Diagnosis Of Adrenal Insufficiency Research Articles

Adrenal insufficiency in pediatric kidney transplantation recipients.

Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients. This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects. AI risk was assessed using morning cortisol (MC) and diagnosis confirmed by an ACTH stimulation test. Potential risk factors and adverse effects were tested for associations with MC levels and AI diagnosis. Fifty-one patients (60.8% male, age 7.4 (IQR 3.8, 13.1) years; 1 patient counted twice for repeat transplant) were included. Patients at risk for AI (MC < 240 nmol/L) underwent definitive ACTH stimulation testing, confirming AI in 13/51 (25.5%) patients. Identified risk factors for AI included current prednisone dosage (p = .001), 6-month prednisone exposure (p = .02), daily prednisone administration (p = .002), and rejection episodes since transplant (p = .001). MC level (2.5 years (IQR 1.1, 5.1) post-transplant) was associated with current prednisone dosage (p < .001), 6-month prednisone exposure (p = .001), daily prednisone administration (p = .006), rejection episodes since transplant (p = .003), greater number of medications (β = -16.3, p < .001), 6-month hospitalization days (β = -3.3, p = .013), creatinine variability (β = -2.4, p = .025), and occurrence of acute kidney injury (β = -70.6, p = .01). Greater corticosteroid exposure was associated with a lower MC level and confirmatory diagnosis of AI noted with an ACTH stimulation test. Adverse clinical findings with AI included greater medical complexity and kidney function lability. These data support systematic clinical surveillance for AI in PKT recipients treated with corticosteroids.

Redefining ITT cortisol thresholds on Abbott platforms to prevent misdiagnosis of adrenal insufficiency.

Adrenal insufficiency (AI) is a life-threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut-off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut-off used to diagnose AI is also founded on outdated assays. Use of this cut-off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk. This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre. Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut-off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%. This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut-off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement.

Predictive value of different thresholds of morning cortisol in diagnosing adrenal insufficiency

ObjectiveAdrenal insufficiency (AI) is diagnosed with morning cortisol but ACTH stimulation test is usually needed to confirm the diagnosis. In this study we investigated different morning cortisol thresholds that can safely rule out AI without requiring a confirmatory ACTH stimulation test. DesignRetrospective cohort study. MethodsWe included patients aged 18 and above who underwent the 250 mcg ACTH stimulation test from June 2018 to June 2022. Basal and post-ACTH serum cortisol values at 30 and 60 min were documented. Sensitivity, specificity and logistic regression analysis were employed to assess morning cortisol level's ability to predict AI as confirmed by ACTH stimulation test. Results237 patients were included, 66 diagnosed with AI and 171 had normal ACTH results. Hypertension and type 2 Diabetes correlated with lower AI incidence. Median morning cortisol was 138.0 nmol/L for AI group and 286.0 nmol/L for non-AI patients. A morning cortisol of 285 nmol/L had 90.6 % sensitivity, 50.3 % specificity, and a negative predictive value of 93.3 % for ruling out AI. A threshold of 306 nmol/L increased sensitivity to 95.3 % with 40 % specificity. ConclusionMorning cortisol is an effective diagnostic tool for ruling out AI. Using multiple thresholds based on clinical suspicion and the integration of predictive pre-test probability can reduce the need for excessive ACTH stimulation tests. This study contributes to the growing evidence of utilizing morning serum cortisol in the diagnosis of adrenal insufficiency. Clinical relevance statementDiagnosing Adrenal Insufficiency (AI) can be challenging due to debate regarding the cortisol cut-off value that can exclude AI without additional tests. The confirmatory short synacthen test has certain limitations including financial implications and time restrictions. We investigated the performance of various morning cortisol levels that can diagnose AI without additional testing.

Usefulness of salivary cortisol in the diagnosis of adrenal insufficiency and evaluation of the hypothalamic-pituitary-adrenal axis

Usefulness of salivary cortisol in the diagnosis of adrenal insufficiency and evaluation of the hypothalamic-pituitary-adrenal axis

The diagnosis of adrenal insufficiency and its implications in primary care

Adrenal insufficiency can be clinically challenging to diagnose, due to relatively low incidence rates in the European population. It is a condition requiring active consideration to achieve diagnosis. The main pathologies discussed here are primary adrenal insufficiency (PAI) and tertiary adrenal insufficiency. PAI is also commonly termed Addison’s disease. Secondary adrenal insufficiency is not considered in detail in this article. The article will address the underlying pathophysiology, presentation and investigation of adrenal insufficiency. It will also consider iatrogenic adrenal insufficiency and management of adrenal insufficiency in the primary care setting.

Opioid-induced adrenal insufficiency: diagnostic and management considerations.

The dramatic rise in opioid use over the last two decades has led to a surge in their harmful health effects. Lesser known among clinicians is the impact of opioids on the endocrine system, especially with regard to cortisol. Opioids can suppress the hypothalamus-pituitary-adrenal (HPA) axis and may result in clinically significant adrenal insufficiency, especially in those treated at higher doses and for a longer time. A high clinical suspicion is necessary in this population for early diagnosis of opioid-induced adrenal insufficiency (OAI). Diagnosis of OAI is challenging, as the symptoms are often vague and overlap with those due to opioid use or the underlying pain disorder. Traditional assays to diagnose adrenal insufficiency have not been widely studied in this population, and more investigation is needed to determine how opioids might affect assay results. Once a diagnosis of adrenal insufficiency has been made, glucocorticoid replacement in the form of hydrocortisone is likely the mainstay of treatment, and effort should be made to taper down opioids where possible. Cortisol levels should be retested periodically, with the goal of stopping glucocorticoid replacement once the HPA axis has recovered. In this review, we provide context for diagnostic challenges in OAI, suggest diagnostic tools for this population based on available data, and offer recommendations for the management of this disorder. There is a paucity of literature in this field; given the widespread use of opioids in the general population, more investigation into the effects of opioids on the HPA axis is sorely needed.

Bilateral adrenal hemorrhage: learning notes from clinical practice and literature review.

Adrenal hemorrhage is a rare, but important, diagnosis to recognize, in particular when there is involvement of both adrenal glands. Bilateral adrenal hemorrhage can in fact lead to adrenal insufficiency, with dramatic consequences if not promptly recognized and treated. It is normally caused by systemic conditions that lead to the vasoconstriction and thrombosis of the adrenal vein. Oftentimes, the clinical diagnosis of this condition can be very challenging, as its signs and symptoms are generalized and nonspecific (abdominal pain, nausea, and fatigue). Here, we present the cases of two patients admitted to the Emergency Department in 2016 and 2022 with acute abdominal pain, having recently undergone surgery and subsequently prescribed low-molecular-weight heparin. In both cases, laboratory results revealed neutrophilic leukocytosis and an unexplained anemia. Due to the persistence of abdominal pain despite medication, a CT scan was performed, showing an enlargement of both adrenal glands suggestive of bilateral adrenal hemorrhage. Adrenal function was tested that correlated with a diagnosis of adrenal insufficiency, and both patients were promptly treated with parenteral hydrocortisone as a result. On 5 years' follow-up from the acute event, the second patient's adrenal function had returned to normal, and he has not needed further adrenal replacement therapy; the first patient however demonstrated persistence of adrenal failure requiring replacement therapy. In this paper, through our experience and a literature analysis, we will aim to outline some clues to identify patients at potential risk of bilateral adrenal hemorrhage.

Increased risk of hospitalization, intensive care and death due to COVID-19 in patients with adrenal insufficiency: A Swedish nationwide study.

Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

SAT317 Adrenal Insufficiency Diagnosed During Pregnancy

Abstract Disclosure: A. Rosado-Burgos: None. L.N. Madera Marin: None. M.A. Ortiz-Rivera: None. L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. Introduction: Primary adrenal insufficiency (AI) that is a potentially life-threatening condition and commonly associated to destruction of adrenal cortex by autoantibodies. AI predominantly affects women of reproductive age and can affect the outcome and course of pregnancy, causing reduced parity, risk of preterm birth, and low birth weight. Symptoms of AI are nonspecific and can result in a challenging diagnosis. Clinical case: 25 year-old pregnant female G1P0A0 at 12 weeks gestational age (WGA) with long standing history of Type 1 Diabetes Mellitus (DMT1) and Hypothyroidism. She was evaluated while hospitalized for metabolic control during pregnancy. The patient had been previously admitted at 7 WGA with hyperglycemic episodes requiring insulin dosing adjustments. Now, 5 weeks later, was found with numerous hypoglycemic episodes even after omitting pre-prandial insulins. Additionally, she had persistent fatigue, general malaise, nausea, vomits, anorexia, and difficulty concentrating. Laboratory workup showed a TSH of 22.96 uIU/mL (nl 0.4-4.0), FreeT4 0.91 (nl 0.89-1.74), that had been within normal limits 6 weeks prior. She reported taking pre-natal vitamins only one hour after LT4, therefore malabsorption was suspected. Insulin requirements were decreased by 50%. Vitals signs without evidence of hemodynamic instability and laboratory workup without electrolyte nor acid base disturbances. However, due to clinical presentation and history of other autoimmune diseases, AI was suspected. Severe hypothyroidism, AI and hyperemesis gravidarum can mimic several features of each other’s clinical presentation. Midmorning cortisol level was found at 7.8 ug/dl (nl for pregnancy &amp;gt;19) but no ACTH levels taken prior to replacement. Considering acuteness and severity of symptoms it was decided to administer IV LT4 equivalent dose which can increase cortisol metabolism precipitating adrenal crisis. For this reason, stress dose hydrocortisone (HC) was empirically administered. Rapid clinical improvement was observed after LT4 and corticosteroid replacement therapy with resolution of nausea, vomits, anorexia as well as hypoglycemic episodes and was discharge home with her usual LT4 PO dose and corticosteroid replacement therapy. Twenty-one-alpha hydroxylase antibodies were positive, making the diagnosis of primary adrenal insufficiency highly suspected. Conclusion: Presentation was consistent with Polyglandular Autoimmune Syndrome Type 2. Diagnosis of AI during pregnancy is rare as it is considered a hypercortisolemic state. Changes in cortisol levels during pregnancy make the diagnosis of AI even more challenging. Dynamic testing can be considered, however, most of these studies have not been validated in pregnancy. In this case patient continues with HC replacement therapy while in her 3rd trimester of pregnancy without any maternal of fetal complications. Presentation: Saturday, June 17, 2023

FRI259 Antiphospholipid Syndrome And Adrenal Insufficiency: An Underrated Association

Abstract Disclosure: S. Khalid: None. M. Arumugam: None. P. Passarella: None. Introduction: Catastrophic Antiphospholipid Syndrome (CAPS) is a rare and life-threatening subtype of Antiphospholipid Syndrome (APS) that causes widespread vascular thrombi. Endocrine complications of APS are very rare, however the most common is Adrenal Insufficiency (AI). Overt AI is only found in 0.4% of patients with APS while only 0.5% of patients with AI are diagnosed with APS. Either thrombosis leading to infarction or hemorrhage can cause AI in patients with APS. Sometimes, adrenal insufficiency or crisis can be the primary presentation of APS. Here, we present a case of AI in the setting of CAPS. Case Presentation: A 17-year-old woman with past medical history of chronic immune thrombocytopenia was admitted to the intensive care unit due to cardiogenic and distributive shock. One week prior to her presentation she had developed a sore throat followed by progressive lethargy that eventually evolved into a state of unconsciousness and she was brought to the emergency department. Her presenting vital signs included temperature of 40.7 C and blood pressure of 89/36 mmHg. On physical exam, she appeared somnolent and pale, and had cool extremities. Labs on admission (11 pm) revealed cortisol level of 3.6 UG/DL (reference range 3.8-19.4 UG/DL), TSH 4.61 UIU/ml (reference range 0.45-4.5 UIU/ml), free T4 1.3 ng/dl (reference range 0.6-1.3 ng/dl), aldosterone 11.3 ng/dl (reference range supine &amp;lt; 3-39.2 ng/dl), sodium 135 MEQ/L (reference range 135-145 MEQ/L), and potassium 4.7 MEQ/L (reference range 3.5-5.2 MEQ/L). Echocardiogram was remarkable for new onset reduced ejection fraction of 25-30% and left ventricular thrombi. Additionally, brain MRI showed acute infarcts. Due to concern for an underlying rheumatological disease, extensive autoimmune work up was initiated, and she was started empirically on methylprednisolone 30 mg intravenous twice daily. To further evaluate thrombi, CT scan of the abdomen and pelvis was performed, revealing bilaterally enlarged and hypoenhancing adrenal glands likely related to ischemia or infarction along with left renal vein thrombosis. Laboratory work-up returned positive for anti-cardiolipin IgM and IgG antibodies. In the setting of multiple vascular thrombi and positive antibodies, she was diagnosed with CAPS. The diagnosis of AI was made due to a low cortisol level in a state of shock and was deemed secondary to CAPS. For the treatment of CAPS she was continued on methylprednisolone with a plan for a slow taper. To ensure mineralocorticoid replacement was adequate fludrocortisone was also added at a dose of 0.1 mg with close monitoring of electrolytes and vital signs. Conclusion: Our case illustrates a rare though potentially fatal endocrine complication of CAPS and highlights the importance of its awareness. Undiagnosed and untreated adrenal insufficiency can lead to extremely poor outcomes, including death. Presentation: Friday, June 16, 2023

FRI262 Can Selective Serotonin Reuptake Inhibitors Unmask Underlying Polyglandular Autoimmune Syndrome Type II?

Abstract Disclosure: S. Dehghani: None. S. Kalik: None. J. Zaidan: None. A. Nisar: None. Background: Patients with chronic use of SSRIs are at increased risk of developing hyponatremia secondary to SIADH but a full work up to exclude other etiologies might still be warranted if patient has risk factors. Clinical Case: 63-year-old female with past medical history of rheumatoid arthritis and hypothyroidism secondary to Hashimoto thyroiditis presented to the hospital for evaluation of syncopal episodes associated with dizziness, loss of consciousness and weight loss. She was started three weeks prior to presentation on Escitalopram 10 mg for mild depression. On exam she had orthostatic hypotension, she looked tanned but there was no buccal or palmar pigmentation. Admission blood work showed Na level of (111 mmol/L, n:135-145 mmol/L), Potassium of (5.7 mmol/L, n: 3.5-5 mmol/L), Creatinine of (0.8 mg/dL, n:0.7-1.5 mg/dL). Urine Sodium was (59 mEq/L, n: 20 mEq/L) and Urine osm (306 mOsm/Kg, n:50-1200 mOsm/kg). TSH was normal and 8 AM cortisol level was (6.0 ug/dL, n: 6.0-18.4 ug/dL). Initially Hyponatremia was attributed to SIADH secondary to use of Selective Serotonin Reuptake inhibitors, however her autoimmune comorbidities, orthostatic hypotension and physical exam findings warranted more work up to rule out Adrenal insufficiency. The 250 mcg Cosyntropin Stimulation test was done with baseline cortisol of (4.6 ug/dL, n: 6-18.4 ug/dL) and cortisol at 30 minutes and 60 minutes of (5.2 ug/dL and 5.1 ug/dL respectively) confirming failure to respond to ACTH and diagnosis of adrenal insufficiency. She denied taking exogenous steroids. Later her ACTH came back very high (956 pg/mL, n:7-63 pg/mL), aldosterone was (5.3 ng/dL, n&amp;lt;23 ng/dL), plasma renin activity was high at (20.095 ng/mL/hr, n:0.1-1.3ng/mL/hr) and anti-adrenal antibodies were positive confirming the diagnosis of Addison disease. Patient was started on IV hydrocortisone with slow resolution of hyponatremia and symptoms. She was discharged on maintenance hydrocortisone and fludrocortisone. Given the presence of Hashimoto thyroid disease and Rheumatoid arthritis, patient was diagnosed as having polyglandular autoimmune Syndrome type II. Conclusion: The signs and symptoms of adrenal insufficiency are often nonspecific, resulting in long delays in diagnosis or even misdiagnosis. Hyponatremia is one of the manifestations of adrenal insufficiency which can be inevitably missed or misdiagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) as both can manifest as euvolemic hyponatremia and inappropriate urinary Na concentration. This case demonstrates the importance of thorough investigation of underlying etiologies of patients with symptomatic hyponatremia who are also at risk SIADH secondary to SSRIs use. Presentation: Friday, June 16, 2023

SAT299 Comparison Of Plasma Cortisol-, Salivary Cortisol- And Salivary Cortisone-response To The Short Synacthen Test In Women Using Oral Contraceptives

Abstract Disclosure: N. Bäcklund: None. S. Lundstedt: None. T. Olsson: None. P.M. Dahlqvist: None. G. Brattsand: None. Introduction: The short Synacthen test (SST) is a cornerstone in the diagnosis of adrenal insufficiency (AI). However, cortisol levels in serum or plasma may be misleadingly elevated by estrogen containing oral contraceptives (OCs), due to increased levels of cortisol binding protein (CBG). This may falsely declare a woman with AI to be cortisol sufficient. Salivary cortisol and cortisone closely correlate with the unbound fraction of plasma cortisol and is thus less likely to be influenced by variations in CBG levels. Our hypothesis was that the salivary cortisol and cortisone response to SST would be similar in women with and without OC use. Materials and methods: A standard intravenous 250 µg SST was performed in 87 women without known diseases or medications affecting the cortisol axis, 41 using OCs containing ethinylestradiol and 46 controls. Plasma cortisol was analyzed by Roche Elecsys Cortisol II assay and salivary cortisol and cortisone by LC-MS/MS in samples collected at baseline (time 0), and 30 and 60 minutes after Synacthen injection. The effect of OCs upon plasma cortisol, salivary cortisol and salivary cortisone was assessed by a two-way ANOVA with sampling time after SST as repeated measure. Results: There was an overall effect of OCs on plasma cortisol, but not on salivary cortisol or cortisone. Plasma cortisol levels were considerably higher in the OC group vs. controls at all time points; +150% at 0 minutes; +90% at 30 minutes; and +86% at 60 minutes. There was a significant interaction between OC use and sample time point for both salivary cortisol and cortisone. Mean salivary cortisol in women using OCs was 37% higher vs. controls at 0 minutes but was instead lower in the OCs group at 30 and 60 minutes after SST (-13% and -11%, respectively). Similarly, mean salivary cortisone was also slightly higher in the OC group than controls at baseline (+13%) and somewhat lower at 30 and 60 minutes (-6% and -7%). Conclusion: Plasma cortisol levels during an SST were significantly elevated in women using OCs containing estrogen whereas OC effects upon salivary cortisol and cortisone levels were modest, especially for salivary cortisone. Analysis of salivary cortisone is a promising alternative to plasma cortisol for diagnosis of AI in women using OCs. Presentation: Saturday, June 17, 2023

FRI562 Not JUST Severe Hypothyroidism: Recognizing Autoimmune Polyglandular Syndrome

Abstract Disclosure: S.R. Jafarian-Kerman: None. A. Razzeto: None. G. Saini: None. M. Siddiqui: None. M. Islam: None. D. Behman: None. M. Carson: None. Background: Recognizing Autoimmune Polyglandular Syndrome (AIPS) in a patient who has chronic hypothyroidism, specifically with a non-classic presentation, is challenging. Clinical Case: A woman in her 50’s with hypothyroidism presented with one week of progressive dizziness and weakness. Medications include levothyroxine 125 μg weekly (per the patient, her PCP started this dose 8 months ago based on lab results). On physical examination: BP 101/74 mmHg; HR 56 bpm; T: 98.1 F (36.7 C); RR: 23/min; O2 Sat: 98%. Skin: vitiligo. Lab results demonstrated TSH: 839.6 μIU/mL (0.5-4.5) from 0.28 one year ago, free T4: 0.15 ng/dL (0.4-4.5), phosphorus: 2.3 mg/dL (2.7-4.5), vitamin D: 17.4 ng/dL (&amp;gt;30). She was started on daily levothyroxine 125 μg and intravenous fluids. On day 3 of admission, Rapid Response was called for blood pressure 54/39 mmHg. Myxedema coma was unlikely as she lacked altered mental status, hypothermia, hypoventilation, hyponatremia, or hypoglycemia; CT head was normal. On the same day, hydrocortisone 100 mcg q8h started due to high suspicion of adrenal insufficiency given low normal cortisol [7.1 ug/dL (6-20)] and hypotension. Due to the history of hypothyroidism, vitiligo, and the new diagnosis of adrenal insufficiency, we suspected AIPS. two days later, primary adrenal insufficiency was established by a positive Cosyntropin stimulation test (1 hour cortisol of 14.8 ug/dL; not reaching &amp;gt;18 μg/dL), elevated ACTH 72 pg/mL (6-50), Aldosterone &amp;lt;1 ng/dL (3-16), and low DHEA of 52 ng/dL (345-2030). Other labs were as follow: normal FSH 85.7 mIU/mL (23-116), elevated PTH 153 pg/mL (16-77) which decreased to 62 pg/mL with vitamin D supplementation, normal Vitamin B12, and negative renin and intrinsic factor antibodies. A diagnosis of AIPS was established and she was discharged on levothyroxine, fludrocortisone, and hydrocortisone. Conclusion: AIPS is typically idiopathic and may affect endocrine organ systems either simultaneously or sequentially. The 3 classic patterns are: Type 1 (most common): younger women, presents with candidiasis, hypoparathyroidism, and Addison’s disease. Type 2: middle-aged women, Addison’s disease, autoimmune thyroid disease and/or Type 1 diabetes. Type 3: Type 1 diabetes, pernicious anemia, vitiligo or alopecia, and normal adrenal cortical function. This patient is unique in that she has characteristics of both type 1 and 3 AIPS, but not diabetes. In this case, the combination of hypotension even in the setting of profoundly undertreated hypothyroidism, prompted the expanded evaluation. While isolated hypothyroidism is common among our internal medicine patients, those with additional symptoms, or in this case unexplained hypotension, should be evaluated for AIPS. Presentation: Friday, June 16, 2023

SAT301 Patient-centered Outcomes Measures To Assess Quality Of Life In Adrenal Insufficiency Treatment

Abstract Disclosure: W.J. Hover: None. K.E. Lowe: None. M.E. Lowe: None. J.G. Kallet: None. M.F. Slovick: None. S.L. Majka: None. M.T. McDermott: None. E.A. Regan: None. Individuals with adrenal insufficiency (AI) have been shown to have reduced quality of life in spite of hormone replacement. Although late-stage insufficiency and adrenal crisis may show signs including hypotension and electrolyte abnormalities, patient-reported symptoms may predict outcomes in AI and can be a key factor in understanding poor quality of life in adrenal insufficiency. The SF-36, a generic quality of life (QoL) survey has been reported in adrenal insufficiency but may lack disease-specific domains to define QoL deficits in AI. An AI disease-specific QoL survey, the AddiQoL has also been validated. We evaluated the AddiQol and SF-36 for distinguishing the health status of AI patients in terms of diagnosis, medication use and risk of crisis using a patient registry. Methods: We identified 344 individuals from the MyAI patient registry who had provided responses to both the AddiQoL and SF-36. We compared the AddiQoL overall score with three domains of the SF-36: physical function, role physical, vitality, and the physical and mental component scores (PCS and MCS). Results: Respondents were from all 50 US states with 83% female and mean (SD) age of 50 (15) years. AI diagnosis was Primary 63%, Central 32% and congenital adrenal hyperplasia 5% based on self-report and confirmation with medical records. Both the SF-36 and AddiQoL identified reduced QoL in the AI participants and were significantly correlated: PCS to AddiQoL 0.73 and MCS to AddiQoL 0.63. Role Physical, Vitality and General Health were the most reduced domains with mean values of 38.4 (43.5), 35.6 (24.5) and 40.8 (24.7) respectively. Primary AI showed significantly better QoL than Central AI by both SF-36 and AddiQol [80.3(15.1) vs 69.9 (14.2), p&amp;lt;0.001]. Respondents who reported an adrenal crisis within the past year had significantly lower AddiQol [72.8(15.4) vs 82.3 (15.4), p&amp;lt;0.001] and SF-36 scores. Respondents who were currently treated with hydrocortisone (HC) had better QoL than those on Prednisone [HC 78.1 (15.2), Prednisone 74.1 (15.9), p=0.02 adjusted for diagnosis group]. Conclusions: In a geographically broad cohort of US AI patients, we confirm significant reductions in QoL in spite of treatment. Both the SF-36 and AddiQoL were able to distinguish differences in QoL by diagnosis, risk of adrenal crisis and medication. Further work to define specific patterns of high-risk symptoms may improve early diagnosis of impending crisis. Presentation: Saturday, June 17, 2023

FRI253 Concurrent Adrenal Insufficiency And Hyperthyroidism In A Breast Cancer Patient Treated With Pembrolizumab Therapy

Abstract Disclosure: A.U. Kulkarni: None. D.T. Patel: None. E.B. Ruby: None. Anti-programmed cell death-1 (Anti-PD1) antibodies (e.g., Pembrolizumab) are immune checkpoint inhibitors that are widely in use for the treatment of many advanced malignancies. This has resulted in various side effects known as irAEs (immune-related adverse events). Endocrine irAEs include hypophysitis, adrenal insufficiency (AI), hypothyroidism, and hyperthyroidism. A 40-yo female with a history of recently diagnosed triple-negative breast cancer, status post chemotherapy, and immunotherapy with Pembrolizumab (last treatment a month prior to presentation) came in with fatigue, weight loss, and persistent vomiting for two weeks. Her initial BP was noted to be 80/50 mmHg, with HR 108bpm. She appeared weak and tired with no other abnormalities on physical exam. The thyroid was normal with no enlargement. Significant labs were creatinine 1.4mg/dL (0.4-1.3mg/dL), corrected calcium 12.8mg/dL, TSH of &amp;lt;0.01mUI/L and fT4 of 4.47ng/dL (0.61-1.12ng/dL) (thyroid tests were previously normal). The patient was admitted to the ICU for hypovolemic shock refractory to IV fluids and endocrinology was consulted for multiple hormonal abnormalities. AKI and hypercalcemia were likely from dehydration as they subsequently resolved with IV fluids. AM cortisol level was low at 0.7ug/dL(3-16ug/dL). The cosyntropin test was positive, confirming AI. ACTH level was &amp;lt;5pg/mL (normal&amp;lt;46pg/mL) indicating a diagnosis of secondary AI, likely from immunotherapy. She was initiated on IV hydrocortisone. MRI brain was obtained to evaluate for hypophysitis which was unremarkable. Further thyroid testing was pursued which showed negative Thyroid peroxidase and anti-thyroglobulin antibodies. Thyroid scan showed a focal hot nodule in the left lobe suspicious for an autonomous nodule. She was started on beta blockers and methimazole with the goal of optimizing her thyroid function prior to her elective mastectomy. Pembrolizumab was discontinued with the plan to re-challenge after surgery. BP stabilized and she was discharged home on hydrocortisone with close outpatient follow-up with Endocrinology and Oncology. The clinical manifestations of Anti-PD1-associated AI are very non-specific and difficult to diagnose as they can be confused with the cancer-related illness itself or chemotherapy. Multiple endocrine abnormalities on initial labs with recent Pembrolizumab therapy in our patient raised suspicion for irAEs. Even though the occurrence of AI from anti-PD1 drugs is extremely rare, being &amp;lt;1%, it can be life-threatening. Very few cases of Anti-PD1-induced thyroid dysfunction have been reported, however further testing in our patient confirmed hyperthyroidism from a toxic thyroid nodule. With the increasing popularity of these drugs, endocrinological complications are on the rise, and we as clinicians need to be vigilant and intervene at an early stage to prevent irreversible and fatal outcomes. Presentation: Friday, June 16, 2023

SAT298 Adrenal Insufficiency Presenting With Isolated Severe Hyponatremia: A Case Series

Abstract Disclosure: A. Shafi: None. J. Berardo: None. J. Hwang: None. Background: Adrenal insufficiency (AI) is an overlooked cause of severe hyponatremia (defined as serum Na &amp;lt;120); especially when it is not accompanied by other classic features (i.e., hypotension, hypoglycemia or other electrolyte dysfunction) leading to delayed diagnosis, treatment and increased length of hospital stay (LOS).Case series: We report 14 cases (9 distinct patients) of hospital admission for severe hyponatremia either on presentation or during course of hospitalization attributable to adrenal insufficiency. Four of the nine patients had multiple admissions. These cases were divided into 2 groups based on if they were newly diagnosed (n=6) or had a known diagnosis (n = 8) of AI. Mean age was 56 for both groups, serum Na was 117 vs 114, systolic BP was 126 vs 123. Endocrine was consulted on day 4.5 vs 1.8 and hydrocortisone was started on day 4.8 vs 1.3 resulting in length of stay 8 vs 5 days, respectively. 80% of the subjects also had hypothyroidism with a mean free T4 of 0.87 vs 0.71. In the newly diagnosed group, cortisol was checked on day 3.5. The majority (86%) of admissions were attributed to a secondary adrenal insufficiency crisis. Conclusion: This case series presents several important conclusions which impact endocrine consultation, treatment and length of hospital stay. A) Despite various hyponatremia guidelines suggesting ruling out AI and hypothyroidism before empirical diagnosis of SIADH, there can still be delay in checking cortisol status. B) AI presentation can lack hemodynamic instability or other electrolyte abnormalities so a high clinical index of suspicion should be exercised in diagnosing this potentially fatal condition when encountering isolated severe hyponatremia. C) There is a significant rate of readmission in cases of severe hyponatremia related to adrenal insufficiency. Presentation: Saturday, June 17, 2023

FRI255 Polyglandular Autoimmune Syndrome Type 2 Presenting With Severe Hyponatremia

Abstract Disclosure: A. West: None. A.N. Davis: None. A. Warner: None. S. Salcin: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is a polygenic autoimmune syndrome which presents with two or more specific autoimmune manifestations. The combination of Addison’s disease and Hashimoto’s thyroiditis has been referred to as Schmidt Syndrome. Treatment of hypothyroidism without recognition of concomitant adrenal insufficiency may result in exacerbation of adrenal insufficiency (AI). We present a case of PAS-2 presenting with severe hyponatremia. Case: A 28-year-old male presented to an outside hospital with fatigue and weakness. His sodium was 121mEq/L and TSH &amp;gt;356mcIU/mL, and he was admitted for management of hyponatremia. He was started on oral levothyroxine, urea tablets, and fluid restriction. In the weeks following discharge, the patient had worsening fatigue, weakness, dizziness, nausea, and weight loss, and he presented to our ED. His vital signs were stable without tachycardia or hypotension. He was lethargic but fully oriented. Hyperpigmented areas of the tongue and nose were noted. Laboratory evaluation revealed sodium 111mEq/L, potassium 4.5mEq/L, TSH 43.56 (0.4-4.7mcIU/mL), and free T4 of 1.12 (0.58-1.76ng/dL). He was admitted to the medical intensive care unit for management of severe hyponatremia. Repeat sodium was 112mEq/L with serum cortisol 4.57mcg/dL. Hypertonic saline was given without improvement in hyponatremia. Cortisol level was determined to be inappropriately normal in the setting of severe hyponatremia. Cosyntropin stimulation test was performed with baseline, 30 minute, and 60 minute cortisol levels of 5.31, 6.17, and 6.26, respectively, consistent with AI. ACTH level was not obtained due to the blood sample being hemolyzed. Other results include positive 21-hydroxylase antibody, TPO antibody &amp;gt;900 IU/mL, and undetectable GAD 65 antibody. He received IV stress dose steroids with resolution of his symptoms and his hyponatremia. Oral hydrocortisone replacement therapy was started prior to discharge. Discussion: Patients with one autoimmune endocrinopathy are at risk of developing a second one. Our patient’s hyponatremia was initially attributed to his hypothyroidism without recognition of concomitant AI. Early diagnosis of AI is important prior to initiation of levothyroxine, as treatment of hypothyroidism may exacerbate AI. The sodium level in our patient worsened from 121mEq/L at the previous admission to 111mEq/L when he presented to our hospital, related to worsening of his AI while being treated for his hypothyroidism. Timely diagnosis of associated AI requires high index of suspicion in such patients, particularly in patients with signs or symptoms which may overlap with hypothyroidism, such as hyponatremia in our patient. AI should be considered in any patient who presents with hyponatremia, even those who lack other classic features such as hypotension, hyperkalemia, and hypoglycemia. Presentation: Friday, June 16, 2023

FRI129 Adrenal Insufficiency In Olmsted County, MN, USA: A Population-Based Study

Abstract Disclosure: M. Moazzami: Grant Recipient; Self; Rochester Epidemiology Project. S. Achenbach: None. E. Atkinson: None. I. Bancos: None. Background: Epidemiology of adrenal insufficiency (AI) is incompletely characterized with most data originating from referral centers and registries. We aimed to determine the incidence, morbidity index, risk of hospitalizations, and mortality in patients with AI living in Olmsted County, Minnesota. Methods: We assessed the standardized incidence rate, morbidity index, risk of hospitalizations and mortality of AI in residents (aged 18+) in Olmsted County, MN, USA, from Jan 1, 2005, to December 31, 2021. The data was collected using the Rochester Epidemiology Project (REP), a database of medical records for all Olmsted County residents since 1966. Incidence rates were standardized for age and sex according to the 2020 US white population. Sex- and age- matched referent subjects were selected from the REP. AI was defined based on presence of oral chronic glucocorticoid therapy (hydrocortisone, prednisone, prednisolone, or dexamethasone) defined as (1) any hydrocortisone use or (2) 6 months of consecutive use of prednisone, prednisolone, or dexamethasone or (3) two AI diagnosis codes 6+ months apart plus at least one glucocorticoid prescription within 1 year of the second diagnosis. Elixhauser morbidity index was used. Findings: Between 2005 and 2021, 5419 patients were diagnosed with AI (median age of 62 years, range 18-103), 56% women). Overall standardized incidence rates for AI increased from 206 (95% CI 174-238) in 2005 to 252 (223-280) per 100 000 person-years in 2021. At baseline, patients with AI had a higher morbidity index (median 3 vs median 1, p &amp;lt;0.001) and a higher history of hospitalizations within 5 years prior to baseline (57% vs 30%; p&amp;lt;0.001) when compared to referent subjects. When comparing patients with AI to referent subjects, and after adjusting for age, sex, morbidity index and prior history of hospitalizations, patients with AI were more likely to be hospitalized during follow-up (aHR 1.4, 95% CI 1.3-1.5). When comparing patients with AI to referent subjects, and after adjusting age, sex, and morbidity index, patients with AI had higher mortality (aHR 1.7, 95% CI 1.6-1.9). Patients with AI demonstrated a higher risk of dying from musculoskeletal disorders (aHR 4.9, 95% CI 2.2-10.8), respiratory disorders (aHR 4.7, 95% CI 3.3-6.6), neoplasms (aHR 2.4, 95% CI 2.0-2.9), and infectious disorders (aHR 2.3, 95% CI 1.2-4.3) than referent subjects. Interpretation: We demonstrate an increase in AI incidence between 2005 and 2021. Surprisingly, even after controlling for morbidity and prior hospitalizations, patients with AI were more likely to be hospitalized. In comparison to referent subjects, mortality was higher in patients with AI, even after adjustment for morbidity index. Presentation: Friday, June 16, 2023

Immune checkpoint inhibitor-associated adrenal insufficiency in Chinese cancer patients: a retrospective analysis.

Immune checkpoint inhibitors (ICIs) are of great success in cancer therapy. This study aimed to identify adrenal insufficiency (AI) associated with immune checkpoint inhibitor (ICI) treatment in cancer patients receiving steroid replacement therapy and report the clinical characteristics of ICI-associated AI and concurrent immune-associated adverse events (irAEs). Patients prescribed cortisone acetate between January 2020 and March 2022 were reviewed to identify AI associated with ICI treatment. Data collected included indication of ICI (cancer type), drug characteristics, and outcomes. A total of 101 patients were diagnosed with AI following treatment with ICIs. The median age was 64years (range 22-83years); 73.3% of the patients were male. Median time to develop primary AI and secondary AI after starting ICI therapy was 200.5 (35-280) days and 178 (16-562) days, respectively. Concurrent irAEs occurred in 67 (66.3%) patients and included 63 (62.4%) endocrine irAEs. Log-rank test showed that there was a trend toward higher likelihood of death at 120-day follow-up in patients initially receiving intravenous hydrocortisone compared with those receiving oral cortisone acetate after diagnosis of AI (p = 0.029). This retrospective study comprehensively documented the clinical characterization of ICI-associated AI. Those initially receiving intravenous hydrocortisone after diagnosis of AI were associated with higher likelihood of death. Physicians should be aware of the variability of ICI-associated irAEs early in the treatment, early diagnoses, and timely management should be made.

New Cut-off Value for Low-Dose Acth Stimulation Test in the Diagnosis of Adrenal Insufficiency

New Cut-off Value for Low-Dose Acth Stimulation Test in the Diagnosis of Adrenal Insufficiency