Endocrinology Clinic Research Articles

8125 Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. D. Tripathy: None. There is differential effect of long-term Estrogen and Testosterone therapy on lipid profile. While oral estradiol therapy in post-menopausal women has been associated with increased serum triglyceride and HDL, testosterone therapy in hypogonadal men decreases total cholesterol, LDL and HDL cholesterol. However, the long-term effects of Estrogen and Testosterone on lipid profile in transgender patients are not clear. We conducted a retrospective study to analyze the long-term effects of GAHT in transgender men and women followed in Endocrinology Clinic at Veterans Affairs Hospital. 36 transgender men (age 38 ± 2 years, on IM Testosterone cypionate) and 54 transgender women (age 46 ± 2 years, 36 on E2 tablet, 12 on patch, 6 on IM) were followed for 46 ± 5 months and 61 ± 5 months, respectively. Total cholesterol, triglyceride, HDL, LDL cholesterol, systolic and diastolic blood pressures, and BMI were compared before and after initiation of therapy. As expected, following GAHT, total testosterone was higher (546 ± 48 vs. 35 ± 9 ng/dL, P<0.001) in transgender men; in transgender women, serum E2 was higher (110 ± 9 vs. 26 ± 2 pg/dL, P<0.001) and total testosterone was suppressed (444 ± 29 ng/dL vs. 66 ± 13 ng/dL). In transgender men, after a follow-up period of approximately 4 years, there were no significant changes in lipid profile (total cholesterol 178 ± 8 vs. 175 ± 8 mg/dL, triglyceride 121 ± 4 vs 134 ± 12 mg/dL, HDL 47 ± 2 vs. 44 ± 2 mg/dL, LDL 107 ± 7 vs. 106 ± 8 mg/dL, all p=NS). Similarly in transgender women, no difference in lipid profile (total cholesterol 170 ± 5 vs. 175 ± 4 mg/dL, triglyceride 118 ± 7 vs 140 ± 9 mg/dL, HDL 49 ± 2 vs. 53 ± 3 mg/dL, LDL 99 ± 4 vs. 97 ± 4 mg/dL, all p=NS) was observed after 5 years of GAHT. There were no differences in lipid profile regardless of E2 tablet, patch or IM therapy. In transgender men, there was an increase in diastolic blood pressure (72 ± 3 vs. 76 ± 2 mmHg, P<0.05) while in transgender women there was decrease in systolic blood pressure (124 ± 2 vs. 118 ± 2 mmHg, p<0.005), and slight increase in BMI (28 ± 0.9 vs. 30 ± 1 kg.m2, P<0.005). In conclusion, long-term testosterone therapy in transgender men and estrogen therapy in transgender women was not associated with worsening lipid profile. Estrogen therapy was associated with lower BP in transgender women and testosterone therapy led to higher BP in transgender men. Presentation: 6/2/2024

12261 Association Of Geographic And Demographic Factors With Receipt Of Endocrinology Care Among Adults With T2D And ASCVD Before And After Telemedicine Uptake

Abstract Disclosure: M. Zupa: None. J. Bauer: None. S. Rothenberger: None. Y. Zheng: None. A. Johnson: None. E. Kinnee: None. A. Rosland: None. Care from endocrinologists has been linked to improved care quality and uptake of novel treatments which may improve outcomes for adults with T2D and ASCVD, who are at high risk for adverse health outcomes. However, transportation, geographic, and other barriers may impact access to specialty care for under-resourced populations. We sought to evaluate the impact of patient-level geographic and sociodemographic factors on receipt of endocrinology care before and after widespread telemedicine uptake. We conducted a retrospective cohort study of adults with T2D and ASCVD in a large health system from 1/2018-6/2022. ZIP Code centroids were used to map patients to their home geographic area, and multivariable logistic regression models evaluated associations between sociodemographic and geographic predictors with receipt of endocrinology care. Analyses were stratified into pre- (1/1/2018-3/15/20) and post- (3/16/2020-6/30/2022) telemedicine periods. Mixed effects models tested for differences in associations between the pre- and post-telemedicine periods. The cohort included 9,546 patients, with mean age 68.5 (SD 10.0), 39% female, 89% white, 83% urban residents; 1,725 patients received endocrinology care. In the pre-telemedicine period, geographic factors associated with receipt of endocrinology care included distance to the nearest endocrinology clinic (aOR 0.74 (95% CI 0.64-0.84) per 10 miles) and neighborhood walkability (aOR 1.38 (1.00-1.91) per 10 point increase on 0-20 scale); sociodemographic factors included age (aOR 0.70 (0.66-0.75 per 10 years), male gender (aOR 0.81 (0.72-0.92), race (aOR 1.21 for Black vs white, aOR 2.55 for Asian vs white, p=0.003), social deprivation index (0.95 (0.91-0.99) per 10 point increase on 0-100 scale, with higher values indicating more local area deprivation), and comorbidity burden (aOR 1.27 (1.02-1.59) for Elixhauser score 14+ vs <0, p<0.001). In the post-telemedicine period, distance to endocrinology clinic (aOR 0.82 (0.73-0.93) per 10 miles), age (aOR 0.67 (0.63-0.71) per 10 years), male gender (aOR 0.83 (0.74-0.94)), and comorbid conditions (aOR 1.13 (0.90-1.43) for Elixhauser score 14+ vs <0, p<0.001) were associated with receipt of endocrinology care. In mixed models comparing pre- vs. post-telemedicine periods, travel distance to endocrinology clinic, race, and social deprivation index had weaker associations with receipt of endocrinology care in the post-telemedicine period compared to pre-telemedicine, while older age was more negatively associated with care receipt post-telemedicine. These findings indicate that both geographic and sociodemographic factors impact receipt of endocrinology care among high-risk adults with T2D and ASCVD. Widespread availability of telemedicine may be associated with more equitable access to endocrinology care for some under-resourced populations. Presentation: 6/3/2024

8561 Association Of Alopecia And Hirsutism With Severity Of Depression In A Sample Of Hispanic Women With Polycystic Ovary Syndrome

Abstract Disclosure: C.M. Casas Loyola: None. Y.G. Rivera-Rodriguez: None. B. Marin Rodriguez: None. J.A. Roque Torres: None. L.A. Gonzalez Rodriguez: Research Investigator; Self; Lilly USA, LLC. J. Romaguera: None. Purpose: Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder in females has been associated with several chronic diseases. Females with PCOS have been found with a higher prevalence of mental disorders. Depression and its severity have been associated with the development and progression of cardiovascular disease. We aimed to assess depression severity and its association with PCOS related comorbidities such as alopecia and hirsutism. Methods: A cross sectional study of females aged 21-45 years was conducted in the endocrinology clinics at the RCM-Clinics. PCOS was diagnosed using the Rotterdam criteria, hirsutism was defined by modified Ferriman-Gallwey score (mFG ≥ 9), alopecia was defined using the Ludwig scale and Depression using the Patient Health Questionnaire (PHQ9). Severity of depression and presence of alopecia and hirsutism were compared among groups. Results: A total of 112 patients were included in this study (85 patients PCOS+ and 27 patients PCOS-). Mean age was 32 ± 6 years. Severity of depression in PCOS- patients was: 44% none to minimal, 30% mild and 27% moderate to severe. Severity of depression in PCOS+ patients was: 28% none to minimal, 35% mild and 36% moderate to severe. Participants with alopecia and PCOS+ had a greater percentage of moderate to severe depression (58%) compared to the control group without alopecia (30%) (p value<0.05). No differences were observed between hirsutism and severity of depression among groups. Conclusion: Our study showed an association between alopecia and severity of depression in patients with PCOS+. The presence of hirsutism was not associated to severity of depression. Currently, there are more available treatments for hirsutism than for alopecia. For this reason, patients with hirsutism have more opportunities to manage their condition than patients with alopecia, which often require more invasive procedures. The presence of alopecia can be considered a risk factor for developing major depressive disorder in patients with PCOS. Treatment of PCOS-related abnormalities should be emphasized soon after diagnosis. Evaluation of mental health is imperative in our PCOS patients. Presentation: 6/3/2024

7336 Decades In The Dark: The Long Road To Diagnosing And Treating Hypophosphatasia

Abstract Disclosure: V.A. Mendpara: None. G. Madrigal Loria: None. L.Z. Khan: None. Background: Hypophosphatasia (HPP) is a rare bone disorder that results from deficient activity of the tissue non-specific isoenzyme alkaline phosphatase (ALP).[1] This case highlights a patient whose diagnosis of this treatable genetic condition was significantly delayed for almost two decades, despite receiving care at a prominent academic institution. The patient's persistently low ALP levels in routine lab tests were overlooked by multiple clinicians, leading to a delay in her care and eventual treatment. Case presentation: A 61-year-old Caucasian woman presented at the endocrinology clinic with complaints of severe fatigue, generalized pain, multiple childhood fractures, and ongoing dental issues. The rheumatology clinic to which she was referred for polyarthralgia diagnosed her with Hypophosphatasia (HPP) after noting chronically low alkaline phosphatase (ALP) levels from her previous charts ranging from 15 to 24 U/L (normal range: 34 to 123 U/L) over two decades. Her serum calcium, parathyroid hormone (PTH), and 25-hydroxy vitamin D levels were within normal ranges. A DEXA scan revealed normal bone density, effectively ruling out osteoporosis. Further investigation showed elevated Vitamin B6 levels at 219.6 nmol/L (normal range: 20.0 to 125.0 nmol/L), raising suspicion for HPP. The patient's family history provided additional insight, with her mother having a history of short stature and fractures and her son experiencing premature tooth loss at the age of 2. A genetic evaluation identified a heterozygous pathogenic variant in the ALPL gene (c.881A>C, p.Asp294Ala), confirming the diagnosis of autosomal dominant HPP. Initiating treatment with Asfotase alfa, a medication targeting HPP, resulted in a marked improvement in the patient's symptoms. Discussion: This case shows the diagnostic complexities of HPP, stressing the significance of actively screening for this condition via ALP levels in routine laboratory testing or during osteoporosis evaluations. The diagnostic process is critical to distinguish HPP from primary osteoporosis, as treatment and potential risks differ significantly. Inadvertent use of bisphosphonates can worsen hypomineralization and lead to atypical femoral fractures in HPP patients. Asfotase alfa enzyme replacement therapy, available since 2015, offers a targeted approach by replacing the enzyme defect, thereby mitigating symptoms. Heightened awareness among healthcare providers of HPP in adults holds the potential to enhance diagnosis rates and facilitate improved treatment outcomes for this highly treatable condition.[1] Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition. ASBMR. Presentation: 6/2/2024

8417 Knowledge Of PCOS and Its Complications In A Population Of Hispanic Women

Abstract Disclosure: Y.G. Rivera-Rodriguez: None. B. Diaz Rios: None. C.M. Casas Loyola: None. B. Marin Rodriguez: None. P.A. Alicea Reyes: None. J. Romaguera: None. L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly & Company. Purpose: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women across their lifespan, with metabolic complications that are often overlooked. Studies have revealed an inadequate understanding of PCOS, its complications, and management. There is also limited information about this condition in Hispanic women. The purpose of this study is to assess the knowledge about PCOS and its complications among a sample of Hispanic women living in Puerto Rico. Methods: This is a descriptive cross-sectional study of Hispanic women aged 21-45 years recruited from the General Endocrinology and Gynecology Clinics at the UPR-RCM Clinics. A self-administered questionnaire assessing their knowledge about PCOS, and its complications was given. Patients were classified according to PCOS diagnosis. Results were compared between the groups. Results: A total of 47 women were included in this study. Approximately 45% of participants had a diagnosis of PCOS. Most participants agreed that PCOS involves a set of symptoms associated with hormonal imbalances (94%) and irregular menses (91%). Only 40% of participants considered PCOS a chronic condition without a cure and only 34% acknowledge weight loss as one of the treatments of this condition. Two-thirds of participants didn’t know that PCOS can be diagnosed with blood tests. When assessing their knowledge about complications related to PCOS, we found that only 36% associated PCOS with an increased risk of cardiovascular disease, 56% with obesity and 62% with abnormal blood glucose levels. When comparing the knowledge about their condition in patients with a diagnosis of PCOS, we found increased knowledge about signs and symptoms such as hirsutism, hair loss and weight gain when compared to controls. However, when assessing their knowledge about complications related to PCOS, neither group recognized PCOS as a chronic condition, or associated PCOS with cardiovascular, metabolic complications and/or increased risk of cancer. Conclusion: Our study suggests that there is a lack of general knowledge about PCOS and its long-term complications among a sample of Hispanic women in reproductive years. Most importantly, our data showed that even patients with a diagnosis of PCOS do not understand their condition or comprehend the associated complications. Our study emphasizes the need to develop educational tools and strategies to improve the general population knowledge about this condition and raise awareness about preventable complications and the importance of early treatment. Presentation: 6/3/2024

8417 Knowledge Of PCOS and Its Complications In A Population Of Hispanic Women

Abstract Disclosure: Y.G. Rivera-Rodriguez: None. B. Diaz Rios: None. C.M. Casas Loyola: None. B. Marin Rodriguez: None. P.A. Alicea Reyes: None. J. Romaguera: None. L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly & Company. Purpose: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women across their lifespan, with metabolic complications that are often overlooked. Studies have revealed an inadequate understanding of PCOS, its complications, and management. There is also limited information about this condition in Hispanic women. The purpose of this study is to assess the knowledge about PCOS and its complications among a sample of Hispanic women living in Puerto Rico. Methods: This is a descriptive cross-sectional study of Hispanic women aged 21-45 years recruited from the General Endocrinology and Gynecology Clinics at the UPR-RCM Clinics. A self-administered questionnaire assessing their knowledge about PCOS, and its complications was given. Patients were classified according to PCOS diagnosis. Results were compared between the groups. Results: A total of 47 women were included in this study. Approximately 45% of participants had a diagnosis of PCOS. Most participants agreed that PCOS involves a set of symptoms associated with hormonal imbalances (94%) and irregular menses (91%). Only 40% of participants considered PCOS a chronic condition without a cure and only 34% acknowledge weight loss as one of the treatments of this condition. Two-thirds of participants didn’t know that PCOS can be diagnosed with blood tests. When assessing their knowledge about complications related to PCOS, we found that only 36% associated PCOS with an increased risk of cardiovascular disease, 56% with obesity and 62% with abnormal blood glucose levels. When comparing the knowledge about their condition in patients with a diagnosis of PCOS, we found increased knowledge about signs and symptoms such as hirsutism, hair loss and weight gain when compared to controls. However, when assessing their knowledge about complications related to PCOS, neither group recognized PCOS as a chronic condition, or associated PCOS with cardiovascular, metabolic complications and/or increased risk of cancer. Conclusion: Our study suggests that there is a lack of general knowledge about PCOS and its long-term complications among a sample of Hispanic women in reproductive years. Most importantly, our data showed that even patients with a diagnosis of PCOS do not understand their condition or comprehend the associated complications. Our study emphasizes the need to develop educational tools and strategies to improve the general population knowledge about this condition and raise awareness about preventable complications and the importance of early treatment. Presentation: 6/3/2024

7466 The Effects Of Various Forms Of Diabetes On Features Of Tumor Aggressiveness In Thyroid Cancer

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. A. Rizoulis: None. A. Boniakos: None. I. Perogamvros: None. D. Bantouna: None. J.C. Jaume: None. Introduction: Diabetes has been linked to increased risk for several cancers and aggressiveness of tumor behavior. A link between thyroid cancer and diabetes appears controversial in the literature as of yet. We designed the present study to assess whether autoimmune (type 1 + LADA = DM1) or type 2 diabetes (DM2) are associated with more aggressive thyroid cancers compared to those found in non-diabetic (non-DM) individuals. Methods: We retrospectively reviewed data from patients undergoing thyroid surgery in 10 Endocrinology and Endocrine Surgery Clinics throughout Greece over 2 years. We collected data on history and type of diabetes, pre-existing to the thyroid surgery, its treatments and duration, the preoperative thyroid function tests and the surgical pathology findings. We compared the incidence of various histological types of thyroid cancer and the features of tumor aggressiveness between patients with diabetes and those with normal glucose homeostasis (non-DM) (DM1 vs. DM2 vs. non-DM). Results: Overall, n=808 subjects with thyroid cancer were included: n=571 were females (70.7%), age 47.3 ± 14.3 years, BMI 27.0 ± 5.0 Kg/m2, mean TSH 1.99 ± 2.21 mIU/L; n= 692 were non-DM, n=10 had DM1 and n=107 had DM2. Histology revealed n=5 poorly differentiated / anaplastic, n=13 medullary, n=12 Hürthle cell, n=17 follicular and n=773 papillary thyroid cancers (PTC); n=20 (2.5%) with aggressive histological subtypes of PTC, n=5 (0.6%) with distant metastases (MET), n=199 (24.6%) with extrathyroidal extension (ETE), n=419 (51.9%) with capsular invasion (CI), n=225 (27.8%) with lymph nodes involvement (LNi) and n=23 with cancer recurrence (CR) (2.8%). The incidence of aggressive histological types, CR, MET or number of I-131 treatments were not different between groups (p>0.05). ETE, CI and LNi were significantly more common in non-DM compared to both diabetes groups, while gross ETE was more common in DM2 over DM1 and non-DM (p<0.001). Conclusions: More DM1 than DM2 seem to confer a protective effect on several features of cancer aggressiveness in affected individuals. On the other hand, more DM2 than DM1 seems to significantly promote gross ETE. No effect was observed pertaining to the risk for more aggressive tumors or histological subtypes of PTC. Although aggressiveness of thyroid cancer seems controlled in DM1 and to a lesser degree in DM2 the complex interplay between autoimmunity, hyperglycemia and thyroid cancer biology requires larger sample size to better determine causative effects. Presentation: 6/2/2024

12396 A Case Of Medullary Thyroid Carcinoma Without Germline RET Mutation

Abstract Disclosure: I. Marranzini Rodriguez: None. M. Lemelman: None. L. Canham: None. Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumor that originates from the parafollicular C cells of the thyroid gland. MTC accounts for approximately 5% of thyroid cancer in children, and the majority of MTC cases are associated with the autosomal dominant tumor predisposition syndrome Multiple Endocrine Neoplasia 2 (MEN2). Sporadic MTC is uncommon in the pediatric population and associated with somatic mutations of RET or RAS (1). Existing management options for metastatic disease have demonstrated some benefit, however, with systemic side effects. Selpercatinib, a highly selective RET kinase inhibitor, is FDA approved for patients >= 12 years of age. Here we present a case of a 10-year-old patient with metastatic MTC with encouraging results. Clinical Case: A previously healthy 10 year 2-month-old male presented with left-sided neck swelling. Imaging showed a 9.7 cm solid mass spanning nearly the entire left neck, occluding the left internal jugular vein, extending to the upper chest, and resulting in high-grade narrowing of the trachea near the thoracic inlet; the mass involved the left thyroid gland and engulfed the left common carotid. His initial lab evaluation showed an elevated TSH of 10.10 mcU/mL (0.6-5.5 mcU/mL) and Free T4 1.22 ng/dL (0.9-1.67 ng/dL). Tumor markers revealed a calcitonin of 32,264 pg/mL (normal range <= 6.0 pg/mL) and carcinoembryonic antigen (CEA) of 200 ng/ml (normal range 0 – 3.4 ng/mL). He underwent biopsy of the mass which showed medullary thyroid carcinoma (MTC) and genetic evaluation of tumoral tissue showed RET c.2753T>C, p.M918T somatic mutation. Evaluation for pheochromocytoma and hyperparathyroidism, given association of MTC with MEN2, was negative. Genetic testing was negative for germline RET mutations. He was started on selpercatinib, 120 mg every 12 hours. Follow up imaging after 2 months of therapy demonstrated a significant decrease in tumor burden. Approximately 5 months after starting he had a decrease in CEA to 14.8 ng/mL and calcitonin to 69 pg/mL, prior to surgery. Given the risk of locoregional recurrence he underwent total thyroidectomy with lateral neck dissection. However, the tumor was noted to be adherent to the trachea, encasing the left recurrent laryngeal nerve, and left carotid artery preventing full resection. He was started on levothyroxine at 62.5 mcg daily on POD#1 and re-started on selpercatinib approximately 2 weeks post-operatively. Conclusion: We present a case of RET-positive metastatic medullary thyroid carcinoma without germline RET mutation successfully treated with selpercatinib. Long-term follow-up for sustained response and tolerability is needed. Reference: 1. Bauer, Andrew J. “Pediatric Thyroid Cancer: Genetics, Therapeutics and Outcome.” Endocrinology and metabolism clinics of North America vol. 49,4 (2020): 589-611. doi:10.1016/j.ecl.2020.08.00 Presentation: 6/2/2024

7466 The Effects of Various Forms of Diabetes on Features of Tumor Aggressiveness in Thyroid Cancer

Abstract Disclosure: R.D. Paparodis: None. E. Karvounis: None. A. Kapezanou: None. S. Livadas: None. G. Simeakis: None. D.P. Askitis: None. I. Androulakis: None. N.G. Angelopoulos: None. D. Zianni: None. A. Rizoulis: None. A. Boniakos: None. I. Perogamvros: None. D. Bantouna: None. J.C. Jaume: None. Introduction: Diabetes has been linked to increased risk for several cancers and aggressiveness of tumor behavior. A link between thyroid cancer and diabetes appears controversial in the literature as of yet. We designed the present study to assess whether autoimmune (type 1 + LADA = DM1) or type 2 diabetes (DM2) are associated with more aggressive thyroid cancers compared to those found in non-diabetic (non-DM) individuals. Methods: We retrospectively reviewed data from patients undergoing thyroid surgery in 10 Endocrinology and Endocrine Surgery Clinics throughout Greece over 2 years. We collected data on history and type of diabetes, pre-existing to the thyroid surgery, its treatments and duration, the preoperative thyroid function tests and the surgical pathology findings. We compared the incidence of various histological types of thyroid cancer and the features of tumor aggressiveness between patients with diabetes and those with normal glucose homeostasis (non-DM) (DM1 vs. DM2 vs. non-DM). Results: Overall, n=808 subjects with thyroid cancer were included: n=571 were females (70.7%), age 47.3 ± 14.3 years, BMI 27.0 ± 5.0 Kg/m[2], mean TSH 1.99 ± 2.21 mIU/L; n= 692 were non-DM, n=10 had DM1 and n=107 had DM2. Histology revealed n=5 poorly differentiated / anaplastic, n=13 medullary, n=12 Hürthle cell, n=17 follicular and n=773 papillary thyroid cancers (PTC); n=20 (2.5%) with aggressive histological subtypes of PTC, n=5 (0.6%) with distant metastases (MET), n=199 (24.6%) with extrathyroidal extension (ETE), n=419 (51.9%) with capsular invasion (CI), n=225 (27.8%) with lymph nodes involvement (LNi) and n=23 with cancer recurrence (CR) (2.8%). The incidence of aggressive histological types, CR, MET or number of I-131 treatments were not different between groups (p>0.05). ETE, CI and LNi were significantly more common in non-DM compared to both diabetes groups, while gross ETE was more common in DM2 over DM1 and non-DM (p<0.001). Conclusions: More DM1 than DM2 seem to confer a protective effect on several features of cancer aggressiveness in affected individuals. On the other hand, more DM2 than DM1 seems to significantly promote gross ETE. No effect was observed pertaining to the risk for more aggressive tumors or histological subtypes of PTC. Although aggressiveness of thyroid cancer seems controlled in DM1 and to a lesser degree in DM2 the complex interplay between autoimmunity, hyperglycemia and thyroid cancer biology requires larger sample size to better determine causative effects. Presentation: 6/2/2024

6629 Pure Androgen Secreting Adrenal Adenoma In A Premenopausal Woman

Abstract Disclosure: S. Syed: None. Background: Pure androgen secreting adrenal adenomas are extremely rare; most of the reported cases occur in post-menopausal women, with significant virilization of acute onset and are usually malignant. Here we present a case of an androgen secreting adrenal adenoma found in a young female with regular menstrual cycles and hirsutism. Clinical Case: A 27-year-old female with no significant past medical history was referred to Endocrinology clinic for evaluation of elevated testosterone level noted on a routine OBGYN exam. Patient had miscarriage six months prior to initial endocrine clinic visit. She had a routine follow up visit with her gynecologist after miscarriage and noted to have mild male pattern hair growth on her chin, worse after stopping birth control pills two years ago. Patient had menarche at 14 years of age and had regular menstrual cycle until started birth control pills. The skin examination revealed coarse male pattern hair on chin. Scattered acne was present on back. No signs of hypercortisolism were present. Labs done at time of initial consultation showed unremarkable comprehensive metabolic panel, thyroid and gonadotropic hormones. Testosterone was elevated at 122ng/dl (0-75ng/dl). Pelvic ultrasound done in the year prior showed normal uterus and adnexal structures. Further work up showed elevated DHEAS 781 µg/dL (18-391 µg/dL) and normal 17 OH progesterone and androstenedione levels. MRI abdomen with and without contrast done at outside facility showed a 4 cm x 3.3 cm x 4.1 cm well-circumscribed round shaped, mildly heterogeneously enhancing mass arising from right adrenal gland, with restricting diffusion, no signal dropout in out-of-phase imaging. Normal ovaries were noted. Given the large size of lesion, adrenalectomy was recommended. Patient underwent laparoscopic right adrenalectomy. The histologic features on pathology specimen were consistent with an adrenal cortical adenoma. No evidence of malignancy was seen (based on modified Weiss criteria). 3 weeks post op labs showed Testosterone level reduced to 19 ng/dl (0-75ng/dl) and DHEAS 138 ug/dl (18-391 µg/dL). Patient is recovering from recent childbirth. Conclusion: In adults, pure androgen secreting adrenal tumors are extremely rare. Diagnosis of malignancy is made with histopathological examination and Weiss score calculation. Our patient has unique presentation of having mild hirsutism in setting of regular menstrual cycles with no other symptoms of virilization and is noted to have unexpectedly large adrenal adenoma. Given the size of adenoma, there was concern for adrenal cortical carcinoma, however histological examination was consistent with a benign lesion. Presentation: 6/1/2024

6426 Pregnancy-induced ACTH-independent Cushing Syndrome: A Rare Phenomenon Secondary To Aberrant Receptors On Adrenal Glands

Abstract Disclosure: K. Manglani: None. S.T. Sharma: None. Pregnancy-induced hypercortisolism is a rare phenomenon with very few cases reported in the literature. The pathogenesis is thought to be secondary to the expression of aberrant LH/hCG receptors on the adrenal gland that stimulate cortisol production in pregnancy. We present a case of a 31-year-old female with no past comorbidities until her first pregnancy in 2017 when she gained around 50lbs, developed violaceous striae, acne, hirsutism, depression with suicidal ideation for which she was hospitalized twice, and underwent emergent C-section at 34 weeks’ gestation due to pre-eclampsia. She was referred to the Endocrinology clinic post-delivery, and screening for Cushing syndrome was negative at that time: 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC) and 1-mg dexamethasone (dex) suppression test (DST) were normal. She presented again in 2020 during her second pregnancy at 14 weeks gestation, with 20lb weight gain in the first trimester, acne, hirsutism, and easy bruising. Labs showed cortisol of 22.4 mcg/dL (6.2-19.4), ACTH <1.5 pg/mL, total testosterone 168 ng/dL (8-48), androstenedione 751 ng/dL (41-262), DHEAS 91.2 mcg/dL (84.8-378), 24-hour UFC 277 mcg/day (6-42), LNSC 0.671 mcg/dL, 1mg DST with post-dex cortisol 24 mcg/dL (dex level 58 ng/dL), and 8-mg DST with post-dex cortisol level of 28.2 mcg/dL (dex level 457 ng/dL). Testing was consistent with ACTH-independent Cushing syndrome. Ultrasound and MRI of the abdomen/pelvis showed normal adrenal glands with no hyperplasia or mass. Given worsening hypercortisolism and her course during a prior pregnancy, medical treatment with metyrapone was initiated. We started at a dose of 500 mg daily and gradually increased to 1500 mg with close monitoring of her blood pressure and cortisol levels. She underwent vaginal delivery at 38 weeks’ gestation, and the baby required a brief stay in the NICU for respiratory distress but was otherwise doing well. The patient developed secondary adrenal insufficiency post-delivery requiring hydrocortisone, with recovery of her HPA axis in around 10 weeks. Since then, she has been off hydrocortisone with normal UFC, ACTH, and cortisol levels. This case enables discussion regarding the underlying etiology, diagnostic difficulties, and management of this rare condition. Although the exact etiology is unknown, the postulated mechanism is aberrant LH/hCG receptor expression given the patient’s presentation during each pregnancy, normal cortisol levels between both pregnancies, and a brief period of adrenal insufficiency post-delivery. Management of hypercortisolism during pregnancy remains challenging. Metyrapone, a steroidogenesis inhibitor, can be considered for control of hypercortisolemia during pregnancy (off-label) in select cases to prevent maternal and fetal complications. Presentation: 6/1/2024

7331 A Rare Case Of Familial Hypoparathyroidism

Abstract Disclosure: N. Sekhon: None. K.Z. Win: None. Background: Autosomal dominant hypoparathyroidism disorders are very rare and mostly asymptomatic. We present an interesting case of autosomal hypoparathyroidism with a new variant of gene defect on genetic analysis. Case: A 66-year-old female was referred to the endocrinology clinic for familial hypoparathyroidism and calcium oxalate nephrolithiasis. She had onset of seizures at age 16. She was diagnosed with hypocalcemia and hypoparathyroidism at age 30 when she had her first episode of nephrolithiasis. She had recurrent nephrolithiasis and lithotripsies, ultimately developing chronic kidney impairment that was at stage 3b at the time of evaluation. Renal Ultrasound revealed bilateral nephrolithiasis, and nephrocalcinosis. There was a history of hypoparathyroidism in her father, paternal uncle, and son. Her medications included calcium carbonate-vitamin D3 600-400 mg-unit oral 2 tablets daily and calcitriol 0.5 mcg daily. The pertinent physical examination finding was a short stature with height 4’11” and calluses in fingers. Her recent serum chemistry showed calcium 8.8 mg/dL (reference range 8.3 - 10.6 mg/dL), PTH < 6.3 pg/mL (reference range 18.4 - 80.1 pg/ mL), and phosphorus 3.3 mg/dL (reference range 2.4 - 5.5 mg/dL). 24 hr urine calcium was 96 mg (reference range 50-300 mg/24h). She was treated with hydrochlorothiazide for nephrolithiasis but was discontinued due to hypokalemia. We performed genetic testing that resulted positive for CASR NM_001178065.1 with heterozygosity and damaging missense predictions inherited as autosomal dominant or recessive. Discussion: The calcium-sensing receptor (CaSR) has an important role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion and urinary calcium excretion. Familial hypoparathyroidism disorders are divided into Autosomal dominant hypocalcemia (ADH) type 1 and Autosomal dominant hypocalcemia (ADH) type 2. ADH1 is caused by an activating mutation of calcium-sensing receptor (CASR). The estimated prevalence of ADH1 ranges from 1 per 70,000 to 3.9 per 100,000. It is characterized by mild to moderate hypocalcemia, hyperphosphatemia, hypercalciuria, and inappropriately low but detectable PTH levels. It can be associated with Bartter syndrome Type 5. ADH2 is due to mutations in the alpha subunit of the G protein G11 (Gα11). Our patient had classic symptoms of hypocalcemia including short stature, seizures, kidney stones and its sequelae. Her 24-hour urine analysis showed inappropriately normal urine calcium with low normal serum calcium, undetectable serum PTH, and normal phosphorus. Our patient’s genetic analysis revealed a heterozygous defect in gene CASR with DNA variants c.2564G>A with damaging missense predictions. There is no such variant reported or listed in the ClinVar database. To our knowledge, this is the first such case of an autosomal dominant hypoparathyroidism with this gene defect. Presentation: 6/1/2024

8226 A Diagnostic Challenge: Factitious Hypobicarbonatemia in Severe Hypertriglyceridemia

Abstract Disclosure: U. Rafat: None. S. Azmat: None. M. Siddiqui: None. R. Alshantti: None. D. Kircheva: None. V. Trendafilova: None. Background: Serum CO2 levels measured by a chemistry analyzer usually correlate with calculated bicarbonate levels on an ABG. There are some instances however, when this is not the case. Severe hypertriglyceridemia can cause serum bicarbonate levels to appear falsely low on metabolic panel. Clinical Case: A 48-year-old man was referred to Endocrinology Clinic for evaluation of hypogonadism and severe hypertriglyceridemia. Routine labs revealed a plasma CO2 of 11 mmol/L (20-31). Na was 133 mmol/L (136-145), K was 4.4 mmol/L (3.5-4.7), Chloride was 101 mmol/L (98-109) and anion gap was 25 (8-20) measured using a Siemens Vista enzymatic chemistry analyzer. His triglycerides were > 1100 mg/dL (0-150), above upper detection limits of the analyzer. The patient reported fatigue and mild abdominal pain. He was admitted to the hospital for further evaluation. His lipase was 41 U/L (12-73), lactic acid 1.2 mmol/L (0.50-2.20). ABG showed pH of 7.41, HCO3 of 26.6 mmol/L (22-29), and anion gap of 7 (10-20). The patient was well-appearing with normal vital signs and normal physical exam. He was made NPO and started on pravastatin, fenofibrate and fish oil. Once his triglycerides were < 1000 mg/dL, he was started on a very low-fat, low-carbohydrate diet. The CO2 level on BMP normalized on day 3 of hospitalization, when triglycerides measured 1010 mg/dL. No other treatment was given for the low CO2 levels. It does not appear that other lab indices were significantly affected by the hypertriglyceridemia. Review of Literature: A BMP measures serum total carbon dioxide using a chemistry analyzer using either an enzymatic/spectro-photometric method, or an electrode-based method; an ABG sample calculates plasma bicarbonate with the Henderson-Hasselbach equation, using the pH and partial pressure of pCO2 in the sample. Enzymatic analyzers measure CO2 using spectrophotometry and decrease in light absorbance is proportional to the sample’s CO2 levels. It is postulated that severely high triglycerides can interfere with this reaction and cause spuriously low CO2 levels, a phenomenon called pseudohypobicarbonatemia. One proposed mechanism for interference with the enzymatic assay method is turbidity causing a falsely low measured CO2 level. Verghese et al found that the severity of the CO2 measurement error positively correlates with the severity of triglyceride elevation. Conclusion: Awareness of the phenomenon of hypertriglyceridemia-induced pseudohypobicarbonatemia can prevent misdiagnosis or delays in diagnosis, as well as unwarranted testing and treatment. Presentation: 6/3/2024

6469 Supplement Misadventures: A Case Of Acute Heart Failure, Cardiogenic Shock, And Hormonal Dysregulation Secondary To Surreptitious Use Of Multiple Hormonal Supplements

Abstract Disclosure: K.N. Grennan: None. S. Thota-Kammili: None. A.L. McKenna: None. C.G. Coyle: None. S.L. Samson: None. Introduction: Supplement misuse in the bodybuilding community is prevalent. With the availability of internet ordering and purchasing, patients have access to hormonal supplements without prescription or regulation. Here we present the case of a patient on self-administered hormonal supplements who presented in acute heart failure leading to cardiogenic shock in the setting of concurrent thyroid, adrenal, and gonadal axis dysfunction. Case Description: A 28-year-old male with no significant medical history was transferred to our hospital after presenting to an outside emergency room with dyspnea, cough, nausea, and a subjective fever. He developed acute hypoxic respiratory failure requiring intubation. Echocardiogram performed showed an ejection fraction (EF) of 10%. He was started on two vasopressors and methylprednisolone 1 g daily for two days, due to concern for myocarditis versus giant cell arteritis. Hormonal work-up showed TSH 0.02 mIU/L (normal range 0.3-4.2), free T4 0.4 ng/dL (0.9-1.7), total T3 48 ng/dL (80-200), FSH <0.3 IU/L (1.2-15.8), LH <0.2 IU/L (1.3-9.6), ACTH <5.0 pg/mL (7.2-63), cortisol 1.7 mcg/dL (2.5-12), estradiol 171 pg/mL (8.0-35), total testosterone 1730 ng/dL (240-950), and prolactin 47 ng/mL (4.0-15.2). He received 10 mg dexamethasone at the outside facility. A medication bag found by his family included online purchases of non-prescribed testosterone cypionate and enanthate, liothyronine, anastrozole, and clomiphene. None were medical grade. He was also taking the anabolic steroid clenbuterol for 3 days prior. Echocardiogram on day 3 of admission showed an improved EF of 36%. Cardiac magnetic resonance imaging (MRI) showed a papillary fibroelastoma and myocarditis. Patient was weaned off vasopressors and the ventilator. He was discharged on levothyroxine 50 mcg daily and hydrocortisone 10 mg twice daily for outpatient reassessment. Transesophageal echocardiogram confirmed diagnosis of papillary fibroelastoma. One month Endocrinology clinic follow-up showed no evidence of posterior pituitary, thyroid, or adrenal axis dysfunction or growth hormone excess, but he continued to have gonadal axis suppression with elevated prolactin and estradiol, the latter thought to be secondary to conversion from testosterone. Pituitary MRI showed no micro or macroadenoma. His EF recovered to 50%. He is pending surgical removal of the aortic valve fibroelastoma. Discussion: With hormonal supplements easily accessible online, it is important for physicians to counsel patients about the dangers of misuse. This case highlights a previously healthy 28-year-old man who presented in critical condition with cardiogenic shock and hypothalamic-pituitary axis dysfunction from supplements he purchased online. There should be targeted educational interventions regarding the harm of supplements aimed at the bodybuilding community to prevent similar cases. Presentation: 6/2/2024

12438 Developing A Natural Language Processing Algorithm To Identify Insulin Pump Users Using Unstructured Clinical Notes From The Electronic Health Record

Abstract Disclosure: E.M. Everett: None. R. Tiu: None. B. Zhu: None. T. Moin: None. A.T. Bui: None. Background: Insulin pumps (pump) have many benefits to patients with type 1 diabetes compared to management with multiple daily injection regimens. Unfortunately, disparities exist in pump therapy access and use, particularly in racial-ethnic minoritized groups, those of lower socioeconomic status or limited English proficiency. Given that these groups are underrepresented in pump clinical trials, evaluating data from real-world populations such as those from large health systems is critical to improve technology use in these groups that also experience disparities in diabetes outcomes. Unfortunately, it is very challenging to identify diabetes technology users using electronic health record data due to the underutilization of ICD and procedure codes for pump use and the documentation of pump use in unstructured form in clinical notes, which is more difficult to extract outside of manual chart review. Consequently, a novel approach is needed to capture this population on a large scale. We aim to develop an algorithm using the machine learning method natural language processing (NLP), to identify these technology users and non-users in health systems, which would allow us to study pump use in real-world settings. Methods: To develop the algorithm, we performed chart review and cataloged documentation styles (keywords, phrases) indicating pump use from 88 clinical notes of adults with type 1 diabetes, authored by physicians and nurse educators in UCLA endocrinology clinics from 2014-2022. After reaching saturation for documentation styles, we used a series of regular expressions (Regex) to encode the algorithm, including code to negate phrases that may lead to false positives. Results: We tested the algorithm performance in an 85 note sample that included 59 pump users and 26 non-users. The algorithm detected 56/59 pump users and 26/26 non-pump users, yielding a sensitivity of 95% (95%CI 87-99%), a specificity of 100% (95%CI 86-100%) specificity, a positive predictive value of 100% (95%CI 94-100%), and a negative predictive value of 90% (95%CI 74-96%). Conversely, an approach using ICD and procedure codes only identified 17/59 pump users with a sensitivity of 28% (95%CI 18-42%), specificity of 100% (95%CI 87-00%), positive predictive value of 100% (95%CI 81-100%), and negative predictive value of 38% (95%CI 35-42%). Incrementally, the NLP algorithm identified ∼70% more pump users than the approach using billing codes. Conclusion: NLP is a promising approach to identify pump users using unstructured electronic health record data. Next steps include testing the current algorithm in a larger sample of clinical notes, revising the algorithm as needed. The final algorithm will be used to understand patterns and disparities of pump prescribing over time and will be leveraged as a recruitment tool to identify potentially eligible patients for future studies aimed at addressing pump disparities. Presentation: 6/3/2024

6450 Leydig Cell Tumor: A Rare Cause of Post-menopausal Hyperandrogenism

Abstract Disclosure: R. Nakdali: None. S. Athimulam: None. Introduction: Ovarian steroid cell tumors are a rare subtype of sex-cord stromal tumors. Leydig cell tumors is a subtype of sex-stromal tumors that is found in < 1% of all ovarian tumors. They are typically benign, unilateral, and secrete androgens which causes virilization. Below we present the case of a postmenopausal woman who presented with signs of virilization and was diagnosed with an ovarian Leydig cell tumor. Case: A 62-year-old postmenopausal woman, with a history of partial hysterectomy with right oophorectomy presented to Endocrinology clinic for evaluation of thyroid nodules. However, clinically she had signs of virilization noted by the provider on examination. She reported progressive androgenic alopecia, cystic acne, oily skin, hoarseness of voice and hirsutism, with increase hair growth over upper lip, chin and jaw line requiring daily shaving. She denied taking any supplements. She reported embarrassment of these physical changes and prior providers had attributed this to aging, therefore not prompting further testing. This caused significant emotional distress to the patient, leading to isolation. Biochemical testing confirmed elevated bioavailable testosterone (193.1 ng/dL) and total testosterone levels (579 ng/dL), with no evidence of hypercortisolemia. Magnetic resonance imaging (MRI) revealed a heterogenous soft tissue mass (2.9 x 2.1 x 2.1 cm) in the left ovary. She underwent a left salpingo-oophorectomy and pathology confirmed a well-differentiated 2.4 cm Leydig cell tumor. Post-operatively, she reported improvement in facial and body hirsutism, reduced shaving frequency decrease in androgenic hair loss, with noticeable hair growth in her frontal scalp, and her skin became less oily with reduced acne. Post-operative labs confirmed cure of hyperandrogenism (Bioavailable testosterone < 2.6 ng/dL; Total testosterone: < 10ng/dL; and Free androgen index < 0.5%). She has been referred to genetics for evaluation. Discussion: Post-menopausal hyperandrogenism poses a diagnostic challenge as it can be mistaken for hormonal imbalances seen with aging. Often times, patients do not report symptoms due to embarrassment unless specifically addressed by provider. Initial testing consists of total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) levels to assess the source of hyperandrogenism. Ruling out hypercortisolemia and assessment for ingestion of testosterone or DHEA supplements is vital. Pelvic ultrasound or cross-sectional imaging (CT or MRI) of abdomen and pelvis can identify structural abnormalities in the ovaries or adrenal glands. Prompt evaluation and management can alleviate significant distress to the patient. Leydig cell tumors represent a rare but important consideration in the differential diagnosis of postmenopausal hyperandrogenism, such as in our patient. Presentation: 6/2/2024

7275 Diverse Reasons for Discontinuing Gender Affirming Hormone Therapy

Abstract Disclosure: A. Jain: None. M.S. Irwig: None. Many Transgender and Gender Diverse (TGD) individuals take Gender Affirming Hormone Therapy (GAHT). A study that included 264 adults [67% assigned male at birth (AMAB)] in Georgia found that 2% (n=5) discontinued GAHT over a follow-up period of 64 months. Reasons identified were change in gender identity (n=2), financial barriers (n=2) and venous thrombosis (n=1). Discontinuation was temporary for 2 and permanent for 2. Here we describe the reasons why four TGD individuals discontinued GAHT. Case Descriptions: Patient 1, AMAB, came out as gay as a teenager. In his mid 30s he became unhappy which he attributed to a conflict between religion and his sexual orientation and failed relationships. He thought that changing his sex would solve his problems. He took injectable estrogen for 3-4 years. He subsequently underwent multiple gender-affirmation surgeries including facial feminization surgery, breast implants, an orchiectomy and vaginoplasty. Immediately following the breast implant surgery he had regrets and wanted them removed. He also regretted the vaginoplasty. He stopped estrogen following the bottom surgery. In his 40s he stated that he would like to detransition as he sees himself "as a fake" when looking in the mirror. Patient 2 was assigned female at birth. Puberty was associated with discomfort from having a large chest. In his late 20s he began injectable testosterone which he took for three years. He then decided to take a two year break as he was frustrated that he had not achieved the desired results and because he was still not able to pass as a man. He resumed testosterone two years ago and underwent top surgery. Patient 3, AMAB, knew from a young age that he was transgender. He took estrogen and an antiandrogen for > 5 years and underwent an orchiectomy and vaginoplasty. He was pleased with the results from the GAHT and surgeries. He presented as a woman for many years. A few years ago, however, he awoke one day with the thought that God wanted him to be a man. He decided to detransition and presented to the endocrinology clinic to start testosterone therapy. Patient 4, AMAB, began GAHT in her late 30s. She discontinued GAHT 4 years later due to lack of results (feminization, larger breasts, wider hips and a more curvy figure). She presented to the endocrinology clinic 2 years later, wanting to resume GAHT. Conclusion: In addition to the reasons identified by Gupta et al for discontinuation of GAHT, we also identified unrealistic expectations, not achieving the desired results and perceived conflict between religion and gender identity. Endocrinologists should be aware of the possibility of discontinuation of GAHT and know how to manage any potential complications such as hypogonadism that may arise. Reference: Gupta P et al. J Clin Endocrinol Metab. 2023. Presentation: 6/2/2024

12572 Incidental Adrenal Enlargement On Ct Scan In South Brooklyn Health, How Often Is It Functional?

Abstract Disclosure: R. Ruggiero: None. N. Simon: None. Background: Incidental findings of adrenal hyperplasia are increased due to the widespread rise in cross sectional imaging, as well as improvement of imaging modalities. There is a lack of literature reporting on the prevalence of incidental adrenal hyperplasia. One study reported a prevalence of 11.3%. Adrenocortical hyperplasia can result from endocrine disorders such as ACTH dependent and independent Cushing syndrome, primary aldosteronism, Multiple Endocrine Neoplasia type 1, and congenital adrenal hyperplasia. Other reported causes are radiographic adrenal enlargement of unknown cause and without clinical or biochemical manifestations, inflammation, neoplasms, and depression. Most cases are a radiographic finding with no clinical significance. One study reported that 69.23% of cases were nonfunctional. There are currently no guidelines in place for biochemical evaluation of incidental adrenocortical hyperplasia. Patients are typically referred to endocrinology services. Objective: The purposes of this study was to: 1. Evaluate the number of patients referred to endocrinology clinic for incidental abnormal adrenal imaging. 2. Examine the percentage of abnormal adrenal imaging findings on CT scan, in particular adrenal hyperplasia, that are hormonally active. Methods: This was a retrospective study of patients who were referred to endocrinology clinic or electronic endocrine consult for incidental abnormal adrenal imaging, excluding those with clear diagnosis of masses, nodules, adenomas, or cysts. Data collected included demographics, type of study imaging and radiologist reader, hormonal studies, comorbid conditions such as diabetes mellitus, hypertension, obesity, osteoporosis, as well as visit type to endocrinology service (e-consult vs in person). Results: The total number of consults referred to endocrinology during this period was 138. Due to repeat referral or having an adrenal pathology other than hyperplasia, 83 patients were excluded from analysis. There were 55 patients with isolated adrenal hyperplasia, 86% of whom were Caucasian, 11% Hispanic, and 78% of patients were female. Median age 63 years old. Hypertension was noted in 69% of patients, 36% had diabetes mellitus or dysglycemia, 36% were obese, and 1.8% had osteoporosis. Imaging reading was performed by 3 radiologists, 75% of cases reported by one reader. Only 5% of referrals were answered as an e-consult. About 27% of patients did not show up to establish care. Hormonal workup was completed by 60% of the patients, with 16 % having abnormal findings. One patient required confirmatory workup. No patients required treatment. Conclusion: Adrenal Hyperplasia is often an incidental radiologic finding, that can be reader dependent. Most cases are nonfunctioning without abnormal findings on hormonal workup. E-Consultation can be an efficient tool to help PCP and reduce endocrine clinic visits. Presentation: 6/1/2024

8401 Genetic Characterization of a Case of Primary Aldosteronism in an 11-Year-Old Girl carrying a Germline VUS of CACNA1H and a Somatic Mutation of CTNNB1

Abstract Disclosure: S. Parisien-La Salle: None. G. Van Vliet: None. G. Corbeil: None. M. Labrecque: None. M. Tétreault: None. I. Bourdeau: None. Introduction: Primary aldosteronism is a frequent cause of secondary hypertension in adults but is rare in children. We report the case and genetic studies of an 11 yo girl presenting with primary aldosteronism at puberty. Case presentation: An 11-year-old female patient was referred to the pediatric endocrinology clinic for hypertension (166/118). Her past medical history and family history were unremarkable. She reported polyuria, polydipsia and occasional headaches and abdominal pain. Her Tanner stage indicated that puberty was initiated (P2M2). An abdominal CT revealed a 9x10x11cm right adrenal mass with calcifications and a necrotic zone. On [1]8F-FDG PET/CT, the mass had an uptake of 2.9 SUVmax. Laboratory results revealed hypokalemia (K: 2.6 mmol/L [N: 3.5-4.5]) and elevated aldosterone (1712.8 pmol/L [N: 110-1330]) with suppressed renin (0.2 ng/ml/h [N: <5.3]). Her urinary aldosterone level was elevated (114 nmol/day [N: <67]). The rest of the biochemical adrenal panel was normal. Patient underwent a right adrenalectomy by laparotomy. The pathology report showed an adrenal tumor without capsular or vascular invasion. The only malignancy criterion was an area of necrosis and the ki-67% proliferation index was < 1%. Genetic investigations: After informed consent, the patient underwent germline analysis for the chimeric gene CYP11B2/CYP11B1 (Ruhr University Bochum, Germany) and a multigene panel including KCNJ5, CACNA1D, CACNA1H and CLCN2 genes (Fulgent, CA), which were both negative except for a variant of unknown significance (VUS) that was identified in CACNA1H (c.3868G>A, p.Val1290Ile) with a minor allele frequency of 3.291E-5 (GnomAD). Tumor DNA was extracted after adrenalectomy from fresh frozen tissues. Somatic genetic analysis of GNAS, CTNNB1, KCNJ5, ATP1A1, ATP2B3 and CACNA1D was performed using direct Sanger Sequencing (Genome Quebec Innovation Centre) and revealed a heterozygous missence pathogenic variant in the CTNNB1 gene (c.121 A>G p.Thr41Ala). This mutation was absent in leukocyte DNA of the patient. Immunohistochemistry of the adrenal tumor disclosed strong cytoplasmic β-catenin staining in most tumor cells (monoclonal anti-β-catenin antibody; BD Transduction Laboratories). RNA-sequencing of patient tumor RNA was performed (Research Center CHU Québec) and compared to human adrenal total RNA (Clontech, Mountain View, CA). Pathway enrichment analysis showed activation of the Wnt signaling pathway. No variant was identified in GNAQ or GNA11 genes. However, GNRHR was upregulated compared to the control sample with a log2 fold change of 3.96 (p=0.000074). Conclusion: We present a rare pediatric case of an aldosterone producing adenoma harbouring a somatic β-catenin pathogenic variant with upregulation of GNRHR. The implication of the germline CACNA1H VUS still needs to be clarified. Presentation: 6/3/2024

8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek

Abstract Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None. Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP). Presentation: 6/1/2024