Cosyntropin Stimulation Test Research Articles

6422 Identifying Predictive Symptoms Of Adrenal Insufficiency

Abstract Disclosure: A.J. Han: None. S.J. Achenbach: None. B.J. Atkinson: None. I. Bancos: None. Background: Diagnosis of adrenal insufficiency (AI) is often delayed due to its vague and non-specific symptomatology. As classic symptoms of AI such as fatigue and nausea are prevalent in the general population, identifying clinical features that are more specific to AI may help clinicians determine which patients require additional testing. Methods: A single-center retrospective study was performed of patients who underwent outpatient Cosyntropin stimulation testing (CST) between 2005-2018. Patients with oral glucocorticoid or estrogen use within 2 months of CST, and patients without available Current Visit Information (CVI) form at the time of CST were excluded. Presence of symptoms was obtained from CVI, and laboratory findings were electronically extracted. Adrenal insufficiency was defined as post-CST peak cortisol <18 mcg/dL. Morbidity was assessed using the Elixhauser index. Variables for multivariable analysis were defined a priori and included fatigue, dizziness, muscle pain, joint pain, weight loss >10 pounds, abdominal pain, nausea/vomiting, and hyponatremia. Results: Among 5347 patients who underwent CST, 376 (7.0%) of patients were found to have AI. There were no sex differences between patients with and without AI, however patients with AI were slightly older (median age 48.9 vs 47.1 years, p=0.026), and had a higher median BMI (26.5 vs 25.6 kg/m2, p=0.002). Prevalence of comorbidities was similar between the two groups, with a median Elixhauser index of 1 (IQR 1-3), however, patients with AI were more likely to report difficulties with activities of daily living (69% vs 57%, p<0.001). Hyponatremia was diagnosed in 4% of patients with AI and 3% of those without AI, p=0.208. Although patients in our cohort reported a high prevalence of fatigue (79%), dizziness (50%), joint pain (50%), muscle pain (48%), nausea (40%), abdominal pain (39%), and weight loss in the past 6 months (29%), there were no statistically significant differences in reported symptoms between patients with and without AI with the exception of joint pain (59% vs 49%, p<0.001) and muscle pain (54% vs 47%, p=0.009). Based on multivariable analysis, only joint pain (OR 1.51, 95% CI 1.14-1.99) and weight loss >10 pounds in the past 6 months (OR 1.31, 95% CI 1.02-1.68) were associated with higher odds of AI diagnosis. Interestingly, patients who reported fatigue had lower odds of AI diagnosis on CST (OR 0.66, 95% CI 0.49-0.88). Conclusions: Commonly associated symptoms of AI such as fatigue, dizziness, nausea, and abdominal pain were poor predictors of AI diagnosis based on CST. Consequently, the presence of these symptoms alone may not warrant additional testing. Notably, clinical features such as myalgia, arthralgia, and weight loss >10 pounds in the past 6 months were found to be more predictive of AI. Presentation: 6/1/2024

8219 Biochemical Disease Severity Score For Hypercortisolism Can Predict Adrenal Insufficiency After Adrenalectomy For Mild Autonomous Cortisol Secretion

Abstract Disclosure: O. Hamidi: Advisory Board Member; Self; Corcept, Neurocrine Biosciences, Amryt Pharma, Recordati Rare Diseases, Lantheus, Xeris. B.H. Salama: None. P. Dogra: None. A.P. Dackiw: None. F. Nwariaku: None. A. Islam: None. A. Mehta: None. S.C. Oltmann: None. S. Mirfakhraee: None. T. McKenzie: None. T.R. Foster: None. M. Lyden: None. B.M. Dy: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) are at risk for adrenal insufficiency (AI) after unilateral adrenalectomy. We aimed to determine the prevalence, predictors, and duration of AI after unilateral adrenalectomy for MACS, and to compare baseline and peak cortisol post cosyntropin stimulation test (CST) in diagnosing AI. Methods: We conducted a dual-center retrospective cohort study of patients with MACS who underwent unilateral adrenalectomy and were evaluated with postoperative cosyntropin stimulation test (CST). AI was diagnosed when postoperative morning cortisol was <10μg/dL and/or CST peak cortisol was <18μg/dL. Baseline and CST peak cortisol levels were considered concordant when both met corresponding cut-offs. Biochemical (BSS) and clinical (CSS) severity scores for hypercortisolism were calculated. Results: In 100 adults with MACS (77% women, median age 56 years, interquartile range [IQR] 48-63), median adenoma size was 2.8 cm (IQR, 2.2-3.7), and 25 (25%) had bilateral nodules. Median BSS was 3 (IQR, 2-5) and median CSS was 4 (IQR, 2-8). After adrenalectomy, AI was diagnosed in 56 (56%) patients. AI was associated with higher BSS, larger tumor size, but not age, sex, BMI, tumor laterality. Baseline and CST peak cortisol levels were concordant in 76% of cases. In 14% of cases morning cortisol was <10μg/dL but CST peak cortisol was ≥18μg/dL, and in 10% of cases morning cortisol was ≥10μg/dL, but CST peak cortisol was <18μg/dL. On a multivariable analysis that included age, sex, BMI, BSS, laterality, and tumor size, only higher BSS (odd ratio [OR] = 1.6 per 1 point) was associated with postoperative baseline cortisol <10μg/dL (P<0.05 for all). Independent predictors of CST peak cortisol <18μg/dL were BSS (OR 1.5 per 1 point) and unilateral adenoma (OR 3.7). During a median postoperative follow up of 13 months, 33 (59%) patients recovered from AI. Median time to recovery was 6.0 months, with AI recovery in 28% of patients by 2 months, 42% by 3 months, 53% by 6 months, and 64% by 12 months. Conclusions: Prevalence of postoperative AI in MACS was 56%. Only 76% of patients had concordant baseline and CST peak cortisol, with peak CST cortisol being more commonly abnormal in patients treated for unilateral MACS. Patients with larger adenomas and higher BSS were at higher risk for AI. Patients with MACS should be counseled about the risk and duration of AI after adrenalectomy. Presentation: 6/3/2024

6664 A Case of Undistinguished Congenital Adrenal Hyperplasiain a Patient with Hypertensive Emergency and Hypokalemia

Abstract Disclosure: V.L. Del Signore: None. S.T. Kaufman: None. CAH is a group of autosomal recessive disorders resulting in alterations of adrenal steroid biosynthesis. With 95% of CAH cases due to 21-hydroxylase deficiency; other causes are rare. The metabolic, phenotypic, and physiologic derangements are specific to the altered enzymatic pathways, most of which are life threatening. Identifying the enzymatic defect is crucial to treat the patient. We present a case of undifferentiated CAH in an adult resulting in significant systemic illness. A 26-year-old well virilized male presented with chief complaint of shortness of breath, lower extremity swelling, and abdominal distension for 3 weeks. He was found to have acute decompensated heart failure with LVEF 20-25%, NSTEMI, atrial fibrillation, hypertensive emergency with BP of 224/102, and potassium (K+) of 2.7 (3.5-5mmol/L). PMH included hypertension and CAH diagnosed at birth. Patient was unsure of his CAH defect. Pediatric endocrinology prescribed glucocorticoids until age 17 at which point he was told steroids were no longer required. He had been lost to follow up for 9 years. Pediatric records were unattainable. Patient remained hypokalemic and hypertensive despite aggressive K+ repletion and multiple IV antihypertensives. Endocrine work up revealed renin 0.19 (0.25- 5.82ng/mL/hr), aldosterone 4 (< or = 21ng/dL), DHEAs 97 (74-617ug/dL), FSH <0.3 (1.4 - 18.1 m[IU]/mL), LH <0.3 (1.5 - 9.3 m[IU]/mL), total testosterone 306 (250-1,100 ng/dL), SHBG 32 (10-50nmol/L), progesterone 7 (0.2-1.4 ng/mL), ACTH 345 (6-50 pg/mL), AM cortisol 4.4 (5-23 ug/dL), 17 hydroxyprogesterone 311 (32-307 ng/dL), androstenedione 1,926 (50-220 ng/dL), 11-deoxycortisol >10,000 (< or = 119 ng/dL). Cosyntropin stimulation test: 30-minute cortisol 11.1 (>18 ug/dL) and 60-minute cortisol 10.4 (>18 ug/dL). Based on clinical and lab findings a diagnosis of 11-beta hydroxylase deficiency was made. Spironolactone was started to counteract the excessive mineralocorticoid effects of deoxycorticosterone and hydrocortisone to decrease ACTH production. With this treatment, patient’s potassium and blood pressure gradually improved. IV antihypertensives were weaned as he transitioned to oral agents. This case demonstrates the importance of understanding and identifying the underlying pathophysiology of CAH to treat patients appropriately. This patient had a mineralocorticoid excess state, but adequate cortisol precursors to prevent adrenal crisis. He requires glucocorticoid therapy to prevent excessive ACTH from driving their BP and metabolic derangements. With appropriate diagnosis of 11-beta hydroxylase deficiency, patient’s excess risk of morbidity and mortality due to the downstream effects of uncontrolled CAH can be minimized. Presentation: 6/3/2024

9202 Characterizing The Physiological Side-Effects Of Over-The-Counter Arthritis Supplements

Abstract Disclosure: K.S. Wei: None. M.O. De La Torre: None. A. Flores: None. C.E. Chiu: None. T.E. Angell: None. Introduction: Over the counter (OTC) health supplements are commonly used by patients for a variety of ailments but may contain active ingredients that are not stated, such as glucocorticoids. Here, we present a case series of 12 patients seen by the Endocrinology Consult service at an urban safety net hospital during 2022-2023 and determined to have iatrogenic adrenal insufficiency (AI) from specific OTC supplements that surreptitiously contained glucocorticoids. Clinical Cases:12 patients using OTC arthritis supplements [Artri King (n=8), Ardosons (n=3), and Ajo Rey (n=1)] were identified. Median age was 52 years and 33.3% were female. All started using the supplements because of joint pain. Median length of use prior to cessation was 6 months. The most common presenting symptoms were nausea/vomiting (42%), fatigue (42%), abdominal pain (33%), and dizziness (17%). The most common physical exam findings of steroid excess included moon facies (66%), central adiposity (66%), abdominal striae (50%), dorsocervical fat pad (33%), and bruising (33%). 3/12 patients required ICU admission. Cortisol assessment was performed in 11/12 patients, which showed normal cortisol level in 1 patient (cortisol ≥16 mcg/dL), AI in 3 patients (cortisol ≤3 mcg/dL), and an equivocal level (cortisol 3-16 mcg/dL) in 7 patients. Cosyntropin stimulation testing in 6/7 patients with equivocal cortisol levels suggested AI in 4 (cortisol level <16 mcg/dL at 60 minutes after ACTH stimulation), whereas 2 showed lower but normal response (cortisol levels 18.2 mcg/dL and 18.4 mcg/dL). In total, 10/12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis. The most common regimens were hydrocortisone 20mg qAM/10mg qPM (33%) and hydrocortisone 5mg qAM/5mg qPM (17%). To date, 2/10 patients have successfully discontinued steroid replacement. Conclusion: These cases demonstrate possible Cushing’s syndrome and/or adrenal insufficiency after unintentional exposure to glucocorticoids in these OTC arthritis supplements, which has only previously been reported in a small number of case reports (1). This series collected over a 2-year period offers important clinical insights: Because patients may not identify or recall a supplement, possible use of OTC medications for arthritis or other anti-inflammatory purposes should be specifically assessed in patients presenting with adrenal insufficiency (especially with concomitant findings suggesting Cushing’s syndrome). For patients on such supplements, immediate discontinuation may not be possible without cortisol replacement and should be done with caution. 1)Boncompagni A.C. et al. A case of iatrogenic Cushing syndrome and subsequent adrenal insufficiency from a hidden ingredient in the supplement Artri Ajo King. J Am Coll Emerg Physicians Open. 2023;4(4):e13007. Presentation: 6/1/2024

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

8764 A Unique Case of Infertility in a Patient with NCCAH

Abstract Disclosure: M. Paravastu: None. R. Patel: None. Background: Non-Classic Congenital Adrenal Hyperplasia (NCCAH) in women often presents with hirsutism, acne, menstrual dysfunction, or infertility. Subfertility in patients with NCCAH can be attributed to menstrual disorders including oligomenorrhea or secondary amenorrhea. We report a unique case in which a patient with NCCAH with consistently normal menstrual cycles is experiencing infertility. Case Description: A 31 y/o female with no PMH was referred to our Endocrinology Clinic for evaluation of Infertility and elevated 17-Hydroxyprogesterone levels (17OHP). Patient has been having trouble conceiving for the past 2 years, no prior successful pregnancies. She started menstrual cycles at age 17, she reports having regular menstrual cycles. Prior to our evaluation, she was seen in Reproductive Endocrinology who completed hormonal and imaging evaluation. Elevated 17OHP: 286ng/dL. Rest of hormonal workup within normal range. Normal Pelvic Ultrasound. Hormonal workup was repeated in our clinic. 17OHP is elevated at 617.01ng/dL. Rest of lab work returned normal with DHEAS:218.9mcg/dL, TSH: 2.826mcUnits/mL, Free Testosterone: 5.4pg/mL, Prolactin:11.7ng/mL, Beta HCG: negative, LH: 13.5mUnits/mL, FSH: 5.3mUnits/mL, Estradiol 79pg/mL. Cosyntropin stimulation test was completed. Baseline AM 17OHP:469.78ng/dL, Baseline Cortisol: 17.9mcg/dL. 17OHP 30 minutes-post:1216.4ng/dL, Cortisol 30 minutes-post: 18.5mcg/dL. 17OHP 60 min-post: 1051ng/dL, Cortisol 60 minutes post:16.4 mcg/dL. Given Inconclusive Cosyntropin stimulation test results, Genetic Testing was recommended. Genetic testing returned positive for NCCAH, patient’s husband is not a carrier of this gene. She was started on Hydrocortisone therapy for treatment of infertility. Shortly after she started on hydrocortisone therapy, patient did successfully conceive, however the pregnancy later resulted in a miscarriage. Conclusion: Subfertility in patients in NCCAH is thought to be due to menstrual irregularities including oligomenorrhea or secondary amenorrhea. We report the first case of a woman with diagnosis of NCCAH who is experiencing infertility despite having normal menstrual cycles. Presentation: 6/1/2024

12224 Addressing Blood Glucose Fluctuations and Fasting Challenges in Sheehan Syndrome: A Case Study

Abstract Disclosure: H.A. Awadalla: None. A.N. Kiani: None. W. Taha: None. N.N. Solanki: None. A. Lattouf: None. A. Shermetaro: None. A. Taweel: None. Introduction: Sheehan's syndrome (SS) is a rare condition characterized by hypopituitarism resultingfrom ischemic necrosis of the pituitary gland due to severe postpartum hemorrhage.Patients may have hormonal insufficiencies, ranging from single pituitary hormoneinsufficiency to total hypopituitarism. The diagnosis of SS is often delayed due to itsnonspecific signs and symptoms, leading to many undiagnosed and untreated cases. Case Presentation:A 33-year-old African American female with a history of panhypopituitarism secondaryto Sheehan Syndrome presented with syncope, lightheadedness, and severehypoglycemia (blood glucose 12mg/dL). Despite regular food intake, she struggled withglycemic control, experiencing recurrent hypoglycemic episodes associated withnausea, vomiting, unintentional weight loss (25kg), and polydipsia/polyuria. Laboratoryfindings revealed low ACTH, sodium, cortisol, and elevated liver enzymes, consistentwith hypopituitarism. Cosyntropin stimulation test confirmed adrenal insufficiency. MRIshowed an empty sella. Initially treated with high-dose hydrocortisone, then transitionedto lower maintenance doses, she continued to experience glycemic fluctuations.Intravenous dextrose and insulin sliding scale were initiated. Upon discharge, she wasprescribed hydrocortisone and levothyroxine. Despite adjustments, hypoglycemiapersisted, managed with dietary modifications. This case underscores the challenges inmanaging Sheehan Syndrome-associated panhypopituitarism and the need for tailoredtreatment approaches to achieve metabolic stability. Conclusion: This case underscores the complexities of managing panhypopituitarism secondary toSheehan syndrome, emphasizing the importance of comprehensive hormonalreplacement therapy and thorough monitoring to achieve symptom control andmetabolic stability. Tailored treatment regimens and continuous assessments arecrucial to addressing individual hormone deficiencies and preventing associatedcomplications effectively in these patients. Presentation: 6/1/2024

7741 Artri King As A Cause Of Adrenal Insufficiency

Abstract Disclosure: Q. Aziz: None. S. Fatima: None. A.L. Champion: None. K.E. Izuora: None. IntroductionDietary supplements are highly unregulated and may have substance that can be harmful. Due to its easy availability, more patients may have access to these supplements which can cause detrimental health outcomes, such as adrenal insufficiency. Clinical Case Patient is a 46 year old female with past medical history of hypertension and obesity presents to the hospital for worsening left hip pain, which started 2 weeks ago. She heard a crack in her left hip and denied any trauma or injury prior. She was found to have subtrochanteric fracture. Nine months ago, she had right hip pain and was unable to bear weight. Physical exam was notable for alopecia in frontal and temporal region, dorsocervical fat pad, multiple bruises, round facies, and multiple purple straie. She also reported a 50 pound weight gain in the last year. She stated that she took an over the counter “pain medication”, but denied any supplements. Due to the non-traumatic fracture and physical features, AM cortisol was ordered for suspicion of Cushing’s Syndrome by primary team and was low at 2.4. Endocrinology team was consulted. Cosyntropin stimulation test showed baseline AM cortisol level 1.4 and 1 hour after cosyntropin, cortisol was 8.3. ACTH 3.4, testosterone undetectable, androstendione undetectable, Aldosterone 42.2, DHEA undetectable. It was found later that patient was taking an over the counter supplement called Artri King, up to 4 tablets a day. Artri King has been advertised as a supplement for joint and muscle pain and contains unknown amount of dexamethasone and diclofenac. She was soon placed on hydrocortisone for adrenal insufficiency and was titrated down. The hypothalamic-pituitary-adrenal (HPA) axis can be suppressed with as low as 5 mg prednisone equivalent a day. This can lead to inadequate adrenal response to stress. If a patient has prolonged exposure to exogenous steroids, insufficient ACTH secretion can lead to atrophy of the zona fasciculata and reticularis, resulting in reduced ability to secrete cortisol. Therefore, it is important to help withdraw patient from glucocorticoids. When initiating glucocorticoid withdrawal, hydrocortisone may be helpful due to short half life, allowing HPA axis more opportunity to recover. Adrenal atrophy may be slowly reversible, but 4 years after diagnosis of glucocorticoid induced adrenal insufficiency, recovery of adrenal function is unlikely to occur. ConclusionsIt is important to obtain a thorough history, especially for supplements. Many supplements are not regulated and can pose harm to our patients. Adrenal insufficiency due to glucocorticoids may not only occur from steroid injections, long course of prescription glucocorticoids, but can include supplements if it is hidden from the ingredient list. Presentation: 6/3/2024

6768 A Rare Presentation of Primary Adrenal Insufficiency with Hypertension & Hypokalemia

Abstract Disclosure: A.M. San Hernandez: None. R. Alshantti: None. G. Espinoza Mercado: None. J.L. San Hernandez: None. Introduction: Adrenal Insufficiency is caused by the failure of the adrenal cortex to produce glucocorticoids +/- mineralocorticoids. This can be due to a defect in the adrenal cortex, or in the hypothalamic pituitary axis. The clinical manifestations are usually non-specific, ranging from mild vague symptoms to life threatening crisis. Therefore, diagnosis requires a high level of suspicion by providers. Unusual presentations of primary adrenal insufficiency (PAI) with hypertension and hypokalemia have been rarely described in the literature. We present a rare case of PAI with hypertension and hypokalemia. Case Presentation: A 68 years old female with a medical history of rheumatoid arthritis, hypothyroidism on Levothyroxine, chronic transaminitis, and bicytopenia presented to the hospital with a 6 weeks history of generalized weakness, loss of appetite, weight loss, and dizziness. Patient denied any diuretic or steroid use within the last 2 years. On arrival, she was afebrile, hypertensive (168/84mmHg), with normal oxygenation and pulse. Physical examination was unremarkable with normal volume status. Initial laboratory results showed low sodium 116 mEq/L, low serum osmolality 247 MEQ/kg, normal potassium 3.6 mEq/L, Creatinine 0.3 mg/dL & BUN 9 mg/dL. She was initially started on IVF normal saline. Further workup revealed normal TSH & FT4 levels. Urine study showed urine osmolality (477 MOSM/KG), & urine sodium (127 mEq/L). Given these findings, SIADH was suspected and fluid restriction was started. Sodium level continued to be low with minimal improvement to 120 mEq/L, potassium levels also dropped (3.3-3.2 mEq/L), requiring daily replacement. BP remained elevated ranging from 150s to 160s systolic and 80s to 90s diastolic. Hypertension was controlled with her home medication Amlodipine. Although atypical presentation with hypertension & hypokalemia, the diagnosis of adrenal insufficiency was considered. Laboratory evaluation showed low morning cortisol 5.2 ug/dL, with album level 3.5 g/dL. Cosyntropin stimulation test showed 1.3 ug/dL (at baseline), 9.9 (30 min post administration), and 14.4 (1 hour post administration); results confirming PAI. ACTH, Renin, Aldosterone, & DHEAS levels were normal. CT adrenal was normal. Patient was started on hydrocortisone; some of her symptoms & Na level improved. Further investigation of the etiology of PAI and possible hyperaldosteronism is pending outpatient follow up. Conclusion: Adrenal insufficiency is a life threatening condition with serious consequences if diagnosis is missed. It manifests by a wide spectrum of symptoms and signs, some can be masked by the presence of other comorbid conditions leading to atypical presentations. Our case highlights the importance of maintaining a high level of suspicion of adrenal insufficiency in patients with atypical presentation, including those with hypertension & hypokalemia. Presentation: 6/3/2024

7761 Unmasking The Uncommon: A Case Of Primary Adrenal Insufficiency Presenting As Severe Hypercalcemia

Abstract Disclosure: A. Misbah: None. Z. Al-Hiti: None. A. Saleh: None. M. Joda: None. K. Rajamani: None. Adrenal insufficiency is a recognized but uncommon cause of hypercalcemia. The exact mechanism remains unknown; however, it is thought to be a combination of the hypovolemic state in adrenal insufficiency leading to decreased urinary clearance, as well as increased bone resorption. We present a case of primary adrenal insufficiency presenting with severe hypercalcemia. A 41 year old female with a past medical history of osteopenia, recently diagnosed postural orthostatic tachycardia syndrome (POTS), and hyponatremia attributed to SIADH presented with complaints of weakness and poor oral intake. She also reported a history of nausea, vomiting, weight loss, fatigue, and dizziness, for the last few months. She reported feeling well prior to a COVID-19 infection a few months back. At presentation, she was hypotensive with a blood pressure of 70/50 mmHg, while her other vital signs were stable. She appeared ill, and was noted to have dry oral mucous membranes. There was no increased pigmentation noted on exam. Initial laboratory evaluation revealed sodium of 130 (135-145 mmol/L), potassium of 5.3 (3.5-5.1 mmol/L), and creatinine of 1.7 (0.5-0.8 mg/dL). She had severe hypercalcemia with a calcium level of 15.5 (8.3-10.6 mg/dL) and had a blood glucose level of 53 (70-100 mg/dL). Venous blood gas indicated metabolic acidosis. Morning cortisol was low at 1 (3-23 ug/dL). Serum ACTH was elevated at 775 (0-46 pg/mL). Cosyntropin stimulation test confirmed primary adrenal insufficiency. She underwent work-up for hypercalcemia, which revealed a suppressed PTH, normal levels of PTHrP, vitamin D, and vitamin A. Serum and urine protein electrophoresis was normal. She was initially managed in the ICU and received aggressive fluid resuscitation. She was started on stress dose of hydrocortisone, which was then tapered to physiological doses of oral hydrocortisone and fludrocortisone. Subsequent improvements were observed in blood pressure, laboratory abnormalities, and normalized serum calcium levels. She was discharged home on hydrocortisone and fludrocortisone. On follow-up, she was doing well with the resolution of her symptoms. This case highlights the importance of recognizing adrenal insufficiency as one of the causes of hypercalcemia. Although hypercalcemia as a consequence of adrenal insufficiency is well-documented, the exact prevalence is not known but is estimated to be around 6%. After excluding more common diseases such as primary hyperparathyroidism and malignancy, the possibility of adrenal insufficiency should be considered as a cause of hypercalcemia. Treatment involves hormone replacement as well as hydration, bringing resolution to symptoms. Her presentation was unique, also due to the fact that her initial symptoms were diagnosed as POTS as well as SIADH. Given the onset of symptoms after a COVID-19 infection a few months ago, there could also be a potential link between the two. Presentation: 6/3/2024

8723 Glucose Metabolism Disturbances in Non-Classic Adrenal Hyperplasia (NCAH)

Abstract Disclosure: B. Domagała: None. A. Gamrat: None. A. Skalniak: None. E. Przybylik-Mazurek(†): None. M. Trofimiuk-Muldner: None. A. Hubalewska-Dydejczyk: None. Introduction: There is data reporting an increased risk of cardiovascular and metabolic complications in patients with NCAH. This is frequently attributed to glucocorticoid (over)use or misdosing. It seems that long-term exposure to increased androgens concentrations may also itself lead to diminished insulin sensitivity and increased risk of prediabetes and diabetes. Aim: The study aimed to assess the link between NCAH diagnosis and glucose metabolism disturbances. Material and methods: The study included 327 subjects (315 females and twelve males, median age 25 years) referred for a cosyntropin stimulation test due to the suspected NCAH. Serum 17-OH-progesterone (17-OHP) was assessed with an ELISA assay. The diagnosis of NCAH was confirmed if the initial or stimulated 17-OHP concentration exceeded 10.0 ng/mL. None of the tested subjects was treated with glucocorticoids. A history of preexisting prediabetes or diabetes was recorded. Anthropometric measurements were obtained to calculate body mass index (BMI). Fasting glucose was measured in each subject. Mann-Whitney U and Yates’ χ2 tests were used in statistical analyses, with p<0.05 as the cut-off value of statistical significance. Results: 62 patients (60 females, two males; median age 26 years) were diagnosed with NCAH; the rest of the tested subjects were considered the control group. Preexisting type 2 diabetes was recorded in ten subjects in the entire study group (6 of them were diagnosed with NCAH). There was no significant difference in the fasting glucose levels (p=0.08) and BMI (p=0.32) between subjects with and without NCAH diagnosis (median fasting glucose: 4.96 mmol/L and 4.86 mmol/L, respectively; median BMI: 23.82 kg/m2 and 23.26 kg/m2, respectively). Diabetes was significantly more frequent in patients with NCAH diagnosis (p = 0.004; power: 0.74). The median 17-OHP was higher in patients with diabetes compared to those without it at both 30 (12.25 ng/mL vs 3.25 ng/mL; p=0.003) and 60 minutes (14.93 ng/mL vs 3.95 ng/mL; p=0.046) after stimulation. Conclusions: NCAH seems to be linked to increased diabetes risk, even in glucocorticoid-naïve patients. It seems advisable to screen NCAH patients for glucose metabolism disorders. Presentation: 6/1/2024

8301 A Rare Case of IgG4-Related Hypophysitis

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (<2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of >10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up. Presentation: 6/2/2024

12343 Cardiac Function Recovery Following Left Adrenalectomy For A Pheochromocytoma With Ectopic ACTH Syndrome

Abstract Disclosure: T.D. Williams: None. D. Lovre: None. R.C. Galagan: None. Background: Pheochromocytoma and Cushing’s Syndrome are implicated in Non-ischemic Cardiomyopathy/Heart Failure with reduced Ejection Fraction (NICM/HfrEF) due to catecholamine induced hypertension and cardiomyocyte toxicity. Subsequent hypoxia and calcium overload in cardiomyocytes results in oxidative stress and cell death. Excess cortisol secretion increases angiotensin II, causing hypertrophy. Subsequent increases in atrogin I lead to myo-fibrinolysis and fibrosis. We present a patient with NICM/HFrEF due to both catecholamine excess and ectopic ACTH syndrome from an adrenal pheochromocytoma. Following adrenalectomy, systolic cardiac function returned to normal. Clinical Case A 42-year-old female was referred to endocrinology after a hypertensive emergency concurrent with NSTEMI, NICM, and HFrEF (EF 45%). Initial work up revealed: Troponin I 0.49 ng/ml; (0 - 0.04 ng/ml), Na+ 140 mmol/L; (136 - 144 mmol/L), K+ 2.3 mmol/L; ​​(3.7 - 5.2 mmol/L), CO2 41 mmol/L; (23 - 29 mmol/L), Glucose 53 mg/dL; (64 - 100 mg/dL), Cortisol 57.2 ug/dL; (5 - 25 ug/dL), ACTH 363.7 pg/mL; (7.2 - 63.3 pg/mL). She failed both 1 mg and 8 mg overnight dexamethasone suppression tests: 0800 cortisol 48.5 ug/dL (< 1.8 ug/dL) & 56.8 ug/dL (> 50% decrease in baseline cortisol level of 57.2 ug/dL) consistent with ectopic ACTH syndrome. Elevated plasma normetanephrine 0.98 nmol/L; (0 - 0.89 nmol/L) and chromogranin A 250 ng/mL; (0 - 103 ng/mL) suggested a neuroendocrine tumor. Pituitary MRI revealed a normal pituitary gland. Abdominal MRI detected a 3.6 x 2.5 cm left adrenal nodule and PET/CT CU-64 showed increased activity (Krenning 4) consistent with a pheochromocytoma. Notwithstanding Ketoconazole (200 mg/day) for 7 months, her EF fell to a low of 15-20%. A left adrenalectomy was performed and post-op 0800 cortisol was 12.3 ug/dL (6.0 - 26.0 ug/dL). Oral hydrocortisone was initiated at 20 mg QAM/10 mg QPM for steroid withdrawal syndrome, tapered over 8 months and withdrawn when a cosyntropin stimulation test 60-min cortisol was 19.3 ug/dL; (>18.0 ug/dL). Eleven months post op, her 0800 cortisol was 8.8 ug/dL and ACTH 27.4 pg/mL. One month post-op, TTE showed EF: 15-20%, six months post-op EF: 25-30%, eight months post-op EF: 35-40% and 15 months post-op EF was normal at 50%. Her heart failure symptoms resolved, and her activity returned to normal. Conclusion This case illustrates a remarkable restoration of cardiac function following resection of a pheochromocytoma. Our patient's case is unique due to the restoration of cardiac function despite the dual impact of excessive catecholamines and cortisol. Our patient’s clinical course contributes to an evolving understanding of cardiomyopathy associated with pheochromocytoma and ectopic ACTH syndrome and highlights the potential for cardiomyopathy reversal with targeted endocrine surgical and medical interventions. Presentation: 6/1/2024

Hypopituitarism, Diabetes Insipidus, and Syndrome of Inappropriate Antidiuretic Hormone Secretion after Pituitary Macroadenoma Surgery with Indocyanine Green Dye.

(1) Background: Pituitary adenomas are benign tumors comprising about 18% of all intracranial tumors, and they often require surgical intervention. Differentiating pituitary tissue from adenoma during surgery is crucial to minimize complications. We hypothesized that using ICG dye would reduce the hormonal complication rates. (2) Methods: A prospective randomized study (February 2019-October 2023) included 34 patients with non-functional macroadenomas of the pituitary gland randomly assigned to receive intraoperative ICG or be in the control group. All underwent endoscopic endonasal transsphenoidal surgery. Pituitary function was assessed preoperatively, immediately postoperatively, and 3-6 months postoperatively. Adenohypophysis function was evaluated with hormonal tests (Cosyntropin stimulation test, TSH, fT3, fT4, prolactin, IGF-1, FSH, LH, and testosterone in men) and neurohypophysis function with fluid balance, plasma and urine osmolality, and serum and urinary sodium. (3) Results: Of the 34 patients (23 men, 11 women; average age 60.9 years), 5.9% in the ICG group developed diabetes insipidus postoperatively, compared to 23.5% in the control group. Adenohypophysis function worsened in 52.9% of the ICG group and in 35.3% of the control group. (4) Conclusions: Our study did not confirm the benefits of using ICG in these surgeries. Further research with a larger sample is needed.

ASO Visual Abstract: Cosyntropin Stimulation Testing is More Selective Than Postoperative Day 1 Basal Cortisol for Diagnosing Secondary Adrenal Insufficiency Following Unilateral Adrenalectomy.

ASO Visual Abstract: Cosyntropin Stimulation Testing is More Selective Than Postoperative Day 1 Basal Cortisol for Diagnosing Secondary Adrenal Insufficiency Following Unilateral Adrenalectomy.

Cosyntropin Stimulation Testing is More Selective than Postoperative Day 1 Basal Cortisol for Diagnosing Secondary Adrenal Insufficiency After Unilateral Adrenalectomy.

Secondary adrenal insufficiency (SAI) may occur in patients after unilateral adrenalectomy for adrenal-dependent hypercortisolism (HC) or primary aldosteronism (PA). This study aimed to assess whether postoperative day (POD) 1 basal cortisol was predictive of an abnormal cosyntropin stimulation test (CST) result and the need for glucocorticoid replacement (GR). A retrospective review of consecutive patients who underwent unilateral adrenalectomy for HC, PA, or both between September 2014 and September 2022 was performed. On POD1, CST was performed for all the patients with HC, and before 2021 for all the patients with PA. The patients with an abnormal CST result were deemed at risk of SAI and discharged with GR. Receiver operating characteristic (ROC) curves were generated to evaluate the sensitivity (SN) and specificity (SP) of basal cortisol thresholds to predict an abnormal CST result. The patients underwent unilateral adrenalectomy for overt hypercortisolism (OH; n = 42), mild autonomous cortisol excess (MACE; n = 70), mixed PA/HC (n = 22), or PA (n = 73). On POD1, CST was performed for 152 patients (93% OH, 96% MACE,73% PA/HC, 41% PA), and 80 patients (53%) had SAI (67% OH, 55% MACE, 44% PA/HC, 33% PA). The SN and SP of a basal cortisol level of 10 µg/dL or lower to predict an abnormal CST were respectively 92% and 77% for OH, 94% and 73% for MACE, 100% and 85% for PA, and 100% and 67% for PA/HC. The optimal basal cortisol level for predicting an abnormal CST for patients with PA or PA/HC was 5µg/dL or lower (SN/SP, 100%). After unilateral adrenalectomy for HC, PA, or mixed PA/HC, POD1 CST improved identification of patients at risk for SAI compared with basal cortisol levels alone. The authors recommend that POD1 CST be performed to determine the risk for SAI and the need for postoperative GR after unilateral adrenalectomy for patients with HC.

A hybrid IA-LC-MS/MS method for adrenocorticotropic hormone(1-24) to support interpretation of low-dose cosyntropin-stimulation test.

Adrenocorticotropic hormone 1-24 (ACTH[1-24]) has a similar effect as endogenous ACTH(1-39) to generate cortisol by targeting the MC2R receptor on the adrenal gland. A new investigational ACTH receptor antagonist drug is being developed to treat diseases of ACTH excess (e.g., Cushing's disease) by binding to the MC2R receptor. Administration of ACTH(1-24) was used in a Phase I clinical study to assess the ability of this drug candidate to suppress the cortisol response to ACTH stimulation. A hybrid immunoaffinity-LCMS assay measuring ACTH(1-24) with a concentration range of 10 to 400pg/ml was developed to support the study. Consistent and acceptable A&P results were achieved. The assay development and qualification will be discussed.

Hypothalamic-Pituitary-Adrenal Axis Response in Patients With Acne Vulgaris Treated With Clascoterone.

Clascoterone cream 1% is a topical androgen receptor inhibitor approved to treat acne vulgaris in patients =>12 years of age. This report provides details of patients who developed laboratory signs of hypothalamic-pituitary-adrenal (HPA) axis suppression without clinical signs of adrenal suppression during the clascoterone development program. Two open-label, multicenter, Phase 2 trials evaluated HPA axis suppression in patients with moderate-to-severe acne vulgaris. Study 1 (NCT01831960) enrolled cohorts of adults =>18 years of age and adolescents =>12 to <18 years of age. Study 2 (NCT02720627) enrolled adolescents 9 to <12 years of age. Patients applied clascoterone twice daily at maximum-exposure dosages for 14 days. Adrenal suppression was evaluated via cosyntropin stimulation test (CST) at baseline and day 14. Patients with an abnormal CST result (serum cortisol level =<18 µg/dL) had a follow-up CST approximately 4 weeks later. Blood was collected for pharmacokinetic analysis. Other safety assessments included adverse events (AEs), physical examination/vital signs, and electrocardiography. Overall, 5/69 clascoterone-treated patients had an abnormal CST result on day 14, including 1/20 adults, 2/22 patients aged =>12 to <18 years, and 2/27 patients aged 9 to <12 years. All patients had normal cortisol levels at follow-up testing approximately 4 weeks later. No relationship was observed between abnormal CST results and clascoterone plasma concentrations or the amount of study drug applied. No clinically relevant AEs or clinically significant changes in safety measures were observed in patients with adrenal suppression. Clascoterone induced laboratory evidence of mild, reversible HPA axis suppression under maximum-use exposure. J Drugs Dermatol. 2024;23(6):433-437.     doi:10.36849/JDD.7997.

Enhancing the specificity of 17-hydroxy progesterone cut-off value for cosyntropin stimulation testing. A retrospective study of Sri Lankan population

Enhancing the specificity of 17-hydroxy progesterone cut-off value for cosyntropin stimulation testing. A retrospective study of Sri Lankan population

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Retrospective cohort study. We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.