ml. Physiologic replacement of hydrocortisone (15 mg on awakening and 5 mg in the afternoon) was started and switched to prednisone 5mg daily for ACTH deficiency and convenience. The pituitary-adrenal axis remained suppressed at her 6-month follow-up visit. Conclusion: Cyclic CS poses a diagnostic challenge. Here, desmopressin helped to exclude Cushing's Disease. Although ACTH-producing Pheo is rare, it should be considered in the context of ACTH-dependent hypercortisolism if an adrenal mass is present.
Presentation: Saturday, June 17, 2023
THU456 Beyond Guidelines: Treatment Of Concurrent Osteogenesis Imperfecta And Metastatic Bone Disease
Authors: Kanin Maralee , Lechner Melissa 
Published: October 2023

Abstract
Disclosure: M. Kanin: None. M. Lechner: None.
Introduction: Osteogenesis imperfecta (OI) is a rare inherited skeletal dysplasia characterized by bone fragility and skeletal malformation predisposing patients to multiple, recurrent fractures. Treatment of OI is challenging and requires a multidisciplinary approach with emphasis on physical therapy and exercise in addition to medications. There is limited guidance on treatment in adults given truncated life expectancy. Furthermore, guidance on the treatment of OI in the setting of cancer bone metastases is lacking. We present the unique case of a woman with OI and new fracture in the setting of bone-metastatic endometrial cancer. Clinical Case: A 70 year old woman with Type I OI and endometrial adenocarcinoma initially presented to clinic with left hip and groin pain. Prior OI therapy included at least 10 years of bisphosphonate therapy and 3 years of intranasal calcitonin in her fifties. CT imaging revealed a lytic lesion in the L inferior pubic ramus with an associated pathologic fracture. She was treated with denosumab 120mg s.c. every 3 months for six total doses and palliative radiation to the pubic ramus. She developed osteonecrosis of the jaw and further treatment was terminated. She represented 2 years later with right hip pain and was found to have cancer involvement of her right iliac bone. Labs showed creatinine of 0.48 mg/dL, Calcium 9.8 mg/dl, bone specific alkaline phosphatase 17.9ug/L (7.0-22.4 ug/L), n-telopeptide 18.6 nM BCE (6.2-19.0 nM BCE), and vitamin D-25 48ng/ml. DEXA scan showed T scores at the AP spine of -3.2, LFN of -2.1, and RFN of -2.5. Our patient had a high functional status, minimal pain and acceptable quality of life. Given the presence of active bone metastases, we favored treatment with zolendronic acid 4mg i.v. monthly given her high fracture risk, combined with continued cancer therapy targeted to bone metastases. Clinical Lesson: To our knowledge, there are no guidelines or case reports for optimal treatment of patients with concurrent OI and bone metastases. While bisphosphonates are typically a first line treatment for OI, osteoporosis and metastatic bone disease, the duration and dosing of bisphosphonates varies for each condition. For example, zolendronic acid 4mg i.v. monthly is recommended for cancer patients with metastatic bone disease, while a dose of 5mg i.v. yearly is used for osteoporosis, depending on the severity. Additionally, no clear consensus exists for how often or how long bisphosphonates may be given in adults with OI and treatment durations vary markedly. Other agents that may be considered include denosumab, with indications across bone metastases, osteoporosis, and OI, though this was not available to our patient given her prior complication. Data for newer agents PTH analogs and romosuzumab are lacking. We present this case to highlight the need for an individualized treatment approach in these patients.
Presentation: Thursday, June 15, 2023
THU464 An Uncommon Case Of Adult-Onset Hypophosphatemic Osteomalacia
Authors: Lockhart Paola M , Maalouf Naim M 
Published: October 2023

Abstract
Disclosure: P.M. Lockhart Pastor: None. N.M. Maalouf: None.
Introduction: Hypophosphatemic conditions that interfere with bone mineralization and cause osteomalacia comprise many hereditary and acquired diseases. We describe a case of acquired hypophosphatemic osteomalacia associated with Multiple Myeloma (MM). Case Report: A 45-year-old man with MM and systemic AL amyloidosis was referred to our clinic for evaluation of low bone mass on DXA scan. He presented with progressive back pain, proximal muscle weakness, weight loss, and worsening proteinuria, eventually leading to the diagnosis of AL amyloidosis on fat pad biopsy and MM on bone marrow biopsy. Biochemical work up was remarkable for elevated serum alkaline phosphatase at 463 U/L (reference range 46-116) determined to be of skeletal origin. Additional studies included serum phosphorus 1.9 mg/dl (2.4-4.5), creatinine 1.0 mg/dl (0.7-1.2), calcium 9.0 mg/dl (8.4-10.2), albumin 4.1 g/dl (3.5-5.2), PTH 17.1 pg/ml (15-77), and 25-OH-D 52 ng/ml (30-80). Skeletal survey and PET/CT identified diffuse osteopenia but no fracture or lytic lesion. DXA scan showed Z-score of -5.0 at the L-spine and -4.2 at the femoral neck. Further work-up of hypophosphatemia was notable for fractional excretion (FE) phosphate of 37% (&lt;20), serum 1,25-OH2-D 74 pg/ml (18-64), FGF-23 &lt;14 pg/ml (&lt;59), hypouricemia with high FE uric acid, and normoglycemia with glucosuria. Given his marked bone pain, hypophosphatemia, hypouricemia, glucosuria, and elevated alkaline phosphatase, he was diagnosed with hypophosphatemic osteomalacia presumably secondary to light chain accumulation in kidneys leading to proximal tubule dysfunction (acquired Fanconi syndrome). In addition to MM treatment (5 cycles of Dara-CyBorD then stem cell transplantation), he was started on phosphate supplementation, with marked improvement in bone pain, muscle strength, and serum alkaline phosphatase over 6 months. No anti-resorptive agents were used in treating his MM. Conclusion: This case highlights an unusual presentation of hypophosphatemic osteomalacia. It is important to recognize that bone pain in patients with MM is not only caused by osteolytic lesion but can also result from osteomalacia due to Fanconi syndrome due to light chain kappa deposition. In this patient, treatment with phosphate supplementation resulted in clinical improvement of bone pain and biochemical markers. To date, there are only few reported cases of hypophosphatemic osteomalacia due to Fanconi syndrome in the setting of MM.
Presentation: Thursday, June 15, 2023
OR13-05 Longitudinal Changes In Bone Turnover Following Withdrawal Of RANKL Inhibition
Authors: Kim Albert S , Castro-Martinez Ariel , Taylor Victoria , Center Jacqueline , Girgis Christian M , Croucher Peter I , Mcdonald Michelle M 
Published: October 2023

Abstract
Disclosure: A.S. Kim: None. A. Castro-Martinez: None. V. Taylor: None. J. Center: None. C.M. Girgis: None. P.I. Croucher: None. M.M. Mcdonald: None.
Denosumab is an effective osteoporosis treatment, preventing bone loss by inhibiting RANKL. However, stopping denosumab leads to rebound bone mineral density(BMD) loss. This is due to accelerated bone resorption by osteoclasts. Serum bone turnover markers such as P1NP and CTX have been utilised in clinical practice to guide sequential therapy following denosumab discontinuation. However, an optimal strategy has not been established. Understanding the temporal changes in osteoclast activity will guide safe, effective sequential therapy following denosumab discontinuation. We hypothesised that serum TRAP5b, a marker of enzymatic activity of osteoclasts, would be a more useful marker in this context to guide sequential treatment following denosumab discontinuation. Seven-week-old female C57BL/6 mice were treated with 2-weeks of thrice-weekly OPG:Fc(10mg/kg) to inhibit RANKL then withdrawn from therapy (OPG-W) or saline(vehicle). Longitudinal BMD and serum TRAP5b were measured throughout the study. Mice were harvested at weeks 2, 8, 11 and 13 to allow a large volume of serum to be collected to concurrently measure serum TRAP5b and the products of collagen formation and breakdown, serum P1NP and CTX respectively . Following OPG:Fc withdrawal, BMD peaked at week 8 in OPG-W mice (92.94 vs75.09mg/cm2, p&lt;0.0001), started to decline at week 10 and normalised to vehicle levels by week 13. Longitudinally, serum TRAP was suppressed by week 2 (0.05 vs 11.90U/L, p&lt;0.0001) and remained suppressed until week 8, following which serum TRAP levels rose progressively to 64% above vehicle levels at week 12 (17.86 vs 10.92U/L, p&lt;0.0001). The rise in TRAP between weeks 8 to 10 preceded the decline in BMD.Serum TRAP was significantly elevated in OPG-W mice at week 11 (15.45 vs 11.46U/L, p=0.01) whereas serum P1NP and CTX remained equivalent to vehicle levels. Serum TRAP, P1NP and CTX were significantly higher in OPG-W mice at week 13 by which time BMD had reached vehicle levels. Our findings show that rebound decline in BMD has already occurred by the time bone turnover markers used in clinical practice (P1NP and CTX) rise above vehicle levels. A significant overshoot in serum TRAP occurs earlier and prior to bone loss and may better inform sequential therapy following denosumab discontinuation.
Presentation: Friday, June 16, 2023
SAT192 Non-syndromal Primary Hyperparathyroidism Presenting As Asymptomatic Hypercalcemia In A Teenage Patient.
Authors: Humayon Salman , Shah Mahabir , Nighat Kabir Purnima , Penaherrera Carlos A 
Published: October 2023

Abstract
Disclosure: S. Humayon: None. M. Shah: None. P.N. Kabir: None. C.A. Penaherrera: None.
Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia in the general population, and is often discovered incidentally. The condition rarely presents in patients under age 18, particularly when it is not associated with genetic syndromes such as MEN 1. Case presentation: A previously healthy 17-year-old female was referred to Endocrinology clinic for evaluation of positive thyroid peroxidase antibodies with normal TSH and free T4. Review of laboratory results from 6 months prior, revealed an elevated total calcium level of 12.3 mg/dl. Patient at the time denied any symptoms of hypercalcemia. Repeat testing revealed a calcium level of 13.1 mg/dl, PTH level of 183 pg/ml, alkaline phosphatase 232 IU/L. Her vitamin D level was 28 ng/ml, with elevated calcitriol level of 362 ng/ml. The patient denied a history of kidney stones or other endocrine abnormalities in the past. She did mention a family history of hypercalcemia in her father requiring neck surgery. Patient was admitted to the hospital for management of hypercalcemia with intravenous fluid hydration. Subsequent work-up included a sestamibi parathyroid scan which revealed an asymmetric area of delayed uptake in the left thyroid gland, suggestive of a single parathyroid adenoma. The patient underwent single-gland parathyroidectomy, during which PTH levels decreased from 134 pg/ml to 15 pg/ml. She recovered uneventfully from the procedure and was started on oral calcium supplementation, which was tapered two months after surgery since there was no evidence of post-operative hypoparathyroidism. Conclusion: Primary hyperparathyroidism, when presenting prior to the age of 30, is most commonly associated with genetic syndromes such as MEN1 and typically presents as multi-glandular hyperplasia. Isolated primary hyperparathyroidism, secondary to a single parathyroid adenoma is seen less frequently in this younger subset of patients. This can be found in the absence of other endocrine abnormalities, with or without the presence of a family history. Prompt identification of hypercalcemia followed by evaluation of the same, may prevent delays in diagnosis and subsequent management of primary hyperparathyroidism. This can help prevent morbidity associated with hypercalcemia.
Presentation: Saturday, June 17, 2023
SAT207 Parathyroid Carcinoma: A Case Report
Authors: Te Sy Katrina Vina , Cating-Cabral Monica Therese 
Published: October 2023

Abstract
Disclosure: K.T. Sy: None.
Background: Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of causes of primary hyperparathyroidism. Case reports have mentioned of parathyroid carcinoma arising in patients with prior neck irradiation, in secondary and tertiary hyperparathyroidism and in patients with history of thyroid cancer and parathyroid adenoma. However, none of these reported associations have been completely established. Clinical Case: The is a case of a 59-year old male presenting with hypercalcemia. He was diagnosed with primary hyperparathyroidism secondary to a parathyroid adenoma, underwent parathyroidectomy with resolution of the hypercalcemia. Six years later, patient had recurrence of hypercalcemia with elevated PTH levels. Parathyroid imaging revealed a mild sestamibi-avid focus in the left retrosternal region, suggestive of an ectopic parathyroid gland and radio-guided neck exploration was done with excision of lesion. Histopathological report revealed parathyroid carcinoma. Two years later, there was recurrence of parathyroid carcinoma but mediastinal exploration revealed no lesions consistent with parathyroid carcinoma. Hypercalcemia with hyperparathyroidism persisted, and cinacalet was started but the patient could not tolerate the nausea associated with the medication. Repeat parathyroid imaging revealed sestamibi-avid lesions in the right retroclavicular, left prevascular/retrosternal, and a left paratracheal areas. Surgical exploration was offered but the patient refused. The patient also developed hypertension and low bone density was noted on dual X-ray absorptiometry (DXA) scan. He was started on denosumab 60 mg subcutaneously every 6 months, which was increased to 60mg every month and then 120mg every month to maintain normal calcium levels. The patient also developed chronic kidney disease, eventually requiring hemodialysis for elevated creatinine levels and hypercalcemic crisis. Soon after hemodialysis was started, the patient had a myocardial infarction and eventually expired. Conclusion: Complete surgical resection is the primary mode of therapy in parathyroid carcinoma, although hypercalcemia is the main cause of morbidity and mortality, rather than the tumor burden. The adjuvant use of radiotherapy and chemotherapy are still controversial. Some studies have shown that long term survival is favorable, but recurrences are frequent and patients tend to live a life filled with long-term follow up, multiple laboratory exams and imaging, hospitalizations and frequent reoperations. Mortality is usually due to uncontrollable hypercalcemia, leading to renal failure and cardiac arrhythmias.
Presentation: Saturday, June 17, 2023
SAT220 Rare Case Of Pembrolizumab Induced Primary Hypoparathyroidism
Authors: Goud Sarita G , Siddiqui Ayesha , Alkhathlan Mujahed , Ying Fan Chris 
Published: October 2023

Abstract
Disclosure: S.G. Goud: None. A. Siddiqui: None. M. Alkhathlan: None. C.Y. Fan: None.
Introduction: Immune checkpoint inhibitors such as pembrolizumab (Keytruda) used in the treatment of various cancers are associated with immune mediated endocrinopathies, among which thyroid dysfunction and pituitary hypophysitis are common, whereas hypoparathyroidism is rare. We report a case of primary hypoparathyroidism and hypocalcemia with pembrolizumab. Clinical Case: 58-year-old male with metastatic urothelial cell carcinoma, status post neoadjuvant chemotherapy with gemcitabine and cisplatin in 2017, followed by radical cystectomy with recurrence of metastasis in 2018, who was started on Keytruda every three weeks. After 10 months, he developed immune mediated hypothyroidism treated with levothyroxine. After 33 months on Keytruda, he developed hematochezia with constipation and intermittent abdominal pain. Colonoscopy showed findings consistent with autoimmune colitis; Keytruda was held and colitis was treated with tapering steroids. Surveillance imaging showed stable disease, so Keytruda continued to be held. After 7 months of holding Keytruda, on routine blood work he had a critically low calcium level of 5.5 mg/dl (8.4-10.2 mg/dl) with tingling and numbness in his hands, muscle spasms, generalized weakness, and fatigue for the past few weeks. On exam there was no Trousseau’s sign, Chvostek's sign, or gait ataxia. Hemodynamically stable. Labs showed lowest corrected calcium of 5.5, normal renal function, low vitamin D of 8 ng/ml (30-100 ng/ml), elevated phosphorus of 6.3 mg/dl (2.5-4.5 mg/dl), and normal magnesium. PTH was frankly low at 12.7 pg/ml (15-65 pg/ml), indicating primary hypoparathyroidism. ACTH stimulation test was normal. Retrospective review of the labs from oncology office records showed gradual, progressive hypocalcemia for a few months prior to presentation, with calcium levels ranging between 6.7 to 7.7 mg/dl. Of note, calcium prior to pembrolizumab was normal at 9.4 mg/dl. He was treated with IV calcium gluconate and then transitioned to calcium carbonate (CaCO3) 500 mg TID, calcitriol 0.5 mg BID, and Vit D 50,000 IU twice weekly. Hydrochlorothiazide (HCTZ) added as calcium remained low. After three days calcium improved to 7 mg/dl range and he was discharged. Calcium levels checked periodically after discharge ranged from 8 to 9 mg/dl (8.4-10.2 mg/dl), and phosphorus levels normalized. CaCO3 dose was adjusted accordingly, Vit D was changed to 50,000 IU weekly based on a level of 71 ng/dl after 3 months, and HCTZ was discontinued after 6 months. PTH was still low at 9.7 pg/ml (15-65 pg/ml) 6 months after discharge, off pembrolizumab for over a year. Calcium sensing receptor (CaSR) activating antibody was not checked in our case. Conclusion: It is important clinicians be aware of the risk for hypocalcemia and its unpredictable presentation to help with timely recognition and management.
Presentation: Saturday, June 17, 2023