bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI262 Can Selective Serotonin Reuptake Inhibitors Unmask Underlying Polyglandular Autoimmune Syndrome Type II?
Authors: Dehghani Shabnam , Kalik Salina , Zaidan Julie , Nisar Aqsa
Published: October 2023

Disclosure: S. Dehghani: None. S. Kalik: None. J. Zaidan: None. A. Nisar: None.

Background: Patients with chronic use of SSRIs are at increased risk of developing hyponatremia secondary to SIADH but a full work up to exclude other etiologies might still be warranted if patient has risk factors. Clinical Case: 63-year-old female with past medical history of rheumatoid arthritis and hypothyroidism secondary to Hashimoto thyroiditis presented to the hospital for evaluation of syncopal episodes associated with dizziness, loss of consciousness and weight loss. She was started three weeks prior to presentation on Escitalopram 10 mg for mild depression. On exam she had orthostatic hypotension, she looked tanned but there was no buccal or palmar pigmentation. Admission blood work showed Na level of (111 mmol/L, n:135-145 mmol/L), Potassium of (5.7 mmol/L, n: 3.5-5 mmol/L), Creatinine of (0.8 mg/dL, n:0.7-1.5 mg/dL). Urine Sodium was (59 mEq/L, n: 20 mEq/L) and Urine osm (306 mOsm/Kg, n:50-1200 mOsm/kg). TSH was normal and 8 AM cortisol level was (6.0 ug/dL, n: 6.0-18.4 ug/dL). Initially Hyponatremia was attributed to SIADH secondary to use of Selective Serotonin Reuptake inhibitors, however her autoimmune comorbidities, orthostatic hypotension and physical exam findings warranted more work up to rule out Adrenal insufficiency. The 250 mcg Cosyntropin Stimulation test was done with baseline cortisol of (4.6 ug/dL, n: 6-18.4 ug/dL) and cortisol at 30 minutes and 60 minutes of (5.2 ug/dL and 5.1 ug/dL respectively) confirming failure to respond to ACTH and diagnosis of adrenal insufficiency. She denied taking exogenous steroids. Later her ACTH came back very high (956 pg/mL, n:7-63 pg/mL), aldosterone was (5.3 ng/dL, n<23 ng/dL), plasma renin activity was high at (20.095 ng/mL/hr, n:0.1-1.3ng/mL/hr) and anti-adrenal antibodies were positive confirming the diagnosis of Addison disease. Patient was started on IV hydrocortisone with slow resolution of hyponatremia and symptoms. She was discharged on maintenance hydrocortisone and fludrocortisone. Given the presence of Hashimoto thyroid disease and Rheumatoid arthritis, patient was diagnosed as having polyglandular autoimmune Syndrome type II. Conclusion: The signs and symptoms of adrenal insufficiency are often nonspecific, resulting in long delays in diagnosis or even misdiagnosis. Hyponatremia is one of the manifestations of adrenal insufficiency which can be inevitably missed or misdiagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) as both can manifest as euvolemic hyponatremia and inappropriate urinary Na concentration. This case demonstrates the importance of thorough investigation of underlying etiologies of patients with symptomatic hyponatremia who are also at risk SIADH secondary to SSRIs use.

Presentation: Friday, June 16, 2023
FRI263 Challenges In Management Of Biochemically Silent Pheochromocytoma
Authors: Gannamani Gowtham , Gourdin Theodore Stewart , Fernandes Jyotika Kanwar
Published: October 2023

Disclosure: G. Gannamani: None. T. Gourdin: None. J.K. Fernandes: None.

Background: Incidental adrenal tumors are a common radiological finding. Biochemical work up is important as functioning adrenal tumors increase mortality and morbidity. Missing diagnosis of Pheochromocytoma can result in fatal outcomes. There have been case reports with asymptomatic and mildly elevated biochemical markers or symptomatic but no biochemical evidence which pose challenges in diagnosis. Here we describe a case of Metastatic Pheochromocytoma which was biochemically silent. Case Description: 61-year-old female with incidental finding of left adrenal mass measuring 8.7 x 5.6 x 5.7 cm on CT (Computed Tomography) scan for back pain 10 years prior to presentation. She was told no further testing was needed then as she was asymptomatic. She now has uncontrolled hypertension requiring multiple anti-hypertensives that prompted further work up. Biochemical work up at outside facility reported as normal aldosterone, renin activity, AM cortisol, ACTH, DHEA-S, plasma metanephrine and normetanephrine, epinephrine, norepinephrine, and dopamine. Elevated Chromogranin A of 5608 (normal < 93 ng/mL). Repeat CT Abdomen showed multiple enhancing lesions in liver, large lobulated adrenal mass measuring 15 x 10 x 14 cm (previously 8.7 x 5.6 x 5.7 cm) with central necrosis, absolute washout is 63%. This mass extended into gastro-hepatic space, obliterating fat space between the left adrenal mass and tail of pancreas was also reported. Imaging was concerning adrenal malignancy vs Pheochromocytoma. Further work up with MRI (Magnetic Resonance Imaging) Abdomen showed 14 cm centrally necrotic mass suggestive of adrenal neoplasm with loco-regional involvement. CT chest with bilateral pulmonary nodules and diffuse sclerotic and lucent bone lesions concerning osseous metastatic disease. Liver biopsy positive for metastatic neuroendocrine neoplasm consistent with Pheochromocytoma, immunohistochemical stains positive for Synaptophysin, Chromogranin, S100, GATA3, Inhibin. Dotatate PET CT with large centrally necrotic left adrenal mass. Abnormal radiotracer uptake in left kidney, stomach, gastrohepatic lymph nodes, widespread osseous lesions suggesting metastatic disease. She was not a surgical candidate given extension of mass and metastasis to multiple organs. Treatment started with Sunitinib (Tyrosine kinase inhibitor), plan to repeat imaging in 4-6 months hoping for tumor shrinkage. References: 1. Pheochromocytoma without specific symptoms. Jpn J Surg. 1984 May 2. A diagnostic dilemma in diagnosing and managing an incidental pheochromocytoma. Exp Clin Endocrinol Diabetes. 2006 Apr 3. Asymptomatic and Biochemically Silent Pheochromocytoma with Characteristic Findings on Imaging. Case Rep Endocrinol. 2020 Sep 26

Presentation: Friday, June 16, 2023
FRI264 A Case Of Composite Pheochromocytoma And Ganglioneuroma
Authors: He Diana , Pullman James , Stefan Simona , Wong Beatrice Y
Published: October 2023

Disclosure: D. He: None. J. Pullman: None. S. Stefan: None. B.Y. Wong: None.

Background: Pheochromocytomas are catecholamine-secreting tumors that arise from chromaffin cells in the adrenal medulla or paraganglia. Representing 1-9% of pheochromocytomas, composite pheochromocytomas are rare tumors composed of pheochromocytoma and neural tumor components such as neuroblastoma, ganglioneuroblastoma, ganglioneuroma or peripheral nerve sheath tumor1. We present a case of composite pheochromocytoma and ganglioneuroma. Clinical Case: A 69-year-old man presented with recurrent dyspnea at rest, diaphoresis and tachycardia. He was diagnosed with heart failure with reduced ejection fraction and management included metoprolol 50 mg daily. On work-up, he was incidentally found to have a 1.2 cm left upper lobe lung lesion and an indeterminate 2.4 cm right adrenal mass on CTA chest. PET/CT scan showed an intensely avid left upper lobe lung nodule and a right adrenal mass with mild FDG uptake (SUV max 3.8). MRI abdomen demonstrated a 3.1 cm right adrenal lesion with a mildly thickened enhancing rim and a central enhancing nodular component suspicious for pheochromocytoma, metastases, schwannoma or ganglioneuroma. He then had a stroke with mild residual right-sided weakness. Oncological work-up of his lung and adrenal lesions eventually directed tissue sampling to biopsy of the adrenal lesion and pathology was consistent with pheochromocytoma. Subsequent biochemical evaluation revealed elevated plasma metanephrines of 194 pg/mL (<= 57 pg/mL), plasma normetanephrines of 474 pg/mL (<= 148 pg/mL), 24-hour urine metanephrines of 389 mcg (90-315 mcg) and 24-hour urine normetanephrines of 428 mcg (122-676 mcg). Pre-operatively, he was placed on phenoxybenazmine 10 mg twice daily and metoprolol 62.5 mg every 8 hours. The patient then underwent right adrenalectomy. The tumor nodule was adherent to and dissected off the inferior vena cava. Pathology showed composite pheochromocytoma with a small component of ganglioneuroma. Conclusion: This rare case of a composite pheochromocytoma with ganglioneuroma was diagnosed through histopathology as composite pheochromocytomas are clinically and radiographically indistinguishable from pheochromocytomas1. Management of composite pheochromocytomas with ganglioneuroma is similar to the management of pheochromocytomas, and surgical resection remains the first line treatment. Combined alpha and beta-adrenergic blockade is recommended to prevent intraoperative hypertensive crisis. However, more studies are needed to further understand these rare composite pheochromocytomas. References: 1.Shida Y, Igawa T, Abe K, Hakariya T, Takehara K, Onita T, Sakai H. Composite pheochromocytoma of the adrenal gland: a case series. BMC Res Notes. 2015 Jun 24;8:257. doi: 10.1186/s13104-015-1233-6. PMID: 26104921; PMCID: PMC4477526.

Presentation: Friday, June 16, 2023
FRI268 Late Onset Polyglandular Autoimmune Syndrome Type 2
Authors: Nicholson Matthew S , Barnett Anne
Published: October 2023

Disclosure: M.S. Nicholson: None. A. Barnett: None.

A 66-year old white female was admitted for weakness, acute kidney injury, and hypotension. This is her 3rd hospital or ER visit in the last 12 months for similar complaints. She has a 25 year history of type 2 diabetes on insulin and oral therapy and 30 year history of hypothyroidism on levothyroxine 75 mcg daily. She was on oral estrogen replacement therapy for post-menopausal symptoms with a hysterectomy in her early 50s. She has a sister with type 2 diabetes on oral meds and hypothyroidism. She has a brother with type 1 diabetes. Her serum sodium was 135 mmol/L (135-145), potassium was 5.4 mEq/L (3.5 -5.1), and calcium was 9.2 (8.5-10.1). Her Creatinine was 1.2 with a GFR of 48. A random cortisol in the ED was 9.2 (no ref range). Blood pressure was low and she was tachycardic and her weight was 68 kg. She was a well developed female with a a tanned complexion. Areas of vitiligo were noted on her arms. A cosyntropin stimulation test was done midday with a baseline, 30, and 60 minute cortisol levels of 9.2, 8.8, and 9.3 respectively. Baseline ACTH was 877.6 pg/mL (7.2-63.6). Her TSH was 4.09 mIU/mL (0.358-3.74) and free T4 was 1.29 ng/dL (0.76-1.46). DHEA-S was 14 mcg/dL (13-130). She was started on stress dose steroids with rapid improvement in BP, hyponatremia, and symptoms. GAD-65 antibodies were above 250 IU/mL and 21-hydroxylase antibodies were positive. Her TPO antibodies were negative. Non-insulin diabetes medications were stopped and she was discharged home after stabilization on prednisone 5 mg daily and fludrocortisone 0.1 mg daily. This patient has an atypical presentation of polyglandular autoimmune syndrome type 2 (PAS2). She presented with an Addisons crisis at the age of 66. She was already diagnosed with hypothyroidism and insulin requiring diabetes and evidence of vitiligo. A majority of patients with PAS2 are female and present in their 20s to 40s with primary adrenal insufficiency and primary hypothyroidism. Her initial manifestation was hypothyroidism and then diabetes and vitiligo with adrenal insufficiency many years later. Her random cortisol was not suppressed and this lead to a delay in her diagnosis. This was likely due to oral estrogen therapy raising cortisol-binding globulin. Her elevated baseline ACTH and lack of response to ACTH stimulation confirmed her diagnosis of primary adrenal insufficiency. An ACTH stimulation test was repeated as an outpatient with similar response. This case highlights the importance of provocative testing for adrenal disorders and testing for autoimmune causes of endocrine disorders when patients are not responding as expected.

Presentation: Friday, June 16, 2023
FRI269 Two Cases Of Familial Polyglandular Autoimmune Syndrome Type II Presenting With Adrenal Insufficiency Precipitated By SARS-CoV-2 Infection
Authors: Sassic Jessica , Hosein Nadeen , Jackson Gavin
Published: October 2023

Disclosure: J. Sassic: None. N. Hosein: None. G. Jackson: None.

Introduction: Polyglandular autoimmune syndrome (PGA) type II is characterized primarily by autoimmune adrenal disease and thyroid disease. Additionally, about 50% of patients will experience autoimmune diabetes mellitus. The incidence of PGA type II is around 1:20,000 but shows strong familial clustering, and predominantly affects women in a 3:1 ratio. Here we report a case of two patients, a woman and her son, who were diagnosed 6 months apart with type II PGA who presented with adrenal insufficiency acutely affected by SARS-CoV-2 infection. Clinical Case: Patient 1 is a 59 year-old female with history significant for previously-diagnosed autoimmune thyroiditis who presented with complaint of generalized fatigue and weight loss for months following a SARS-CoV-2 infection, who was found to have severe hyponatremia with serum sodium of 106 mmol/L (137-145 mmol/L) and was admitted to the intensive care unit. There, she received cosyntropin testing which revealed severe adrenal insufficiency, with post-cosyntropin cortisol level at 1.2 mcg/dL (>14 mcg/dL). Anti-21-hydroxylase antibodies were positive. Her A1c was found to be 5.8% (<5.7%), indicating prediabetes in a patient with BMI of 18.5 kg/m2. Glutamic acid decarboxylase antibodies were tested and were also positive. Patient’s sodium was repleted and she was tapered from stress-dose to physiologic steroid dosing and was discharged on hydrocortisone and fludrocortisone. About 6 months later, Patient 2, a 25-year-old male and the son of Patient 1 presented to the emergency department with complaint of a week of nausea and vomiting, and three months of generalized fatigue. He was found to be SARS-CoV-2 positive and was also hyponatremic with serum sodium of 122 mmol/L. He also received cosyntropin testing which was revealed undetectably low cortisol levels both pre- and post-cosyntropin administration. Anti-21-hydroxylase antibodies and anti-thyroid peroxidase antibodies were positive, the latter at 243.3 IU/mL (<5.61 IU/mL). Patient responded well to stress-dose steroids and normal saline to normalize his sodium levels. Due to his mother’s positive antibodies, glutamic acid decarboxylase, anti-islet, and anti-insulin antibodies were also tested, which were negative. Patient was discharged on physiologic hydrocortisone and fludrocortisone. Conclusion: Polyglandular autoimmune syndrome is a relatively uncommon disease but with strong polygenic inheritance. This case was an interesting presentation where SARS-CoV-2 infection likely precipitated the symptoms and acute effects of adrenal insufficiency. Additionally, knowledge of the patient’s family history resulted in rapid diagnosis and management of the patient’s underlying pathophysiology.

Presentation: Friday, June 16, 2023
SAT267 BMP4, GDF11 And TGFβ2 Repress Adrenal Cell Cortisol Production By Blocking CYP17A1 And CYP11B1 Expression
Authors: Fischbach Emily Catherine , Lopez Antoine-Guy , Ullenbruch Matthew , Rege Juilee , Rainey William E
Published: October 2023

Disclosure: E.C. Fischbach: None. A. Lopez: None. M. Ullenbruch: None. J. Rege: None. W.E. Rainey: None.

Introduction: The adrenal cortex is responsible for the biosynthesis of multiple steroid hormones that regulate electrolyte and carbohydrate balance. Cortisol, the principal glucocorticoid in humans, is primarily produced in the middle zone of the cortex known as the zona fasciculata (ZF). The enzymes responsible for cortisol biosynthesis include cytochrome P450c17 (17α-hydroxylase), encoded by CYP17A1 and cytochrome P450c11 (11β-hydroxylase), encoded by CYP11B1. Several paracrine/autocrine regulators, including members of the transforming growth factor beta (TGFβ) superfamily, have been implicated in controlling adrenocortical cell homeostasis and steroid hormone production. Previously, we reported a bone morphogenetic protein 4 (BMP4) expression gradient in the adrenal cortex with higher levels in the zona glomerulosa (ZG) and outer ZF compared to the zona reticularis (ZR). In this study, we sought to compare adrenal expression of members of the TGFβ family including BMP4, growth differentiation factor 11 (GDF11), and transforming growth factor beta 2 (TGFβ2), and determine their effect on adrenal cell cortisol biosynthesis. Methods: Growth factor mRNA levels were studied using microarray analysis of laser captured ZG, ZF and ZR from human adrenals. The adrenal cell line, HAC15 was used to determine the effects of the TGFβ family members alone and in combination. Output measures included cell cortisol production and mRNA levels of steroidogenic enzymes using ELISA and quantitative RT-PCR, respectively. Results: Microarray analysis indicated higher mRNA levels of BMP4, GDF11 and TGFβ2 in the ZG compared with the ZF and ZR regions of the adrenal. Treatment of HAC15 cells with either BMP4 (50 ng/mL), GDF11 (50 ng/mL) or TGFβ2 (10 ng/mL) significantly inhibited cortisol production, as well as CYP11B1 and CYP17A1 mRNA levels. The inhibition was observed under basal and forskolin-stimulated conditions. Furthermore, the inhibitory effects on cortisol production and enzyme expression were additive when factors were added together. Summary: Overall, our findings suggest that the human adrenal has a gradient of multiple members of the TGFβ family. The additive action of these growth factors on adrenal cell differentiation may explain, in part, the inability of the ZG to produce cortisol and its low expression of CYP11B1 and CYP17A1.

Presentation: Saturday, June 17, 2023
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

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

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 <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 < 0.9 nmol/L); metanephrine 0.6 nmol/L (NL <0.5 nmol/L); norepinephrine 1493 pg/mL (NL 70-750 pg/mL); epinephrine 298 pg/mL (NL <111 pg/mL); chromogranin A 1314 ng/mL (NL <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 <1 mcg/dl and <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

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

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% (<20), serum 1,25-OH2-D 74 pg/ml (18-64), FGF-23 <14 pg/ml (<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

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<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<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<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

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

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

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
SAT246 Ectopic (Penile) Calcification in 1, 25 Vitamin D Induced Hypercalcemia
Authors: Berquist John , Santosh Reddy Deepika
Published: October 2023

Disclosure: J. Berquist: None. D.S. Reddy: None.

A 60-year-old male with a history of well controlled type 2 diabetes and HTN presented with acute renal failure (initial creatinine 19.9 mg/dL, GFR 11). Kidney biopsy during admission was consistent with acute tubular necrosis and mild diabetic nephropathy. Serum calcium was normal at that time. He received temporary dialysis and eventually discharged home with improved (though still elevated) creatinine. On follow up labs a month later, he was noted to have high serum calcium. He was temporarily lost to follow up and was readmitted four months later due to persistent severe hypercalcemia. Peak serum calcium on his new admission was 13.2 mg/dL. Phosphorus level three months prior was 5.9 mg/dL, though had now improved to 2.7 mg/dL. Other labs this admission include creatinine 2.54 and GFR 33 (which was consistent with previous months), PTH 11 pg/mL, 25-OH Vitamin D 10 ng/mL, 1,25-Dihydroxy Vitamin D elevated at 84.8 pg/mL and magnesium low at 1.5 mg/dL. SPEP and UPEP were both negative and PTHrP was not measured. Kappa/Lamda free light chain ratio was mildly elevated at 1.77 (0.26-1.65). QuantiFERON Gold, HIV, Beta-2 microglobulin, ANA, and flow cytometry were negative. He received calcitonin x 2, IVF, zoledronic acid, and denosumab (three days later), which improved his calcium to 11.5 by discharge 11 days later. He underwent a CT Chest/Abdomen/Pelvis, T spine, and L spine that were remarkable for multiple bilateral partially calcified pulmonary nodules and hepatic steatosis with splenomegaly. PET CT showed 20 hypermetabolic osseous lesions throughout axial skeleton, multiple pulmonary, liver, and splenic lesions and lymphadenopathy in the head, neck, chest, abdomen. There was also diffuse calcification of the penile corpora. Pathology via biopsies of a retroperitoneal lymph node as well as bone marrow showed non-caseating granulomas.

Lastly, 1-2 months ago, he noticed pain and hardening of his penis. On exam, there is a deep firmness with palpation and distal penile tenderness. There are no cutaneous lesions on the penis or anywhere else on the skin. Calciphylaxis was a consideration, but isolated penile involvement is rare. Additionally, it is rare to develop calciphylaxis without end stage renal disease. A review of the literature showed many cases of penile calciphylaxis, though none were without cutaneous involvement. Sarcoidosis of the penis is also very rare and cases in the literature cite either a cutaneous or intraurethral lesion. This case appears unique in the findings of penile calcification palpable on exam and visible on imaging, without any cutaneous manifestations, in the setting of previous though recovered acute renal failure and 1, 25 Vitamin D-mediated hypercalcemia in sarcoidosis.

Presentation: Saturday, June 17, 2023
THU589 Positivity Rates Of Screening Criteria For Primary Aldosteronism: A Cohort Comparison Study
Authors: Marcelli Marco , Panov Alexandra , Bi Caixia , Funder John W , John McPhaul Michael
Published: October 2023

Disclosure: M. Marcelli: None. A. Panov: None. C. Bi: None. J.W. Funder: None. M.J. McPhaul: None.

Current screening for primary aldosteronism (PA) relies on a single blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). However, ARR cutoff levels vary between expert centers. Many studies have demonstrated that PAC may not represent a patient’s actual aldosterone status, suggesting the possible fallibility of the ARR. To investigate this possibility, we compared the positivity rates of 2 indicators of probable PA—ARR>28.9 and suppressed renin (PRA<1 ng/ml/hr)—in a cohort of 38,507 paired PAC and PRA samples. For each indicator, we also assessed positivity rates by self-reported sex (20578 [53.5%] women, 17882 [46.5%] men). Of the cohort, 1623 (4.2%) tested positive for possible PA based on an ARR of 28.9; 19551 (50.8%) tested positive for suppressed renin. Among the latter group, 2585 (6.7%) had PAC>15 ng/dL, 8465 (22%) between 5-15 ng/dL, and 8501 (22.1%) < 5 ng/dL. A recent algorithm suggested by Vaidya (1) defines the first of these groups as overtly positive screening and the second, intermediate group as positive screening, for a total positivity rate of 28.7%. Given the suppressed renin, there are probably a handful of positive PA cases, even in the 22.1 % group with PAC<5 ng/dL. A second finding was that rates of probable PA differed by sex. These differences were minor for the ARR criterion (4.3% of women vs. 4.1% of men tested positive) but major for the suppressed renin criterion with PAC>15 ng/dL (5.7% of women vs. 7.9% of men tested positive) and 5-15 ng/dL (23.6% of women vs. 20.2 of men tested positive). Florid PA was the only condition where more males than females tested positive, a finding deserving further expert consideration and study. In comparing two indicators of probable PA, the ARR criterion yielded a lower positivity rate than the suppressed renin criterion, suggesting that most PA cases may remain undetected if using AAR as a screening test.Reference: (1) JCEM 2020;105:3771

Presentation: Thursday, June 15, 2023