bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI233 Adrenal Insufficiency Due To An Unusual Culprit
Authors: Decamps Scarlett , Yeung Kay T , McCowen Karen
Published: October 2023

Disclosure: S. Decamps: None. K.T. Yeung: None. K. McCowen: None.

Background: Chronic exogenous use of glucocorticoids is the most common cause of reversible secondary adrenal insufficiency (AI). There is a significant risk of cortisol deficiency if the medication is abruptly discontinued. Chronic glucocorticoid therapy may cause hypothalamic-pituitary-adrenal (HPA) axis suppression, resulting in low ACTH, atrophy of the adrenal zona fasciculata and decreased cortisol production. Immunotherapy rarely causes reversible central AI, usually permanent. We present a case of an immunotherapy-receiving patient who presented with biochemical evidence of adrenal insufficiency after using an oral solution (swish and spit) of dexamethasone as prophylaxis for mucositis. Patient Summary: A 52-year-old woman with stage IIb triple negative breast cancer receiving neoadjuvant Datopotamab, Dertuxtecan and Durvalumab was evaluated for adrenal insufficiency. Prior to starting therapy, serum cortisol level measured 7.9 mcg/dL at 11 AM (normal 6.0-18.4 mcg/dL at 6-10 A.M). She had received a single dose of dexamethasone 10 mg IV with her first cycle, but not thereafter. As part of the immunotherapy protocol, serial cortisol levels were obtained, and 2 weeks after the baseline, noon serum cortisol was 1.0 ug/dL. Patient was asymptomatic. At no point were glucocorticoids replaced, but 1-week later serum cortisol level was 0.6ug/dL at 11:00 AM along with an ACTH of 5 pg/mL. Immunotherapy-induced AI was strongly suspected. Her only glucocorticoid exposure had been a dexamethasone oral mouth rinse (swish 10mL for 1 minute and spit out, four times daily). Cortisol level at 7AM a week later measured 3.5 mcg/dL with ACTH 18.7 pg/mL and a dexamethasone level 108.2 ng/dL (normal < 50 ng/dL for patients not on dexamethasone). Technique of swish and spit was reviewed with the patient, and she was not ingesting the medication. An observational approach was pursued at this time given hemodynamic stability, treatment was continued and several weeks later repeat labs showed cortisol levels of 3.3 (7AM), with a dexamethasone level of 84.3 ng/dL. Her course of therapy has been completed, so she has been off the dexamethasone solution, continues to be asymptomatic and repeat labs now show a 9AM Cortisol level of 9.5 mcg/dL and, given lack of other sources, it is most likely that these low cortisol levels along with elevated dexamethasone levels are related to the use of dexamethasone swish and spit rather than immunotherapy induced permanent HPA axis suppression. Conclusion: There is no literature on dexamethasone swish and spit being absorbed systemically possibly leading to potentially reversible HPA suppression. Our case will raise awareness of help guide clinicians expand their differential when working up these patients.

Presentation: Friday, June 16, 2023
FRI243 Hypertension And Virilization In A 4 Year Old Female
Authors: Ismail Esraa , Miller Jennifer Lynne , Bernier Angelina Valladares
Published: October 2023

Disclosure: E. Ismail: None. J.L. Miller: None. A.V. Bernier: None.

Background: Congenital adrenal hyperplasia (CAH) is the most common cause of virilization of an XX female neonate. More than 95% of CAH cases are due to 21 hydroxylase deficiency which is detected in the newborn screen by detection of elevated 17 hydroxyprogesterone (17 OHP). 11 beta hydroxylase deficiency (11 BOHD) is the second most common cause of CAH, but considered extremely rare accounting for only 0.2-8% of cases. 11-BOHD is not part of the newborn screen, as it does not present with life-threatening salt wasting crisis. Hypertension (HTN) is observed in 2/3 of cases and is due to mineralocorticoid excess in the form of deoxycorticosterone (DOC). Therefore, 11-BOHD should be strongly considered in a virilized female with HTN and accelerated growth. Clinical case: 4-year-old female admitted for evaluation of severe persistent HTN. She had surgical repair of posterior labial fusion at 5 months of age. She was seen at 21 months of age for concerns of precocious puberty and virilization. Her work up included XX karyotype, 17 OHP and electrolytes within normal limits, however, she had an elevated DHEAS and testosterone level, with a bone age of 5 years at 21 months of age. Hypertension was recorded at the visit, but she was lost to follow up. At a primary care appointment her blood pressure was notably elevated, so she was sent to the ED. On admission, she was found to have both weight and height >99% for age, hyperpigmentation of gums and scars, and virilization (clitoromegaly with tanner 3 pubic hair). She had no thelarche. Initial hormonal evaluation revealed prepubertal gonadotropins, low aldosterone and low plasma renin activity. High dose ACTH stimulation test revealed elevated 11 deoxycortisol and 11 deoxycorticosterone levels. Her peak stimulated cortisol was inadequate at 8.7 mcg/dl (normal=>18 mcg/dl). Genetic testing for CAH revealed compound heterozygosity for 2 variants in the CYP11B1 gene, confirming the diagnosis of 11-BOHD. She was started on hydrocortisone replacement (12 mg/m2/day) and required spironolactone to achieve adequate blood pressure control. At the time of diagnosis, her father reported that he also had hypertension before 10 years of age, as well as early puberty, and significantly darker skin color than his family members. Conclusions: The HTN seen with 11-OHD is associated with suppressed aldosterone/renin activity and hypokalemia and is responsive to glucocorticoid therapy. However, this cause of CAH is not included in the newborn screen so can go unrecognized until features of virilization and rapid growth with bone age advancement are noted. If HTN is persistent despite glucocorticoid treatment, spironolactone is the preferred antihypertensive, as it is both a mineralocorticoid and androgen receptor antagonist. This case serves as a reminder to pay attention to BP at every clinic visit.

Presentation: Friday, June 16, 2023
FRI252 Novel Mutation Presenting With Hypoaldosteronism In X-Linked Adrenal Hypoplasia Congenita
Authors: Ismail Esraa , Jacobsen Laura
Published: October 2023

Disclosure: E. Ismail: None. L. Jacobsen: None.

Background: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder due to a mutation in DAX-1/NR0B1, a nuclear factor that is important for the development and function of the adrenals and reproductive system. It usually presents with adrenal insufficiency in infancy and later hypogonadotropic hypogonadism. Here we describe a patient who presented with a salt wasting crisis due to hypoaldosteronism and genetic testing revealed a novel frameshift mutation in NR0B1/DAX-1 resulting in premature protein termination. Clinical Case: A 4 week old male presented with poor feeding, failure to thrive, hyponatremia, hyperkalemia, and acidosis. No hypoglycemia present. He also had an undetectable aldosterone level, high renin, normal cortisol, high ACTH, and normal 17OHP. Adrenal ultrasound (US) failed to show the right adrenal gland. With suspicion for primary hypoaldosteronism, he was started on salt supplementation and fludrocortisone with improved growth, electrolytes, and renin. His genitalia were that of a typical male infant without cutaneous hyperpigmentation. ACTH level continued to trend up despite appropriate baseline cortisol. Stimulation test with 250 mcg of Cosyntropin was done which revealed suboptimal peak cortisol of 11.5 mcg/dL (normal >18 mcg/dL), so he was started on stress dose precautions of hydrocortisone without physiologic replacement. Repeat US 2 months later did not visualize his adrenals. With suspicion for AHC, genetic testing was obtained which revealed a novel frame shift variant in NR0B1 (c.1069del, p.Gln357Argfs*15, hemizygous), resulting in premature protein termination. He was then started on daily hydrocortisone replacement. As this is an X-linked mutation, genetic testing for mother and older brother is pending. To the best of our knowledge this variant has not been reported in the literature. Conclusion: DAX-1 mutations should be considered in male infants presenting with primary hypoaldosteronism. ACTH stimulation testing is necessary to assess glucocorticoid function, especially if ACTH is elevated, which can precede cortisol deficiency. There is a wide heterogeneity in the presentation of this rare disorder, so genetic diagnosis is important to guide management, later monitoring for hypogonadism and fertility, and family testing.

Presentation: Friday, June 16, 2023
SAT266 Transcriptional Changes Associated With Loss Of Function Of Fumarate Hydratase In A Cellular Model Of Pheochromocytoma
Authors: Hall Charlotte Louise , Read Jordan Elise , Salsbury Grace , Lim Eugénie , Akker Scott , Chapple Paul
Published: October 2023

Disclosure: C.L. Hall: None. J.E. Read: None. G. Salsbury: None. E. Lim: None. S. Akker: None. P. Chapple: None.

Mutations in fumarate hydratase (FH) predispose to development of pheochromocytomas and paragangliomas (PPGLs), as well as leiomyomas and renal cell carcinoma. Loss of FH function leads to accumulation of fumarate which acts as an oncometabolite to drive tumorigenesis, although the molecular mechanisms leading to the development of these rare tumours are not fully understood. We have used CRISPR/Cas9 genome editing to generate a series of FH knockouts in the PC-12 cell line, derived from MAX-mutated pheochromocytoma in rat. Our knockout cell lines were used as a model to investigate the molecular consequences of loss of FH function. Comparison of the transcriptome of FH knockout cells with isogenic controls identified 1016 differentially expressed genes (adjusted p<0.05 Log2fold±1). This list of differentially expressed genes was then analysed to identify cellular pathways that were dysregulated in the absence of FH. Canonical pathways that were significantly altered, based on transcript expression relative to controls, included axonal signalling pathway (p=7.29x10-11), wound healing signalling pathway (p=1.74x10-07), pulmonary fibrosis idiopathic signalling pathway (p=4.10x10-07) and IL-15 production (p=1.03x10-05). Our results suggest cell adhesion and immune regulation pathways may be relevant to the development of PPGLs with germline mutations in FH, but will require validation in the context of human tissue. We have also performed metabolic flux analysis to identify differences in metabolite profile associated with loss of FH. Interestingly, changes in gene expression, revealed by our transcriptomic analysis, may explain some alterations in cellular metabolism of FH knockout cells.

Presentation: Saturday, June 17, 2023
SAT274 Multilocus Imprinting Disorder Due To Genome-wide Paternal Uniparental Disomy Associated With Adrenocortical Tumors
Authors: Pinto Emilia Modolo , Lalli Enzo , Wu Gang , Ribeiro Raul , Zambetti Gerard
Published: October 2023

Disclosure: E.M. Pinto: None. E. Lalli: None. G. Wu: None. R. Ribeiro: None. G. Zambetti: None.

Pediatric adrenocortical tumor (ACT) is an uncommon malignancy frequently associated with Li-Fraumeni syndrome, a familial cancer predisposition disorder caused by germline mutations in the tumor suppressor TP53. ACT is also associated with other genetic constitutional disorders, such as Beckwith-Wiedemann syndrome (BWS) which results from the deregulation of a gene cluster on chromosome 11p15. We report here the identification of three pediatric patients with ACT and additional tumors, two of which received a clinical diagnosis of BWS. Family histories of these two probands include multiple unsuccessful pregnancies. All patients have wild-type TP53 sequence and no evidence for germline chromosome 11p15 alterations. Molecular analyses by whole genome sequencing revealed genome-wide copy neutral loss of heterozygosity (cnLOH) in all tumors. Microsatellite STR and MS-MLPA confirmed genome-wide cnLOH with the selective loss of all maternal chromosomes and duplication of paternal chromosomes in each tumor. Analysis of skin fibroblasts showed mosaic paternal uniparental disomy with partial LOH for all chromosomes, while no LOH was detected in blood DNA. The most prominent clinical feature of genome-wide cnLOH is an unbalanced monoallelic and parent-of-origin specific expression of imprinted genes known as multilocus imprinting disorder (MID). MID has been associated with maternal-effect variants that alter the maintenance of methylation at germline-derived differentially methylated regions (DMRs) in early embryogenesis. In addition, causative trans-acting factors in imprinting disorders, including the subcortical maternal complex (SCMC), have the potential to affect multiple DMRs across the genome, resulting in a multilocus imprinting disorder. Our study identifies three pediatric patients who developed ACT and other tumors that have undergone genome wide cnLOH that specifically selected against all maternal chromosomes. None of three patients presented with germline alterations in TP53 or 11p15, typical of pediatric ACT. WGS data revealed a germline mutation (p.M573T) in the histone methyltransferase NSD1 in the mother of patient #2. NSD1 mutations are reportedly associated with recurrent miscarriages, tissue overgrowth and increased cancer risk. Alterations in other epigenetic regulators, such as SETD1B (p.R226C), a component of a histone methyltransferase complex and TNRC18 (p.P454L), that enables chromatin binding activity were observed in both mother and child in each family. Further analysis of maternal-effect variants associated with abnormal pregnancies and MID will be important for understanding the mechanisms underlying genome-wide cnLOH. Our results support the molecular testing of multiple loci in atypical clinical presentations of patients with pediatric ACT.

Presentation: Saturday, June 17, 2023
SAT276 Glucocorticoid Excess Elevates Metabolic Rate Via A 11b-HSD1 Dependent Mechanism In C57BL/6J Mice
Authors: Heaselgrave Samuel , Heising Silke , Morgan Stuart Andrew , Kabli Ali , Sagmeister Michael , Doig Craig , Hardy Rowan Samuel , Morton Nicholas M , Tsintzas Kostas , Lavery Gareth Geoffrey
Published: October 2023

Disclosure: S. Heaselgrave: None. S. Heising: None. S.A. Morgan: None. A. Kabli: None. M. Sagmeister: None. C. Doig: None. R.S. Hardy: None. N.M. Morton: None. K. Tsintzas: None. G.G. Lavery: None.

Introduction: Glucocorticoids are vital metabolic regulators. However, glucocorticoid excess (GE) causes severe metabolic dysfunction, ultimately leading to Cushing’s Syndrome. This dysfunction is often dependent on the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Whether GE also alters metabolic rate, and whether this is also dependent on 11β-HSD1, remains unclear and merits investigation in a mouse model of GE and 11β-HSD1 inhibition. Methods: Male and female wild type (WT) C57BL/6J and 11β-HSD1KO mice were treated with corticosterone or vehicle control ad libitum via drinking water for 3 weeks whilst being fed a standard chow diet (n=12). Mice were housed in a TSE Phenomaster system for the final week of treatment for comprehensive metabolic assessment. Results: Corticosterone treatment in WT mice resulted in a phenotype typical of GE, however female mice experienced greater fat accumulation and bodyweight gain compared to males. 11β-HSD1KO mice did not experience this phenotype. Corticosterone treatment elevated energy expenditure (EE) in female WT mice during the day alone (25±5.9%). Male WT mice did not experience a significant increase. Corticosterone did significantly elevate the respiratory exchange ratio (RER) towards 1 in both male (10.7±5.7%) and female (11.8±7.0%) WT mice during the day. RER remained elevated in female WT mice (7.6±4.8%) and moderately so in male WT mice (3.2±2.6%) at night, indicating a continued suppression of lipid oxidation in favour of carbohydrate oxidation. Activity, assessed in female WT mice only, was continually decreased by corticosterone treatment (-53.1±54.8%). Corticosterone treated WT mice became hyperphagic and polydipsic, continuously eating and drinking more than controls. Male and female 11β-HSD1KO mice treated with corticosterone did not experience these effects. Conclusion: These findings provide further insights into the metabolic consequences of GE as well as the dependency on 11β-HSD1 to facilitate them. Whilst elevations are seen in both male and female WT mice, they are greater in females. Activity is decreased meaning it is not responsible for the elevations. However, hyperphagia and the subsequent chemical energy cost of de novo lipogenesis might be responsible and merits further investigation.

Presentation: Saturday, June 17, 2023
SAT340 Matters Of The HAART - Ritonavir Induced CYP3A4 Inhibition of Intranasal Fluticasone Leading To Cushing’s Syndrome
Authors: Ramachandran Aishwarya , Ghaith Sarah , Ramachandran Akshaya
Published: October 2023

Disclosure: A. Ramachandran: None. S. Ghaith: None. A. Ramachandran: None.

Background: Ritonavir, a potent inhibitor of the CYP3A4 enzyme, can lead to high systemic concentrations of even intranasal steroids causing Cushing’s syndrome. Case: A fifty-seven-year-old man with history of HIV on HAART presented with a 3-month history of fatigue, weight gain and easy bruising. History was negative for heat/cold intolerance, hair loss, constipation, erectile dysfunction. Medications included emtricitabine-tenofovir-alafenamide and ritonavir at stable doses for several years. He denied taking any oral or topical steroids, but reported using over the counter (OTC) fluticasone propionate (FP) for the past 6 months for seasonal allergies. Physical examination was significant for moon facies and abdominal striae. Labs were remarkable for low serum morning cortisol of 0.6 µg/dl (0.4-22.6 µg/dl), and low serum ACTH of <5 pg/ml (7-69 pg/ml). A diagnosis of exogenous steroid induced Cushing’s syndrome, as a result of ritonavir induced increase in FP levels was made. FP was gradually tapered and stopped. Serum cortisol and ACTH levels normalized at 15 µg/dl and 13 pg/ml respectively and his symptoms resolved completely after three months. Discussion: Ritonavir, a protease inhibitor (PI), is one of the strongest known inhibitors of CYP3A4 and is generally used to boost the plasma levels of other PIs. FP, a potent glucocorticoid, is generally used as monotherapy or as a combination inhaler in the treatment of asthma. It is rapidly metabolized by CYP3A4 and hence produces minimal side effects. However, its concurrent use with ritonavir results in increased serum concentration of FP leading to systemic adverse effects of glucocorticoids. Due to emerging awareness about this drug-drug interaction among physicians, prescription of inhalational steroids in patients on ritonavir is avoided. However, FP is an OTC intranasal glucocorticoid that is easily accessible, and its self-use is often times not reported by patients which makes it difficult for physicians to track on their patient’s medication list. A thorough review of OTC medications/supplements needs to be done when Cushing’s syndrome from exogenous steroids is suspected. It is also imperative that patients on ritonavir be counseled about the risks of taking any form of steroid formulations by any route. Conclusion: Educating patients on ritonavir about steroids being a component of many OTC medications/supplements, and a careful medication history and drug-drug interaction assessment is important in preventing steroid related adverse effects.

Presentation: Saturday, June 17, 2023
THU400 Parameters Of Vitamin D Metabolism, Calcium And Phosphate Homeostasis In Patients Undergoing Bariatric Surgery
Authors: Zhukov Artem , Povaliaeva Alexandra , Abilov Zaur , Usoltseva Liliia , Trukhina Diana , Pigarova Ekaterina , Rozhinskaya Liudmila
Published: October 2023

Disclosure: A. Zhukov: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). A. Povaliaeva: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). Z. Abilov: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). L. Usoltseva: None. D. Trukhina: None. E. Pigarova: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). L. Rozhinskaya: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P).

Objective: to evaluate the parameters of vitamin D metabolism and calcium and phosphate homeostasis in patients undergoing bariatric surgery. Materials and Methods: The study included 10 patients without chronic kidney disease and mineral metabolism disorders who underwent laparoscopic gastric bypass surgery for obesity. After surgery, all patients were recommended to take cholecalciferol depending on the initial level of 25-OH D in blood in accordance with the Endocrine Society Clinical Practice Guideline. Ninety nine [96; 130] days after the surgery, the levels of vitamin D metabolites: D3, 25-OH D3, 24,25-OH2 D3, 1,25-OH2 D3 were determined by ultra-high performance liquid chromatography in combination with tandem mass spectrometry (certified by DEQAS) as well as the PTH, total calcium, albumin, creatinine, phosphorus, magnesium levels in serum. Results: Median age of the patients was 39 [34; 50] years, 80% women, 90% initially had type 2 diabetes mellitus (BMI before surgery 49.1 [39.7; 51.0] kg/m2, median decrease in BMI by the time of inclusion in the study 8.3 [8.0; 9.2] kg/m2). The median level of 25-OH D3 was 28.5 [24.6; 32.0] ng/ml (1 patient had a level less than 20 ng/ml, 6 patients from 20 to 30 ng/ml), D3 levels were below the laboratory sensitivity threshold (12.5 ng/ml) in all participants. The median 24,25-OH2 D3 level was 1.49 [1.04; 1.95] ng/ml (reference interval (RI) 0.5-5.6 ng/ml), the median 25-OH D3/24,25-OH2 D3 ratio was 21.87 [15.57; 22.55] (RI 7-23). All patients had normal levels of 1,25-OH2 D3 (median 45.95 [35.18; 53.65] pg/ml, RI 25-66). One patient had secondary hyperparathyroidism (albumin-adjusted calcium 2.14 mmol/l, RI 2.15-2.55; PTH 73.8 pg/ml, RI 15-65; 25-OH D3 24.8 ng/ml) while other biochemical parameters were normal. The remaining patients had normal levels of PTH, calcium, phosphorus and magnesium. Conclusions: The revealed changes in the levels of D3 and 25-OH D3 in patients undergoing bariatric surgery may be due to malabsorption, increased deposition in adipose tissue, an insufficient dosage of cholecalciferol or low patient compliance. At the subsequent stages of vitamin D metabolism, no abnormalities were identified. It is likely that this cohort of patients requires higher doses of cholecalciferol.

Presentation: Thursday, June 15, 2023
THU436 Small Intestinal Bacterial Overgrowth Causing Osteoporosis In An Adult Male
Authors: Aziz Shima , Patrick Stephanie Arana , Mupparaju Vamsee , Kode Sudha
Published: October 2023

Disclosure: S. Aziz: None. S.A. Patrick: None. V. Mupparaju: None. S. Kode: None.

Background: Small intestinal bacterial overgrowth (SIBO) is a disease caused by intestinal dysbacteriosis which can lead to nutrients malabsorption and chronic metabolic acidosis which affect bones health and cause osteoporosis. Clinical Case: A 45-year-old man with medical issues of GERD presents to the endocrinology clinic in 02/2022 for evaluation of incidental finding of T5 vertebral fracture noted in the chest x-ray done for evaluation of chest tightness. During the clinic visit the patient reported chronic bloating and gassiness. Denied symptoms suggestive of eating disorders, chronic fatigue, decreased libido, recurrent fractures, elastic skin, hypermobile joints or joint dislocation, and steroid use. Patient is married and has two biological children. He drinks alcohol socially and denied tobacco use. Patient was taking cholecalciferol 1000 IU daily at home. His weight is 64 kg with a BMI of 21 kg/m2. Physical examination did not reveal any abnormality. Bone mineral density showed the worst Z-score of -2.3 in his spine. Workup for osteoporosis included 24-hour urine calcium, CBC, CMP (including serum calcium, phosphorus, electrolytes, ALP, and creatinine), PTH, TSH, free plasma cortisol, ACTH, morning total testosterone, 25-hydroxyvitamin D level, SPEP, UPEP, celiac disease screening tests (tissue transglutaminase IgA and tTG IgG), IGF-1 and HbA1c were all within normal limits. The patient was started on alendronate 70 mg once weekly and was referred to a local gastroenterologist for further evaluation of his GI symptoms; he subsequently was diagnosed with SIBO which is the most likely cause for his osteoporosis. Conclusion: SIBO is a disease caused by intestinal dysbacteriosis, which is caused by replacement of physiologic bacteria by pathogenic bacteria from the large intestine leading to maldigestion and malabsorption of nutrients including fat, carbohydrates and protein leading to vitamins deficiencies and metabolic acidosis. Due to impaired absorption of nutrients it can cause systemic complications including osteoporosis. Fat malabsorption can lead to deficiencies of fat-soluble vitamins A, D, K and E. SIBO can also result in protein-losing enteropathy. The state of chronic metabolic acidosis caused by SIBO increases alkali mobilization from the bone and induces dissolution of the bone thus promotes the development of osteoporosis. Gastrointestinal diseases including SIBO should be considered in cases of osteoporosis of unknown origin.

Presentation: Thursday, June 15, 2023
THU439 Baby's Coming, Break A Leg! A Case Of Transient Osteoporosis Of The Hip
Authors: Khan Aysha , Syeda Asma , Aftab Hassaan B
Published: October 2023

Disclosure: A. Khan: None. A. Syeda: None. H.B. Aftab: None.

Introduction: Pregnancy-associated osteoporosis (PAO) is a rare condition presenting as fragility fractures usually in the latter part of pregnancy or immediate postpartum period. Vertebral fractures are more commonly reported but femoral fractures have also been described in the literature as a distinct entity: transient osteoporosis of the hip (TOH). We present a case of bilateral (B/L) femoral fractures in a woman during pregnancy and in the postpartum period. Case: A 31-year-old, gravida 1 female developed left leg pain at 26 weeks of gestation. The pain radiated from her left lower back to her left knee. It was severe in intensity resulting in her walking with crutches. Subsequent MRI of the left hip showed subchondral insufficiency fracture of the femoral head with prominent bone marrow edema extending from the head into the femoral neck. She was managed conservatively with non-weight bearing status and oral analgesics. She had an uncomplicated vaginal delivery at 39 weeks of gestation. During the first postpartum week she developed right hip pain. MRI of right hip revealed nondisplaced right femoral head subchondral insufficiency fracture with associated effusion and synovitis. She recovered within the next 3 months with resolution of her pain with conservative management. Other than limited calcium intake in childhood, there were no other identifiable risk factors for osteoporosis. Bone density scan revealed normal Z-scores at the lumbar spine and non-dominant wrist. The hips were not evaluated. Workup for secondary causes of osteoporosis was unremarkable including normal serum calcium, PTH, phosphorus, magnesium, SPEP, tissue transglutaminase antibodies, estradiol, LH, FSH, prolactin levels. However, 24-hour urine calcium level was low at 11 (35-250) mg/24hr. Elevated levels of bone specific alkaline phosphatase and urine N-telopeptide (NTX) were noted at 19.9 (5.3-19.5) mcg/L and 110 (4-64) nM BCE/mM creatinine, respectively. Patient was continued on vitamin D and calcium supplements. She breastfed for the initial 2 months but was advised to stop. At her most recent follow up visit 4 months postpartum patient was doing well. Discussion: TOH is a rare entity, and presentation as B/L femoral fractures is exceedingly rare. During pregnancy and lactation, the skeletal system undergoes bone loss to compensate for the calcium demand of the fetal skeletal system. In TOH, venous stasis from the gravid uterus resulting in bone marrow edema is the proposed mechanism in addition to pregnancy associated bone loss. In our patient, a low 24-hr urine calcium could suggest low calcium intake which could have contributed to the fracture as well. While recurrence of PAO has been described, no recurrence of TOH has been reported in subsequent pregnancies. Our case highlights the importance of keeping this rare entity on the differential in pregnant women presenting with back or hip pain.

Presentation: Thursday, June 15, 2023
THU451 Low Bone Mineral Density In A Patient With Thalassemia Minor
Authors: Woron Felicia , Madhavan Parvathy
Published: October 2023

Disclosure: F. Woron: None. P. Madhavan: None.

Osteoporosis is a known complication of thalassemia major and thalassemia intermedia, but is not typically considered in patients with thalassemia minor. Here, we present a 74-year-old Caucasian male patient with thalassemia minor who presented to us for follow-up of osteoporosis. The patient reports a history of osteoporosis that was diagnosed prior to 2004. Additionally, he has a history of radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019, and atrial fibrillation, for which he has been on apixaban since 2021. He was treated with risedronate for his osteoporosis from approximately 2004 to about 2011 by other providers, with improvement in bone density to osteopenia. Free testosterone, parathyroid hormone, calcium, and serum protein electrophoresis levels evaluated prior to his diagnosis of osteoporosis were all noted to be normal. He has not had a fracture as an adult. He is being monitored with conservative management and currently aims for a daily calcium intake of 1000-1200 mg, including diet and supplements, and a daily Vitamin D intake of 2000 IU. He engages in frequent weight-bearing exercise. As of September 2021, his bone mineral density was osteopenic in the lumbar spine (T score of −2) and left hip (total T score of the left hip −1.6, and −1.8 in the femoral neck). The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. Adding to one existing case report in the literature, we propose that thalassemia minor may potentially be a risk factor for osteopenia and osteoporosis, and that we should consider screening thalassemia minor patients with DXA for evaluation of bone health.

Presentation: Thursday, June 15, 2023
THU454 Paget’s Disease Of Bone As An Atypical Cause Of Headaches
Authors: Delgado Nieves Andrea Nicole , Hernandez Christian Gomez , Nassar Rawann , Goulden Peter Anthony
Published: October 2023

Disclosure: A.N. Delgado Nieves: None. C. Gomez Hernandez: None. R. Nassar: None. P.A. Goulden: None.

Background: Worsening Paget’s disease of bone (PDB) typically manifests as pelvic or spine bone pain. Headache as a primary presenting symptom of PDB is uncommon. Case Presentation: A 54-year-old female with Paget’s disease on alendronate presented at our institution with progressively worsening headaches, frontal bossing, alkaline phosphatase (ALP) of 1,668 U/L, and serum C-telopeptide of 986 pg/mL, indicating active disease. Subsequently, a bone scan confirmed active PDB, and zoledronic acid injection was administered in clinic. When re-evaluated, repeat laboratory values showed an ALP of 191 U/L, serum C-telopeptide of 511 pg/mL, PTH of 103 pg/mL, and vitamin D of 25.6 ng/mL, consistent with improved yet persistently active disease. Likewise, the patient complained of ongoing headaches, dizziness, hearing loss, and jaw pain. An X-ray of the skull showed diffuse expansile mixed Paget's disease, predominantly sclerotic, involving the calvarium with some basilar invagination noted. Subsequent whole-body bone scan showed intensely increased uptake in the skull. Audiology evaluation revealed slight to mild sensorineural hearing loss in bilateral ears. A second dose of zoledronic acid infusion was administered, and the patient’s ALP and C-telopeptide decreased to normal levels. Conclusion: We describe a case of advanced Paget’s disease presenting with persistent headaches. Clinicians should identify Paget’s disease as an atypical cause of headaches to provide appropriate treatment and prevent complications of skull involvement such as hearing loss.

Presentation: Thursday, June 15, 2023
THU471 Resolution Of Elevated Alkaline Phosphatase After Joint Replacement In Severe Osteoarthritis
Authors: Rakholiya Jigisha , Nagaraj Sanchitha , Sharma Pranjali
Published: October 2023

Disclosure: J. Rakholiya: None. S. Nagaraj: None. P. Sharma: None.

Introduction: Alkaline phosphatase (ALP) elevation is commonly seen in hepatobiliary disorders. Conditions of high turnover such as healing fractures, hyperparathyroidism, Pagets’ disease of the bone, also lead to ALP elevation (1). Osteoarthritis (OA), characterised by degeneration of articular cartilage, joint space narrowing, and osteophyte formation, rarely causes ALP elevation. We present a case of ALP elevation that resolved after the arthritic joint was replaced. Case Presentation: A 60-year-old female with history of bilateral knee OA presented to the endocrinology clinic due to elevated ALP for over a year. She reported chronic fatigue, sleep disturbance, dry skin, hair loss, inability to lose weight and anxiety. ALP level at presentation was 165 U/L. An extensive work-up showed unremarkable serum and ionized calcium, serum phosphorus, parathyroid hormone, vitamin D 25-OH, calcitriol, 24-hour urine calcium, serum protein electrophoresis, and 24-hour urine protein electrophoresis. Dual x-ray absorptiometry (DXA) scan was normal with Fracture risk assessment tool (FRAX) score 5.9% for major osteoporotic fracture and 0.2% for hip fracture. Patient underwent total left knee arthroplasty following which ALP improved from 165 U/L to 135 U/L within 9 weeks of the procedure. Five months later, ALP was elevated (164 U/L) again. She then underwent right knee arthroplasty and ALP dropped to normal level (114 U/L) within 1 week post-surgery. Discussion: We report the rare phenomenon of ALP elevation in severe OA, that resolved after joint replacement. OA is characterised by inflammation mediated cartilage destruction, subchondral bone change, osteophyte formation, and alterations of ligaments and meniscuses. Bone change in severe OA is associated with increased synovial fluid ALP level. However, there is a paucity of literature studying the association of ALP with OA. A cross-sectional study of 3060 patients demonstrated higher serum ALP with symptomatic knee OA. Another study showed higher ALP levels with increased joint stiffness. The ALP elevation was attributed to low grade inflammation causing an inflammatory response in chondrocytes, and osteoarthritic pain. There is a need for more studies to evaluate the utility of serum ALP as a biomarker for severe OA.

Presentation: Thursday, June 15, 2023
FRI671 Association Of Insulin-like Growth Factor-1 (igf-1) With Bone Mineral Density (bmd) In Survivors Of Childhood Acute Leukemia
Authors: Kim Seulki , Park Su Jin , Sim Soo Yeun , Eon Kim Sung , Bae Ahn Moon , Shin Hee Kim , Kyung Cho Won , Kyung Soon Cho , Ho Jung Min , Suh Byung-Kyu
Published: October 2023

Disclosure: S. Kim: None. S. Park: None. S. Sim: None. S. Kim: None. M. Ahn: None. K. Shin Hee: None. W. Cho: None. C. Kyung Soon: None. M. Jung: None. B. Suh: None.

Purpose: To investigate bone mineral deficit in children survivors of childhood acute leukemia and analyze the association of IGF-1 with BMD status Methods : A total 214 patients (aged 8.47±4.42 for girls and 8.31±4.09 for boys at diagnosis) who were treated for acute leukemia were retrospectively reviewed. Types of leukemia, transplantation, and radiation therapy were investigated. Standard deviation scores (SDSs) of height, weight, body mass index (BMI), and lumbar spine BMD were measured at the end of treatment. Lumbar spine BMD was measured using dual-energy x-ray absorptiometry (DXA). Its relationships with calcium, phosphorus, alkaline phosphatase, bone specific alkaline phosphatase, calcitriol, parathyroid hormone, growth hormone, IGF-1, and insulin-like growth factor-binding protein-3 (IGFBP-3) were analyzed. Low BMD was defined lumbar spine BMD SDS less than -2.0 according to International Society for Clinical Densitometry guideline. Results: The overall prevalence of low BMD was found to be 15% (32/214). Age at diagnosis, transplantation, and radiation therapy were not significantly different between low BMD and normal BMD groups, however, BMI SDS and IGF-1 SDS were different between those two groups (-0.84±1.94 vs. 0.17±2.09, P = 0.012; -1.23 ±0.82 vs. -0.72 ± 0.78, P = 0.001, respectively). Correlation analysis showed that IGF-1 SDS is associated with BMI SDS and lumbar spine BMD SDS (rho=0.19, P=0.006; rho=0.248, P=0.001, respectively). Lumbar spine BMD SDS was related to BMI SDS and IGF-1 SDS by multivariate linear regression analysis (β = 0.15, P = 0.003; β = 0.31, P = 0.021, respectively). Multivariate logistic regression analysis showed that higher IGF-1 SDS was associated with a decreased of prevalence of low BMD (odds ratio: 0.42, 95% confidence interval: 0.24-0.75, P = 0.003). Conclusion: IGF-1 SDS was related to BMD, especially lumbar spine BMD, and a risk of prevalence of low BMD in children and adolescents. IGF-1 SDS seems to be a good tool for evaluating and predicting osteoporosis in children and adolescents.

Presentation: Friday, June 16, 2023
FRI692 Severe Hyperparathyroidism And Nephrolithiasis In An Adolescent Male Due To CDC73 Positive Parathyroid Carcinoma
Authors: Nguyen Jennifer T , Geller David Harry , Ryabets-Lienhard Anna
Published: October 2023

Disclosure: J.T. Nguyen: None. D.H. Geller: None. A. Ryabets-Lienhard: None.

Introduction: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism in the pediatric population, with only 20 previously reported cases. Variations in the CDC73 gene have been associated with sporadic parathyroid carcinoma, autosomal dominant hyperparathyroidism-jaw tumor syndrome (HPT-JT), and familial isolated hyperparathyroidism (FIHP). To our knowledge, only 3 cases of pediatric parathyroid carcinoma with confirmed variants of CDC73 have been reported. We present a case of severe hyperparathyroidism and nephrolithiasis due to parathyroid carcinoma caused by a pathogenic variant in CDC73 in a pediatric patient, highlighting the importance of early recognition and management. Clinical Case: An otherwise asymptomatic 14-year-old male presented with one year of recurrent nephrolithiasis. Initial tests demonstrated hypercalcemia (13.8 mg/dL, 8.4-10.2 mg/dL), normal phosphorous, elevated PTH (1,379 pg/mL, 7.5-53.5 pg/mL), and elevated alkaline phosphatase (514 U/L, 30-250 U/L). The hypercalcemia was treated with hyperhydration, furosemide, and pamidronate. Sestamibi scan revealed a focus of abnormal uptake suggestive of a left parathyroid mass, with ultrasonographic demonstration of a predominantly solid, hypoechoic, and vascular mass centered posterior to the inferior left thyroid lobe. Skeletal survey was notable for trabecular abnormalities and osteopenia. He underwent a left parathyroid mass excision. Final pathology confirmed the parathyroid carcinoma, with multiple foci of vascular invasion without evidence of capsular involvement. Immunohistochemistry demonstrated diffuse positivity for PTH and loss of parafibromin expression by the tumor cells. Genetic testing revealed a pathogenic germline heterozygous nonsense variant in CDC73 (c.376C>T(p.Arg126Ter)) resulting in protein truncation. Post-operative PTH was undetectable with normal calcium and phosphorous. Calcitriol, cholecalciferol, and calcium carbonate supplementation were implemented to prevent further hypocalcemia due to transient hypoparathyroidism and hungry bone syndrome. Calcium supplementation was discontinued within one year of his surgery. Serial thyroid ultrasounds and CT scans have been negative for recurrent or residual disease without evidence of metastasis. Mandibular x-ray showed no evidence of tumors or lesions involving the jaw. He has been noted to have small right renal cysts without other kidney abnormalities. Conclusion: Severe hyperparathyroidism due to parathyroid carcinoma can present as recurrent nephrolithiasis in an otherwise asymptomatic individual. Pediatric patients with a longstanding history of kidney stones should undergo screening for hypercalcemia and hyperparathyroidism even in the absence of other signs and symptoms of elevated calcium to ensure timely diagnosis and appropriate management.

Presentation: Friday, June 16, 2023
FRI695 Hypercalcemia Mediated By Granulomatous Disease Due To Polymethylmethacrylate (pmma) Injection Utilization For Gluteal Augmentation
Authors: Mishra Tinni , Craven James
Published: October 2023

Disclosure: T. Mishra: None. J. Craven: None.

Introduction: While etiologies for hypercalcemia commonly include hyperparathyroidism, malignancy or vitamin D intoxication, unusual causes should also be considered. We present a case that describes a patient who presented with hypercalcemia in the setting of granulomatous reaction to PMMA filler for gluteal augmentation. Clinical case: A 52 year old female with a past medical history of hypertension, stage III chronic kidney disease, nephrolithiasis, depression was admitted to the hospital with a peak calcium of 15.8 mg/dl (n: 8.4-10.4mg/dl). Hypercalcemia was incidentally noted while she was undergoing workup for her chronic kidney disease. Initial testing revealed PTH of 22 pg/ml (n: 22-94). 25 hydroxy vitamin D 24ng/ml, (n: 30-80), 1, 25 dihydroxy D2 markedly elevated at 258 pg/ml (n: 19-79). SPEP/UPEP normal. PTHrp was found to be 5.9 pmol/L(n: 0-3.4pmol/L). High-resolution CT chest did not show evidence of granulomatous disease or lung masses. A PET scan was obtained which showed extensive hypermetabolic activity in the bilateral gluteus medius and maximus muscle consistent with her history of PMMA injection for buttock augmentation. She was placed on aggressive maintenance intravenous fluid hydration. In addition, Lasix, zoledronic acid and calcitonin were administered. With these measures her calcium improved to a level of 10.7mg/dl. She did not tolerate high dose glucocorticoids. With her treatment intolerance and progressive renal disease in mind, plastic surgery has been consulted to explore surgical options for PMMA debulking. Conclusion: This represents a case of hypercalcemia mediated by elevated levels of calcitriol due to granulomatous inflammation caused by a foreign body reaction to PMMA injection. Polymethylmethacrylate is primarily used in South/Central America as a synthetic filling agent in cosmetic procedures, but is not FDA approved for gluteal injection. To our knowledge, there is only one other case report of MMA mediated hypercalcemia in the US. Given the rise in cosmetic tourism and the lag time between PMMA injection and development of hypercalcemia (mean time to presentation of 7 years), this complication is likely to become increasingly prevalent in North America.

Presentation: Friday, June 16, 2023
SAT179 Germline And Somatic Inactivating FLCN Variants In Parathyroid Cancer and Atypical Parathyroid Tumors
Authors: Jha Smita , Welch James , Tora Rana , Lack Justin , Warner Andrew , Del Rivero Jaydira , Mercedes Sadowski Samira , Nilubol Naris , Schmidt Laura , Linehan W M , Scott Weinstein Lee , Simonds William F , Kishore Agarwal Sunita
Published: October 2023

Disclosure: S. Jha: None. J. Welch: None. R. Tora: None. J. Lack: None. A. Warner: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. L. Schmidt: None. W.M. Linehan: None. L.S. Weinstein: None. W.F. Simonds: None. S.K. Agarwal: None.

Background: Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and patients usually succumb to severe hypercalcemia. There is no effective systemic therapy for the disease. Methods: We analyzed the germline DNA of 19 patients with “sporadic” (PC) and 2 with atypical parathyroid tumors (APT) who did not have germline CDC73 or MEN1 pathogenic variants. Sequencing of available tumor tissue from 14 patients with PC and 2 with APT was also performed (including two patients with no available germline DNA). In addition, sporadic parathyroid adenomas from 74 patients were analyzed for FLCN variants. FIindings: We identified germline FLCN variants in three unrelated patients with PC. The two frameshift variants have been described in patients with Birt-Hogg-Dubé (BHD) syndrome while the pathogenicity of the missense variant c.124G>C (p.G42R) has not been definitively established. Functional analysis of the missense variant showed a potential impact on post-translational modification. All three patients with germline FLCN variants were noted to have renal cysts and two had lung cysts, features associated with BHD syndrome. Somatic FLCN variants were identified in tumors from 2 (one APT) of 16 patients with PC/APT and in none of the 74 sporadic parathyroid adenomas. No second hits in FLCN were noted on sequencing however, LOH at the locus was demonstrated in 2 of 3 patients with identified germline FLCN variant. Interpretation: The finding of FLCN variants associated with PC may provide the foundation for the development of therapy for this malignancy.

Presentation: Saturday, June 17, 2023
SAT184 Improving Access To Osteoporosis Specialists Using Electronic Consultations
Authors: Sethuram Claire , Brown Warren , Gill Gurleen , Liddy Clare , Afkham Amir , Keely Erin
Published: October 2023

Disclosure: C. Sethuram: None. W. Brown: None. G. Gill: None. C. Liddy: None. A. Afkham: None. E. Keely: None.

Background: Timely access to osteoporosis specialists remains a challenge in Canada, where patients face long wait times for specialist care. Electronic consultations (eConsults) help address this issue by allowing primary care providers (PCPs) to pose clinical questions to specialists using a secure online platform. This study identifies the types of osteoporosis-related questions being asked by PCPs and describes the impact of the advice provided by osteoporosis specialists using eConsult. Methods: We performed a cross-sectional study of osteoporosis-related eConsults submitted to endocrinologists between January 2018 and December 2020 on the Champlain BASE™ eConsult Service in Ontario, Canada. Each eConsult was coded according to clinical question and answer type through consensus between two authors, based on pre-determined taxonomies established by the reviewers. We analyzed eConsult utilization data, including response times, PCP satisfaction, and referral outcomes, which were collected via PCP surveys following completion of the eConsult. Results: Of the 2534 eConsults sent to endocrinologists during the study period, 408 (16%) were specific to osteoporosis. The most common questions asked by PCPs were regarding whether or not to start treatment (18%), the initial therapy choice (13%), and how often to complete bone mineral density scans (8%). The most common responses from specialists included recommendations for bone mineral density scanning (13%), recommendation to start therapy (9%), and recommendation to treat using a bisphosphonate without the dose specified (9%). The median response interval was 3.1 days, and the median time spent by endocrinologists responding to the eConsult was 10.0 minutes. Eighty-four percent of cases were resolved without requiring an in-person referral. A course of action that PCPs already had in mind was confirmed in 42% of cases. Clear advice for a new course of action for PCPs to implement was provided in 54% of cases. Conclusion: Osteoporosis eConsults provide timely access to valuable specialist advice while avoiding unnecessary face-to-face clinic visits. Further, we identified commonly recurring osteoporosis questions asked by PCPs, which can be used to inform planning of future continuing professional development events.

Presentation: Saturday, June 17, 2023