Adrenal Insufficiency Research Articles

7550 Case Report On Concurrent Metastases To The Pituitary And Adrenal From A Primary Breast Cancer

Abstract Disclosure: M.V. David-santos: None. M.C. Isidro: None. Background: Metastatic Cancer to the pituitary gland is a rare condition accounting for 0.5% of all pituitary tumors. It rarely manifests clinically and is often found incidentally. Endocrine dysfunction usually arise, with 38.4% of cases presenting with Diabetes Insipidus, while 37.7% as Panhypopituitarism. On the other hand, prevalence of adrenal metastases is at 0.5 to 3.8% with 43% occurring bilaterally. Primary adrenal insufficiency occurs at 12.4% among those with bilateral metastases. Case: A 32-year old Chinese woman was diagnosed with Stage 4 breast adenocarcinoma ER PR Her2 Neu positive with metastases to the axillary lymph nodes, bone and right adrenal in July 2021. She underwent chemotherapy with Paclitaxel and Trastuzumab then radical mastectomy of the left breast in April 2022.5 months post op, PET scan was done which showed a 11 x 18 x 21 mm pituitary mass. In light of the primary malignancy, lesion was considered a metastatic focus. At that time, patient did not exhibit any neurologic symptoms such as blurring of vision or headaches. No polyuria, polydipsia, nocturia, easy fatigability, nausea or vomiting. Physical examination findings were normal. A hormonal panel showed the following: elevated Prolactin at 150 ng/ml (NV 3-20), normal plasma ACTH IRMA 10 pg/ml (NV < 50 pg/ml), low 8AM plasma cortisol at 1.55 ug/dL (Ref 5- 25 ug/dL), TSH was low at 0.15iIU/ml (0.27-3.75) while FT4 was normal at 0.87 ng/dl (NV 0.68 - 2.56).ACTH stimulation showed low cortisol at the 30th minute and 1st hour post ACTH infusion. Serum sodium and urine Osmolality were both normal. The hyperprolactinemia was attributed to Stalk effect, while the decreased cortisol was considered as central adrenal insufficiency. She was then started on Prednisone 5mg tab daily. Repeat TSH and FT4 5 months after showed normal TSH at 1.209, low FT4 at 5.97 pmol/L (NV 9.01-19.05). She was started on Levothyroxine 50mcg daily for the central hypothyroidism.Repeat Cranial MRI 4 months post diagnosis of the pituitary mass showed increased in its size. An endoscopic transsphenoidal resection and biopsy of the pituitary mass showed metastatic carcinoma of the pituitary gland. Staining of the sellar tumor were compatible with a metastatic carcinoma of breast origin. Intensity-modulated radiation therapy (IMRT) at 400 gray was done for 5 fractions and Trastuzumab was continued. Cranial MRI done 6 months post IMRT showed decreasing size of the pituitary mass to its latest size of 6 x 9 x 13 mm as of November 2023. Latest Whole abdominal CT scan of the adrenals showed clearing of the right adrenal Nodule. Conclusion: Breast cancer may also metastasize to endocrine organs causing hormonal dysfunction. Although curative treatment is no longer the goal for Metastatic breast cancer, prolongation of the quality of life is an important aspect to consider. Hormonal work up, surveillance and hormonal replacement can help in attaining this goal. Presentation: 6/3/2024

7443 Severe Hypothyroidism and Adrenal Insufficiency in a 27-Year-Old Male with Klippel-Feil Syndrome: A Case Report

Abstract Disclosure: S. Almardini: None. F. Haddadin: None. L. Aoun: None. F. Saliba: None. J. Zaidan: None. Background: Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by improper segmentation of the cervical vertebrae. The classical clinical triad consists of short neck, low posterior hairline, and limited neck mobility. It is uncommonly associated with endocrine abnormalities. We present a rare case of KFS with severe primary hypothyroidism. Case Presentation: A 27-year-old male with KFS presented for evaluation of profound fatigue and lack of energy. His vital signs revealed a heart rate of 50 and a borderline low blood pressure. On physical exam patient was noted to be lethargic and icteric, thyroid exam was limited due to patient short neck. Labs were consistent with severe hypothyroidism TSH of 825 mIU/L, total T4 <0.4 mcg/dL, low 8 AM cortisol of 4.3 mcg/dL, elevated LDL at 333 mg/dL, elevated liver enzymes AST 491 U/L, ALT 294 U/L, neutropenia with WBC 2.69 x10^3/uL 20% neutrophils and anemia Hb 12 g/dL. TPO and thyroglobulin antibodies were positive at 149.0 and 109.0 IU/mL respectively, 21 hydroxylase antibodies were negative. Thyroid Ultrasound showed small and diffusely heterogenous thyroid. Patient was started on Levothyroxine 125 mcg daily and hydrocortisone with improvement in his symptoms as well as normalization of his lipid panel, liver enzymes and neutropenia. The patient was continued on levothyroxine 125 mcg, hydrocortisone was tapered and repeat cortisol levels were normal. Discussion: This case demonstrates an unusual association between KFS and hypothyroidism secondary to Hashimoto thyroiditis, likely representing an incidental finding rather than a causative relationship. The cervical spinal abnormalities and short neck characteristic of KFS could potentially lead to compression of neurological and vascular structures in the neck. However, this is unlikely to fully explain our patient's hypothyroidism. There are few published case reports of KFS with endocrine disorders in the literature that describe incidental findings like autoimmune thyroiditis and hypoparathyroidism, but there is no known biological mechanism linking KFS and endocrine dysfunction. Moreover, there is no evidence in either our patient's case or in existing literature to suggest a higher occurrence of autoimmune disorders like Hashimoto in such individuals. Conclusion: we present a novel case of KFS found incidentally with primary hypothyroidism. While these endocrine disorders could compound the growth delay and developmental issues typically seen in KFS, they do not appear to be causally related. This case highlights the need to monitor endocrine function in KFS patients and serves as a reminder that common conditions may co-occur simply by chance. Presentation: 6/3/2024

7236 Long Term Extension of Osilodrostat Therapy in Canadian Patients with Cushing’s Disease Benefiting from the LINC 3 and LINC 4 Studies

Abstract Disclosure: L.M. Martel: Other; Self; LMD receives partial fellowship salary support though educational grants from Recordati Rare Disease Canada Inc and Pfizer Canada. G. Houde: Other; Self; GH served as a consultant for Novartis. C. Chik: Other; Self; grants and/or consulting fees from Pfizer, Ipsen, Novartis and Novo Nordisk Canada. S.A. Imran: Other; Self; consulting fees from Pfizer, Recordati and Novartis. E. Paron: Other; Self; employees of Recordati Rare Disease Canada Inc. F. Lebel: Other; Self; employees of Recordati Rare Disease Canada Inc. A. Lacroix: Other; Self; reports grants and personal consulting fees from Novartis, Recordati and Pfizer. Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained cortisol normalization in Cushing’s disease (CD) patients in two Phase III trials (LINC 3, NCT02180217; LINC 4, NCT02697734); persistent biochemical and clinical improvement of CD were reported after 72 and 96 weeks of therapy, respectively (10.1530/EJE-22-0317; 10.3389/fendo.2023.1236465). After study completion and continued clinical benefit with osilodrostat, patients could transition in a roll-over study (CLCI699C2X01B , NCT03606408). As osilodrostat is now approved for therapy of CS in Europe and CD in USA, but not in Canada, seven Canadian patients who had benefited from osilodrostat were transitioned to an investigator initiated study ((ISS-CA-2023, NCT06131580). Objective: To analyze the course of therapy with osilodrostat which allowed long-term biochemical and clinical control of CD since initiation of LINC 3 and LINC 4 core studies for up to 105 months. Methods: Retrospective review of clinical, biochemical and imaging data were collected through chart review of 11patients enrolled in four Canadian centers in LINC 3 and 4 in LINC 4 parent studies. Seven patients remained in the roll-over study until termination and initiation of the Canadian study on October 24 2023. Data from initiation of therapy until October 24 2023 were analyzed. Results: Of the eleven enrolled patients, four discontinued treatment due to muscle cramps, repeat transsphenoidal surgery (TSS) for corticotroph adenoma progression in 2 cases, and hyperandrogenism and opting for bilateral adrenalectomy in one case. Seven cases (5 LINC 3 and 2 LINC 4) pursued therapy in the extension study: 2 men and 5 women, mean age 46 y.o. (range 28-72). All but one had previous TSS, one Gamma Knife and 4 received previous medical therapy. The median 24 hour urinary free cortisol (UFC) before starting osilodrostat was 334 nnmol/d (2.4 x ULN; range 133-414). The median treatment duration was 82 months (range 67-105) and median time to normalize UFC was 36 days. The median maximal dose required to normalize UFC was 10 mg/day (4-60); dose was frequently reduced because of symptoms of relative cortisol withdrawal or adrenal insufficiency (n: 5) to 6.5 mg/day (range: 1 mg every 6 days to 30 mg/d) currently. Last median UFC was 60 nmol/d (range 22-154; 6/7 in normal range < 138nmol/d). Tumor growth occurred in 1 patient (2mm). All patients presented partial to complete improvement of CD features, whereas one patient developed moderate clinical hyperandrogenism, hypertension and borderline prolongation of QTc that normalized after a dose reduction. Conclusions: Osilodrostat can provide sustained biochemical and clinical control of hypercortisolism in patients with CD for up to 9 years; however drug efficacy and dose requirement varies greatly between patients and must be adjusted carefully and regularly during course of therapy. Presentation: 6/3/2024

6927 Metyrapone To Reset The Nocturnal Cortisol Rhythm In Mild Autonomous Cortisol Secretion (MACS) - Safety And Impact On Cardiometabolic Risk Factors

Abstract Disclosure: S. Berry: None. A. Iqbal: None. J.D. Newell-Price: Consulting Fee; Self; HRA Pharmaceuticals. M. Debono: Consulting Fee; Self; HRA Pharmaceuticals. Grant Recipient; Self; HRA Pharmaceuticals. Speaker; Self; HRA Pharmaceuticals. Background: MACS is associated with increased cardiometabolic risk including hypertension, type 2 diabetes and dyslipidemia. In MACS, serum and salivary cortisol and cortisone levels are significantly higher in the nocturnal period but follow the usual daytime pattern. Combined early and late evening dosing with the short-acting 11-beta hydroxylase inhibitor, metyrapone, has previously been shown to acutely ‘re-set’ this abnormal part of the cortisol curve to normal. We have now assessed the impact of long-term evening metyrapone on cardiometabolic dysfunction in MACS. Method: A retrospective, controlled, longitudinal study evaluated the safety and tolerability of nocturnal metyrapone and its impact on cardiometabolic risk factors. We included all patients (n=15) who were initiated on metyrapone treatment, 250mg-500mg at 6pm and 250mg at 10pm, for MACS at a tertiary endocrinology center between 2015 and 2022. Age and sex-matched controls were selected from patients with adrenal incidentalomas and non-suppressed serum cortisol following 1mg overnight dexamethasone suppression testing. Systolic blood pressure (SBP), diastolic blood pressure (DBP), weight, HbA1c and non-HDL cholesterol were assessed at baseline and after 6 months. Morning serum cortisol values were evaluated to check for adrenal axis over-suppression. Wilcoxon signed-rank test was used to compare pre/post-treatment, and Mann-Whitney U test was used to compare metyrapone group to controls. Results: Metyrapone was tolerated by 12/15 patients - two stopped due to diarrhea and one due to high androgens in a female. There were no occurrences of adrenal crises. The morning cortisol after metyrapone was 365 nmol/L (IQR 254-431nmol/L, n=13). ACTH increased from 4.5 pg/ml to 7.5 pg/ml (SE±2.15, n=12) after treatment. In the metyrapone group compared to controls, there were significant decreases in SBP (-26.4 SE±8.1mmHg, p=0.008, n=9) and DBP (-12.9 SE±5.5mmHg, p=0.024). Four patients in the control group had up-titration of antihypertensive medication between measurements compared to only one in the metyrapone group. The differences between groups in HbA1c, weight and non-HDL cholesterol were not statistically significant. However, the increase in HbA1c was less in the metyrapone group compared to the control group by 3.0 SE±4.5mmol/mol, as was the non-HDL cholesterol by 0.4 SE±0.33mmol/L (n=10). Conclusion: Evening metyrapone is associated with significant reductions in SBP and DBP in patients with MACS, without causing adrenal insufficiency and with preservation of normal morning serum cortisol. Monitoring 9am cortisol is important to avoid over-treatment. A larger, powered, prospective study is needed to definitively investigate the broader metabolic outcomes and assess the clinical utility of metyrapone in MACS. Presentation: 6/3/2024

6766 Cortisol Pumps: Hospitalizations And Quality Of Life

Abstract Disclosure: A. Tiwari: None. R. Berry: None. A. Mokbel: None. A. Abotouk: None. A.R. Alrifai: None. J. Waleed: None. O. Alzohaili: None. Introduction: Oral regimens of exogenous cortisol fail to mimic physiologic levels. The discrepancy leads to complications, notably nausea, hyperglycemia, and susceptibility to infection. Finer control over cortisol delivery may be achievable with infusion pumps. While international groups have published their experiences with cortisol pumps, these studies often include less than ten patients. We share the largest, single-center cohort ever documented and the first from an American clinic. Methods: We conducted a retrospective cohort study. Through chart review, we identified all patients who received a cortisol pump at a private clinic; these pumps were originally designed to deliver insulin, but we repurposed them for patients with adrenal insufficiency. Clinic notes allowed collection of cortisol dosing pre- and post-exposure to the cortisol pump. We supplemented this information with telephone and digital surveys on the frequency of hospitalization, symptoms, and quality of life; patients provided verbal consent before participation. A Wilcoxon signed rank test and Fisher exact test evaluated significant differences between groups. Results: We identified thirty patients who received a cortisol infusion pump. Our study revealed a statistically significant decrease in hospitalization rate after exposure to a cortisol pump (n=26, mean difference = -5.94 hospitalizations per year, p=0.003), a decrease in the frequency of fatigue (n=25, p=0.0001) and a decrease in the frequency of hypotension (n=25, p=0.005). A validated, quality of life survey corroborated these findings with improvement in twenty-seven out of twenty-eight questions (n=22, p<0.05). However, we did not detect a statistically significant difference in the frequency of eighteen other symptoms nor cortisol dosing between pre- and post-exposure groups. Conclusion: Infusion pumps can better mimic physiological variations in cortisol than oral dosing regimens. We show the extent to which cortisol dosing may reduce hospitalization rate - and therefore cost - as well as improve quality of life. We hope our findings encourage the availability of infusion pumps for adrenal insufficiency, a smaller market that may not otherwise attract commercial investment for a dedicated, randomized trial. Presentation: 6/3/2024

8131 A Rare Case of Autoimmune Polyendocrine Syndrome; a Menopause Despite Replacement Therapy

Abstract Disclosure: M.E. Chacon Cruz: None. M. Sanchez Cordero: None. R.M. Roman Torres: None. G. Guerra Velazquez: None. Polyendocrinopathy is a heterogeneous group of disorders leading to dysfunction of multiple endocrine glands and other tissues. The syndromes can occur in patients from early infancy to old age and new components of a given syndrome can appear throughout life. APS can be classified into APS type 1 and APS2-4. APS-1 is a rare monogenic autosomal recessive autoimmune disorder consisting of the triad of chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. APS2 require presence of Addison disease, autoimmune thyroid disorder and type 1 diabetes. APS 3 requires presence of Thyroid autoimmune disease associated with other autoimmune diseases. APS4 is a combination of organ specific autoimmune disease non included in a previous group. Autoimmune oophoritis is found in approximately 4 percent of females who presented with spontaneous primary ovarian insufficiency and may occur in type I and II syndromes of polyglandular autoimmune failure. This is the case of 44 year old female patient with history of hypertension, hypoparathyroidism diagnose at the age of 9 year old, vitiligo and premature ovarian failure diagnose at the age of 16 year old. Patient reported that started with multiple episodes of watery non bloody diarrhea and arthralgia. Patient went to her Pediatrician and they found hypocalcemia hyperphospathemia. Patient mineral was replaced with medication and then followed by pediatric endocrinologist. Patient continues with normal life, but menstrual periods had not started even at age 16th. Laboratory work up was done and premature ovarian failure was diagnosed after that, patient started with progesterone and estrogen to induce menstrual periods. Menstrual periods began regularly and monthly. Patient continues taking medication regularly, phoslo, calcitriol, progestin and estradiol without problem until this year that despite regular medication, started with signs and symptoms of menopause with irregular menstrual periods, palpitations hot flashes, sweating, anxiety and sleep problems. Patient met criteria for APS4 due to combination of organ specific autoimmune disease such premature ovarian failure, vitiligo and hypoparathryroidism. This case is extremely important since despite the fact that there is no family history of either endocrinological or autoimmune diseases, our patient debuts throughout her life with several autoimmune diseases, such as premature ovarian failure and vitiligo. Patient had Schedule appointment with gynecologist who increased the dose of progestin and estradiol. This case highlights the importance of being vigilant about new components of a syndrome developing at different times though a patient's life. As described, autoimmune diseases commonly are related to other diseases, but without a good clinical history and physical examination could be misdiagnosed affecting the quality of life of those patients. Presentation: 6/2/2024

8705 Autoimmune Polyglandular Syndrome Type 2 Presenting As Recurrent Cardiac Tamponade

Abstract Disclosure: E.M. Niedzialkowska: None. D. Shelden: None. Introduction: Autoimmune polyglandular syndrome type 2 (APS2) is a rare endocrinopathy with co-occurrence of autoimmune adrenal insufficiency, autoimmune thyroiditis and/or type 1 diabetes. In rare cases, APS2 can predispose patients to recurrent pericardial effusion and tamponade. Case presentation: 32 y.o male with medical history of hypothyroidism on replacement therapy diagnosed 2 weeks prior to admission presented with progressive dyspnea and hypotension. The patient was found to have pericardial effusion with tamponade requiring pressor support. Initial lab tests showed TSH 148.7 uIU/ml (N 0.4-4.5), free t4 0.7 ng/dl(N 0.7-1.5 ), free t3 2 pg/ml (N 1.7-3.5), Hb a1c 4.7% (N <5.6%), thyroglobulin antibody 851 IU/ml (N <20), TPO antibody >1 000 IU/ml (N<=35), TSI 0.1 IU/l (<0.1), sodium 127 mmol/l (N 135-145), and a negative adrenal antibody panel. The patient was started on IV levothyroxine (400 mcg daily) and stress dose steroids in the setting of shock requiring 4 pressors. Shock resolved after pericardiocentesis and the patient was weaned off pressor support. Pericardial fluid showed neutrophil predominance and was negative for an infectious process, lab tests showed negative ANA, ANCA and GBM. The day following admission lab tests showed TSH of 23.86 uIU/ml, ft4 1.3 ng/dl, the patient was transitioned to oral levothyroxine 125 mcg and the steroid regimen was tapered and discontinued. Follow up tests showed normal TSH and resolution of pericardial effusion. Four weeks after initial admission the patient was readmitted due to hypotension. Laboratory tests showed random cortisol <1.0 ug/dl (N 2.9-19.4), ACTH 17 pg/ml (N 6-48), adrenal antibody titers 1:20 (N < 1:10), cosyntropin stimulation test was positive for adrenal insufficiency and the patient was started on steroid regimen with symptomatic improvement. He was diagnosed with APS type 2 based on his constellation of endocrinopathies. Repeat echocardiogram was negative for pericardial effusion. Two months later, the patient presented with chest pain. Imaging was positive for recurrent pericardial effusion requiring pressor support and pericardiocentesis. The patient was subsequently started on colchicine. Infectious and rheumatologic workup continued to be negative. The patient did not exhibit symptoms of connective tissue disease. Seven months after the initial presentation the patient was readmitted with COVID-19 infection complicated by hypotension and a small pericardial effusion. Symptoms improved after initiation of stress dose steroids. Conclusion: Cardiac tamponade is a rare presentation of APS2 with 9 cases reported in the literature up to date. Increased incidence of pericardial effusion is presumed to be a result of autoimmune inflammation leading to fluid accumulation. The patients are prone to tamponade due to intravascular volume depletion, decreased vascular tone and impaired stress response. Presentation: 6/3/2024

9296 A Novel LC-MS/MS Salivary Fludrocortisone Method With Potential for Monitoring in Adrenal Insufficiency Patients

Abstract Disclosure: M. Dolan: None. D. Marshall: None. J. Hawley: None. N. Reisch: None. B.G. Keevil: None. Fludrocortisone (FC) is a fluorinated exogenous mineralocorticoid used to treat conditions associated with adrenal insufficiency including Addison’s disease and classic congenital adrenal hyperplasia (CAH). The mineralocorticoid action of FC allows the drug to compensate for aldosterone deficiency, thus helping to maintain blood pressure and other homeostatic mechanisms. Optimising FC replacement is vital as under-replacement can cause dizziness and hypotension, whereas over-replacement can lead to cardiometabolic disturbances. Treatment in classic CAH patients, who are typically diagnosed as new-borns, is even more complex as the requirement for mineralocorticoid replacement decreases with age. Endocrine Society guidelines recommend that FC monitoring should involve the clinical assessment of symptoms, which can be non-specific, and regular blood pressure measurements. Plasma renin activity (PRA) should be measured if clinical changes occur, aiming towards the upper end of the reference range. The utility of PRA is debated due to methodological issues and the inherent variability of the analyte itself, which may not always represent FC replacement status. Therefore, investigation into alternative biochemical markers of FC replacement is required. Here we aimed to facilitate this by developing an LC-MS/MS method for the measurement of salivary FC. Method: A salivary FC LC-MS/MS assay has been developed and validated for use according to FDA and EMA guidelines. Passive drool samples from 10 clinical trial patients with classic CAH were collected on two separate occasions at select time points throughout the day (0800, 1200, 1600, 2000 and 2300h). In most patients the 0800h sample was taken pre-FC dose. Once in the laboratory the patient samples were extracted and analysed using the FC method to produce a FC concentration day curve. Results: The method analysis time was 2.1 minutes, with a mean recovery of 102% and limit of quantification of 5 pmol/L (2.1 pg/mL). No analytical interference was identified. Analysis of patient samples using the method showed the presence of FC allowing the production of day curves. In most patients, the pre-dose sample contained no FC, with the subsequent samples showing a peak FC concentration corresponding to the Cmax. After this the FC concentration gradually tapered off throughout the remainder of the day. Conclusions: We have developed a novel assay for the measurement of salivary FC, which may allow the calculation of the area under the curve. As an optimal FC dose has yet to be determined this method may facilitate more in-depth pharmacokinetic studies into FC metabolism and blood pressure control. Thereby identifying patients that are fast metabolisers or poor absorbers of the medication, enabling a non-invasive strategy to optimise patient care. Presentation: 6/1/2024

6985 Intravenous Immunoglobulin induced Type 1 diabetes remission

Abstract Disclosure: N. Shahid: None. D. Newbern: None. Introduction: Intravenous immunoglobulin [IVIG] is an immunomodulatory agent used for treatment of autoimmune and inflammatory conditions. However, it is not indicated in patients with type 1 diabetes [T1D] as its efficacy has not been established. Clinical Case: A 9-year-old previously healthy boy presented to the Emergency Department with several days of unexplained bruising and mucosal bleeding with no prior history of trauma, bleeding disorders or other systemic symptoms. Physical examination showed generalized petechiae, ecchymosis and purpura. Vitals were normal including weight and BMI. Initial labs confirmed Immune thrombocytopenic purpura [ITP] as his platelets were less than 1K/µL with otherwise normal peripheral blood cell counts and smear. Concomitantly, labs showed significant hyperglycemia [260mg/dL] with glycosuria and trace ketonuria. Glycated hemoglobin [Hba1c] was elevated at 10.5% and ultimately Pancreatic autoantibodies [GAD65, Zinc transporter-8 and islet cell antibody] came back positive confirming T1D. Other autoimmune disorders such as adrenal insufficiency, thyroiditis, and celiac disease were ruled out. For the treatment of ITP, he the patient received 1 dose of IVIG 1g/kg and responded well with a rise in platelets to 6K/µL. The morning following the infusion, due to fasting hyperglycemia, the patient was started on basal-bolus insulin regimen. By 2nd day post IVIG, he had hypoglycemia, so insulin was discontinued with normalization of blood sugars. He is now 7 months post IVIG with no recurrent episodes of thrombocytopenia. He also remains off insulin with Hba1c in the 5.9-6.5% range. He eats a regular diet with avoidance of simple carbohydrates. He wears onwears a a continuous glucose monitor, which shows that blood sugars are in range 93% of the time He remains euglycemic overnight with transient self-resolving mild post-prandial hyperglycemia. Pancreatic autoantibodies have been reassessed and remain positive Conclusions: This case demonstrates that IVIG used for the treatment of ITP has induced a state of remission in our patient with newly diagnosed with T1D. IVIG is not a standard of treatment for T1D, however, when given for other autoantibody- or T-cell-mediated autoimmune conditions, it may reduce the insulin need in patients with known diabetes or induce remission in patients with newly diagnosed diabetes.

8380 Pituitary Stalk Interruption Syndrome, A Rare Cause of Panhypopituitarism

Abstract Disclosure: F. Abdulkarim: None. E. Alshdifat: None. P. Henriquez Feliz: None. J. Vargas-Jerez: None. T. Zahra: None. Pituitary Stalk Interruption Syndrome, A Rare Cause of Panhypopituitarism Faridat Abdulkarim, MD. Esra’a Alshdifat, MD. Pamela Henriquez Feliz, MD. Julia Vargas- Jerez, MD. and Tasneem Zahra, MD. Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital pituitary anatomical abnormality with reported incidence of 0.5 per 100,000 live births. It is characterized by the triad of thin or interrupted pituitary stalk, absent or ectopic posterior lobe and hypoplastic or aplastic anterior lobe seen on MRI. The anterior pituitary function is usually impaired however the posterior pituitary is usually intact and normal. We report a case of a Now 34-year-old Female who presented to the endocrine clinic with underdeveloped sexual characteristics. MRI done was consistent with PSIS. This is the second case of PSIS we report from our Institution. Case Presentation: A Now 34-year -old Hispanic American Female presented to our endocrine clinic with underdeveloped secondary sexual characteristics. She had panhypopituitarism, including Growth hormone deficiency and was treated with growth hormone from early childhood until age 13-14 years. She re-presented to our clinic at the age of 28 years after being lost to follow up for many years. On physical examination, she was 175cm tall, weighed 89.4kg and BMI 29.1kg/m2Patient has pre-pubertal breast, tanner stage 1, no axillary hair, small external genitalia with scanty pubic hair. Hormonal analysis revealed Estradiol <5 pg/mL (low), FSH 0.4 IU/L (low), LH <0.3 IU/L (low), Progesterone 0.1ng/mL (Low), Testosterone <2.5 ng/dL (8.4- 48.1ng/dl) Prolactin 22.3ng/mL (3.4-24.1 ng/ml), TSH 0.88uIU/mL (0.27-4.20), Free T4 0.5ng/dl (0.9-1.8) , ACTH 7.7pg/mL (7.2-63.3), Baseline AM Cortisol 0.7ug/dL (6.0-18.4) and 5.5 ug/dL after Cosyntropin test, IGF-1 17ng/mL (83-280). Urinalysis revealed normal specific gravity. Chromosome analysis with Normal Karyotype 46XX. Pelvic US revealed Markedly diminutive uterus and ovaries. MRI of the pituitary was highly suggestive of PSIS. She is currently being treated with levothyroxine and hydrocortisone Conclusion: PSIS is a rare congenital abnormality. Fortunately has good prognosis, however if left undiagnosed/untreated has high mortality mainly from Adrenal insufficiency and Myxedema coma. The patient discussed above, has underdeveloped sexual characteristics and primary amenorrheaLaboratory finding consistent with Panhypopituitarism with Normal prolactin which is the case in most patient with PSIS. Imaging revealed atrophic uterus and ovaries, and MRI revealed Findings which are highly suggestive of PSISShe previously had problems with outpatient clinic visits and medication compliance. However, she is currently compliant with hormonal replacement therapy which is the mainstay of treatment. Presentation: 6/3/2024

6570 Treatment of Cushing’s With Levoketoconazole: A Case Series

Abstract Disclosure: N. Chamorro-Pareja: None. M. Haines: None. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Research Investigator; Self; Recordati, NovoNordisk, Perspectum Ltd, Lumos Pharma, Pfizer, Inc.. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. B.M. Biller: Consulting Fee; Self; Xeris Pharmaceuticals, Recordati Rare Diseases, Sparrow, Lundbeck. Background: Endogenous Cushing’s syndrome (CS) is a rare condition of excess cortisol secretion; the most common cause is a pituitary corticotroph tumor (Cushing’s disease [CD]). Medical treatment for CD is primarily used to control hypercortisolism in patients with persistent or recurrent disease after transsphenoidal surgery (TSS). Levoketoconazole (LKCZ), a steroidogenesis inhibitor, was FDA approved in January 2022 for CS treatment. This reports 3 cases of patients who were treated with LKCZ for recurrent CS. Clinical Cases: Case 1: 44-year-old (yo) male (M) with a history of CD with urinary free cortisol (UFC) >26x upper limit of normal (ULN) who was treated preoperatively with ketoconazole (KCZ) 1000 mg/day with UFC improved to 6x ULN. KCZ was discontinued at TSS, and he achieved remission post-operatively. He was lost to follow-up and re-presented after several years with worsening hypertension, muscle weakness, edema, and anxiety with UFC 28x ULN and a recurrent pituitary lesion on MRI. He declined repeat TSS and underwent radiation therapy (RT) and medical treatment. LKCZ was initiated at 150 mg twice daily (BID) and increased to 300 mg BID. At LKCZ 300 mg BID, he had a low UFC and mild nausea but an adequate serum morning cortisol (10.4 ug/dL, ref:6-18.4 ug/dL); LKCZ was reduced to 150 mg BID with resolution of symptoms (sxs) and normal UFC. Case 2: 56 yo M with a history of CD (UFC >3x ULN) who underwent 2 TSSs and RT over 10 years prior with eventual remission, but later recurred. Sxs included brain fog and mood disturbances. He achieved control with pasireotide but discontinued due to abnormal liver function tests. He was then treated with KCZ 400 mg/day but remained hypercortisolemic (LNSC 1.1x ULN) and was interested in trying a new medication, so was switched to LKCZ 150 mg BID with significant improvement of sxs and normalization of LNSC. Case 3: 54 yo F with presumed cyclic CD (negative whole-body and octreotide scans) with UFC 1.7x ULN and LNSC 3x ULN. TSS was performed with negative pathology; she had persistent hypercortisolemia and sxs including insomnia, fatigue, and mood disturbances. She was intolerant to and/or uncontrolled on 4 medications, including KCZ at 1000 mg/day that was discontinued due to a rash. She was started on LKCZ 150 mg BID and achieved normal LNSC and UFC after about 1 month. The drug was discontinued due to the development of a rash similar to that with KCZ. Conclusion: LKCZ is a new option for the treatment of CS in patients whose disease persists after TSS. These 3 patients had improvement of sxs and normalization of cortisol levels while on LKCZ, although one patient discontinued LKCZ due to a rash that was previously experienced with KCZ. The other two patients are being carefully monitored for liver function test elevation, QTc abnormalities and adrenal insufficiency with no issues to date. To our knowledge, this is the first case series of CS patients treated clinically with LKCZ. Presentation: 6/1/2024

8691 Recovery Of Adrenal Function After Stopping Mitotane In Patients With Adrenocortical Carcinoma

Abstract Disclosure: B. Altieri: None. O. Kimpel: None. F. Megerle: None. M. Detomas: None. I.O. Chifu: None. C.T. Fuss: None. M. Quinkler: None. M. Kroiss: None. M. Fassnacht: None. Background: Mitotane is the standard therapy of adrenocortical carcinoma (ACC), both adjuvantly in patients with high risk of recurrence and palliative setting, due to its relative selectivity of its cytotoxic effects towards adrenocortical cells. Therefore, it virtually always leads to adrenal insufficiency. However, frequency and characteristics of hypothalamic-pituitary-adrenal (HPA) axis recovery after discontinuation are not well defined. Methods: Retrospective study of patients with ACC adjuvantly treated with mitotane for ≥12 months who were disease-free at mitotane stop and had a minimum follow-up ≥1 year. Data on patients and tumor characteristics, mitotane treatment, and information on HPA axis were analyzed. Primary endpoint was the adrenal recovery. Explorative analysis of predictive factors (e.g. sex, age, follow-up in reference center, cumulative mitotane dose and plasma levels, duration of treatment, and dose of hydrocortisone-equivalent replacement) was performed using Cox regression. Mitotane plasma elimination rate and hormonal changes after mitotane stop were also investigated. Results: 56 patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8 g (interquartile range 1.8-3.4) were included. The average hydrocortisone-equivalent replacement daily dose during mitotane treatment was in median 49.4 mg (41.1-53.5). Mitotane plasma levels decreased slowly after discontinuation, but with a very high variability between individual patients. Median time until mitotane levels dropped below 5 mg/L, 2 mg/L, and the detection limit was 152 days (114-202), 280 days (192- 37 370), and 395 days (227-546), respectively. Full adrenal recovery was documented in 32 (57%) patients after a median time of 26 months (95%CI=19.6-32.4). Among these, 22 (69%) achieved HPA recovery within 24 months. To note, a complete recovery after more than 67 months did not occur. Partial and insufficient recovery were observed in 10 (18 %) and 14 (25%) patients, respectively. In four patients (7.1%) adrenal insufficiency persisted >5 years after discontinuation. Mitotane peak ≥27mg/L significantly correlated with longer time to adrenal recovery (HR=0.2, 95%CI=0.1-0.8, p=0.03). 27/38 patients (71%) followed in reference centers achieved adrenal recovery compared to only 5/18 (28%) followed-up in non-reference centers (HR=4.51, 95%CI=1.71-11.89, p=0.002). Other investigated factors were not associated with adrenal function after discontinuation. Conclusions: Our study demonstrates that adrenal recovery occurs in most patients after stopping mitotane, particularly when followed-up in specialized centers, but not in all. Elimination time of mitotane after treatment discontinuation is very long, but individually quite variable. Presentation: 6/2/2024

7963 Analysis of the inhibition of adrenal synthesis and peripheral metabolism of corticosteroids by oteseconazole and two preclinical tetrazole antifungals

Abstract Disclosure: M. Jäger: None. V. González-Ruiz: None. F.L. Joos: None. D.V. Winter: None. J. Boccard: None. T. Degenhardt: Employee; Self; Mycovia Inc. S. Brand: Employee; Self; Mycovia Inc.. S. Rudaz: None. G.R. Thompson: None. A. Odermatt: None. The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia by blocking adrenal cortisol synthesis and its peripheral inactivation [1]. Mechanisms of pseudohyperaldosteronism include inhibition of adrenal cytochrome P450 enzymes CYP11B1 and CYP17A1, as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazole compounds have been developed [2]. Here, we used adrenal H295R cells and enzyme activity assays to assess the inhibition of steroidogenesis by the tetrazoles oteseconazole, VT-1129 and VT-1598. In addition, the three tetrazoles were tested for inhibition of 11β-HSD2. Steroidomic footprint analyses of H295R cell supernatants using untargeted LC-HRMS with steroid annotation indicated common features of the oteseconazole and VT-1129 patterns with that of the triazole itraconazole, and similarities between VT-1598 and the triazole isavuconazole. Targeted quantification of nine adrenal steroids by UHPLC-MS/MS in supernatants of treated H295R cells showed an overall inhibition of steroidogenesis by the tetrazoles and the triazoles itraconazole and isavuconazole. Experiments using recombinant human enzymes suggested that this effect is not caused by direct inhibition of steroidogenic enzymes because no or very weak inhibition could be observed. Furthermore, oteseconazole, VT-1129 and VT-1598 did not inhibit 11β-HSD2, suggesting that they unlikely cause pseudohyperaldosteronism. Further research needs to uncover the exact mechanism for the observed overall inhibition of steroidogenesis by the tetrazoles as well as itraconazole and isavuconazole, and whether concentrations reached in patients are high enough to cause adrenal insufficiency and hyperplasia.

6538 Find me if you can! A Case of a "Well Placed Solitary Insulinoma" in "The Center" of an SACST

Abstract Disclosure: R. Kennedy: None. D.A. D'Alessio: None. A.V. Vella: None. Introduction: Selective arterial calcium stimulation testing (SACST) can be utilized in patients to localize solitary insulinomas when imaging is non diagnostic. While a heterogenous stimulation pattern suggests NIPHS, or multiple insulinomas this case uniquely demonstrates such a pattern with a solitary insulinoma. Clinical Case: The patient is a 48 year old female who presented to the emergency department (ED) for bizarre behavior which resolved with a sweetened drink. Serum glucose was 62 mg/dL, she was treated with IV dextrose and was discharged from the ED. She was referred to outpatient endocrinology for further evaluation where continuous glucose monitoring confirmed predominantly fasting hypoglycemia. Adrenal insufficiency was excluded. She was admitted for a 72 hour inpatient fast where the patient achieved hypoglycemia within 24 hours, with glucose 46 mg/dL (associated with neuroglycopenic symptoms), beta hydroxybutyrate < 0.18 mmol/L, insulin 3.9 mcIU/mL, proinsulin 157pmol/L, c-peptide 1.4 ng/mL and a glucose rise greater than 25mg/dL after glucagon administration. Sulfonylurea screen and insulin antibodies were negative; IGF1 within normal limits. These labs were consistent with hyperinsulinemic hypoglycemia. An MRI pancreas however did not reveal an insulinoma. The patient therefore underwent a SACST, demonstrating a 10 fold response in the territory of the gastroduodenal artery and splenic artery, as well as a 3 fold response in the superior mesenteric artery. This heterogenous pattern in addition to the marked response in each arterial territory raised the possibility of multiple insulinomas. However as there were no tumors present on imaging, medical management was initiated with close follow up. She was trialed with months of somatostatin analogs and diazoxide with minimal improvement in the frequency and severity of her hypoglycemia. About a year after her initial diagnosis, repeat abdominal imaging (CT and MRI) revealed an 8 mm arterial hyper-enhancing lesion in the body of the pancreas concerning for neuroendocrine tumor. Repeat SACST was performed, this time showing a greater than 10 fold response in all three arterial territories. Angiography showed a tumor blush that was visible when each of the three major arteries were injected sequentially. She underwent laparoscopic pancreatic enucleation. The lesion was located on the body of the pancreas, with histology confirming an insulinoma. The patient responded promptly post operatively; her symptoms resolved without further need of medical management. Conclusion: Our case shows that the interpretation of an SACST should take into account the arterial anatomy before ascribing a non-focal response to multiple territories of insulin hypersecretion. Presentation: 6/1/2024

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (< 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (<1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

9337 Postprandial And “Fasting” Hypoglycemia In A Patient With A History Of Gastric Bypass Surgery And Carcinoid Syndrome

Abstract Disclosure: S. Ntelis: None. M. Pennant: None. Background: Hypoglycemia is an increasingly recognized complication of bariatric surgery that can occur years after the procedure. Episodes most commonly occur 1-3 hours after meals. Fasting hypoglycemia is not typical and raises concerns for other etiologies, including adrenal insufficiency and other causes of endogenous hyperinsulinism. Clinical Case: A 51-year-old woman with a history of carcinoid tumor of unknown origin with liver metastases, treated with monthly octreotide injections, and history of Roux-en-Y gastric bypass presented with multiple episodes of symptomatic hypoglycemia up to 24 mg/dl. Symptoms included tremor and diaphoresis and improved with juice. Morning cortisol was 22.7 mcg/dL (n > 19.4 mc/dL), ruling out adrenal insufficiency. A continuous glucose monitor (CGM) was placed, and she was advised to have frequent low-carbohydrate meals mixed with healthy fats and protein. She was also advised to add cornstarch to meals, until mixed-meal testing could be performed. She was hospitalized for a seizure provoked by hypoglycemia after a heavy high-carbohydrate meal, and treatment with acarbose 25 mg three times daily was started. Mixed-meal testing was consistent with post-prandial hyper-insulinemic hypoglycemia, with elevated insulin (58 mcIU/ml, n: 2.6-24.9 mcIU/ml) and c-peptide (11.2 ng/ml, n: 1.1-4.4 ng/ml) levels during an episode of symptomatic hypoglycemia (glucose 22 mg/dL) 2.5 hours after the patient’s meal. CGM showed hypoglycemia mostly occurring after meals and some episodes of hypoglycemia early in the morning, that occurred after late-night snacks. Clinical picture and laboratory testing were suggestive of post-bariatric surgery hypoglycemia. Poor hepatic glycogen reserve, secondary to the liver metastases, was considered a contributing factor. Interestingly, although hypoglycemia was mediated by hyperinsulinemia, treatment with a somatostatin analogue provided no benefit. The frequency of hypoglycemia decreased with adherence to a low-carbohydrate diet, and episodes mostly occurred when acarbose use was delayed. Octreotide was transitioned to lantreotide. Due to persistence of early-morning low glucose values on follow-up, further work-up was pursued to rule out etiologies of fasting hypoglycemia. Glucose values remained >70 mg/dl during 72 hours of fasting. IGF-I (115 ng/ml, n: 53-287 ng/ml) and IGF-II (608 ng/ml, n: 267-616 ng/ml) levels were normal, and insulin antibodies were undetectable. Post-bariatric surgery hypoglycemia was confirmed and acarbose dose was increased to 50 mg three times daily. Conclusion: Postprandial hypoglycemia is a late complication of bariatric surgery. Early-morning hypoglycemia can also be seen after bariatric surgery in patients who have late-night meals and snacks. Presentation: 6/1/2024

7187 Non-islet Cell Tumor Hypoglycemia in a Patient With Metastatic Renal Cell Carcinoma

Abstract Disclosure: G.W. Bao: None. A.Y. Yin: None. We report a rare case of non-islet cell tumor hypoglycemia (NICTH) in a patient with metastatic renal cell carcinoma. NICTH is a paraneoplastic syndrome due to increased production of an incompletely processed form of insulin-like growth factor 2 (“big IGF-2”). It requires a high-level of suspicion for diagnosis and is challenging to manage. Our patient is a 69 year old gentleman with a history of deceased donor renal transplant in 1994 and 2008. He was diagnosed with renal cell carcinoma (RCC) metastatic to bone, lymph nodes, and lungs, which was initially treated with cabozantinib, later switched to lenvatinib and everolimus due to disease progression. On admission, he presented with anasarca and weakness. He had recurrent fasting hypoglycemia associated with confusion and lethargy. The lowest serum glucose was 28 mg/dL. He was also diagnosed with primary hypothyroidism (TSH 25.1 uIU/mL and free T4 0.31 ng/dL), suspected to be due to tyrosine kinase inhibitor therapy. Levothyroxine was initiated. Cosyntropin stimulation resulted in a post-stimulation cortisol of 7 ug/dL, although this was felt not to be reliably diagnostic of adrenal insufficiency in the setting of profound hypoalbuminemia. IGF-1 and IGF-2 were 16 ng/mL and 388 ng/mL, respectively; IGF-2: IGF-1 ratio was 24.3. He was treated with intravenous dextrose and prednisone 30mg daily with stabilization of glucoses for a few days. On hospital day 19, he acutely decompensated and passed away shortly after being transitioned to comfort-focused care. Non-diabetic hypoglycemia is relatively uncommon, and may be seen in patients with liver disease, sepsis, adrenal insufficiency, and malignancy. We report a case of NICTH in a patient with metastatic RCC, which is a particularly rare cause of hypoglycemia. NICTH is due to tumor production of “big IGF-2”, a precursor of IGF-2, which mimics the effects of insulin and causes fasting hypoglycemia. NICTH is more commonly associated with mesenchymal and epithelial tumors such as fibromas, fibrosarcomas, and hepatocellular carcinomas. NICTH due to RCC appears to be a much more rare entity, with as few as four cases reported in the literature. Laboratory findings of NICTH include low insulin, pro-insulin, C-peptide, and β-hydroxybutyrate during hypoglycemia. An IGF-2: IGF-1 ratio >10 is considered virtually diagnostic. Surgical excision is curative, although often delayed or not feasible, and patients frequently require intravenous dextrose. High-dose steroids (ie, prednisone 30-60mg daily) can be used, which promotes “big IGF-2” clearance. NICTH is likely under-recognized in patients with advanced malignancies. This diagnosis should be considered in those with refractory hypoglycemia, although management is challenging if tumor control cannot be achieved. Presentation: 6/1/2024

8673 Exploring A Case Study On Navigating Complexities In Endocrine Health And Reproductive Challenges

Abstract Disclosure: S.Y. Rizvi: None. E. Villanueva: None. Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting many reproductive-age women, characterized by irregular menstrual cycles, hirsutism, and challenges with fertility. In this case study, we delve into the medical history of a 24-year-old female presenting with PCOS-related symptoms, hirsutism, and infertility, unraveling the multifaceted aspects of her healthcare journey. Case Description: This patient's diagnostic path began when she received an initial diagnosis of PCOS in her home country due to irregular menstrual periods and clinical signs of hirsutism. Her treatment included metformin, but it was interrupted when she relocated to the United States. Upon her arrival in the U.S., her medical course took an unexpected turn as further evaluations revealed elevated salivary cortisol (++), and a 24-hour urine free cortisol recorded 94.2 mcg (normal 4-50 mcg), indicating hypercortisolism. DHEAS: 730 mcg/dl (normal 18-390 mcg/dl), 17-hydroxyprogesterone: 508 (pre-midluteal: 431), free testosterone: 13 pg/ml (normal 0.1-6.4 pg/ml), with normal CBC, TSH, prolactin, and TPO. CT scan showed large 4.8 cm left adrenal mass. These findings indicated adrenal Cushing's syndrome, leading to referral to a tertiary care hospital's endocrine surgeon. Two months post-adrenalectomy, successful removal of the adrenal mass left the patient with relative adrenal insufficiency. Hydrocortisone replacement therapy was initiated, addressing Cushing's syndrome and revealing a potential factor contributing to infertility. Postoperatively, the patient entered the first trimester unexpectedly, complicating her case. Ensuring proper hydrocortisone levels became crucial for her well-being and the fetus, prompting a collaborative approach with obstetricians and maternal-fetal medicine specialists for optimal pregnancy care. Despite ongoing PCOS effects, including hirsutism, treatment options were limited by pregnancy constraints, deferring Aldactone due to its contraindication during pregnancy. Continuous monitoring included hormonal assessments, metabolic panels, and thyroid tests, aiming to balance adrenal insufficiency, PCOS symptoms, and a healthy pregnancy. Conclusion: This case emphasizes challenges in differentiating PCOS from adrenal Cushing's due to overlapping symptoms. Despite classic symptoms, the initial PCOS misdiagnosis highlights the need for vigilance and comprehensive diagnostics. Complex cases underscore the importance of individualized management and interdisciplinary collaboration. Positive outcomes in complex endocrine disorders and pregnancy are attainable through accurate diagnoses and tailored treatments. The case underscores the critical importance of meticulous evaluation for successful outcomes in challenging medical scenarios. Presentation: 6/3/2024

7560 Using a Single Pre-test Cortisol Level To Reduce The Need For Dynamic Testing For Adrenal Insufficiency In A Southeast Asian Population

Abstract Disclosure: V. Ramadoss: None. L. Tan: None. A.E. Teo: None. K. Lazarus: None. K. Meeran: None. D. Deepak: None. L. Ong: None. C. Khoo: None. P. Eng: None. Introduction: The Short Synacthen Test (SST) is widely used in clinical practice to assess Adrenal Insufficiency (AI). Despite its relative ease of administration, Synacthen use is limited by its availability and its administration demands supervision by experienced staff, resulting in increased testing cost. A single measurement of serum cortisol has been shown to predict AI, but the suggested threshold varies according to the patient cohort studied, assay variation and the prevalence of the condition relative to the size of population tested. This study aims to (a) identify a threshold cortisol level to screen for AI in a South-East Asian population and (b) to determine the utility of a stimulated 60-minute cortisol level in the diagnosis of AI. Methods: This is a retrospective analysis of SSTs (250 micrograms) performed in our institution between 28th February 2022 to 28th February 2023. Serum cortisol in our institution was measured by Abbott Alinity analysers. We defined a normal response as a stimulated cortisol value of ≥ 420nmol/L at either 30-minutes, 60-minutes, or at both time points. Logistic regression analysis was performed to predict normal responses based on baseline cortisol level. Results: Median cortisol level at baseline, 30-minutes, and 60-minutes after Synacthen stimulation were 254 (IQR 191-320) nmol/L, 499 (IQR 415 -585) nmol/L, 574 (IQR 476 -662) nmol/L respectively. A total of 785 SSTs were performed, out of which 83.1% were normal and 16.9% were abnormal. Of the 785 SSTs, 55 (7.0%) would have failed if only the 30-minute cortisol was assessed without the 60-minute value, whereas 10 (1.4%) would have failed if only the 60-minute cortisol was assessed without the 30-minutes value. An early morning basal cortisol (0800am to 1200pm) cut-off of <300nmol/L identified subnormal cortisol with 95.0% sensitivity and an afternoon cortisol (1200pm to 1700) of < 312nmol/L achieved 95.2% sensitivity. A basal cortisol level of < 100nmol/L will confirm AI with 97.3% specificity. Using a basal cortisol level of ≥ 300nmol/L, 94.8% of individuals go on to pass the SST. Use of this basal cortisol value would avoid 252 (32.1%) SSTs. Conclusion: A single measurement of basal cortisol of ≥ 300nmol/L has the potential to exclude AI with 95% sensitivity on Abbott Alinity platform in our cohort of patients. Using a threshold cortisol level of 300nmol/L, at least 32% of the SSTs could be avoided. This would have improved patients experience with cost savings implications. Furthermore, a stimulated 60-minute cortisol level identifies 55 (7%) of individuals who would otherwise be misclassified as AI, thereby avoiding unnecessary long-term glucocorticoid replacement. Presentation: 6/1/2024

8536 Unusual Finding of Familial Adenomatous Polyposis in a Patient with X Linked Adrenoleukodystrophy

Abstract Disclosure: A. Deswal: None. A. Dwarakanathan: None. Introduction: X Linked Adrenal Leukodystrophy (X-ALD) is a rare hereditary genetic disorder of impaired peroxisomal metabolism due to a defective transmembrane protein, ADLP. Defective ADLP impairs transport of VLCFA-CoA esters across cytosol into peroxisomes leading to build-up of toxic VLCFA in the cells. X-ALD is caused by mutation in ABCD1 gene, located on X chromosome, which codes for ADLP. It has a broad clinical spectrum including Cerebral ALD, Adrenomyeloneuropathy and Adrenocortical insufficiency. X-ALD has a general prevalence of 1 in 17,000 newborns. Approximately 80% of males with X-ALD develop primary adrenal insufficiency in their lifetime. It can be diagnosed by measuring VLCFA levels in plasma , checking for ABCD1 gene mutation or by doing Brain MRI (depending upon phenotypical presentation ). Case presentation: We report a case of a 23 year old man who had primary adrenocortical insufficiency subtype of X-ALD. His mother was a carrier of ABCD1 gene mutation. He himself tested hemizygous for ABCD1 gene. He came to our office for a follow up visit after an episode of adrenal crisis for which he was hospitalized. He was started on replacement therapy with prednisone and fludrocortisone. Over the next couple of years, he was diagnosed with diabetes mellitus with initial HbA1C of 8.8%. GAD antibody test for type I DM came out negative. His diabetes was managed with metformin and pioglitazone( later discontinued) .By the age of 25,he was found to have polyposis of colon. He tested positive for APC gene mutation . He underwent a J pouch surgery . He also developed PICA aneurysm. Discussion: X-ALD is a hereditary progressive disease with no association between genetic and phenotypic presentations. Adrenal insufficiency type is usually the first to present. Cerebral ALD is typically diagnosed between the ages of 3-18 presenting as psychiatric illness. Myelopathy typically starts by middle age and involves the spinal cord, causing the affected individuals to develop gait disturbances , bladder and bowel dysfunction, with severe mobility dysfunction by 5th-6th decade of life. We present a unique case of a young man with adrenal insufficiency type of X-ALD who also developed gastrointestinal pathology. Per our literature review, X-ALD has not been seen associated with APC gene mutations or colon carcinomas . Pathology behind XLD revolves around ABCD1 gene mutaion causing VLCFA accumulation in plasma, fibroblasts, adrenal glands, oligodendrocytes , astrocytes etc. Whereas FAP involves APC gene mutation which affects the intestinal epithelial cells leading to their apoptosis and polyp formation. X-ALD and FAP are disorders of two different gene mutations with varied clinical presentations. But the question arises regarding finding of APC gene mutation in a patient with ABCD1 gene mutation that if it is a mere co-incidence or common mutation pathway linking these two disorders exists. Presentation: 6/2/2024