ACTH Stimulation Research Articles

Thyroid and Adrenal Dysfunction in Hemoglobinopathies Before and After Allogeneic Hematopoietic Cell Transplant.

To determine the rate and clinical characteristics associated with abnormal thyroid and adrenal function in recipients of nonmyeloablative hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) and beta-thalassemia. We retrospectively reviewed patients who enrolled in 4 nonmyeloablative HCT regimens with alemtuzumab and total body irradiation (TBI). Baseline and annual post-HCT data were compared, which included age, sex, sickle phenotype, thyroid panel (total T3, free T4, thyroid stimulating hormone, antithyroid antibodies), cortisol level, ACTH stimulation testing, ferritin, medications, and other relevant medical history. Among 43 patients in haploidentical transplant and 84 patients in the matched related donor protocols with mostly SCD, the rate of any thyroid disorder pre-HCT was 3.1% (all subclinical hypothyroidism) and post-HCT was 29% (10 hypothyroidism, 4 Grave's disease, and 22 subclinical hypothyroidism). Ninety-two (72%) patients had ferritin >1000 ng/dL, of which 33 patients (35.8%) had thyroid dysfunction. Iron overload was noted in 6 of 10 patients with hypothyroidism and 12 of 22 patients with subclinical hypothyroidism.Sixty-one percent were on narcotics for pain control. With respect to adrenal insufficiency (AI) pre-HCT, 2 patients were maintained on corticosteroids for underlying rheumatologic disorder and 8 had AI diagnosed during pre-HCT ACTH stimulation testing (total 10, 7.9%). Post-HCT, an additional 4 (3%) developed AI from corticosteroid use for acute graft vs host disease, Evans syndrome, or hemolytic anemia. Although iron overload was common in SCD, thyroid dysfunction pre-HCT related to excess iron was less common. Exposure to alemtuzumab or TBI increased the rates of thyroid dysfunction post-HCT. In contrast, AI was more common pre-HCT, but no risk factor was identified. AI post-HCT was infrequent and associated with corticosteroid use for HCT-related complications.

Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism

Adrenal venous sampling (AVS) is usually recommended to distinguish between unilateral and bilateral primary aldosteronism (PA) before definitive surgical or medical treatment is offered. Whether a treatment decision based on AVS with or without corticotropin (ACTH) stimulation leads to different biochemical and clinical remission rates in patients with PA remains unclear. To evaluate whether treatment decisions based on AVS with or without ACTH stimulation lead to different biochemical and clinical remission rates in patients with PA. This randomized clinical trial (RCT) was conducted at a tertiary hospital in China from July 8, 2020, to February 20, 2023, among patients with PA aged 18 to 70 years. Patients were followed up for 12 months after the initiation of treatment. An intention-to-diagnose analysis was conducted. Patients were randomly assigned to undergo either ACTH-stimulated or non-ACTH-stimulated AVS. The primary end point was the proportion of patients with complete biochemical remission after 12 months of follow-up. Secondary outcomes included the proportion of patients who achieved complete clinical remission after 12 months of follow-up, dosages of antihypertensive agents, rate of successful bilateral AVS, and adverse events. Of 228 patients with PA, 115 were randomized to the non-ACTH-stimulated group (median age, 50.0 years [IQR, 41.0-57.0 years]; 70 males [60.9%]) and 113 to the ACTH-stimulated group (median age, 50.0 years [IQR, 43.5-56.5 years]; 63 males [55.8%]). A total of 68 patients (59.1%) underwent adrenalectomy in the non-ACTH group and 65 (57.5%) in the ACTH group. There was no significant difference in the proportion of patients with complete biochemical remission who were managed on the basis of AVS with vs without ACTH stimulation (with: 56 of 113 [49.6%]; without: 59 of 115 [51.3%]; P = .79). There also was no significant difference in the proportion of patients who achieved complete clinical remission between the non-ACTH and ACTH groups (26 of 115 [22.6%] and 31 of 113 [27.4%], respectively; P = .40). The intensity of therapy with antihypertensives, successful catheterization of bilateral adrenal veins, and incidence of adverse events did not significantly differ between the non-ACTH and ACTH groups. In this RCT, treatment of PA on the basis of non-ACTH-stimulated or ACTH-stimulated AVS did not lead to significant differences in clinical outcomes for the patients. These results suggest that ACTH stimulation during AVS may not have clinical benefit, at least in the Chinese population. ClinicalTrials.gov Identifier: NCT04461535.

Real world evidence supports waking salivary cortisone as a screening test for adrenal insufficiency.

Worldwide, adults and children are at risk of adrenal insufficiency largely due to infectious diseases and adrenal suppression from use of anti-inflammatory glucocorticoids. Home waking salivary cortisone is an accurate screening test for adrenal insufficiency, it has potential to reduce costs, and patients prefer it to the adrenocorticotropin (ACTH) (synacthen) stimulation test. We carried out a service evaluation of home waking salivary cortisone in clinical care to identify implementation barriers. Service evaluation in a centre where 212 patients referred for adrenal insufficiency had a waking salivary cortisone. Problems encountered during testing were recorded and patient feedback, via focus groups,collected. From all patients providing a waking salivary cortisone 55% had a normal test, 23% adrenal suppression, and 22% an equivocal result requiring a clinical centre ACTH stimulation test. The median (interquartile range [IQR]) for the time of the saliva sample was 07:40 (07:00-08:40). The median (IQR) days between collection and (i) delivery to local laboratory was1 (0.25-2) day; (ii) reporting by local laboratory was 13 (11-18) days. Patients considered the test is "easy to do" and preferred it to the inpatient ACTH stimulation test. The principal challenge to clinical implementation was results reporting to clinicians due to delays at the local laboratory. This service evaluation provides real-world evidence that home waking salivary cortisone is an effective, practical screening test for adrenal insufficiency. It identified key barriers to testing implementation that need to be addressed when introducing the test to a health service.

FRI140 Impact Of Circadian Rhythm Of Aldosterone And Cortisol Levels Upon Adrenal Vein Sampling In Primary Aldosteronism

Abstract Disclosure: M. Kometani: None. M. Yoneda: None. K. Aiga: None. D. Aono: None. S. Karashima: None. Y. Takeda: None. T. Yoneda: None. Purpose: Adrenal venous sampling (AVS) is the gold standard technique for subtype differentiation of primary aldosteronism (PA). AVS is an invasive and challenging test; however, because of the high frequency of PA, it is currently performed at many institutions in Japan. Considering the effects of diurnal variations in the levels of aldosterone and cortisol, the guidelines recommends that AVS without ACTH loading should be performed in the morning. However, owing to staffing issues and general limitations, AVS is performed in the afternoon in many facilities. In this study, we examined the effects of AVS timing (AM/PM) on AVS results. Methods: This multicenter, retrospective, observational study included a total of 753 patients diagnosed with PA at four specialized institutions. The patients were divided into two groups according to the timing of the AVS procedure. The group classification of patients according to the time of the day when AVS was performed was not prospectively designed but rather determined based on feasible conditions at each facility. Among them, 504 and 249 patients underwent AVS in the morning (AM-AVS) and in the afternoon (PM-AVS), respectively. Results: The success rate of basal AVS in the AM-AVS group was 81% and that of ACTH-stimulated AVS was 92%. The success rate of basal AVS in the PM-AVS group was 74% and that of ACTH-stimulated AVS was 88%. There was no significant difference in the AVS success rate between the AM-AVS and PM-AVS groups. There was no significant difference between the AM-AVS and PM-AVS groups concerning the rate of unilateral diagnosis by AVS before ACTH stimulation, the rate of unilateral PA diagnosis by AVS after ACTH stimulation, and the percentage of cases with discrepancies between the two AVSs. Regarding patients with unilateral PA, aldosterone concentrations in adrenal venous blood did not differ between the two groups on the dominant or non-dominant side. Conversely, regarding patients with bilateral PA, aldosterone concentrations in adrenal venous blood were significantly higher in the AM-AVS than in the PM-AVS group. Conclusions: This study evaluated the effect of AVS timing. Although this was a multicenter study, there were no differences in the success rate of AVS, diagnostic rate of subtype, or frequency of deviation in the subtypes between the AM-AVS and PM-AVS groups. These results are relevant for facilities that can perform AVS only in the afternoon. Concerning aldosterone levels, no differences were observed between patients with unilateral lesions in the AM-AVS and PM-AVS groups, whereas its levels were different between patients with bilateral lesions in the AM-AVS and PM-AVS groups, suggesting the involvement of different mechanisms that regulate aldosterone secretion according to the circadian rhythm in patients with unilateral or bilateral lesions. Presentation: Friday, June 16, 2023

FRI128 Hiding In Plain Sight: Late Diagnosis Of Primary Hyperaldosteronism In Patient With Atypical Presentation

Abstract Disclosure: R.A. Zielinski: None. A. Syeda: None. B. Esayag-Tendler: None. Background: Primary hyperaldosteronism (PHA) can go undiagnosed in patients with primary hypertension without hypokalemia and increased plasma aldosterone concentration (PAC). Case: The patient is a 72-year-old male with a history of hypertension (HTN) diagnosed at age 55 who presented to the endocrinology clinic for further evaluation. He was asymptomatic. His antihypertensive regimen included atenolol 25 mg daily and amlodipine-benazepril 10-40 mg daily. Blood pressure (BP) was well-controlled with a goal BP under 130/80 mm Hg. Physical exam was without AV nicking in a limited retina exam, no abdominal tenderness, and no peripheral edema. Family history is notable for HTN in his father and HTN complicated by stroke in a sister and a brother, all diagnosed at an older age. Labs done 5 years prior showed potassium (K) of 4.3 mmol/L [3.6 - 5.1 mmol/L], PAC of 3.2 ng/dl [upright 4.0 - 31.0 ng/dl], and plasma renin activity (PRA) of 0.1 ng/ml/hr [upright 0.5-4.0 ng/ml/hr]. More recent labs showed K of 3.8 mmol/L, PAC of 21.5 ng/dl and PRA of 0.3 ng/ml/hr. Repeat labs 6 months later showed K of 3.4 mmol/L, PAC of 15 ng/dL and PRA of 0.2 ng/mL/hr. A 3-day dexamethasone suppression test was performed to exclude familial hyperaldosteronism or glucocorticoid remediable aldosteronism. Following the test, K was 3.6 mmol/L, PAC was 11.3 ng/dl, and cortisol was undetectable. CT abdomen showed bilateral nodular thickening of the adrenal glands without a distinct adenoma. Adrenal venous sampling was done before and after ACTH stimulation. Prior to ACTH stimulation, the mean ratio of the dominant adrenal aldosterone concentration corrected with cortisol from left to right was 1.32. Following ACTH stimulation, the ratio was 2.79. A ratio greater than 4 is consistent with a good outcome after adrenalectomy. Hence, it was decided to pursue medical management. The cause of our patient’s primary hyperaldosteronism is likely due to bilateral idiopathic hyperplasia. He was started on eplerenone 25 mg twice daily and salt restriction with a goal of increasing the PRA above 1 ng/ml/hr. Discussion and Conclusion: It was initially thought that PHA represents 1% of all patients with primary HTN. However, more recent studies indicate that the prevalence is significantly higher. Additionally, the PAC in patients with PHA can fluctuate and patients can present with normokalemia, making the diagnosis more difficult to establish. It is an important diagnosis to establish and treat appropriately because there is a higher risk of cardiovascular morbidity and mortality in patients with PHA compared to patients with primary HTN. Presentation: Friday, June 16, 2023

OR30-02 Salivary Cortisol Response To The High Dose ACTH Stimulation Test Provides A Reliable Alternative To Serum Cortisol Measurement In The Evaluation of Suspected Hypoadrenalism, And Is Unaffected By Cortisol-Binding Concentration

Abstract Disclosure: N. El-Farhan: None. S. Rees: None. S. Tennant: None. C. Evans: None. A. Rees: None. Context The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected in conditions of altered cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. Objectives: 1. To establish the salivary cortisol response to the high dose ACTH stimulation test in healthy volunteers and in patients with altered CBG concentrations. 2. To evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism. Design: A high dose (250 µg) intravenous ACTH stimulation test was undertaken in 139 (60 male, 79 female) healthy volunteers, 24 women taking an oestradiol-containing oral contraceptive pill (OCP females), 10 patients with low serum protein concentration secondary to the nephrotic syndrome or liver cirrhosis (LP patients) and 29 patients with suspected hypoadrenalism (SH patients). Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. The mean and estimated LRL of the 30-minute salivary cortisol response to ACTH stimulation (mean - 1.96 SD) were derived from log-transformed concentrations. The LRL was subsequently applied as a diagnostic cut-off in SH patients. Results: CBG concentrations were 58 [42-81] mg/L), 64 mg/L [43-95], 41 [28-60] mg/L and116 [84-159] mg/L in male volunteers, female volunteers, LP patients and OCP females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 [2.5th-97.5th percentile 10.3-36.2] nmol/l in healthy volunteers, with no difference between genders. Corresponding values were not different in OCP females (19.7 [9.5-41.2] nmol/l; p=0.59) and LP patients (19.0 [7.7-46.9] nmol/l; p=0.97), in contrast to 30-minute mean serum cortisol responses which differed between healthy female volunteers (555 [421-731] nmol/l) and OCP females (869 [649-1162] nmol/l; p<0.001). Overall diagnostic agreement between 30-minute salivary and serum responses in patients undergoing evaluation for SH was high (79%). Conclusions: Salivary cortisol response to intravenous ACTH stimulation offers a reliable alternative to serum cortisol measurement in the assessment of patients with suspected hypoadrenalism and may be especially useful in conditions of altered CBG concentration. Presentation: Sunday, June 18, 2023

SAT321 Ectopic ACTH Cushing's Syndrome Caused By A Large-cell Neuroendocrine Lung Carcinoma Responding To Desmopressin

Abstract Disclosure: S. Larose: None. D. Rioux: None. R. Albadine: None. A. Lacroix: None. Background: Ectopic ACTH secretion (EAS) is a less frequent cause of ACTH-dependent Cushing’s syndrome (CS), most often caused by a thoracic neuroendocrine tumor (NET). Large-cell neuroendocrine carcinomas (LCNEC) with EAS are rare and usually present a more severe phenotype of ACTH secretion and hypercortisolism. Clinical Case: We report the case of a 44-yo non-smoking man, who presented clinical and biochemical evidence of ACTH-dependent severe CS complicated by pulmonary emboli. In the context of an initial equivocal pituitary MRI, desmopressin and CRH stimulation tests were performed. Desmopressin produced a 157% increase in ACTH (basal: 59.0 pmol/L to peak: 151.9 pmol/L) and a 25% increase in cortisol from baseline; there was no stimulation of ACTH or cortisol during a CRH test and no suppression with high dose dexamethasone tests. Repeat pituitary MRI identified a 5 mm lesion, but inferior petrosal venous sinus sampling (IPSS) under desmopressin did not identify a central ACTH source. Thorax and abdominal imaging including Indium-111 octreoscan identified a left lung 3 mm micronodule which became more evident when pulmonary emboli resolved. In this context of probable ectopic ACTH secretion, the patient was treated with left inferior lung lobectomy for a suspected NET. Pathological studies confirmed a lung LCNEC with morphologic features of carcinoid tumor and strongly positive ACTH immunohistochemistry (IHC) in the primary lesion and lymph node metastasis. The patient was in CS remission after surgery and adjuvant chemotherapy, but developed a CS recurrence 9.5 years later, with a morning ACTH of 56.9 pmol/L, (N <11.0 pmol/L), a non-suppressed AM cortisol of 633 nmol/L after 1mg of dexamethasone overnight and urinary free cortisol of 1717 nmol/24 hours (N:< 789). Imaging showed signs of recurrence, with a hypermetabolic, 14 x 11 mm left hilar lymph node lesion on a TEP-DOTATATE scan in the left lung, near the surgical suture. An endobronchial ultrasound-guided biopsy confirmed the recurrence of the LCNEC. Surgery was performed and demonstrated again positive ACTH IHC of the lesion. The patient achieved remission of CS with secondary adrenal insufficiency, treated with hydrocortisone. Six months later, there was no response of ACTH or cortisol to a desmopressin test. Conclusion: This is the first report of LCNEC with morphologic feature of carcinoid tumor of the lung with ectopic ACTH secretion stimulated by desmopressin. Long delay prior to metastatic recurrence indicates relatively indolent NET. This case report indicates that response to desmopressin can occur in malignant LCNEC. Combining the desmopressin test with other dynamic tests, sellar MRI, IPSS and thoraco-abdominal functional imaging improves diagnostic accuracy of ectopic ACTH source. Presentation: Saturday, June 17, 2023

FRI145 Prevalence Of Type 2 Diabetes Mellitus And Risk Factors For Its Development In Patients With Primary Aldosteronism

Abstract Disclosure: M. Araujo-Castro: None. M. Paja Fano: None. M. González Boillos: None. B. Pla Peris: None. E. Pascual-Corrales: None. A. García Cano: None. P. Parra: None. P. Martín Rojas-Marcos: None. J. Ruiz-Sanchez: None. A. Vicente Delgado: None. E. Gómez Hoyos: None. R. Ferreira: None. I. García Sanz: None. M. Recasens Sala: None. R. Barahona San Millan: None. M. Picón César: None. P. Díaz Guardiola: None. J. García González: None. C.M. Perdomo: None. L. Manjón Miguélez: None. R. García Centeno: None. Á. Rebollo Román: None. P. Gracia Gimeno: None. C. Robles Lázaro: None. M. Morales-Ruiz: None. M. Calatayud Gutiérrez: None. S. Simone Andree Furio Collao: None. D. Meneses: None. M. Sampedro Nuñez: None. V. Escudero Quesada: None. E. Mena Ribas: None. A. Sanmartin Sánchez: None. C. Gonzalvo Diaz: None. C. Lamas: None. F. Hanzu: None. Purpose: To evaluate the prevalence of type 2 diabetes mellitus (T2DM) in patients with primary aldosteronism (PA) and the risk factors for its development. Methods: A retrospective multicenter study of PA patients in follow-up in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Adrenal venous sampling (AVS) was informative of laterality in 128 out of 226 patients and adrenalectomy was performed in 201 patients. Unilateral PA was defined as biochemical cure after adrenalectomy or as a lateralization index in AVS > 2 with ACTH or >3 without ACTH stimulation. Results: Overall, 649 patients with PA were included. Median age was 55.5 (range 27.3-81.6) years, 59.1% were female and 58.5% had hypokalemia at diagnosis. A total of 224 patients were classified as unilateral PA (142 based on biochemical cure after adrenalectomy and 82 based also on AVS results) and 49 as bilateral PA. At diagnosis, 21.2% (n=137) had T2DM and 25 of them had microvascular complications, being diabetic kidney disease the most common (n=19). We identified as risk factors of type 2 diabetes: male sex (OR 2.80 [1.81-4.34], P<0.001), older age (OR 1.05 [1.03-1.07], P<0.001), familiar history of T2DM (OR 4.64 [2.39-8.99]), P<0.001), dyslipidemia (OR 4.05 [2.67-6.14], P<0.001), cardiovascular (OR 1.30 [1.14-1.48], P<0.001) and cerebrovascular disease (OR 1.59 [0.92-2.74], P=0.003), sleep apnea syndrome (SAS) (OR 2.21 [1.34-3.63], P=0.003), higher BMI (OR 1.06 per unit [1.03-1.10], <0.001), hypertension duration (OR 1.04 per year [1.02-1.06], P<0.001) and the number of antihypertensive drugs (OR 1.50 [1.29-1.74], P<0.0001). In the multivariant analysis, all these variables were independent risk factors for T2DM except for SAS, hypertension duration, sex, and BMI. No association was observed with plasma aldosterone concentration, potassium levels, unilaterality of PA or other parameters. No significant differences in the evolution of the glycemic control (fasting plasma glucose and HBA1c) were observed between T2DM who underwent surgery and those medically treated (P>0.05). Conclusion: Type 2 diabetes affects about one quarter of patients with PA and risk factors for its development are common than to the general population. Medical and surgical treatment provide a similar benefit in terms of glucose control in patients with PA and T2DM. Presentation: Friday, June 16, 2023

OR27-05 Two-pronged Mediation Of Adrenal Steroidogenesis By Oxytocin

Abstract Disclosure: U. Cheliadinova: None. G. Pevnev: None. V. Ryu: None. T. Frolinger: None. S.L. Sims: None. M. Ofer: None. F. Korkmaz: None. O. Barak: None. J. Gimenez Roig: None. F. Sultana: None. N. Kramskiy: None. S. Wizman: None. M. Orloff: None. T. Yuen: None. D. Lizneva: None. M. Zaidi: None. A. Gumerova: None. Stress–stimulated glucocorticoid release affects diverse biological processes, including pregnancy and childbirth. The controversy surrounding effects of OXT on stress prompted us to investigate its actions on adrenal cortical function in mice. RNAscope and immunohistochemistry provided unequivocal evidence for abundant OXT receptor (OXTR) expression in the adrenal cortex, predominantly in zona fasciculata and zona reticularis. Female mice displayed higher adrenal cortical Oxtr expression, more than a range of other tissues under study. Oxtr expression was also detected in the adenohypophysis solely in female mice, while both male and female mice expressed Oxtr in the pars intermedia of the hypophysis. Aging impressively attenuated Oxtr expression in female mice in both the adrenal gland and adenohypophysis. For loss–of–function studies, we generated tissue–specific Star-CreERT2/Oxtrfl/fl mice in which the Oxtr was deleted from steroidogenic tissues, namely adrenals and ovaries. Deletion was confirmed by RNAscope and immunohistochemistry. We found no difference in serum corticosterone between tamoxifen–induced and uninduced mice; however, the elevation of serum corticosterone upon ACTH stimulation or after four weeks of stress was attenuated in tamoxifen–induced mice. Bulk RNAseq of adrenals from tamoxifen–induced mice revealed the downregulation of key steroidogenic genes, namely Cyp17a1, Hsd3b3, Hsd17b2, Cyp3a41b, and Serpina6 (a corticosteroid–binding globulin). In gain–of–function studies, a single OXT injection led to a rise of serum ACTH in tamoxifen–induced mice, which was greater in magnitude than uninduced controls. However, after five days of OXT injections, corticosterone levels became elevated, whereas ACTH levels declined to baseline. This suggests that OXT acts directly on OXTRs on corticotropes to initiate a stress–like response, with a negative feedback loop that inhibits further ACTH secretion. Of note is that male mice did not display any difference between tamoxifen–induced and uninduced groups, consistent with their low hypophyseal Oxtr expression. In all, we describe a novel gender–specific two–pronged circuit through which OXT may precisely regulates the production of corticosterone from the adrenal cortex. In the first arm, OXT directly stimulates ACTH secretion through adenohypophysis OXTRs. In the second arm, OXT prevents excessive stress–induced adrenal stimulation by downregulating steroidogenic genes. Our discovery lays the foundation for the emergence of new physiology that may relate to a fundamental role for oxytocin in the stress response during procreation, notably, when levels are elevated during pregnancy and lactation. Presentation: Saturday, June 17, 2023

FRI268 Late Onset Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: M.S. Nicholson: None. A. Barnett: None. A 66-year old white female was admitted for weakness, acute kidney injury, and hypotension. This is her 3rd hospital or ER visit in the last 12 months for similar complaints. She has a 25 year history of type 2 diabetes on insulin and oral therapy and 30 year history of hypothyroidism on levothyroxine 75 mcg daily. She was on oral estrogen replacement therapy for post-menopausal symptoms with a hysterectomy in her early 50s. She has a sister with type 2 diabetes on oral meds and hypothyroidism. She has a brother with type 1 diabetes. Her serum sodium was 135 mmol/L (135-145), potassium was 5.4 mEq/L (3.5 -5.1), and calcium was 9.2 (8.5-10.1). Her Creatinine was 1.2 with a GFR of 48. A random cortisol in the ED was 9.2 (no ref range). Blood pressure was low and she was tachycardic and her weight was 68 kg. She was a well developed female with a a tanned complexion. Areas of vitiligo were noted on her arms. A cosyntropin stimulation test was done midday with a baseline, 30, and 60 minute cortisol levels of 9.2, 8.8, and 9.3 respectively. Baseline ACTH was 877.6 pg/mL (7.2-63.6). Her TSH was 4.09 mIU/mL (0.358-3.74) and free T4 was 1.29 ng/dL (0.76-1.46). DHEA-S was 14 mcg/dL (13-130). She was started on stress dose steroids with rapid improvement in BP, hyponatremia, and symptoms. GAD-65 antibodies were above 250 IU/mL and 21-hydroxylase antibodies were positive. Her TPO antibodies were negative. Non-insulin diabetes medications were stopped and she was discharged home after stabilization on prednisone 5 mg daily and fludrocortisone 0.1 mg daily. This patient has an atypical presentation of polyglandular autoimmune syndrome type 2 (PAS2). She presented with an Addisons crisis at the age of 66. She was already diagnosed with hypothyroidism and insulin requiring diabetes and evidence of vitiligo. A majority of patients with PAS2 are female and present in their 20s to 40s with primary adrenal insufficiency and primary hypothyroidism. Her initial manifestation was hypothyroidism and then diabetes and vitiligo with adrenal insufficiency many years later. Her random cortisol was not suppressed and this lead to a delay in her diagnosis. This was likely due to oral estrogen therapy raising cortisol-binding globulin. Her elevated baseline ACTH and lack of response to ACTH stimulation confirmed her diagnosis of primary adrenal insufficiency. An ACTH stimulation test was repeated as an outpatient with similar response. This case highlights the importance of provocative testing for adrenal disorders and testing for autoimmune causes of endocrine disorders when patients are not responding as expected. Presentation: Friday, June 16, 2023

OR30-01 Waking Salivary 11-hydroxyandrostenedione And Cortisone As A Novel Non-invasive Test For Adrenal Insufficiency

Abstract Disclosure: N.R. Lawrence: None. B.G. Keevil: None. C. Elder: None. J. Fearnside: None. S. Caunt: None. S. Dixon: None. J.D. Newell-Price: Consulting Fee; Self; Diurnal, Recordati, Crinetics, HRA Pharma. R.J. Ross: Employee; Self; Diurnal. M. Debono: None. Background: The ACTH (Cosyntropin) stimulation test (AST) is the reference standard for diagnosis of adrenal insufficiency. We have demonstrated recently that home waking salivary cortisone accurately predicts the ACTH stimulation test outcome and confirms or excludes adrenal insufficiency in 70% of high-risk patients (in press: Home Waking Salivary Cortisone to Screen for Adrenal Insufficiency NEJM Evidence). 11-hydroxyandrostenedione (11-OHA4) is a weak adrenal androgen whose synthesis is dependent on CYP11B1. Since ACTH drives steroidogenesis, and adrenal androgens are low in patients with adrenal insufficiency, we hypothesised that waking 11-OHA4 could also predict adrenal status. Methods: A prospective, diagnostic accuracy study of waking salivary cortisone was performed in 173 patients at high risk of AI. All patients collected a salivary sample on waking, and then attended the endocrine clinic for an AST with the 30-minute cortisol used to diagnose AI. Salivary cortisone and 11-OHA4 was measured in the waking salivary sample. Biomarker discrimination was assessed by calculation of area under the curve (AUC) of the receiver operator characteristics (ROC) plot. Equivocal results were defined to maintain a sensitivity of 95% and specificity of 95%, and percentage of AST saved by calculating the number of AST needed if used only in equivocal cases. Results: The median (IQR) for 11-OHA4 for patients with AI and no AI was 55 (45 to 110) pmol/l vs 508 (255 to 765) pmol/l; p<0.0001. Salivary 11-OHA4 on waking was highly predictive of adrenal insufficiency (R2=0.63, ROC AUC 0.94), similar to waking salivary cortisone alone (R2=0.65, AUC 0.94). Waking 11-OHA4 performed better than either serum cortisol (R2=0.65, AUC 0.88) or salivary cortisone (R2=0.74, AUC 0.93) collected at the baseline of the AST. Combining both waking salivary 11-OHA4 with waking salivary cortisone further improved discrimination (R2=0.70, AUC 0.96), and using this combination would mean that 78% of ACTH-stimulation tests could be avoided. Conclusion: Waking salivary 11-OHA4 can accurately predict AI with similar discriminatory value as waking salivary cortisone. Combining waking 11-OHA4 with waking salivary cortisone improves discrimination for adrenal insufficiency, is a simple non-invasive test that can be used widely in clinical practice in the ambulatory setting, and obviates the need for AST in 78% of cases with greater patient convenience and lower costs. Presentation: Sunday, June 18, 2023

THU023 Sparse Granulation In Growth Hormone Secreting Adenomas: Clinical Implications Of A Rare Histological Finding

Abstract Disclosure: A. Merrill: None. R. Varughese: None. G. Campbell: None. L. Belalcazar: None. Introduction: Acromegaly is an uncommon disease. Endocrinologists may be unfamiliar with the clinical implications of granularity findings on the histology of growth hormone (GH)-secreting adenomas. We present the case of a patient with acromegaly in whom a sparsely granulated (SG) histological subtype was identified post-operatively. We discuss the clinical presentation and therapeutic implications of this finding. Case Presentation: A 36-year-old man was admitted to the hospital with rectal bleeding and incidentally found to have features consistent with acromegaly. Patient reported that over 1 year he had noticed changes in his facial features, enlargement of his hands and had developed hand and knee arthralgias. During the 6 months prior to admission, he experienced worsening fatigue, but denied severe headaches or vision changes. Past medical history was significant for osteosarcoma as a young child treated with an above the knee amputation. Family history was negative for pituitary tumors or colon cancer. Physical exam revealed a blood pressure of 104/53 mmHg and an amputation-adjusted body mass index of 27.4 _kg/ m2 . He had mild frontal bossing, enlarged nose, macroglossia, swollen hands and foot. Rectal examination revealed hemorrhoids but no masses. Gross visual field deficits were identified at bedside. Laboratory findings were significant for an elevated IGF-1 at 975 ng/mL (83-240 ng/mL) and GH 45.2 ng/mL (0.3-9 ng/mL). Patient was also found to have panhypopituitarism: TSH 1.54 mIU/L (0.45-4.70 mIU/L), Free T4 0.62 ng/dl (0.78 - 2.20 ng/dL); ACTH 13.3 pg/ml (7.2 - 63.3 pg/mL), cortisol AM 3.6 ug/dL (4.5-23.0 ug/dL), peak cortisol after ACTH stimulation 16.0 ug/dL; testosterone 31.6 ng/dl (132-813 ng/dL), LH 1.75 mIU/ml (1.2-8.6 mIU/mL). His hemoglobin A1c was 5.7%. MRI of the brain revealed a large enhancing lobulated sellar/suprasellar lesion of 5.0 x 2.4 x 2.8 cm, with extension to the third ventricle and mass effect on the optic chiasm. Patient underwent partial surgical resection of the large tumor. Pathology identified a SG somatotroph tumor with most cells being negative or weakly positive for GH on immunohistochemical staining. TSH, prolactin, and ACTH stains were negative. There was evidence of residual tumor, which was located superiorly, not accessible through the transsphenoidal route.A colonoscopy and formal visual field testing are pending currently. Patient is waiting for a second surgery via craniotomy and, given the SG finding on histology, pasireotide therapy will be offered. Discussion: The sparsely granulated (SG) subtype is an uncommon variant of GH-producing. Our patient illustrates the aggressive nature of SG GH-producing adenomas. These tumors express more invasive growth and resistance to standard somatostatin analogue therapy. There is a growing recognition that adenoma granulation is an important consideration in the management of acromegaly. Presentation: Thursday, June 15, 2023

THU213 Posterior Reversible Encephalopathy Syndrome As A Rare Presentation Of ACTH-dependent Cushing Syndrome In A Pediatric Patient

Abstract Disclosure: E.E. Bell-Sambataro: None. C. Tatsi: None. P. Chittiboina: None. S.A. Bowden: None. Background: Cushing disease (CD), caused by ACTH-secreting pituitary adenoma, is the most common cause of Cushing Syndrome (CS) in children > 5 years of age. Hypertension is reported in up to 50% of pediatric cases with CS. We report a challenging pediatric case with a rare presentation of hypertensive emergency associated with CD. Clinical Case: A 6-year-old female with 3 month-history of rapid weight gain (8 kg), round face, and hypertrichosis presented to emergency department for abdominal pain from nephrolithiasis and was noted to have severe hypertension. While in ED, she developed status epilepticus and altered mental status. Brain MRI findings were consistent with posterior reversible encephalopathy syndrome (PRES). Her hypertensive encephalopathy gradually improved with aggressive anti-hypertensive and anti-epileptic therapy. Further studies confirmed hypercortisolism with markedly elevated urine free cortisol of 1288 ug/day (<18 ug/day) and lack of diurnal variation of serum cortisol (8 AM cortisol of 47.9 ug/dL, midnight cortisol of 20.3 ug/dL). ACTH level of 23 pg/mL suggested ACTH-dependent CS. Low dose (1 mg) dexamethasone suppression test (DST) failed to suppress 8 am cortisol (31.4 ug/dL). High dose DST (120 mcg/kg) suppressed serum cortisol to 67%- borderline threshold for CD, likely due to increased dexamethasone clearance by anticonvulsant. Pituitary MRI did not reveal a visible lesion. Desmopressin stimulation test showed stimulation of ACTH by 700% and cortisol by 160% suggesting pituitary source. Inferior petrosal sinus sampling showed a mildly increased gradient in central to peripheral plasma ACTH of 1.7 at baseline (>2) and post-stimulation of 2.5 (>3). ACTH gradient did not reach cutoffs for pituitary source, likely due to insufficient catheterization of petrosal sinus from anatomically small blood vessels. Given her severity, she underwent surgical pituitary exploration. Postoperative morning cortisol was <5 mcg/dL, with decreased midnight salivary cortisol level obtained 2 months after surgery. She developed post-operative central hypothyroidism but did not have diabetes insipidus. She had a 4 kg weight loss with increased height percentile 5 months after surgery and remains under close monitoring. Conclusion: PRES is a clinical-radiographic disorder characterized by seizures, encephalopathy with neuroimaging findings of reversible cortical and subcortical vasogenic edema. Hypertension induced by marked hypercortisolism precipitated by pain is likely the etiologic factor. Prompt recognition and treatment of PRES are crucial to prevent further life-threatening complications and permanent neurological damage. Early diagnosis and treatment of CD are critical to prevent associated morbidities. Pituitary exploration by expert neurosurgery team should be considered in patients with MRI-negative CD. Presentation: Thursday, June 15, 2023

FRI235 Primary Adrenal Insufficiency As Presenting Symptom Of Disseminated Histoplasmosis And Cryptococcus Co-Infection In Immunocompetent Patient

Abstract Disclosure: A. Thompson: None. Background: Autoimmune adrenalitis remains the most common cause of primary adrenal insufficiency in the United States. Infectious etiologies from fungal sources are much less commonly seen. Below we discuss a case of disseminated histoplasmosis and cryptococcus that initially presented with primary adrenal insufficiency. Case: A 74 y/o F with history of Type 2 DM presented to the hospital with 3 months of fatigue and weight loss. She was initially found to be in DKA and shock requiring vasopressor support. Following the resolution of DKA, she remained hypotensive without obvious cause. A random cortisol was found to be 8.2 [6-25 ug/dL]. She then underwent an ACTH stimulation test and her cortisol level at 30 minutes was 5.9 ug/dL and at 60 minutes was 4.2 ug/dL. An ACTH level was obtained and found to be elevated at 69 [7.2-63 pg/mL]. She was subsequently started on Hydrocortisone and her shock resolved. CT adrenal glands were notable for bilateral adrenal masses measuring 4.5 cm on the right and 4.6 cm on the left with HU of 27. No other suspicious lesions were noted on imaging. An infectious work up was initiated, which was notable for fungal serologies positive of Histoplasmosis with titer of 1:8 (<1:8). Histoplasmosis urine antigen was positive as well. She was tested for Cryptococcus, which was positive with a titer of 1:8 (<1:8). She started treatment with Amphotericin B for 4 weeks followed by Itraconazole for maintenance therapy. Discussion: Primary adrenal insufficiency from invasive fungal infection remains uncommon and is found in less than 10% of cases. Disseminated fungal infections are identified as causes like histoplasmosis and paracoccidiomycosis. Disseminated cryptococcus is an exceedingly rare cause of adrenal insufficiency. These invasive infections can lead to bilateral enlargement of the adrenal glands and calcifications are seen on radiographic imaging. Such cases can also lead to perivasculitis and cause thrombosis and subsequent infarction of the adrenal glands. Disseminated fungal infections are more commonly seen in patients with underlying immunodeficiency such as HIV or those receiving immunosuppressant therapy. This case highlights that these infections can still be seen in those without a compromised immune system. Diagnosis can be challenging given the vague symptoms of adrenal insufficiency but should be considered in patients with electrolyte disturbances, hypoglycemia, and hypotension. There is potential for adrenal recovery following treatment with antifungal therapy. Conclusion: Although autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in the US, this case highlights the importance of evaluating for other potential causes such as infectious sources, which can be treated and potentially have adrenal recovery. Presentation: Friday, June 16, 2023

FRI252 Novel Mutation Presenting With Hypoaldosteronism In X-Linked Adrenal Hypoplasia Congenita

Abstract Disclosure: E. Ismail: None. L. Jacobsen: None. Background: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder due to a mutation in DAX-1/NR0B1, a nuclear factor that is important for the development and function of the adrenals and reproductive system. It usually presents with adrenal insufficiency in infancy and later hypogonadotropic hypogonadism. Here we describe a patient who presented with a salt wasting crisis due to hypoaldosteronism and genetic testing revealed a novel frameshift mutation in NR0B1/DAX-1 resulting in premature protein termination. Clinical Case: A 4 week old male presented with poor feeding, failure to thrive, hyponatremia, hyperkalemia, and acidosis. No hypoglycemia present. He also had an undetectable aldosterone level, high renin, normal cortisol, high ACTH, and normal 17OHP. Adrenal ultrasound (US) failed to show the right adrenal gland. With suspicion for primary hypoaldosteronism, he was started on salt supplementation and fludrocortisone with improved growth, electrolytes, and renin. His genitalia were that of a typical male infant without cutaneous hyperpigmentation. ACTH level continued to trend up despite appropriate baseline cortisol. Stimulation test with 250 mcg of Cosyntropin was done which revealed suboptimal peak cortisol of 11.5 mcg/dL (normal >18 mcg/dL), so he was started on stress dose precautions of hydrocortisone without physiologic replacement. Repeat US 2 months later did not visualize his adrenals. With suspicion for AHC, genetic testing was obtained which revealed a novel frame shift variant in NR0B1 (c.1069del, p.Gln357Argfs*15, hemizygous), resulting in premature protein termination. He was then started on daily hydrocortisone replacement. As this is an X-linked mutation, genetic testing for mother and older brother is pending. To the best of our knowledge this variant has not been reported in the literature. Conclusion: DAX-1 mutations should be considered in male infants presenting with primary hypoaldosteronism. ACTH stimulation testing is necessary to assess glucocorticoid function, especially if ACTH is elevated, which can precede cortisol deficiency. There is a wide heterogeneity in the presentation of this rare disorder, so genetic diagnosis is important to guide management, later monitoring for hypogonadism and fertility, and family testing. Presentation: Friday, June 16, 2023

THU232 Genetic Study In A Series Of 29 Triple A Syndrome Patients From 19 Sudanese Families - Identification Of Two Novel AAAS Mutations

Abstract Disclosure: K. Koehler: None. F. Quitter: None. D. Landgraf: None. E. Streiff: None. M.A. Abdullah: None. S.S. Hassan: None. A. Huebner: None. S.A. Musa: None. Triple A syndrome (MIM*231550) is a rare autosomal recessive multisystemic disorder characterized by adrenal insufficiency, achalasia, alacrima and neurologic impairments. It is caused by defects in the nucleoporin ALADIN due to mutations in the encoding AAAS gene. We report the genetic and clinical data of triple A syndrome in a series of Sudanese children treated at the Gaafar Ibn Auf Children’s Tertiary Hospital, the largest children's referral hospital in Sudan. The initial diagnosis of triple A syndrome was based on pathognomonic clinical signs and symptoms. Furthermore, early morning serum cortisol levels below the reference range (<6 μg/dl) with high ACTH levels (>100 pg/ml) and/or cortisol below 500 nmol/l in an ACTH stimulation test as well as pathological barium swallow and Schirmer-test were criteria for diagnosis. The medical diagnosis was finally confirmed by mutation detection in the AAAS gene.We genetically investigated 19 families including 29 patients with clinically diagnosed triple A syndrome. We identified six different AAAS mutations mainly in a homozygous form including three nonsense mutations, one frameshift mutation leading to a truncated protein and two splice defects, among them the North African founder mutation c.1331+1G>A (intron 14) in 32 % (6 families). An 8 bp-deletion at the junction of exon 4/intron 4 in two families is a novel, yet undescribed mutation (c.394_399+2delCTGTCTGT). As this mutation destroys a donor splice site, it results in alternative splicing skipping exon 4, altering the protein sequence after amino acid E102 and leading to a premature stop codon shortly after. This is most likely associated with functional impairment of the truncated ALADIN protein. The second novel AAAS mutation is a 1 bp-deletion in exon 9 in three families, which results in a frameshift at amino acid tryptophan 284 and consequently a premature stop codon at position 7 of the new reading frame (c.852_852delG, p.Trp284Cysfs*7, or shortly p.W284fs). The most frequent mutation in this large Sudanese patient series was a previously described mutation in exon 9 (c.934C>T, p.Arg312*) present in 37 % (seven families).Genotype/phenotype analyses revealed a highly variable occurrence of the three main symptoms, age of onset and severity of the disease between patients with the same AAAS mutation and even within one family. The rate of 95 % mutations in a homozygous form reflects the high rate of consanguinity in the Sudanese population.In summary, triple A syndrome seems to be an underdiagnosed disease outside a specialized paediatric endocrinological department in Sudan as many cases presented late with adrenal crises. An early molecular genetic diagnosis, e.g. in siblings, can be important to avoid hypoglycaemic crises with a potential lethal outcome. Presentation: Thursday, June 15, 2023

FRI261 A Case Of Cushing Syndrome And Hyperandrogenism Secondary To An Adrenal Cortical Oncocytoma

Abstract Disclosure: E. Hall: None. S. Gupta: None. J. Lee: None. Background: Adrenal cortical oncocytomas are rare neoplasms that are often non-functional, but there have been case reports of associated hypercortisolism, hyperandrogenism, and in even rarer cases, multiple hormonal excesses. Clinical Case: A 30 year old woman with history of hypertension, prediabetes and obesity presented with 3 years of oligomenorrhea, hirsutism, weight gain, and voice deepening. She did not take any medications and had no family history of endocrine diseases. Labs revealed hyperandrogenism: elevated total testosterone of 390 ng/dL and 435 ng/dL (nl 6-82), suppressed FSH of 0.2 mIU/mL (nl 1.7-21.5) and LH of <0.1 mIU/mL (nl 1.0-95.6), normal DHEA-S of 290 ug/dL (nl 98.8-340). Morning 17-hydroxyprogesterone was elevated to 944 ng/dL and increased to 1031 ng/dL (nl 23-431) on ACTH stimulation test, which did not meet diagnostic criteria for non-classical congenital adrenal hyperplasia. Also, genetic testing for CYP21A2 gene mutations was negative. Pelvic ultrasound was unremarkable. CT of the adrenal glands showed a 4.6 x 3.8 x 4.4 cm mildly heterogeneous left adrenal mass that measured 35 HU on non-contrast images with absolute washout of 50% and relative washout of 31%. The mass was concerning for malignancy based on HU >20, size >4cm, and 50% contrast washout (borderline). Overnight 1mg dexamethasone suppression test showed non-suppressed morning cortisol of 7.1 ug/dL (nl <1.8), with dexamethasone level of 246 ng/dL (nl 180-550) and ACTH of <5 pg/ml (nl 6-50). Twenty four hour urinary free cortisol level was slightly elevated to 52.3 mcg/24h (nl 4-50). Plasma metanephrines and aldosterone/renin ratio were normal. The patient underwent left laparoscopic adrenalectomy without complications. Pathology was consistent with adrenal cortical oncocytoma. Post-operatively, morning cortisol was <0.3 ug/dL, so she was started on hydrocortisone replacement twice daily but was tapered off within three months. Three weeks after surgery, total testosterone was <8 ng/dL. Two months after surgery, her menstrual cycles resumed. Fifteen months after surgery, she had regular menstrual cycles, 20 lb weight loss, resolution of hirsutism, hypertension and prediabetes. Conclusions: Adrenal cortical oncocytomas are rare tumors of the adrenal glands that should be considered in the differential for large adrenal tumors that appear suspicious for malignancy on imaging. They may or may not be functional, and in this case, the tumor secreted both androgens and cortisol. Although androgen-secreting tumors are frequently malignant, such as adrenocortical carcinomas, androgen-secreting oncocytomas are generally considered benign. However, there have been rare reports of malignant oncocytomas and oncocytomas of uncertain malignant potential. Presentation: Friday, June 16, 2023

SAT220 Rare Case Of Pembrolizumab Induced Primary Hypoparathyroidism

Abstract Disclosure: S.G. Goud: None. A. Siddiqui: None. M. Alkhathlan: None. C.Y. Fan: None. Introduction: Immune checkpoint inhibitors such as pembrolizumab (Keytruda) used in the treatment of various cancers are associated with immune mediated endocrinopathies, among which thyroid dysfunction and pituitary hypophysitis are common, whereas hypoparathyroidism is rare. We report a case of primary hypoparathyroidism and hypocalcemia with pembrolizumab. Clinical Case: 58-year-old male with metastatic urothelial cell carcinoma, status post neoadjuvant chemotherapy with gemcitabine and cisplatin in 2017, followed by radical cystectomy with recurrence of metastasis in 2018, who was started on Keytruda every three weeks. After 10 months, he developed immune mediated hypothyroidism treated with levothyroxine. After 33 months on Keytruda, he developed hematochezia with constipation and intermittent abdominal pain. Colonoscopy showed findings consistent with autoimmune colitis; Keytruda was held and colitis was treated with tapering steroids. Surveillance imaging showed stable disease, so Keytruda continued to be held. After 7 months of holding Keytruda, on routine blood work he had a critically low calcium level of 5.5 mg/dl (8.4-10.2 mg/dl) with tingling and numbness in his hands, muscle spasms, generalized weakness, and fatigue for the past few weeks. On exam there was no Trousseau’s sign, Chvostek's sign, or gait ataxia. Hemodynamically stable. Labs showed lowest corrected calcium of 5.5, normal renal function, low vitamin D of 8 ng/ml (30-100 ng/ml), elevated phosphorus of 6.3 mg/dl (2.5-4.5 mg/dl), and normal magnesium. PTH was frankly low at 12.7 pg/ml (15-65 pg/ml), indicating primary hypoparathyroidism. ACTH stimulation test was normal. Retrospective review of the labs from oncology office records showed gradual, progressive hypocalcemia for a few months prior to presentation, with calcium levels ranging between 6.7 to 7.7 mg/dl. Of note, calcium prior to pembrolizumab was normal at 9.4 mg/dl. He was treated with IV calcium gluconate and then transitioned to calcium carbonate (CaCO3) 500 mg TID, calcitriol 0.5 mg BID, and Vit D 50,000 IU twice weekly. Hydrochlorothiazide (HCTZ) added as calcium remained low. After three days calcium improved to 7 mg/dl range and he was discharged. Calcium levels checked periodically after discharge ranged from 8 to 9 mg/dl (8.4-10.2 mg/dl), and phosphorus levels normalized. CaCO3 dose was adjusted accordingly, Vit D was changed to 50,000 IU weekly based on a level of 71 ng/dl after 3 months, and HCTZ was discontinued after 6 months. PTH was still low at 9.7 pg/ml (15-65 pg/ml) 6 months after discharge, off pembrolizumab for over a year. Calcium sensing receptor (CaSR) activating antibody was not checked in our case. Conclusion: It is important clinicians be aware of the risk for hypocalcemia and its unpredictable presentation to help with timely recognition and management. Presentation: Saturday, June 17, 2023

FRI215 Rifampin Induced Adrenal Insufficiency

Abstract Disclosure: S.R. Campbell: None. R.M. Tierney: None. J. Lim: None. Introduction: Rifampin is a main component of antimycobacterial therapy in active tuberculosis disease. Although adrenal insufficiency can be caused by infiltration of the pituitary or adrenal glands by Mycobacterium tuberculosis, rifampin has also been suggested as a potential causative agent. This case shows a rare example of rifampin-induced adrenal insufficiency in the setting of active tuberculosis disease. Case Presentation: A 42-year-old man with a history of gout and anemia presented with fevers, chills, unintentional weight loss, and productive cough for two weeks. He immigrated from Guatemala 20 years prior and was treated for tuberculosis disease as a child. Upon presentation, he was borderline hypertensive with chest CT showing bilateral nodular opacities in a pattern suggestive of atypical pneumonia. Acid fast bacilli stains were positive and cultures grew Mycobacterium tuberculosis. The patient was started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy. Serum cortisol levels on day 4 of RIPE therapy were appropriate in the setting of acute illness (>20 mcg/dl). On day 6 of RIPE therapy, the patient became hypotensive requiring vasopressor support. Labs at that time showed hyponatremia, hypokalemia, and inappropriately low cortisol levels (<20 mcg/dl). ACTH stimulation testing was performed and was blunted with values of 14.50 mcg/dL at 30 minutes and 16.32 mcg/dl at 60 minutes. CT abdomen was also performed and showed no evidence of infiltration. He was started on IV hydrocortisone 50 mg every 6 hours with plans to taper after shock resolved. Following steroid taper, the patient again became hypotensive requiring vasopressors. IV hydrocortisone was resumed, and RIPE therapy was held. He was restarted on PO hydrocortisone 40 mg every 12 hours. Isoniazid, ethambutol, pyrazinamide, and rifampin were sequentially resumed. Pyrazinamide was replaced with moxifloxacin due to recurrent gout flares. The reintroduction of rifampin and rifabutin both resulted in fevers leading to the stoppage of rifamycin therapy. The patient was discharged with stable vital signs on isoniazid 300 mg daily, ethambutol 800 mg daily, moxifloxacin 400 mg daily, and hydrocortisone 30 mg every 12 hours with plans to follow-up with the State Department of Health, internal medicine, and endocrinology. Conclusion: Many drugs are known to cause adrenal insufficiency. There are a few examples in which rifampin has been suggested as a potential cause of adrenal insufficiency. Classically, adrenal insufficiency has been associated with infiltration of the adrenal glands or pituitary gland with Mycobacterium tuberculosis. This case, however, shows further clinical evidence of adrenal insufficiency caused by rifampin therapy and highlights the need for further research to be done to study this adverse effect. Presentation: Friday, June 16, 2023

SAT172 Unmasking A Pediatric Disease In Adult, A Belated Diagnosis

Abstract Disclosure: H. Syed: None. P. Au: None. M.J. Gardner: None. Background: Glycogen storage diseases (GSD) are a rare group of diseases that change the way the body uses and stores glycogen. They are usually diagnosed in the pediatric population. Hypoglycemia can be a sign. Clinical Case: A 32 year old female presented with worsening and more frequent episodes of hypoglycemia. She had no history of diabetes and was not on any hypoglycemic agents. She had been having episodes of spontaneous hypoglycemia since childhood and would get symptomatic as well. No comprehensive workup had been done prior. The episodes were becoming more frequent. A blinded continuous glucose monitor was placed on the patient to monitor her glucose levels. Results indeed showed few episodes of hypoglycemia with glucose levels in the 40s. Interestingly, she also had postprandial hyperglycemia with glucose level above 180 following an episode of hypoglycemia. She underwent a 72 hour fast in the hospital and became hypoglycemic within 24 hours with a low blood glucose of 55, consistent with hypoglycemia, and she was also symptomatic as well. At the same time, her beta hydroxybutyrate increased to 3.91 mmol/L, consistent with ketosis. Her insulin level and C-peptide level at the time of hypoglycemia were 4.35 mcunit/mL and 0.239 nmol/L, respectively, and thus insulinoma was ruled out. She next underwent a mixed meal study during which her postprandial blood glucose increased to at least 198 indicating postprandial hyperglycemia. At the same time, patient's postprandial lactate also elevated to 4 mmol/L, consistent with lactic acidosis. Her symptoms of hypoglycemia resolved once her blood sugar (BG) improved. She met criteria for Whipple’s triad. She also had had an 8 am cortisol of 13.06 mcg/dL and had an appropriate response to the ACTH stimulation test with a 60 minute post cortisol above 20 mcg/dL, thus ruling out adrenal insufficiency as a cause of hypoglycemia. These findings of the 72 hour fast that resulted in hypoglycemia, followed by postprandial hyperglycemia with lactic acidosis are consistent with Glycogen Storage Disorder Type 0. Treatment involves intake of uncooked cornstarch with protein. Patient incorporated both uncooked cornstarch along with increasing amount of protein in her diet and started using a continuous glucose monitor with alarm to monitor her BGs. As a result her episodes of frequent hypoglycemia improved. Conclusion: This case illustrates a rare case of hypoglycemia in an adult that was not thoroughly investigated when she was in her childhood and adolescence. This case teaches the importance of being familiar with pediatric conditions since it is possible that pediatric conditions, especially if they are missed by providers and not appropriately diagnosed. Presentation: Saturday, June 17, 2023