Hormone Excess Research Articles

ODP306 Diplopia as Presenting Manifestation of Acromegaly

Abstract Introduction Acromegaly is a chronic disorder characterized by excess growth hormone production, withclinical manifestations ranging from subtle signs to significant systemic complications. We describe a patient who presented with diplopia as initial symptom of acromegaly. Clinical case: A 72-year-old female patient was referred for diplopia. Upon questioning, she reported headache, muscle aches and heavy sweating. On physical assessment, she had coarse facial features, thickened tongue and hand enlargement. Orbital CT images revealed a mild to moderate symmetric enlargement of the extraocular muscle which spared myotendinous junction. MRI sella showed a 12 mm pituitary adenoma. The diagnosis of acromegaly was confirmed with high IGF-1 and oral glucose tolerance test. The patient underwent endoscopic debulking of the pituitary tumor and pathology showed a densely granulated GH producing adenoma. Upon follow up, she reported improvement of the diplopia which was completely corrected with prism glasses. Remission of acromegaly was confirmed biochemically and repeated MRI sella showed no residual tumor. Conclusion Acromegaly is the most likely cause of extraocular muscle enlargement with subsequent diplopia in this patient. Ocular manifestations in patients with acromegaly include visual field defect, excessive lacrimation, proptosis and double vision. This case adds to previous literature that diplopia could be the presenting manifestation of acromegaly. This is the first case reporting of improvement of diplopia following remission of acromegaly. Comprehensive ophthalmic assessment of patients presenting with eye symptoms and features suggestive of acromegaly is of value as it helps with early diagnosis as well as improving the outcome of this condition. Presentation: No date and time listed

PMON66 A Systematic Literature Review to Evaluate Extended Dosing Intervals in the Pharmacological Management of Acromegaly

Abstract Background Acromegaly is a rare, lifelong disorder characterized by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Extended dosing intervals (EDIs) of pharmacological treatments may reduce patient burden and costs compared with standard dosing. This systematic literature review (SLR) investigated outcomes in patients with acromegaly receiving treatment at EDIs. Methods MEDLINE/Embase/the Cochrane Library (2001–June 2021) and key congresses (2018–2021) were searched for relevant literature; identified SLR bibliographies were also reviewed. A dual reviewer process was utilized. Included publications reported clinical effectiveness, safety, humanistic, and economic outcomes in longitudinal/cross-sectional studies in adult patients with acromegaly. Interventions included EDIs of lanreotide autogel (LAN), octreotide long-acting release (OCT), and pasireotide (all administered less often than every four weeks), oral octreotide (less than twice daily), pegvisomant (PEG; less than once daily), and cabergoline (less than twice weekly), with no comparator required. PROSPERO 2021: CRD42021278922. Results In total, 35 publications reported on 27 studies: 14 on PEG, 9 on LAN, and 4 on OCT as monotherapies or combination therapies at EDIs. No identified studies assessed EDIs of oral octreotide, pasireotide, or cabergoline. At Baseline, disease control and treatment history differed across studies. As compared with Baseline, treatment at EDIs resulted in reduced IGF-1 levels in 12/16 studies assessing LAN, OCT, or PEG (7–104 patients treated at EDIs) and GH levels in 5/6 studies (LAN/OCT; 15–32 patients). Normalized IGF-1 and/or GH, using study definitions, was achieved/maintained in 70%–100% of patients in 12/13 studies (LAN/OCT/PEG; 15–124 patients). Proportions of patients experiencing adverse events (n=4 studies reporting overall events; LAN/OCT/PEG; 8–96 patients) or discontinuing treatment (n=9; LAN/OCT/PEG; 7–124 patients) were similar across EDI and standard regimens. Health-related quality of life (HRQoL) improvement from Baseline was reported in 9/10 studies after treatment at EDIs (LAN/OCT/PEG; 7–109 patients); HRQoL did not deteriorate versus standard regimens. Patients preferred EDIs (2/2 studies; LAN/OCT; 8–112 patients), and satisfaction with EDIs was high (2/2 studies; LAN/OCT; 13–109 patients). Substantially reduced costs were observed with EDIs versus standard regimens in 3/3 studies (9–23 patients) with LAN (120 mg every 6 versus 4 weeks), OCT (20–30 mg every 6–12 versus 4 weeks), and PEG (40–160 mg weekly versus 15–60 mg daily, both with LAN/OCT). Conclusion Clinical, safety, and HRQoL outcomes in patients with acromegaly were similar and costs lower with EDIs versus standard regimens. Satisfaction was high with EDIs. Limitations, including variation in study design and endpoints, and small, heterogenous patient populations, precluded conducting meta-analyses. Physicians should consider EDIs where appropriate. Further clinical research may substantiate reduced patient and healthcare system burden with EDIs versus standard regimens. Study funded by Ipsen. Medical writing support provided by Costello Medical. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP340 NOVEL THERAPY OSILODROSTAT AS AN OPTION FOR RECURRENT CUSHING'S DISEASE

Abstract Introduction Cushing's Disease (CD) denotes a pathologic endogenous hypercortisolism secondary to excessive adrenocorticotropic hormone (ACTH) production. Cushing Disease is a rare condition with an estimated incidence of approximately 1.2-1.4 new cases / 1. 000. 000 per year. Although surgical intervention is the gold standard in the management of CD, many patients may present persistence or recurrence of disease despite surgical intervention, resulting in significant deterioration of their quality of life (QoL). For those in whom pituitary surgery is not an option or has not been curative, medical therapies have been developed. One of these newer treatments is the drug Osilodrostat, an inhibitor of the enzyme 11-beta-hydroxylase, responsible for the final step of cortisol biosynthesis in the adrenal glands. Case Discussion Case of a 21 year-old female patient with history of Cushing's Disease status post-transsphenoidal surgery (TSS) in 2017, obesity and oligomenorrhea who presented to our clinics showing signs and symptoms of hypercortisolism despite previously documented post-surgical remission in 2017. Patient reported recent development of acne, weight gain, round face, elevated blood pressure and mood changes. At the moment of evaluation, her most recent MRI showed post-surgical changes without a discrete lesion. Work-up was compatible with recurrence of Cushing's with an ACTH at 75pg/mL (nl, 10-60pg/mL), urinary free cortisol (UFC) at 1,122mcg/24h (nl, 4-50mcg/24h) and serum morning cortisol at 24. 0mcg/dL (nl, 5-20mcg/dL). In view of a negative MRI for a pituitary lesion, a Bilateral Inferior Petrosal Sinus Sampling (BIPSS) was performed. The BIPSS procedure revealed a pituitary source with a right pituitary lateralization suggestive of a right ACTH-producing tumor. The patient was consulted to Neurosurgery Service, but while waiting for repeat surgery, control of hypercortisolism was needed. The patient was started on Osilodrostat 2mg twice a day and was able to achieve normalization of UFC to 4mcg/24h, serum morning cortisol 5mcg/dL and late-night salivary cortisol (LNSC) of 30ng/dl (<90ng/dL) with significant improvement in her QoL, depression and clinical manifestations. The patient tolerated therapy well. Conclusion Cushing's Disease is a complex condition with potential serious complications if untreated. Even though TSS is the first line therapy, approximately 25% of patients show persistence of disease, and a similar proportion may experience recurrence. When surgery fails, medical treatment such as Osilodrostat, can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations improving patients’ QoL while more definitive therapy is established. Presentation: No date and time listed

ODP097 Hyperparathyroidism as a major risk factor of fracture and its prevalence in patients with hip fracture

Abstract 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

RF19 | PSUN33 Adrenocortical Carcinoma as a Rare Manifestation of Birt-Hogg-Dubé Syndrome

Abstract Adrenocortical carcinoma (ACC) can occur as part of hereditary cancer syndromes, particularly Lynch syndrome and Li-Fraumeni syndrome. Here we describe 5 patients (3 women) with adrenal tumors and Birt-Hogg-Dubé syndrome (BHDS). BHDS is a hereditary tumor syndrome characterized by fibrofolliculomas/trichodiscomas, renal tumors, lung cysts, and spontaneous pneumothoraces. All five patients had a confirmed germline FLCN pathogenic variant. One case was previously reported by our institution. Age of diagnosis (AD) ranged from 36 to 62 years with a mean AD of 46 years. All patients identified as Caucasian. Three patients had non-functioning adrenal tumors, while the remaining two patients did not undergo biochemical assessment preoperatively but did not have symptoms or history of adrenal hormone excess. Histologically, four patients had confirmed ACC while one had an adrenocortical tumor of uncertain malignant potential, most consistent with an oncocytoma. All patients were initially treated with mitotane. Three patients developed metastatic disease requiring additional systemic chemotherapy, immunotherapy, and/or radiation. A total of 8 confirmed ACCs in patients with BHDS have been reported to date, raising suspicions that these tumors might be a part of the BHDS tumor spectrum. When BHDS patients are screened for renal malignancies, special attention should be paid to the adrenal glands. Adrenal nodules should undergo prompt assessment as >50% of reported cases developed metastatic disease. Given possible association with BHDS, testing for FLCN pathogenic variants should be considered during the genetic evaluation of patients with ACC. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m.

RF09 | PSUN05 Increased Frailty in Patients With Functioning Adrenal Adenomas

Abstract Introduction Frailty is characterized by multisystem function decline related to aging and can be measured using frailty Index (FI). FI is constructed based on the proportion of deficits present in an individual out of the total number of health variables considered. FI in various populations has been shown to predict adverse health outcomes. We aimed to determine the impact of hormone excess on frailty in a prospective cohort of patients with adrenal adenomas. Methods We conducted a multicenter prospective observational study of adult patients with adrenal adenomas and referent subjects without adrenal disorders (Jan 2019-Dec 2021). Adrenal adenomas comprised non-functioning adrenal adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS), defined as dexamethasone suppression test (DST)>1.8 mcg/dL, Cushing syndrome (CS), and primary aldosteronism (PA). FI was calculated as a sum of 47 variables (20 comorbidities, 13 symptoms, 14 activities of daily living) divided by 47.1 Frailty was defined as FI>0.25. In a subset of patients (n=176), functional measurements (handgrip strength, timed up and go test, gait speed) were performed and compared to FI. Results Of 233 patients (72.1% women), 71 were diagnosed with NFA (median age 64.5 years), 108 with MACS (median age 60.7 years), 11 with CS (median age 58.0 years), 46 with PA (median age 52.4 years), and 33 were referent subjects (median age 51.3 years). When compared to referent subjects, age- and sex-adjusted frailty prevalence was highest in CS (OR 29, 95%CI 4.3-202), followed by MACS (OR 16, 95%CI 3.5-73.7), and PA (OR 11.7, 95%CI 2.4-56), but not in patients with NFA (OR 5.1, 95%CI 0.99-25.8). Compared to patients with NFA, age- and sex-adjusted frailty prevalence was higher in CS (OR 5.8, 95%CI 1.4-24.4) and in MACS (OR 3.2, 95%CI 1.5-6.7), but not in PA (OR 2.3, 95%CI 0.9-6.1) group. Subgroup-analysis based on DST demonstrated a similar increase in age- and sex-adjusted frailty prevalence in patients with DST>5 mcg/dL (OR 3.1, 95%CI 1.2-8.2) and DST 1.9-5 mcg/dL (OR 3.3, 95%CI 1.5-7.4) when compared to patients with DST<1.8 mcg/dL. Higher FI was associated with lower handgrip measurement (P<0.0001), longer time during timed up and go test (P <0.0001), and decreased gait speed (P<0.0001). Conclusions Patients with functional adrenal adenomas are more likely to be frail. In patients with MACS, the prevalence of frailty was not associated with the degree of DST abnormality. FI correlated with currently validated but more cumbersome functional measurements and is a valuable tool that could be easily used in clinical practice and help individualize management decisions in patients with adrenal adenomas. 1 Singh S et al. Frailty in Patients With Mild Autonomous Cortisol Secretion is Higher Than in Patients with Nonfunctioning Adrenal Tumors. JCEM 2020 Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

OR29-2 Comprehensive Steroid and Global Metabolome Analysis by Mass Spectrometry and Machine Learning to Understand Metabolic Risk in Benign Adrenal Tumours With Mild Autonomous Cortisol Secretion

Abstract Background Benign adrenal tumours are found in 3-10% of adults and can be non-functioning (NFAT) or associated with adrenal hormone excess. Analysing 1305 prospectively recruited patients with benign adrenal tumours, we recently demonstrated that 45% of patients had mild autonomous cortisol secretion (MACS), i.e. biochemical evidence of cortisol excess without distinct signs of Cushing syndrome (CS). We found that MACS increases the prevalence and severity of type 2 diabetes and hypertension and primarily affects women (Ann Int Med. 2022 Doi: 10.7326/M21-1737). Here we analysed the cohort's steroid metabolome and non-targeted global metabolome to reveal underlying metabolic processes. Methods We analysed 24-h urine samples from 1305 patients (649 NFAT, 591 MACS, 65 CS) using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-steroid profiling assay. In addition, we performed non-targeted serum metabolome analysis in a representative sub-cohort (104 NFAT, 140 MACS, 47 CS) employing two complementary LC-MS assays, HILIC and C18-lipidomics. The steroid and global metabolome data were analysed by two supervised machine learning approaches, generalized matrix learning vector quantization and ordinal regression, to identify the most relevant metabolic changes. Findings Urine steroid metabolome analysis revealed an increase in glucocorticoid excretion from NFAT over MACS to CS, whereas androgen excretion decreased. Increased glucocorticoid metabolites were also the major differentiators between MACS patients with and without type 2 diabetes and hypertension, respectively. Lipidome analysis by machine learning identified glycerophospholipids, lysoglycerophospholipids, triacylglycerides, ceramides, sphingolipids, and acylcarnitines as the most relevant metabolite classes exhibiting gradually progressive changes with increasing cortisol excess (NFATInterpretation: We show a gradual change in the lipidome towards lipotoxicity with increasing cortisol excess. MACS patients with type 2 diabetes and hypertension had higher glucocorticoid output than other MACS patients, suggestive of a causative contribution of cortisol excess to their increased cardiometabolic burden. Observed changes may hold promise for risk stratification in MACS, a highly relevant and previously largely overlooked metabolic risk condition. Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.

OR12-4 Metabolic Profiling in Adrenal Tumors Demonstrates Enhanced Chronic Inflammation, Branched Chain Amino Acids and Ketone Bodies, Biomarkers that Predict High Cardiometabolic Risk

Abstract Background Patients with adrenal hormone excess demonstrate an increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal hormone excess on the metabolic profile that included plasma lipoproteins, total branched-chain amino acids (BCAA), ketone bodies, and GlycA (a proinflammatory glycoprotein biomarker). Method: We conducted a single-center cross-sectional study of consecutive patients with adrenal adenomas, Cushing syndrome (CS), and pheochromocytoma/paragangliomas (PPGL) between January 2015 and May 2021. Adrenal adenomas comprised nonfunctioning adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS), and primary aldosteronism (PA). Malignant and other benign tumors were excluded. Collected fasting plasma samples were measured using nuclear magnetic resonance spectroscopy for lipoproteins, BCCA, ketone bodies and GlycA. The results were compared to referent subjects from PREVEND (Prevention of Renal and Vascular End-stage Disease) study. Lipoprotein Insulin Resistance Index (LP-IR) which predicts incident diabetes was calculated based on 6 lipoprotein parameters. Results NFA (n=166, median age 60.1years, 63.3% women), MACS (n=158 (median age 61.8 years, 62. 0% women), CS (n=101, median age 43.8 years, 85.1% women), PA (n=71 (median age 55.8 years, 31. 0% women), PPGL (n=43, median age 55.5 years, 46.5% women) was diagnosed in 539 patients. Referent subjects (n=6540) were younger with a median age of 48.4, 50.2% women. When compared to referent subjects, and after age and sex-adjustment, GlycA was highest in patients with CS (OR 3.3, 95% CI 2.8-3.8), followed by PPGL (OR 2.3, 95%CI 1.8-2.9), MACS (OR 2, 95%CI 1.7-2.3), NFA (OR 1.9, 95%CI 1.7-2.2), and PA (OR 1.5, 95%CI 1.2-1.8). When compared to referent subjects, and after sex- and age adjustment, all patient groups demonstrated increase in BCAA: CS (OR 2.7 (95%CI 2.3-3.2), PPGL (OR 2.3, 95% CI 1.8-2.9), NFA (OR 2.4, 95% CI 2.1-2.7), PA (OR 2. 0, 95%CI 1.7-2.5), MACS (OR 2.2, 95% CI 1.7-2.6). Total ketone bodies were increased in patients with cortisol excess (OR of 1.4, 95%CI 1.2-1.5 in CS, and OR of 1.2, 95%CI 1-1.3 in MACS) and NFA (OR 1.2, 95%CI 1.1-1.3), but not in PA or PPGL. All patient groups except PPGL were more likely to have a higher LP-IR score. When compared to referent subjects, the highest sex- and age-adjusted LP-IR increase was in patients with CS (OR 1.9 (95%CI 1.5-2.2), followed by MACS (OR 1.4, 95% CI 1.2-1.7), PA (OR 1.4, 95%CI 1.1-1.8), and NFA (OR 1.4, 95% CI 1.2-1.7). Conclusion Patient with adrenal adenomas and PPGL demonstrate an increase in GlycA, BCAA, and ketone bodies - biomarkers associated with adverse cardiometabolic disorders and mortality. All patients except those with PPGL also demonstrated a higher LP-IR index that was reported to predict incident diabetes. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

ODP319 IGF-1 and BMI are Associated in Obese Patients with Acromegaly

Abstract Regulation of the growth hormone (GH) axis is complex and influenced by factors including age and nutritional status. Studies of individuals across the weight spectrum demonstrate an inverted U-shaped correlation between BMI and total IGF-1 levels; in both individuals with anorexia nervosa-range BMIs and those who are severely obese, total IGF-1 levels are low. Acromegaly is a disorder of the GH/IGF-1 axis characterized by IGF-1 excess secondary to autonomous GH secretion. The relationship between BMI and IGF-1 levels has not been well studied in acromegaly and whether the association between BMI and IGF-1 observed in non-acromegalic individuals is also present in acromegaly is not known. Patients who underwent endoscopic endonasal resection of pituitary adenomas at our institution between 1/2015-6/1/2021 were studied to investigate the association between BMI and preoperative IGF-1 in acromegaly. Ninety-nine patients were identified who either had evidence of preop biochemical hormone excess [elevated IGF-1 level and/or GH >1ng/ml following 75g oral glucose tolerance test] (n=40) or who had a clinically non-functioning, non-staining (NF) pituitary adenoma, or non-functioning GH-staining adenomas (n=59). We excluded anyone with a prior history of surgery/radiation, those on medical therapy (including somatostatin analogues, cabergoline), and those on oral contraceptives in the 3-months preceding surgery (n=8 in each group). Median age of acromegaly patients (n=32) was 39.5 years [29.3, 51.8], mean BMI was 30.2 +5.3 (SD) kg/m 2 (range: 20.9-40.4 kg/m 2) and 50% were female. Preoperative IGF-1 levels were measured using a clinically available assay. To control for differences in IGF-1 levels based on age/sex, we calculated % upper limit of normal (ULN) for IGF-1 based on age/sex determined normal ranges (mean %ULN IGF-1: 219.7+74.8%). In the acromegalic group, univariate analysis demonstrated a significant positive association between both BMI and IGF-1 (R=0.44, p=0. 01) as well as BMI and IGF-1%ULN (R=0.35, p=0. 047). In contrast, in the NF group (n=51 with 49% female and mean age: 56.4+16.7 years), there was no significant association between BMI (mean: 31.3+6.5 kg/m 2; range: 19.1-47 kg/m 2) and %ULN IGF-1 (median: 38.9% [26.8, 61.4]) (rho=0.15, p=0.30). However, in the subgroup of NF patients with severe obesity (BMI >35 kg/m 2; n=17), a significant inverse association between BMI and %ULN IGF-1 was observed (rho: -0.54; p=0. 03) . These data demonstrate that in contrast to the inverse relationship that is typically observed between total IGF-1 and BMI in obese individuals, which is preserved in a NF adenoma group, there is a significant positive association between %ULN IGF-1 and BMI in patients with acromegaly, including those with severe obesity. Further study is necessary to determine whether obese patients with acromegaly exhibit more severe symptoms related to their disease due to this positive association between BMI and IGF-1 or whether obesity is a secondary effect of their acromegaly. Presentation: No date and time listed

ODP050 Oncocytic Adrenocortical Carcinoma Presenting with Hematuria

Abstract Introduction Adrenocortical carcinoma (ACC) is rare and aggressive endocrine tumor. It is commonly noticed due to symptoms of hormone excess, mass-effect, or incidentalomas. Different histological variants are noted, which include: oncocytic, myxoid, sarcomatoid, and the conventional subtype. The oncocytic variant is usually seen on the left side, and usually presents with symptoms of mass-effect. Only around 17% were noted to be functional. We present an interesting case of ACC (oncocytic type) which presented with hematuria. Case Presentation 70-year-old female with a history of morbid obesity, hypertension, anxiety, GERD, tubular adenoma, hyperlipidemia, and lumbar radiculopathy came in to see her primary care for hematuria and back pain. She has a long-standing history of back pain, for which she has had an EMG, which showed mild axonal polyneuropathy and bilateral L5 radiculopathy. Apart from hematuria, she denies any other urinary complaints. Additionally, she denied any fever, chills, nausea, abdominal pain, sweating, tremor, headache, palpitations, easy bruising, fractures, muscle weakness, hirsutism, or changes in her weight. She has a family history of pancreatic cancer and is currently retired, and denies alcohol, tobacco, or recreational drug use. A KUB X-ray was ordered which showed calcification in the left upper quadrant, concerning for a splenic artery aneurysm; this led to a CTA abdomen, which showed a large 7.2 cm heterogenous enhancing solid left adrenal mass, concerning for primary adrenal carcinoma, which was new compared to imaging 2 years ago. Also seen was a 0.7 cm enhancing right hepatic lobe lesion, along with a 1.5 cm splenic artery aneurysm. Following this, an abdomen MRI with contrast showed a 7×7×7 cm solid heterogeneously enhancing left upper quadrant mass beside the left adrenal gland and pancreas. Subsequently, a CT guided needle biopsy was done, which revealed scant adrenal tissue. PET scan showed a hypermetabolic mass, arising from the left adrenal, consistent with adrenal carcinoma. At this point, an endocrinology referral was placed, and other lab work including 24-hour urine free cortisol, DHEA-S, 24-hour urine metanephrine, and aldosterone/renin ratio was done. DHEA-S level was elevated at 264 mcg/dl (12-133). She was then transferred to a tertiary care facility, where she underwent a left adrenalectomy, para-aortic lymphadenectomy, nephrectomy, splenectomy, and distal pancreatectomy. Pathology confirmed adrenal cortical carcinoma (oncocytic type), with negative margins, Ki-67 labelling index of 25%, and no lymphovascular invasion, pT2pNO. She was then discharged home with visiting nurses. Conclusion Oncocytic ACC is an infrequent tumor, which presents with symptoms of mass effect, and definitive diagnosis requires histopathological assessment. The Lin–Weiss–Bisceglia (LWB) system and Helsinki score help establish malignant potential. Fortunately, it has a decreased tendency to metastasize and a better prognosis than other ACC subtypes. Further studies to understand oncocytic ACC are needed. Presentation: No date and time listed

PMON99 A Rare Case of an Intrasellar Epidermoid Cyst And Panhypopituitarism

Abstract Introduction Epidermoid cysts are rare intracranially occurring mainly in subarachnoid spaces such as parasellar cisterns, middle fossa and cerebellopontine angle. Only few cases of infundibular/sellar epidermoid cysts have been described. We present the case of a large sellar epidermoid cyst resulting in panhypopituitarism. Case 49 year old male with history of obesity and hypertension presented to the emergency department with acute onset progressively worsening headaches. He denied vision changes, nausea, vomiting or dizziness. Examination showed stable vital signs and ophthalmologic exam did not reveal any visual deficits. Further, he did not have any signs of pituitary hormone excess including hypercortisolemia or acromegaly. Brain MRI with and without IV contrast revealed a peripherally enhancing multilobulated cystic pituitary mass measuring 19.5 mm×17 mm×20.5 mm deviating the infundibulum to the left causing compression of the caudal aspect of the optic chiasm. Initial endocrinology work-up revealed noon time cortisol of 10.7 mcg/dL (range 7-23), 7 pm ACTH of 34.6 pg/mL (range 7.2-63.3), TSH of 1.71 mIU/mL (range 0.35- 4.94), free T4 of 0.93 ng/dL (range 0.5-1.39), FSH of 4.45 mIU/mL (range 1.27-19.26), LH 5.51 mIU/mL (range 1.24-8.62), IGF-1 level of 199 ng/mL (range 68-225), prolactin <0.60 ng/mL (range 2.64-13.13), and testosterone level of 186 ng/dL (range 175-800). A presumed diagnosis of non- functioning pituitary macroadenoma with compression of chiasm was made and he underwent transsphenoidal hypophysectomy after evaluation by a multi-disciplinary team including neurosurgery, ENT and endocrinology. Post-operative course was uneventful, he was started on empiric steroids which were tapered slowly. Final pathology of surgical specimen demonstrated epidermoid cyst, focal necrosis, lymphocytes and macrophages infiltration consistent with reactive granulation tissue. On subsequent laboratory evaluation, he was found to have hypogonadotropic hypogonadism with an undetectable testosterone. FT4 was also low at 0.61 ng/dL (range 0.5-1.39). He is closely following with endocrinology for management of hypogonadotropic hypogonadism and hypothyroidism. Conclusion Intracranial epidermoid cysts are uncommon benign congenital lesions arising from trapped surface of ectodermal elements. Very rarely, they are found in the sellar region. Sellar epidermoid cysts tend to present late and often after significant growth and mass effects. Complete resection is challenging and recurrence is a feared complication. Our patient presented with acute symptoms from expansion of a large epidermoid sellar cyst mimicking a pituitary macroadenoma. It also resulted in hypopituitarism. Although, a rare entity, early recognition and prompt management of such lesions is key. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

LBSAT141 Bone Health In Patients With Adrenal Disorders

Abstract Introduction Limited data suggest low bone density in patients with adrenal adenomas. However, most studies are retrospective, single-center, and none were conducted in the United States. We aimed to determine the impact of cortisol and aldosterone excess on bone density. Methods We conducted a preliminary analysis of data from our multicenter, prospective observational study of adult patients with adrenocortical hormone excess and referent subjects without adrenal disorders (January 2019 - March 2022). Patients were diagnosed with non-functioning adenomas (NFA), adenomas with mild autonomous cortisol secretion, MACS (defined as cortisol following an overnight 1-mg dexamethasone suppression test (DST)>1.8 mcg/dL), adrenal or pituitary Cushing syndrome (CS), primary aldosteronism (PA), and concomitant PA-MACS. Referent subjects were patients undergoing cross-sectional imaging for reasons other than adrenal disease. All participants were interviewed about their bone health, and had bone density measurements at the spine, hips, and/or radius. Bone disease was defined as osteopenia (T-score -1.1 to -2.4), or osteoporosis (T-score < -2.5). Results A total of 417 participants included 156 referent subjects (88, 56% women, median age 65, range 2-95 years) and 261 patients (190, 73% women, median age 59, range 21-88 years). Patients were diagnosed with NFA (51, 19%), PA (46, 17%), MACS (122, 47%), PA-MACS (12, 5%), and CS (30,12%). When compared to referent subjects, sex- and age-adjusted analysis demonstrated an increased prevalence of bone disease only in patients with CS (OR 4.8, 95%CI 1.7-13), but not in other adrenal disorders. After excluding patients with CS, those with post-DST cortisol >5 mcg/dL demonstrated a higher prevalence of bone disease when compared to patients with post-DST cortisol between 1.8-5 mcg/dL (OR 2.8, 95%CI 1.2-6.5) and those with post-DST cortisol <1.8 mcg/dL (OR 2.7, 95% CI 1.1-6.7). Patients with MACS and post-DST cortisol between 1.8-5 mcg/dL did not demonstrate increased sex and age-adjusted prevalence of bone disease compared to those with post-DST <1.8 mcg/dL or referent subjects. However, using post-DST cortisol as a continuous variable, we found that after adjusting for sex and age, the risk of bone disease in patients increased by 13% (OR 1.13, 95%CI 1.6-1.2) for every 1 mcg/dL increase in post-DST cortisol. Conclusions The prevalence of osteopenia and osteoporosis increases proportional to the increase in post-DST cortisol concentrations. Patients with CS, and those with MACS and post-DST cortisol > 5mcg/dL have the highest prevalence of bone disease. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP345 Pituitary Metastasis from Clear Cell Renal Cell Carcinoma

Abstract A 63-year-old female presented with a two month history of intermittent diplopia and headaches. Her past medical history was relevant for renal carcinoma status post right nephrectomy four years prior, she did not receive any adjuvant therapy. She underwent MRI brain which showed a 2.1×2. 0×1.6 cm sellar/suprasellar enhancing mass with mass effect on the optic chiasm and extending into the right cavernous sinus, consistent with pituitary macroadenoma. Visual field testing was also done showing mild bitemporal quadrantanopia. Lab evaluation did not show evidence of pituitary hormone excess or deficiency. Serum sodium was normal, IGF-1 117 ng/ml (reference range 35-201 ng/ml), GH 0.19 ng/ml (0. 01 -3.61 ng/ml), alpha subunit 0.4 ng/ml (<1.8 in postmenopausal females), ACTH 15 pg/ml (7-63 pg/ml), prolactin 20.8 ng/ml (3.3 -26.7 ng/ml), TSH 2.36 MCU/ml (0.35-5 MCU/ml) and FT4 0.9 ng/dl (0.6 -1.6 ng/dl). Neurosurgery evaluated the patient and she underwent transsphenoidal surgery. Her postoperative period was unremarkable without evidence of diabetes insipidus or secondary adrenal insufficiency. Final pathology revealed clear cell lesion/carcinoma consistent with metastatic renal cell carcinoma. Transcription marker testing was positive for SF1, consistent with a gonadotroph pituitary adenoma. Presentation: No date and time listed

PSAT009 Cushing's Syndrome Developing 42 Years After Successful Treatment for Metastatic Adrenocortical Carcinoma

Abstract Introduction ACC is a rare malignancy with poor prognosis. ACC is associated with CS in about 10% of the cases. Herein we report a case of a patient with metastatic ACC who developed contralateral functional adrenal adenoma causing Cushing's syndrome 42 years later. Clinical Case A 72-year-old female presented for evaluation of right adrenal incidentaloma, measuring 4.4×3 cm, on CT abdomen and pelvis (CTAP), done as part of the evaluation for hip pain. In addition to the adrenal incidentaloma, a large left adnexal mass (8×7 cm) was also observed. Her past medical history was significant for left adrenal ACC diagnosed at the age of 30, The patient's initial presentation included virilization and menstrual abnormalities. Laboratory evaluation revealed hyperandrogenism and hypercortisolism. There was no evidence of metastatic disease, and the patient was managed surgically (total left adrenalectomy) with normalization of laboratory abnormalities and resolution of symptoms. Four years later, patient pulmonary metastasis were observed in a surveillance scan and the patient underwent wedge resection and chemotherapy. The patient did not have any evidence of recurrent disease thereafter. At the current presentation, there were no symptoms or signs of adrenal hormone excess. Hormonal workup revealed borderline elevation of plasma metanephrines, with normal 24 h urinary metanephrines and catecholamines. DHEA-S and testosterone levels, as well as other androgens, were normal. 1 mg dexamethasone suppression (DST) was abnormal, with cortisol of 5.5 mcg/dL 8 h after dexamethasone administration (normal <1.8 mcg/dL). High dose DST was repeatedly abnormal, with cortisol levels at 4.0 and 4.4 mcg/dL (normal <1.8 mcg/dL). AM cortisol was elevated, at 23.4 mcg/dL (normal 4-22 mcg/dL) with ACTH at 12 pg/mL (normal <45 pg/dL). 24 h urinary free cortisol (UFC) was repeatedly elevated at 123.2 and 83.8 mcg/d (normal <45.0 mcg/d). CA 125 was normal. As there are case reports of ectopic Cushing's syndrome related to ovarian malignancies, and the patient had a large adnexal mass, adrenal and ovarian vein sampling was performed. Cortisol levels were higher in the right adrenal vein compared to the periphery, and the gradient was normal for the left ovarian vein. The right ovary was not visualized, and it was not possible to catheterize the right ovarian vein. Whole body FDG scan revealed intermediate uptake by right adrenal mass and normal uptake by left adnexal mass. Based on these results, it was determined that the right adrenal was the source of excess cortisol, and the patient underwent laparoscopic right adrenalectomy. Pathology evaluation showed adrenal adenoma, without evidence of ACC. The patient was started on physiologic replacement doses of hydrocortisone and fludrocortisone. The patient has been doing very well clinically. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP550 Giant Cell Tumor of Bone: A Diagnostic Consideration of Sellar Lesions

Abstract Background Giant cell tumor of bone (GCTB) is a skeletal neoplasm that most commonly occurs in long bones and rarely in the skull. These tumors are considered benign but tend to be locally aggressive and carry a high rate of local recurrence. True malignant transformation is rare and even metastatic disease carries a rather benign course. Clinical manifestations depend on tumor location and are mostly due to mass effect into the surrounding tissues. We describe a patient with a GCTB, located at the sellar-suprasellar region which resulted in optic chiasm compression and panhypopituitarism. Clinical Case Case of a 28-years-old female who initially presented with recurrent headaches for which brain imaging was done and a suprasellar mass was noted. It initially measured2.3x 3.2x 2. 0 cm. The mass was invading the left cavernous sinus and displacing the pituitary gland and infundibulum to the right. At that time no optic chiasm compression was noted, and no pituitary hormonal excess or deficiency was identified. The mass was treated conservatively with gamma knife radiation, with reduction in size. About 10 months later, patient complained of visual problems for which brain imaging was repeated and noted with interval increase in tumor size. Patient was started on dexamethasone due to mass effect and referred to ER. Review of systems at that time was remarkable for oligomenorrhea and decreased peripheral vision. Patient denied general malaise, dizziness, galactorrhea, weight changes, palpitations, dry skin or striae, bowel changes, polyuria, increased thirst nor changes in shoe or ring size. Physical examination showed unremarkable vital signs. Upon confrontation there was evidence of bitemporal hemianopsia confirmed on formal visual field testing. Laboratory studies showed mildly elevated prolactin, low-normal TSH with mildly low FT4 suggesting overt central hypothyroidism and suppressed morning cortisol. Patient was scheduled for craniotomy, which resulted in an overall decrease of tumor bulk. After the surgery, patient developed DI requiring desmopressin administration. Currently, patient continues with panhypopituitarism treated with hormonal replacement. Pathology report was compatible with a GCTB. On follow up MRI about 6 months after surgery, there was mild interval increase in size, no distant metastases identified. Treatment with denosumab was started as recommended by oncology service in an attempt to control tumor growth. At this time, patient has tolerated denosumab well and has not developed further headaches or visual symptoms. Follow up imaging is pending to assess response to treatment. Conclusion GCTB of the sella-suprasellar region, albeit rare, have been described and always should be included in the differential diagnosis of sellar lesions. Imaging alone is insufficient to make a definitive diagnosis of these tumors and tissue sampling either by biopsy or surgical resection should be considered in order to determine treatment alternatives. Presentation: No date and time listed

ODP445 If You Can't Beat Them, Join Them: A Therapeutic Strategy for Maintaining Euthyroidism in Non-Compliant Patients

Abstract Levothyroxine (LT4) has been the mainstay therapy for hypothyroidism since synthesized in 1949, and it was depicted to be a daily, usually lifelong, therapy. LT4 may have many interactions with other medications, food, and supplements, for which it should also be taken on an empty stomach, at least thirty minutes before consuming any other product, to achieve adequate absorption. These two characteristics of LT4 therapy are two of the main reasons for patient non-compliance, leading to uncontrolled hypothyroid state shown by abnormal thyroid stimulating hormone (TSH) levels, and associated symptoms. LT4 properties, such as seven-day half-life, as well as increased peripheral conversion to metabolically active T3 by local deiodinase enzyme when there are low T4 levels, provide a scenario where it can be used at longer dosing intervals than the traditional daily dosing. This is the case of a 27-year-old female with past medical history of hypothyroidism on daily replacement therapy with 50mcg of branded LT4, presenting to the endocrinologist for continuation of care. Over the course of visits, patient showed uncontrolled thyroid disease with altered levels of TSH, ranging from 5.4 uIU/mL up to 46.8 uIU/mL (N: 0.45-5. 0 uIU/mL), despite appropriate dose adjustments and frequent TSH and free T4 (FT4) monitoring. Due to persistent clinical and biochemical hypothyroidism requiring dosage increases up to 300mcg, patient was referred for a thyroxine absorption test to rule out LT4 malabsorption versus medication non-compliance. A supervised dose of 812mcg of the same branded LT4 was provided, based on body weight, and TSH, free T3, and free T4 levels were measured before administration and sequentially at 30, 45, 60, 90, 120, 240, and 360 minutes after dose, yielding TSH values ranging from 0.11 uIU/mL to 0.18 uIU/mL, consistent with adequate TSH suppression. Patient admitted to erratic medication ingestion for which a dose of 150 mcg LT4 orally daily was started. TSH levels remained above 9. 0 uIU/mL, for which a trial of complete weekly dosage was offered and accepted by patient. Two months after therapeutic adjustment, patient became both clinically and biochemically euthyroid, with TSH level of 1.35 uIU/mL without any adverse effects from excess hormone intake. Medication non-compliance is an issue every physician must battle with. This case serves as an example of the great impact of individualized modification of LT4 administration to establish a therapeutic regimen that adjusts to each patient's lifestyle while allowing them to remain clinically stable, which is a great benefit for both the patient and the clinician. Although studies already exist in proving the benefits of weekly versus daily therapy in such patients without major risks, further investigation should be conducted, as therapeutic guidelines could potentially change altogether in the future to avoid, or at least reduce, non-compliance consequences. Presentation: No date and time listed

PMON104 Sellar Gangliocytoma-Pituitary Neuroendocrine Tumor (PitNET) Presenting As Acromegaly

Abstract Growth hormone (GH)-secreting pituitary neuroendocrine tumors (PitNET) arising from somatotrophs is the most common cause of acromegaly. It may rarely develop in the setting of a growth hormone-secreting PitNET associated with a neuronal tumor composed of neoplastic ganglion cells, the so-called mixed gangliocytoma somatotroph PitNET. We present a case of acromegaly which proved to be due to a mixed gangliocytoma somatotroph PitNET on pathology.A 58-year-old, healthy woman presented to the ER with a 3-day history of left-sided vision loss and worsening headache. MRI revealed 4.5×4.2×3.8 cm heterogeneously enhancing bilobed mass consistent with a pituitary PitNET with suprasellar extension causing compression of the optic chiasm, invasion into the left cavernous sinus and partial encasement of the left internal carotid artery. She had coarse facial features, wide feet, multiple skin tags, and a history of multiple colonic polyps. Biochemical work up revealed an IGF-I of 664 ng/ml (50-317), AM cortisol 19.7 mg/dl, ACTH 30 pg/ml, prolactin 15.5 ng/ml, FSH 35.6 mIU/ml, LH 11.3 mIU/ml, and FT4 0.7 ng/dl (0.70-1.48). She underwent endoscopic transsphenoidal resection of the tumor. Histopathology demonstrated mature ganglion cells with neuropil-like areas, intermixed with small cell components. The neuronal population was immunopositive for NeuN (Neuronal nuclei antibody), synaptophysin, and NF (Neurofilament). PitNET cells were positive for GH, prolactin, Pit- 1 transcription factor and the somatostatin 5 receptor, histological features consistent with mixed gangliocytoma and sparsely granulated somatotroph pitNET. Some ganglion cells also showed weak immunostaining with Pit-1. A 3-month follow-up MRI showed a residual 3 cm lesion. IGF-I improved but was still elevated at 456 ng/ml associated with a GH 2.9 ng/ml. Medical treatment with pasireotide was recommended, but the patient temporarily declined further treatment to explore other options with her Naturopath.Gangliocytomas are a rare, benign, slow-growing, differentiated form of neuroblastic tumors of sympathetic nerve fibers, largely extracranial and rarely present in the sellar region, most frequently in association with a PitNET, forming the so-called mixed gangliocytoma PitNET. Definitive diagnosis is established by histological and immunohistochemical studies. Though PitNET components of mixed gangliocytoma PitNET are known to frequently secrete an excess hormone, the ganglionic components also show immunoreactivity for hypothalamic releasing hormones along with other neuroendocrine markers. The histological origin of these mixed tumors is controversial, but the small population of ganglionic cells that express the acidophilic lineage transcription factor, Pit-1, favors the theory of transdedifferentiation of neuroendocrine cells into neuronal elements. Treatment of mixed gangliocytoma- PitNET is similar to other PitNETs and the presence of neural components does not modify aggressiveness or risk of recurrence after surgical resection, as gangliocytomas have a low proliferative index. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Targeted treatment with somatostatin analogues: widening horizons of clinical practice

Targeted treatment with somatostatin analogues (SA) in acromegaly and neuroendocrine neoplasms may have some benefits compared to curative treatments, because these agents decrease excessive hormone secretion and exert a tumor-suppressive effect. Monotherapy and combination therapy with SA is well tolerated and bears no risk of debilitating iatrogenic complications. In acromegaly caused by somatotropin producing pituitary tumor, first generation SA are treatment of choice after non-radical adenomectomy, as well as in the cases when patients reject surgery. Treatment efficacy depends on the pathomorphological types of somatotropic tumors, which are different in their receptor phenotype, clinical scenario and proliferative activity. The first generation SA are successfully used for medical treatment of other pituitary tumors (thyrotropic, corticotropic, gonadotropic, lactotropic with resistance to dopamine agonists), as well as for adjuvant therapy of neuroendocrine and non-endocrine neoplasms and elimination of various gastrointestinal disorders. The anti-secretory and anti-tumor effects of SA have been proven for gastroenteropancreatic tumors (carcinoid syndrome, vipomas, gastrinomas, insulinomas, glucagonomas, somatostatinomas). Targeted selection of patients for treatment with first generation SA based on the receptor phenotypes of malignant cells would facilitate more rapid achievement of biochemical remission, improvement of quality of life and survival.

Activation of persulfate by vanadium oxide modified carbon nanotube for 17β-estradiol degradation in soil: Mechanism, application and ecotoxicity assessment

Steroid hormones in the environment have attracted public attention because of their high endocrine-disrupting activity even at rather low exposure level. Excessive hormones in the soil from the pollutant discharge of intensive farming would pose a potential threat to the ecology and the human health. Vanadium oxide modified carbon nanotube (VOX-CNT) was synthesized and applied as persulfate (PDS) activator to reduce17β-estrogen (17β-E2) in soil. 86.06 % 17β-E2 could be degraded within 12 h. Process of materials exchange during oxidation was interfered by soil, resulting in insufficient degradation of 17β-E2, but the active species involved in 17β-E2 degradation would also be enriched by it. 17β-E2 was adsorbed on the VOX-CNT surface and directly degraded mainly by the active species generated on the catalyst surface, and •OH dominated the degradation of 17β-E2 in VOX-CNT/PDS system. CO, defective sites and vanadium oxides on the surface of VOX-CNT contributed to the generation of activate species. Oxidizer dosage, catalyst dosage, water-soil ratio and soil properties would affect the degradation of 17β-E2. The ecotoxicological impact on soil caused by VOX-CNT/PDS was acceptable, and would be weakened with time. Additionally, a rapid decrease in the concentration of 17β-E2 and the promotion of maize growth were observed with VOX-CNT/PDS in situ pilot-scale remediation. Those results reveal that VOX-CNT/PDS is a potential technology to remove excessive steroid hormone from soil around large-scale livestock and poultry farms.

Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis?

Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. Mean frontal bone thickness was 6.75mm in acromegaly, 4.85mm in group 1, and 5.1mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.