Endocrine Society Clinical Practice Guideline Research Articles

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D.Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

The Association of Free Testosterone with Sarcopenic Obesity in Community-Dwelling Older Men: A Cross-Sectional Study.

Background and Objectives: Sarcopenic obesity, a clinical condition coexisting with obesity and sarcopenia, is associated with a high risk of functional impairment, reduced quality of life, and increased mortality. A decline in age-related free testosterone (FT) levels has been reported to be associated with decreased muscle mass and muscle strength and increased fat mass. However, the association between low FT levels and risk of sarcopenic obesity has not been well studied. This study aimed to investigate the direct association between low FT levels and sarcopenic obesity. Materials and Methods: This cross-sectional study used data of 982 community-dwelling men aged 70-84 years from the Korean Frailty and Aging Cohort Study. Sarcopenia was defined according to the criteria of the Asian Group for Sarcopenia (AWGS) 2019. Obesity was defined as a body fat mass ≥28.3%. Participants who met both sarcopenia and obesity criteria were defined as having sarcopenic obesity. Low FT levels were defined as FT levels <17.35 pmol/L according to the Endocrine Society Clinical Practice Guidelines. Results: The prevalence of sarcopenia, obesity, and sarcopenic obesity was significantly higher in the low-FT group than in the normal-FT group. Low FT levels were significantly associated with a higher risk of obesity (odds ratio [OR], 2.09, 95% confidence interval [CI], 1.11-3.92), sarcopenia (2.57, 95% CI 1.08-6.10), and sarcopenic obesity (3.66, 95% CI 1.58-8.47) compared with the healthy control group. The risk of low appendicular skeletal muscle mass index (ASMI) (1.78, 95% CI 1.04-3.02) and high fat mass (1.92, 95% CI 1.12-3.31) was significantly higher in the low-FT group than in the normal-FT group. Conclusions: This study showed that low FT levels were associated with a higher risk of sarcopenic obesity. Low FT levels were mainly related to body composition parameters such as low ASMI and high fat mass.

THU624 Opioid Induced Adrenal Insufficiency (OIAI) Presenting With Altered Mental Status

Abstract Disclosure: D. Bondarenko: None. M. Ahmad: None. G.A. McGrath: None. Background: Opioid suppression of the hypothalamic-pituitary-adrenal (HPA) axis via inhibition of corticotropin releasing hormone secretion leading to secondary adrenal insufficiency (AI) has been described in literature. Biochemical secondary AI is evident in 6-50% of patients on chronic opioids; fewer cases are reported presenting with clinical AI.1 We present a rare case of symptomatic opioid-induced AI (OIAI) with clinical improvement on initiation of hydrocortisone. Clinical Case: A 49-year-old female on daily buprenorphine (20 mg) and naltrexone (5 mg) presented to the hospital with syncope and hypotension (79/49 mmHg). AM cortisol was 6.2 mcg/dL, a cosyntropin stimulation test was performed, but there was technical difficulty with the results. She was started on midodrine 2.5 mg three times daily and referred to outpatient endocrinology for follow up. Weeks later, outpatient cosyntropin stimulation test showed baseline cortisol of 18 mcg/dL with increase to 26 mcg/dL. Simultaneous adrenocorticotrophic hormone (ACTH) was 16.9 pg/mL. AI was ruled out. Seven years later she presented with acute lethargy, confusion, and memory loss over several days. AM cortisol was 1.6 mcg/dL and cosyntropin stimulation test increased cortisol to 15.1 mcg/dL (normal response being 18 mcg/dL or greater). ACTH was 24 pg/mL. The abnormal cosyntropin stimulation test results are consistent with AI, and lack of elevation of morning ACTH is consistent with secondary AI.2 Hydrocortisone therapy was started and midodrine was held due to elevated blood pressure after initiation of steroids. She was discharged on hydrocortisone 15 mg each morning and 5 mg each afternoon. Within 10 days of initiation of glucocorticoid replacement therapy her neurologic symptoms improved and midodrine discontinued. Prescription Drug Monitoring Program (PDMP) review shows reduction of buprenorphine (16 mg) and naltrexone (4 mg). Conclusion: Data on management of OIAI and recovery of the HPA axis with or without cessation of opioid therapy is limited. This case highlights that opioids should be considered as a potential cause of secondary AI. Further follow-up of this case and other OIAI cases would provide insight into management of opioid therapy, continuation of glucocorticoid therapy, and recovery of HPA axis. This data could provide basis for OIAI management recommendations. Reference: (1) Fountas, A., Prof, S.V.U., Karavitaki, N. Opioid-induced endocrinopathies. Lancet Diabetes Endocrinol. 2020;8(1);68-80. (2) Bornstein, S.R., Allolio, B., Arlt, W., et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocr. 2016;101(2);364-389. Presentation: Thursday, June 15, 2023

FRI416 Primary Hyperaldosteronism in Pregnancy

Abstract Disclosure: S.M. Seav: None. M. Basina: None. Background: Primary hyperaldosteronism is extremely rare in pregnancy. Since 1962, only approximately 30 cases have been reported in the literature.1 Clinical Case: A 40-year-old female was referred for work-up of primary hyperaldosteronism (PHA). She was first diagnosed with hypertension (HTN) at age 29 during her first pregnancy. Laboratory work-up was consistent with PHA: serum aldosterone 22.6 ng/dL, renin activity 0.1 ng/mL/hr, aldosterone:renin ratio of 226. Post-saline infusion aldosterone level was 10.7 ng/dL. Adrenal CT scan showed a 6mm left-sided adenoma. Surgery was not recommended because adrenal vein sampling did not show lateralization. She was started on Spironolactone 25 mg/day. Despite the significant pregnancy risks, patient continued to desire conception and was switched to Labetolol. She was lost to follow-up and returned to the emergency room for dizziness at 26 weeks pregnant with twins with BP 180/109 mmHg. She had not been taking any anti-hypertensives and there was evidence of severe fetal growth restriction in both babies. After a goals of care discussion, patient deferred emergent C-section and suffered intrauterine fetal demise on hospital day 9. Conclusion: PHA in pregnancy is rare and difficult to diagnose and manage. Newer studies estimate that &amp;gt; 5-10% of patients with HTN have PHA.2 Hence, maintaining high vigilance of this disease in pregnant patients is even more imperative, including screening for PHA during pre-conception period in hypertensive women. A systematic review of 38 cases of PHA in pregnancy showed that 19% of cases were diagnosed with HTN prior to pregnancy without PHA screening.1 The average age of women in this study was 29.8 years. Additionally, there is a correlation in women with younger age at diagnosis and having unilateral PHA, in which case adrenalectomy should be performed prior to conception.3 In pregnancy, first line anti-hypertensive therapies include alpha methyl dopa, labetolol, and nifedipine. In PHA, diuretics such as amiloride and mineralocorticoid receptors should also be considered if BP is not at goal. Spironolactone and eplerenone have been safely used in pregnancy with both male and female fetuses.1,4 If surgery is not an option and medical therapy is ineffective, then physicians should have a low threshold to admit patients for close BP monitoring. 1Landau, et al. Primary Aldosteronism and Pregnancy. Annales d’Endocrinologie. 2016;77:148–160 2Funder, et al. Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(5):1889–1916 3Akasaka, et al. Sex Difference in the Association Between Subtype Distribution and Age at Diagnosis in Patients With Primary Aldosteronism. Hypertension. 2019;74(2):368-374 4Cabassi, et al. Eplerenone Use in Primary Aldosteronism in Pregnancy. Hypertension. 2012;59:e18-e19 Presentation: Friday, June 16, 2023

THU400 Parameters Of Vitamin D Metabolism, Calcium And Phosphate Homeostasis In Patients Undergoing Bariatric Surgery

Abstract Disclosure: A. Zhukov: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). A. Povaliaeva: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). Z. Abilov: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). L. Usoltseva: None. D. Trukhina: None. E. Pigarova: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). L. Rozhinskaya: Grant Recipient; Self; Russian Science Foundation (project 19-15-00243-P). Objective: to evaluate the parameters of vitamin D metabolism and calcium and phosphate homeostasis in patients undergoing bariatric surgery. Materials and Methods: The study included 10 patients without chronic kidney disease and mineral metabolism disorders who underwent laparoscopic gastric bypass surgery for obesity. After surgery, all patients were recommended to take cholecalciferol depending on the initial level of 25-OH D in blood in accordance with the Endocrine Society Clinical Practice Guideline. Ninety nine [96; 130] days after the surgery, the levels of vitamin D metabolites: D3, 25-OH D3, 24,25-OH2 D3, 1,25-OH2 D3 were determined by ultra-high performance liquid chromatography in combination with tandem mass spectrometry (certified by DEQAS) as well as the PTH, total calcium, albumin, creatinine, phosphorus, magnesium levels in serum. Results: Median age of the patients was 39 [34; 50] years, 80% women, 90% initially had type 2 diabetes mellitus (BMI before surgery 49.1 [39.7; 51.0] kg/m2, median decrease in BMI by the time of inclusion in the study 8.3 [8.0; 9.2] kg/m2). The median level of 25-OH D3 was 28.5 [24.6; 32.0] ng/ml (1 patient had a level less than 20 ng/ml, 6 patients from 20 to 30 ng/ml), D3 levels were below the laboratory sensitivity threshold (12.5 ng/ml) in all participants. The median 24,25-OH2 D3 level was 1.49 [1.04; 1.95] ng/ml (reference interval (RI) 0.5-5.6 ng/ml), the median 25-OH D3/24,25-OH2 D3 ratio was 21.87 [15.57; 22.55] (RI 7-23). All patients had normal levels of 1,25-OH2 D3 (median 45.95 [35.18; 53.65] pg/ml, RI 25-66). One patient had secondary hyperparathyroidism (albumin-adjusted calcium 2.14 mmol/l, RI 2.15-2.55; PTH 73.8 pg/ml, RI 15-65; 25-OH D3 24.8 ng/ml) while other biochemical parameters were normal. The remaining patients had normal levels of PTH, calcium, phosphorus and magnesium. Conclusions: The revealed changes in the levels of D3 and 25-OH D3 in patients undergoing bariatric surgery may be due to malabsorption, increased deposition in adipose tissue, an insufficient dosage of cholecalciferol or low patient compliance. At the subsequent stages of vitamin D metabolism, no abnormalities were identified. It is likely that this cohort of patients requires higher doses of cholecalciferol. Presentation: Thursday, June 15, 2023

THU588 Sparing Confirmatory Testing In Primary Aldosteronism: The Combination Of Renin, Aldosterone And Potassium Levels

Abstract Disclosure: A.C. Ong Lopez: None. D.M. Dimayuga: None. L.E. Tiu: None. O.C. Dampil: None. E. Mendoza: None. M.L. Villa: None. A.M. Macabuag-Oliva: None. Background and Objective: The diagnosis of primary aldosteronism (PA) is comprehensive which includes case-detecting testing, case confirmation followed by subtype classification. In certain instances, one may not proceed with further confirmatory testing in the setting of spontaneous hypokalemia, suppressed renin, and PAC &amp;gt; 15 ng/dL. However, this quality of evidence is very low. This study sought to determine the optimal laboratory combination patterns that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various combination settings and correlating to the recent evidence and clinical practice guidelines. Methodology: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study with a sampling total of 116 participants aged 18 years and above who underwent saline infusion test between January 2010 to March 2023. The main outcome measures comprise the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia) which include the sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.0.0 &amp; MedCalc 20.218. Results: Of the 116 patients who underwent saline infusion test, 76 (65.52%) were diagnosed with PA. A PAC of &amp;gt; 25 ng/dL plus PRA &amp;lt; 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 89.11%, 100.00%) and positive predictive value at 100% (95% CI 82.35, 100.00%). The optimal combination criteria with the best balance of the diagnostic performance indices were determined to be a PAC of &amp;gt; 20 ng/dL plus PRA &amp;lt; 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has a sensitivity of 34.72% (95% CI 23.88% , 46.86%), specificity of 93.75% (95% CI 79.19%, 99.23%), positive predictive value (PPV) of 92.59% (95% CI 75.71%, 99.09%), negative predictive value (NPV) of 38.96% (95% CI 28.05%, 50.75%), positive likelihood ratio (LR+) of 5.56 (95% CI 1.40, 22.06), negative likelihood ratio (LR-) of 0.70 (95% CI 0.58, 0.84), and a diagnostic accuracy of 52.88% (95% CI 42.85%, 62.75%). Conclusion: Hypertensive patients with spontaneous hypokalemia who had initial screening test results of PAC &amp;gt; 20 ng/dL and PRA &amp;lt; 0.6 ng/ml/hr can be diagnosed as overt primary aldosteronism and may not proceed with dynamic confirmatory testing. This is in line with the 2016 Endocrine Society Clinical Practice Guideline recommendation. Presentation: Thursday, June 15, 2023

Treatment of hypercalcaemia of malignancy in adults

Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced malignancies with a prevalence varying from 2-30%, depending on cancer type and disease stage. HCM is associated with impaired quality of life, increased risk of hospitalisation and limited survival. Evidence-based guidelines for management of HCM have been lacking to date, despite its prevalence and detrimental impact. This concise guidance highlights key recommendations from the recent Endocrine Society Clinical Practice Guidelines on Treatment of Hypercalcaemia of Malignancy in Adults, published in December 2022. A systematic review and meta-analysis was commissioned to support the guideline development process. Key suggestions include the use of denosumab in preference to intravenous bisphosphonates as first-line treatment for HCM and the use of denosumab in cases of recurrent or refractory HCM in patients previously treated with intravenous bisphosphonates. The guideline also identifies priority areas for future research.

Current and Perspective Approaches to the Treatment of Prolactinomas.

Along with the presence of the 2011 Endocrine Society Clinical Practice Guidelines and numerous large-scale studies on the treatment of hyperprolactinemia of different origin, there are some unresolved questions, ambiguous and sometimes contradictory points of view regarding the management of patients with prolactinomas. This overview is devoted to the analysis of the results of modern clinical studies and the approaches towards the management of hyperprolactinemia caused by prolactinoma. A systematic research of the literature for the appropriate keywords published mainly for the last 10 years was done; also, a reference list of each selected article was analysed. We included to our review the articles reporting controversial issues or new data on the treatment of hyperprolactinemia. The review describes various problems arising during the treatment of prolactinoma. The presence of primary and secondary dopamine agonist resistance in each case requires an individual approach, and sometimes may include the use of the antineoplastic agent t emozolomide. The side effects of dopamine agonists are discussed, with quite rare ones, including valvulopathy, pathological psychological conditions and cerebrospinal rhinorrhea. The controversial issue of the duration and doses of the drug used to achieve a lasting effect in the treatment of prolactinomas is considered. There are some points connected with the frequency of relapses. Thus, recurrence is correlated to the duration of treatment with dopamine agonists, prolactin levels at diagnosis, and the initial tumor size. Metformin, somatostatin analogues, selective estrogen receptor modulators, tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, epidermal growth factor receptor antagonists are investigated nowadays as potential alternative methods of drug treatment of prolactinomas. Drug therapy with dopamine agonists makes it possible to achieve the desired results in the vast majority of patients. However, despite the proven safety of this group of medicines, the risk of side effects should still be taken into account. The therapy regimen should be determined by the clinical course of prolactinoma and the patient's response to treatment. Other options of treatment should be considered in patients intolerant to medical therapy, with contraindication or resistance to dopamine agonists, in the case of a malignant tumor. The presence of refractory to any of the applied methods of treatment and aggressive prolactinomas leads to the search for new drugs.

Part I: Interactive case: Menopause

Part I: Interactive case: Menopause

Part II: Interactive case: Drug‐induced endocrine disorders

Part <scp>II</scp>: Interactive case: <scp>Drug‐induced</scp> endocrine disorders

Correlation of Body Mass Index with Vitamin D and Parathormone (PTH) in Obese and Overweight Children, Study from a Tertiary Care Hospital of Bangladesh

Introduction with aim and objectives: Childhood obesity and vitamin D deficiency both are emerging health issues. Vitamin D is essential for normal growth and development and frequently found low in obese and overweight children. The aim of this study was to assess serum vitamin D level, calcium, inorganic phosphate, alkaline phosphatase and parathormone (PTH) in obese and overweight children and to see the correlation between BMI, vitamin D and parathormone. Materials and Methods: This study was conducted at Pediatric Endocrinology clinic of department of Paediatrics of Bangabandhu Sheikh Mujib Medical University from the period of November 2016 to October 2018. We assessed 50 obese and overweight children for serum vitamin D, calcium, inorganic phosphate, alkaline phosphatase, and parathormone and we also tried to find out the correlations among the parameters in this cross sectional study. Results: Endocrine society clinical practice guideline was used to define vitamin D status. Result found that all of the obese/overweight children had low vitamin D (82% had deficiency and 18% had insufficiency). There was a statistically significant negative correlation between BMI and serum vitamin D level and positive correlation between BMI and the parathormone level (p value &lt; 0.05). In this study significant negative association was found between vitamin D level and the PTH level p value &lt;0.05. Conclusion: All the studied obese and overweight had vitamin D deficiency or insufficiency. There was negative correlation between BMI and serum vitamin D level and positive correlation between BMI and the parathormone level (PTH). Medicine Today 2023 Vol.35(1): 52-55

Commentary on the endocrine society clinical practice guideline on the “treatment of hypercalcemia of malignancy in adults”

Commentary on the endocrine society clinical practice guideline on the “treatment of hypercalcemia of malignancy in adults”

In Search of the Hyperglycemic Threshold Required to Induce Growth Hormone (GH) Suppression.

Introduction According to the 2014 Endocrine Society Clinical Practice Guideline on acromegaly, the confirmation of acromegaly diagnosis is established by finding a lack of suppression of growth hormone (GH) to < 1 ug/L following documented hyperglycemia during an oral glucose tolerance test. However, in this setting, the concept of hyperglycemia has never been clearly defined. Objective This study aimed to define the hyperglycemic threshold required to induce GH suppression. Methods We retrieved the glycemia profile of 44 individuals after a standard 2-h 75g oral glucose tolerance test prescribed to assess GH suppression and performed a comprehensive analysis of two subgroups of individuals (28 reaching GH suppression and 16 in whom GH suppression was not observed). All of the data were analyzed with the program Graph Pad Prism. Differences between means were assessed by Student's unpaired t-test or Mann-Whitney U test as deemed appropriate. Fisher's exact test was used for categorical variables. Results Individuals in G1 and G2 were different only for the median basal GH and median IGF-1. No significant differences in terms of the prevalence of diabetes and prediabetes were found. The glucose peak was achieved earlier in the group that reached GH suppression. The median of the highest glucose values of both subgroups was not different. A correlation between peak and baseline glucose value was found only among those in whom GH suppression was reached. Among these, the median glucose peak (P50) was 177 mg/dl, whereas the 75th percentile (P75) and 25th percentile (P25) were 199 mg/dl and 120 mg/dl, respectively. Conclusion Considering that 75% of those in whom GH suppression was observed after an oral glucose overload test reached blood glucose values above 120 mg/dl, we propose to use this value as the blood glucose threshold for inducing GH suppression. In light of our results, whenever GH suppression is not observed; and the highest glycemic value is below 120 mg/dl, it might be useful to repeat the test prior to any conclusion.

PS-C21-10: A LC-MS/MS-EQUIVALENT VALUE OF ALDOSTERONE MEASUREMENT BY A NEW CHEMILUMINESCENT ENZYME IMMUNOASSAY USING A TWO-STEP SANDWICH METHOD

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Patients with PA have an increased risk of cardiovascular events, such as cerebral infarction, myocardial infarction, and chronic kidney disease, compared to those with essential hypertension, and early diagnosis makes PA a treatable disease. In clinical practice, accurate measurement of plasma aldosterone concentration (PAC) is crucial because entire diagnostic tests critically depend on aldosterone concentrations. Recently, we developed a new chemiluminescent enzyme immunoassay (CLEIA) using a two step sandwich method to measure aldosterone concentrations. We measured PAC in blood samples from patients using a radioimmunoassay (RIA) and the CLEIA (with current and newly improved reagents) as well as liquid chromatography tandem mass spectrometry (LC MS/MS). Based on the results of the Passing Bablok regression analysis, the aldosterone levels measured using CLEIA with the new reagents and those measured by LC MS/MS were found to be significantly correlated. However, aldosterone levels were lower with the improved CLEIA method than with RIA and CLEIA using the current reagent. Since April 2021, the plasma aldosterone concentration has been measured by CLEIA in Japan. As a provisional response due to changes of the measurement method, the Japan Endocrine Society Clinical Practice Guideline for the Diagnosis and Management of Primary Aldosteronism 2021 was announced. This time, we will report on the new measuring method.

Vitamin D status & bone health in patients with liver cirrhosis.

Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.

Gender confirmation hormonal treatment use in young Polish transgender binary and non-binary persons.

Gender confirmation hormonal treatment (GCHT) is a cornerstone of medical treatments for persistent gender dysphoria, which is expected and required by many transgender binary and non-binary individuals. Many protocols have been published, and the qualification process is guided by the World Professional Association for Transgender Health Standards of Care. The standards and other documents such as the Endocrine Society Clinical Practice Guideline provide gender confirmation hormonal care also for minors. However, the issue of starting these treatments in younger populations is still marked by controversy. This preliminary study aimed to inquire into GCHT (medications used, timing of its initiation, its tolerance, and sources of information on the treatment) in a convenience sample of young Polish transgender binary and non-binary persons. A total of 166 adult transgender participants answered our online questionnaire between November 2020 and December 2021. The population was divided into 2 groups: assigned male at birth (AMB, n = 37) and assigned female at birth (AFB, n = 126). Subsequently, division into binary and non-binary was applied to these groups. Most patients (91.9% AMB and 92.2% AFB) did not use gender confirmation medical treatments before the age of 18 years. The most common medication used for GCHT before the age of 18 was cyproterone acetate for AMB and testosterone for AFB. When asked about their opinion on the timing (age) of initiating GCHT, 73.1% of the AMB and 59.2% of the AFB participants shared the view that it had been initiated much too late. By far the most common source of information on GCHT and gender confirmation surgery (GCS) was the Internet (92.2%). These treatments (including pubertal blocking) seem to be rarely commenced in Poland before the age of 18 years. In adults, treatment consists mostly of either testosterone or oestradiol, and cyproterone acetate and, more seldom, spironolactone are used as antiandrogens in persons assigned male at birth. In turn, gonadotropin-releasing hormone agonists are barely used at all. Specialists need to be more aware that withholding treatment in minors with gender dysphoria is not a health-neutral option. Gonadotropin-releasing hormone agonists should also be more often considered as an alternative to cyproterone acetate in the context of long-term safety.

Management of Individuals With Diabetes at High Risk for Hypoglycemia: An Endocrine Society Clinical Practice Guideline.

Hypoglycemia in people with diabetes is common, especially in those taking medications such as insulin and sulfonylureas (SU) that place them at higher risk. Hypoglycemia is associated with distress in those with diabetes and their families, medication nonadherence, and disruption of life and work, and it leads to costly emergency department visits and hospitalizations, morbidity, and mortality. To review and update the diabetes-specific parts of the 2009 Evaluation and Management of Adult Hypoglycemic Disorders: Endocrine Society Clinical Practice Guideline and to address developing issues surrounding hypoglycemia in both adults and children living with diabetes. The overriding objectives are to reduce and prevent hypoglycemia. A multidisciplinary panel of clinician experts, together with a patient representative, and methodologists with expertise in evidence synthesis and guideline development, identified and prioritized 10 clinical questions related to hypoglycemia in people living with diabetes. Systematic reviews were conducted to address all the questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. The panel agreed on 10 questions specific to hypoglycemia risk and prevention in people with diabetes for which 10 recommendations were made. The guideline includes conditional recommendations for use of real-time continuous glucose monitoring (CGM) and algorithm-driven insulin pumps in people with type 1 diabetes (T1D), use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia, use of long-acting and rapid-acting insulin analogs, and initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia. Strong recommendations were made for structured diabetes education programs for those at high risk for hypoglycemia, use of glucagon preparations that do not require reconstitution vs those that do for managing severe outpatient hypoglycemia for adults and children, use of real-time CGM for individuals with T1D receiving multiple daily injections, and the use of inpatient glycemic management programs leveraging electronic health record data to reduce the risk of hypoglycemia. The recommendations are based on the consideration of critical outcomes as well as implementation factors such as feasibility and values and preferences of people with diabetes. These recommendations can be used to inform clinical practice and health care system improvement for this important complication for people living with diabetes.

OR01-3 Lack of Bone Mineral Density Testing in Men with Hypogonadism: A Clinical Conundrum

Abstract Objective Hypogonadism is a known risk factor for decreased bone mineral density (BMD) and increased risk of fractures in men. The 2012 Endocrine Society Clinical Practice Guidelines recommend that men ≥ 50 years of age with a diagnosis of hypogonadism undergo BMD testing.1 The objective of this study was to determine the frequency at which men aged ≥ 50 with a diagnosis of hypogonadism underwent BMD testing, and among those that underwent testing, the percentage of men diagnosed with osteopenia or osteoporosis and subsequently treated with an osteoporosis medication. Methods A retrospective chart review was conducted using the enterprise-wide electronic health record system at our institution. Inclusion requirements were an ICD-9 or -10 code for hypogonadism at any time between 7/1/2012 and 9/30/2020, and at least two subsequent visits with providers from primary care, endocrinology, or urology. Patients with a diagnosis of osteoporosis or who had undergone treatment with an osteoporosis medication, prior to the diagnosis of hypogonadism, were excluded. Patients were followed until the date of BMD assessment or censoring (9/30/2021). The testing results and documentation of treatment with an osteoporosis medication were recorded. Categorical variables and continuous variables were summarized using N (%) and median (IQR) or mean (SD), respectively. Results A total of 10,169 men with hypogonadism were identified. General characteristics included mean age of 63.4 years (±9.2), 85.2% white, 52.7% with history of smoking, 68.2% with hypertension, 36.9% with type 2 diabetes, and mean BMI of 31.3 kg/m2 (±6.0). Median follow-up time was 6.6 years (3.8, 8.5). Of 728 (7.2%) patients who underwent BMD testing, 352 (48.4%) had osteopenia and 87 (12.0%) had osteoporosis. A total of 5,633 (55.4%) men underwent treatment with testosterone replacement therapy. Of the 87 patients identified as having osteoporosis, 50 (57.5%) were treated with an osteoporosis medication. Conclusion Despite a recommendation from the 2012 Endocrine Society for men ≥ 50 years of age with hypogonadism to undergo BMD testing, the rate at which this testing is performed in real-world practice is quite low. The high rate (60.3%) at which low BMD was discovered in hypogonadal men who underwent testing, and further observation of a low rate of treatment with osteoporosis medication when indicated, is alarming and necessitates a call to action for more hypogonadal men to undergo testing and receive appropriate treatment. Further studies are needed to determine the reasons why so few men with hypogonadism undergo BMD assessment and what systems can be put in place to overcome this clinical conundrum. Reference 1. Watts NB, et al. Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology &amp; Metabolism, Volume 97, Issue 6, 1 June 2012, Pages 1802–1822, https://doi.org/10.1210/jc.2011-304 Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.

ODP356 The Cortisol Conundrum: The Diagnostic Work up for Patients With Suspected Cushing's Disease and Hypercortisolaemia in Australia. Results of a Survey and Clinical Audit

Abstract Cushing's syndrome (CS) and the pituitary tumour causing hypercortisolaemia, known as Cushing's Disease (CD), is a rare and challenging diagnosis. It is complicated by nonspecific symptoms and a range of diagnostic tests, with an average diagnostic delay of 3 years. Our objective was to compare the intended diagnostic workup by clinicians and medical students (students) against Endocrine Society Clinical Practice Guidelines (Guidelines). Comparisons were also drawn between the Guidelines and the workup of patients with suspected CS, aiming to identify areas to improve diagnosis and reduce diagnostic delay. This study had two parts. The first was a mixed cohort cross-sectional study involving an anonymised online survey, which examined the clinical experience of respondents, intended diagnostic pathway for CD and recommendations for improvement. The survey was distributed to clinicians and students in Australia, at four tertiary hospital facilities and students at two tertiary centres. The second part was a retrospective clinical audit of the diagnostic workup for patients with suspected CS, performed by senior endocrinologists, associated with an Australian tertiary health facility. Survey responses were received from 102 individuals (52 doctors and 50 students). Most doctors were trained in endocrinology (77%). Most doctors had seen &amp;lt;10 CS or CD patients throughout their careers and training (79%). The most common initial screening tests for clinicians and students were 24-hour urinary free cortisol (80% and 82%, respectively) and low dose overnight dexamethasone suppression testing (67% and 50%, respectively). Plasma adrenocorticotropic hormone (ACTH) and Magnetic Resonance Imaging (MRI) were selected by most clinicians (80% and 74%, respectively) and most students (70% and 82%, respectively), as tests for localising confirmed hypercortisolism. Recommendations suggested by respondents were broadly categorised into: greater clarity of the diagnostic process, by means such as flow charts (50%); increasing awareness (44%); and non-endocrine physician training (31%). Audit inclusion criteria was met by 15 patients (53% female; 47% male; mean age 46.9 years). The mean time from endocrinology referral to diagnosis was 13.5 months. Hypercortisolism was confirmed in 11 patients; including 4 patients with CD and 1 patient with ectopic CS. ACTH was ordered prior to confirming hypercortisolism in 14 patients and 1 patient was tested prior to excluding exogenous steroid use. Our study demonstrated that the majority of clinicians and students when surveyed, would make diagnostic decisions in line with the Guidelines. Half of respondents suggested there was a lack of clarity in diagnostic algorithms available. Minor discrepancies were seen between Guideline recommendations and patients’ assessments amongst the cohort audited. However, ACTH was consistently sent during screening and a patient was assessed with iatrogenic Cushing's, which are not recommended. Our findings suggest improved resources for the diagnostic workup of hypercortisolism, such as comprehensive flowcharts, may be helpful for clinicians and students. Presentation: No date and time listed

PSAT018 Management of Pheochromocytoma in the Setting of a Patient with Multiple Vasculopathies

Abstract A 66-year-old male with history of Type 2 diabetes and adrenal incidentaloma presented to the hospital with significant left lower limb edema and was found to have severe peripheral vascular disease. CT surgery was consulted and performed an angiogram as well as an angioplasty; however, the patient had severe stenosis and stenting was not possible. Femoral popliteal bypass was planned. Due to the patient's acute kidney injury from renovacular hypertension, preoperative evaluation included a MRI abdomen w/wo contrast which showed a 1.4 cm right adrenal nodule with early contrast enhancement which appeared fairly avid and uniform. This nodule had been previously noted by CT scan three years prior. Previous outpatient labs showed elevated metanephrines of 543 pg/mL, which determined the adrenal nodule to be consistent with a pheochromocytoma. Subsequently, femoral popliteal bypass was postponed and the patient was started on an alpha blocker, doxazosin. Urology was consulted and right laproscopic adrenalectomy was planned. Preoperatively, patient developed chest pain due to ventricular tachycardia and NSTEMI was diagnosed by EKG. Patient then underwent a LHC which revealed severe left main 3 vessel coronary artery disease, postponing planned adrenalectomy. CABG was performed with pericardiectomy. After initial recovery, patient was discharged to in-patient rehabilitation, indefinitely delaying definitive pheochromocytoma therapy. Reference Jacques W. M. Lenders, Quan-Yang Duh, Graeme Eisenhofer, Anne-Paule Gimenez-Roqueplo, Stefan K. G. Grebe, Mohammad Hassan Murad, Mitsuhide Naruse, Karel Pacak, William F. Young, Jr, Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology &amp; Metabolism, Volume 99, Issue 6, 1 June 2014, Pages 1915–1942, https://doi.org/10.1210/jc.2014-1498 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.