bluuebunny/crossref_metadata_2025 huggingface dataset:
PSUN26 Radiation For Adrenal Metastases: Should Patients be Monitored For Primary Adrenal Insufficiency?
Authors: Herndon Justine , Bancos Irina
Published: November 2022

Background

Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Risk of primary adrenal insufficiency (PAI) in bilateral metastases is 12%. Adrenal radiation is one of the options available to treat adrenal metastases. The risk of PAI after bilateral adrenal radiation is unclear.

Objective

We aimed to determine the incidence and the timeline of PAI in patients undergoing adrenal radiation for bilateral metastases.

Design, Setting, and Participants: Single center retrospective study of adult patients with adrenal metastases treated with adrenal radiation between 2010 and 2021.

Results

Of 55 patients with adrenal metastases treated with adrenal radiation, 7 (12.7%) had bilateral therapy, of whom 5 (all with lung adenocarcinoma) developed PAI. Another patient with history of unilateral adrenal radiation and previous contralateral adrenalectomy also developed PAI. Following the radiation therapy (median dose 50 Gy [range 20-65 Gy]), administered in a median of 5 fractions (range 5-18 fractions) in 6 patients who developed PAI, all treated metastases either decreased in size during imaging follow up or demonstrated a decrease in SUV uptake on PET scan. PAI developed at a median time of 6.1 months after radiation (range 0.5-20.4 months). PAI was diagnosed based on laboratory monitoring in 3 patients and based on treating endocrinologist's discretion (e.g., symptoms, clinical context) in the other 3 patients. Patients were initiated on hydrocortisone (median daily dose of 20 mg, range 15-80 mg) and fludrocortisone (median dose of 0.05 mg, range 0.05-0.1 mg)

At the end of the study period, daily replacement dose was higher for both for hydrocortisone (median of 35 mg, range 15-160 mg) and for fludrocortisone (median of 0.0625 mg, range 0.05-0.1 mg). All but one patient with PAI had passed away at the end of the study, at a median time of 19.7 months (range 6.1-55.8 months) since radiation and median time of 7.7 months (range 1.2-55.3 months) since the diagnosis of PAI. In the two patients with bilateral adrenal radiation who did not develop PAI, the follow up was short: 1 patient passed away six-months post-radiation and another patient had only 4 months of follow up.

Conclusion

Adrenal radiation is an effective therapy for patients with adrenal metastases. Risk of PAI is very high when bilateral adrenal radiation is administered, and patients need to be counseled about it. We observed that daily glucocorticoid replacement dose was excessive in some patients possibly reflecting the use of stress dosing due to underlying sickness. Both clinical and biochemical monitoring every 3-6 months should be instituted in patients undergoing bilateral adrenal radiation.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN28 Factors Associated with False-positive Fractionated Metanephrines in Plasma and Urine
Authors: Yu Kai , Young William F , Achenbach Sara , Atkinson Elizabeth , Singh Ravinder , Grebe Stefan , Bancos Irina
Published: November 2022

Context

Plasma and 24-hr urine metanephrine (M) and normetanephrine (NM) are the standard of care tests used in the biochemical diagnosis of pheochromocytoma and paraganglioma (PPGL). Considering the rarity of PPGL, false positive (FP) results represent a challenge because they lead to additional investigations, healthcare burden, and uncertainty for the patient. The impact of medications on the rate of FP results is not fully established.

Objective

We aimed to identify the medications associated with the FP rate of 24-hr urine and plasma M and NM measured by the HPLC-MS/MS method.

Methods

We conducted a single-center study of patients who had 24-hour urine or plasma M and NM testing between 09/27/2015 and 02/15/2021, and who had a follow-up of at least 6 months. Results were considered FP if M/NM were > upper limit of the normal ranges (ULN) and there was absence of PPGL. Results were considered true negative (TN) when M/NM were within the reference ranges in patients without PPGL. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models.

Results

Plasma M/NM testing was performed in 3152 patients and 24-hr urine M/NM was performed in 2008 patients. The FP rate for the M fraction (plasma: 0.8%, urine: 1.3%) was much lower than the FP rate for NM (plasma: 16%, urine: 4.4%); thus, the impact of medications on FP rate was examined only for NM. In those with FP NM, the median degrees of elevation were 24% (IQR 10-46) >ULN in plasma and 26% (IQR 11-45) >ULN in urine.

When compared to patients with TN results, patients with FP plasma NM were more likely to be treated with opioids (OR=1.29, 95%CI, 1.04-1.60), tricyclic antidepressants (OR=1.61, 95%CI,1.14-2.27), serotonin–norepinephrine reuptake inhibitors (OR=1.85, 95%CI, 1.35-2.53), second generation antipsychotics (OR=2.32, 95%CI, 1.28-4.20), but not first generation antipsychotics (OR=1.23, 95% CI, 0.86-1.75) when compared to the TN group.

When compared to patients with TN results, patients with FP urine NM were more likely to be treated with opioids (OR=1.96 95%CI, 1.26-3.06), tricyclic antidepressants (OR=2.61, 95%CI, 1.47-4.65), serotonin–norepinephrine reuptake inhibitors (OR=2.20, 95%CI, 1.20-4.02), and both first (OR=3.06, 95%CI, 1.74-5.38) and second generation antipsychotics (OR=2.51, 95%CI, 1.03-6.13).

Conclusion

The plasma NM FP rate was 16% and 3-fold higher than the same measurement in urine (4.4%). Several classes of medications had a significant impact on the rate of FP NM. Clinicians should consider use of 24-hr urine M and NM in low suspicion cases of PPGL where the diagnosis simply needs to be excluded.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF21 | PSAT76 Epigenetic Programs Stabilize a Differentiated Cell State Required for Sustained Proliferation in Adrenocortical Carcinoma
Authors: Mohan Dipika , Borges Kleiton , Finco Isabella , LaPensee Christopher , Rege Juilee , Little Donald , Else Tobias , Almeida Madson , Latronico Ana Claudia , Mendonca Berenice , Auchus Richard , Rainey William , Marie Suely , Giordano Thomas , Venneti Sriram , Candida Fragoso Maria , Breault David , Lerario Antonio , Hammer Gary
Published: November 2022

Adrenocortical carcinoma (ACC) is a rare, aggressive, and poorly understood cancer of the adrenal cortex. Abnormal epigenetic patterning is a major predictor of dismal disease outcomes. Patients with genome-wide CpG island hypermethylation (CIMP-high) experience rapidly recurrent and routinely fatal disease. A deeper understanding of how epigenetic programs coordinate tumorigenesis is essential to develop improved medical therapies. We identify that DNA hypermethylation is directed to targets of a histone modifying complex, PRC2, suggesting cross-talk between DNA and histone methylation in CIMP-high ACC. In contrast to our expectations, we discovered that DNA methylation and PRC2-directed histone methylation are mutually exclusive. Additionally, we identified that EZH2 (a canonical member of the PRC2) forms a separate complex with tissue-specific proteins to coordinate sustained proliferation and steroidogenic differentiation in vitro and in vivo. These complexes persist through advanced stages of human malignancy and are conserved in mouse models of adrenal carcinogenesis. Taken together, our studies illustrate how CpG island hypermethylation exposes a pharmacologically targetable tissue-specific therapeutic vulnerability, and stabilizes a differentiation state required for sustained proliferation. Ultimately, we hope this work illuminates novel strategies for tissue-specific disruption of the aberrant epigenetic wiring supporting this devastating disease.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:24 p.m. - 1:30 p.m.
RF21 | PSUN08 Morphologic or Molecular Imaging - Diagnostic Capabilities in von Hippel-Lindau related pheochromocytoma
Authors: Patel Mayank , Jha Abhisek , Ling Alexander , Chen Clara C , Millo Corina , Talvacchio Sara , Ezemobi Josephine , Kailah Charles , David Taïeb , Carrasquillo Jorge A , Pacak Karel
Published: November 2022

Background

Within a spectrum of cancers implicated by VHL germline pathogenic variants, one rare cancer which may present in patients are pheochromocytomas (PHEOs). These tumors occur in the adrenal glands and predispose patients to a variety of morbid clinical symptoms due to the excess secretion of catecholamines. As a part of these patients’ management, imaging is important to localize the tumors of which there are both morphologic (CT and MRI) and molecular (PET/CT with 18F-FDG, 68Ga-DOTATATE, 18F-DOPA, and 18F-DA) imaging modalities.

Purpose

To determine which imaging modalities provided the optimal detection of VHL-related PHEO.

Methods

The study compared detection of 19 PHEOs (18 histologically proven and 1 is a contralateral tumor awaiting resection) in 12 patients. The CT and MRI were evaluated by a body radiologist and the PET/CT of18F-FDG, 68Ga-DOTATATE, 18F-DOPA, and 18F-DA were evaluated by a nuclear medicine physician in a blinded fashion. Both experts graded using a five-point Likert scale (1 – not PHEO and 5 – PHEO). For analysis, the Likert scale was dichotomized with 1-3 designating negative for PHEO and 4-5 positive for PHEO. The findings were reported as detection rates of positive PHEOs found on imaging to the gold standard of pathologically (aside from one contralateral PHEO awaiting surgery) proven PHEOs. The McNemar test was performed to compare the statistical relevance of detection rates between histology and the imaging modalities. Two-sided p values <0.05 were considered significant.

Results

The detection rates were CT 17/19 [89.5%, 95% CI = 66.9%-98.7%], MRI 17/17 [100%, 95% CI = 80.5%-100%], 18F-FDG PET/CT 16/17 [94.1%, 95% CI = 80.5%-100%], 68Ga-DOTATATE 5/9 [55.6%, 95% CI = 21.2%-86.3%], 18F-DOPA 12/14 [85.7%, 95% CI = 57.2%-98.2%], and 18F-DA 4/6 [66.7%, 95% CI = 22.3%–95.7%]. All McNemar tests showed p-values greater than 0.05, which were not statistically significant.

Conclusion

The study was performed in a small patient set with VHL-related PHEO showed MRI, with the highest detection percent followed by 18F-FDG PET/CT. More trials with a larger patient set are needed to support the statistical relevance as it was not seen in this study. Furthermore, performing a study on a patient cohort with additional VHL associated cancers could prove clinically beneficial for patients.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:18 p.m. - 1:23 p.m.
RF33 | PSAT68 Gonadotropin-Releasing Hormone Agonist Therapy Does Not Affect Bone Mineral Density in Congenital Adrenal Hyperplasia: a Clinical Study
Authors: Flokas Myrto , Kollender Sarah , Wakim Paul , Sinaii Ninet , Parker Megan , Mallappa Ashwini , Merke Deborah
Published: November 2022

Background

Children with congenital adrenal hyperplasia (CAH) are at risk for early central puberty, and gonadotropin-releasing hormone analogs (GnRHa) are frequently used aiming to improve adult height. However, their effect on bone health among the CAH population has not been previously studied. GnRHa reduce sex steroid levels and delay central puberty, which may negatively affect the achievement of peak bone mass. In healthy children, bone mass increases with time, reaching its peak between the second and third decades of life. The purpose of this study was to investigate the short-term and long-term effect of GnRHa therapy on the bone mineral density (BMD) of patients with classic CAH.

Methods

Sixty patients with classic CAH due to 21OH deficiency were followed longitudinally at our institution with DXA scans at the time they achieved adult height. Adult height was considered attained when bone age exceeded 15 years in girls and 17 years in boys. Twenty-one patients treated with GnRHa (81% male, 57% salt wasting, treated for mean ± SD: 4.3 ±2 years) were compared to 39 patients not treated with GnRHa (49% male, 79.5% salt wasting). BMD z scores, adjusted for height and age, were evaluated at the time they reached adult height and on average 8.3 years later.

Results

There was no difference between GnRHa groups in total body (p=0.96), femoral neck (p=0.24), lumbar spine (p=0.59), forearm (p=0.38), and total hip (p= 0.31) z scores at adult height attainment. In multivariable analyses, there was no effect of GnRHa on BMD z scores at any site. In reduced models, increased 17-hydroxyprogesterone (17-OHP) levels correlated with higher BMD z scores for total body (p=0.003), lumbar spine (p<0.001), and forearm (p<0.001). Higher BMI (p=0.014) and no treatment with dexamethasone (p=0.022) were also associated with higher femoral BMD z score. Overall, the follow up DXA during young adulthood (n=28) showed significant decreases in z scores at total body (p=0.019), femoral neck (p=0.036), lumbar spine (p<0.001), forearm (p<0.001), and total hip (p=0.024), and use of GnRHa did not contribute. Interestingly, when adjusting for midparental height, those treated with GnRHa had lower adult height z scores than those without GnRHa (p=0.037).

Conclusion

Treatment with GnRHa for approximately 4 years does not impact BMD in adolescents and young adults with CAH, and exposure to adrenal androgens may play a protective role. In patients with CAH, BMD decreases with time and during the second and third decades of life, which may reflect the effect of long-term supraphysiologic glucocorticoid therapy. Although intended to preserve height, children with CAH who experience early puberty have loss of adult height, despite treatment with GnRHa.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.
RF33 | PSUN03 Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations
Authors: Grigoryan Seda , Nhan Winnie , Zhang Lei , Urban Caitlin , Holevinski Lynn , Zhao Lily , Turcu Adina
Published: November 2022

Background

Hypertension is estimated to affect 1: 2 adults in the USA, and secondary hypertension accounts for up to 40% cases. Pheochromocytomas and paragangliomas (PPGL) are thought to be rare causes of hypertension, although their true prevalence might be underestimated. Less than half of patients with PPGL have prototypical symptoms. PPGL can lead to serious complications, including death, particularly if unrecognized. Expert guidelines recommend screening for secondary causes of hypertension in patients with resistant hypertension, patients with early-onset hypertension, and in those with hypertension and an adrenal mass. The rates of PPGL screening are unknown.

Objective

To evaluate the rates and patterns of PPGL screening among candidate patients.

Methods

We conducted a retrospective review of adult patients (age ≥ 18 years) with hypertension seen in a university-based outpatient setting between 01/01/2017 - 06/30/2020, and we included patients with: 1) resistant hypertension (uncontrolled hypertension while taking at least 3 antihypertensive agents OR taking ≥4 antihypertensive agents); 2) hypertension at age <35 years; 3) adrenal nodule(s). We excluded patients with renovascular hypertension, advanced chronic kidney disease (CKD stage ≥4), stage III and IV heart failure, adrenal insufficiency, and congenital adrenal hyperplasia.

Results

Of 203,535 patients with hypertension, 71,088 (35%) met at least one of the above criteria, and only 2013 (2.83%) were screened for PPGL. Overall, patients screened were younger (56.2 ± 17.4 vs. 63.9±17.1 years, p <0.001), more often women (54.1% vs. 44.2%, p=0.001), and non-smokers (54.6% vs. 47.5%, p<0.001) than those not screened. While most patients included in the study were white (80%), the proportion of black patients was larger among those screened (19.9% vs.13.3% of those not screened, p<0.001). Of the three indications for PPGL screening, the rates were highest in patients with hypertension and adrenal nodule(s) (51.7%), while patients with early onset hypertension and those with resistant hypertension were rarely screened (3.9% and 2.4%, respectively). Multivariable logistic regression with LASSO selection showed that the odds of PPGL screening were higher in black vs. white patients (1.35 [1.19-1.53]); those who never smoked (1.68 [1.41-2.00]); patients with stroke (1.34 [1.16-1.54]); dyslipidemia (1.41 [1.26-1.57]), CKD (1.40 [1.26-1.56); obstructive sleep apnea (1.96 [1.76-2.19]); and adrenal nodules (55.1 [44.53-68.17]).

Conclusions

Screening for PPGL is conducted in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with resistant or early onset hypertension. Screening occurs more often in patients with complications known to be associated with PPGL, including cardiovascular accidents.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
LBODP018 Hypercalcemia In A Child On Ketogenic Diet For Intractable Epilepsy
Authors: Gurnurkar Shilpa , Gafen Noah , Carakushansky Mauri , Vyas Neha
Published: November 2022

Introduction

Ketogenic diets have been shown to significantly reduce seizures in patients with intractable epilepsy refractory to common antiepileptic medications. There have been reports of hypercalcemia in diet-controlled epilepsy patients. The exact cause of hypercalcemia in ketogenic diets is unclear but decreased bone formation and impaired calcium excretion are suggested mechanisms.

Case

An 8-year-old male with Lennox-Gastaut syndrome was noted to have incidental hypercalcemia on admission (serum calcium 11.5 mg/dL, n = 8.8-10.1) for aspiration pneumonia, UTI, and increased seizure-like activity. Hypercalcemia persisted throughout his hospitalization (range: 10.8-12.4 mg/dL). Evaluation of hypercalcemia indicated normal serum phosphate (5.6 mg/dL, n = 3. 0-6. 0), appropriately low PTH (9.5 pg/mL, n = 10. 0-65. 0), undetectable PTHrP (<2. 0 pmol/L), low 25 (OH) vitamin D (19ng/ml, n=30-100), low 1,25 (OH)2 vitamin D (7.1 pg/mL, n = 19.9-79.3), normal creatinine (0.3 mg/dL, n = 0.31-0.61), slightly elevated TSH (5.13 mIU/L, n = 0.5-4.5) with a normal free T4 (1.4 ng/dL, n = 0.8-2. 0), and physiologic CBC. Alkaline phosphatase was low (88 U/L, n = 156-386) and skeletal survey showed diffuse demineralization. Urine calcium creatinine ratio was elevated at 0.6 when serum calcium was 11.6 mg/dl. Patient was 7 months into a ketogenic diet that successfully reduced seizure frequency and the plan was to further intensify the diet. On hospital day 11 when serum calcium was 12mg/dl, he was started on IV normal saline and furosemide up to a daily dose of 60 mg. On hospital day 12, patient was started on calcitonin (3 U/kg twice daily SQ). Serum calcium normalized (10 mg/dl), but calcitonin had to be discontinued due to severe nausea and vomiting. GI symptoms did not improve on a lower calcitonin dose. Calcium gradually corrected on fluids and furosemide, but hypercalcemia recurred (11mg/dl) after furosemide was weaned. The patient was then transferred to a higher level of neurologic care to continue treatment and increase the intensity of the ketogenic diet. There, on cumulative hospital day 26, he received zoledronic acid (0. 0125 mg/kg) which was tolerated well and resulted in normalization of the serum calcium levels (10.9mg/dl, 10.2mg/dl and 9.8mg/dl on days 26, 28 and 29 respectively).

Conclusions

This case adds to the limited literature available on the evidence that management of refractory epilepsy with ketogenic diets may cause acute hypercalcemia. Although the underlying cause is unclear, decreased osteogenesis as marked by low alkaline phosphatase activity remains the likely explanation. Other risk factors such as immobilization also need to be explored. The successful implementation of protocols used to treat our patient and similar patients in the literature may help create screening protocols for early detection and management of the hypercalcemia to prevent complications.

Presentation: No date and time listed
LBODP065 Rare Cause Of Bone Pain In MEN Syndrome
Authors: Ramdhanie Lisa Indira , Pinsker Richard , Cervellione Kelly
Published: November 2022

Introduction: MEN 1 syndrome is a rare disease in children and young adults, with prevalence reported as 2 per 100,000. MEN 1 caused by mutations in the MEN1 tumor suppressor gene, characterized by 2 or more MEN1 tumors: parathyroid, anterior pituitary, pancreatic islet tumors. To the best of our knowledge, osteomyelitis of the pelvis has not been reported as a complication in the literature in patients who were diagnosed with MEN1Case21 yo male from Honduras with PMHx of remote asthma presented with a common complaint of abdomen pain but found to have a rare diagnosis. He had 2 days of lower abdomen pain associated with non-bilious non bloody vomiting. Initial were significant for calcium 12.9, phosphorus 1.5 magnesium 1.8 and PTH 360. 4 mm renal stone 4 mm was detected on CT abdomen/pelvis. The initial EKG demonstrated J point elevation due to the hypercalcemia. He was admitted to the PICU for continuous telemetry monitoring due to the abnormal EKG related to electrolyte abnormalities. Hypercalcemia treatment was initiated with aggressive hydration, calcitonin administration as well as zoledronic acid administration. The patient's calcium levels improved as well as EKG. The parathyroid scan was positive for a right-sided parathyroid adenoma. He underwent right Inferior Parathyroidectomy, Intraoperative Nerve Monitoring, Cryopreservation of Parathyroid Tissue. As part of his diagnostic work-up for hyperparathyroidism, he was screened for MEN. His pituitary function was abnormal: ACTH and cortisol levels were high, his testosterone and gonadotropins were inappropriately low as well as TSH and T4. A microadenoma was present on brain MRI. No Pancreatic Neuroendocrine Neoplasia was found. The diagnosis of MEN 1 was made. Despite the improvements in his endocrinopathies, he continued to have lower abdomen pain associated with intermittent fevers. He was seen by urology and orthopedics. Initially MRI demonstrated bone erosion thought to be secondary to hypercalcemia but repeat MRI imaging of the pelvis was suspicious for phlegmon vs. developing abscess secondary to osteitis pubis. His blood cultures were positive for MSSA. He was started on antibiotics with continued clinical improvementThis patient presented with one of the most common complaints in the ED, abdomen pain and was found to have two rare and potentially fatal diagnosis which was identified and treated with a good clinical outcome Discussion: This case highlights a rare disease in the setting of osteomyelitis which could easily be missed as a manifestation of bone pain from hypercalcemia. The patient did experience fevers and malaise that was initially attributed to zoledronic acid administration. When his pain did not resolve MRI found osteomyelitis, allowing early antibiotic administration and prevention of sepsis.

Presentation: No date and time listed
LBSAT130 Hypercalcemia In Pregnancy Due To CYP24A1 Mutation
Authors: Agu Chinyere , Cho Ei , Resta Christine , Luba Rakhlin
Published: November 2022

Background

The active form of vitamin D (1,25 OH2 vitamin D) is catabolized by a key enzyme 1,25 OH vitamin D-24 hydroxylase, which is encoded by the CYP24A1 gene. Loss of function mutation in the CYP24A1 leads to elevated levels of active vitamin D, causing PTH independent hypercalcemia with nephrolithiasis and nephrocalcinosis. Two phenotypic variants have been identified: idiopathic infantile hypercalcemia, which is a more severe form presenting in infancy, and a milder form with onset in adulthood as is this case. Pregnancy is known to initiate or worsen the hypercalcemia.

Clinical Case

A 27-year-old woman presented at 11 weeks gestation with hyperemesis, noted to have hypercalcemia calcium 15.7mg/dl (8.2 to 10.1 pg/ml), low PTH 2pg/ml (24 -85 pg/ml) with high serum 1,25 OHD 309pg/ml (nl 19.9-79.3 pg/ml). She had low PTHrp, normal ACE level, and negative TB testing. Pre-pregnancy calcium was normal (9.8mg/dl). She had a history of hypercalcemia in previous pregnancy (Calcium 13mg/dl) that ended in IUFD. Family history revealed nephrolithiasis in her sister, mother, and paternal aunt as well as a consanguineous marriage in our patient and her parents. Vitamin D metabolites evaluated via liquid chromatography showed low serum 24,25(OH)2D (0.29ng/ml nl N/A) and elevated 25OHD 138 ng/mL (20-80 ng/ml). Ratio of 25 (OH) Vit D to 24,25(OH)2D was 475.86 (values >80 indicate probable bi-allelic CYP24A1 deletion or mutation. Genetic test pending.

Conclusion

This case highlights the fact that patients with 24 hydroxylase deficiency may be normocalcemic with hypercalcemia unveiled during pregnancy due to increased 1alpha hydroxylase production by the placenta and kidneys as well as intake of prenatal vitamins containing calciferol. An index of suspicion for CYP24A1 mutation is needed in patients with high active vitamin D metabolites, high or normal calcium, low PTH, family history of kidney stones or worsening hypercalcemia in pregnancy.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
LBSAT308 A Tale Of Two Endocrinopathies: Hyperthyroidism And Hypophysitis In A Case of Metastatic Melanoma
Authors: Loughner Chelsea L , Mahmood Ejaz
Published: November 2022

Introduction: Several endocrinopathies have been associated with immunomodulator therapy, including hyperthyroidism, hypophysitis, and adrenal insufficiency. However, there have not yet been reports of more than one endocrinopathy in a single patient undergoing treatment with these agents. Clinical case: A 35 year old male was referred to Endocrinology after labs revealed hyperthyroidism. He had recently been diagnosed with melanoma that had metastasized to the liver and had been receiving dual immunotherapy with Nivolumab and Ipilimumab for 2 months. Routine labs from Oncology revealed TSH 0. 005 mIU/L (n 0.358-3.740 mIU/L), free T4 2.23 ng/dL (n 0.89-1.76 ng/dL), and total T3 232.3 ng/dL (n 60. 0-181. 0 ng/dL). Dual immunotherapy was discontinued given these findings. When he presented to Endocrinology, he endorsed nausea, vomiting, and chills. He was started on propranolol and a thyroid uptake scan was ordered. Two weeks later, the patient was unable to complete imaging due to fatigue, nausea, vomiting, and extremity pain. Labs at that time revealed PM cortisol 0.69 mcg/dL (n 3.44-16.76 mcg/dL), plasma ACTH <5 pg/mL (n 6-50 pg/mL), testosterone 74.5 ng/dL (n 123.1-813.9 ng/dL), prolactin 20.2 ng/mL (n 2.1-17.7 ng/mL), LH 9.80 mIU/mL (n 1.5-9.3 mIU/mL), and FSH 5.3 IU/L (n 1.4-18.1 IU/L). Interestingly, the patient's TSH and free T4 continued to reveal hyperthyroidism. A pituitary MRI demonstrated a 9 mm hypoechoic area at the posterior aspect of the pituitary. Given the lab and imaging findings, a diagnosis of hypophysitis was made. The patient was started on glucocorticoid therapy with good response. Over the next several months, a slow prednisone taper was initiated. Thyroid function returned to baseline normal values. He continued to be followed by Oncology for surveillance but has not been restarted on immunotherapy. Clinical lesson: Although there have been several reports of hyperthyroidism or hypophysitis in response to immunotherapy, this is the first reported case of a patient with dual endocrinopathies associated with immune modulator inhibition.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP083 Burosumab Treatment for Fibrous dysplasia/McCune-Albright Syndrome with Severe Spine Deformity
Authors: Sato Tetsuhiko , Azuma Yoshinori , Tauchi Ryoji , Matsushita Masaki , Ozone Chikafumi
Published: November 2022

Introduction

Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) is a rare multi-endocrine disorder with bone abnormalities called polyostonic fibrous dysplasia, presumably related to fibrous growth factor 23 (FGF23). We present a case of a patient with FD/MAS who successfully underwent spinal fusion surgery after efficacious anti-FGF23 treatment using its monoclonal antibody (burosumab).

Clinical Case

A late teenage boy, clinically diagnosed with FD/MAS, was referred to our hospital for possible treatment of burosumab, because he desperately needed promising medical intervention for bisphosphonate-resistant severe polyostonic fibrous dysplasia with enormously high turnover bone disease. On presentation, he had severe scoliosis (>80 degree-thoracic spine curve) with mild hypophosphatemia (2.5 mg/dL), low 25-hydroxyvitamin D (7.3 ng/mL), normal corrected calcium (9.6mg/dL) and high intact PTH (95.7 pg/mL). His FGF23 level was 90.4pg/mL, which was inappropriately high. He had a history of previous bilateral hip fractures with partially removed Café au macules on the back. Baseline laboratory findings revealed no remarkable signs of endocrinopathies, whereas serum bone markers were remarkably high (tartrate-resistant acid phosphatase 5b, >1500 mU/dL; procollagen type 1 N-propeptide, >1200 ng/mL, alkaline phosphatase, 2638 U/L). He was started on monthly 50mg of burosumab therapy subcutaneously. Interestingly enough, his alkaline phosphatase levels gradually decreased down to 1619 U/L at month 6 post-anti-FGF23 treatment. Subsequent spine fusion surgery was successfully underwent with his thoracic curve corrected by instrumentation.

Discussion

This is, to our knowledge, the first case with FD/MAS, who was given monthly burosumab, followed by orthopedic spinal instrumentation to straighten the spine curve. Burosumab treatment for FD/MAS may enhance bone flexibility by blocking abnormal FGF23-related signaling, enabling safer approach to promising orthopedic surgeries.

Presentation: No date and time listed
ODP089 Familial correlation and heritability of muscle strength in Korean adults (KNHANES 2014-2019)
Authors: Hee Ahn Seong , Cho Yongin , Hong Seongbin , Kim So Hun , Park Eun Byeol , Seo Da Hea , Seo Seongha , Ju Seo Young
Published: November 2022

Objective

The onset and progression of sarcopenia are highly variable between individuals due to genetic and environmental factors. However, studies that have measured muscle strength directly in large numbers of matched parent-adult offspring pairs are limited. In this study, we investigated familial correlation and heritability of handgrip strength (HGS) in Korean adults.

Methods

This was a family-based cohort study from the Korea National Health and Nutrition Examination Survey (2014-2019) including 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations for HGS were calculated in different types of relative pairs. Variance component methods were used to obtain heritability estimates.

Results

Mean HGS of parents were 39.3 ± 7.5 kg in fathers and 24.4 ± 5. 0 kg in mothers and those of offspring were 41.8 ± 8. 0 kg in sons and 24. 0 ± 4.8 kg in daughters. Correlation coefficient estimates between parent-offspring pairs, sibling pairs, and spouse pairs for HGS were significant as 0. 07, 0.10, and 0.23 (p <0. 001, p = 0. 041, and p <0. 001), respectively. The total variance of the phenotype under study was explained by additive genetic (15.4%), common shared environmental (11. 0%), and unique environmental (73.6%) influences. The risk of low HGS conferred by parents’ low HGS were found to be significant for individuals whose parents had low HGS (OR 3.10, 95%CI 1.14-8.45).

Conclusion

Muscle strength showed a familial correlation in Korean adults. A significant heritable tendency of muscle strength from parents to their adult offspring and common shared environmental influence can explain this correlation.

Presentation: No date and time listed
ODP092 Guideline Adherence for Age-based Screening of Osteoporosis in Men at a Veterans Affairs Medical Center
Authors: Alsamarraie Henin , Clark Alexandra
Published: November 2022

Background

Osteoporosis is one of the leading causes of morbidity and mortality in older women and men. Men with osteoporosis have higher fracture-related morbidity and mortality rates compared to women, but screening rates in men remain much lower. Moreover, there is limited veteran-specific data despite the suggestion that veterans may be at higher risk for osteoporosis. (1) Objective: To assess current dual energy X-ray absorptiometry (DEXA) ordering practices within a veteran cohort. Design: A retrospective cohort study of male veterans aged71-75 years who were evaluated by a primary care provider (PCP) within the last 5 years (n = 13,174).

Results

DEXAs wereordered for ∼7% of the population (920/13,174), and 91.6% were completed (843/920). Over 60% of completed DEXAs were ordered due to the presence of risk factors (308/843, 36.5%), history of fractures (60/843, 7%), known osteopenia or osteoporosis (59/843, 7%), or osteopenia mentioned on another imaging modality (78/843, 9.3%), while only 33.5% (282/843) were ordered for screening purposes. Of those with DEXA results reported (838/843, 99.4%), 34.5% (289/838) were normal, 51% (427/838) were in the osteopenia range and 14.5% (122/838) were in the osteoporosis range. Regarding DEXAs obtained for screening purposes, 42% (118/282) were normal, 48% (136/282) were in the osteopenia range, and 10% (28/282) were in the osteoporosis range.

Conclusions

Despite the Endocrine Society and National Osteoporosis Foundation recommending screening men aged ≥70 years, less than 10% of male veterans eligible for osteoporosis screening based on age alone had a DEXA scan. Of those male veterans who received a DEXA for screening purposes, almost 60% were found to have an abnormal result. The lack of screening for osteoporosis in this population has the potential to worsen the disparity in bone health between men and women, and between veterans and non-veterans, making it difficult to determine the scope of a problem which has the potential to cause significant morbidity and mortality.

References

1. Nahm ES et al. Osteoporosis Preventive Practice Between Veteran and Nonveteran Older Adults: Findings From Patient-Reported Data. Orthopedic Nursing. 2016 Nov/Dec;35(6): 401-410.

Presentation: No date and time listed
ODP096 Hypercalcemia Secondary to Vitamin D Supplementation with Normal 25-Hydroxyvitamin D Level in an Elderly Female - Case Report
Authors: Arora Gunjan , Patel Toral
Published: November 2022

Case presentation

A 92-year-old female with a history of heart failure, dementia (alert and oriented to time, place and person at baseline), osteoporosis and hypothyroidism presented to the emergency department with altered mental status and constipation. She was oriented to time and person only. Labs included: WBC count 6.2 (4 - 11k/mm cu), Creatinine 1.23 (0.6 - 1.2 mg/dL), Calcium 12.8 (8.6 - 10.3 mg/dL), Albumin 3.9 (3.5 - 5.7 g/dL) and Glucose 94 (70 - 99 mg/dL). CT head showed no acute abnormality. Medication reconciliation revealed that she was taking Cholecalciferol (Vitamin D3) 2000 units daily, which was held. Intravenous fluids were started and further workup was done: PTH < 6 (12 - 88 pg/mL), serum 25 Hydroxyvitamin D 45.1 (30 - 100 ng/mL), serum 1, 25 Dihydroxyvitamin D 79 (19.9 - 79.3 pg/ml) and PTHrP 2.6 (0 - 3.4 pmol/L). Endocrinology was consulted for management of PTH independent hypercalcemia and recommended Zoledronic acid. Serum calcium levels normalized with bisphosphonate therapy and withholding of Vitamin D3 supplementation in addition to symptomatic improvement. Repeat 1-25-Dihydroxyvitamin D level decreased to 38.3 pg/mL while repeat PTH normalized at 20.8 pg/mL. Subsequently, serum calcium levels remained within normal limits, and she was discharged.

Discussion

Vitamin D, the "sunshine Vitamin", has claimed much fame and popularity for its varied benefits. With a growing user base, there is concern for potential adverse effects, primarily involving the population with an underlying propensity for hypercalcemia. According to the NIH, the safe upper limit of daily Vitamin D intake is 4000 IU; however, for adults > 70 years of age, 800 IU is the recommended dose. Our patient was taking 2000 IU (almost 2.5 times the recommended dose) of Vitamin D3, the most potent form which raises Vitamin D levels twice as fast as Vitamin D2. In addition, her serum 1,25 Dihydroxyvitamin D levels normalized when supplementation was withheld pointing to a cause - effect relationship and thus, effectively ruling out an endogenous source. Moreover, other factors such as prolonged duration of supplement intake, advanced age, immobility, osteoporosis and hypothyroidism contributed to her hypercalcemia. Current review of literature suggests that serum concentrations of 25-Hydroxyvitamin D at which hypercalcemia arises remains undefined. With this case, we wish to emphasize that a holistic approach should be utilized to advise patients regarding Vitamin D supplementation considering pre-existing risk factors for hypercalcemia, concurrent medical conditions, diet and functional status. Although current guidelines detail the ideal dosage and duration of Vitamin D supplementation therapy for different sectors of population, streamlining and individualizing therapy to mitigate potential harm to patients is pivotal.

Presentation: No date and time listed
ODP097 Hyperparathyroidism as a major risk factor of fracture and its prevalence in patients with hip fracture
Authors: Tan Lok Yi Joyce , Asri Nur Atikah Mohd
Published: November 2022

Introduction

Hyperparathyroidism is a risk factor of osteoporosis. Excess parathyroid hormone (PTH) accelerates bone loss via bone reabsorption and increases the risk of fragility fracture. Fragility fractures are associated with serious consequences in older patients. [1] This study aimed to look at the prevalence of hyperparathyroidism and vitamin D deficiency in geriatric patients (age >60) who presented with hip fractures in an Irish tertiary hospital.

Methods

Data was collected from Irish hip fracture Database (IHFD) and the Ortho-geriatric Electronic Patient Medical System (EPMS) between July 2019 and April 2020 (n=207). Demographic data and bone health profile (PTH, Vitamin D, and Calcium) were analysed using SPSS for statistical analysis.

Results

The median age of patients was 81 years (SD 8.7), and 68.3% of patients were female. Median 10-year probability of major osteoporotic and hip fracture risk is 22.5% and 12.2%, respectively. 29.9% was diagnosed with hyperparathyroidism with prevalence of primary and secondary hyperparathyroidism of 6.7% and 23.1%, respectively. The majority of these (87.3%) were normocalcaemic hyperparathyroidism. 50.7% were vitamin D deficient, with 11.5% being severely deficient (Vitamin D <20nmol/L).

Conclusion

The prevalence of hyperparathyroidism is higher in the hip fracture group than in the general population. [2] Vitamin D deficiency is also prevalent in this group. FRAX score indicated significant proportion of patients with high major osteoporosis and hip fracture risks. Routine bone health profile checks in this high-risk group allow early identification and management of hyperparathyroidism and vitamin D depletion, which can potentially reduce the risk of future fracture. Reference: 1. Bukata SV, DiGiovanni BF, Friedman SM, Hoyen H, Kates A, Kates SL, Mears SC, Mendelson DA, Serna Jr FH, Sieber FE, Tyler WK. A guide to improving the care of patients with fragility fractures. Geriatric Orthopaedic Surgery & Rehabilitation. 2011 Jan;2(1): 5-37.2. Press DM, Siperstein AE, Berber E, Shin JJ, Metzger R, Jin J, Monteiro R, Mino J, Swagel W, Mitchell JC. The prevalence of undiagnosed and unrecognized primary hyperparathyroidism: a population-based analysis from the electronic medical record. Surgery. 2013 Dec 1;154(6): 1232-8

Presentation: No date and time listed
ODP107 Oral Ulcerations, A Rare Side Effect of Intravenous Zoledronic Acid
Authors: Del Mar Morales Hernandez Maria , Ghayee Hans Kumar , Kadiyala Sushma , Xhikola Majlinda
Published: November 2022

Introduction

Zoledronic acid is an intravenous bisphosphonate known for its anti-resorptive effects and osteoporotic fracture risk reduction. A common adverse reaction with this medication is mild to moderate flu-like symptoms, which are transient and attributed to an acute phase reaction post treatment. A less common side effect, of oral ulcers is associated with oral bisphosphonates, attributed to incorrect oral intake but the real mechanism is still not well understood. We present a patient that developed oral ulcers after use of both oral and intravenous bisphosphonates, leading to suspicion of other underlying mechanisms other than incorrect oral intake of bisphosphonates.

Case Report

We present a 73 year old male with history of mild primary hyperparathyroidism and osteoporosis. Patient opted for medical management of his mild primary hyperparathyroidism in addition to having non-localizing studies. Treatment for osteoporosis was recommended due to femoral neck T score -2.4, FRAX score of 3.3% risk for hip fractures and history of low impact right foot fracture. The primary care team started treatment with alendronate 70 mg once a week, but patient developed oral blisters within a week of starting the treatment. Stopping alendronate led to resolution of the oral symptoms without any additional supportive treatment. Patient was later started on intravenous zoledronic acid, attributing the previous history of oral ulcers to a local effect of the oral bisphosphonates. Two days after the zoledronic acid infusion patient developed fatigue, fever, and oral ulcers. The oral ulcers were described as painful, located at the base and lateral aspects of the tongue. The ulcers later progressed to the buccal mucosa. No gingival ulcers were reported. Development of the oral blisters led to significant discomfort in eating and talking. Patient was treated with liquid nystatin 10,000 units/mL and lidocaine 2% viscous liquid. Patient had resolution of the painful ulcers approximately 2 weeks after the initial appearance. No recurrence of the oral ulcers has been reported, 4 months post treatment with zoledronic acid.

Discussion

Intuitively oral bisphosphonate induced mucosal injury is thought to be related to direct contact of the tablet with the oral mucosa or inappropriate ingestion of the medication and is not thought to be a systemic reaction. Our patient developed oral ulcers from both oral and intravenous bisphosphonates suggesting a possible systemic mechanism involved. Understanding potential side effects such as mucosal injury from intravenous bisphosphonates will be helpful for patient education and timely care.

Presentation: No date and time listed
ODP108 Palovarotene for the Treatment of Fibrodysplasia Ossificans Progressiva: Methodology of the Phase III Open-Label PIVOINE Rollover Trial
Authors: Artyomenko Alex , Houchard Aude
Published: November 2022

Objectives

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized byheterotopic ossification (HO) and progressive restriction of mobility. To date, no approved disease-modifying treatments for FOP exist, but interim phaseIII MOVE trial (NCT03312634) results suggest marked efficacy for palovarotene (PVO). 1 The PIVOINE rollover trial (NCT05027802) has been designed to allow treatment continuity and further evaluation of PVO safety and efficacy; the methodology is given here.

Methods

Patients will receive 5 mg PVO daily, or the parent study completion dose, for a maximum of 3 years; during flare-ups, patients will receive 20 mg daily for 4 weeks, then 10 mg daily for 8 weeks. Enrollment criteria: completion of a parent study (end of study/treatment visit of NCT03312634 or NCT02279095/NCT02979769), ≥14 years of age, full skeletal maturity if aged <18 or deemed to be final adult height. PIVOINE aims to enroll 61 patients; recruitment has not begun. The primary outcome will be the incidence and description of all treatment-emergent adverse events, collected continuously over the study period. Secondary outcomes (collected every 6 months; reported as raw values and change from the inclusion visit for outcomes specified by *) include: range of motion* (using Cumulative Analogue Joint Involvement Scale total score), the use of aids, assistive devices and adaptations*, physical function* (using adult form of the FOP-Physical Function Questionnaire; total score and upper extremities and mobility sub-scores), the frequency of healthcare utilization, and physical and mental health* (using Patient Reported Outcomes Measurement Information System Global Health Scale). Lung function will be assessed via observed and percentage predicted (PP) forced vital capacity (FVC)*, forced expiratory volume in 1 second (FEV 1)*, diffusion capacity of the lung for carbon monoxide*, and the absolute and PP FEV 1 /FVC ratio*. The number of investigator-reported flare-ups*, including duration and outcomes, will be reported along with the percentage of patients with new bone growth.

Results from PIVOINE, estimated to end in November 2024, will allow further evaluation of PVO in FOP.

References

1. Pignolo R et al. ASBMR 2020;35(Suppl 1): 16–17 Funding: Sponsored by Ipsen.

Presentation: No date and time listed
ODP111 PERSISTENT TERTIARY HYPERPARATHYROIDISM AFTER TOTAL PARATHYROIDECTOMY AND KIDNEY TRANSPLANTATION: THE CASE OF THE SUPERNUMERARY GLANDS
Authors: Grigorie Daniel , Sucaliuc Alina , Tacu Dorina
Published: November 2022

Secondary hyperparathyroidism in patients with kidney failure and hemodialysis usually resolves after total parathyroidectomy or kidney transplantation.

Case report

We report a case of a 53 year-old women polycystic kidney disease diagnosed at the age of 32, with end-stage renal disease and hemodialysis between 45-51 yrs. At the age of 50 she developed hypercalcemia (10.4-10.8 mg/dl) with very high PTH levels of 1100 pg/ml, and was referred forparathyroidectomy. Intraoperatively the four parathyroid glands were identified in canonical sites and a total parathyroidectomy was performed; postoperative total serum Calcium 8.9-9.6 mg/dl, PTH 510-680 pg/ml, suggesting the presence of a functional remnant parathyroid tissue. One year later she underwent kidney transplantation, immediate preoperative serum Calcium 10.4 mg/dl. 2 yrs later, she was referred to our clinic for hypercalcemia (11.8-12.5 mg/dl; increasing 5 mo post-transplant), high serum PTH 229-316 pg/ml) and low bone mass (lumbar spine T-score = -4.4 DS, femoral neck T-score = - 2.6 DS). She was asymptomatic and the biochemistries were: total serum calcium 12.8 mg/dl (11.8 mg/dl after hydration), serum PTH 228 pg/ml, hypophosphatemia 1.9 mg/dl, Alkaline Phosphatase 102 U/l, creatinine 1.13 mg/dl (0.85 mg/dl after hydration). 99m Tc-sestamibi SPECT-CT imaging revealed an ectopic hyperfunctional parathyroid gland above pulmonary artery bifurcation. Waiting for surgical decision, the patient was treated with denosumab 60 mg, lowering serum Calcium at 11 mg/dl at 1 mo, 11.5 mg/dl at 3 mo, PTH 511 pg/ml.

Conclusion

This case illustrates the needfor more accurate preoperative localization of abnormal parathyroid glands in patients with tertiary hyperparathyroidism besides the standard 4-gland exploration.

Presentation: No date and time listed